Master Class

The levels of burnout in our specialty are increasing as too many of us—90% of the 42,000 ob.gyns in the United States—continue to pursue generalist careers.

We attempt to do it all, from primary care to obstetrics to surgery, and are being pulled in too many directions while losing any sense of control in our professional and personal lives.

There are alternatives to the model of being everything to every patient, however, and adopting office-based procedures can be a key component to making changes successfully.

Most of us perform in-office endometrial biopsies, colposcopy with biopsies, LEEP (loop electrosurgical excision procedures), and IUD insertions. Yet it is estimated that fewer than 30% of ob.gyns. do appreciable hysteroscopy in any setting, and fewer than 5%–10% do office hysteroscopy.

Many of us believe that office-based procedures are potentially dangerous and that they are painful and will not be tolerated by patients.

We argue against an increased level of office-based procedures on the premise that the equipment costs too much, the required skill level is too high, we don't see enough patients who are candidates for these procedures, we don't have procedure rooms, or the integration of more procedures into our existing schedules is just too complex or difficult.

Increasingly, these beliefs are countered by contrasting realities: more medical knowledge, more training opportunities, more reasonably priced equipment, and appropriate third-party reimbursement for office-based hysteroscopic procedures.

These realities have made hysteroscopy the base technology for a successful gynecology-focused office-based practice.

With commitment, those ob.gyns. who enjoy doing procedures can build successful office-based practices by offering a full spectrum of diagnostic and minor operative hysteroscopic procedures that are just as safe, tolerable, and effective as they are in the hospital.

In doing so, they can provide more thorough and efficient care in a more comfortable, familiar, and cost-effective setting.

Less Anesthesia, More Accuracy

The most significant misconception among ob.gyns.–and probably the largest barrier to wider use of in-office hysteroscopy—relates to pain.

The perceptions are fueled by the operating room experience, where intravenous sedation causes patients to lose inhibition and the ability to follow directions and control their actions.

Patients perceive touch and other stimuli as pain, and the loss of inhibition often escalates as the anesthesist applies even more IV sedation in an effort to make them more comfortable.

This is often perceived as intolerance for pain, and ob.gyns. leave the operating room thinking that if patients cannot tolerate hysteroscopy in that setting, they will certainly not tolerate it in the office.

In reality, patients can tolerate procedures very well—and with less anesthesia—if they know what to expect and if they're in control of their bodies and the overall situation. This happens more readily in the office environment, which is familiar, less intimidating, and more comfortable for patients.

In addition to the comfort that comes with familiarity, the office environment offers distractions that lessen the perception and feeling of pain, and the small-diameter hysteroscopes that are available to us today are no larger than a Pipelle curette and can usually be guided easily through the cervix without dilation, paracervical blocks, or the use of a tenaculum. A simple diagnostic hysteroscopy takes, on average, 5 minutes or less and is extremely well tolerated. It is less painful than an endometrial biopsy.

Patients are often interested in watching the video monitor during a hysteroscopic procedure. Their understanding and comfort level are greater when they can see the findings—can see in living color, for instance, what polyps, fibroids, or intrauterine adhesions are.

Of equal or more importance, hysteroscopy provides a focused view that has significant and measurable clinical benefits.

Ob.gyns. are more attuned to ultrasound; it's readily available, and the global view of the pelvis, uterus, and adnexa that it provides is often viewed as adequate. Saline infusion sonography has certainly improved diagnostic accuracy.

Hysteroscopy, however, offers a more focused view and gives us the ability to investigate and to do a targeted biopsy under direct vision. It simply provides for greater accuracy and more thorough care. Hysteroscopy should be viewed as complementary to ultrasound rather than as an alternative.

Hysteroscopy is the standard for evaluating abnormal uterine bleeding (AUB), a problem that affects more than 10 million women a year and is the reason for 25% of all gynecologic clinic visits.

Although endometrial biopsy is effective for diagnosing diffuse disease such as hyperplasia and carcinoma, it often misses focal lesions like endometrial polyps and fibroids, which are common causes of AUB.

Hysteroscopy should be considered in all patients who require an endometrial biopsy. It has been shown to have a sensitivity of 100% and a specificity of 95% in evaluating the uterine cavity.

It allows us both to diagnose more accurately and often to “see and treat” at the same time, avoiding the courses of unsuccessful hormonal therapy and multiple visits and procedures that too often result from a reliance on endometrial biopsy and ultrasound alone.

Office cystoscopy is a routine part of urologists' practice. With hysteroscopy, we have the technology and capability as ob.gyns. to similarly diagnose and treat common problems in a cost-effective, readily acceptable way. We must more seriously ask ourselves, why not?

Are our reasons not to embrace hysteroscopy really good enough?

Better Fits for a New Era

Ob.gyns. are often at a loss to explain why they seem to be working harder and harder while not getting anywhere, or while losing control, income, and/or the gratification of strong physician-patient relationships.

In a 2004 survey of approximately 830 District III ob.gyns., 64% reported symptoms of burnout; 16% wanted to quit medicine, and 40% said they planned to retire early. To maintain income or prevent a significant decrease in earnings, many had increased patient volume by 20%–30%.

Part of the challenge we face stems from declining reimbursement and the loss of entrepreneurship that often comes with larger group practices. But we also have an inefficient specialty. Many of us leave our offices for labor and delivery and for long OR cases that are unpredictable, that challenge the flow and efficiency of our office practices and the stability of our family lives, and that bring us reimbursement rates that do not account for waiting and time lost between cases. Often the reimbursement we receive when we are away from the office will not cover the cost of office overhead.

This is something we ought to analyze now. Depending on our professional interests, personal needs, and surgical and labor/delivery volumes, such a mix may be gratifying and completely acceptable, or it may be taxing, inefficient, and a cause of burnout.

An office-based ob.gyn. model of care can give us greater control of our practice, our scheduling, our patient relationships, and our lifestyle. Given the elimination of unproductive time, and the fact that professional fees remain the same regardless of setting and that facility fees go to the physician, we can also increase our reimbursement.

Substantial time and financial savings, moreover, are passed on to patients and payers. There is no wasted time: no separate office visits, for instance, for preoperative histories and physicals. When it comes to procedures, patients can arrive 10-30 minutes beforehand and leave in less than 30 minutes. In many cases a patient will be responsible for the cost of an office visit copay, compared with a large deductible and percentage of hospital costs.

I recently saw an interview with Warren Buffett in which he was asked why he is so successful in choosing investments. How was he able to predict the future? He replied that he could not predict the future, but he could recognize what was becoming obsolete. The era in which the model of care relied on a single ob.gyn. who could provide equally competent general primary care, obstetrical care, and the full spectrum of gynecologic surgery to the patient is rapidly becoming obsolete.

The specialty of ob.gyn. is destined to change. Many of us eventually will need to discover and carve out or fine-tune our roles. Today's generalist model of ob.gyn. will evolve into three components in the future: the office-based ob.gyn., the hospital laborist, and the pelvic surgeon.

Greatest in number will be the office-based ob.gyns. who provide well-woman primary care, office-based obstetrics (prenatal care), and a range of office-based procedures, from hysteroscopy and endometrial ablations to incontinence procedures, ultrasound, IUDs, cystoscopy, LEEP cones, and perhaps some “lifestyle” procedures such as laser hair reduction and varicose vein treatment. Considering the demand for such services, they likely will make up about 70% of the specialty.

The ability to have one office, fewer partners, no hospital responsibilities, and control over one's schedule can provide a career that is interesting and rewarding.

Ob.gyn. laborists will be modeled after internal medicine “hospitalists,” and will handle routine deliveries and inpatient obstetrical management. The laborist will work a certain number of shifts each month and will have enough time to be able to balance his or her personal and professional life.

Pelvic surgeons will perform laparoscopy, operative hysteroscopy, and abdominal, vaginal, and robotic surgery. They will provide women with state-of-the-art surgical care and will not have to balance surgery with primary care.

Skills and Set-Up

Ob.gyns. who are performing endometrial biopsies and inserting IUDs are more than capable of doing diagnostic and minor operative hysteroscopy in the office.

The average ob.gyn., in fact, will be competent with the basic hysteroscopic technique for diagnosis after just two to five cases, and the skills honed by doing office diagnostic hysteroscopy will often lay the foundation for adding operative procedures for which there is growing demand, such as hysteroscopic sterilization and global endometrial ablation.

A 2002 survey of women found that sterilization is the most popular method of contraception (favored by 28%), and that women today rarely favor a tubal ligation. Since it has been on the market, the Essure procedure has had successful placement rates of more than 96%.

Hysteroscopic sterilization and global endometrial ablation are both safe and effective for the general ob.gyn. to perform in the office—and just as capably as the best gynecologic surgeon—if he or she is credentialed in the procedure and first has experience and comfort with the procedure in the hospital setting. As a transition, the office setting can be simulated in the OR, with the office staff brought in to observe and prepare for assisting, for instance, and implementing various pain management strategies. The office staff can also learn how to clean and care for the equipment.

Many physicians wonder what will happen if they are unable to complete a procedure in the office. Attempts will inevitably sometimes fail because of access problems, patient intolerance, equipment failure, or a complication. But with experience and proper patient selection, this will rarely happen. And if it does—if you're having some difficulty with the ablation set-up, for instance—keep in mind that it is only an office visit, and that the patient can be rescheduled for the operating room.

It is not necessary to remodel your office or have a “procedure room.” A normal exam room will almost always suffice for diagnostic and simple operative hysteroscopic procedures. Increasingly, equipment is reasonably priced and companies are able to work with ob.gyns. on favorable leasing arrangements. This has taken away the hurdle of price; in fact, one hysteroscopy procedure a week will pay for the equipment.

The reimbursement issues are also favorable. Office hysteroscopy with biopsy is reimbursed at the same rate in the office as in the OR, and in 2005 global codes were approved for hysteroscopic sterilization and endometrial ablation—another development that makes the investment in hysteroscopy equipment a financially sound decision.

Preparing for office-based procedures takes initiative: Anesthesia guidelines and requirements for facility maintenance must be learned, for instance, and a policy and procedures manual that includes protocols for managing complications must be developed.

There is an unappreciated amount of training support, however—both for technical procedural training and for the range of logistical issues—to be had from experienced colleagues, professional societies, and industry. Ob.gyns. who enjoy procedures are better positioned than ever before to take advantage of it.

Diagnostic hysteroscopy with a small hysteroscope is less painful than an endometrial biopsy. Such a hysteroscope is smaller than an IUD (left).

A typical diagnostic hysteroscopy tray for in-office procedures includes a small hysteroscope and sheath, an os finder, and a single-tooth tenaculum. Photos courtesy Dr. James B. Presthus

It is not necessary to remodel your office. A normal exam room will almost always suffice for diagnostic and simple operative hysteroscopic procedures. Courtesy Dr. James B. Presthus

In-Office Surgery Can Boost Practice

Given the constant threat of falling reimbursement, ob.gyns. throughout the country are exercising options on how to maintain a successful practice. For some, introducing new treatments has proved successful. We are all well aware of gynecologists who get involved in various aesthetic techniques and plastic procedures. However, for others, this option represents a marked departure from their practice profile.

It would appear that the introduction of in-office gynecologic surgery will offer many ob.gyns. the opportunity to add value to their practice, yet stay within the limits of the procedures they were trained to perform while in residency—that is, within an ob.gyn.'s “comfort zone.”

A second advantage of in-office gynecologic surgery is that it allows the physician to maintain efficiency.

Let's face it: Operating rooms are fraught with delays. Performing surgery within the confines of the office allows the gynecologist to be free of the yoke of OR tardiness.

Finally, procedures may actually be compensated better in the office than in the operating room, whether that OR is in an outpatient surgery center or in a hospital. Examples are hysteroscopic tubal occlusion or endometrial ablation.

I have invited Dr. James B. Presthus, who is currently practicing gynecology at Minnesota Gynecology and Surgery in Edina, Minn., to lead this discussion on office-based surgery. Dr. Presthus is an active member of the American Association of Gynecologic Laparoscopists, the American Urogynecology Association, the International Pelvic Pain Society, and many other professional organizations. He is a clinical professor of obstetrics and gynecology at the University of Minnesota, Minneapolis.

The levels of burnout in our specialty are increasing as too many of us—90% of the 42,000 ob.gyns in the United States—continue to pursue generalist careers.

We attempt to do it all, from primary care to obstetrics to surgery, and are being pulled in too many directions while losing any sense of control in our professional and personal lives.

There are alternatives to the model of being everything to every patient, however, and adopting office-based procedures can be a key component to making changes successfully.

Most of us perform in-office endometrial biopsies, colposcopy with biopsies, LEEP (loop electrosurgical excision procedures), and IUD insertions. Yet it is estimated that fewer than 30% of ob.gyns. do appreciable hysteroscopy in any setting, and fewer than 5%–10% do office hysteroscopy.

Many of us believe that office-based procedures are potentially dangerous and that they are painful and will not be tolerated by patients.

We argue against an increased level of office-based procedures on the premise that the equipment costs too much, the required skill level is too high, we don't see enough patients who are candidates for these procedures, we don't have procedure rooms, or the integration of more procedures into our existing schedules is just too complex or difficult.

Increasingly, these beliefs are countered by contrasting realities: more medical knowledge, more training opportunities, more reasonably priced equipment, and appropriate third-party reimbursement for office-based hysteroscopic procedures.

These realities have made hysteroscopy the base technology for a successful gynecology-focused office-based practice.

With commitment, those ob.gyns. who enjoy doing procedures can build successful office-based practices by offering a full spectrum of diagnostic and minor operative hysteroscopic procedures that are just as safe, tolerable, and effective as they are in the hospital.

In doing so, they can provide more thorough and efficient care in a more comfortable, familiar, and cost-effective setting.

Less Anesthesia, More Accuracy

The most significant misconception among ob.gyns.–and probably the largest barrier to wider use of in-office hysteroscopy—relates to pain.

The perceptions are fueled by the operating room experience, where intravenous sedation causes patients to lose inhibition and the ability to follow directions and control their actions.

Patients perceive touch and other stimuli as pain, and the loss of inhibition often escalates as the anesthesist applies even more IV sedation in an effort to make them more comfortable.

This is often perceived as intolerance for pain, and ob.gyns. leave the operating room thinking that if patients cannot tolerate hysteroscopy in that setting, they will certainly not tolerate it in the office.

In reality, patients can tolerate procedures very well—and with less anesthesia—if they know what to expect and if they're in control of their bodies and the overall situation. This happens more readily in the office environment, which is familiar, less intimidating, and more comfortable for patients.

In addition to the comfort that comes with familiarity, the office environment offers distractions that lessen the perception and feeling of pain, and the small-diameter hysteroscopes that are available to us today are no larger than a Pipelle curette and can usually be guided easily through the cervix without dilation, paracervical blocks, or the use of a tenaculum. A simple diagnostic hysteroscopy takes, on average, 5 minutes or less and is extremely well tolerated. It is less painful than an endometrial biopsy.

Patients are often interested in watching the video monitor during a hysteroscopic procedure. Their understanding and comfort level are greater when they can see the findings—can see in living color, for instance, what polyps, fibroids, or intrauterine adhesions are.

Of equal or more importance, hysteroscopy provides a focused view that has significant and measurable clinical benefits.

Ob.gyns. are more attuned to ultrasound; it's readily available, and the global view of the pelvis, uterus, and adnexa that it provides is often viewed as adequate. Saline infusion sonography has certainly improved diagnostic accuracy.

Hysteroscopy, however, offers a more focused view and gives us the ability to investigate and to do a targeted biopsy under direct vision. It simply provides for greater accuracy and more thorough care. Hysteroscopy should be viewed as complementary to ultrasound rather than as an alternative.

Hysteroscopy is the standard for evaluating abnormal uterine bleeding (AUB), a problem that affects more than 10 million women a year and is the reason for 25% of all gynecologic clinic visits.

Although endometrial biopsy is effective for diagnosing diffuse disease such as hyperplasia and carcinoma, it often misses focal lesions like endometrial polyps and fibroids, which are common causes of AUB.

Hysteroscopy should be considered in all patients who require an endometrial biopsy. It has been shown to have a sensitivity of 100% and a specificity of 95% in evaluating the uterine cavity.

It allows us both to diagnose more accurately and often to “see and treat” at the same time, avoiding the courses of unsuccessful hormonal therapy and multiple visits and procedures that too often result from a reliance on endometrial biopsy and ultrasound alone.

Office cystoscopy is a routine part of urologists' practice. With hysteroscopy, we have the technology and capability as ob.gyns. to similarly diagnose and treat common problems in a cost-effective, readily acceptable way. We must more seriously ask ourselves, why not?

Are our reasons not to embrace hysteroscopy really good enough?

Better Fits for a New Era

Ob.gyns. are often at a loss to explain why they seem to be working harder and harder while not getting anywhere, or while losing control, income, and/or the gratification of strong physician-patient relationships.

In a 2004 survey of approximately 830 District III ob.gyns., 64% reported symptoms of burnout; 16% wanted to quit medicine, and 40% said they planned to retire early. To maintain income or prevent a significant decrease in earnings, many had increased patient volume by 20%–30%.

Part of the challenge we face stems from declining reimbursement and the loss of entrepreneurship that often comes with larger group practices. But we also have an inefficient specialty. Many of us leave our offices for labor and delivery and for long OR cases that are unpredictable, that challenge the flow and efficiency of our office practices and the stability of our family lives, and that bring us reimbursement rates that do not account for waiting and time lost between cases. Often the reimbursement we receive when we are away from the office will not cover the cost of office overhead.

This is something we ought to analyze now. Depending on our professional interests, personal needs, and surgical and labor/delivery volumes, such a mix may be gratifying and completely acceptable, or it may be taxing, inefficient, and a cause of burnout.

An office-based ob.gyn. model of care can give us greater control of our practice, our scheduling, our patient relationships, and our lifestyle. Given the elimination of unproductive time, and the fact that professional fees remain the same regardless of setting and that facility fees go to the physician, we can also increase our reimbursement.

Substantial time and financial savings, moreover, are passed on to patients and payers. There is no wasted time: no separate office visits, for instance, for preoperative histories and physicals. When it comes to procedures, patients can arrive 10-30 minutes beforehand and leave in less than 30 minutes. In many cases a patient will be responsible for the cost of an office visit copay, compared with a large deductible and percentage of hospital costs.

I recently saw an interview with Warren Buffett in which he was asked why he is so successful in choosing investments. How was he able to predict the future? He replied that he could not predict the future, but he could recognize what was becoming obsolete. The era in which the model of care relied on a single ob.gyn. who could provide equally competent general primary care, obstetrical care, and the full spectrum of gynecologic surgery to the patient is rapidly becoming obsolete.

The specialty of ob.gyn. is destined to change. Many of us eventually will need to discover and carve out or fine-tune our roles. Today's generalist model of ob.gyn. will evolve into three components in the future: the office-based ob.gyn., the hospital laborist, and the pelvic surgeon.

Greatest in number will be the office-based ob.gyns. who provide well-woman primary care, office-based obstetrics (prenatal care), and a range of office-based procedures, from hysteroscopy and endometrial ablations to incontinence procedures, ultrasound, IUDs, cystoscopy, LEEP cones, and perhaps some “lifestyle” procedures such as laser hair reduction and varicose vein treatment. Considering the demand for such services, they likely will make up about 70% of the specialty.

The ability to have one office, fewer partners, no hospital responsibilities, and control over one's schedule can provide a career that is interesting and rewarding.

Ob.gyn. laborists will be modeled after internal medicine “hospitalists,” and will handle routine deliveries and inpatient obstetrical management. The laborist will work a certain number of shifts each month and will have enough time to be able to balance his or her personal and professional life.

Pelvic surgeons will perform laparoscopy, operative hysteroscopy, and abdominal, vaginal, and robotic surgery. They will provide women with state-of-the-art surgical care and will not have to balance surgery with primary care.

Skills and Set-Up

Ob.gyns. who are performing endometrial biopsies and inserting IUDs are more than capable of doing diagnostic and minor operative hysteroscopy in the office.

The average ob.gyn., in fact, will be competent with the basic hysteroscopic technique for diagnosis after just two to five cases, and the skills honed by doing office diagnostic hysteroscopy will often lay the foundation for adding operative procedures for which there is growing demand, such as hysteroscopic sterilization and global endometrial ablation.

A 2002 survey of women found that sterilization is the most popular method of contraception (favored by 28%), and that women today rarely favor a tubal ligation. Since it has been on the market, the Essure procedure has had successful placement rates of more than 96%.

Hysteroscopic sterilization and global endometrial ablation are both safe and effective for the general ob.gyn. to perform in the office—and just as capably as the best gynecologic surgeon—if he or she is credentialed in the procedure and first has experience and comfort with the procedure in the hospital setting. As a transition, the office setting can be simulated in the OR, with the office staff brought in to observe and prepare for assisting, for instance, and implementing various pain management strategies. The office staff can also learn how to clean and care for the equipment.

Many physicians wonder what will happen if they are unable to complete a procedure in the office. Attempts will inevitably sometimes fail because of access problems, patient intolerance, equipment failure, or a complication. But with experience and proper patient selection, this will rarely happen. And if it does—if you're having some difficulty with the ablation set-up, for instance—keep in mind that it is only an office visit, and that the patient can be rescheduled for the operating room.

It is not necessary to remodel your office or have a “procedure room.” A normal exam room will almost always suffice for diagnostic and simple operative hysteroscopic procedures. Increasingly, equipment is reasonably priced and companies are able to work with ob.gyns. on favorable leasing arrangements. This has taken away the hurdle of price; in fact, one hysteroscopy procedure a week will pay for the equipment.

The reimbursement issues are also favorable. Office hysteroscopy with biopsy is reimbursed at the same rate in the office as in the OR, and in 2005 global codes were approved for hysteroscopic sterilization and endometrial ablation—another development that makes the investment in hysteroscopy equipment a financially sound decision.

Preparing for office-based procedures takes initiative: Anesthesia guidelines and requirements for facility maintenance must be learned, for instance, and a policy and procedures manual that includes protocols for managing complications must be developed.

There is an unappreciated amount of training support, however—both for technical procedural training and for the range of logistical issues—to be had from experienced colleagues, professional societies, and industry. Ob.gyns. who enjoy procedures are better positioned than ever before to take advantage of it.

Diagnostic hysteroscopy with a small hysteroscope is less painful than an endometrial biopsy. Such a hysteroscope is smaller than an IUD (left).

A typical diagnostic hysteroscopy tray for in-office procedures includes a small hysteroscope and sheath, an os finder, and a single-tooth tenaculum. Photos courtesy Dr. James B. Presthus

It is not necessary to remodel your office. A normal exam room will almost always suffice for diagnostic and simple operative hysteroscopic procedures. Courtesy Dr. James B. Presthus

In-Office Surgery Can Boost Practice

Given the constant threat of falling reimbursement, ob.gyns. throughout the country are exercising options on how to maintain a successful practice. For some, introducing new treatments has proved successful. We are all well aware of gynecologists who get involved in various aesthetic techniques and plastic procedures. However, for others, this option represents a marked departure from their practice profile.

It would appear that the introduction of in-office gynecologic surgery will offer many ob.gyns. the opportunity to add value to their practice, yet stay within the limits of the procedures they were trained to perform while in residency—that is, within an ob.gyn.'s “comfort zone.”

A second advantage of in-office gynecologic surgery is that it allows the physician to maintain efficiency.

Let's face it: Operating rooms are fraught with delays. Performing surgery within the confines of the office allows the gynecologist to be free of the yoke of OR tardiness.

Finally, procedures may actually be compensated better in the office than in the operating room, whether that OR is in an outpatient surgery center or in a hospital. Examples are hysteroscopic tubal occlusion or endometrial ablation.

I have invited Dr. James B. Presthus, who is currently practicing gynecology at Minnesota Gynecology and Surgery in Edina, Minn., to lead this discussion on office-based surgery. Dr. Presthus is an active member of the American Association of Gynecologic Laparoscopists, the American Urogynecology Association, the International Pelvic Pain Society, and many other professional organizations. He is a clinical professor of obstetrics and gynecology at the University of Minnesota, Minneapolis.

The levels of burnout in our specialty are increasing as too many of us—90% of the 42,000 ob.gyns in the United States—continue to pursue generalist careers.

We attempt to do it all, from primary care to obstetrics to surgery, and are being pulled in too many directions while losing any sense of control in our professional and personal lives.

There are alternatives to the model of being everything to every patient, however, and adopting office-based procedures can be a key component to making changes successfully.

Most of us perform in-office endometrial biopsies, colposcopy with biopsies, LEEP (loop electrosurgical excision procedures), and IUD insertions. Yet it is estimated that fewer than 30% of ob.gyns. do appreciable hysteroscopy in any setting, and fewer than 5%–10% do office hysteroscopy.

Many of us believe that office-based procedures are potentially dangerous and that they are painful and will not be tolerated by patients.

We argue against an increased level of office-based procedures on the premise that the equipment costs too much, the required skill level is too high, we don't see enough patients who are candidates for these procedures, we don't have procedure rooms, or the integration of more procedures into our existing schedules is just too complex or difficult.

Increasingly, these beliefs are countered by contrasting realities: more medical knowledge, more training opportunities, more reasonably priced equipment, and appropriate third-party reimbursement for office-based hysteroscopic procedures.

These realities have made hysteroscopy the base technology for a successful gynecology-focused office-based practice.

With commitment, those ob.gyns. who enjoy doing procedures can build successful office-based practices by offering a full spectrum of diagnostic and minor operative hysteroscopic procedures that are just as safe, tolerable, and effective as they are in the hospital.

In doing so, they can provide more thorough and efficient care in a more comfortable, familiar, and cost-effective setting.

Less Anesthesia, More Accuracy

The most significant misconception among ob.gyns.–and probably the largest barrier to wider use of in-office hysteroscopy—relates to pain.

The perceptions are fueled by the operating room experience, where intravenous sedation causes patients to lose inhibition and the ability to follow directions and control their actions.

Patients perceive touch and other stimuli as pain, and the loss of inhibition often escalates as the anesthesist applies even more IV sedation in an effort to make them more comfortable.

This is often perceived as intolerance for pain, and ob.gyns. leave the operating room thinking that if patients cannot tolerate hysteroscopy in that setting, they will certainly not tolerate it in the office.

In reality, patients can tolerate procedures very well—and with less anesthesia—if they know what to expect and if they're in control of their bodies and the overall situation. This happens more readily in the office environment, which is familiar, less intimidating, and more comfortable for patients.

In addition to the comfort that comes with familiarity, the office environment offers distractions that lessen the perception and feeling of pain, and the small-diameter hysteroscopes that are available to us today are no larger than a Pipelle curette and can usually be guided easily through the cervix without dilation, paracervical blocks, or the use of a tenaculum. A simple diagnostic hysteroscopy takes, on average, 5 minutes or less and is extremely well tolerated. It is less painful than an endometrial biopsy.

Patients are often interested in watching the video monitor during a hysteroscopic procedure. Their understanding and comfort level are greater when they can see the findings—can see in living color, for instance, what polyps, fibroids, or intrauterine adhesions are.

Of equal or more importance, hysteroscopy provides a focused view that has significant and measurable clinical benefits.

Ob.gyns. are more attuned to ultrasound; it's readily available, and the global view of the pelvis, uterus, and adnexa that it provides is often viewed as adequate. Saline infusion sonography has certainly improved diagnostic accuracy.

Hysteroscopy, however, offers a more focused view and gives us the ability to investigate and to do a targeted biopsy under direct vision. It simply provides for greater accuracy and more thorough care. Hysteroscopy should be viewed as complementary to ultrasound rather than as an alternative.

Hysteroscopy is the standard for evaluating abnormal uterine bleeding (AUB), a problem that affects more than 10 million women a year and is the reason for 25% of all gynecologic clinic visits.

Although endometrial biopsy is effective for diagnosing diffuse disease such as hyperplasia and carcinoma, it often misses focal lesions like endometrial polyps and fibroids, which are common causes of AUB.

Hysteroscopy should be considered in all patients who require an endometrial biopsy. It has been shown to have a sensitivity of 100% and a specificity of 95% in evaluating the uterine cavity.

It allows us both to diagnose more accurately and often to “see and treat” at the same time, avoiding the courses of unsuccessful hormonal therapy and multiple visits and procedures that too often result from a reliance on endometrial biopsy and ultrasound alone.

Office cystoscopy is a routine part of urologists' practice. With hysteroscopy, we have the technology and capability as ob.gyns. to similarly diagnose and treat common problems in a cost-effective, readily acceptable way. We must more seriously ask ourselves, why not?

Are our reasons not to embrace hysteroscopy really good enough?

Better Fits for a New Era

Ob.gyns. are often at a loss to explain why they seem to be working harder and harder while not getting anywhere, or while losing control, income, and/or the gratification of strong physician-patient relationships.

In a 2004 survey of approximately 830 District III ob.gyns., 64% reported symptoms of burnout; 16% wanted to quit medicine, and 40% said they planned to retire early. To maintain income or prevent a significant decrease in earnings, many had increased patient volume by 20%–30%.

Part of the challenge we face stems from declining reimbursement and the loss of entrepreneurship that often comes with larger group practices. But we also have an inefficient specialty. Many of us leave our offices for labor and delivery and for long OR cases that are unpredictable, that challenge the flow and efficiency of our office practices and the stability of our family lives, and that bring us reimbursement rates that do not account for waiting and time lost between cases. Often the reimbursement we receive when we are away from the office will not cover the cost of office overhead.

This is something we ought to analyze now. Depending on our professional interests, personal needs, and surgical and labor/delivery volumes, such a mix may be gratifying and completely acceptable, or it may be taxing, inefficient, and a cause of burnout.

An office-based ob.gyn. model of care can give us greater control of our practice, our scheduling, our patient relationships, and our lifestyle. Given the elimination of unproductive time, and the fact that professional fees remain the same regardless of setting and that facility fees go to the physician, we can also increase our reimbursement.

Substantial time and financial savings, moreover, are passed on to patients and payers. There is no wasted time: no separate office visits, for instance, for preoperative histories and physicals. When it comes to procedures, patients can arrive 10-30 minutes beforehand and leave in less than 30 minutes. In many cases a patient will be responsible for the cost of an office visit copay, compared with a large deductible and percentage of hospital costs.

I recently saw an interview with Warren Buffett in which he was asked why he is so successful in choosing investments. How was he able to predict the future? He replied that he could not predict the future, but he could recognize what was becoming obsolete. The era in which the model of care relied on a single ob.gyn. who could provide equally competent general primary care, obstetrical care, and the full spectrum of gynecologic surgery to the patient is rapidly becoming obsolete.

The specialty of ob.gyn. is destined to change. Many of us eventually will need to discover and carve out or fine-tune our roles. Today's generalist model of ob.gyn. will evolve into three components in the future: the office-based ob.gyn., the hospital laborist, and the pelvic surgeon.

Greatest in number will be the office-based ob.gyns. who provide well-woman primary care, office-based obstetrics (prenatal care), and a range of office-based procedures, from hysteroscopy and endometrial ablations to incontinence procedures, ultrasound, IUDs, cystoscopy, LEEP cones, and perhaps some “lifestyle” procedures such as laser hair reduction and varicose vein treatment. Considering the demand for such services, they likely will make up about 70% of the specialty.

The ability to have one office, fewer partners, no hospital responsibilities, and control over one's schedule can provide a career that is interesting and rewarding.

Ob.gyn. laborists will be modeled after internal medicine “hospitalists,” and will handle routine deliveries and inpatient obstetrical management. The laborist will work a certain number of shifts each month and will have enough time to be able to balance his or her personal and professional life.

Pelvic surgeons will perform laparoscopy, operative hysteroscopy, and abdominal, vaginal, and robotic surgery. They will provide women with state-of-the-art surgical care and will not have to balance surgery with primary care.

Skills and Set-Up

Ob.gyns. who are performing endometrial biopsies and inserting IUDs are more than capable of doing diagnostic and minor operative hysteroscopy in the office.

The average ob.gyn., in fact, will be competent with the basic hysteroscopic technique for diagnosis after just two to five cases, and the skills honed by doing office diagnostic hysteroscopy will often lay the foundation for adding operative procedures for which there is growing demand, such as hysteroscopic sterilization and global endometrial ablation.

A 2002 survey of women found that sterilization is the most popular method of contraception (favored by 28%), and that women today rarely favor a tubal ligation. Since it has been on the market, the Essure procedure has had successful placement rates of more than 96%.

Hysteroscopic sterilization and global endometrial ablation are both safe and effective for the general ob.gyn. to perform in the office—and just as capably as the best gynecologic surgeon—if he or she is credentialed in the procedure and first has experience and comfort with the procedure in the hospital setting. As a transition, the office setting can be simulated in the OR, with the office staff brought in to observe and prepare for assisting, for instance, and implementing various pain management strategies. The office staff can also learn how to clean and care for the equipment.

Many physicians wonder what will happen if they are unable to complete a procedure in the office. Attempts will inevitably sometimes fail because of access problems, patient intolerance, equipment failure, or a complication. But with experience and proper patient selection, this will rarely happen. And if it does—if you're having some difficulty with the ablation set-up, for instance—keep in mind that it is only an office visit, and that the patient can be rescheduled for the operating room.

It is not necessary to remodel your office or have a “procedure room.” A normal exam room will almost always suffice for diagnostic and simple operative hysteroscopic procedures. Increasingly, equipment is reasonably priced and companies are able to work with ob.gyns. on favorable leasing arrangements. This has taken away the hurdle of price; in fact, one hysteroscopy procedure a week will pay for the equipment.

The reimbursement issues are also favorable. Office hysteroscopy with biopsy is reimbursed at the same rate in the office as in the OR, and in 2005 global codes were approved for hysteroscopic sterilization and endometrial ablation—another development that makes the investment in hysteroscopy equipment a financially sound decision.

Preparing for office-based procedures takes initiative: Anesthesia guidelines and requirements for facility maintenance must be learned, for instance, and a policy and procedures manual that includes protocols for managing complications must be developed.

There is an unappreciated amount of training support, however—both for technical procedural training and for the range of logistical issues—to be had from experienced colleagues, professional societies, and industry. Ob.gyns. who enjoy procedures are better positioned than ever before to take advantage of it.

Diagnostic hysteroscopy with a small hysteroscope is less painful than an endometrial biopsy. Such a hysteroscope is smaller than an IUD (left).

A typical diagnostic hysteroscopy tray for in-office procedures includes a small hysteroscope and sheath, an os finder, and a single-tooth tenaculum. Photos courtesy Dr. James B. Presthus

It is not necessary to remodel your office. A normal exam room will almost always suffice for diagnostic and simple operative hysteroscopic procedures. Courtesy Dr. James B. Presthus

In-Office Surgery Can Boost Practice

Given the constant threat of falling reimbursement, ob.gyns. throughout the country are exercising options on how to maintain a successful practice. For some, introducing new treatments has proved successful. We are all well aware of gynecologists who get involved in various aesthetic techniques and plastic procedures. However, for others, this option represents a marked departure from their practice profile.

It would appear that the introduction of in-office gynecologic surgery will offer many ob.gyns. the opportunity to add value to their practice, yet stay within the limits of the procedures they were trained to perform while in residency—that is, within an ob.gyn.'s “comfort zone.”

A second advantage of in-office gynecologic surgery is that it allows the physician to maintain efficiency.

Let's face it: Operating rooms are fraught with delays. Performing surgery within the confines of the office allows the gynecologist to be free of the yoke of OR tardiness.

Finally, procedures may actually be compensated better in the office than in the operating room, whether that OR is in an outpatient surgery center or in a hospital. Examples are hysteroscopic tubal occlusion or endometrial ablation.

I have invited Dr. James B. Presthus, who is currently practicing gynecology at Minnesota Gynecology and Surgery in Edina, Minn., to lead this discussion on office-based surgery. Dr. Presthus is an active member of the American Association of Gynecologic Laparoscopists, the American Urogynecology Association, the International Pelvic Pain Society, and many other professional organizations. He is a clinical professor of obstetrics and gynecology at the University of Minnesota, Minneapolis.

The array-CGH test, which is already being used postnatally, will give obstetricians, geneticists, and their patients the opportunity in the prenatal setting to detect significantly more and smaller changes in the amount of chromosomal material present in individuals—and in significantly less time than a standard chromosome karyotype would take.

It may someday take the place of our standard techniques for cytogenetic analysis, but for now, it is a valuable addition to the available diagnostic tests.

Advances Over FISH

The technology, which has also been called chromosomal microarray, was first used to analyze gains and losses in chromosomal material in tumors and tumor cell lines. It is now a valuable tool in the postnatal testing of individuals with birth defects.

Between one-half and two-thirds of children with serious developmental abnormalities go undiagnosed and have a normal karyotype, so from a postnatal perspective, this new test has been welcomed at Johns Hopkins University and the Kennedy Krieger Institute, both in Baltimore, as well as at other institutions. Having a diagnosis facilitates the most appropriate therapy and allows parents to plan for future pregnancies and possible prenatal testing.

Yet it is the prenatal period for which array-CGH may have an even greater impact. Phenotypic features are not as apparent in the womb as at birth, making it more difficult to target testing with technology like rapid fluorescent in situ hybridization (FISH).

Along with standard karyotype analysis, the FISH technique has been the mainstay of cytogenetic analysis. It provides a targeted look at areas of the karyotype that are known to be associated with disease as a result of either the duplication or deletion of genetic material. In other words, it detects gains and losses in chromosomal material for just one or a few chromosome regions at a time.

Performing array-CGH is like doing FISH hundreds of times at once. Array-CGH testing may target the same chromosomal regions (and thus similar disorders) as a series of FISH tests, but array-CGH will target these regions at a much higher resolution, enabling the detection of much smaller deletions and duplications; it can also assess many regions associated with genetic disorders in a single test.

If we see on a prenatal ultrasound that a fetus has cardiac problems, for example, we might suspect the DiGeorge syndrome. The obstetrician today would probably perform an amniocentesis and order both a karyotype and FISH with a specific probe for the DiGeorge syndrome, which we know is caused by a deletion on chromosome 22, just as he or she would do in the postnatal period for a child with the syndrome's more obvious phenotypic features.

In the near future, the obstetrician facing this prenatal situation will likely proceed differently than he or she would in the postnatal period. The obstetrician will use array-CGH instead of FISH in order to cast a wider net—one that can catch a deletion on chromosome 22, as well as other possible deletions which may cause the heart defect.

Right now, the available array-CGH platforms can detect more than 40 syndromic chromosomal disorders. Just as with FISH, a normal result rules out only those conditions that correspond to the deletions or duplications that are covered on the array.

How Array-CGH Works

The technique involves labeling the patient's DNA in one fluorescent dye, labeling DNA from a normal control with a different fluorescent dye, allowing the DNA from both to mix, and then applying the mixture to a slide that contains small segments of DNA from known chromosomal regions.

The slide serves as the platform or the array. The mixture of the patient's DNA and the normal control DNA is allowed to match up, or hybridize, with the complementary DNA segments on the slide.

A scanner then reads the intensities of the two different dyes, determining their relative strength at each of the DNA spots on the array. If a patient has less DNA in a specified region of the genome—a deletion of chromosomal material—then the color of the control sample will be stronger at that point on the array. If a patient has more DNA in this specific region—a duplication of chromosomal material—then the color of the patient's sample will be stronger at that location.

Analysis can be performed on direct chorionic villi or amniotic fluid, or alternatively on cultured cells. For direct analysis, it might be necessary to amplify the amount of DNA obtained before running it on an array. In this case, it is essential that the amplification is uniform and does not introduce any bias.

Although many laboratories are using cultured cells at this point, some studies are demonstrating the feasibility of relying on uncultured samples, and ultimately, this is the direction in which we're heading. Direct testing of fetal DNA will save time and give us rapid results.

The Limitations of Array-CGH

Unlike standard karyotyping, array-CGH cannot detect defects in which the total amount of chromosomal material is unchanged. The test cannot, for instance, detect balance rearrangements, such as balanced reciprocal translocations, balanced Robertsonian translocations, and inversions.

In a couple with multiple miscarriages, a karyotype is still the appropriate test to perform on the parents' blood because a balanced rearrangement is what you would be looking for. You would not request array-CGH because balanced rearrangements are not detectable with this technique. On the other hand, array-CGH could be very useful on the products of conception from a miscarriage because very small deletions and duplications could be found.

Array-CGH also cannot detect point mutations, or small changes in the genes, like those that cause hemophilia or sickle cell disease. It is designed to detect the syndromes caused by duplications or deletions of larger amounts of chromosomal material. And it will not detect abnormalities that are not covered by the array.

Chromosomal mosaicism, in which only some cells show a particular abnormality, may or may not be more readily detected by array-CGH than by standard techniques.

On one hand, mosaicism may be more readily detected with array-CGH than with standard karyotype analysis because abnormal cells often do not divide as well and may be lost during the culture process that is part of the standard karyotyping methodology. On the other hand, experts believe that array-CGH may not detect mosaicism below a certain level—below the level, some say, at which the abnormality affects fewer than 15%–30% of cells.

Array-CGH will also inevitably detect normal variants (benign duplications and deletions that are not associated with any abnormal phenotype). Some variants will be difficult to explain. This has been true for karyotyping as well, and just as we have in the past, we will want to minimize parents' anxiety over the unknowns.

When we find variants of uncertain significance, we will turn to the parents, checking their blood samples for the same losses or gains of chromosomal material.

The Near Future

The clinicians and cytogeneticists who are using and offering array-CGH are on a learning curve. Experts seem to have been successful in ensuring that the test works for the disorders that are covered; there is an enormous amount of information and data being shared by centers and labs on what variants are associated with the normal phenotype, and on other issues as well.

At Johns Hopkins University and the Kennedy Krieger Institute, we have postnatal experience to draw upon as we bring array-CGH into the prenatal arena. Of the children with developmental delay and dysmorphic features who have had array-CGH, we have been able to give a specific syndromic diagnosis to approximately 5%–8%, depending on the array platform we utilize. In about 12%, we have detected variants that we know—through parental testing and the use of databases—are normal. In a much smaller percentage (3.4%) of these children, we have found variants that we cannot yet explain.

Until we learn more, we plan to limit prenatal array-CGH to cases in which there is a known abnormality on ultrasound, rather than offer the test more broadly as a screening tool for chromosomal abnormalities in high-risk pregnancies. And although we are moving in the postnatal setting toward more of a whole-genome screening, we will use targeted arrays in the prenatal setting.

Within this context—that of ultrasound-detected anomalies and targeted arrays—we can expect that 5%–10% of tests will provide a clear diagnosis.

The question of whether array-CGH could replace a karyotype in prenatal testing is an interesting one. For now, there are too many questions and issues (mosaicism and normal variants, for instance) to do away with karyotyping. We believe the role of array-CGH is to enhance our current approaches to prenatal testing, and in this sense, it is an exciting development.

Figure A shows a hybridized array of >4,200 BAC clones; B, one area enlarged; C, plot for chromosome 1 based on fluorescence ratios (patient vs. control DNA) showing normal copy number. Courtesy Dr. Denise Batista

Prenatal Diagnosis

In our contemporary society, where women and their physicians continue to seek as much information as possible early in their pregnancies, the field of prenatal diagnosis has rapidly become a well-established and central part of obstetrics. Prenatal diagnosis performed in the first trimester has become common practice—a far cry from the days in the not-so-distant past when the ultimate outcome of the fetus was not learned until the day of delivery.

As obstetricians and perinatologists, we benefit from being aware of and fully informed about the evolving technology that continues to move the field of prenatal diagnosis forward. The array of current prenatal diagnostic tools includes both invasive and noninvasive techniques that enable parents to assess the genetic, chromosomal, and biochemical aspects of their fetus considerably before the time of viability.

Parents and their physicians are using this information to guide them in pursuing potential therapeutic applications and interventions or, in some cases, interruption of the pregnancy.

Now there is a new technique called array-based comparative genomic hybridization, or array-CGH, which is entering the prenatal arena with promises of more comprehensive and faster detection capabilities than we now are afforded with the two current “gold standard” techniques: microscopic karyotype analysis and rapid fluorescent in situ hybridization.

Array-CGH is far from perfect in evaluating chromosomal material. It can only detect instances where there is a significant addition or deletion of genetic material. And, of course, it can only evaluate those genes encoded on the array.

As with every other prenatal diagnostic tool developed to date, the future use of this new technique involves many questions, including which variants are normal as opposed to abnormal, the technique's potential role as a screening tool, and other often vexing ambiguities and issues. However, its use in prenatal diagnosis will build upon a body of national experience in the postnatal setting.

To familiarize us with the new technology and discuss its role in prenatal diagnosis, I have invited Dr. Karin J. Blakemore to serve as the guest professor of this month's Master Class.

Dr. Blakemore is the director of maternal-fetal medicine and the Prenatal Genetics Service at Johns Hopkins University School of Medicine in Baltimore—an institution that is gearing up to use array-CGH as part of its armamentarium for prenatal diagnosis.

She is joined by her colleague Denise Batista, Ph.D., who is an assistant professor in the Johns Hopkins department of pathology and codirector of the university's prenatal cytogenetics laboratory. Dr. Batista also serves as the director of the cytogenetics laboratory at the Kennedy Krieger Institute in Baltimore.

Key Points for Array-CGH

▸ Detects: Unbalanced rearrangements, aneuploidy, gains and losses of regions represented in the array.

▸ Won't detect: Balanced rearrangements, point mutations, (possibly) low-level mosaicism.

▸ Pick-up rate: Estimated as 5%–10% from postnatal studies of developmentally delayed/dysmorphic children.

▸ Confirmation: By FISH probes.

▸ Parental studies: Might be necessary to sort out normal variants versus clinically significant changes.

▸ Copy number variants: Might find copy number variants of unknown significance.

▸ Platforms: Several commercial and home-brew arrays available with different genomic coverage.

The array-CGH test, which is already being used postnatally, will give obstetricians, geneticists, and their patients the opportunity in the prenatal setting to detect significantly more and smaller changes in the amount of chromosomal material present in individuals—and in significantly less time than a standard chromosome karyotype would take.

It may someday take the place of our standard techniques for cytogenetic analysis, but for now, it is a valuable addition to the available diagnostic tests.

Advances Over FISH

The technology, which has also been called chromosomal microarray, was first used to analyze gains and losses in chromosomal material in tumors and tumor cell lines. It is now a valuable tool in the postnatal testing of individuals with birth defects.

Between one-half and two-thirds of children with serious developmental abnormalities go undiagnosed and have a normal karyotype, so from a postnatal perspective, this new test has been welcomed at Johns Hopkins University and the Kennedy Krieger Institute, both in Baltimore, as well as at other institutions. Having a diagnosis facilitates the most appropriate therapy and allows parents to plan for future pregnancies and possible prenatal testing.

Yet it is the prenatal period for which array-CGH may have an even greater impact. Phenotypic features are not as apparent in the womb as at birth, making it more difficult to target testing with technology like rapid fluorescent in situ hybridization (FISH).

Along with standard karyotype analysis, the FISH technique has been the mainstay of cytogenetic analysis. It provides a targeted look at areas of the karyotype that are known to be associated with disease as a result of either the duplication or deletion of genetic material. In other words, it detects gains and losses in chromosomal material for just one or a few chromosome regions at a time.

Performing array-CGH is like doing FISH hundreds of times at once. Array-CGH testing may target the same chromosomal regions (and thus similar disorders) as a series of FISH tests, but array-CGH will target these regions at a much higher resolution, enabling the detection of much smaller deletions and duplications; it can also assess many regions associated with genetic disorders in a single test.

If we see on a prenatal ultrasound that a fetus has cardiac problems, for example, we might suspect the DiGeorge syndrome. The obstetrician today would probably perform an amniocentesis and order both a karyotype and FISH with a specific probe for the DiGeorge syndrome, which we know is caused by a deletion on chromosome 22, just as he or she would do in the postnatal period for a child with the syndrome's more obvious phenotypic features.

In the near future, the obstetrician facing this prenatal situation will likely proceed differently than he or she would in the postnatal period. The obstetrician will use array-CGH instead of FISH in order to cast a wider net—one that can catch a deletion on chromosome 22, as well as other possible deletions which may cause the heart defect.

Right now, the available array-CGH platforms can detect more than 40 syndromic chromosomal disorders. Just as with FISH, a normal result rules out only those conditions that correspond to the deletions or duplications that are covered on the array.

How Array-CGH Works

The technique involves labeling the patient's DNA in one fluorescent dye, labeling DNA from a normal control with a different fluorescent dye, allowing the DNA from both to mix, and then applying the mixture to a slide that contains small segments of DNA from known chromosomal regions.

The slide serves as the platform or the array. The mixture of the patient's DNA and the normal control DNA is allowed to match up, or hybridize, with the complementary DNA segments on the slide.

A scanner then reads the intensities of the two different dyes, determining their relative strength at each of the DNA spots on the array. If a patient has less DNA in a specified region of the genome—a deletion of chromosomal material—then the color of the control sample will be stronger at that point on the array. If a patient has more DNA in this specific region—a duplication of chromosomal material—then the color of the patient's sample will be stronger at that location.

Analysis can be performed on direct chorionic villi or amniotic fluid, or alternatively on cultured cells. For direct analysis, it might be necessary to amplify the amount of DNA obtained before running it on an array. In this case, it is essential that the amplification is uniform and does not introduce any bias.

Although many laboratories are using cultured cells at this point, some studies are demonstrating the feasibility of relying on uncultured samples, and ultimately, this is the direction in which we're heading. Direct testing of fetal DNA will save time and give us rapid results.

The Limitations of Array-CGH

Unlike standard karyotyping, array-CGH cannot detect defects in which the total amount of chromosomal material is unchanged. The test cannot, for instance, detect balance rearrangements, such as balanced reciprocal translocations, balanced Robertsonian translocations, and inversions.

In a couple with multiple miscarriages, a karyotype is still the appropriate test to perform on the parents' blood because a balanced rearrangement is what you would be looking for. You would not request array-CGH because balanced rearrangements are not detectable with this technique. On the other hand, array-CGH could be very useful on the products of conception from a miscarriage because very small deletions and duplications could be found.

Array-CGH also cannot detect point mutations, or small changes in the genes, like those that cause hemophilia or sickle cell disease. It is designed to detect the syndromes caused by duplications or deletions of larger amounts of chromosomal material. And it will not detect abnormalities that are not covered by the array.

Chromosomal mosaicism, in which only some cells show a particular abnormality, may or may not be more readily detected by array-CGH than by standard techniques.

On one hand, mosaicism may be more readily detected with array-CGH than with standard karyotype analysis because abnormal cells often do not divide as well and may be lost during the culture process that is part of the standard karyotyping methodology. On the other hand, experts believe that array-CGH may not detect mosaicism below a certain level—below the level, some say, at which the abnormality affects fewer than 15%–30% of cells.

Array-CGH will also inevitably detect normal variants (benign duplications and deletions that are not associated with any abnormal phenotype). Some variants will be difficult to explain. This has been true for karyotyping as well, and just as we have in the past, we will want to minimize parents' anxiety over the unknowns.

When we find variants of uncertain significance, we will turn to the parents, checking their blood samples for the same losses or gains of chromosomal material.

The Near Future

The clinicians and cytogeneticists who are using and offering array-CGH are on a learning curve. Experts seem to have been successful in ensuring that the test works for the disorders that are covered; there is an enormous amount of information and data being shared by centers and labs on what variants are associated with the normal phenotype, and on other issues as well.

At Johns Hopkins University and the Kennedy Krieger Institute, we have postnatal experience to draw upon as we bring array-CGH into the prenatal arena. Of the children with developmental delay and dysmorphic features who have had array-CGH, we have been able to give a specific syndromic diagnosis to approximately 5%–8%, depending on the array platform we utilize. In about 12%, we have detected variants that we know—through parental testing and the use of databases—are normal. In a much smaller percentage (3.4%) of these children, we have found variants that we cannot yet explain.

Until we learn more, we plan to limit prenatal array-CGH to cases in which there is a known abnormality on ultrasound, rather than offer the test more broadly as a screening tool for chromosomal abnormalities in high-risk pregnancies. And although we are moving in the postnatal setting toward more of a whole-genome screening, we will use targeted arrays in the prenatal setting.

Within this context—that of ultrasound-detected anomalies and targeted arrays—we can expect that 5%–10% of tests will provide a clear diagnosis.

The question of whether array-CGH could replace a karyotype in prenatal testing is an interesting one. For now, there are too many questions and issues (mosaicism and normal variants, for instance) to do away with karyotyping. We believe the role of array-CGH is to enhance our current approaches to prenatal testing, and in this sense, it is an exciting development.

Figure A shows a hybridized array of >4,200 BAC clones; B, one area enlarged; C, plot for chromosome 1 based on fluorescence ratios (patient vs. control DNA) showing normal copy number. Courtesy Dr. Denise Batista

Prenatal Diagnosis

In our contemporary society, where women and their physicians continue to seek as much information as possible early in their pregnancies, the field of prenatal diagnosis has rapidly become a well-established and central part of obstetrics. Prenatal diagnosis performed in the first trimester has become common practice—a far cry from the days in the not-so-distant past when the ultimate outcome of the fetus was not learned until the day of delivery.

As obstetricians and perinatologists, we benefit from being aware of and fully informed about the evolving technology that continues to move the field of prenatal diagnosis forward. The array of current prenatal diagnostic tools includes both invasive and noninvasive techniques that enable parents to assess the genetic, chromosomal, and biochemical aspects of their fetus considerably before the time of viability.

Parents and their physicians are using this information to guide them in pursuing potential therapeutic applications and interventions or, in some cases, interruption of the pregnancy.

Now there is a new technique called array-based comparative genomic hybridization, or array-CGH, which is entering the prenatal arena with promises of more comprehensive and faster detection capabilities than we now are afforded with the two current “gold standard” techniques: microscopic karyotype analysis and rapid fluorescent in situ hybridization.

Array-CGH is far from perfect in evaluating chromosomal material. It can only detect instances where there is a significant addition or deletion of genetic material. And, of course, it can only evaluate those genes encoded on the array.

As with every other prenatal diagnostic tool developed to date, the future use of this new technique involves many questions, including which variants are normal as opposed to abnormal, the technique's potential role as a screening tool, and other often vexing ambiguities and issues. However, its use in prenatal diagnosis will build upon a body of national experience in the postnatal setting.

To familiarize us with the new technology and discuss its role in prenatal diagnosis, I have invited Dr. Karin J. Blakemore to serve as the guest professor of this month's Master Class.

Dr. Blakemore is the director of maternal-fetal medicine and the Prenatal Genetics Service at Johns Hopkins University School of Medicine in Baltimore—an institution that is gearing up to use array-CGH as part of its armamentarium for prenatal diagnosis.

She is joined by her colleague Denise Batista, Ph.D., who is an assistant professor in the Johns Hopkins department of pathology and codirector of the university's prenatal cytogenetics laboratory. Dr. Batista also serves as the director of the cytogenetics laboratory at the Kennedy Krieger Institute in Baltimore.

Key Points for Array-CGH

▸ Detects: Unbalanced rearrangements, aneuploidy, gains and losses of regions represented in the array.

▸ Won't detect: Balanced rearrangements, point mutations, (possibly) low-level mosaicism.

▸ Pick-up rate: Estimated as 5%–10% from postnatal studies of developmentally delayed/dysmorphic children.

▸ Confirmation: By FISH probes.

▸ Parental studies: Might be necessary to sort out normal variants versus clinically significant changes.

▸ Copy number variants: Might find copy number variants of unknown significance.

▸ Platforms: Several commercial and home-brew arrays available with different genomic coverage.

The array-CGH test, which is already being used postnatally, will give obstetricians, geneticists, and their patients the opportunity in the prenatal setting to detect significantly more and smaller changes in the amount of chromosomal material present in individuals—and in significantly less time than a standard chromosome karyotype would take.

It may someday take the place of our standard techniques for cytogenetic analysis, but for now, it is a valuable addition to the available diagnostic tests.

Advances Over FISH

The technology, which has also been called chromosomal microarray, was first used to analyze gains and losses in chromosomal material in tumors and tumor cell lines. It is now a valuable tool in the postnatal testing of individuals with birth defects.

Between one-half and two-thirds of children with serious developmental abnormalities go undiagnosed and have a normal karyotype, so from a postnatal perspective, this new test has been welcomed at Johns Hopkins University and the Kennedy Krieger Institute, both in Baltimore, as well as at other institutions. Having a diagnosis facilitates the most appropriate therapy and allows parents to plan for future pregnancies and possible prenatal testing.

Yet it is the prenatal period for which array-CGH may have an even greater impact. Phenotypic features are not as apparent in the womb as at birth, making it more difficult to target testing with technology like rapid fluorescent in situ hybridization (FISH).

Along with standard karyotype analysis, the FISH technique has been the mainstay of cytogenetic analysis. It provides a targeted look at areas of the karyotype that are known to be associated with disease as a result of either the duplication or deletion of genetic material. In other words, it detects gains and losses in chromosomal material for just one or a few chromosome regions at a time.

Performing array-CGH is like doing FISH hundreds of times at once. Array-CGH testing may target the same chromosomal regions (and thus similar disorders) as a series of FISH tests, but array-CGH will target these regions at a much higher resolution, enabling the detection of much smaller deletions and duplications; it can also assess many regions associated with genetic disorders in a single test.

If we see on a prenatal ultrasound that a fetus has cardiac problems, for example, we might suspect the DiGeorge syndrome. The obstetrician today would probably perform an amniocentesis and order both a karyotype and FISH with a specific probe for the DiGeorge syndrome, which we know is caused by a deletion on chromosome 22, just as he or she would do in the postnatal period for a child with the syndrome's more obvious phenotypic features.

In the near future, the obstetrician facing this prenatal situation will likely proceed differently than he or she would in the postnatal period. The obstetrician will use array-CGH instead of FISH in order to cast a wider net—one that can catch a deletion on chromosome 22, as well as other possible deletions which may cause the heart defect.

Right now, the available array-CGH platforms can detect more than 40 syndromic chromosomal disorders. Just as with FISH, a normal result rules out only those conditions that correspond to the deletions or duplications that are covered on the array.

How Array-CGH Works

The technique involves labeling the patient's DNA in one fluorescent dye, labeling DNA from a normal control with a different fluorescent dye, allowing the DNA from both to mix, and then applying the mixture to a slide that contains small segments of DNA from known chromosomal regions.

The slide serves as the platform or the array. The mixture of the patient's DNA and the normal control DNA is allowed to match up, or hybridize, with the complementary DNA segments on the slide.

A scanner then reads the intensities of the two different dyes, determining their relative strength at each of the DNA spots on the array. If a patient has less DNA in a specified region of the genome—a deletion of chromosomal material—then the color of the control sample will be stronger at that point on the array. If a patient has more DNA in this specific region—a duplication of chromosomal material—then the color of the patient's sample will be stronger at that location.

Analysis can be performed on direct chorionic villi or amniotic fluid, or alternatively on cultured cells. For direct analysis, it might be necessary to amplify the amount of DNA obtained before running it on an array. In this case, it is essential that the amplification is uniform and does not introduce any bias.

Although many laboratories are using cultured cells at this point, some studies are demonstrating the feasibility of relying on uncultured samples, and ultimately, this is the direction in which we're heading. Direct testing of fetal DNA will save time and give us rapid results.

The Limitations of Array-CGH

Unlike standard karyotyping, array-CGH cannot detect defects in which the total amount of chromosomal material is unchanged. The test cannot, for instance, detect balance rearrangements, such as balanced reciprocal translocations, balanced Robertsonian translocations, and inversions.

In a couple with multiple miscarriages, a karyotype is still the appropriate test to perform on the parents' blood because a balanced rearrangement is what you would be looking for. You would not request array-CGH because balanced rearrangements are not detectable with this technique. On the other hand, array-CGH could be very useful on the products of conception from a miscarriage because very small deletions and duplications could be found.

Array-CGH also cannot detect point mutations, or small changes in the genes, like those that cause hemophilia or sickle cell disease. It is designed to detect the syndromes caused by duplications or deletions of larger amounts of chromosomal material. And it will not detect abnormalities that are not covered by the array.

Chromosomal mosaicism, in which only some cells show a particular abnormality, may or may not be more readily detected by array-CGH than by standard techniques.

On one hand, mosaicism may be more readily detected with array-CGH than with standard karyotype analysis because abnormal cells often do not divide as well and may be lost during the culture process that is part of the standard karyotyping methodology. On the other hand, experts believe that array-CGH may not detect mosaicism below a certain level—below the level, some say, at which the abnormality affects fewer than 15%–30% of cells.

Array-CGH will also inevitably detect normal variants (benign duplications and deletions that are not associated with any abnormal phenotype). Some variants will be difficult to explain. This has been true for karyotyping as well, and just as we have in the past, we will want to minimize parents' anxiety over the unknowns.

When we find variants of uncertain significance, we will turn to the parents, checking their blood samples for the same losses or gains of chromosomal material.

The Near Future

The clinicians and cytogeneticists who are using and offering array-CGH are on a learning curve. Experts seem to have been successful in ensuring that the test works for the disorders that are covered; there is an enormous amount of information and data being shared by centers and labs on what variants are associated with the normal phenotype, and on other issues as well.

At Johns Hopkins University and the Kennedy Krieger Institute, we have postnatal experience to draw upon as we bring array-CGH into the prenatal arena. Of the children with developmental delay and dysmorphic features who have had array-CGH, we have been able to give a specific syndromic diagnosis to approximately 5%–8%, depending on the array platform we utilize. In about 12%, we have detected variants that we know—through parental testing and the use of databases—are normal. In a much smaller percentage (3.4%) of these children, we have found variants that we cannot yet explain.

Until we learn more, we plan to limit prenatal array-CGH to cases in which there is a known abnormality on ultrasound, rather than offer the test more broadly as a screening tool for chromosomal abnormalities in high-risk pregnancies. And although we are moving in the postnatal setting toward more of a whole-genome screening, we will use targeted arrays in the prenatal setting.

Within this context—that of ultrasound-detected anomalies and targeted arrays—we can expect that 5%–10% of tests will provide a clear diagnosis.

The question of whether array-CGH could replace a karyotype in prenatal testing is an interesting one. For now, there are too many questions and issues (mosaicism and normal variants, for instance) to do away with karyotyping. We believe the role of array-CGH is to enhance our current approaches to prenatal testing, and in this sense, it is an exciting development.

Figure A shows a hybridized array of >4,200 BAC clones; B, one area enlarged; C, plot for chromosome 1 based on fluorescence ratios (patient vs. control DNA) showing normal copy number. Courtesy Dr. Denise Batista

Prenatal Diagnosis

In our contemporary society, where women and their physicians continue to seek as much information as possible early in their pregnancies, the field of prenatal diagnosis has rapidly become a well-established and central part of obstetrics. Prenatal diagnosis performed in the first trimester has become common practice—a far cry from the days in the not-so-distant past when the ultimate outcome of the fetus was not learned until the day of delivery.

As obstetricians and perinatologists, we benefit from being aware of and fully informed about the evolving technology that continues to move the field of prenatal diagnosis forward. The array of current prenatal diagnostic tools includes both invasive and noninvasive techniques that enable parents to assess the genetic, chromosomal, and biochemical aspects of their fetus considerably before the time of viability.

Parents and their physicians are using this information to guide them in pursuing potential therapeutic applications and interventions or, in some cases, interruption of the pregnancy.

Now there is a new technique called array-based comparative genomic hybridization, or array-CGH, which is entering the prenatal arena with promises of more comprehensive and faster detection capabilities than we now are afforded with the two current “gold standard” techniques: microscopic karyotype analysis and rapid fluorescent in situ hybridization.

Array-CGH is far from perfect in evaluating chromosomal material. It can only detect instances where there is a significant addition or deletion of genetic material. And, of course, it can only evaluate those genes encoded on the array.

As with every other prenatal diagnostic tool developed to date, the future use of this new technique involves many questions, including which variants are normal as opposed to abnormal, the technique's potential role as a screening tool, and other often vexing ambiguities and issues. However, its use in prenatal diagnosis will build upon a body of national experience in the postnatal setting.

To familiarize us with the new technology and discuss its role in prenatal diagnosis, I have invited Dr. Karin J. Blakemore to serve as the guest professor of this month's Master Class.

Dr. Blakemore is the director of maternal-fetal medicine and the Prenatal Genetics Service at Johns Hopkins University School of Medicine in Baltimore—an institution that is gearing up to use array-CGH as part of its armamentarium for prenatal diagnosis.

She is joined by her colleague Denise Batista, Ph.D., who is an assistant professor in the Johns Hopkins department of pathology and codirector of the university's prenatal cytogenetics laboratory. Dr. Batista also serves as the director of the cytogenetics laboratory at the Kennedy Krieger Institute in Baltimore.

Key Points for Array-CGH

▸ Detects: Unbalanced rearrangements, aneuploidy, gains and losses of regions represented in the array.

▸ Won't detect: Balanced rearrangements, point mutations, (possibly) low-level mosaicism.

▸ Pick-up rate: Estimated as 5%–10% from postnatal studies of developmentally delayed/dysmorphic children.

▸ Confirmation: By FISH probes.

▸ Parental studies: Might be necessary to sort out normal variants versus clinically significant changes.

▸ Copy number variants: Might find copy number variants of unknown significance.

▸ Platforms: Several commercial and home-brew arrays available with different genomic coverage.

A variety of operations now exists for the treatment of vaginal vault prolapse and the reestablishment of apical support—from abdominal sacral colpopexy and abdominal uterus sacral suspensions, to sacrospinous vaginal vault suspensions, sacrospinous hysteropexies, and iliococcygeal vaginal vault suspensions.

All options have been described in the literature as being effective operations with minimal complications and varying degrees of success, but the optimal approach for vaginal vault prolapse remains a subject of debate. Unfortunately, many surgeons are not comfortable with vaginal surgery, despite the safety, speed, and effectiveness that sacrospinous vaginal vault suspension and its modifications can provide in experienced hands.

Sacrospinous vaginal vault suspension was originally described by Dr. Paul Zweifel in Germany in 1892. It was “rediscovered” in 1951 by Dr. I.A. Amreich in Austria, modified by Dr. J. Sederl, and then studied and described extensively in 1968 by fellow Austrian Dr. K. Richter.

The operation received more attention when Dr. C.L. Randall and Dr. D.H. Nichols reported on it (Obstet. Gynecol. 1971;38:327–32). Since then, the posterior approach to sacrospinous vaginal vault suspension that was described by Dr. Nichols has been modified, and an alternative approach through the anterior compartment of the vagina has been developed and described. Several newer devices, in the meantime, have offered improved safety and simplicity.

The Original Posterior Approach

The posterior approach to sacrospinous vaginal vault suspension involves a posterior vaginal incision, perforation of the rectal pillars, and blunt dissection of the pararectal space anterior to the ligament.

In the original posterior approach described by Dr. Nichols, two Allis clamps are placed at the level of the hymenal ring, approximately 1 cm from the midline, and a dilute vasopressin solution can be used to infiltrate underneath the posterior vaginal wall to within 1 cm of the apex of the vagina. The scalpel is used to make a transverse incision between the Allis clamps, and then the Metzenbaum scissors are used to dissect underneath the vaginal epithelium in the midline, vertically to within 1 cm of the apex of the vagina.

The Metzenbaum scissors can be used to spread beneath the vaginal epithelium and smooth muscle to free the underlying endopelvic connective tissue from its attachments on the undersurface of the vaginal epithelium and smooth muscle. (See photo.) The scissors can then be used to make a vertical incision in the posterior vaginal wall to about 1–2 cm away from the vaginal apex.

Placement of Allis clamps—or self-restraining retractor hooks—on the incised edges of the vaginal epithelium and smooth muscle can allow for exposure and resection of the endopelvic connective tissue from the undersurface of the vaginal epithelium and smooth muscle laterally to the level of the rectal pillars. This may be facilitated by countertraction from your assistant, using tissue forceps on the endopelvic connective tissue.

Once this dissection is complete, the ischial spine on the patient's right side may be palpated, and—with either sharp dissection with the tips of the Metzenbaum scissors or blunt dissection with the operator's right index finger—the endopelvic connective tissue can be swept from anterior-lateral to medial of the ischial spine across the coccygeus muscle to remove the fatty tissue that overlies the ischial spine and the sacrospinous ligament.

The entire coccygeus muscle with its anterior sacrospinous ligament should be palpated, and the rectum and pararectal attachments mobilized bluntly with the index finger from lateral to medial. This is a relatively blood-free plane, and such a maneuver is possible with minimal bleeding so long as the affecting finger remains anterior to the ischial spine and sacrospinous ligament.

A short Breisky-Navratil retractor can then be placed at the 10 o'clock position, resting on the ischial spine. By maintaining your right index finger against the ischial spine, you can then insert a long Breisky-Navratil retractor directly opposing the short retractor over the ventral surface of your finger, against the ischial spine with its posterior edge just anterior to the coccygeus muscle.

Sweeping this long retractor counterclockwise immediately across the coccygeus muscle, keeping its posterior blade in contact with the muscle throughout, will mobilize the rectal and pararectal fat medially and expose the coccygeus muscle and sacrospinous ligament. This retractor should be held at approximately the 2 o'clock position, creating a 60- to 90-degree angle with the other Breisky-Navratil retractor. (The exact angle will depend on the angle of the pubic arch.)

At this point, the right-angle Haney retractor can be placed at approximately the 7 o'clock position over the coccygeus muscle and then, with posterior traction, withdrawn distally until it pops down in front of the coccygeus muscle, exposing this muscle and sacrospinous ligament.

A Deschamps ligature carrier then can be inserted through the middle of the coccygeus muscle and rotated clockwise to expose its tip around the sacrospinous ligament. The initial bite should be placed 1 cm medial to the ischial spine to avoid the pudendal complex. A second suture can then be placed 1–2 cm medial to the first, again with care taken to place it through the middle of the coccygeus muscle and not posterior to this muscle, where it could injure the vessel and nerve of the pudendal complex.

When the Deschamps ligature carrier is brought through the muscle, a colpotomy or nerve hook can be used to mobilize one end of the suture and withdraw it back out into the operative field. Once this is mobilized, the Deschamps ligature carrier can be rotated counterclockwise—in an arc exactly opposite to that in which it was placed—to withdraw the posterior end of the suture.

Care should be taken to identify the posterior end of the suture and differentiate it from the anterior end. This may be accomplished through the use of a straight hemostat on one end and the placement of a curved hemostat across both ends of the suture.

(When we perform the surgery, we use a straight hemostat to identify the posterior end of suture on the patient's right side, or the lateral suture, and a straight Kocher clamp to identify the posterior end on the patient's left side.)

The Breisky-Navratil retractors can then be slowly withdrawn one at a time to allow for observation of the entire paravaginal space and assessment for any bleeders, which can be easily grasped and electrocoagulated or sutured.

The suture can then be placed on the undersurface of the apex of the vagina by use of a free Mayo needle. The anterior arm of the lateral suture can be placed approximately 1–2 cm away from the right apex of the vagina in a figure-eight fashion, and this one arm of the suture can be tied to itself with a loose surgeon's knot.

The same process can be followed with the left or medial anterior arm of the second sacrospinous suture, 1–2 cm away from the left apex of the vagina, and tied down in the same fashion. Care needs to be taken on the patient's left side to place the suture approximately 0.5 cm further away from the apical edge of the vagina, as this suture will traverse a longer distance to reach the sacrospinous ligament.

Now the sutures can be retracted anteriorly, and a rectocele repair and/or enterocele repair can be performed as needed.

After successful completion of such repairs, excess vaginal epithelium and smooth muscle can be resected as indicated and the posterior vaginal wall closed with either interrupted sutures or a running, locking suture approximately halfway down the posterior vaginal wall.

At this point, the sacrospinous sutures should be tied down, with the suture on the patient's right lateral side tied down first. The posterior arm of the sacrospinous suture should be taken in the nondominant hand, and slow traction should be applied while the apex of the vagina is guided back into position in the pelvis, toward the right sacrospinous ligament.

Once the excess slack is taken up by mobilization of this suture, the suture may be tied down, with care taken to leave no gap between the vaginal apex and the sacrospinous ligament. This suture is then held while the second suture is mobilized in the same fashion and then tied down similarly.

Retraction of the undersurface of the closed posterior vaginal wall will allow for visualization of the sacrospinous sutures, which can be cut approximately 1 cm above the knot. The posterior vaginal wall may be closed, and perineorrhaphy performed as indicated.

The choice of sutures is up to the individual operator. Although Dr. Nichols originally described using delayed-absorbable sutures, later in his career he changed to using one Gore-Tex suture and one polyglycolic acid suture. He informed me that his reason for this was that the permanent suture would offer longer-lasting strength, whereas the delayed-absorbable suture would create more inflammatory response and possibly elicit more scarring.

Variations of the Original Approach

Some surgeons have suggested that a bilateral attachment of the vaginal apex—or attachment of the cervix, when the uterus is preserved—may offer a superior anatomical reconstruction of the vaginal vault, and may avoid deviation of the vagina to the right or the left side.

Instead of placing two sutures on one sacrospinous ligament, a single suture can be placed on the right sacrospinous ligament at its midportion and on the left sacrospinous ligament at its midportion. These sutures are attached to the right and left apex of the vagina, respectively.

This approach, the thinking goes, allows for a wider width of the vaginal apex in the posthysterectomy patient, as well as good lateral support.

Often, a bilateral sacrospinous ligament suspension may be augmented by bilateral paravaginal defect repairs performed through the vagina, with or without the use of an adjuvant graft. The dissection for placement of these sutures is identical to the ipsilateral dissection for sacrospinous vaginal vault suspension, just described, on the patient's right side; it also can be performed on the patient's left side, with care taken to mobilize the rectum medially (which is often a more challenging task on the patient's left side).

Bilateral suspension to the sacrospinous ligament has not, however, been compared directly to unilateral sacrospinous vaginal vault suspension. Sometimes, when scarring exists in the midline from prior vaginal hysterectomy, or when an enterocele repair has been performed, there may be indentation in the midline of the vaginal vault, creating a somewhat Y-shaped vagina.

In a report published in 1997, Dr. J.F. Pohl and Dr. J.L. Frattarelli concluded that bilateral suspension is feasible in many patients, but that it requires significant intraoperative judgment both as to its feasibility and as to the width of the vaginal cuff that will allow a bilateral suspension without tension (Am. J. Obstet. Gynecol. 1997;177:1356–61).

In our practice, we tend to prefer right-sided vaginal vault suspensions in which we utilize either an anterior approach or a posterior approach, with a left-sided iliococcygeus vaginal vault suspension. This requires less dissection and less risk of bleeding, as the sutures are placed lateral to the ischial spine.

It also creates a vagina with further cephalad elevation of the right vaginal apex than the left vaginal apex, as well as an ample apical width.

Anterior sacrospinous suspension is an approach that we have pursued and described in order to address possible shortcomings or limitations of the conventional posterior approach—chiefly, recurrence of anterior vaginal wall prolapse and a deep posterior angle and narrowing of the upper one-third of the vaginal vault.

Whereas posterior suspension uses a posterior vaginal incision and pararectal dissection, anterior suspension uses an anterior vaginal incision, perforation into the right retropubic space, and dissection of the ipsilateral paravaginal space from the level of the bladder neck to the ischial spine, to create a wide space to accommodate the vaginal vault.

In our experience—Dr. Harvey A. Winkler, Dr. Janet E. Tomeszko, and I first reported on the technique in 2000—the anterior approach appears to reduce postoperative proximal vaginal narrowing and lateral deviation of the upper vagina by avoiding passage through the rectal pillars (Obstet. Gynecol. 2000;95:612–5).

The technique involves opening the anterior vaginal wall and separating the endopelvic connective tissue on the patient's right from the pubic ramus at the level of the bladder neck to the ischial spine, exposing the paravesical and pararectal space. The sacrospinous ligament is identified and isolated through this space.

Two permanent sutures are placed approximately 2 cm apart through the ligament, anchored with pulley stitches underneath the vaginal epithelium and smooth muscle, and tied down to the ligament.

An Evolution in Instrumentation

The Deschamps ligature carrier is the device originally used for applying sutures through the coccygeus muscle and sacrospinous ligament. However, because the ligature carrier is delivered posterior-laterally to anterior-medially, there always has been concern about potential damage to the pudendal artery, vein, and nerve.

With the advent of newer devices that deliver the suture in a limited arc from the anterior to posterior direction, the risk of damage to the pudendal complex has been significantly minimized and the need for extensive dissection is often unnecessary. The newer devices have thus improved not only the safety of the procedure but also its simplicity, and they have reduced the operative time required.

The first of these devices described for applying sutures in a defined arc from anterior to posterior was the Miya hook, described by Dr. F. Miyazaki.

Another new device, the Capio device, is a push-and-catch suture delivery system that allows the suture to be delivered over a defined arc into a catch device. The Capio device has enabled placement of sacrospinous sutures through palpation and without direct visualization of the ligament. This further limits the need for dissection of the perirectal space, potentially improving safety and reducing blood loss.

Other authors have described using the Schutt device, which also delivers a suture from anterior to posterior in a defined arc to improve the safety and speed of the procedure.

Evolving Research

At this time, there are relatively few studies that have compared vaginal sacrospinous colpopexy with abdominal sacral colpopexy for the treatment of upper vaginal prolapse.

The two prospective, randomized trials that appear to be most often cited and referred to—a study by Dr. Christopher F. Maher published in 2004 and a study by Dr. J. Thomas Benson published in 1996—were quite different in their scope and methodology (Am. J. Obstet. Gynecol. 2004;190:20–6; 1996;175:1418–21).

Dr. Benson's group reported data for 80 women with uterovaginal or vault prolapse and concluded that the abdominal approach was more effective, but this study involved the use of multiple concomitant procedures that may have confounded the outcomes.

Needle suspensions of the bladder neck were used in the vaginal surgery group, compared with retropubic urethropexies in the abdominal surgery group. Needle suspensions have been associated with a significant increased risk of subsequent recurrent cystocele and have affected the high recurrent prolapse rate for the vaginal surgery group.

The outcomes for both groups in the Benson study were very poor and markedly different from other results in the literature, which makes it difficult to generalize these outcomes to other populations.

Dr. Maher's study was better designed and has been more reflective of my experience and the experience of many other surgeons. His group reported on 95 women with posthysterectomy vaginal vault prolapse, and concluded that both surgeries are highly effective and significantly improve the patient's quality of life.

Similarly, in the same year of Dr. Benson's publication, Dr. P.J. Hardiman and Dr. H.P. Drutz reported that in a case series of 130 sacrospinous vaginal vault suspensions and 80 abdominal sacral colpopexies, the failure rate in terms of the recurrent vault prolapse was 2.4% with the vaginal approach and 1.3% with the abdominal approach (Am. J. Obstet. Gynecol. 1996;175[3, pt. 1]:612–6).

They concluded that both approaches were associated with a low incidence of complications and recurrent vault prolapse.

Although it was not a randomized trial, the Hardiman-Drutz study is noteworthy and the outcomes are more comparable with real-life experience. I believe that surgeons who are expert at performing both surgeries find them to be equally successful, with the vaginal approach having less morbidity.

Success, in most cases, has been defined through rates of recurrent apical or anterior vaginal prolapse, and few studies have addressed anatomical outcomes more directly relevant to vaginal function, such as length, axis, and sexual satisfaction.

We are challenged by the lack of universally accepted standards for quantifying such outcomes, but nevertheless, such outcomes should be pursued.

In a study reported in 2001 (with Dr. R. Goldberg as lead author), we found that sexual function was well preserved regardless of the sacrospinous suspension technique, with equally low rates of postoperative dyspareunia in both groups (Obstet. Gynecol. 2001;98:199–204).

Metzenbaum scissors are used to free the endopelvic connective tissue from the vaginal epithelium. Courtesy Dr. Peter Sand

The dissection finger is placed adjacent to the suture site.

The upper vaginal vault is sutured to the sacrospinous ligament.

Vaginal wall suturing is done at the upper portion of the vaginal apex. Images courtesy Dr. Peter Sand

A Vaginal Approach to Pelvic Floor Prolapse

In a recent Master Class (OB.GYN. NEWS, Aug. 1, 2007, p. 24), abdominal sacral colpopexy via a laparoscopic approach was featured for the treatment of vaginal vault prolapse. However, for the gynecologic surgeon who is more adroit with vaginal surgery, sacrospinous vaginal vault suspension also offers a safe and effective remedy for this disorder. As a review, the ischial spine is located approximately halfway between the pubic bones and the sacrum. Posterior to the spine is the sacrospinous ligament with the overlying coccygeus muscle. The sacrospinous ligament marks the posterior limit of the pelvic diaphragm.

Because he is a nationally recognized expert in the vaginal approach to pelvic floor prolapse, I have asked Dr. Peter Sand to discuss vaginal vault suspension, the evolution of the procedure, and the prevailing literature that compares this technique with abdominal sacral colpopexy.

Dr. Sand is currently a professor of ob.gyn. at Northwestern University, Chicago, and the director of urogynecology and reconstructive pelvic surgery at Evanston (Ill.) Northwestern Healthcare. Dr. Sand is a prolific researcher and much-sought-after lecturer. As this year's scientific program chairman of the American Association of Gynecologic Laparoscopists' Global Congress of Minimally Invasive Gynecology, I invited Dr. Sand to present a surgical tutorial on the vaginal approach to prolapse. Just as the participants found his discussion interesting and informative, I am sure our readers will feel the same.

A variety of operations now exists for the treatment of vaginal vault prolapse and the reestablishment of apical support—from abdominal sacral colpopexy and abdominal uterus sacral suspensions, to sacrospinous vaginal vault suspensions, sacrospinous hysteropexies, and iliococcygeal vaginal vault suspensions.

All options have been described in the literature as being effective operations with minimal complications and varying degrees of success, but the optimal approach for vaginal vault prolapse remains a subject of debate. Unfortunately, many surgeons are not comfortable with vaginal surgery, despite the safety, speed, and effectiveness that sacrospinous vaginal vault suspension and its modifications can provide in experienced hands.

Sacrospinous vaginal vault suspension was originally described by Dr. Paul Zweifel in Germany in 1892. It was “rediscovered” in 1951 by Dr. I.A. Amreich in Austria, modified by Dr. J. Sederl, and then studied and described extensively in 1968 by fellow Austrian Dr. K. Richter.

The operation received more attention when Dr. C.L. Randall and Dr. D.H. Nichols reported on it (Obstet. Gynecol. 1971;38:327–32). Since then, the posterior approach to sacrospinous vaginal vault suspension that was described by Dr. Nichols has been modified, and an alternative approach through the anterior compartment of the vagina has been developed and described. Several newer devices, in the meantime, have offered improved safety and simplicity.

The Original Posterior Approach

The posterior approach to sacrospinous vaginal vault suspension involves a posterior vaginal incision, perforation of the rectal pillars, and blunt dissection of the pararectal space anterior to the ligament.

In the original posterior approach described by Dr. Nichols, two Allis clamps are placed at the level of the hymenal ring, approximately 1 cm from the midline, and a dilute vasopressin solution can be used to infiltrate underneath the posterior vaginal wall to within 1 cm of the apex of the vagina. The scalpel is used to make a transverse incision between the Allis clamps, and then the Metzenbaum scissors are used to dissect underneath the vaginal epithelium in the midline, vertically to within 1 cm of the apex of the vagina.

The Metzenbaum scissors can be used to spread beneath the vaginal epithelium and smooth muscle to free the underlying endopelvic connective tissue from its attachments on the undersurface of the vaginal epithelium and smooth muscle. (See photo.) The scissors can then be used to make a vertical incision in the posterior vaginal wall to about 1–2 cm away from the vaginal apex.

Placement of Allis clamps—or self-restraining retractor hooks—on the incised edges of the vaginal epithelium and smooth muscle can allow for exposure and resection of the endopelvic connective tissue from the undersurface of the vaginal epithelium and smooth muscle laterally to the level of the rectal pillars. This may be facilitated by countertraction from your assistant, using tissue forceps on the endopelvic connective tissue.

Once this dissection is complete, the ischial spine on the patient's right side may be palpated, and—with either sharp dissection with the tips of the Metzenbaum scissors or blunt dissection with the operator's right index finger—the endopelvic connective tissue can be swept from anterior-lateral to medial of the ischial spine across the coccygeus muscle to remove the fatty tissue that overlies the ischial spine and the sacrospinous ligament.

The entire coccygeus muscle with its anterior sacrospinous ligament should be palpated, and the rectum and pararectal attachments mobilized bluntly with the index finger from lateral to medial. This is a relatively blood-free plane, and such a maneuver is possible with minimal bleeding so long as the affecting finger remains anterior to the ischial spine and sacrospinous ligament.

A short Breisky-Navratil retractor can then be placed at the 10 o'clock position, resting on the ischial spine. By maintaining your right index finger against the ischial spine, you can then insert a long Breisky-Navratil retractor directly opposing the short retractor over the ventral surface of your finger, against the ischial spine with its posterior edge just anterior to the coccygeus muscle.

Sweeping this long retractor counterclockwise immediately across the coccygeus muscle, keeping its posterior blade in contact with the muscle throughout, will mobilize the rectal and pararectal fat medially and expose the coccygeus muscle and sacrospinous ligament. This retractor should be held at approximately the 2 o'clock position, creating a 60- to 90-degree angle with the other Breisky-Navratil retractor. (The exact angle will depend on the angle of the pubic arch.)

At this point, the right-angle Haney retractor can be placed at approximately the 7 o'clock position over the coccygeus muscle and then, with posterior traction, withdrawn distally until it pops down in front of the coccygeus muscle, exposing this muscle and sacrospinous ligament.

A Deschamps ligature carrier then can be inserted through the middle of the coccygeus muscle and rotated clockwise to expose its tip around the sacrospinous ligament. The initial bite should be placed 1 cm medial to the ischial spine to avoid the pudendal complex. A second suture can then be placed 1–2 cm medial to the first, again with care taken to place it through the middle of the coccygeus muscle and not posterior to this muscle, where it could injure the vessel and nerve of the pudendal complex.

When the Deschamps ligature carrier is brought through the muscle, a colpotomy or nerve hook can be used to mobilize one end of the suture and withdraw it back out into the operative field. Once this is mobilized, the Deschamps ligature carrier can be rotated counterclockwise—in an arc exactly opposite to that in which it was placed—to withdraw the posterior end of the suture.

Care should be taken to identify the posterior end of the suture and differentiate it from the anterior end. This may be accomplished through the use of a straight hemostat on one end and the placement of a curved hemostat across both ends of the suture.

(When we perform the surgery, we use a straight hemostat to identify the posterior end of suture on the patient's right side, or the lateral suture, and a straight Kocher clamp to identify the posterior end on the patient's left side.)

The Breisky-Navratil retractors can then be slowly withdrawn one at a time to allow for observation of the entire paravaginal space and assessment for any bleeders, which can be easily grasped and electrocoagulated or sutured.

The suture can then be placed on the undersurface of the apex of the vagina by use of a free Mayo needle. The anterior arm of the lateral suture can be placed approximately 1–2 cm away from the right apex of the vagina in a figure-eight fashion, and this one arm of the suture can be tied to itself with a loose surgeon's knot.

The same process can be followed with the left or medial anterior arm of the second sacrospinous suture, 1–2 cm away from the left apex of the vagina, and tied down in the same fashion. Care needs to be taken on the patient's left side to place the suture approximately 0.5 cm further away from the apical edge of the vagina, as this suture will traverse a longer distance to reach the sacrospinous ligament.

Now the sutures can be retracted anteriorly, and a rectocele repair and/or enterocele repair can be performed as needed.

After successful completion of such repairs, excess vaginal epithelium and smooth muscle can be resected as indicated and the posterior vaginal wall closed with either interrupted sutures or a running, locking suture approximately halfway down the posterior vaginal wall.

At this point, the sacrospinous sutures should be tied down, with the suture on the patient's right lateral side tied down first. The posterior arm of the sacrospinous suture should be taken in the nondominant hand, and slow traction should be applied while the apex of the vagina is guided back into position in the pelvis, toward the right sacrospinous ligament.

Once the excess slack is taken up by mobilization of this suture, the suture may be tied down, with care taken to leave no gap between the vaginal apex and the sacrospinous ligament. This suture is then held while the second suture is mobilized in the same fashion and then tied down similarly.

Retraction of the undersurface of the closed posterior vaginal wall will allow for visualization of the sacrospinous sutures, which can be cut approximately 1 cm above the knot. The posterior vaginal wall may be closed, and perineorrhaphy performed as indicated.

The choice of sutures is up to the individual operator. Although Dr. Nichols originally described using delayed-absorbable sutures, later in his career he changed to using one Gore-Tex suture and one polyglycolic acid suture. He informed me that his reason for this was that the permanent suture would offer longer-lasting strength, whereas the delayed-absorbable suture would create more inflammatory response and possibly elicit more scarring.

Variations of the Original Approach

Some surgeons have suggested that a bilateral attachment of the vaginal apex—or attachment of the cervix, when the uterus is preserved—may offer a superior anatomical reconstruction of the vaginal vault, and may avoid deviation of the vagina to the right or the left side.

Instead of placing two sutures on one sacrospinous ligament, a single suture can be placed on the right sacrospinous ligament at its midportion and on the left sacrospinous ligament at its midportion. These sutures are attached to the right and left apex of the vagina, respectively.

This approach, the thinking goes, allows for a wider width of the vaginal apex in the posthysterectomy patient, as well as good lateral support.

Often, a bilateral sacrospinous ligament suspension may be augmented by bilateral paravaginal defect repairs performed through the vagina, with or without the use of an adjuvant graft. The dissection for placement of these sutures is identical to the ipsilateral dissection for sacrospinous vaginal vault suspension, just described, on the patient's right side; it also can be performed on the patient's left side, with care taken to mobilize the rectum medially (which is often a more challenging task on the patient's left side).

Bilateral suspension to the sacrospinous ligament has not, however, been compared directly to unilateral sacrospinous vaginal vault suspension. Sometimes, when scarring exists in the midline from prior vaginal hysterectomy, or when an enterocele repair has been performed, there may be indentation in the midline of the vaginal vault, creating a somewhat Y-shaped vagina.

In a report published in 1997, Dr. J.F. Pohl and Dr. J.L. Frattarelli concluded that bilateral suspension is feasible in many patients, but that it requires significant intraoperative judgment both as to its feasibility and as to the width of the vaginal cuff that will allow a bilateral suspension without tension (Am. J. Obstet. Gynecol. 1997;177:1356–61).

In our practice, we tend to prefer right-sided vaginal vault suspensions in which we utilize either an anterior approach or a posterior approach, with a left-sided iliococcygeus vaginal vault suspension. This requires less dissection and less risk of bleeding, as the sutures are placed lateral to the ischial spine.

It also creates a vagina with further cephalad elevation of the right vaginal apex than the left vaginal apex, as well as an ample apical width.

Anterior sacrospinous suspension is an approach that we have pursued and described in order to address possible shortcomings or limitations of the conventional posterior approach—chiefly, recurrence of anterior vaginal wall prolapse and a deep posterior angle and narrowing of the upper one-third of the vaginal vault.

Whereas posterior suspension uses a posterior vaginal incision and pararectal dissection, anterior suspension uses an anterior vaginal incision, perforation into the right retropubic space, and dissection of the ipsilateral paravaginal space from the level of the bladder neck to the ischial spine, to create a wide space to accommodate the vaginal vault.

In our experience—Dr. Harvey A. Winkler, Dr. Janet E. Tomeszko, and I first reported on the technique in 2000—the anterior approach appears to reduce postoperative proximal vaginal narrowing and lateral deviation of the upper vagina by avoiding passage through the rectal pillars (Obstet. Gynecol. 2000;95:612–5).

The technique involves opening the anterior vaginal wall and separating the endopelvic connective tissue on the patient's right from the pubic ramus at the level of the bladder neck to the ischial spine, exposing the paravesical and pararectal space. The sacrospinous ligament is identified and isolated through this space.

Two permanent sutures are placed approximately 2 cm apart through the ligament, anchored with pulley stitches underneath the vaginal epithelium and smooth muscle, and tied down to the ligament.

An Evolution in Instrumentation

The Deschamps ligature carrier is the device originally used for applying sutures through the coccygeus muscle and sacrospinous ligament. However, because the ligature carrier is delivered posterior-laterally to anterior-medially, there always has been concern about potential damage to the pudendal artery, vein, and nerve.

With the advent of newer devices that deliver the suture in a limited arc from the anterior to posterior direction, the risk of damage to the pudendal complex has been significantly minimized and the need for extensive dissection is often unnecessary. The newer devices have thus improved not only the safety of the procedure but also its simplicity, and they have reduced the operative time required.

The first of these devices described for applying sutures in a defined arc from anterior to posterior was the Miya hook, described by Dr. F. Miyazaki.

Another new device, the Capio device, is a push-and-catch suture delivery system that allows the suture to be delivered over a defined arc into a catch device. The Capio device has enabled placement of sacrospinous sutures through palpation and without direct visualization of the ligament. This further limits the need for dissection of the perirectal space, potentially improving safety and reducing blood loss.

Other authors have described using the Schutt device, which also delivers a suture from anterior to posterior in a defined arc to improve the safety and speed of the procedure.

Evolving Research

At this time, there are relatively few studies that have compared vaginal sacrospinous colpopexy with abdominal sacral colpopexy for the treatment of upper vaginal prolapse.

The two prospective, randomized trials that appear to be most often cited and referred to—a study by Dr. Christopher F. Maher published in 2004 and a study by Dr. J. Thomas Benson published in 1996—were quite different in their scope and methodology (Am. J. Obstet. Gynecol. 2004;190:20–6; 1996;175:1418–21).

Dr. Benson's group reported data for 80 women with uterovaginal or vault prolapse and concluded that the abdominal approach was more effective, but this study involved the use of multiple concomitant procedures that may have confounded the outcomes.

Needle suspensions of the bladder neck were used in the vaginal surgery group, compared with retropubic urethropexies in the abdominal surgery group. Needle suspensions have been associated with a significant increased risk of subsequent recurrent cystocele and have affected the high recurrent prolapse rate for the vaginal surgery group.

The outcomes for both groups in the Benson study were very poor and markedly different from other results in the literature, which makes it difficult to generalize these outcomes to other populations.

Dr. Maher's study was better designed and has been more reflective of my experience and the experience of many other surgeons. His group reported on 95 women with posthysterectomy vaginal vault prolapse, and concluded that both surgeries are highly effective and significantly improve the patient's quality of life.

Similarly, in the same year of Dr. Benson's publication, Dr. P.J. Hardiman and Dr. H.P. Drutz reported that in a case series of 130 sacrospinous vaginal vault suspensions and 80 abdominal sacral colpopexies, the failure rate in terms of the recurrent vault prolapse was 2.4% with the vaginal approach and 1.3% with the abdominal approach (Am. J. Obstet. Gynecol. 1996;175[3, pt. 1]:612–6).

They concluded that both approaches were associated with a low incidence of complications and recurrent vault prolapse.

Although it was not a randomized trial, the Hardiman-Drutz study is noteworthy and the outcomes are more comparable with real-life experience. I believe that surgeons who are expert at performing both surgeries find them to be equally successful, with the vaginal approach having less morbidity.

Success, in most cases, has been defined through rates of recurrent apical or anterior vaginal prolapse, and few studies have addressed anatomical outcomes more directly relevant to vaginal function, such as length, axis, and sexual satisfaction.

We are challenged by the lack of universally accepted standards for quantifying such outcomes, but nevertheless, such outcomes should be pursued.

In a study reported in 2001 (with Dr. R. Goldberg as lead author), we found that sexual function was well preserved regardless of the sacrospinous suspension technique, with equally low rates of postoperative dyspareunia in both groups (Obstet. Gynecol. 2001;98:199–204).

Metzenbaum scissors are used to free the endopelvic connective tissue from the vaginal epithelium. Courtesy Dr. Peter Sand

The dissection finger is placed adjacent to the suture site.

The upper vaginal vault is sutured to the sacrospinous ligament.

Vaginal wall suturing is done at the upper portion of the vaginal apex. Images courtesy Dr. Peter Sand

A Vaginal Approach to Pelvic Floor Prolapse

In a recent Master Class (OB.GYN. NEWS, Aug. 1, 2007, p. 24), abdominal sacral colpopexy via a laparoscopic approach was featured for the treatment of vaginal vault prolapse. However, for the gynecologic surgeon who is more adroit with vaginal surgery, sacrospinous vaginal vault suspension also offers a safe and effective remedy for this disorder. As a review, the ischial spine is located approximately halfway between the pubic bones and the sacrum. Posterior to the spine is the sacrospinous ligament with the overlying coccygeus muscle. The sacrospinous ligament marks the posterior limit of the pelvic diaphragm.

Because he is a nationally recognized expert in the vaginal approach to pelvic floor prolapse, I have asked Dr. Peter Sand to discuss vaginal vault suspension, the evolution of the procedure, and the prevailing literature that compares this technique with abdominal sacral colpopexy.

Dr. Sand is currently a professor of ob.gyn. at Northwestern University, Chicago, and the director of urogynecology and reconstructive pelvic surgery at Evanston (Ill.) Northwestern Healthcare. Dr. Sand is a prolific researcher and much-sought-after lecturer. As this year's scientific program chairman of the American Association of Gynecologic Laparoscopists' Global Congress of Minimally Invasive Gynecology, I invited Dr. Sand to present a surgical tutorial on the vaginal approach to prolapse. Just as the participants found his discussion interesting and informative, I am sure our readers will feel the same.

A variety of operations now exists for the treatment of vaginal vault prolapse and the reestablishment of apical support—from abdominal sacral colpopexy and abdominal uterus sacral suspensions, to sacrospinous vaginal vault suspensions, sacrospinous hysteropexies, and iliococcygeal vaginal vault suspensions.

All options have been described in the literature as being effective operations with minimal complications and varying degrees of success, but the optimal approach for vaginal vault prolapse remains a subject of debate. Unfortunately, many surgeons are not comfortable with vaginal surgery, despite the safety, speed, and effectiveness that sacrospinous vaginal vault suspension and its modifications can provide in experienced hands.

Sacrospinous vaginal vault suspension was originally described by Dr. Paul Zweifel in Germany in 1892. It was “rediscovered” in 1951 by Dr. I.A. Amreich in Austria, modified by Dr. J. Sederl, and then studied and described extensively in 1968 by fellow Austrian Dr. K. Richter.

The operation received more attention when Dr. C.L. Randall and Dr. D.H. Nichols reported on it (Obstet. Gynecol. 1971;38:327–32). Since then, the posterior approach to sacrospinous vaginal vault suspension that was described by Dr. Nichols has been modified, and an alternative approach through the anterior compartment of the vagina has been developed and described. Several newer devices, in the meantime, have offered improved safety and simplicity.

The Original Posterior Approach

The posterior approach to sacrospinous vaginal vault suspension involves a posterior vaginal incision, perforation of the rectal pillars, and blunt dissection of the pararectal space anterior to the ligament.

In the original posterior approach described by Dr. Nichols, two Allis clamps are placed at the level of the hymenal ring, approximately 1 cm from the midline, and a dilute vasopressin solution can be used to infiltrate underneath the posterior vaginal wall to within 1 cm of the apex of the vagina. The scalpel is used to make a transverse incision between the Allis clamps, and then the Metzenbaum scissors are used to dissect underneath the vaginal epithelium in the midline, vertically to within 1 cm of the apex of the vagina.

The Metzenbaum scissors can be used to spread beneath the vaginal epithelium and smooth muscle to free the underlying endopelvic connective tissue from its attachments on the undersurface of the vaginal epithelium and smooth muscle. (See photo.) The scissors can then be used to make a vertical incision in the posterior vaginal wall to about 1–2 cm away from the vaginal apex.

Placement of Allis clamps—or self-restraining retractor hooks—on the incised edges of the vaginal epithelium and smooth muscle can allow for exposure and resection of the endopelvic connective tissue from the undersurface of the vaginal epithelium and smooth muscle laterally to the level of the rectal pillars. This may be facilitated by countertraction from your assistant, using tissue forceps on the endopelvic connective tissue.

Once this dissection is complete, the ischial spine on the patient's right side may be palpated, and—with either sharp dissection with the tips of the Metzenbaum scissors or blunt dissection with the operator's right index finger—the endopelvic connective tissue can be swept from anterior-lateral to medial of the ischial spine across the coccygeus muscle to remove the fatty tissue that overlies the ischial spine and the sacrospinous ligament.

The entire coccygeus muscle with its anterior sacrospinous ligament should be palpated, and the rectum and pararectal attachments mobilized bluntly with the index finger from lateral to medial. This is a relatively blood-free plane, and such a maneuver is possible with minimal bleeding so long as the affecting finger remains anterior to the ischial spine and sacrospinous ligament.

A short Breisky-Navratil retractor can then be placed at the 10 o'clock position, resting on the ischial spine. By maintaining your right index finger against the ischial spine, you can then insert a long Breisky-Navratil retractor directly opposing the short retractor over the ventral surface of your finger, against the ischial spine with its posterior edge just anterior to the coccygeus muscle.

Sweeping this long retractor counterclockwise immediately across the coccygeus muscle, keeping its posterior blade in contact with the muscle throughout, will mobilize the rectal and pararectal fat medially and expose the coccygeus muscle and sacrospinous ligament. This retractor should be held at approximately the 2 o'clock position, creating a 60- to 90-degree angle with the other Breisky-Navratil retractor. (The exact angle will depend on the angle of the pubic arch.)

At this point, the right-angle Haney retractor can be placed at approximately the 7 o'clock position over the coccygeus muscle and then, with posterior traction, withdrawn distally until it pops down in front of the coccygeus muscle, exposing this muscle and sacrospinous ligament.

A Deschamps ligature carrier then can be inserted through the middle of the coccygeus muscle and rotated clockwise to expose its tip around the sacrospinous ligament. The initial bite should be placed 1 cm medial to the ischial spine to avoid the pudendal complex. A second suture can then be placed 1–2 cm medial to the first, again with care taken to place it through the middle of the coccygeus muscle and not posterior to this muscle, where it could injure the vessel and nerve of the pudendal complex.

When the Deschamps ligature carrier is brought through the muscle, a colpotomy or nerve hook can be used to mobilize one end of the suture and withdraw it back out into the operative field. Once this is mobilized, the Deschamps ligature carrier can be rotated counterclockwise—in an arc exactly opposite to that in which it was placed—to withdraw the posterior end of the suture.

Care should be taken to identify the posterior end of the suture and differentiate it from the anterior end. This may be accomplished through the use of a straight hemostat on one end and the placement of a curved hemostat across both ends of the suture.

(When we perform the surgery, we use a straight hemostat to identify the posterior end of suture on the patient's right side, or the lateral suture, and a straight Kocher clamp to identify the posterior end on the patient's left side.)

The Breisky-Navratil retractors can then be slowly withdrawn one at a time to allow for observation of the entire paravaginal space and assessment for any bleeders, which can be easily grasped and electrocoagulated or sutured.

The suture can then be placed on the undersurface of the apex of the vagina by use of a free Mayo needle. The anterior arm of the lateral suture can be placed approximately 1–2 cm away from the right apex of the vagina in a figure-eight fashion, and this one arm of the suture can be tied to itself with a loose surgeon's knot.

The same process can be followed with the left or medial anterior arm of the second sacrospinous suture, 1–2 cm away from the left apex of the vagina, and tied down in the same fashion. Care needs to be taken on the patient's left side to place the suture approximately 0.5 cm further away from the apical edge of the vagina, as this suture will traverse a longer distance to reach the sacrospinous ligament.

Now the sutures can be retracted anteriorly, and a rectocele repair and/or enterocele repair can be performed as needed.

After successful completion of such repairs, excess vaginal epithelium and smooth muscle can be resected as indicated and the posterior vaginal wall closed with either interrupted sutures or a running, locking suture approximately halfway down the posterior vaginal wall.

At this point, the sacrospinous sutures should be tied down, with the suture on the patient's right lateral side tied down first. The posterior arm of the sacrospinous suture should be taken in the nondominant hand, and slow traction should be applied while the apex of the vagina is guided back into position in the pelvis, toward the right sacrospinous ligament.

Once the excess slack is taken up by mobilization of this suture, the suture may be tied down, with care taken to leave no gap between the vaginal apex and the sacrospinous ligament. This suture is then held while the second suture is mobilized in the same fashion and then tied down similarly.

Retraction of the undersurface of the closed posterior vaginal wall will allow for visualization of the sacrospinous sutures, which can be cut approximately 1 cm above the knot. The posterior vaginal wall may be closed, and perineorrhaphy performed as indicated.

The choice of sutures is up to the individual operator. Although Dr. Nichols originally described using delayed-absorbable sutures, later in his career he changed to using one Gore-Tex suture and one polyglycolic acid suture. He informed me that his reason for this was that the permanent suture would offer longer-lasting strength, whereas the delayed-absorbable suture would create more inflammatory response and possibly elicit more scarring.

Variations of the Original Approach

Some surgeons have suggested that a bilateral attachment of the vaginal apex—or attachment of the cervix, when the uterus is preserved—may offer a superior anatomical reconstruction of the vaginal vault, and may avoid deviation of the vagina to the right or the left side.

Instead of placing two sutures on one sacrospinous ligament, a single suture can be placed on the right sacrospinous ligament at its midportion and on the left sacrospinous ligament at its midportion. These sutures are attached to the right and left apex of the vagina, respectively.

This approach, the thinking goes, allows for a wider width of the vaginal apex in the posthysterectomy patient, as well as good lateral support.

Often, a bilateral sacrospinous ligament suspension may be augmented by bilateral paravaginal defect repairs performed through the vagina, with or without the use of an adjuvant graft. The dissection for placement of these sutures is identical to the ipsilateral dissection for sacrospinous vaginal vault suspension, just described, on the patient's right side; it also can be performed on the patient's left side, with care taken to mobilize the rectum medially (which is often a more challenging task on the patient's left side).

Bilateral suspension to the sacrospinous ligament has not, however, been compared directly to unilateral sacrospinous vaginal vault suspension. Sometimes, when scarring exists in the midline from prior vaginal hysterectomy, or when an enterocele repair has been performed, there may be indentation in the midline of the vaginal vault, creating a somewhat Y-shaped vagina.

In a report published in 1997, Dr. J.F. Pohl and Dr. J.L. Frattarelli concluded that bilateral suspension is feasible in many patients, but that it requires significant intraoperative judgment both as to its feasibility and as to the width of the vaginal cuff that will allow a bilateral suspension without tension (Am. J. Obstet. Gynecol. 1997;177:1356–61).

In our practice, we tend to prefer right-sided vaginal vault suspensions in which we utilize either an anterior approach or a posterior approach, with a left-sided iliococcygeus vaginal vault suspension. This requires less dissection and less risk of bleeding, as the sutures are placed lateral to the ischial spine.

It also creates a vagina with further cephalad elevation of the right vaginal apex than the left vaginal apex, as well as an ample apical width.

Anterior sacrospinous suspension is an approach that we have pursued and described in order to address possible shortcomings or limitations of the conventional posterior approach—chiefly, recurrence of anterior vaginal wall prolapse and a deep posterior angle and narrowing of the upper one-third of the vaginal vault.

Whereas posterior suspension uses a posterior vaginal incision and pararectal dissection, anterior suspension uses an anterior vaginal incision, perforation into the right retropubic space, and dissection of the ipsilateral paravaginal space from the level of the bladder neck to the ischial spine, to create a wide space to accommodate the vaginal vault.

In our experience—Dr. Harvey A. Winkler, Dr. Janet E. Tomeszko, and I first reported on the technique in 2000—the anterior approach appears to reduce postoperative proximal vaginal narrowing and lateral deviation of the upper vagina by avoiding passage through the rectal pillars (Obstet. Gynecol. 2000;95:612–5).

The technique involves opening the anterior vaginal wall and separating the endopelvic connective tissue on the patient's right from the pubic ramus at the level of the bladder neck to the ischial spine, exposing the paravesical and pararectal space. The sacrospinous ligament is identified and isolated through this space.

Two permanent sutures are placed approximately 2 cm apart through the ligament, anchored with pulley stitches underneath the vaginal epithelium and smooth muscle, and tied down to the ligament.

An Evolution in Instrumentation

The Deschamps ligature carrier is the device originally used for applying sutures through the coccygeus muscle and sacrospinous ligament. However, because the ligature carrier is delivered posterior-laterally to anterior-medially, there always has been concern about potential damage to the pudendal artery, vein, and nerve.

With the advent of newer devices that deliver the suture in a limited arc from the anterior to posterior direction, the risk of damage to the pudendal complex has been significantly minimized and the need for extensive dissection is often unnecessary. The newer devices have thus improved not only the safety of the procedure but also its simplicity, and they have reduced the operative time required.

The first of these devices described for applying sutures in a defined arc from anterior to posterior was the Miya hook, described by Dr. F. Miyazaki.

Another new device, the Capio device, is a push-and-catch suture delivery system that allows the suture to be delivered over a defined arc into a catch device. The Capio device has enabled placement of sacrospinous sutures through palpation and without direct visualization of the ligament. This further limits the need for dissection of the perirectal space, potentially improving safety and reducing blood loss.

Other authors have described using the Schutt device, which also delivers a suture from anterior to posterior in a defined arc to improve the safety and speed of the procedure.

Evolving Research

At this time, there are relatively few studies that have compared vaginal sacrospinous colpopexy with abdominal sacral colpopexy for the treatment of upper vaginal prolapse.

The two prospective, randomized trials that appear to be most often cited and referred to—a study by Dr. Christopher F. Maher published in 2004 and a study by Dr. J. Thomas Benson published in 1996—were quite different in their scope and methodology (Am. J. Obstet. Gynecol. 2004;190:20–6; 1996;175:1418–21).

Dr. Benson's group reported data for 80 women with uterovaginal or vault prolapse and concluded that the abdominal approach was more effective, but this study involved the use of multiple concomitant procedures that may have confounded the outcomes.

Needle suspensions of the bladder neck were used in the vaginal surgery group, compared with retropubic urethropexies in the abdominal surgery group. Needle suspensions have been associated with a significant increased risk of subsequent recurrent cystocele and have affected the high recurrent prolapse rate for the vaginal surgery group.

The outcomes for both groups in the Benson study were very poor and markedly different from other results in the literature, which makes it difficult to generalize these outcomes to other populations.

Dr. Maher's study was better designed and has been more reflective of my experience and the experience of many other surgeons. His group reported on 95 women with posthysterectomy vaginal vault prolapse, and concluded that both surgeries are highly effective and significantly improve the patient's quality of life.

Similarly, in the same year of Dr. Benson's publication, Dr. P.J. Hardiman and Dr. H.P. Drutz reported that in a case series of 130 sacrospinous vaginal vault suspensions and 80 abdominal sacral colpopexies, the failure rate in terms of the recurrent vault prolapse was 2.4% with the vaginal approach and 1.3% with the abdominal approach (Am. J. Obstet. Gynecol. 1996;175[3, pt. 1]:612–6).

They concluded that both approaches were associated with a low incidence of complications and recurrent vault prolapse.

Although it was not a randomized trial, the Hardiman-Drutz study is noteworthy and the outcomes are more comparable with real-life experience. I believe that surgeons who are expert at performing both surgeries find them to be equally successful, with the vaginal approach having less morbidity.

Success, in most cases, has been defined through rates of recurrent apical or anterior vaginal prolapse, and few studies have addressed anatomical outcomes more directly relevant to vaginal function, such as length, axis, and sexual satisfaction.

We are challenged by the lack of universally accepted standards for quantifying such outcomes, but nevertheless, such outcomes should be pursued.

In a study reported in 2001 (with Dr. R. Goldberg as lead author), we found that sexual function was well preserved regardless of the sacrospinous suspension technique, with equally low rates of postoperative dyspareunia in both groups (Obstet. Gynecol. 2001;98:199–204).

Metzenbaum scissors are used to free the endopelvic connective tissue from the vaginal epithelium. Courtesy Dr. Peter Sand

The dissection finger is placed adjacent to the suture site.

The upper vaginal vault is sutured to the sacrospinous ligament.

Vaginal wall suturing is done at the upper portion of the vaginal apex. Images courtesy Dr. Peter Sand

A Vaginal Approach to Pelvic Floor Prolapse

In a recent Master Class (OB.GYN. NEWS, Aug. 1, 2007, p. 24), abdominal sacral colpopexy via a laparoscopic approach was featured for the treatment of vaginal vault prolapse. However, for the gynecologic surgeon who is more adroit with vaginal surgery, sacrospinous vaginal vault suspension also offers a safe and effective remedy for this disorder. As a review, the ischial spine is located approximately halfway between the pubic bones and the sacrum. Posterior to the spine is the sacrospinous ligament with the overlying coccygeus muscle. The sacrospinous ligament marks the posterior limit of the pelvic diaphragm.

Because he is a nationally recognized expert in the vaginal approach to pelvic floor prolapse, I have asked Dr. Peter Sand to discuss vaginal vault suspension, the evolution of the procedure, and the prevailing literature that compares this technique with abdominal sacral colpopexy.

Dr. Sand is currently a professor of ob.gyn. at Northwestern University, Chicago, and the director of urogynecology and reconstructive pelvic surgery at Evanston (Ill.) Northwestern Healthcare. Dr. Sand is a prolific researcher and much-sought-after lecturer. As this year's scientific program chairman of the American Association of Gynecologic Laparoscopists' Global Congress of Minimally Invasive Gynecology, I invited Dr. Sand to present a surgical tutorial on the vaginal approach to prolapse. Just as the participants found his discussion interesting and informative, I am sure our readers will feel the same.

Indeed, the majority of women who deliver prematurely will deliver at term in the next pregnancy without any intervention. However, their risk is increased, compared with that of women who delivered at term. About 15% of all preterm births in the United States occur in women who had a previous preterm birth; the risk increases in women with more than one prior preterm birth and in women whose preterm birth was early (before 32 weeks' gestation).

It's important to recognize these women as being at risk, because there is now good evidence that we can reduce the risk of recurrent preterm birth by about one-third by using prophylactic treatment with progesterone.

This development—our ability to prevent a sizeable portion of the leading cause of infant mortality in the United States—puts the onus on obstetricians to investigate each patient's history and to be aware of recent literature on the use of progesterone prophylaxis.

Information available in 2007 is stronger than it was in 2003, when the American College of Obstetricians and Gynecologists (ACOG) issued a Committee Opinion endorsing consideration of progesterone for women with a history of preterm birth.

More research is needed to fully understand how progesterone reduces the risk of preterm birth—and we must continue to monitor its long-term safety—but current evidence indicates that progesterone should be considered for women with a previous preterm birth that was spontaneous (that is, resulting from preterm labor or preterm ruptured membranes).

Risk for Recurrence

Recognizing that women with a previous preterm birth are at increased risk of having another preterm birth is the first step. However, the assessment of risk should go beyond the usual estimate that risk increases by a factor of two after a woman has one preterm birth.

We need to consider each woman's initial risk, beginning with her risk in the first pregnancy. Asian, and Hispanic, and white women, for instance, have an initial risk of preterm birth of about 10%; this rises to 20% after a history of one preterm birth. On the other hand, a black woman—regardless of her education or socioeconomic status—has a risk of preterm birth in the first pregnancy that exceeds 15%–16%; for her, a twofold increase becomes 30% or greater.

The other major component of risk assessment may well require medical records. If the first preterm baby was delivered early (before 32 weeks' gestation, and usually weighing less than 1,500 g), the risk of recurrent preterm birth rises by an additional factor of 1.5–2.0.

For a woman who is not black, then, the risk of preterm birth after a prior birth before 32 weeks can be estimated to be 25%–30%, or greater. For a black woman, the estimated risk of another preterm birth under these circumstances rises to 45%–50%.

Moreover, in women with more than one preterm birth, the risk estimate goes up by another factor of 1.5–2.0, so that a woman with two previous early preterm births may have a recurrence risk that exceeds 50%.

Knowledge of the gestational age of the previous infant at delivery and the woman's racial and ethnic background, therefore, is essential to the assessment of a woman's personal level of risk.

Determinations of risk that are as precise as possible can help guide our discussions about the potential benefits of progesterone therapy.

I like to consider preterm birth as the obstetric equivalent of a cardiac event. If a patient moves to town having had a previous heart attack, most physicians would seek and carefully examine the medical records, looking for risk factors and ways to reduce the patient's risk of another heart attack. In obstetrics, we should do the same.

Early Research

The notion that progesterone may improve pregnancy outcome has been considered for decades, most notably in papers by Dr. Arpad Csapo. Dr. Csapo's pioneering animal research led him to suggest that progesterone relaxes the uterus, and that if progesterone therapy were used, labor would occur only when the relaxing effect of progesterone is withdrawn.

In 1975, a report in the New England Journal of Medicine described the results of a small trial of 17 alpha-hydroxyprogesterone caproate (17P) for 43 women who had a history of two preterm deliveries, two miscarriages, or one miscarriage and one preterm delivery (N. Engl. J. Med. 1975;293:675–80).

The finding—that preterm delivery (defined in this study as fewer than 36 weeks' gestation) occurred in 41% of the women in the placebo group and in no women in the treatment group—stimulated interest in the use of 17P, and the treatment became popular for women with recurrent pregnancy loss.

Progesterone use fell out of favor, however, after studies linked diethylstilbestrol (DES) to uterine malformations and cervical cancer in the offspring of treated women. Even though progesterone's actions differ from those of estrogen, hormones in general were deemed to be worrisome.

The net result of this brief period of progesterone use, however, was a series of observational studies tracking the outcomes and health of individuals who were treated in the late 1970s and early 1980s as fetuses.

Although they were not rigorously scientific, the studies provided reassuring findings about the long-term safety of progesterone, as discussed in a thorough review of 17P by Dr. Paul Meis (Obstet. Gynecol. 2005;105:1128–35).

In 1990, Dr. Marc Keirse revived the idea that progesterone could be effective in protecting against preterm birth with a meta-analysis of trials employing 17P. He found “no support for the view that 17 alpha-hydroxyprogesterone caproate protects against miscarriage,” but said that trials did collectively “suggest that that [the therapy] does reduce the occurrence of preterm birth.” (Br. J. Obstet. Gynaecol. 1990;97:149–54).

His review prompted investigators to start looking at progesterone again. Perhaps it had been discarded a little too early, they thought.

More Recent Studies

The study that eventually led to the reintroduction of progesterone for the prevention of spontaneous preterm birth—and the study that led to the cautious endorsement of progesterone therapy by ACOG—was a much larger, randomized, double-blind trial conducted by the Maternal-Fetal Medicine Units (MFMU) Network of the National Institute of Child Health and Human Development, and published in the New England Journal of Medicine in 2003.

Investigators enrolled women at 19 clinical centers who had had at least one previous spontaneous preterm delivery and randomized them, using a 2:1 ratio, to receive weekly injections of 17P (250 mg) or a placebo. Treatment was begun between 16 and 20 weeks and was continued until either delivery or 37 weeks' gestation. (N. Engl. J. Med. 2003;348:2379–85).

The study planned to enroll 500 women, but enrollment was stopped at approximately 450 women by an independent data-monitoring panel when data showed that the rate of preterm delivery (defined as fewer than 37 weeks' gestation) was almost 55% in the one group but just over 36% in the other group. When the data were unmasked, the treatment group was found to have the lower rate of recurrent preterm birth.

This reduction in preterm birth of about one-third took members of the MFMU Network by surprise. When Dr. Meis, the lead author on this paper, first proposed in the mid-1990s that the network study 17P, network investigators—myself included—expected to find minimal, if any, benefit of 17P prophylaxis.

The network, in existence since the late 1980s, is known for conducting unbiased research on interventions that are part of routine obstetric care but are not yet backed by rigorous study. Rarely had the network published a study showing benefit for interventions or processes that many had hoped would be proven beneficial. (For this reason, study designers did not incorporate a full array of outcomes measures—particularly long-term outcomes measures—in the study of 17P.)

Also surprising was a secondary finding that progesterone was more effective in preventing premature births in women whose previous premature delivery occurred earlier than 32 weeks' gestation than in women whose previous delivery occurred later.

Our original theory was based on the expectation that progesterone would act primarily as a uterine relaxant, so—if progesterone worked—we thought it would likely be most effective in women whose previous premature delivery occurred later in gestation (after 32–34 weeks). To our surprise, the network study found that the earlier the previous preterm birth occurred, the more likely progesterone would be to prevent another preterm birth.

Some criticized the study, usually for reasons related to misunderstandings of the rigorous rules under which the MFMU Network operates. The study was stopped and restarted, for instance, because the initial supplier of 17P could not guarantee its purity and therapeutic effect. This required us to set these data aside and start all over again with study medication provided by a new supplier whose product was consistently prepared.

Critics have also said that the high rates of preterm birth raise suspicions about the study's design. What has not been appreciated, however, is that the mean gestational age of previous preterm deliveries was 31 weeks in both the treatment and placebo groups. Moreover, a significant portion (30%–40%) of women in both groups had more than one previous preterm birth, and almost 60% of the women enrolled were black.

The rate of premature birth in the placebo group was thus exactly what one would expect to see in such a study population, based on existing epidemiologic literature. These women were exactly the kind of patients one would expect to sign up for a research trial: women whose index pregnancy resulted in an early preterm birth, an experience they were anxious to avoid.

The Issue Today

Two additional studies published just this year have addressed the issue of progesterone use in women with two other high-risk conditions: multiple gestations and a short cervix.

The trial of progesterone therapy for twin pregnancy—again using 17P—found no benefit for 17P prophylaxis in a study conducted by the MFMU Network (N. Engl. J. Med. 2007;357:454–61). This suggests to me that the mechanism of early delivery of twins is likely to be somewhat different from the mechanism of early delivery in women with a singleton preterm birth.

The recent trial of progesterone therapy for a short cervix, which was conducted by the Fetal Medicine Foundation in England, reported positive results. In this trial, 250 women with a cervical length of 15 mm or less were randomly assigned to receive vaginal progesterone (not 17P) or placebo (N. Engl. J. Med. 2007;357:462–9).

Spontaneous delivery before 34 weeks' gestation was less frequent in the progesterone group (19%) than in the placebo group (34%).

The exact mode of action of 17P therapy in preventing preterm birth is unknown, but we do know that progesterone does many things. It relaxes the uterus and, we now know, it alters or blunts the body's response to inflammation.

My interpretation of the research to date is that progesterone is effective when inflammation is the key element of the pathway to preterm birth (as is often the case for a short cervix) and that it does not work when uterine stretch and contractions are the critical pathway elements (as in twins).

These and other studies need to be repeated and confirmed, however. The MFMU Network has just begun a study of 17P injections for women with a short cervix who are pregnant for the first time. If it turns out that progesterone really does help prevent premature birth in women with a short cervix, then measurement of the cervix using transvaginal ultrasonography could be a useful test to identify women who might benefit from 17P prophylaxis.

For now, I believe that any woman with a previous spontaneous preterm birth should be informed of progesterone therapy. The higher her risk for recurrence—the earlier her previous preterm birth, for instance, or the higher the number of previous preterm births—the more likely it is that she might benefit from this therapy.

A woman whose previous preterm delivery occurred at 35 weeks' gestation, for instance, may well choose to decline the therapy. My discussions with women who have this history are more of a conversation than a recommendation. On the other hand, a woman with two previous preterm births, both before 32 weeks' gestation, should be strongly urged to have the therapy.

Again, a personal estimate of recurrence risk forms the basis for these recommendations. There are currently no data available to support the use of cervical ultrasound in women with a prior preterm birth to identify women who are more or less likely to benefit from progesterone prophylaxis, so we offer it to any woman with an appropriate history. Someday, we may be able to use progesterone more selectively than we do today.

There is no evidence to suggest that progesterone will help women with preterm labor or ruptured membranes in the current pregnancy, so we do not use it in these women.

Any risks of progesterone therapy are primarily theoretical, based on concern about continuing a pregnancy in which inflammation may favor allowing delivery. Fortunately, there are no signs of that in the original Meis study or in the two more recent large studies in women with twins and a short cervix.

A study recently published of the babies born in the 2003 Meis study found no differences in neurologic development between those who received progesterone and those who took placebo. MFMU Network investigators evaluated the children with various neurologic, physical, and developmental examinations, up to the ages of 4–6 years.

I tell my patients that potential risks continue to be monitored, but that progesterone prophylaxis is backed by a lot more evidence than are many other treatments and practices that are considered “standard” in obstetrics today.

Prematurity is a common and major contributor to the relatively high U.S. infant mortality rate. Therapeutic approaches have been only marginally successful. PhotoDisc, Inc.

Prematurity and Infant Mortality

Infant mortality in the United States was more than 6 per 1,000 live births in 2004, the latest year for which data are available from the Centers for Disease Control and Prevention. This troubling rate places the United States low in the ranking of industrialized nations.

The death rate varies among different geographic areas and among various ethnic and racial groups. A common and major contributor to this relatively high infant mortality rate, however, is prematurity.

The causation of prematurity has been elusive, and therapeutic approaches have been only marginally successful. In recent years, however, a more scientific approach has been taken to understand the biology of premature labor that results in premature birth. This approach has been informing our understanding of this condition.

The National Institute of Child Health and Human Development (NICHD) has made prematurity a major part of its portfolio. The institute has a branch, in fact, whose research is dedicated to this significant obstetric problem. Many years ago, the NICHD also launched the Maternal-Fetal Medicine Units (MFMU) Network, which is a national collaborative that attempts to study difficult problems in obstetrics and tries to propose scientific solutions.

Most recently, the network engaged in a study in which it attempted to reexamine a preventive approach using hormone therapy. The network employed a randomized clinical trial methodology.

In this month's Master Class, I've invited Dr. Jay Iams, a professor of obstetrics and maternal-fetal medicine at Ohio State University, Columbus, and a member of the NICHD's MFMU Network, to address the issue of hormone prophylaxis for women who have already had one preterm birth. He will update us on the network's trial and other related research, and provide us with recommendations for applying these findings to current practice.

Take Home Points For Prevention

▸ When caring for a woman with a prior preterm birth, take a thorough history of the entire pregnancy, and look for events that might have contributed. Think like an internist who is taking care of someone with a previous heart attack: Are these risks still present? Can they be eliminated or reduced?

▸ Estimate each woman's individual risk of recurrent preterm birth, taking into account the gestational age at the time of the previous preterm birth, her racial/ethnic background, and the number of prior preterm births.

▸ Consider and discuss supplemental progesterone prophylaxis with women who have had a prior spontaneous preterm birth, especially women who have had a prior early (before 32 weeks) preterm birth, or more than one prior preterm birth. Think of spontaneous preterm birth as one that did not follow a specific indication for delivery, such as fetal distress, preeclampsia, or bleeding due to placenta previa. Spontaneous preterm births are those between 17 and 36 weeks that followed premature cervical dilation and effacement with or without contractions, or preterm premature rupture of membranes.

▸ Don't use progesterone prophylaxis in women with multiple gestation.

▸ Don't use progesterone prophylaxis in women with preterm labor in the current pregnancy, or as a tocolytic.

Indeed, the majority of women who deliver prematurely will deliver at term in the next pregnancy without any intervention. However, their risk is increased, compared with that of women who delivered at term. About 15% of all preterm births in the United States occur in women who had a previous preterm birth; the risk increases in women with more than one prior preterm birth and in women whose preterm birth was early (before 32 weeks' gestation).

It's important to recognize these women as being at risk, because there is now good evidence that we can reduce the risk of recurrent preterm birth by about one-third by using prophylactic treatment with progesterone.

This development—our ability to prevent a sizeable portion of the leading cause of infant mortality in the United States—puts the onus on obstetricians to investigate each patient's history and to be aware of recent literature on the use of progesterone prophylaxis.

Information available in 2007 is stronger than it was in 2003, when the American College of Obstetricians and Gynecologists (ACOG) issued a Committee Opinion endorsing consideration of progesterone for women with a history of preterm birth.

More research is needed to fully understand how progesterone reduces the risk of preterm birth—and we must continue to monitor its long-term safety—but current evidence indicates that progesterone should be considered for women with a previous preterm birth that was spontaneous (that is, resulting from preterm labor or preterm ruptured membranes).

Risk for Recurrence

Recognizing that women with a previous preterm birth are at increased risk of having another preterm birth is the first step. However, the assessment of risk should go beyond the usual estimate that risk increases by a factor of two after a woman has one preterm birth.

We need to consider each woman's initial risk, beginning with her risk in the first pregnancy. Asian, and Hispanic, and white women, for instance, have an initial risk of preterm birth of about 10%; this rises to 20% after a history of one preterm birth. On the other hand, a black woman—regardless of her education or socioeconomic status—has a risk of preterm birth in the first pregnancy that exceeds 15%–16%; for her, a twofold increase becomes 30% or greater.

The other major component of risk assessment may well require medical records. If the first preterm baby was delivered early (before 32 weeks' gestation, and usually weighing less than 1,500 g), the risk of recurrent preterm birth rises by an additional factor of 1.5–2.0.

For a woman who is not black, then, the risk of preterm birth after a prior birth before 32 weeks can be estimated to be 25%–30%, or greater. For a black woman, the estimated risk of another preterm birth under these circumstances rises to 45%–50%.

Moreover, in women with more than one preterm birth, the risk estimate goes up by another factor of 1.5–2.0, so that a woman with two previous early preterm births may have a recurrence risk that exceeds 50%.

Knowledge of the gestational age of the previous infant at delivery and the woman's racial and ethnic background, therefore, is essential to the assessment of a woman's personal level of risk.

Determinations of risk that are as precise as possible can help guide our discussions about the potential benefits of progesterone therapy.

I like to consider preterm birth as the obstetric equivalent of a cardiac event. If a patient moves to town having had a previous heart attack, most physicians would seek and carefully examine the medical records, looking for risk factors and ways to reduce the patient's risk of another heart attack. In obstetrics, we should do the same.

Early Research

The notion that progesterone may improve pregnancy outcome has been considered for decades, most notably in papers by Dr. Arpad Csapo. Dr. Csapo's pioneering animal research led him to suggest that progesterone relaxes the uterus, and that if progesterone therapy were used, labor would occur only when the relaxing effect of progesterone is withdrawn.

In 1975, a report in the New England Journal of Medicine described the results of a small trial of 17 alpha-hydroxyprogesterone caproate (17P) for 43 women who had a history of two preterm deliveries, two miscarriages, or one miscarriage and one preterm delivery (N. Engl. J. Med. 1975;293:675–80).

The finding—that preterm delivery (defined in this study as fewer than 36 weeks' gestation) occurred in 41% of the women in the placebo group and in no women in the treatment group—stimulated interest in the use of 17P, and the treatment became popular for women with recurrent pregnancy loss.

Progesterone use fell out of favor, however, after studies linked diethylstilbestrol (DES) to uterine malformations and cervical cancer in the offspring of treated women. Even though progesterone's actions differ from those of estrogen, hormones in general were deemed to be worrisome.

The net result of this brief period of progesterone use, however, was a series of observational studies tracking the outcomes and health of individuals who were treated in the late 1970s and early 1980s as fetuses.

Although they were not rigorously scientific, the studies provided reassuring findings about the long-term safety of progesterone, as discussed in a thorough review of 17P by Dr. Paul Meis (Obstet. Gynecol. 2005;105:1128–35).

In 1990, Dr. Marc Keirse revived the idea that progesterone could be effective in protecting against preterm birth with a meta-analysis of trials employing 17P. He found “no support for the view that 17 alpha-hydroxyprogesterone caproate protects against miscarriage,” but said that trials did collectively “suggest that that [the therapy] does reduce the occurrence of preterm birth.” (Br. J. Obstet. Gynaecol. 1990;97:149–54).

His review prompted investigators to start looking at progesterone again. Perhaps it had been discarded a little too early, they thought.

More Recent Studies

The study that eventually led to the reintroduction of progesterone for the prevention of spontaneous preterm birth—and the study that led to the cautious endorsement of progesterone therapy by ACOG—was a much larger, randomized, double-blind trial conducted by the Maternal-Fetal Medicine Units (MFMU) Network of the National Institute of Child Health and Human Development, and published in the New England Journal of Medicine in 2003.

Investigators enrolled women at 19 clinical centers who had had at least one previous spontaneous preterm delivery and randomized them, using a 2:1 ratio, to receive weekly injections of 17P (250 mg) or a placebo. Treatment was begun between 16 and 20 weeks and was continued until either delivery or 37 weeks' gestation. (N. Engl. J. Med. 2003;348:2379–85).

The study planned to enroll 500 women, but enrollment was stopped at approximately 450 women by an independent data-monitoring panel when data showed that the rate of preterm delivery (defined as fewer than 37 weeks' gestation) was almost 55% in the one group but just over 36% in the other group. When the data were unmasked, the treatment group was found to have the lower rate of recurrent preterm birth.

This reduction in preterm birth of about one-third took members of the MFMU Network by surprise. When Dr. Meis, the lead author on this paper, first proposed in the mid-1990s that the network study 17P, network investigators—myself included—expected to find minimal, if any, benefit of 17P prophylaxis.

The network, in existence since the late 1980s, is known for conducting unbiased research on interventions that are part of routine obstetric care but are not yet backed by rigorous study. Rarely had the network published a study showing benefit for interventions or processes that many had hoped would be proven beneficial. (For this reason, study designers did not incorporate a full array of outcomes measures—particularly long-term outcomes measures—in the study of 17P.)

Also surprising was a secondary finding that progesterone was more effective in preventing premature births in women whose previous premature delivery occurred earlier than 32 weeks' gestation than in women whose previous delivery occurred later.

Our original theory was based on the expectation that progesterone would act primarily as a uterine relaxant, so—if progesterone worked—we thought it would likely be most effective in women whose previous premature delivery occurred later in gestation (after 32–34 weeks). To our surprise, the network study found that the earlier the previous preterm birth occurred, the more likely progesterone would be to prevent another preterm birth.

Some criticized the study, usually for reasons related to misunderstandings of the rigorous rules under which the MFMU Network operates. The study was stopped and restarted, for instance, because the initial supplier of 17P could not guarantee its purity and therapeutic effect. This required us to set these data aside and start all over again with study medication provided by a new supplier whose product was consistently prepared.

Critics have also said that the high rates of preterm birth raise suspicions about the study's design. What has not been appreciated, however, is that the mean gestational age of previous preterm deliveries was 31 weeks in both the treatment and placebo groups. Moreover, a significant portion (30%–40%) of women in both groups had more than one previous preterm birth, and almost 60% of the women enrolled were black.

The rate of premature birth in the placebo group was thus exactly what one would expect to see in such a study population, based on existing epidemiologic literature. These women were exactly the kind of patients one would expect to sign up for a research trial: women whose index pregnancy resulted in an early preterm birth, an experience they were anxious to avoid.

The Issue Today

Two additional studies published just this year have addressed the issue of progesterone use in women with two other high-risk conditions: multiple gestations and a short cervix.

The trial of progesterone therapy for twin pregnancy—again using 17P—found no benefit for 17P prophylaxis in a study conducted by the MFMU Network (N. Engl. J. Med. 2007;357:454–61). This suggests to me that the mechanism of early delivery of twins is likely to be somewhat different from the mechanism of early delivery in women with a singleton preterm birth.

The recent trial of progesterone therapy for a short cervix, which was conducted by the Fetal Medicine Foundation in England, reported positive results. In this trial, 250 women with a cervical length of 15 mm or less were randomly assigned to receive vaginal progesterone (not 17P) or placebo (N. Engl. J. Med. 2007;357:462–9).

Spontaneous delivery before 34 weeks' gestation was less frequent in the progesterone group (19%) than in the placebo group (34%).

The exact mode of action of 17P therapy in preventing preterm birth is unknown, but we do know that progesterone does many things. It relaxes the uterus and, we now know, it alters or blunts the body's response to inflammation.

My interpretation of the research to date is that progesterone is effective when inflammation is the key element of the pathway to preterm birth (as is often the case for a short cervix) and that it does not work when uterine stretch and contractions are the critical pathway elements (as in twins).

These and other studies need to be repeated and confirmed, however. The MFMU Network has just begun a study of 17P injections for women with a short cervix who are pregnant for the first time. If it turns out that progesterone really does help prevent premature birth in women with a short cervix, then measurement of the cervix using transvaginal ultrasonography could be a useful test to identify women who might benefit from 17P prophylaxis.

For now, I believe that any woman with a previous spontaneous preterm birth should be informed of progesterone therapy. The higher her risk for recurrence—the earlier her previous preterm birth, for instance, or the higher the number of previous preterm births—the more likely it is that she might benefit from this therapy.

A woman whose previous preterm delivery occurred at 35 weeks' gestation, for instance, may well choose to decline the therapy. My discussions with women who have this history are more of a conversation than a recommendation. On the other hand, a woman with two previous preterm births, both before 32 weeks' gestation, should be strongly urged to have the therapy.

Again, a personal estimate of recurrence risk forms the basis for these recommendations. There are currently no data available to support the use of cervical ultrasound in women with a prior preterm birth to identify women who are more or less likely to benefit from progesterone prophylaxis, so we offer it to any woman with an appropriate history. Someday, we may be able to use progesterone more selectively than we do today.

There is no evidence to suggest that progesterone will help women with preterm labor or ruptured membranes in the current pregnancy, so we do not use it in these women.

Any risks of progesterone therapy are primarily theoretical, based on concern about continuing a pregnancy in which inflammation may favor allowing delivery. Fortunately, there are no signs of that in the original Meis study or in the two more recent large studies in women with twins and a short cervix.

A study recently published of the babies born in the 2003 Meis study found no differences in neurologic development between those who received progesterone and those who took placebo. MFMU Network investigators evaluated the children with various neurologic, physical, and developmental examinations, up to the ages of 4–6 years.

I tell my patients that potential risks continue to be monitored, but that progesterone prophylaxis is backed by a lot more evidence than are many other treatments and practices that are considered “standard” in obstetrics today.

Prematurity is a common and major contributor to the relatively high U.S. infant mortality rate. Therapeutic approaches have been only marginally successful. PhotoDisc, Inc.

Prematurity and Infant Mortality

Infant mortality in the United States was more than 6 per 1,000 live births in 2004, the latest year for which data are available from the Centers for Disease Control and Prevention. This troubling rate places the United States low in the ranking of industrialized nations.

The death rate varies among different geographic areas and among various ethnic and racial groups. A common and major contributor to this relatively high infant mortality rate, however, is prematurity.

The causation of prematurity has been elusive, and therapeutic approaches have been only marginally successful. In recent years, however, a more scientific approach has been taken to understand the biology of premature labor that results in premature birth. This approach has been informing our understanding of this condition.

The National Institute of Child Health and Human Development (NICHD) has made prematurity a major part of its portfolio. The institute has a branch, in fact, whose research is dedicated to this significant obstetric problem. Many years ago, the NICHD also launched the Maternal-Fetal Medicine Units (MFMU) Network, which is a national collaborative that attempts to study difficult problems in obstetrics and tries to propose scientific solutions.

Most recently, the network engaged in a study in which it attempted to reexamine a preventive approach using hormone therapy. The network employed a randomized clinical trial methodology.

In this month's Master Class, I've invited Dr. Jay Iams, a professor of obstetrics and maternal-fetal medicine at Ohio State University, Columbus, and a member of the NICHD's MFMU Network, to address the issue of hormone prophylaxis for women who have already had one preterm birth. He will update us on the network's trial and other related research, and provide us with recommendations for applying these findings to current practice.

Take Home Points For Prevention

▸ When caring for a woman with a prior preterm birth, take a thorough history of the entire pregnancy, and look for events that might have contributed. Think like an internist who is taking care of someone with a previous heart attack: Are these risks still present? Can they be eliminated or reduced?

▸ Estimate each woman's individual risk of recurrent preterm birth, taking into account the gestational age at the time of the previous preterm birth, her racial/ethnic background, and the number of prior preterm births.

▸ Consider and discuss supplemental progesterone prophylaxis with women who have had a prior spontaneous preterm birth, especially women who have had a prior early (before 32 weeks) preterm birth, or more than one prior preterm birth. Think of spontaneous preterm birth as one that did not follow a specific indication for delivery, such as fetal distress, preeclampsia, or bleeding due to placenta previa. Spontaneous preterm births are those between 17 and 36 weeks that followed premature cervical dilation and effacement with or without contractions, or preterm premature rupture of membranes.

▸ Don't use progesterone prophylaxis in women with multiple gestation.

▸ Don't use progesterone prophylaxis in women with preterm labor in the current pregnancy, or as a tocolytic.

Indeed, the majority of women who deliver prematurely will deliver at term in the next pregnancy without any intervention. However, their risk is increased, compared with that of women who delivered at term. About 15% of all preterm births in the United States occur in women who had a previous preterm birth; the risk increases in women with more than one prior preterm birth and in women whose preterm birth was early (before 32 weeks' gestation).

It's important to recognize these women as being at risk, because there is now good evidence that we can reduce the risk of recurrent preterm birth by about one-third by using prophylactic treatment with progesterone.

This development—our ability to prevent a sizeable portion of the leading cause of infant mortality in the United States—puts the onus on obstetricians to investigate each patient's history and to be aware of recent literature on the use of progesterone prophylaxis.

Information available in 2007 is stronger than it was in 2003, when the American College of Obstetricians and Gynecologists (ACOG) issued a Committee Opinion endorsing consideration of progesterone for women with a history of preterm birth.

More research is needed to fully understand how progesterone reduces the risk of preterm birth—and we must continue to monitor its long-term safety—but current evidence indicates that progesterone should be considered for women with a previous preterm birth that was spontaneous (that is, resulting from preterm labor or preterm ruptured membranes).

Risk for Recurrence

Recognizing that women with a previous preterm birth are at increased risk of having another preterm birth is the first step. However, the assessment of risk should go beyond the usual estimate that risk increases by a factor of two after a woman has one preterm birth.

We need to consider each woman's initial risk, beginning with her risk in the first pregnancy. Asian, and Hispanic, and white women, for instance, have an initial risk of preterm birth of about 10%; this rises to 20% after a history of one preterm birth. On the other hand, a black woman—regardless of her education or socioeconomic status—has a risk of preterm birth in the first pregnancy that exceeds 15%–16%; for her, a twofold increase becomes 30% or greater.

The other major component of risk assessment may well require medical records. If the first preterm baby was delivered early (before 32 weeks' gestation, and usually weighing less than 1,500 g), the risk of recurrent preterm birth rises by an additional factor of 1.5–2.0.

For a woman who is not black, then, the risk of preterm birth after a prior birth before 32 weeks can be estimated to be 25%–30%, or greater. For a black woman, the estimated risk of another preterm birth under these circumstances rises to 45%–50%.

Moreover, in women with more than one preterm birth, the risk estimate goes up by another factor of 1.5–2.0, so that a woman with two previous early preterm births may have a recurrence risk that exceeds 50%.

Knowledge of the gestational age of the previous infant at delivery and the woman's racial and ethnic background, therefore, is essential to the assessment of a woman's personal level of risk.

Determinations of risk that are as precise as possible can help guide our discussions about the potential benefits of progesterone therapy.

I like to consider preterm birth as the obstetric equivalent of a cardiac event. If a patient moves to town having had a previous heart attack, most physicians would seek and carefully examine the medical records, looking for risk factors and ways to reduce the patient's risk of another heart attack. In obstetrics, we should do the same.

Early Research

The notion that progesterone may improve pregnancy outcome has been considered for decades, most notably in papers by Dr. Arpad Csapo. Dr. Csapo's pioneering animal research led him to suggest that progesterone relaxes the uterus, and that if progesterone therapy were used, labor would occur only when the relaxing effect of progesterone is withdrawn.

In 1975, a report in the New England Journal of Medicine described the results of a small trial of 17 alpha-hydroxyprogesterone caproate (17P) for 43 women who had a history of two preterm deliveries, two miscarriages, or one miscarriage and one preterm delivery (N. Engl. J. Med. 1975;293:675–80).

The finding—that preterm delivery (defined in this study as fewer than 36 weeks' gestation) occurred in 41% of the women in the placebo group and in no women in the treatment group—stimulated interest in the use of 17P, and the treatment became popular for women with recurrent pregnancy loss.

Progesterone use fell out of favor, however, after studies linked diethylstilbestrol (DES) to uterine malformations and cervical cancer in the offspring of treated women. Even though progesterone's actions differ from those of estrogen, hormones in general were deemed to be worrisome.

The net result of this brief period of progesterone use, however, was a series of observational studies tracking the outcomes and health of individuals who were treated in the late 1970s and early 1980s as fetuses.

Although they were not rigorously scientific, the studies provided reassuring findings about the long-term safety of progesterone, as discussed in a thorough review of 17P by Dr. Paul Meis (Obstet. Gynecol. 2005;105:1128–35).

In 1990, Dr. Marc Keirse revived the idea that progesterone could be effective in protecting against preterm birth with a meta-analysis of trials employing 17P. He found “no support for the view that 17 alpha-hydroxyprogesterone caproate protects against miscarriage,” but said that trials did collectively “suggest that that [the therapy] does reduce the occurrence of preterm birth.” (Br. J. Obstet. Gynaecol. 1990;97:149–54).

His review prompted investigators to start looking at progesterone again. Perhaps it had been discarded a little too early, they thought.

More Recent Studies

The study that eventually led to the reintroduction of progesterone for the prevention of spontaneous preterm birth—and the study that led to the cautious endorsement of progesterone therapy by ACOG—was a much larger, randomized, double-blind trial conducted by the Maternal-Fetal Medicine Units (MFMU) Network of the National Institute of Child Health and Human Development, and published in the New England Journal of Medicine in 2003.

Investigators enrolled women at 19 clinical centers who had had at least one previous spontaneous preterm delivery and randomized them, using a 2:1 ratio, to receive weekly injections of 17P (250 mg) or a placebo. Treatment was begun between 16 and 20 weeks and was continued until either delivery or 37 weeks' gestation. (N. Engl. J. Med. 2003;348:2379–85).

The study planned to enroll 500 women, but enrollment was stopped at approximately 450 women by an independent data-monitoring panel when data showed that the rate of preterm delivery (defined as fewer than 37 weeks' gestation) was almost 55% in the one group but just over 36% in the other group. When the data were unmasked, the treatment group was found to have the lower rate of recurrent preterm birth.

This reduction in preterm birth of about one-third took members of the MFMU Network by surprise. When Dr. Meis, the lead author on this paper, first proposed in the mid-1990s that the network study 17P, network investigators—myself included—expected to find minimal, if any, benefit of 17P prophylaxis.

The network, in existence since the late 1980s, is known for conducting unbiased research on interventions that are part of routine obstetric care but are not yet backed by rigorous study. Rarely had the network published a study showing benefit for interventions or processes that many had hoped would be proven beneficial. (For this reason, study designers did not incorporate a full array of outcomes measures—particularly long-term outcomes measures—in the study of 17P.)

Also surprising was a secondary finding that progesterone was more effective in preventing premature births in women whose previous premature delivery occurred earlier than 32 weeks' gestation than in women whose previous delivery occurred later.

Our original theory was based on the expectation that progesterone would act primarily as a uterine relaxant, so—if progesterone worked—we thought it would likely be most effective in women whose previous premature delivery occurred later in gestation (after 32–34 weeks). To our surprise, the network study found that the earlier the previous preterm birth occurred, the more likely progesterone would be to prevent another preterm birth.

Some criticized the study, usually for reasons related to misunderstandings of the rigorous rules under which the MFMU Network operates. The study was stopped and restarted, for instance, because the initial supplier of 17P could not guarantee its purity and therapeutic effect. This required us to set these data aside and start all over again with study medication provided by a new supplier whose product was consistently prepared.

Critics have also said that the high rates of preterm birth raise suspicions about the study's design. What has not been appreciated, however, is that the mean gestational age of previous preterm deliveries was 31 weeks in both the treatment and placebo groups. Moreover, a significant portion (30%–40%) of women in both groups had more than one previous preterm birth, and almost 60% of the women enrolled were black.

The rate of premature birth in the placebo group was thus exactly what one would expect to see in such a study population, based on existing epidemiologic literature. These women were exactly the kind of patients one would expect to sign up for a research trial: women whose index pregnancy resulted in an early preterm birth, an experience they were anxious to avoid.

The Issue Today

Two additional studies published just this year have addressed the issue of progesterone use in women with two other high-risk conditions: multiple gestations and a short cervix.

The trial of progesterone therapy for twin pregnancy—again using 17P—found no benefit for 17P prophylaxis in a study conducted by the MFMU Network (N. Engl. J. Med. 2007;357:454–61). This suggests to me that the mechanism of early delivery of twins is likely to be somewhat different from the mechanism of early delivery in women with a singleton preterm birth.

The recent trial of progesterone therapy for a short cervix, which was conducted by the Fetal Medicine Foundation in England, reported positive results. In this trial, 250 women with a cervical length of 15 mm or less were randomly assigned to receive vaginal progesterone (not 17P) or placebo (N. Engl. J. Med. 2007;357:462–9).

Spontaneous delivery before 34 weeks' gestation was less frequent in the progesterone group (19%) than in the placebo group (34%).

The exact mode of action of 17P therapy in preventing preterm birth is unknown, but we do know that progesterone does many things. It relaxes the uterus and, we now know, it alters or blunts the body's response to inflammation.

My interpretation of the research to date is that progesterone is effective when inflammation is the key element of the pathway to preterm birth (as is often the case for a short cervix) and that it does not work when uterine stretch and contractions are the critical pathway elements (as in twins).

These and other studies need to be repeated and confirmed, however. The MFMU Network has just begun a study of 17P injections for women with a short cervix who are pregnant for the first time. If it turns out that progesterone really does help prevent premature birth in women with a short cervix, then measurement of the cervix using transvaginal ultrasonography could be a useful test to identify women who might benefit from 17P prophylaxis.

For now, I believe that any woman with a previous spontaneous preterm birth should be informed of progesterone therapy. The higher her risk for recurrence—the earlier her previous preterm birth, for instance, or the higher the number of previous preterm births—the more likely it is that she might benefit from this therapy.

A woman whose previous preterm delivery occurred at 35 weeks' gestation, for instance, may well choose to decline the therapy. My discussions with women who have this history are more of a conversation than a recommendation. On the other hand, a woman with two previous preterm births, both before 32 weeks' gestation, should be strongly urged to have the therapy.

Again, a personal estimate of recurrence risk forms the basis for these recommendations. There are currently no data available to support the use of cervical ultrasound in women with a prior preterm birth to identify women who are more or less likely to benefit from progesterone prophylaxis, so we offer it to any woman with an appropriate history. Someday, we may be able to use progesterone more selectively than we do today.

There is no evidence to suggest that progesterone will help women with preterm labor or ruptured membranes in the current pregnancy, so we do not use it in these women.

Any risks of progesterone therapy are primarily theoretical, based on concern about continuing a pregnancy in which inflammation may favor allowing delivery. Fortunately, there are no signs of that in the original Meis study or in the two more recent large studies in women with twins and a short cervix.

A study recently published of the babies born in the 2003 Meis study found no differences in neurologic development between those who received progesterone and those who took placebo. MFMU Network investigators evaluated the children with various neurologic, physical, and developmental examinations, up to the ages of 4–6 years.

I tell my patients that potential risks continue to be monitored, but that progesterone prophylaxis is backed by a lot more evidence than are many other treatments and practices that are considered “standard” in obstetrics today.

Prematurity is a common and major contributor to the relatively high U.S. infant mortality rate. Therapeutic approaches have been only marginally successful. PhotoDisc, Inc.

Prematurity and Infant Mortality

Infant mortality in the United States was more than 6 per 1,000 live births in 2004, the latest year for which data are available from the Centers for Disease Control and Prevention. This troubling rate places the United States low in the ranking of industrialized nations.

The death rate varies among different geographic areas and among various ethnic and racial groups. A common and major contributor to this relatively high infant mortality rate, however, is prematurity.

The causation of prematurity has been elusive, and therapeutic approaches have been only marginally successful. In recent years, however, a more scientific approach has been taken to understand the biology of premature labor that results in premature birth. This approach has been informing our understanding of this condition.

The National Institute of Child Health and Human Development (NICHD) has made prematurity a major part of its portfolio. The institute has a branch, in fact, whose research is dedicated to this significant obstetric problem. Many years ago, the NICHD also launched the Maternal-Fetal Medicine Units (MFMU) Network, which is a national collaborative that attempts to study difficult problems in obstetrics and tries to propose scientific solutions.

Most recently, the network engaged in a study in which it attempted to reexamine a preventive approach using hormone therapy. The network employed a randomized clinical trial methodology.

In this month's Master Class, I've invited Dr. Jay Iams, a professor of obstetrics and maternal-fetal medicine at Ohio State University, Columbus, and a member of the NICHD's MFMU Network, to address the issue of hormone prophylaxis for women who have already had one preterm birth. He will update us on the network's trial and other related research, and provide us with recommendations for applying these findings to current practice.

Take Home Points For Prevention

▸ When caring for a woman with a prior preterm birth, take a thorough history of the entire pregnancy, and look for events that might have contributed. Think like an internist who is taking care of someone with a previous heart attack: Are these risks still present? Can they be eliminated or reduced?

▸ Estimate each woman's individual risk of recurrent preterm birth, taking into account the gestational age at the time of the previous preterm birth, her racial/ethnic background, and the number of prior preterm births.

▸ Consider and discuss supplemental progesterone prophylaxis with women who have had a prior spontaneous preterm birth, especially women who have had a prior early (before 32 weeks) preterm birth, or more than one prior preterm birth. Think of spontaneous preterm birth as one that did not follow a specific indication for delivery, such as fetal distress, preeclampsia, or bleeding due to placenta previa. Spontaneous preterm births are those between 17 and 36 weeks that followed premature cervical dilation and effacement with or without contractions, or preterm premature rupture of membranes.

▸ Don't use progesterone prophylaxis in women with multiple gestation.

▸ Don't use progesterone prophylaxis in women with preterm labor in the current pregnancy, or as a tocolytic.

CHICAGO — Provocative findings from two studies presented at the annual meeting of the American Society of Clinical Oncology suggest that some patients with HER2-negative breast cancer may benefit from trastuzumab.

A retrospective analysis of the phase III Cancer and Leukemia Group B (CALGB) 9840 trial revealed that human epidermal growth factor 2 (HER2)-negative metastatic breast cancer patients with multiple copies of the chromosome carrying HER2 had significantly better response rates (63% vs. 26%) when they were treated with trastuzumab (Herceptin) in addition to paclitaxel.

In the adjuvant setting, another retrospective analysis showed that a small group of HER2-negative patients in the phase III National Surgical Adjuvant Breast and Bowel Project (NSABP) B-31 trial had significantly better disease-free survival with a relative risk of 0.40 when given trastuzumab after completing treatment for early breast cancer.

Both studies drew considerable attention, with investigators and discussants discouraging attendees from using findings in the clinical setting before they can be verified.

“We emphasize that additional study is needed. At the moment we don't feel that these data should be used clinically,” Dr. Peter A. Kaufman concluded in his presentation of the CALGB data.

He stressed that only a small number of patients were analyzed and noted that trastuzumab did not improve progression-free survival or overall survival for the HER2-negative patients with polysomy of chromosome 17.

Dr. Soonmyung Paik of the NSABP called for a randomized clinical trial to test adjuvant trastuzumab in HER2-negative women.

A favorable outcome might lead to expansion of trastuzumab's indication from 20% to about 60% of breast cancer patients, he said.

“The major question raised by this paper is, what now?” Dr. James H. Doroshow said, advising that the NSABP study needs to be confirmed before new standards for HER2 positivity can be developed.

“It is critical that all appropriate adjuvant breast cancer sets be reevaluated, so that a new consensus can be established for HER2 testing,” said Dr. Doroshow, director of the National Cancer Institute's division of cancer treatment and diagnosis.

After a lengthy audience discussion in which one physician demanded a reason not to expand use of trastuzumab, Dr. Vered Stearns advocated further investigation of HER2 copy number in available data sets from large clinical trials in the metastatic and adjuvant settings.

“Until additional information is available, HER2 copy number and proteomics are not ready for prime time,” said Dr. Stearns of the cancer center at Johns Hopkins University, Baltimore.

Investigators were limited to available tissue blocks in the two retrospective studies of completed trials. They also grappled with disparities between local and central laboratories testing for HER2 positivity, and with standards for making the determination by immunohistochemistry (IHC) and/or fluorescent in situ hybridization (FISH).

The original report from the CALGB 9840 trial indicated that weekly paclitaxel was superior to paclitaxel taken every 3 weeks in metastatic breast cancer. Although more HER2-negative women responded when trastuzumab was added to paclitaxel, the difference was not significant.

For the new report (CALGB 150002), a laboratory correlative science study associated with CALGB 9840, Dr. Kaufman and his associates found that 303 tissue blocks were available from the original 585 patients.

These included samples from 129 patients whom local pathologists and/or central testing had classified as HER2-negative at the time that the data were collected.

Within this group, the new investigation determined that 25 patients (19%) had polysomy (defined as 2.2 copies or more per cell) of chromosome 17.

Because the HER2 gene is located on chromosome 17, polysomy is typically associated with increased copies of the HER2 gene as well, according to Dr. Kaufman of the cancer center at the Dartmouth-Hitchcock Medical Center, Lebanon, N.H.

Retesting all the available samples, the investigators classified 192 patients as FISH-negative and identified 38 patients with extra copies of the chromosome. This group included the original 25 HER2-negative patients plus 7 patients who had been classified previously as HER2-positive and 6 whose original HER2 status was unknown.

New central IHC testing of 37 of the 38 cases determined that only 3 (8%) were HER2-positive based on an IHC count of 3+. The remaining 34 (92%) were HER2-negative with IHC counts of 0–2+.

Although trastuzumab significantly increased response in the 38 women, Dr. Kaufman reported that it added no benefit for 103 women who were HER2-negative and did not have polysomy of chromosome 17. An identical proportion (36%) responded to paclitaxel with and without trastuzumab.

Reporting on the reevaluation of the NSABP trial, Dr. Paik noted that the protocol was changed during the trial to require that IHC testing for HER2 be done by qualified laboratories. He said the proportion of patients classified as HER2-negative by IHC and FISH fell from 16.4% before the amendment to 6.8% afterward. Of the trial population, 9.5% (171/1,795) was negative by both measures.

“This is the bottom line. We couldn't find any subset that didn't benefit from trastuzumab,” he said, acknowledging the subsets were small.

In patients deemed negative by both IHC and FISH, the relative risk of recurrence was 0.34.

Noting that the parameters of HER2 positivity originated in the metastatic setting, Dr. Paik and his associates concluded that the “current definition of HER2 overexpression/gene amplification based on data from advanced disease may need to be modified for the adjuvant setting.”

CHICAGO — Provocative findings from two studies presented at the annual meeting of the American Society of Clinical Oncology suggest that some patients with HER2-negative breast cancer may benefit from trastuzumab.

A retrospective analysis of the phase III Cancer and Leukemia Group B (CALGB) 9840 trial revealed that human epidermal growth factor 2 (HER2)-negative metastatic breast cancer patients with multiple copies of the chromosome carrying HER2 had significantly better response rates (63% vs. 26%) when they were treated with trastuzumab (Herceptin) in addition to paclitaxel.

In the adjuvant setting, another retrospective analysis showed that a small group of HER2-negative patients in the phase III National Surgical Adjuvant Breast and Bowel Project (NSABP) B-31 trial had significantly better disease-free survival with a relative risk of 0.40 when given trastuzumab after completing treatment for early breast cancer.

Both studies drew considerable attention, with investigators and discussants discouraging attendees from using findings in the clinical setting before they can be verified.

“We emphasize that additional study is needed. At the moment we don't feel that these data should be used clinically,” Dr. Peter A. Kaufman concluded in his presentation of the CALGB data.

He stressed that only a small number of patients were analyzed and noted that trastuzumab did not improve progression-free survival or overall survival for the HER2-negative patients with polysomy of chromosome 17.

Dr. Soonmyung Paik of the NSABP called for a randomized clinical trial to test adjuvant trastuzumab in HER2-negative women.

A favorable outcome might lead to expansion of trastuzumab's indication from 20% to about 60% of breast cancer patients, he said.

“The major question raised by this paper is, what now?” Dr. James H. Doroshow said, advising that the NSABP study needs to be confirmed before new standards for HER2 positivity can be developed.

“It is critical that all appropriate adjuvant breast cancer sets be reevaluated, so that a new consensus can be established for HER2 testing,” said Dr. Doroshow, director of the National Cancer Institute's division of cancer treatment and diagnosis.

After a lengthy audience discussion in which one physician demanded a reason not to expand use of trastuzumab, Dr. Vered Stearns advocated further investigation of HER2 copy number in available data sets from large clinical trials in the metastatic and adjuvant settings.

“Until additional information is available, HER2 copy number and proteomics are not ready for prime time,” said Dr. Stearns of the cancer center at Johns Hopkins University, Baltimore.

Investigators were limited to available tissue blocks in the two retrospective studies of completed trials. They also grappled with disparities between local and central laboratories testing for HER2 positivity, and with standards for making the determination by immunohistochemistry (IHC) and/or fluorescent in situ hybridization (FISH).

The original report from the CALGB 9840 trial indicated that weekly paclitaxel was superior to paclitaxel taken every 3 weeks in metastatic breast cancer. Although more HER2-negative women responded when trastuzumab was added to paclitaxel, the difference was not significant.

For the new report (CALGB 150002), a laboratory correlative science study associated with CALGB 9840, Dr. Kaufman and his associates found that 303 tissue blocks were available from the original 585 patients.

These included samples from 129 patients whom local pathologists and/or central testing had classified as HER2-negative at the time that the data were collected.

Within this group, the new investigation determined that 25 patients (19%) had polysomy (defined as 2.2 copies or more per cell) of chromosome 17.

Because the HER2 gene is located on chromosome 17, polysomy is typically associated with increased copies of the HER2 gene as well, according to Dr. Kaufman of the cancer center at the Dartmouth-Hitchcock Medical Center, Lebanon, N.H.

Retesting all the available samples, the investigators classified 192 patients as FISH-negative and identified 38 patients with extra copies of the chromosome. This group included the original 25 HER2-negative patients plus 7 patients who had been classified previously as HER2-positive and 6 whose original HER2 status was unknown.

New central IHC testing of 37 of the 38 cases determined that only 3 (8%) were HER2-positive based on an IHC count of 3+. The remaining 34 (92%) were HER2-negative with IHC counts of 0–2+.

Although trastuzumab significantly increased response in the 38 women, Dr. Kaufman reported that it added no benefit for 103 women who were HER2-negative and did not have polysomy of chromosome 17. An identical proportion (36%) responded to paclitaxel with and without trastuzumab.

Reporting on the reevaluation of the NSABP trial, Dr. Paik noted that the protocol was changed during the trial to require that IHC testing for HER2 be done by qualified laboratories. He said the proportion of patients classified as HER2-negative by IHC and FISH fell from 16.4% before the amendment to 6.8% afterward. Of the trial population, 9.5% (171/1,795) was negative by both measures.

“This is the bottom line. We couldn't find any subset that didn't benefit from trastuzumab,” he said, acknowledging the subsets were small.

In patients deemed negative by both IHC and FISH, the relative risk of recurrence was 0.34.

Noting that the parameters of HER2 positivity originated in the metastatic setting, Dr. Paik and his associates concluded that the “current definition of HER2 overexpression/gene amplification based on data from advanced disease may need to be modified for the adjuvant setting.”

CHICAGO — Provocative findings from two studies presented at the annual meeting of the American Society of Clinical Oncology suggest that some patients with HER2-negative breast cancer may benefit from trastuzumab.

A retrospective analysis of the phase III Cancer and Leukemia Group B (CALGB) 9840 trial revealed that human epidermal growth factor 2 (HER2)-negative metastatic breast cancer patients with multiple copies of the chromosome carrying HER2 had significantly better response rates (63% vs. 26%) when they were treated with trastuzumab (Herceptin) in addition to paclitaxel.

In the adjuvant setting, another retrospective analysis showed that a small group of HER2-negative patients in the phase III National Surgical Adjuvant Breast and Bowel Project (NSABP) B-31 trial had significantly better disease-free survival with a relative risk of 0.40 when given trastuzumab after completing treatment for early breast cancer.

Both studies drew considerable attention, with investigators and discussants discouraging attendees from using findings in the clinical setting before they can be verified.

“We emphasize that additional study is needed. At the moment we don't feel that these data should be used clinically,” Dr. Peter A. Kaufman concluded in his presentation of the CALGB data.

He stressed that only a small number of patients were analyzed and noted that trastuzumab did not improve progression-free survival or overall survival for the HER2-negative patients with polysomy of chromosome 17.

Dr. Soonmyung Paik of the NSABP called for a randomized clinical trial to test adjuvant trastuzumab in HER2-negative women.

A favorable outcome might lead to expansion of trastuzumab's indication from 20% to about 60% of breast cancer patients, he said.

“The major question raised by this paper is, what now?” Dr. James H. Doroshow said, advising that the NSABP study needs to be confirmed before new standards for HER2 positivity can be developed.

“It is critical that all appropriate adjuvant breast cancer sets be reevaluated, so that a new consensus can be established for HER2 testing,” said Dr. Doroshow, director of the National Cancer Institute's division of cancer treatment and diagnosis.

After a lengthy audience discussion in which one physician demanded a reason not to expand use of trastuzumab, Dr. Vered Stearns advocated further investigation of HER2 copy number in available data sets from large clinical trials in the metastatic and adjuvant settings.

“Until additional information is available, HER2 copy number and proteomics are not ready for prime time,” said Dr. Stearns of the cancer center at Johns Hopkins University, Baltimore.

Investigators were limited to available tissue blocks in the two retrospective studies of completed trials. They also grappled with disparities between local and central laboratories testing for HER2 positivity, and with standards for making the determination by immunohistochemistry (IHC) and/or fluorescent in situ hybridization (FISH).

The original report from the CALGB 9840 trial indicated that weekly paclitaxel was superior to paclitaxel taken every 3 weeks in metastatic breast cancer. Although more HER2-negative women responded when trastuzumab was added to paclitaxel, the difference was not significant.

For the new report (CALGB 150002), a laboratory correlative science study associated with CALGB 9840, Dr. Kaufman and his associates found that 303 tissue blocks were available from the original 585 patients.

These included samples from 129 patients whom local pathologists and/or central testing had classified as HER2-negative at the time that the data were collected.

Within this group, the new investigation determined that 25 patients (19%) had polysomy (defined as 2.2 copies or more per cell) of chromosome 17.

Because the HER2 gene is located on chromosome 17, polysomy is typically associated with increased copies of the HER2 gene as well, according to Dr. Kaufman of the cancer center at the Dartmouth-Hitchcock Medical Center, Lebanon, N.H.

Retesting all the available samples, the investigators classified 192 patients as FISH-negative and identified 38 patients with extra copies of the chromosome. This group included the original 25 HER2-negative patients plus 7 patients who had been classified previously as HER2-positive and 6 whose original HER2 status was unknown.

New central IHC testing of 37 of the 38 cases determined that only 3 (8%) were HER2-positive based on an IHC count of 3+. The remaining 34 (92%) were HER2-negative with IHC counts of 0–2+.

Although trastuzumab significantly increased response in the 38 women, Dr. Kaufman reported that it added no benefit for 103 women who were HER2-negative and did not have polysomy of chromosome 17. An identical proportion (36%) responded to paclitaxel with and without trastuzumab.

Reporting on the reevaluation of the NSABP trial, Dr. Paik noted that the protocol was changed during the trial to require that IHC testing for HER2 be done by qualified laboratories. He said the proportion of patients classified as HER2-negative by IHC and FISH fell from 16.4% before the amendment to 6.8% afterward. Of the trial population, 9.5% (171/1,795) was negative by both measures.

“This is the bottom line. We couldn't find any subset that didn't benefit from trastuzumab,” he said, acknowledging the subsets were small.

In patients deemed negative by both IHC and FISH, the relative risk of recurrence was 0.34.

Noting that the parameters of HER2 positivity originated in the metastatic setting, Dr. Paik and his associates concluded that the “current definition of HER2 overexpression/gene amplification based on data from advanced disease may need to be modified for the adjuvant setting.”

Urology has long claimed the procedure as one that belongs within its realm of care, but for hundreds of years, gynecologic surgeons have used the cystoscope to examine the bladder. In doing so, they have not only evaluated fistulas and other occurrences, but have also authored many of the medical literature's notable papers on cystoscopy.

Gynecologists have also used the instrumentation to examine the urethra as well as the bladder. Dr. J.R. Robertson, an ob.gyn., is in fact the father of the urethroscope, which consists of an external sheath and a 0-degree lens.

In recent years, gynecologists have become more involved in evaluating problems such as bladder and pelvic pain, including interstitial cystitis, as well as recurrent urinary tract infection and overactive bladder symptoms.

Moreover, they have been performing increasing numbers of pelvic reconstruction procedures—and they have increasingly turned to cystoscopy, both to aid them in office diagnosis and to ensure surgical safety.

The evaluation of hematuria is still mainly within the realm of urologists.

Gynecologists' use of cystoscopy has become less controversial over the past decade as the lines between urology and gynecology have blurred, with gynecologists addressing more traditionally urologic issues and performing more procedures that were previously considered urologic, and vice versa.

Many gynecologists are using hysteroscopy to evaluate fibroids, abnormal uterine bleeding, and other symptoms, and for them, learning cystoscopy is an especially natural fit.

Even without the hysteroscopy backdrop, embracing cystoscopy with proper training is a natural and logical evolution for the specialty. In fact, an American College of Obstetricians and Gynecologists' Committee Opinion, issued in July, stated that cystoscopy is an important diagnostic and therapeutic tool, and that practicing gynecologists, especially gynecologic surgeons, should become comfortable with the routine performance of the procedure.

Office Cystoscopy

Cystoscopy is but one of several diagnostic tools and methods available for evaluating a number of indications, but it is proving to be a useful one. It can readily be performed in the office without the need for sedation.

The equipment needed to perform office cystoscopy includes a good light source; an endoscopic video system; a suitable hookup for a sterile water bag and related tubing; a cystoscope—preferably a narrow-angle scope (0–12.5 degrees)—to examine the urethra; and a wider-angle scope (70 degrees) to examine the bladder itself.

The urethra should be visualized first, with attention given to its anatomy, tone, and vasculature. It will look pink and spongy in a patient who is well estrogenized but pale and flat in someone who is atrophic. In a patient who has had a previous sling, the urethra should be evaluated for evidence of erosion.

Openings in the urethral wall that suggest diverticula, evidence of infection, and any other abnormalities can be identified. In women with stress incontinence, the severity of sphincteric deficiency can be evaluated by assessing urethral tone; someone with intrinsic sphincteric deficiency will have a patulous urethra and bladder neck.

We can also then evaluate mobility of the bladder neck—an area at which fronds, polyps, and cysts are normal variants—and the appearance of the trigone, or the posterior wall of the bladder right above the bladder neck.

Cystoscopy enables us to visualize various degrees of inflammation and to detect chronic trigonitis, an inflammatory condition that can present in women who have symptoms of recurrent urinary tract infection but negative urine cultures. Confirmation of the condition can usually be achieved with vaginal palpation of the trigone.

In visualizing the ureters, which is the next step in the office evaluation, our goal is to thoroughly evaluate the anatomy of the lower urinary tract. We can then examine the rest of the bladder, looking for evidence of obvious abnormalities like stones, tumors, diverticula, and inflammation. A 70-degree scope allows visualization of the entire bladder wall, including the lateral walls where a sling/suture erosion could occur.

We can also look for trabeculations, which are thick ridges observed in the middle of the bladder wall. Such patterns are sometimes a result of normal aging but they are also often found in patients with detrusor overactivity. Diverticula of the bladder can also be visualized; such abnormalities can be responsible for urinary retention.

Bladder tumors can take on various appearances, from flat white areas to cauliflowerlike papillary lesions. Although some cancers are obvious, other low-grade cancers can be extremely subtle in appearance. Persistent hematuria, especially in a smoker, should prompt us to perform a careful cystoscopy to look for tumors. If there is any question of malignancy, a biopsy can be performed in the office or upon referral to a urologist.

In women with bladder pain, we should look out for inflammatory changes, including glomerulations, which can suggest interstitial cystitis.

We also have the option of performing cystoscopy under anesthesia for patients with bladder pain. This process enables us to hydrodistend the bladder—the bladder is filled with fluid to capacity, emptied, and refilled—for an examination both of bladder capacity and of abnormalities like bleeding from glomerulations, while eliminating the pain component. A bladder that holds less than 400 mL of fluid under anesthesia is a bladder that is chronically scarred.

Bladder biopsies can be performed at the time of hydrodistention. Unfortunately, there is no consensus on indications for biopsy or on criteria for diagnosing interstitial cystitis (indeed, much about interstitial cystitis is controversial), but I believe that the scope can be an important diagnostic tool.

There also often is a therapeutic benefit to performing a cystoscopy and hydrodistention under anesthesia: Many patients remain relatively free of pain for 6 months or longer after the procedure. The urethral pain and dysuria that sometimes occur with cystoscopy can be treated with a preprocedure intraurethral injection of lidocaine jelly or oral phenazopyridine (Pyridium). Prophylactic oral antibiotics should be given routinely either right before or right after the procedure.

Intraoperative Cystoscopy

With more advanced incontinence and prolapse surgeries being performed by both urologists and gynecologists, it has become ever more important to use intraoperative cystoscopy to ensure that the bladder and ureters remain undamaged and unobstructed. In fact, we have reached a point where cystoscopy should be performed routinely for most advanced pelvic reconstructive procedures, whether the procedures are done vaginally or abdominally.

It is absolutely imperative that cystoscopy be performed with every retropubic sling that uses the tension-free vaginal tape (TVT) procedure.

With transobturator tape (TOT), its necessity is more debatable because needles don't pass as close to the bladder. Surgeons who have comfortably and successfully performed a significant number of TOT procedures can probably forgo cystoscopy.

There is one exception, however: cases in which TOT is performed before the prolapse is repaired. In this case, cystoscopy remains imperative.

Intraoperative cystoscopy has a fringe benefit as well, in that it sometimes leads to the identification of pathology—bladder stones, for instance—that went undiagnosed during the preoperative work-up.

Cystoscopy can also be used to guide the placement of suprapubic catheters intraoperatively, although its most significant purpose is to document ureteral patency. When examining for patency, most surgeons inject indigo carmine intravenously and examine the bladder approximately 10 minutes later to document flow of the dye through both ureteral openings.

Instruments and Training

A urethroscope with a 0-degree lens allows appropriate examination of the urethra; however, a 70-degree lens is preferable for examination of the bladder because it enables visualization of the entire circumference of the bladder in more detail.

Some surgeons are using flexible cystoscopes—the optics of flexible cystoscopy have improved significantly in recent years—but the 70-degree rigid scope is sufficient in the vast majority of procedures.

Gynecologists who perform trans- or periurethral bulking agent injections for intrinsic sphincteric deficiency must be comfortable with using a 0-degree scope in the office. In this process, which typically is done under cystoscopic guidance, a needle is placed either through the cystoscope or lateral to the urethra, and the agent—collagen (Contigen), silicone (Macroplastique), carbon beads (Durasphere), or another agent—is injected to add bulk around the urethral lumen and to increase urethral resistance.

For many gynecologists, cystoscopy is a natural progression from hysteroscopy. The two procedures are very similar when used for diagnostic purposes. Others are starting to perform cystoscopy even without the background in hysteroscopy, however.

In any case, the main issue we face is the need for training. We must learn how to use the instrumentation and advance the scope safely, without causing bladder trauma or perforation; how to approach various indications; and how to judge abnormal and normal aspects of the images obtained.

Although there are no courses including certification at this time, ACOG and others do offer various training courses designed to allow ob.gyns. to develop an expertise in cystoscopy.

Bladder trabeculations are in a patient with overactive bladder.

Urethral changes reflecting different levels of estrogenation: Atrophic looks pale and flat (top), normal looks pink and spongy (bottom). Photos courtesy Dr. G. Willy Davila

Tension-free vaginal tape mesh is shown in the urethra.

Ureteral opening is shown via cystoscopy, after injection of indigo carmine dye to document ureteral integrity. Photos courtesy Dr. G. Willy Davila

Cystoscopy

As a physician on the teaching faculty of two different residency programs in metropolitan Chicago—and as one whose surgical practice is limited to minimally invasive techniques—I see residents rotating through my service routinely performing cystoscopy in conjunction with total laparoscopic hysterectomy, resection of deep endometriosis over the pelvic sidewall or bladder, placement of a sling for the treatment of stress urinary incontinence, or evaluation of the bladder for interstitial cystitis.

Unfortunately, less than a generation ago, most trainees in our field had virtually no exposure to cystoscopy. Generally, as in my own case, gynecologists interested in gaining cystoscopy skills had to be mentored by a friendly urologist.

With this in mind, I have enlisted Dr. G. Willy Davila to present cystoscopy for this Master Class in gynecologic surgery.

Dr. Davila not only chairs the department of gynecology at the Cleveland Clinic in Weston, Fla., he also heads the clinic's section of urogynecology and reconstructive pelvic surgery.

Dr. Davila serves on the editorial boards of the Journal of Female Urinary Incontinence, Revista Latinoamericana de Uroginecologia y Disfunciones Pelvianas, and the International Urogynecology Journal. He is a prolific writer and has edited three books on the specialty subject matter of urogynecology.

Urology has long claimed the procedure as one that belongs within its realm of care, but for hundreds of years, gynecologic surgeons have used the cystoscope to examine the bladder. In doing so, they have not only evaluated fistulas and other occurrences, but have also authored many of the medical literature's notable papers on cystoscopy.

Gynecologists have also used the instrumentation to examine the urethra as well as the bladder. Dr. J.R. Robertson, an ob.gyn., is in fact the father of the urethroscope, which consists of an external sheath and a 0-degree lens.

In recent years, gynecologists have become more involved in evaluating problems such as bladder and pelvic pain, including interstitial cystitis, as well as recurrent urinary tract infection and overactive bladder symptoms.

Moreover, they have been performing increasing numbers of pelvic reconstruction procedures—and they have increasingly turned to cystoscopy, both to aid them in office diagnosis and to ensure surgical safety.

The evaluation of hematuria is still mainly within the realm of urologists.

Gynecologists' use of cystoscopy has become less controversial over the past decade as the lines between urology and gynecology have blurred, with gynecologists addressing more traditionally urologic issues and performing more procedures that were previously considered urologic, and vice versa.

Many gynecologists are using hysteroscopy to evaluate fibroids, abnormal uterine bleeding, and other symptoms, and for them, learning cystoscopy is an especially natural fit.

Even without the hysteroscopy backdrop, embracing cystoscopy with proper training is a natural and logical evolution for the specialty. In fact, an American College of Obstetricians and Gynecologists' Committee Opinion, issued in July, stated that cystoscopy is an important diagnostic and therapeutic tool, and that practicing gynecologists, especially gynecologic surgeons, should become comfortable with the routine performance of the procedure.

Office Cystoscopy

Cystoscopy is but one of several diagnostic tools and methods available for evaluating a number of indications, but it is proving to be a useful one. It can readily be performed in the office without the need for sedation.

The equipment needed to perform office cystoscopy includes a good light source; an endoscopic video system; a suitable hookup for a sterile water bag and related tubing; a cystoscope—preferably a narrow-angle scope (0–12.5 degrees)—to examine the urethra; and a wider-angle scope (70 degrees) to examine the bladder itself.

The urethra should be visualized first, with attention given to its anatomy, tone, and vasculature. It will look pink and spongy in a patient who is well estrogenized but pale and flat in someone who is atrophic. In a patient who has had a previous sling, the urethra should be evaluated for evidence of erosion.

Openings in the urethral wall that suggest diverticula, evidence of infection, and any other abnormalities can be identified. In women with stress incontinence, the severity of sphincteric deficiency can be evaluated by assessing urethral tone; someone with intrinsic sphincteric deficiency will have a patulous urethra and bladder neck.

We can also then evaluate mobility of the bladder neck—an area at which fronds, polyps, and cysts are normal variants—and the appearance of the trigone, or the posterior wall of the bladder right above the bladder neck.

Cystoscopy enables us to visualize various degrees of inflammation and to detect chronic trigonitis, an inflammatory condition that can present in women who have symptoms of recurrent urinary tract infection but negative urine cultures. Confirmation of the condition can usually be achieved with vaginal palpation of the trigone.

In visualizing the ureters, which is the next step in the office evaluation, our goal is to thoroughly evaluate the anatomy of the lower urinary tract. We can then examine the rest of the bladder, looking for evidence of obvious abnormalities like stones, tumors, diverticula, and inflammation. A 70-degree scope allows visualization of the entire bladder wall, including the lateral walls where a sling/suture erosion could occur.

We can also look for trabeculations, which are thick ridges observed in the middle of the bladder wall. Such patterns are sometimes a result of normal aging but they are also often found in patients with detrusor overactivity. Diverticula of the bladder can also be visualized; such abnormalities can be responsible for urinary retention.

Bladder tumors can take on various appearances, from flat white areas to cauliflowerlike papillary lesions. Although some cancers are obvious, other low-grade cancers can be extremely subtle in appearance. Persistent hematuria, especially in a smoker, should prompt us to perform a careful cystoscopy to look for tumors. If there is any question of malignancy, a biopsy can be performed in the office or upon referral to a urologist.

In women with bladder pain, we should look out for inflammatory changes, including glomerulations, which can suggest interstitial cystitis.

We also have the option of performing cystoscopy under anesthesia for patients with bladder pain. This process enables us to hydrodistend the bladder—the bladder is filled with fluid to capacity, emptied, and refilled—for an examination both of bladder capacity and of abnormalities like bleeding from glomerulations, while eliminating the pain component. A bladder that holds less than 400 mL of fluid under anesthesia is a bladder that is chronically scarred.

Bladder biopsies can be performed at the time of hydrodistention. Unfortunately, there is no consensus on indications for biopsy or on criteria for diagnosing interstitial cystitis (indeed, much about interstitial cystitis is controversial), but I believe that the scope can be an important diagnostic tool.

There also often is a therapeutic benefit to performing a cystoscopy and hydrodistention under anesthesia: Many patients remain relatively free of pain for 6 months or longer after the procedure. The urethral pain and dysuria that sometimes occur with cystoscopy can be treated with a preprocedure intraurethral injection of lidocaine jelly or oral phenazopyridine (Pyridium). Prophylactic oral antibiotics should be given routinely either right before or right after the procedure.

Intraoperative Cystoscopy

With more advanced incontinence and prolapse surgeries being performed by both urologists and gynecologists, it has become ever more important to use intraoperative cystoscopy to ensure that the bladder and ureters remain undamaged and unobstructed. In fact, we have reached a point where cystoscopy should be performed routinely for most advanced pelvic reconstructive procedures, whether the procedures are done vaginally or abdominally.

It is absolutely imperative that cystoscopy be performed with every retropubic sling that uses the tension-free vaginal tape (TVT) procedure.

With transobturator tape (TOT), its necessity is more debatable because needles don't pass as close to the bladder. Surgeons who have comfortably and successfully performed a significant number of TOT procedures can probably forgo cystoscopy.

There is one exception, however: cases in which TOT is performed before the prolapse is repaired. In this case, cystoscopy remains imperative.

Intraoperative cystoscopy has a fringe benefit as well, in that it sometimes leads to the identification of pathology—bladder stones, for instance—that went undiagnosed during the preoperative work-up.

Cystoscopy can also be used to guide the placement of suprapubic catheters intraoperatively, although its most significant purpose is to document ureteral patency. When examining for patency, most surgeons inject indigo carmine intravenously and examine the bladder approximately 10 minutes later to document flow of the dye through both ureteral openings.

Instruments and Training

A urethroscope with a 0-degree lens allows appropriate examination of the urethra; however, a 70-degree lens is preferable for examination of the bladder because it enables visualization of the entire circumference of the bladder in more detail.

Some surgeons are using flexible cystoscopes—the optics of flexible cystoscopy have improved significantly in recent years—but the 70-degree rigid scope is sufficient in the vast majority of procedures.

Gynecologists who perform trans- or periurethral bulking agent injections for intrinsic sphincteric deficiency must be comfortable with using a 0-degree scope in the office. In this process, which typically is done under cystoscopic guidance, a needle is placed either through the cystoscope or lateral to the urethra, and the agent—collagen (Contigen), silicone (Macroplastique), carbon beads (Durasphere), or another agent—is injected to add bulk around the urethral lumen and to increase urethral resistance.

For many gynecologists, cystoscopy is a natural progression from hysteroscopy. The two procedures are very similar when used for diagnostic purposes. Others are starting to perform cystoscopy even without the background in hysteroscopy, however.

In any case, the main issue we face is the need for training. We must learn how to use the instrumentation and advance the scope safely, without causing bladder trauma or perforation; how to approach various indications; and how to judge abnormal and normal aspects of the images obtained.

Although there are no courses including certification at this time, ACOG and others do offer various training courses designed to allow ob.gyns. to develop an expertise in cystoscopy.

Bladder trabeculations are in a patient with overactive bladder.

Urethral changes reflecting different levels of estrogenation: Atrophic looks pale and flat (top), normal looks pink and spongy (bottom). Photos courtesy Dr. G. Willy Davila

Tension-free vaginal tape mesh is shown in the urethra.

Ureteral opening is shown via cystoscopy, after injection of indigo carmine dye to document ureteral integrity. Photos courtesy Dr. G. Willy Davila

Cystoscopy

As a physician on the teaching faculty of two different residency programs in metropolitan Chicago—and as one whose surgical practice is limited to minimally invasive techniques—I see residents rotating through my service routinely performing cystoscopy in conjunction with total laparoscopic hysterectomy, resection of deep endometriosis over the pelvic sidewall or bladder, placement of a sling for the treatment of stress urinary incontinence, or evaluation of the bladder for interstitial cystitis.

Unfortunately, less than a generation ago, most trainees in our field had virtually no exposure to cystoscopy. Generally, as in my own case, gynecologists interested in gaining cystoscopy skills had to be mentored by a friendly urologist.

With this in mind, I have enlisted Dr. G. Willy Davila to present cystoscopy for this Master Class in gynecologic surgery.

Dr. Davila not only chairs the department of gynecology at the Cleveland Clinic in Weston, Fla., he also heads the clinic's section of urogynecology and reconstructive pelvic surgery.

Dr. Davila serves on the editorial boards of the Journal of Female Urinary Incontinence, Revista Latinoamericana de Uroginecologia y Disfunciones Pelvianas, and the International Urogynecology Journal. He is a prolific writer and has edited three books on the specialty subject matter of urogynecology.

Urology has long claimed the procedure as one that belongs within its realm of care, but for hundreds of years, gynecologic surgeons have used the cystoscope to examine the bladder. In doing so, they have not only evaluated fistulas and other occurrences, but have also authored many of the medical literature's notable papers on cystoscopy.

Gynecologists have also used the instrumentation to examine the urethra as well as the bladder. Dr. J.R. Robertson, an ob.gyn., is in fact the father of the urethroscope, which consists of an external sheath and a 0-degree lens.

In recent years, gynecologists have become more involved in evaluating problems such as bladder and pelvic pain, including interstitial cystitis, as well as recurrent urinary tract infection and overactive bladder symptoms.

Moreover, they have been performing increasing numbers of pelvic reconstruction procedures—and they have increasingly turned to cystoscopy, both to aid them in office diagnosis and to ensure surgical safety.

The evaluation of hematuria is still mainly within the realm of urologists.

Gynecologists' use of cystoscopy has become less controversial over the past decade as the lines between urology and gynecology have blurred, with gynecologists addressing more traditionally urologic issues and performing more procedures that were previously considered urologic, and vice versa.

Many gynecologists are using hysteroscopy to evaluate fibroids, abnormal uterine bleeding, and other symptoms, and for them, learning cystoscopy is an especially natural fit.

Even without the hysteroscopy backdrop, embracing cystoscopy with proper training is a natural and logical evolution for the specialty. In fact, an American College of Obstetricians and Gynecologists' Committee Opinion, issued in July, stated that cystoscopy is an important diagnostic and therapeutic tool, and that practicing gynecologists, especially gynecologic surgeons, should become comfortable with the routine performance of the procedure.

Office Cystoscopy

Cystoscopy is but one of several diagnostic tools and methods available for evaluating a number of indications, but it is proving to be a useful one. It can readily be performed in the office without the need for sedation.

The equipment needed to perform office cystoscopy includes a good light source; an endoscopic video system; a suitable hookup for a sterile water bag and related tubing; a cystoscope—preferably a narrow-angle scope (0–12.5 degrees)—to examine the urethra; and a wider-angle scope (70 degrees) to examine the bladder itself.

The urethra should be visualized first, with attention given to its anatomy, tone, and vasculature. It will look pink and spongy in a patient who is well estrogenized but pale and flat in someone who is atrophic. In a patient who has had a previous sling, the urethra should be evaluated for evidence of erosion.

Openings in the urethral wall that suggest diverticula, evidence of infection, and any other abnormalities can be identified. In women with stress incontinence, the severity of sphincteric deficiency can be evaluated by assessing urethral tone; someone with intrinsic sphincteric deficiency will have a patulous urethra and bladder neck.

We can also then evaluate mobility of the bladder neck—an area at which fronds, polyps, and cysts are normal variants—and the appearance of the trigone, or the posterior wall of the bladder right above the bladder neck.

Cystoscopy enables us to visualize various degrees of inflammation and to detect chronic trigonitis, an inflammatory condition that can present in women who have symptoms of recurrent urinary tract infection but negative urine cultures. Confirmation of the condition can usually be achieved with vaginal palpation of the trigone.

In visualizing the ureters, which is the next step in the office evaluation, our goal is to thoroughly evaluate the anatomy of the lower urinary tract. We can then examine the rest of the bladder, looking for evidence of obvious abnormalities like stones, tumors, diverticula, and inflammation. A 70-degree scope allows visualization of the entire bladder wall, including the lateral walls where a sling/suture erosion could occur.

We can also look for trabeculations, which are thick ridges observed in the middle of the bladder wall. Such patterns are sometimes a result of normal aging but they are also often found in patients with detrusor overactivity. Diverticula of the bladder can also be visualized; such abnormalities can be responsible for urinary retention.

Bladder tumors can take on various appearances, from flat white areas to cauliflowerlike papillary lesions. Although some cancers are obvious, other low-grade cancers can be extremely subtle in appearance. Persistent hematuria, especially in a smoker, should prompt us to perform a careful cystoscopy to look for tumors. If there is any question of malignancy, a biopsy can be performed in the office or upon referral to a urologist.

In women with bladder pain, we should look out for inflammatory changes, including glomerulations, which can suggest interstitial cystitis.

We also have the option of performing cystoscopy under anesthesia for patients with bladder pain. This process enables us to hydrodistend the bladder—the bladder is filled with fluid to capacity, emptied, and refilled—for an examination both of bladder capacity and of abnormalities like bleeding from glomerulations, while eliminating the pain component. A bladder that holds less than 400 mL of fluid under anesthesia is a bladder that is chronically scarred.

Bladder biopsies can be performed at the time of hydrodistention. Unfortunately, there is no consensus on indications for biopsy or on criteria for diagnosing interstitial cystitis (indeed, much about interstitial cystitis is controversial), but I believe that the scope can be an important diagnostic tool.

There also often is a therapeutic benefit to performing a cystoscopy and hydrodistention under anesthesia: Many patients remain relatively free of pain for 6 months or longer after the procedure. The urethral pain and dysuria that sometimes occur with cystoscopy can be treated with a preprocedure intraurethral injection of lidocaine jelly or oral phenazopyridine (Pyridium). Prophylactic oral antibiotics should be given routinely either right before or right after the procedure.

Intraoperative Cystoscopy

With more advanced incontinence and prolapse surgeries being performed by both urologists and gynecologists, it has become ever more important to use intraoperative cystoscopy to ensure that the bladder and ureters remain undamaged and unobstructed. In fact, we have reached a point where cystoscopy should be performed routinely for most advanced pelvic reconstructive procedures, whether the procedures are done vaginally or abdominally.

It is absolutely imperative that cystoscopy be performed with every retropubic sling that uses the tension-free vaginal tape (TVT) procedure.

With transobturator tape (TOT), its necessity is more debatable because needles don't pass as close to the bladder. Surgeons who have comfortably and successfully performed a significant number of TOT procedures can probably forgo cystoscopy.

There is one exception, however: cases in which TOT is performed before the prolapse is repaired. In this case, cystoscopy remains imperative.

Intraoperative cystoscopy has a fringe benefit as well, in that it sometimes leads to the identification of pathology—bladder stones, for instance—that went undiagnosed during the preoperative work-up.

Cystoscopy can also be used to guide the placement of suprapubic catheters intraoperatively, although its most significant purpose is to document ureteral patency. When examining for patency, most surgeons inject indigo carmine intravenously and examine the bladder approximately 10 minutes later to document flow of the dye through both ureteral openings.

Instruments and Training

A urethroscope with a 0-degree lens allows appropriate examination of the urethra; however, a 70-degree lens is preferable for examination of the bladder because it enables visualization of the entire circumference of the bladder in more detail.

Some surgeons are using flexible cystoscopes—the optics of flexible cystoscopy have improved significantly in recent years—but the 70-degree rigid scope is sufficient in the vast majority of procedures.

Gynecologists who perform trans- or periurethral bulking agent injections for intrinsic sphincteric deficiency must be comfortable with using a 0-degree scope in the office. In this process, which typically is done under cystoscopic guidance, a needle is placed either through the cystoscope or lateral to the urethra, and the agent—collagen (Contigen), silicone (Macroplastique), carbon beads (Durasphere), or another agent—is injected to add bulk around the urethral lumen and to increase urethral resistance.

For many gynecologists, cystoscopy is a natural progression from hysteroscopy. The two procedures are very similar when used for diagnostic purposes. Others are starting to perform cystoscopy even without the background in hysteroscopy, however.

In any case, the main issue we face is the need for training. We must learn how to use the instrumentation and advance the scope safely, without causing bladder trauma or perforation; how to approach various indications; and how to judge abnormal and normal aspects of the images obtained.

Although there are no courses including certification at this time, ACOG and others do offer various training courses designed to allow ob.gyns. to develop an expertise in cystoscopy.

Bladder trabeculations are in a patient with overactive bladder.

Urethral changes reflecting different levels of estrogenation: Atrophic looks pale and flat (top), normal looks pink and spongy (bottom). Photos courtesy Dr. G. Willy Davila

Tension-free vaginal tape mesh is shown in the urethra.

Ureteral opening is shown via cystoscopy, after injection of indigo carmine dye to document ureteral integrity. Photos courtesy Dr. G. Willy Davila

Cystoscopy

As a physician on the teaching faculty of two different residency programs in metropolitan Chicago—and as one whose surgical practice is limited to minimally invasive techniques—I see residents rotating through my service routinely performing cystoscopy in conjunction with total laparoscopic hysterectomy, resection of deep endometriosis over the pelvic sidewall or bladder, placement of a sling for the treatment of stress urinary incontinence, or evaluation of the bladder for interstitial cystitis.

Unfortunately, less than a generation ago, most trainees in our field had virtually no exposure to cystoscopy. Generally, as in my own case, gynecologists interested in gaining cystoscopy skills had to be mentored by a friendly urologist.

With this in mind, I have enlisted Dr. G. Willy Davila to present cystoscopy for this Master Class in gynecologic surgery.

Dr. Davila not only chairs the department of gynecology at the Cleveland Clinic in Weston, Fla., he also heads the clinic's section of urogynecology and reconstructive pelvic surgery.

Dr. Davila serves on the editorial boards of the Journal of Female Urinary Incontinence, Revista Latinoamericana de Uroginecologia y Disfunciones Pelvianas, and the International Urogynecology Journal. He is a prolific writer and has edited three books on the specialty subject matter of urogynecology.

Our understanding of its causes and effects has expanded rapidly. We now know that a spectrum of disease can result when unequal placental sharing and/or unequal blood-volume sharing occurs in monochorionic pregnancies, for instance, and that a significant imbalance in blood-flow exchange between twins' circulations is the primary contributor to the development of TTTS. On the other hand, our knowledge is still quite simplistic: We have much to learn about the pathophysiology and the natural history and progression of the syndrome.

The observations we have made, however, are significant enough to justify the treatment of severe TTTS—especially given the advances in ultrasound assessment, which allow us to detect the syndrome early, as well as the dramatic improvements in technology for minimally invasive intrauterine therapy that have come about in recent years.

Endoscopic laser ablation (or laser coagulation) of placental anastomoses has been shown in numerous studies—including a multicenter, randomized trial comparing it with serial amnioreduction—to be an effective treatment for TTTS, and a preferable first-line approach for severe TTTS that is diagnosed before 26 weeks' gestation.

Because intrauterine procedures require a high level of expertise and infrastructure, it is likely that the management of these conditions will remain regionalized. Improved referral patterns and support for families, however, will promote the development of a nationwide network of designated centers, making such therapy more accessible.

Pathophysiology and Consequences

Identical twins are monochorionic, and these pregnancies present several potential risks: the risk that one baby will not get its fair share of the placenta, the risk that blood volume will be shared unequally, and an overall risk of vascular instability in each twin.

When the predominant issue in an identical twin pregnancy is unequal placental sharing, the growth of one baby becomes restricted and the other baby grows normally, resulting in a condition called selective intrauterine growth restriction (selective IUGR).

The other main issue—that of unequal blood-volume sharing—is what fuels TTTS. In uncomplicated pregnancies, blood is exchanged equally through the vascular anastomoses that characterize all monochorionic pregnancies. In complicated pregnancies, however, the exchange is unbalanced, and blood is shared in one direction without adequate return.

Arteries emanating from the placental cord insertion of one twin, for instance, can drain into a vein returning to the other twin. Such arteriovenous anastomoses are in the substance of the placenta and act as one-way valves for blood flow. If the amount of blood flow in one direction is not balanced by enough flow in the opposite direction—that is, if the magnitude of blood flow through unidirectional arteriovenous anastomoses is not compensated by vascular channels that permit flow in the opposite direction—then an imbalance develops that is potentially harmful to both babies.

In TTTS, which develops in about 15% of monochorionic pregnancies, the imbalance progresses to the extent that one twin becomes a “donor” of blood volume and the other becomes the “recipient” twin.

The donor twin moves blood across the anastomoses to the placenta and to the recipient twin, and does not receive an equal amount in return. A decline in blood volume leads to decreased urine output to the extent that, eventually, bladder filling in the donor twin virtually ceases. Under these circumstances, oligohydramnios may progress to anhydramnios, and the twin may become “stuck” in an essentially empty amniotic sac.

The recipient twin, in the meantime, receives an excess amount of venous blood volume. The increase in intravascular blood volume drives an increase of filtration in the kidneys, which results in excess urination. The increased urinary frequency, which may even result in constant bladder filling, leads to polyhydramnios.

When the sac of the recipient twin becomes distended by amniotic fluid, and the donor twin is no longer producing urine, the membrane between the twins may become wrapped so tightly around the donor twin that it is barely visible on ultrasound (See image below.) When the donor twin is “stuck” to the uterine wall in such a way, the ultrasound appearance resembles that of identical twins with one amniotic cavity (monoamniotic twins).

Untreated TTTS has serious consequences for each twin and for the whole pregnancy. First, the resultant polyhydramnios can stimulate preterm labor because of uterine distention. Second, abnormalities in blood volume can lead to cardiac problems and cardiovascular compromise for the babies, most often for the recipient twin. The excess blood cells and volume overload that this twin faces can lead to cardiac failure and hydrops.

The donor twin, meanwhile, is at risk for abnormalities and long-term effects resulting from compression, failing placental function, malnutrition, and hypovolemia.

If one baby dies in utero, the placental anastomoses that cause TTTS in the first place—that is, the open vessel connections that exist between the twins—carry an additional danger. In artery-to-artery and vein-to-vein anastomoses, the direction of blood flow is determined by the difference in blood pressure on either side. If one twin dies, the resultant drop in blood pressure causes the surviving twin to lose a large amount of blood volume across the connecting vessels and into the dying twin. This puts the surviving twin at risk of hemorrhagic shock and a heart attack or stroke.

It is estimated that the risk for white-matter injury in the surviving twin at the time of birth may be as high as 50% following such an intrauterine event. The fates of both twins are thus essentially linked to each other through their placental anastomoses.

Although exact contributors still need to be determined, it is well established that, compared with nonidentical twins, identical twins have a higher incidence of cerebral palsy and other anomalies, and a higher rate of developmental delay at 2 years. Because the development of TTTS is one well-recognized contributor to these statistics, perinatal interventions in monochorionic pregnancies have primarily focused on its treatment.

Evolution of Management

It's most interesting to look at the evolution of management from a historical perspective. When TTTS was clinically recognized, before the days of multivessel Doppler assessment, patients would most often present with a massively distended uterus and preterm labor.

The natural management approach was amnioreduction, which involved the removal of large volumes of amniotic fluid in an effort to relieve uterine distention and prevent preterm delivery. Physicians recognized the need for serial amnioreduction, as the procedure leaves anastomoses open and does nothing to address the underlying problem.

This approach was often satisfactory when it was started at 26–27 weeks' gestation because chances to prolong pregnancy to 32–34 weeks with repeated drainage were reasonable. The patients who presented with massive polyhydramnios and severe TTTS at 20 weeks, however, were another story. Their outcomes with serial amnioreduction were poor; in fact, many physicians would offer pregnancy termination under these circumstances.

In the late 1990s several groups began to address the underlying problem by closing the problem vessels. Dr. Julian De Lia, at that time practicing in Utah, was the first to describe fetoscopic laser ablation of placental anastomoses. He and the team of Prof. Kypros Nicolaides in Europe used a nonselective technique that involved ablating blood vessels and the placental mass along a dividing line between the twins—essentially making the placenta functionally dichorionic—and then draining the amniotic fluid.

Developmental research on the equipment and modification of the technique proceeded. In 1999, Dr. Rubén A. Quintero in Florida published a five-stage classification system for the progression of TTTS, with stages I and II characterized primarily by imbalances in blood volume, stages III and IV signified by cardiovascular compromise, and stage V signified by the death of one or both twins.

This staging system marked a significant step in the management of TTTS because it established a unified diagnostic approach that was based on prenatal criteria. Until this point, the definitions of TTTS were based on an extrapolation of pediatric diagnostic criteria that were used at birth. The application of Dr. Quintero's staging system allowed a more objective comparison of treatment strategies, but required familiarity with arterial and venous Doppler techniques.

Dr. Quintero also argued that a nonselective approach with the laser—one that coagulates vessels that do not contribute to TTTS, as well as those that do—can rob one or both twins of placental territory that is vital for their survival. He developed a selective laser technique that involves identification and coagulation of the vessels that pass from one twin to the other, leaving normal placental territory and noncontributing vessels untouched.

In the meantime, the Eurofetus research consortium had formed in Europe, and had begun designing a trial to compare laser therapy with amnioreduction, with one of their premises being that laser therapy would most benefit twin pregnancies that are complicated by TTTS before 26 weeks' gestation. Perinatal mortality for untreated severe TTTS, they knew, was as high as 90%, with significant handicap in the survivors.

Results of the multicenter randomized study were published in 2004 (N. Engl. J. Med. 2004;351:136-44). Complication rates were basically comparable (approximately 9% in each arm), but the rates of survival of at least one twin at 28 days and at 6 months of age were significantly better in the group that underwent selective laser coagulation than in the amnioreduction group (76% vs. 56% at 28 days, and 76% vs. 51% at 6 months).

The differences existed in both the early and later stages of TTTS, although fetuses in the Quintero stages I or II had better outcomes than did those with higher stages in both treatment groups. (The study had been concluded early, after 72 women had been assigned to the laser group and 70 to the amnioreduction group, when an interim analysis demonstrated significant benefits.)

Gestational ages at the time of delivery were also significantly different: Patients in the laser group delivered, on average, at 33 weeks, whereas those in the amnioreduction group delivered at 29 weeks.

An intermediate-term look at neurologic outcomes favored laser surgery as well: At 6 months of age, infants in the laser group were more likely than those in the amnioreduction group to be free of neurologic deficits (52% vs. 31%, respectively).

At the center for advanced fetal care at the University of Maryland, Baltimore, which has served for almost a decade as a referral resource for minimally invasive fetal therapy, I have applied the identical technique utilized in the Eurofetus trial using a selective approach. Our treatment results have consistently mirrored the published statistics.

Our research, which we presented at the annual meeting of the Society for Maternal-Fetal Medicine, confirms that successful laser ablation corrects the abnormal blood volume distribution. This effect is first apparent for the donor twin and clinically presents with the reappearance of bladder filling, often on the day after the procedure.

Urination gradually normalizes in the recipient twin, typically over 1–2 weeks after the procedure. The mother feels better immediately after the procedure and continues to improve as fetal status normalizes.

Longer-term follow-up of neurologic abnormalities in the Eurofetus trial is underway. For now, however, an analysis of a series of patients who received intrauterine laser treatment for TTTS has shown that 78% of 89 surviving children had a normal neurodevelopmental status at about 2 years of age, whereas 11% had minor neurologic deficiencies and 11% had major neurologic deficits (Am. J. Obstet. Gynecol. 2003;188:876-80).

Although comparisons of patients managed in the randomized trial are pending, these rates of neurologic handicap compare favorably with those seen after amnioreduction.

Two large series indicate that severe TTTS is associated with poor neurodevelopment, and that up to 27% of survivors may have abnormal brain ultrasounds at the time of delivery. It is therefore widely accepted that the neuroprotective benefit of laser therapy is most marked in early onset TTTS (prior to 26 weeks), and that the difference in outcomes is attributable to lower rates of preterm delivery and prematurity-associated complications as well as to the elimination of the risks of ongoing TTTS.

Moving Into the Future

In Europe, the randomized trial basically brought the controversy over optimal treatment for TTTS to a close. In the United States, there are some who still lean toward performing an initial amnioreduction and moving on to laser surgery if necessary.

There are disadvantages to such an approach. An initial amnioreduction removes the amniotic fluid pocket that is necessary to successfully maneuver the fetoscope. Decompression of the placenta not only unpredictably affects shunt dynamics but also can create placental “valleys” that can impair visualization of anastomoses. Potential bleeding from the procedure, as well as advancing gestational age until a suitable fluid pocket has reestablished, can also make the fluid cloudier.

Investigators who have looked at the factors that influence outcomes of selective laser coagulation of placental anastomoses have reported that those who do poorly have more advanced TTTS; have shorter cervical length, and thus a higher incidence of preterm labor; have a history of prior amnioreduction; and have technically difficult laser procedures with poor visualization of anastomoses as contributing factors.

Amnioreduction still has a role, however, particularly for patients who present with TTTS beyond 26 weeks' gestation. These patients are not candidates for laser therapy because the efficacy and safety of the procedure at this gestational age has not been studied.

Even with the improved outcomes, the therapies are still not optimal, and our knowledge of TTTS is still full of gaps and differences in opinion. Some experts believe, for instance, that with selective laser therapy there is a risk of recurring TTTS—that is, as visible anastomoses are closed, intravascular pressures are diverted to very small vessels that are barely visible at the time of the laser procedure. Over time, it is believed, these vessels may expand and therefore become hemodynamically relevant contributors to recurring TTTS.

At this time, I believe it's important to keep an open mind after presumably successful laser therapy, and to follow the fetuses closely after surgery for TTTS. Continued evaluation of bladder filling, amniotic fluid volumes, and placental and venous Doppler studies may be necessary over extended periods of time.

It is also important to inform neonatologists and referring obstetricians of the special circumstances of these babies, who behave very differently—both in the NICU and beyond—than do other babies of similar size or with other underlying conditions.

Babies who matured in utero as TTTS “recipients” are chronically hypervolemic and will not respond well, for instance, to dopamine given in the NICU as the primary agent to boost blood pressure. Careful attention to fluid balance is essential to prevent neonatal complications under these circumstances.

Fortunately, technologic advances in equipment are making intrauterine therapy much more minimally invasive. The development of fetoscopes with a 2-mm lens offers superior visual resolution and facilitates a minimally invasive approach. Digital camera technology also enhances the visualization of the smallest blood vessels. Steerable and angulated optical devices tackle the problems of anterior placenta. The smaller caliber of the entry site also decreases the risk for complications.

Today, laser surgery is typically performed under local anesthesia that requires minimal hospitalization with only perioperative tocolysis. The average length of patient stay is 1 day at the University of Maryland Medical Center.

The initiation of the North American Fetal Therapy Network (NAFTNet), a research consortium, is a significant development in the United States.

The membrane is seen folding around the donor who becomes a “stuck twin.” Courtesy Dr. Ahmet A. Baschat

When bladder filling of the donor can no longer be demonstrated, progression to stage 2 TTTS is diagnosed. (Left arrow, small bladder; right arrow, empty bladder.)

Critically abnormal waveforms in the umbilical artery (left) and ductus venosus (right) indicate stage 3 TTTS.

Ultrasound findings of hydrops (arrows point to fluid in fetal abdomen) indicate stage 4 TTTS. Photos courtesy Dr. Ahmet A. Baschat

Twin-to-Twin Transfusion Syndrome

Despite the advances that have occurred in obstetrics over the years, who would have imagined that fetal surgery would be a viable therapeutic approach today? Well, indeed, this is where we are in the history of obstetrics.

Fetal evaluation has been conducted over the years using a variety of noninvasive techniques, most notably electronic fetal monitoring. More invasive techniques, such as amniocentesis, have also been used with very good success and with relatively low risk to mother and fetus. Certain conditions, however, cannot be addressed with noninvasive or slightly invasive approaches, but rather require either open surgery or more involved surgery of a minimally invasive nature.

One of these conditions is twin-to-twin transfusion syndrome, in which one of the fetuses may succumb during intrauterine life. Over the years, amniocentesis has been used with limited success. However, newer techniques involving endoscopic laser therapy are being introduced with improved outcomes. In this Master Class, we review both modalities in the management of these patients, with careful attention to advances in fetal laser therapy.

We are pleased to introduce Dr. Ahmet A. Baschat, of the department of obstetrics, gynecology, and reproductive sciences at the University of Maryland School of Medicine, Baltimore, as our guest professor this month. Dr. Baschat is considered a national expert in fetal therapy, including laser and other intrauterine surgical procedures.

EMILY BRANNAN, ILLUSTRATION

Our understanding of its causes and effects has expanded rapidly. We now know that a spectrum of disease can result when unequal placental sharing and/or unequal blood-volume sharing occurs in monochorionic pregnancies, for instance, and that a significant imbalance in blood-flow exchange between twins' circulations is the primary contributor to the development of TTTS. On the other hand, our knowledge is still quite simplistic: We have much to learn about the pathophysiology and the natural history and progression of the syndrome.

The observations we have made, however, are significant enough to justify the treatment of severe TTTS—especially given the advances in ultrasound assessment, which allow us to detect the syndrome early, as well as the dramatic improvements in technology for minimally invasive intrauterine therapy that have come about in recent years.

Endoscopic laser ablation (or laser coagulation) of placental anastomoses has been shown in numerous studies—including a multicenter, randomized trial comparing it with serial amnioreduction—to be an effective treatment for TTTS, and a preferable first-line approach for severe TTTS that is diagnosed before 26 weeks' gestation.

Because intrauterine procedures require a high level of expertise and infrastructure, it is likely that the management of these conditions will remain regionalized. Improved referral patterns and support for families, however, will promote the development of a nationwide network of designated centers, making such therapy more accessible.

Pathophysiology and Consequences

Identical twins are monochorionic, and these pregnancies present several potential risks: the risk that one baby will not get its fair share of the placenta, the risk that blood volume will be shared unequally, and an overall risk of vascular instability in each twin.

When the predominant issue in an identical twin pregnancy is unequal placental sharing, the growth of one baby becomes restricted and the other baby grows normally, resulting in a condition called selective intrauterine growth restriction (selective IUGR).

The other main issue—that of unequal blood-volume sharing—is what fuels TTTS. In uncomplicated pregnancies, blood is exchanged equally through the vascular anastomoses that characterize all monochorionic pregnancies. In complicated pregnancies, however, the exchange is unbalanced, and blood is shared in one direction without adequate return.

Arteries emanating from the placental cord insertion of one twin, for instance, can drain into a vein returning to the other twin. Such arteriovenous anastomoses are in the substance of the placenta and act as one-way valves for blood flow. If the amount of blood flow in one direction is not balanced by enough flow in the opposite direction—that is, if the magnitude of blood flow through unidirectional arteriovenous anastomoses is not compensated by vascular channels that permit flow in the opposite direction—then an imbalance develops that is potentially harmful to both babies.

In TTTS, which develops in about 15% of monochorionic pregnancies, the imbalance progresses to the extent that one twin becomes a “donor” of blood volume and the other becomes the “recipient” twin.

The donor twin moves blood across the anastomoses to the placenta and to the recipient twin, and does not receive an equal amount in return. A decline in blood volume leads to decreased urine output to the extent that, eventually, bladder filling in the donor twin virtually ceases. Under these circumstances, oligohydramnios may progress to anhydramnios, and the twin may become “stuck” in an essentially empty amniotic sac.

The recipient twin, in the meantime, receives an excess amount of venous blood volume. The increase in intravascular blood volume drives an increase of filtration in the kidneys, which results in excess urination. The increased urinary frequency, which may even result in constant bladder filling, leads to polyhydramnios.

When the sac of the recipient twin becomes distended by amniotic fluid, and the donor twin is no longer producing urine, the membrane between the twins may become wrapped so tightly around the donor twin that it is barely visible on ultrasound (See image below.) When the donor twin is “stuck” to the uterine wall in such a way, the ultrasound appearance resembles that of identical twins with one amniotic cavity (monoamniotic twins).

Untreated TTTS has serious consequences for each twin and for the whole pregnancy. First, the resultant polyhydramnios can stimulate preterm labor because of uterine distention. Second, abnormalities in blood volume can lead to cardiac problems and cardiovascular compromise for the babies, most often for the recipient twin. The excess blood cells and volume overload that this twin faces can lead to cardiac failure and hydrops.

The donor twin, meanwhile, is at risk for abnormalities and long-term effects resulting from compression, failing placental function, malnutrition, and hypovolemia.

If one baby dies in utero, the placental anastomoses that cause TTTS in the first place—that is, the open vessel connections that exist between the twins—carry an additional danger. In artery-to-artery and vein-to-vein anastomoses, the direction of blood flow is determined by the difference in blood pressure on either side. If one twin dies, the resultant drop in blood pressure causes the surviving twin to lose a large amount of blood volume across the connecting vessels and into the dying twin. This puts the surviving twin at risk of hemorrhagic shock and a heart attack or stroke.

It is estimated that the risk for white-matter injury in the surviving twin at the time of birth may be as high as 50% following such an intrauterine event. The fates of both twins are thus essentially linked to each other through their placental anastomoses.

Although exact contributors still need to be determined, it is well established that, compared with nonidentical twins, identical twins have a higher incidence of cerebral palsy and other anomalies, and a higher rate of developmental delay at 2 years. Because the development of TTTS is one well-recognized contributor to these statistics, perinatal interventions in monochorionic pregnancies have primarily focused on its treatment.

Evolution of Management

It's most interesting to look at the evolution of management from a historical perspective. When TTTS was clinically recognized, before the days of multivessel Doppler assessment, patients would most often present with a massively distended uterus and preterm labor.

The natural management approach was amnioreduction, which involved the removal of large volumes of amniotic fluid in an effort to relieve uterine distention and prevent preterm delivery. Physicians recognized the need for serial amnioreduction, as the procedure leaves anastomoses open and does nothing to address the underlying problem.

This approach was often satisfactory when it was started at 26–27 weeks' gestation because chances to prolong pregnancy to 32–34 weeks with repeated drainage were reasonable. The patients who presented with massive polyhydramnios and severe TTTS at 20 weeks, however, were another story. Their outcomes with serial amnioreduction were poor; in fact, many physicians would offer pregnancy termination under these circumstances.

In the late 1990s several groups began to address the underlying problem by closing the problem vessels. Dr. Julian De Lia, at that time practicing in Utah, was the first to describe fetoscopic laser ablation of placental anastomoses. He and the team of Prof. Kypros Nicolaides in Europe used a nonselective technique that involved ablating blood vessels and the placental mass along a dividing line between the twins—essentially making the placenta functionally dichorionic—and then draining the amniotic fluid.

Developmental research on the equipment and modification of the technique proceeded. In 1999, Dr. Rubén A. Quintero in Florida published a five-stage classification system for the progression of TTTS, with stages I and II characterized primarily by imbalances in blood volume, stages III and IV signified by cardiovascular compromise, and stage V signified by the death of one or both twins.

This staging system marked a significant step in the management of TTTS because it established a unified diagnostic approach that was based on prenatal criteria. Until this point, the definitions of TTTS were based on an extrapolation of pediatric diagnostic criteria that were used at birth. The application of Dr. Quintero's staging system allowed a more objective comparison of treatment strategies, but required familiarity with arterial and venous Doppler techniques.

Dr. Quintero also argued that a nonselective approach with the laser—one that coagulates vessels that do not contribute to TTTS, as well as those that do—can rob one or both twins of placental territory that is vital for their survival. He developed a selective laser technique that involves identification and coagulation of the vessels that pass from one twin to the other, leaving normal placental territory and noncontributing vessels untouched.

In the meantime, the Eurofetus research consortium had formed in Europe, and had begun designing a trial to compare laser therapy with amnioreduction, with one of their premises being that laser therapy would most benefit twin pregnancies that are complicated by TTTS before 26 weeks' gestation. Perinatal mortality for untreated severe TTTS, they knew, was as high as 90%, with significant handicap in the survivors.

Results of the multicenter randomized study were published in 2004 (N. Engl. J. Med. 2004;351:136-44). Complication rates were basically comparable (approximately 9% in each arm), but the rates of survival of at least one twin at 28 days and at 6 months of age were significantly better in the group that underwent selective laser coagulation than in the amnioreduction group (76% vs. 56% at 28 days, and 76% vs. 51% at 6 months).

The differences existed in both the early and later stages of TTTS, although fetuses in the Quintero stages I or II had better outcomes than did those with higher stages in both treatment groups. (The study had been concluded early, after 72 women had been assigned to the laser group and 70 to the amnioreduction group, when an interim analysis demonstrated significant benefits.)

Gestational ages at the time of delivery were also significantly different: Patients in the laser group delivered, on average, at 33 weeks, whereas those in the amnioreduction group delivered at 29 weeks.

An intermediate-term look at neurologic outcomes favored laser surgery as well: At 6 months of age, infants in the laser group were more likely than those in the amnioreduction group to be free of neurologic deficits (52% vs. 31%, respectively).

At the center for advanced fetal care at the University of Maryland, Baltimore, which has served for almost a decade as a referral resource for minimally invasive fetal therapy, I have applied the identical technique utilized in the Eurofetus trial using a selective approach. Our treatment results have consistently mirrored the published statistics.

Our research, which we presented at the annual meeting of the Society for Maternal-Fetal Medicine, confirms that successful laser ablation corrects the abnormal blood volume distribution. This effect is first apparent for the donor twin and clinically presents with the reappearance of bladder filling, often on the day after the procedure.

Urination gradually normalizes in the recipient twin, typically over 1–2 weeks after the procedure. The mother feels better immediately after the procedure and continues to improve as fetal status normalizes.

Longer-term follow-up of neurologic abnormalities in the Eurofetus trial is underway. For now, however, an analysis of a series of patients who received intrauterine laser treatment for TTTS has shown that 78% of 89 surviving children had a normal neurodevelopmental status at about 2 years of age, whereas 11% had minor neurologic deficiencies and 11% had major neurologic deficits (Am. J. Obstet. Gynecol. 2003;188:876-80).

Although comparisons of patients managed in the randomized trial are pending, these rates of neurologic handicap compare favorably with those seen after amnioreduction.

Two large series indicate that severe TTTS is associated with poor neurodevelopment, and that up to 27% of survivors may have abnormal brain ultrasounds at the time of delivery. It is therefore widely accepted that the neuroprotective benefit of laser therapy is most marked in early onset TTTS (prior to 26 weeks), and that the difference in outcomes is attributable to lower rates of preterm delivery and prematurity-associated complications as well as to the elimination of the risks of ongoing TTTS.

Moving Into the Future

In Europe, the randomized trial basically brought the controversy over optimal treatment for TTTS to a close. In the United States, there are some who still lean toward performing an initial amnioreduction and moving on to laser surgery if necessary.

There are disadvantages to such an approach. An initial amnioreduction removes the amniotic fluid pocket that is necessary to successfully maneuver the fetoscope. Decompression of the placenta not only unpredictably affects shunt dynamics but also can create placental “valleys” that can impair visualization of anastomoses. Potential bleeding from the procedure, as well as advancing gestational age until a suitable fluid pocket has reestablished, can also make the fluid cloudier.

Investigators who have looked at the factors that influence outcomes of selective laser coagulation of placental anastomoses have reported that those who do poorly have more advanced TTTS; have shorter cervical length, and thus a higher incidence of preterm labor; have a history of prior amnioreduction; and have technically difficult laser procedures with poor visualization of anastomoses as contributing factors.

Amnioreduction still has a role, however, particularly for patients who present with TTTS beyond 26 weeks' gestation. These patients are not candidates for laser therapy because the efficacy and safety of the procedure at this gestational age has not been studied.

Even with the improved outcomes, the therapies are still not optimal, and our knowledge of TTTS is still full of gaps and differences in opinion. Some experts believe, for instance, that with selective laser therapy there is a risk of recurring TTTS—that is, as visible anastomoses are closed, intravascular pressures are diverted to very small vessels that are barely visible at the time of the laser procedure. Over time, it is believed, these vessels may expand and therefore become hemodynamically relevant contributors to recurring TTTS.

At this time, I believe it's important to keep an open mind after presumably successful laser therapy, and to follow the fetuses closely after surgery for TTTS. Continued evaluation of bladder filling, amniotic fluid volumes, and placental and venous Doppler studies may be necessary over extended periods of time.

It is also important to inform neonatologists and referring obstetricians of the special circumstances of these babies, who behave very differently—both in the NICU and beyond—than do other babies of similar size or with other underlying conditions.

Babies who matured in utero as TTTS “recipients” are chronically hypervolemic and will not respond well, for instance, to dopamine given in the NICU as the primary agent to boost blood pressure. Careful attention to fluid balance is essential to prevent neonatal complications under these circumstances.

Fortunately, technologic advances in equipment are making intrauterine therapy much more minimally invasive. The development of fetoscopes with a 2-mm lens offers superior visual resolution and facilitates a minimally invasive approach. Digital camera technology also enhances the visualization of the smallest blood vessels. Steerable and angulated optical devices tackle the problems of anterior placenta. The smaller caliber of the entry site also decreases the risk for complications.

Today, laser surgery is typically performed under local anesthesia that requires minimal hospitalization with only perioperative tocolysis. The average length of patient stay is 1 day at the University of Maryland Medical Center.

The initiation of the North American Fetal Therapy Network (NAFTNet), a research consortium, is a significant development in the United States.

The membrane is seen folding around the donor who becomes a “stuck twin.” Courtesy Dr. Ahmet A. Baschat

When bladder filling of the donor can no longer be demonstrated, progression to stage 2 TTTS is diagnosed. (Left arrow, small bladder; right arrow, empty bladder.)

Critically abnormal waveforms in the umbilical artery (left) and ductus venosus (right) indicate stage 3 TTTS.

Ultrasound findings of hydrops (arrows point to fluid in fetal abdomen) indicate stage 4 TTTS. Photos courtesy Dr. Ahmet A. Baschat

Twin-to-Twin Transfusion Syndrome

Despite the advances that have occurred in obstetrics over the years, who would have imagined that fetal surgery would be a viable therapeutic approach today? Well, indeed, this is where we are in the history of obstetrics.

Fetal evaluation has been conducted over the years using a variety of noninvasive techniques, most notably electronic fetal monitoring. More invasive techniques, such as amniocentesis, have also been used with very good success and with relatively low risk to mother and fetus. Certain conditions, however, cannot be addressed with noninvasive or slightly invasive approaches, but rather require either open surgery or more involved surgery of a minimally invasive nature.

One of these conditions is twin-to-twin transfusion syndrome, in which one of the fetuses may succumb during intrauterine life. Over the years, amniocentesis has been used with limited success. However, newer techniques involving endoscopic laser therapy are being introduced with improved outcomes. In this Master Class, we review both modalities in the management of these patients, with careful attention to advances in fetal laser therapy.

We are pleased to introduce Dr. Ahmet A. Baschat, of the department of obstetrics, gynecology, and reproductive sciences at the University of Maryland School of Medicine, Baltimore, as our guest professor this month. Dr. Baschat is considered a national expert in fetal therapy, including laser and other intrauterine surgical procedures.

EMILY BRANNAN, ILLUSTRATION

Our understanding of its causes and effects has expanded rapidly. We now know that a spectrum of disease can result when unequal placental sharing and/or unequal blood-volume sharing occurs in monochorionic pregnancies, for instance, and that a significant imbalance in blood-flow exchange between twins' circulations is the primary contributor to the development of TTTS. On the other hand, our knowledge is still quite simplistic: We have much to learn about the pathophysiology and the natural history and progression of the syndrome.

The observations we have made, however, are significant enough to justify the treatment of severe TTTS—especially given the advances in ultrasound assessment, which allow us to detect the syndrome early, as well as the dramatic improvements in technology for minimally invasive intrauterine therapy that have come about in recent years.

Endoscopic laser ablation (or laser coagulation) of placental anastomoses has been shown in numerous studies—including a multicenter, randomized trial comparing it with serial amnioreduction—to be an effective treatment for TTTS, and a preferable first-line approach for severe TTTS that is diagnosed before 26 weeks' gestation.

Because intrauterine procedures require a high level of expertise and infrastructure, it is likely that the management of these conditions will remain regionalized. Improved referral patterns and support for families, however, will promote the development of a nationwide network of designated centers, making such therapy more accessible.

Pathophysiology and Consequences

Identical twins are monochorionic, and these pregnancies present several potential risks: the risk that one baby will not get its fair share of the placenta, the risk that blood volume will be shared unequally, and an overall risk of vascular instability in each twin.

When the predominant issue in an identical twin pregnancy is unequal placental sharing, the growth of one baby becomes restricted and the other baby grows normally, resulting in a condition called selective intrauterine growth restriction (selective IUGR).

The other main issue—that of unequal blood-volume sharing—is what fuels TTTS. In uncomplicated pregnancies, blood is exchanged equally through the vascular anastomoses that characterize all monochorionic pregnancies. In complicated pregnancies, however, the exchange is unbalanced, and blood is shared in one direction without adequate return.

Arteries emanating from the placental cord insertion of one twin, for instance, can drain into a vein returning to the other twin. Such arteriovenous anastomoses are in the substance of the placenta and act as one-way valves for blood flow. If the amount of blood flow in one direction is not balanced by enough flow in the opposite direction—that is, if the magnitude of blood flow through unidirectional arteriovenous anastomoses is not compensated by vascular channels that permit flow in the opposite direction—then an imbalance develops that is potentially harmful to both babies.

In TTTS, which develops in about 15% of monochorionic pregnancies, the imbalance progresses to the extent that one twin becomes a “donor” of blood volume and the other becomes the “recipient” twin.

The donor twin moves blood across the anastomoses to the placenta and to the recipient twin, and does not receive an equal amount in return. A decline in blood volume leads to decreased urine output to the extent that, eventually, bladder filling in the donor twin virtually ceases. Under these circumstances, oligohydramnios may progress to anhydramnios, and the twin may become “stuck” in an essentially empty amniotic sac.

The recipient twin, in the meantime, receives an excess amount of venous blood volume. The increase in intravascular blood volume drives an increase of filtration in the kidneys, which results in excess urination. The increased urinary frequency, which may even result in constant bladder filling, leads to polyhydramnios.

When the sac of the recipient twin becomes distended by amniotic fluid, and the donor twin is no longer producing urine, the membrane between the twins may become wrapped so tightly around the donor twin that it is barely visible on ultrasound (See image below.) When the donor twin is “stuck” to the uterine wall in such a way, the ultrasound appearance resembles that of identical twins with one amniotic cavity (monoamniotic twins).

Untreated TTTS has serious consequences for each twin and for the whole pregnancy. First, the resultant polyhydramnios can stimulate preterm labor because of uterine distention. Second, abnormalities in blood volume can lead to cardiac problems and cardiovascular compromise for the babies, most often for the recipient twin. The excess blood cells and volume overload that this twin faces can lead to cardiac failure and hydrops.

The donor twin, meanwhile, is at risk for abnormalities and long-term effects resulting from compression, failing placental function, malnutrition, and hypovolemia.

If one baby dies in utero, the placental anastomoses that cause TTTS in the first place—that is, the open vessel connections that exist between the twins—carry an additional danger. In artery-to-artery and vein-to-vein anastomoses, the direction of blood flow is determined by the difference in blood pressure on either side. If one twin dies, the resultant drop in blood pressure causes the surviving twin to lose a large amount of blood volume across the connecting vessels and into the dying twin. This puts the surviving twin at risk of hemorrhagic shock and a heart attack or stroke.

It is estimated that the risk for white-matter injury in the surviving twin at the time of birth may be as high as 50% following such an intrauterine event. The fates of both twins are thus essentially linked to each other through their placental anastomoses.

Although exact contributors still need to be determined, it is well established that, compared with nonidentical twins, identical twins have a higher incidence of cerebral palsy and other anomalies, and a higher rate of developmental delay at 2 years. Because the development of TTTS is one well-recognized contributor to these statistics, perinatal interventions in monochorionic pregnancies have primarily focused on its treatment.

Evolution of Management

It's most interesting to look at the evolution of management from a historical perspective. When TTTS was clinically recognized, before the days of multivessel Doppler assessment, patients would most often present with a massively distended uterus and preterm labor.

The natural management approach was amnioreduction, which involved the removal of large volumes of amniotic fluid in an effort to relieve uterine distention and prevent preterm delivery. Physicians recognized the need for serial amnioreduction, as the procedure leaves anastomoses open and does nothing to address the underlying problem.

This approach was often satisfactory when it was started at 26–27 weeks' gestation because chances to prolong pregnancy to 32–34 weeks with repeated drainage were reasonable. The patients who presented with massive polyhydramnios and severe TTTS at 20 weeks, however, were another story. Their outcomes with serial amnioreduction were poor; in fact, many physicians would offer pregnancy termination under these circumstances.

In the late 1990s several groups began to address the underlying problem by closing the problem vessels. Dr. Julian De Lia, at that time practicing in Utah, was the first to describe fetoscopic laser ablation of placental anastomoses. He and the team of Prof. Kypros Nicolaides in Europe used a nonselective technique that involved ablating blood vessels and the placental mass along a dividing line between the twins—essentially making the placenta functionally dichorionic—and then draining the amniotic fluid.

Developmental research on the equipment and modification of the technique proceeded. In 1999, Dr. Rubén A. Quintero in Florida published a five-stage classification system for the progression of TTTS, with stages I and II characterized primarily by imbalances in blood volume, stages III and IV signified by cardiovascular compromise, and stage V signified by the death of one or both twins.

This staging system marked a significant step in the management of TTTS because it established a unified diagnostic approach that was based on prenatal criteria. Until this point, the definitions of TTTS were based on an extrapolation of pediatric diagnostic criteria that were used at birth. The application of Dr. Quintero's staging system allowed a more objective comparison of treatment strategies, but required familiarity with arterial and venous Doppler techniques.

Dr. Quintero also argued that a nonselective approach with the laser—one that coagulates vessels that do not contribute to TTTS, as well as those that do—can rob one or both twins of placental territory that is vital for their survival. He developed a selective laser technique that involves identification and coagulation of the vessels that pass from one twin to the other, leaving normal placental territory and noncontributing vessels untouched.

In the meantime, the Eurofetus research consortium had formed in Europe, and had begun designing a trial to compare laser therapy with amnioreduction, with one of their premises being that laser therapy would most benefit twin pregnancies that are complicated by TTTS before 26 weeks' gestation. Perinatal mortality for untreated severe TTTS, they knew, was as high as 90%, with significant handicap in the survivors.

Results of the multicenter randomized study were published in 2004 (N. Engl. J. Med. 2004;351:136-44). Complication rates were basically comparable (approximately 9% in each arm), but the rates of survival of at least one twin at 28 days and at 6 months of age were significantly better in the group that underwent selective laser coagulation than in the amnioreduction group (76% vs. 56% at 28 days, and 76% vs. 51% at 6 months).

The differences existed in both the early and later stages of TTTS, although fetuses in the Quintero stages I or II had better outcomes than did those with higher stages in both treatment groups. (The study had been concluded early, after 72 women had been assigned to the laser group and 70 to the amnioreduction group, when an interim analysis demonstrated significant benefits.)

Gestational ages at the time of delivery were also significantly different: Patients in the laser group delivered, on average, at 33 weeks, whereas those in the amnioreduction group delivered at 29 weeks.

An intermediate-term look at neurologic outcomes favored laser surgery as well: At 6 months of age, infants in the laser group were more likely than those in the amnioreduction group to be free of neurologic deficits (52% vs. 31%, respectively).

At the center for advanced fetal care at the University of Maryland, Baltimore, which has served for almost a decade as a referral resource for minimally invasive fetal therapy, I have applied the identical technique utilized in the Eurofetus trial using a selective approach. Our treatment results have consistently mirrored the published statistics.

Our research, which we presented at the annual meeting of the Society for Maternal-Fetal Medicine, confirms that successful laser ablation corrects the abnormal blood volume distribution. This effect is first apparent for the donor twin and clinically presents with the reappearance of bladder filling, often on the day after the procedure.

Urination gradually normalizes in the recipient twin, typically over 1–2 weeks after the procedure. The mother feels better immediately after the procedure and continues to improve as fetal status normalizes.

Longer-term follow-up of neurologic abnormalities in the Eurofetus trial is underway. For now, however, an analysis of a series of patients who received intrauterine laser treatment for TTTS has shown that 78% of 89 surviving children had a normal neurodevelopmental status at about 2 years of age, whereas 11% had minor neurologic deficiencies and 11% had major neurologic deficits (Am. J. Obstet. Gynecol. 2003;188:876-80).

Although comparisons of patients managed in the randomized trial are pending, these rates of neurologic handicap compare favorably with those seen after amnioreduction.

Two large series indicate that severe TTTS is associated with poor neurodevelopment, and that up to 27% of survivors may have abnormal brain ultrasounds at the time of delivery. It is therefore widely accepted that the neuroprotective benefit of laser therapy is most marked in early onset TTTS (prior to 26 weeks), and that the difference in outcomes is attributable to lower rates of preterm delivery and prematurity-associated complications as well as to the elimination of the risks of ongoing TTTS.

Moving Into the Future

In Europe, the randomized trial basically brought the controversy over optimal treatment for TTTS to a close. In the United States, there are some who still lean toward performing an initial amnioreduction and moving on to laser surgery if necessary.

There are disadvantages to such an approach. An initial amnioreduction removes the amniotic fluid pocket that is necessary to successfully maneuver the fetoscope. Decompression of the placenta not only unpredictably affects shunt dynamics but also can create placental “valleys” that can impair visualization of anastomoses. Potential bleeding from the procedure, as well as advancing gestational age until a suitable fluid pocket has reestablished, can also make the fluid cloudier.

Investigators who have looked at the factors that influence outcomes of selective laser coagulation of placental anastomoses have reported that those who do poorly have more advanced TTTS; have shorter cervical length, and thus a higher incidence of preterm labor; have a history of prior amnioreduction; and have technically difficult laser procedures with poor visualization of anastomoses as contributing factors.

Amnioreduction still has a role, however, particularly for patients who present with TTTS beyond 26 weeks' gestation. These patients are not candidates for laser therapy because the efficacy and safety of the procedure at this gestational age has not been studied.

Even with the improved outcomes, the therapies are still not optimal, and our knowledge of TTTS is still full of gaps and differences in opinion. Some experts believe, for instance, that with selective laser therapy there is a risk of recurring TTTS—that is, as visible anastomoses are closed, intravascular pressures are diverted to very small vessels that are barely visible at the time of the laser procedure. Over time, it is believed, these vessels may expand and therefore become hemodynamically relevant contributors to recurring TTTS.

At this time, I believe it's important to keep an open mind after presumably successful laser therapy, and to follow the fetuses closely after surgery for TTTS. Continued evaluation of bladder filling, amniotic fluid volumes, and placental and venous Doppler studies may be necessary over extended periods of time.

It is also important to inform neonatologists and referring obstetricians of the special circumstances of these babies, who behave very differently—both in the NICU and beyond—than do other babies of similar size or with other underlying conditions.

Babies who matured in utero as TTTS “recipients” are chronically hypervolemic and will not respond well, for instance, to dopamine given in the NICU as the primary agent to boost blood pressure. Careful attention to fluid balance is essential to prevent neonatal complications under these circumstances.

Fortunately, technologic advances in equipment are making intrauterine therapy much more minimally invasive. The development of fetoscopes with a 2-mm lens offers superior visual resolution and facilitates a minimally invasive approach. Digital camera technology also enhances the visualization of the smallest blood vessels. Steerable and angulated optical devices tackle the problems of anterior placenta. The smaller caliber of the entry site also decreases the risk for complications.

Today, laser surgery is typically performed under local anesthesia that requires minimal hospitalization with only perioperative tocolysis. The average length of patient stay is 1 day at the University of Maryland Medical Center.

The initiation of the North American Fetal Therapy Network (NAFTNet), a research consortium, is a significant development in the United States.

The membrane is seen folding around the donor who becomes a “stuck twin.” Courtesy Dr. Ahmet A. Baschat

When bladder filling of the donor can no longer be demonstrated, progression to stage 2 TTTS is diagnosed. (Left arrow, small bladder; right arrow, empty bladder.)

Critically abnormal waveforms in the umbilical artery (left) and ductus venosus (right) indicate stage 3 TTTS.

Ultrasound findings of hydrops (arrows point to fluid in fetal abdomen) indicate stage 4 TTTS. Photos courtesy Dr. Ahmet A. Baschat

Twin-to-Twin Transfusion Syndrome

Despite the advances that have occurred in obstetrics over the years, who would have imagined that fetal surgery would be a viable therapeutic approach today? Well, indeed, this is where we are in the history of obstetrics.

Fetal evaluation has been conducted over the years using a variety of noninvasive techniques, most notably electronic fetal monitoring. More invasive techniques, such as amniocentesis, have also been used with very good success and with relatively low risk to mother and fetus. Certain conditions, however, cannot be addressed with noninvasive or slightly invasive approaches, but rather require either open surgery or more involved surgery of a minimally invasive nature.

One of these conditions is twin-to-twin transfusion syndrome, in which one of the fetuses may succumb during intrauterine life. Over the years, amniocentesis has been used with limited success. However, newer techniques involving endoscopic laser therapy are being introduced with improved outcomes. In this Master Class, we review both modalities in the management of these patients, with careful attention to advances in fetal laser therapy.

We are pleased to introduce Dr. Ahmet A. Baschat, of the department of obstetrics, gynecology, and reproductive sciences at the University of Maryland School of Medicine, Baltimore, as our guest professor this month. Dr. Baschat is considered a national expert in fetal therapy, including laser and other intrauterine surgical procedures.

EMILY BRANNAN, ILLUSTRATION

Vaginal prolapse repair kits have gained popularity, as has laparoscopic sacral colpopexy. The learning curve associated with laparoscopic suturing has also fostered an interest in robotic-assisted laparoscopic approaches. Behind this changing landscape, however, is a long history of experience with open abdominal sacral colpopexy.

It is an approach with a record of success that we should know, appreciate, and retain in our armamentarium of surgical options while at the same time continuing to investigate which procedures for vaginal apex prolapse provide optimal effectiveness and safety.

Key Studies on Cure Rates

The sacral colpopexy, introduced in 1957, is a procedure that bridges the support tissue of the anterior and posterior vaginal apex to the anterior longitudinal ligament of the sacrum. A modification of the procedure, called sacral colpoperineopexy, was developed later to treat patients with vaginal apex prolapse and perineal descent; it results in contiguous posterior vaginal wall support from the anterior longitudinal ligament to the perineum.

Indications for sacral colpopexy include a previously failed vaginal route apex suspension procedure, a foreshortened vagina, a weak or denervated pelvic floor, chronic increases in abdominal pressure related to medical comorbidities and/or heavy manual labor, collagen disorders, and the need for concomitant abdominal surgery. Some physicians argue that sacral colpopexy is undoubtedly indicated in young women with severe uterine or vaginal apex prolapse.

A literature review of over 90 articles with outcomes data on sacral colpopexy published in 2004 by Dr. Ingrid E. Nygaard and members of the Pelvic Floor Disorders Network showed anatomic cure rates of 78%-100% when cure was defined as lack of apical prolapse postoperatively, and cure rates of 58%-100% when cure was defined more broadly as lack of any postoperative prolapse (anterior, posterior, apical).

Of interest, the review showed that concomitant paravaginal defect repair or culdoplasty neither improved anatomic cure nor decreased the recurrence of prolapse.

The follow-up for most of the studies in Dr. Nygaard's review ranged from 6 months to 3 years. The longest follow-up duration was almost 14 years in a study conducted by Dr. W.S. Hilger and associates. This long-term outcomes analysis of abdominal sacral colopopexy showed a cure rate of 74%.

A few randomized clinical trials have compared abdominal sacral colpopexy to other vaginal apex suspension procedures for the treatment of vaginal prolapse, with variable outcomes but with an overriding message that abdominal sacral colpopexy is an effective procedure.

In 1996 Dr. J.T. Benson and associates reported an optimal anatomic cure rate of 58% in patients who underwent abdominal sacral colpopexy with concomitant vaginal reconstructive procedures, and 29% in patients who underwent bilateral sacrospinous ligament suspension with pelvic reconstruction. Because of the significant failure rate associated with vaginal surgery, however, this trial was aborted prior to reaching adequate power.

In 2004, Dr. C.F. Maher and associates compared abdominal sacral colpopexy and concomitant Burch procedure with vaginal sacrospinous colpopexy and concomitant Burch procedure. Anatomic cure was similar in both groups after a 2-year follow-up, but abdominal sacral colpopexy was associated with more posterior vaginal wall recurrences, and vaginal sacrospinous colpopexy was associated with more anterior vaginal wall recurrences.

Of recent importance for the future practice of abdominal sacral colpopexy are the results of a randomized, multicenter clinical trial conducted by the Pelvic Floor Disorders Network that compared open sacral colpopexy with or without concomitant Burch colposuspension in women without preoperative stress incontinence.

Investigators of the CARE trial (Colpopexy and Urinary Reduction Efforts) found that stress incontinence was prevalent 3 months postoperatively in almost twice as many women who did not undergo the Burch procedure as in those who did (approximately 44% vs. 24%).

The results, which were reported by Dr. L. Brubaker and associates in the New England Journal of Medicine, clearly support the value of performing a prophylactic retropubic suspension for potential urinary incontinence along with abdominal sacral colpopexy. (These data do not extrapolate to midurethral slings as prophylactic procedures concomitant with sacral colpopexies.)

Regarding the issue of laparoscopic versus open abdominal sacral colpopexies, my colleagues and I found through a chart review of 117 consecutive patients that the two approaches have comparable clinical outcomes. Laparoscopic sacral colpopexy was associated with both a significantly decreased hospital stay and a significantly longer operating room time.

Key Studies on Mesh

The use of various types of mesh material is an issue that has been addressed to some extent in the literature. Certainly there is no ideal biologic or synthetic mesh. But in general, outcomes data addressing any type of biologic graft in abdominal repair of apical prolapse are sparse and inconsistent, while there is good literature to support the use of nonabsorbable synthetic implants.

The overall rate of mesh erosion in Dr. Nygaard's review of abdominal sacral colpopexy (using various types of mesh) was 3.4%, with good evidence to support the use of polypropylene mesh.

Dr. A.G. Visco and associates published a series in 2001 evaluating the prevalence of synthetic mesh erosion (predominantly Mersilene mesh) between abdominal sacral colpopexy and various colpoperineopexy procedures. The erosion rate overall was 4.5%. Vaginally introduced mesh, however, was associated with an erosion rate of 40%, compared with an erosion rate of 16% when sutures were placed by the vaginal route and attached to abdominally placed mesh.

In a more recently published study, Dr. P. J. Culligan and associates randomized patients undergoing sacral colpopexy to receive polyprophylene mesh or solvent-dehydrated cadaveric fascia lata. Of the patients who returned for 1-year follow-up, 91% of the synthetic mesh group, and 68% of the fascia group, were classified as cured. Several case series have had similar results.

With the available data, I see little reason to use biologic tissue. One indication, though, may be sacral colpopexy with concomitant sigmoid resection rectopexy. I prefer a macroporous polypropylene mesh for sacral colpopexy.

The Surgery

Whether we perform abdominal sacral colpoplexy through an open, laparoscopic, or even robotic technique, we must always remember that when working within the presacral space there is a risk of life-threatening bleeding.

For this reason, I always dissect the presacral space first. I have learned to be prepared for many variables: Older women sometimes have undetected aneurysms of the blood vessels bordering this area, and the anatomy of the sacrum can vary.

Surgeons handle bleeding in various ways. Some surgeons prophylactically cauterize the middle sacral vessel. For venous bleeding, I have success when I am working laparoscopically with inserting a sponge through a port and holding pressure for 5 minutes. Sterile thumbtacks, bone wax, and hemostatic agents can also be of value.

Once I've made my presacral dissection, I proceed all the way down into the cul-de-sac, having already visualized or palpated both ureters. I make sure I am at least 4 cm medial to the right ureter when I make my incision in the peritoneum overlying the sacral promontory.

I dissect all the way down to the rectovaginal space in the cul-de-sac. Lately, in laparoscopic surgery, I have been making a tunnel between the sacrum and cul-de-sac, because the peritoneum easily lifts off the retroperitoneal structures.

I usually use end-to-end anastomosis sizers for vaginal manipulation, but others will use vaginal palpation or Lucite probes. I dissect into the rectovaginal space first, which consists of areolar tissue.

I believe that when we're treating vaginal apex prolapse, we must attach the graft over a significant portion of the posterior vaginal length and, in cases of perineal descent, all the way down to the perineum.

There's now a caveat to this procedural modification, however, in that there is a new colorectal procedure used for treatment of outlet dysfunction constipation called the STARR procedure (Stapling Transanal Rectocele Resection). Unfortunately, a patient with mesh running all the way down to her perineum may not be able to undergo this colorectal procedure because of the risk of rectovaginal fistula. I inform my colpopexy patients that this is a contraindication to the STARR procedure.

In laparoscopic and some open cases, I will retrograde fill the bladder in order to delineate the bladder and facilitate the anterior dissection. This may be difficult if a patient has undergone an anterior colporrhaphy in the past.

I like to attach the anterior graft all the way down to the bladder base. Often times, what are thought to be stage III or stage IV cystoceles are in fact high anterior apical prolapses. Aggressive anterior vaginal wall dissection results in a more extensive attachment of the anterior vaginal mesh and decreased need for a paravaginal defect repair. Obviously, keeping the bladder from harm is very important.

The beauty of this procedure is that once you've suspended the anterior and posterior vaginal apex to the anterior longitudinal ligament, you're home free.

Surgeons often use a Y-shaped graft for sacral colpopexy. I currently use two pieces of 4-by-15-cm type 1 polypropylene mesh–a macroporous, monofilament mesh. I tension the posterior and anterior straps separately so as to avoid excess tension on the mesh and hence the vagina, and subsequently attach them to the anterior longitudinal ligament of the sacrum at the level of S1 or S2.

Many believe that if you don't stitch (or tack) at the S3 level, you're not allowing the vagina to be in its normal axis–that by going up to S1, you risk exposing the vagina posteriorly to increases in pressure that change the axis and increase posterior vaginal wall recurrence.

There have not been any studies precisely comparing mesh placement sites and their effect on anatomic success, but after doing a large number of these procedures, it does seem clear to me that it may not be necessary to attach the graft at the level of S3.

There are several reasons: For one, the anterior longitudinal ligament of the sacrum has been shown to have the greatest tensile strength at the level of the sacral promontory. Secondly, attachment of the mesh without tension to S1 or S2 has the same resultant vaginal axis because of retroperitoneal scarring of the mesh in the right pararectal space aided by intraabdominal pressure. Lastly, we risk venous plexus bleeding at the level of S3.

Surgeons use different types of sutures to fix the mesh, and I think there is some literature to support the use of monofilament sutures. I tend to use a braided polyester suture when performing the procedure laparoscopically because it ties much better.

Tying the mesh fairly loosely without strangulating tissue may reduce the risk of mesh erosion. I also tend to treat my patients with vaginal estrogen preoperatively and postoperatively to prevent mesh erosion.

Finally, I always retroperitonealize the mesh in order to decrease the risk of bowel obstruction and bowel adherence to the mesh. This may not be necessary with Mersilene mesh, which is multifilament but possesses macroporous and microporous elements (Type III).

Where We Stand Today

The problem with our literature is that we do not have enough adequately powered comparative trials for any of our vaginal apex suspension procedures. Our lack of adequate outcomes data is of particular concern when it comes to vaginal surgeries for apical prolapse.

The lack of data designating a preferred vaginal-route apical suspension procedure leads most surgeons to argue that abdominal sacral colpopexy is the accepted standard procedure.

In all circumstances, surgeons should do what is best for their patients. Ideally, though, we should have at least one abdominal approach–whether it be open, laparoscopic, or robotic–and at least one vaginal route to offer our patients because no procedure is best for all complaints, anatomic variations, and medical conditions.

Clearly, the pendulum has swung toward minimally invasive approaches for vaginal apex prolapse, as it has for many other conditions, but there are many questions that will remain unanswered until further randomized trials comparing abdominal and vaginal approaches, and new variations of each, are completed. This does not mean, in the meantime, that we should throw out the old.

Two strips of polypropylene mesh are attached to the anterior and posterior vaginal muscularis and passed through a retroperitoneal tunnel. Courtesy Dr. Marie Paraiso

Dissection of the presacral space and rectovaginal space: “I always dissect the presacral space first. I have learned to be prepared for many variables.” Courtesy Dr. Marie Paraiso

Sacral Colpopexy

No area of gynecologic surgery has undergone greater transformation over the past decade than the treatment of pelvic floor prolapse. Among other innovative surgical therapies, vaginal prolapse repair kits are now available to essentially replace the patient's pelvic floor.

Although these approaches are both novel and exciting, studies to date are lacking. Unfortunately, these procedures are too new to have stood the test of time.

Given this situation, it is imperative that the gynecologic surgeon who is involved in the treatment of pelvic floor prolapse maintain within his/her surgical armamentarium “tried-and-true” surgical techniques.

Because of its long-standing use, with excellent long-term outcomes, as can be noted in this edition of the Master Class in gynecologic surgery, the accepted standard continues to be the sacral colpopexy.

It seems especially fitting that this procedure, now a half century old, be reviewed based on approach (laparotomy, laparoscopy, robot-assisted), use of mesh material (biologic versus synthetic), technique (fixation of mesh at S1 versus S3, use of split mesh anterior and posterior versus mesh sheet anterior and posterior), and use of concomitant procedures (paravaginal defect repair, culdoplasty, prophylactic retropubic suspension, prophylactic midurethral slings).

Our discussant is Dr. Marie Paraiso, codirector of the Center for Female Pelvic Medicine and Reconstructive Surgery at the Cleveland Clinic Foundation. Despite the fact that she completed her fellowship training only a little more than 10 years ago, Dr. Paraiso has authored/coauthored 60 peer-reviewed journal articles and 13 book chapters, all pertaining to pelvic floor prolapse and urinary incontinence.

She is a much sought-after lecturer, and is routinely an invited speaker at American Association of Gynecologic Laparoscopists, the American College of Obstetricians and Gynecologists, Society of Gynecologic Surgeons, and American Urological Association.

Currently Dr. Paraiso is senior investigator of a prospective trial of robot-assisted laparoscopic sacral colpopexy versus traditional laparoscopic sacral colpopexy and the principal investigator of a cohort study evaluating the implementation of synthetic mesh for pelvic organ prolapse.

Vaginal prolapse repair kits have gained popularity, as has laparoscopic sacral colpopexy. The learning curve associated with laparoscopic suturing has also fostered an interest in robotic-assisted laparoscopic approaches. Behind this changing landscape, however, is a long history of experience with open abdominal sacral colpopexy.

It is an approach with a record of success that we should know, appreciate, and retain in our armamentarium of surgical options while at the same time continuing to investigate which procedures for vaginal apex prolapse provide optimal effectiveness and safety.

Key Studies on Cure Rates

The sacral colpopexy, introduced in 1957, is a procedure that bridges the support tissue of the anterior and posterior vaginal apex to the anterior longitudinal ligament of the sacrum. A modification of the procedure, called sacral colpoperineopexy, was developed later to treat patients with vaginal apex prolapse and perineal descent; it results in contiguous posterior vaginal wall support from the anterior longitudinal ligament to the perineum.

Indications for sacral colpopexy include a previously failed vaginal route apex suspension procedure, a foreshortened vagina, a weak or denervated pelvic floor, chronic increases in abdominal pressure related to medical comorbidities and/or heavy manual labor, collagen disorders, and the need for concomitant abdominal surgery. Some physicians argue that sacral colpopexy is undoubtedly indicated in young women with severe uterine or vaginal apex prolapse.

A literature review of over 90 articles with outcomes data on sacral colpopexy published in 2004 by Dr. Ingrid E. Nygaard and members of the Pelvic Floor Disorders Network showed anatomic cure rates of 78%-100% when cure was defined as lack of apical prolapse postoperatively, and cure rates of 58%-100% when cure was defined more broadly as lack of any postoperative prolapse (anterior, posterior, apical).

Of interest, the review showed that concomitant paravaginal defect repair or culdoplasty neither improved anatomic cure nor decreased the recurrence of prolapse.

The follow-up for most of the studies in Dr. Nygaard's review ranged from 6 months to 3 years. The longest follow-up duration was almost 14 years in a study conducted by Dr. W.S. Hilger and associates. This long-term outcomes analysis of abdominal sacral colopopexy showed a cure rate of 74%.

A few randomized clinical trials have compared abdominal sacral colpopexy to other vaginal apex suspension procedures for the treatment of vaginal prolapse, with variable outcomes but with an overriding message that abdominal sacral colpopexy is an effective procedure.

In 1996 Dr. J.T. Benson and associates reported an optimal anatomic cure rate of 58% in patients who underwent abdominal sacral colpopexy with concomitant vaginal reconstructive procedures, and 29% in patients who underwent bilateral sacrospinous ligament suspension with pelvic reconstruction. Because of the significant failure rate associated with vaginal surgery, however, this trial was aborted prior to reaching adequate power.

In 2004, Dr. C.F. Maher and associates compared abdominal sacral colpopexy and concomitant Burch procedure with vaginal sacrospinous colpopexy and concomitant Burch procedure. Anatomic cure was similar in both groups after a 2-year follow-up, but abdominal sacral colpopexy was associated with more posterior vaginal wall recurrences, and vaginal sacrospinous colpopexy was associated with more anterior vaginal wall recurrences.

Of recent importance for the future practice of abdominal sacral colpopexy are the results of a randomized, multicenter clinical trial conducted by the Pelvic Floor Disorders Network that compared open sacral colpopexy with or without concomitant Burch colposuspension in women without preoperative stress incontinence.

Investigators of the CARE trial (Colpopexy and Urinary Reduction Efforts) found that stress incontinence was prevalent 3 months postoperatively in almost twice as many women who did not undergo the Burch procedure as in those who did (approximately 44% vs. 24%).

The results, which were reported by Dr. L. Brubaker and associates in the New England Journal of Medicine, clearly support the value of performing a prophylactic retropubic suspension for potential urinary incontinence along with abdominal sacral colpopexy. (These data do not extrapolate to midurethral slings as prophylactic procedures concomitant with sacral colpopexies.)

Regarding the issue of laparoscopic versus open abdominal sacral colpopexies, my colleagues and I found through a chart review of 117 consecutive patients that the two approaches have comparable clinical outcomes. Laparoscopic sacral colpopexy was associated with both a significantly decreased hospital stay and a significantly longer operating room time.

Key Studies on Mesh

The use of various types of mesh material is an issue that has been addressed to some extent in the literature. Certainly there is no ideal biologic or synthetic mesh. But in general, outcomes data addressing any type of biologic graft in abdominal repair of apical prolapse are sparse and inconsistent, while there is good literature to support the use of nonabsorbable synthetic implants.

The overall rate of mesh erosion in Dr. Nygaard's review of abdominal sacral colpopexy (using various types of mesh) was 3.4%, with good evidence to support the use of polypropylene mesh.

Dr. A.G. Visco and associates published a series in 2001 evaluating the prevalence of synthetic mesh erosion (predominantly Mersilene mesh) between abdominal sacral colpopexy and various colpoperineopexy procedures. The erosion rate overall was 4.5%. Vaginally introduced mesh, however, was associated with an erosion rate of 40%, compared with an erosion rate of 16% when sutures were placed by the vaginal route and attached to abdominally placed mesh.

In a more recently published study, Dr. P. J. Culligan and associates randomized patients undergoing sacral colpopexy to receive polyprophylene mesh or solvent-dehydrated cadaveric fascia lata. Of the patients who returned for 1-year follow-up, 91% of the synthetic mesh group, and 68% of the fascia group, were classified as cured. Several case series have had similar results.

With the available data, I see little reason to use biologic tissue. One indication, though, may be sacral colpopexy with concomitant sigmoid resection rectopexy. I prefer a macroporous polypropylene mesh for sacral colpopexy.

The Surgery

Whether we perform abdominal sacral colpoplexy through an open, laparoscopic, or even robotic technique, we must always remember that when working within the presacral space there is a risk of life-threatening bleeding.

For this reason, I always dissect the presacral space first. I have learned to be prepared for many variables: Older women sometimes have undetected aneurysms of the blood vessels bordering this area, and the anatomy of the sacrum can vary.

Surgeons handle bleeding in various ways. Some surgeons prophylactically cauterize the middle sacral vessel. For venous bleeding, I have success when I am working laparoscopically with inserting a sponge through a port and holding pressure for 5 minutes. Sterile thumbtacks, bone wax, and hemostatic agents can also be of value.

Once I've made my presacral dissection, I proceed all the way down into the cul-de-sac, having already visualized or palpated both ureters. I make sure I am at least 4 cm medial to the right ureter when I make my incision in the peritoneum overlying the sacral promontory.

I dissect all the way down to the rectovaginal space in the cul-de-sac. Lately, in laparoscopic surgery, I have been making a tunnel between the sacrum and cul-de-sac, because the peritoneum easily lifts off the retroperitoneal structures.

I usually use end-to-end anastomosis sizers for vaginal manipulation, but others will use vaginal palpation or Lucite probes. I dissect into the rectovaginal space first, which consists of areolar tissue.

I believe that when we're treating vaginal apex prolapse, we must attach the graft over a significant portion of the posterior vaginal length and, in cases of perineal descent, all the way down to the perineum.

There's now a caveat to this procedural modification, however, in that there is a new colorectal procedure used for treatment of outlet dysfunction constipation called the STARR procedure (Stapling Transanal Rectocele Resection). Unfortunately, a patient with mesh running all the way down to her perineum may not be able to undergo this colorectal procedure because of the risk of rectovaginal fistula. I inform my colpopexy patients that this is a contraindication to the STARR procedure.

In laparoscopic and some open cases, I will retrograde fill the bladder in order to delineate the bladder and facilitate the anterior dissection. This may be difficult if a patient has undergone an anterior colporrhaphy in the past.

I like to attach the anterior graft all the way down to the bladder base. Often times, what are thought to be stage III or stage IV cystoceles are in fact high anterior apical prolapses. Aggressive anterior vaginal wall dissection results in a more extensive attachment of the anterior vaginal mesh and decreased need for a paravaginal defect repair. Obviously, keeping the bladder from harm is very important.

The beauty of this procedure is that once you've suspended the anterior and posterior vaginal apex to the anterior longitudinal ligament, you're home free.

Surgeons often use a Y-shaped graft for sacral colpopexy. I currently use two pieces of 4-by-15-cm type 1 polypropylene mesh–a macroporous, monofilament mesh. I tension the posterior and anterior straps separately so as to avoid excess tension on the mesh and hence the vagina, and subsequently attach them to the anterior longitudinal ligament of the sacrum at the level of S1 or S2.

Many believe that if you don't stitch (or tack) at the S3 level, you're not allowing the vagina to be in its normal axis–that by going up to S1, you risk exposing the vagina posteriorly to increases in pressure that change the axis and increase posterior vaginal wall recurrence.

There have not been any studies precisely comparing mesh placement sites and their effect on anatomic success, but after doing a large number of these procedures, it does seem clear to me that it may not be necessary to attach the graft at the level of S3.

There are several reasons: For one, the anterior longitudinal ligament of the sacrum has been shown to have the greatest tensile strength at the level of the sacral promontory. Secondly, attachment of the mesh without tension to S1 or S2 has the same resultant vaginal axis because of retroperitoneal scarring of the mesh in the right pararectal space aided by intraabdominal pressure. Lastly, we risk venous plexus bleeding at the level of S3.

Surgeons use different types of sutures to fix the mesh, and I think there is some literature to support the use of monofilament sutures. I tend to use a braided polyester suture when performing the procedure laparoscopically because it ties much better.

Tying the mesh fairly loosely without strangulating tissue may reduce the risk of mesh erosion. I also tend to treat my patients with vaginal estrogen preoperatively and postoperatively to prevent mesh erosion.

Finally, I always retroperitonealize the mesh in order to decrease the risk of bowel obstruction and bowel adherence to the mesh. This may not be necessary with Mersilene mesh, which is multifilament but possesses macroporous and microporous elements (Type III).

Where We Stand Today

The problem with our literature is that we do not have enough adequately powered comparative trials for any of our vaginal apex suspension procedures. Our lack of adequate outcomes data is of particular concern when it comes to vaginal surgeries for apical prolapse.

The lack of data designating a preferred vaginal-route apical suspension procedure leads most surgeons to argue that abdominal sacral colpopexy is the accepted standard procedure.

In all circumstances, surgeons should do what is best for their patients. Ideally, though, we should have at least one abdominal approach–whether it be open, laparoscopic, or robotic–and at least one vaginal route to offer our patients because no procedure is best for all complaints, anatomic variations, and medical conditions.

Clearly, the pendulum has swung toward minimally invasive approaches for vaginal apex prolapse, as it has for many other conditions, but there are many questions that will remain unanswered until further randomized trials comparing abdominal and vaginal approaches, and new variations of each, are completed. This does not mean, in the meantime, that we should throw out the old.

Two strips of polypropylene mesh are attached to the anterior and posterior vaginal muscularis and passed through a retroperitoneal tunnel. Courtesy Dr. Marie Paraiso

Dissection of the presacral space and rectovaginal space: “I always dissect the presacral space first. I have learned to be prepared for many variables.” Courtesy Dr. Marie Paraiso

Sacral Colpopexy

No area of gynecologic surgery has undergone greater transformation over the past decade than the treatment of pelvic floor prolapse. Among other innovative surgical therapies, vaginal prolapse repair kits are now available to essentially replace the patient's pelvic floor.

Although these approaches are both novel and exciting, studies to date are lacking. Unfortunately, these procedures are too new to have stood the test of time.

Given this situation, it is imperative that the gynecologic surgeon who is involved in the treatment of pelvic floor prolapse maintain within his/her surgical armamentarium “tried-and-true” surgical techniques.

Because of its long-standing use, with excellent long-term outcomes, as can be noted in this edition of the Master Class in gynecologic surgery, the accepted standard continues to be the sacral colpopexy.

It seems especially fitting that this procedure, now a half century old, be reviewed based on approach (laparotomy, laparoscopy, robot-assisted), use of mesh material (biologic versus synthetic), technique (fixation of mesh at S1 versus S3, use of split mesh anterior and posterior versus mesh sheet anterior and posterior), and use of concomitant procedures (paravaginal defect repair, culdoplasty, prophylactic retropubic suspension, prophylactic midurethral slings).

Our discussant is Dr. Marie Paraiso, codirector of the Center for Female Pelvic Medicine and Reconstructive Surgery at the Cleveland Clinic Foundation. Despite the fact that she completed her fellowship training only a little more than 10 years ago, Dr. Paraiso has authored/coauthored 60 peer-reviewed journal articles and 13 book chapters, all pertaining to pelvic floor prolapse and urinary incontinence.

She is a much sought-after lecturer, and is routinely an invited speaker at American Association of Gynecologic Laparoscopists, the American College of Obstetricians and Gynecologists, Society of Gynecologic Surgeons, and American Urological Association.

Currently Dr. Paraiso is senior investigator of a prospective trial of robot-assisted laparoscopic sacral colpopexy versus traditional laparoscopic sacral colpopexy and the principal investigator of a cohort study evaluating the implementation of synthetic mesh for pelvic organ prolapse.

Vaginal prolapse repair kits have gained popularity, as has laparoscopic sacral colpopexy. The learning curve associated with laparoscopic suturing has also fostered an interest in robotic-assisted laparoscopic approaches. Behind this changing landscape, however, is a long history of experience with open abdominal sacral colpopexy.

It is an approach with a record of success that we should know, appreciate, and retain in our armamentarium of surgical options while at the same time continuing to investigate which procedures for vaginal apex prolapse provide optimal effectiveness and safety.

Key Studies on Cure Rates

The sacral colpopexy, introduced in 1957, is a procedure that bridges the support tissue of the anterior and posterior vaginal apex to the anterior longitudinal ligament of the sacrum. A modification of the procedure, called sacral colpoperineopexy, was developed later to treat patients with vaginal apex prolapse and perineal descent; it results in contiguous posterior vaginal wall support from the anterior longitudinal ligament to the perineum.

Indications for sacral colpopexy include a previously failed vaginal route apex suspension procedure, a foreshortened vagina, a weak or denervated pelvic floor, chronic increases in abdominal pressure related to medical comorbidities and/or heavy manual labor, collagen disorders, and the need for concomitant abdominal surgery. Some physicians argue that sacral colpopexy is undoubtedly indicated in young women with severe uterine or vaginal apex prolapse.

A literature review of over 90 articles with outcomes data on sacral colpopexy published in 2004 by Dr. Ingrid E. Nygaard and members of the Pelvic Floor Disorders Network showed anatomic cure rates of 78%-100% when cure was defined as lack of apical prolapse postoperatively, and cure rates of 58%-100% when cure was defined more broadly as lack of any postoperative prolapse (anterior, posterior, apical).

Of interest, the review showed that concomitant paravaginal defect repair or culdoplasty neither improved anatomic cure nor decreased the recurrence of prolapse.

The follow-up for most of the studies in Dr. Nygaard's review ranged from 6 months to 3 years. The longest follow-up duration was almost 14 years in a study conducted by Dr. W.S. Hilger and associates. This long-term outcomes analysis of abdominal sacral colopopexy showed a cure rate of 74%.

A few randomized clinical trials have compared abdominal sacral colpopexy to other vaginal apex suspension procedures for the treatment of vaginal prolapse, with variable outcomes but with an overriding message that abdominal sacral colpopexy is an effective procedure.

In 1996 Dr. J.T. Benson and associates reported an optimal anatomic cure rate of 58% in patients who underwent abdominal sacral colpopexy with concomitant vaginal reconstructive procedures, and 29% in patients who underwent bilateral sacrospinous ligament suspension with pelvic reconstruction. Because of the significant failure rate associated with vaginal surgery, however, this trial was aborted prior to reaching adequate power.

In 2004, Dr. C.F. Maher and associates compared abdominal sacral colpopexy and concomitant Burch procedure with vaginal sacrospinous colpopexy and concomitant Burch procedure. Anatomic cure was similar in both groups after a 2-year follow-up, but abdominal sacral colpopexy was associated with more posterior vaginal wall recurrences, and vaginal sacrospinous colpopexy was associated with more anterior vaginal wall recurrences.

Of recent importance for the future practice of abdominal sacral colpopexy are the results of a randomized, multicenter clinical trial conducted by the Pelvic Floor Disorders Network that compared open sacral colpopexy with or without concomitant Burch colposuspension in women without preoperative stress incontinence.

Investigators of the CARE trial (Colpopexy and Urinary Reduction Efforts) found that stress incontinence was prevalent 3 months postoperatively in almost twice as many women who did not undergo the Burch procedure as in those who did (approximately 44% vs. 24%).

The results, which were reported by Dr. L. Brubaker and associates in the New England Journal of Medicine, clearly support the value of performing a prophylactic retropubic suspension for potential urinary incontinence along with abdominal sacral colpopexy. (These data do not extrapolate to midurethral slings as prophylactic procedures concomitant with sacral colpopexies.)

Regarding the issue of laparoscopic versus open abdominal sacral colpopexies, my colleagues and I found through a chart review of 117 consecutive patients that the two approaches have comparable clinical outcomes. Laparoscopic sacral colpopexy was associated with both a significantly decreased hospital stay and a significantly longer operating room time.

Key Studies on Mesh

The use of various types of mesh material is an issue that has been addressed to some extent in the literature. Certainly there is no ideal biologic or synthetic mesh. But in general, outcomes data addressing any type of biologic graft in abdominal repair of apical prolapse are sparse and inconsistent, while there is good literature to support the use of nonabsorbable synthetic implants.

The overall rate of mesh erosion in Dr. Nygaard's review of abdominal sacral colpopexy (using various types of mesh) was 3.4%, with good evidence to support the use of polypropylene mesh.

Dr. A.G. Visco and associates published a series in 2001 evaluating the prevalence of synthetic mesh erosion (predominantly Mersilene mesh) between abdominal sacral colpopexy and various colpoperineopexy procedures. The erosion rate overall was 4.5%. Vaginally introduced mesh, however, was associated with an erosion rate of 40%, compared with an erosion rate of 16% when sutures were placed by the vaginal route and attached to abdominally placed mesh.

In a more recently published study, Dr. P. J. Culligan and associates randomized patients undergoing sacral colpopexy to receive polyprophylene mesh or solvent-dehydrated cadaveric fascia lata. Of the patients who returned for 1-year follow-up, 91% of the synthetic mesh group, and 68% of the fascia group, were classified as cured. Several case series have had similar results.

With the available data, I see little reason to use biologic tissue. One indication, though, may be sacral colpopexy with concomitant sigmoid resection rectopexy. I prefer a macroporous polypropylene mesh for sacral colpopexy.

The Surgery

Whether we perform abdominal sacral colpoplexy through an open, laparoscopic, or even robotic technique, we must always remember that when working within the presacral space there is a risk of life-threatening bleeding.

For this reason, I always dissect the presacral space first. I have learned to be prepared for many variables: Older women sometimes have undetected aneurysms of the blood vessels bordering this area, and the anatomy of the sacrum can vary.

Surgeons handle bleeding in various ways. Some surgeons prophylactically cauterize the middle sacral vessel. For venous bleeding, I have success when I am working laparoscopically with inserting a sponge through a port and holding pressure for 5 minutes. Sterile thumbtacks, bone wax, and hemostatic agents can also be of value.

Once I've made my presacral dissection, I proceed all the way down into the cul-de-sac, having already visualized or palpated both ureters. I make sure I am at least 4 cm medial to the right ureter when I make my incision in the peritoneum overlying the sacral promontory.

I dissect all the way down to the rectovaginal space in the cul-de-sac. Lately, in laparoscopic surgery, I have been making a tunnel between the sacrum and cul-de-sac, because the peritoneum easily lifts off the retroperitoneal structures.

I usually use end-to-end anastomosis sizers for vaginal manipulation, but others will use vaginal palpation or Lucite probes. I dissect into the rectovaginal space first, which consists of areolar tissue.

I believe that when we're treating vaginal apex prolapse, we must attach the graft over a significant portion of the posterior vaginal length and, in cases of perineal descent, all the way down to the perineum.

There's now a caveat to this procedural modification, however, in that there is a new colorectal procedure used for treatment of outlet dysfunction constipation called the STARR procedure (Stapling Transanal Rectocele Resection). Unfortunately, a patient with mesh running all the way down to her perineum may not be able to undergo this colorectal procedure because of the risk of rectovaginal fistula. I inform my colpopexy patients that this is a contraindication to the STARR procedure.

In laparoscopic and some open cases, I will retrograde fill the bladder in order to delineate the bladder and facilitate the anterior dissection. This may be difficult if a patient has undergone an anterior colporrhaphy in the past.

I like to attach the anterior graft all the way down to the bladder base. Often times, what are thought to be stage III or stage IV cystoceles are in fact high anterior apical prolapses. Aggressive anterior vaginal wall dissection results in a more extensive attachment of the anterior vaginal mesh and decreased need for a paravaginal defect repair. Obviously, keeping the bladder from harm is very important.

The beauty of this procedure is that once you've suspended the anterior and posterior vaginal apex to the anterior longitudinal ligament, you're home free.

Surgeons often use a Y-shaped graft for sacral colpopexy. I currently use two pieces of 4-by-15-cm type 1 polypropylene mesh–a macroporous, monofilament mesh. I tension the posterior and anterior straps separately so as to avoid excess tension on the mesh and hence the vagina, and subsequently attach them to the anterior longitudinal ligament of the sacrum at the level of S1 or S2.

Many believe that if you don't stitch (or tack) at the S3 level, you're not allowing the vagina to be in its normal axis–that by going up to S1, you risk exposing the vagina posteriorly to increases in pressure that change the axis and increase posterior vaginal wall recurrence.

There have not been any studies precisely comparing mesh placement sites and their effect on anatomic success, but after doing a large number of these procedures, it does seem clear to me that it may not be necessary to attach the graft at the level of S3.

There are several reasons: For one, the anterior longitudinal ligament of the sacrum has been shown to have the greatest tensile strength at the level of the sacral promontory. Secondly, attachment of the mesh without tension to S1 or S2 has the same resultant vaginal axis because of retroperitoneal scarring of the mesh in the right pararectal space aided by intraabdominal pressure. Lastly, we risk venous plexus bleeding at the level of S3.

Surgeons use different types of sutures to fix the mesh, and I think there is some literature to support the use of monofilament sutures. I tend to use a braided polyester suture when performing the procedure laparoscopically because it ties much better.

Tying the mesh fairly loosely without strangulating tissue may reduce the risk of mesh erosion. I also tend to treat my patients with vaginal estrogen preoperatively and postoperatively to prevent mesh erosion.

Finally, I always retroperitonealize the mesh in order to decrease the risk of bowel obstruction and bowel adherence to the mesh. This may not be necessary with Mersilene mesh, which is multifilament but possesses macroporous and microporous elements (Type III).

Where We Stand Today

The problem with our literature is that we do not have enough adequately powered comparative trials for any of our vaginal apex suspension procedures. Our lack of adequate outcomes data is of particular concern when it comes to vaginal surgeries for apical prolapse.

The lack of data designating a preferred vaginal-route apical suspension procedure leads most surgeons to argue that abdominal sacral colpopexy is the accepted standard procedure.

In all circumstances, surgeons should do what is best for their patients. Ideally, though, we should have at least one abdominal approach–whether it be open, laparoscopic, or robotic–and at least one vaginal route to offer our patients because no procedure is best for all complaints, anatomic variations, and medical conditions.

Clearly, the pendulum has swung toward minimally invasive approaches for vaginal apex prolapse, as it has for many other conditions, but there are many questions that will remain unanswered until further randomized trials comparing abdominal and vaginal approaches, and new variations of each, are completed. This does not mean, in the meantime, that we should throw out the old.

Two strips of polypropylene mesh are attached to the anterior and posterior vaginal muscularis and passed through a retroperitoneal tunnel. Courtesy Dr. Marie Paraiso

Dissection of the presacral space and rectovaginal space: “I always dissect the presacral space first. I have learned to be prepared for many variables.” Courtesy Dr. Marie Paraiso

Sacral Colpopexy

No area of gynecologic surgery has undergone greater transformation over the past decade than the treatment of pelvic floor prolapse. Among other innovative surgical therapies, vaginal prolapse repair kits are now available to essentially replace the patient's pelvic floor.

Although these approaches are both novel and exciting, studies to date are lacking. Unfortunately, these procedures are too new to have stood the test of time.

Given this situation, it is imperative that the gynecologic surgeon who is involved in the treatment of pelvic floor prolapse maintain within his/her surgical armamentarium “tried-and-true” surgical techniques.

Because of its long-standing use, with excellent long-term outcomes, as can be noted in this edition of the Master Class in gynecologic surgery, the accepted standard continues to be the sacral colpopexy.

It seems especially fitting that this procedure, now a half century old, be reviewed based on approach (laparotomy, laparoscopy, robot-assisted), use of mesh material (biologic versus synthetic), technique (fixation of mesh at S1 versus S3, use of split mesh anterior and posterior versus mesh sheet anterior and posterior), and use of concomitant procedures (paravaginal defect repair, culdoplasty, prophylactic retropubic suspension, prophylactic midurethral slings).

Our discussant is Dr. Marie Paraiso, codirector of the Center for Female Pelvic Medicine and Reconstructive Surgery at the Cleveland Clinic Foundation. Despite the fact that she completed her fellowship training only a little more than 10 years ago, Dr. Paraiso has authored/coauthored 60 peer-reviewed journal articles and 13 book chapters, all pertaining to pelvic floor prolapse and urinary incontinence.

She is a much sought-after lecturer, and is routinely an invited speaker at American Association of Gynecologic Laparoscopists, the American College of Obstetricians and Gynecologists, Society of Gynecologic Surgeons, and American Urological Association.

Currently Dr. Paraiso is senior investigator of a prospective trial of robot-assisted laparoscopic sacral colpopexy versus traditional laparoscopic sacral colpopexy and the principal investigator of a cohort study evaluating the implementation of synthetic mesh for pelvic organ prolapse.

BANFF, ALTA. — Combined spinal epidural produces a transient decrease in uterine but not umbilical artery blood flow that does not impact the fetal circulation, fetal heart rate pattern, or immediate neonatal outcome, according to the results of a small study.

“In normal pregnancies, we were able to a find a statistically but not clinically significant decrease in the uterine blood flow after CSE [combined spinal epidural],” Dr. Cristian Arzola said at the annual meeting of the Society for Obstetric Anesthesia and Perinatology.

The prospective study included 30 healthy patients in active labor with singleton, uncomplicated pregnancies at term. Pain, maternal blood pressure, fetal and maternal heart rate, blood-flow velocity waveforms, and pulsatility indices (PI) of the uterine and fetal umbilical arteries were measured before and at 5, 10, 15, and 30 minutes following administration of CSE (bupivacaine and fentanyl).

Dr. Arzola observed a drop in maternal systolic arterial blood pressure of 20% from baseline that was significant only at 10 and 15 minutes after CSE. Maternal heart rate dropped significantly at all time points, but remained within normal range. Pulsatility indices for the uterine artery were increased significantly at 10 minutes, indicating reduced blood flow; however, the PI for the umbilical artery remained stable, reported Dr. Arzola of the University of Chile, Santiago.

As expected, pain scores dropped dramatically, and with them adrenaline levels, which decreased more than 50% from baseline. Fetal heart rate did not change significantly, and tracings did not show altered patterns. Apgar scores and cord blood gases were all within normal range, and there were no signs of fetal distress, he said.

BANFF, ALTA. — Combined spinal epidural produces a transient decrease in uterine but not umbilical artery blood flow that does not impact the fetal circulation, fetal heart rate pattern, or immediate neonatal outcome, according to the results of a small study.

“In normal pregnancies, we were able to a find a statistically but not clinically significant decrease in the uterine blood flow after CSE [combined spinal epidural],” Dr. Cristian Arzola said at the annual meeting of the Society for Obstetric Anesthesia and Perinatology.

The prospective study included 30 healthy patients in active labor with singleton, uncomplicated pregnancies at term. Pain, maternal blood pressure, fetal and maternal heart rate, blood-flow velocity waveforms, and pulsatility indices (PI) of the uterine and fetal umbilical arteries were measured before and at 5, 10, 15, and 30 minutes following administration of CSE (bupivacaine and fentanyl).

Dr. Arzola observed a drop in maternal systolic arterial blood pressure of 20% from baseline that was significant only at 10 and 15 minutes after CSE. Maternal heart rate dropped significantly at all time points, but remained within normal range. Pulsatility indices for the uterine artery were increased significantly at 10 minutes, indicating reduced blood flow; however, the PI for the umbilical artery remained stable, reported Dr. Arzola of the University of Chile, Santiago.

As expected, pain scores dropped dramatically, and with them adrenaline levels, which decreased more than 50% from baseline. Fetal heart rate did not change significantly, and tracings did not show altered patterns. Apgar scores and cord blood gases were all within normal range, and there were no signs of fetal distress, he said.

BANFF, ALTA. — Combined spinal epidural produces a transient decrease in uterine but not umbilical artery blood flow that does not impact the fetal circulation, fetal heart rate pattern, or immediate neonatal outcome, according to the results of a small study.

“In normal pregnancies, we were able to a find a statistically but not clinically significant decrease in the uterine blood flow after CSE [combined spinal epidural],” Dr. Cristian Arzola said at the annual meeting of the Society for Obstetric Anesthesia and Perinatology.

The prospective study included 30 healthy patients in active labor with singleton, uncomplicated pregnancies at term. Pain, maternal blood pressure, fetal and maternal heart rate, blood-flow velocity waveforms, and pulsatility indices (PI) of the uterine and fetal umbilical arteries were measured before and at 5, 10, 15, and 30 minutes following administration of CSE (bupivacaine and fentanyl).

Dr. Arzola observed a drop in maternal systolic arterial blood pressure of 20% from baseline that was significant only at 10 and 15 minutes after CSE. Maternal heart rate dropped significantly at all time points, but remained within normal range. Pulsatility indices for the uterine artery were increased significantly at 10 minutes, indicating reduced blood flow; however, the PI for the umbilical artery remained stable, reported Dr. Arzola of the University of Chile, Santiago.

As expected, pain scores dropped dramatically, and with them adrenaline levels, which decreased more than 50% from baseline. Fetal heart rate did not change significantly, and tracings did not show altered patterns. Apgar scores and cord blood gases were all within normal range, and there were no signs of fetal distress, he said.

Doppler technology embraces a common phenomenon and a familiar part of our world. We all come to appreciate its principles when we are stopped at a train crossing: We hear the train's horn at one tonal pitch as the train approaches, and at a lower tonal pitch as it passes us and moves away. The change in pitch is a manifestation of the change in sound-wave frequency that our ears can detect, and—when it is transformed into mathematical equations and scientific formulas—the change in frequency is what forms the basis of Doppler technology.

Blood flow is like the moving train that passes a particular point, which in a clinical context is an ultrasound transducer. As blood rushes past it, the transducer detects changes in frequency.

The speed of blood flow, or the resistance the blood encounters downstream, can thus be assessed using these universal Doppler principles.

Doppler technology has been used quite effectively in medicine for a variety of clinical circumstances, from the assessment of thrombi to the assessment of blood flow to the fetus or resistance in the placenta.

Over the past few decades, this technique has been applied to both normal and problem pregnancies with the expectation that as blood-flow changes are detected by Doppler techniques, such detection might be effective in the assessment of fetal well-being and, more importantly, the loss of fetal well-being. The question, however, is how we can best apply Doppler technology in our general practice.

This month's guest professor is Dr. Christopher Harman, who is a well-known international expert in the area of ultrasound and Doppler technology.

Dr. Harman is professor and vice chairman of the department of obstetrics, gynecology, and reproductive sciences at the University of Maryland, Baltimore, as well as director of the school's maternal-fetal medicine division. He will discuss the application of Doppler in general obstetric practice.

Roles and Limitations of Doppler Ultrasound

What is Doppler good for, many of us wonder. And how might it be useful in routine obstetric care and the general, uncomplicated pregnancy?

To answer these questions, it's helpful to understand the basis for Doppler abnormalities, as well as the ways in which this technology is useful in detecting and managing specific clinical problems.

The evolution of Doppler has significantly expanded our understanding of many fetal disease processes, and it is now clear that Doppler is a useful tool for both evaluation and diagnosis. As part of an integrative, contextual approach to evaluation, it has earned a broad role that is not limited to application in intrauterine growth restriction.

Underlying Principles

The Doppler parameters that are used to evaluate pregnancies at risk for placental problems focus on the relationship between resistance in the blood vessels and its effect on blood flow. Especially important is Doppler's depiction of resistance and flow through the maternal uterine arteries and the fetal umbilical arteries.

When the placenta is developing properly, blood-flow resistance on both sides of this exchange surface falls significantly with advancing gestational age. In the uterine arteries, this phenomenon involves both direct mechanical change in the arteries themselves—the vessels lose their muscular coats and their reactive capability—and a change in the volume of blood that's able to run through them into a low-resistance placental bed.

These changes, signifying normal development of the uterine artery circulation, are easily depicted by Doppler ultrasound. The technology shows progressively lower speeds required to perfuse the uterine arteries, as well as significantly more blood flow during diastole. (See

Blood-flow resistance on the other side of the placenta—that is, in the fetal umbilical arteries—begins its progressive drop a little later than does resistance in the maternal uterine arteries. High resistance on the fetal side is a normal feature of first-trimester fetal circulation. (See

Ultimately, however, the development of successive generations of villous vessel branching offers more area for blood to run through, and resistance in the fetal umbilical arteries drops progressively. Much work has been done correlating the anatomical and structural elements of placental development with blood-flow resistance, and Doppler has been shown again and again to be an excellent method of evaluating the function of the placenta.

Specific Clinical Roles

Elevated resistance and persistence of notching in the uterine arteries throughout pregnancy signify a placenta that is not developing well—and often, an intrauterine growth-restricted fetus that has to cope with and invoke compensations for this placental insufficiency.

These compensations can at least in part be depicted by Doppler ultrasound through a more detailed evaluation of the fetal circulation. Here we must examine two additional vascular beds: the middle cerebral artery (MCA), which is used to evaluate brain blood flow, and the ductus venosus (DV), a unique fetal vessel that funnels a proportion of nutrient-rich umbilical venous return directly into the right atrium. Because this direct connection allows reflection of the atrial impulse, we can use the DV to evaluate cardiac status. Because the DV is very sensitive to fetal oxygen status, we can also use it to evaluate fetoplacental respiratory status.

In combination, Doppler assessment of these four vessels—the maternal uterine arteries, the fetal umbilical arteries, the MCA, and the DV—is key to evaluating maternal responses, placental responses, and fetal responses to altered resistance and subsequent intrauterine growth restriction (IUGR). It also can guide us in the timing of intervention for IUGR, mainly in decisions about when the baby should be delivered and when we should wait a few more days. In a critical sense, then, Doppler is useful in managing the pregnancy.

Doppler can be useful in several other specific instances as well. When assessing and monitoring a fetus for a heart problem—sustained tachycardia, for instance—a look at the DV can be key to understanding the effects of medication given to the mother to alter the fetal heart rate.

Doppler evaluation of the MCA, on the other hand, can be used to assess the anemic fetus. Thin blood moves rapidly, and the absolute velocity of blood flow through the MCA can be analyzed with confidence and used to assess the likelihood that the fetus has anemia—as sometimes occurs with Rh disease, maternal infection, or trauma, for instance—and whether the fetus needs intrauterine transfusions.

Screening Potential

In the regular ob.gyn. practice, then, Doppler ultrasound can certainly be employed in cases of inadequate fetal growth and in cases in which we want to know directly how the placenta is doing—in a patient who had a previous stillbirth or previous IUGR baby, for instance, or in patients for whom we have reason to suspect fetal anemia.

We can extrapolate this further, and ask whether there is a role for Doppler screening. Should everyone receive a Doppler evaluation to detect IUGR and other problems?

A significant amount of research has been done, and is ongoing, to determine Doppler's screening roles. In this context, it is important to consider individual vessels separately. There probably is no role for screening with MCA Doppler (

Ductus venosus Doppler can easily be done, in fact, in the context of the first-trimester ultrasound examination. In a study we recently completed at the University of Maryland, abnormal first-trimester DV Doppler findings were predictive of adverse outcomes—including cardiovascular defects, fetal growth restriction, and aneuploidy—in fetuses with normal nuchal translucency. (See

(Doppler assessment had been known previously to increase the predictive accuracy for Down syndrome when NT is increased. In this study we looked at cases with normal NT.) With respect to the uterine artery and umbilical artery, Doppler's screening applications (in the first half of pregnancy) is not as reliable as its diagnostic role. Patients showing abnormal placental blood-flow resistance before 20–22 weeks may still show normal blood -low patterns in the third trimester, with a normal mother and normal fetus, so we should not base major clinical management decisions or therapies on early Doppler screening.

Although there is not perfect correlation, there does appear to be potential value in Doppler screening in the first half of pregnancy. Uterine artery screening has been used in the first and second trimesters to detect cases in which placental development is deficient enough to put mothers at high risk for developing preeclampsia or isolated hypertension, and it turns out that elevated resistance and persistent notching are significantly predictive of the onset—and even, in some trials, the severity—of hypertensive complications.

Evidence has also suggested that detection of these abnormalities at 11–12 weeks, followed by the administration of low-dose aspirin (ranging in trials from 81 mg to 120 mg daily), may be effective in reducing the incidence of hypertension and preeclampsia.

Although larger trials are underway, they have not yet substantiated the benefits of low-dose aspirin that were seen in the small, original trials; nevertheless, at this point the potential of reducing the incidence and severity of hypertensive complications makes Doppler screening a worthwhile consideration.

Ultimately, I believe, trials will prove that uterine artery Doppler by itself is not the only answer for the detection of hypertensive complications, but is a valuable tool to be used in the context of other forms of evaluation—a conclusion that reflects a broader axiom of Doppler technology.

This principle may be even better illustrated when we consider umbilical artery Doppler screening. We might think that the inability of the fetus to properly develop umbilical arterial perfusion of the placenta would be virtually guaranteed to predict poor placental development and subsequent IUGR. Although that is largely true, studies have shown that it can be up to 24–28 weeks before Doppler predicts with optimal precision the likelihood of severe IUGR.

At this point in time, other factors—such as lack of fetal growth and changes in amniotic fluid volume—are also usually apparent, leaving umbilical artery Doppler without singular, populationwide benefit.

On the other hand, when umbilical artery Doppler, uterine artery Doppler, maternal blood pressure, and biochemical markers are combined, we have the ability to more precisely predict the maternal and fetal ramifications of placental insufficiency. In other words, Doppler by itself is not sufficient, but it will likely be a key component in a multifactorial assessment.

Doppler in 2007

We are on the verge, I believe, of accepting first- and early-second-trimester Doppler—DV Doppler in the context of NT screening, uterine and umbilical artery Doppler screening for placental disease—and putting them into practice.

Every ultrasound machine capable of doing fetal measurements and assessing fetal anatomy comes with Doppler capabilities, so access to technology is no longer a pertinent issue. The last 5 years have brought dramatic change in the application of Doppler ultrasound within ob.gyn. residencies as well.

Methodologies need to be standardized, and the issues of advanced training, certification, and quality control will be an ongoing focus of discussion and debate. Within the next 10 years, however, Doppler assessment will be not only an established tool but also a routine part of the first-trimester evaluation, even in low-risk populations.

Right now, it is no longer acceptable to use fetal heart rate testing alone, or fetal heart rate testing with biophysical profile scores, in managing the IUGR fetus. Current management should include detailed Doppler evaluation of multiple vessels in the fetal circulation.

Corresponding intrauterine treatment for placental insufficiency is less than optimal, but its development is positive. Work is underway, for example, on ways to alter maternal blood flow, address nutritional aspects, and deliver oxygen, and all these approaches are showing promise in assisting placental development once problems are detected. If these measures prove effective, the role of Doppler will continue to expand.

Doppler technology embraces a common phenomenon and a familiar part of our world. We all come to appreciate its principles when we are stopped at a train crossing: We hear the train's horn at one tonal pitch as the train approaches, and at a lower tonal pitch as it passes us and moves away. The change in pitch is a manifestation of the change in sound-wave frequency that our ears can detect, and—when it is transformed into mathematical equations and scientific formulas—the change in frequency is what forms the basis of Doppler technology.

Blood flow is like the moving train that passes a particular point, which in a clinical context is an ultrasound transducer. As blood rushes past it, the transducer detects changes in frequency.

The speed of blood flow, or the resistance the blood encounters downstream, can thus be assessed using these universal Doppler principles.

Doppler technology has been used quite effectively in medicine for a variety of clinical circumstances, from the assessment of thrombi to the assessment of blood flow to the fetus or resistance in the placenta.

Over the past few decades, this technique has been applied to both normal and problem pregnancies with the expectation that as blood-flow changes are detected by Doppler techniques, such detection might be effective in the assessment of fetal well-being and, more importantly, the loss of fetal well-being. The question, however, is how we can best apply Doppler technology in our general practice.

This month's guest professor is Dr. Christopher Harman, who is a well-known international expert in the area of ultrasound and Doppler technology.

Dr. Harman is professor and vice chairman of the department of obstetrics, gynecology, and reproductive sciences at the University of Maryland, Baltimore, as well as director of the school's maternal-fetal medicine division. He will discuss the application of Doppler in general obstetric practice.

Roles and Limitations of Doppler Ultrasound

What is Doppler good for, many of us wonder. And how might it be useful in routine obstetric care and the general, uncomplicated pregnancy?

To answer these questions, it's helpful to understand the basis for Doppler abnormalities, as well as the ways in which this technology is useful in detecting and managing specific clinical problems.

The evolution of Doppler has significantly expanded our understanding of many fetal disease processes, and it is now clear that Doppler is a useful tool for both evaluation and diagnosis. As part of an integrative, contextual approach to evaluation, it has earned a broad role that is not limited to application in intrauterine growth restriction.

Underlying Principles

The Doppler parameters that are used to evaluate pregnancies at risk for placental problems focus on the relationship between resistance in the blood vessels and its effect on blood flow. Especially important is Doppler's depiction of resistance and flow through the maternal uterine arteries and the fetal umbilical arteries.

When the placenta is developing properly, blood-flow resistance on both sides of this exchange surface falls significantly with advancing gestational age. In the uterine arteries, this phenomenon involves both direct mechanical change in the arteries themselves—the vessels lose their muscular coats and their reactive capability—and a change in the volume of blood that's able to run through them into a low-resistance placental bed.

These changes, signifying normal development of the uterine artery circulation, are easily depicted by Doppler ultrasound. The technology shows progressively lower speeds required to perfuse the uterine arteries, as well as significantly more blood flow during diastole. (See

Blood-flow resistance on the other side of the placenta—that is, in the fetal umbilical arteries—begins its progressive drop a little later than does resistance in the maternal uterine arteries. High resistance on the fetal side is a normal feature of first-trimester fetal circulation. (See

Ultimately, however, the development of successive generations of villous vessel branching offers more area for blood to run through, and resistance in the fetal umbilical arteries drops progressively. Much work has been done correlating the anatomical and structural elements of placental development with blood-flow resistance, and Doppler has been shown again and again to be an excellent method of evaluating the function of the placenta.

Specific Clinical Roles

Elevated resistance and persistence of notching in the uterine arteries throughout pregnancy signify a placenta that is not developing well—and often, an intrauterine growth-restricted fetus that has to cope with and invoke compensations for this placental insufficiency.

These compensations can at least in part be depicted by Doppler ultrasound through a more detailed evaluation of the fetal circulation. Here we must examine two additional vascular beds: the middle cerebral artery (MCA), which is used to evaluate brain blood flow, and the ductus venosus (DV), a unique fetal vessel that funnels a proportion of nutrient-rich umbilical venous return directly into the right atrium. Because this direct connection allows reflection of the atrial impulse, we can use the DV to evaluate cardiac status. Because the DV is very sensitive to fetal oxygen status, we can also use it to evaluate fetoplacental respiratory status.

In combination, Doppler assessment of these four vessels—the maternal uterine arteries, the fetal umbilical arteries, the MCA, and the DV—is key to evaluating maternal responses, placental responses, and fetal responses to altered resistance and subsequent intrauterine growth restriction (IUGR). It also can guide us in the timing of intervention for IUGR, mainly in decisions about when the baby should be delivered and when we should wait a few more days. In a critical sense, then, Doppler is useful in managing the pregnancy.

Doppler can be useful in several other specific instances as well. When assessing and monitoring a fetus for a heart problem—sustained tachycardia, for instance—a look at the DV can be key to understanding the effects of medication given to the mother to alter the fetal heart rate.

Doppler evaluation of the MCA, on the other hand, can be used to assess the anemic fetus. Thin blood moves rapidly, and the absolute velocity of blood flow through the MCA can be analyzed with confidence and used to assess the likelihood that the fetus has anemia—as sometimes occurs with Rh disease, maternal infection, or trauma, for instance—and whether the fetus needs intrauterine transfusions.

Screening Potential

In the regular ob.gyn. practice, then, Doppler ultrasound can certainly be employed in cases of inadequate fetal growth and in cases in which we want to know directly how the placenta is doing—in a patient who had a previous stillbirth or previous IUGR baby, for instance, or in patients for whom we have reason to suspect fetal anemia.

We can extrapolate this further, and ask whether there is a role for Doppler screening. Should everyone receive a Doppler evaluation to detect IUGR and other problems?

A significant amount of research has been done, and is ongoing, to determine Doppler's screening roles. In this context, it is important to consider individual vessels separately. There probably is no role for screening with MCA Doppler (

Ductus venosus Doppler can easily be done, in fact, in the context of the first-trimester ultrasound examination. In a study we recently completed at the University of Maryland, abnormal first-trimester DV Doppler findings were predictive of adverse outcomes—including cardiovascular defects, fetal growth restriction, and aneuploidy—in fetuses with normal nuchal translucency. (See

(Doppler assessment had been known previously to increase the predictive accuracy for Down syndrome when NT is increased. In this study we looked at cases with normal NT.) With respect to the uterine artery and umbilical artery, Doppler's screening applications (in the first half of pregnancy) is not as reliable as its diagnostic role. Patients showing abnormal placental blood-flow resistance before 20–22 weeks may still show normal blood -low patterns in the third trimester, with a normal mother and normal fetus, so we should not base major clinical management decisions or therapies on early Doppler screening.

Although there is not perfect correlation, there does appear to be potential value in Doppler screening in the first half of pregnancy. Uterine artery screening has been used in the first and second trimesters to detect cases in which placental development is deficient enough to put mothers at high risk for developing preeclampsia or isolated hypertension, and it turns out that elevated resistance and persistent notching are significantly predictive of the onset—and even, in some trials, the severity—of hypertensive complications.

Evidence has also suggested that detection of these abnormalities at 11–12 weeks, followed by the administration of low-dose aspirin (ranging in trials from 81 mg to 120 mg daily), may be effective in reducing the incidence of hypertension and preeclampsia.

Although larger trials are underway, they have not yet substantiated the benefits of low-dose aspirin that were seen in the small, original trials; nevertheless, at this point the potential of reducing the incidence and severity of hypertensive complications makes Doppler screening a worthwhile consideration.

Ultimately, I believe, trials will prove that uterine artery Doppler by itself is not the only answer for the detection of hypertensive complications, but is a valuable tool to be used in the context of other forms of evaluation—a conclusion that reflects a broader axiom of Doppler technology.

This principle may be even better illustrated when we consider umbilical artery Doppler screening. We might think that the inability of the fetus to properly develop umbilical arterial perfusion of the placenta would be virtually guaranteed to predict poor placental development and subsequent IUGR. Although that is largely true, studies have shown that it can be up to 24–28 weeks before Doppler predicts with optimal precision the likelihood of severe IUGR.

At this point in time, other factors—such as lack of fetal growth and changes in amniotic fluid volume—are also usually apparent, leaving umbilical artery Doppler without singular, populationwide benefit.

On the other hand, when umbilical artery Doppler, uterine artery Doppler, maternal blood pressure, and biochemical markers are combined, we have the ability to more precisely predict the maternal and fetal ramifications of placental insufficiency. In other words, Doppler by itself is not sufficient, but it will likely be a key component in a multifactorial assessment.

Doppler in 2007

We are on the verge, I believe, of accepting first- and early-second-trimester Doppler—DV Doppler in the context of NT screening, uterine and umbilical artery Doppler screening for placental disease—and putting them into practice.

Every ultrasound machine capable of doing fetal measurements and assessing fetal anatomy comes with Doppler capabilities, so access to technology is no longer a pertinent issue. The last 5 years have brought dramatic change in the application of Doppler ultrasound within ob.gyn. residencies as well.

Methodologies need to be standardized, and the issues of advanced training, certification, and quality control will be an ongoing focus of discussion and debate. Within the next 10 years, however, Doppler assessment will be not only an established tool but also a routine part of the first-trimester evaluation, even in low-risk populations.

Right now, it is no longer acceptable to use fetal heart rate testing alone, or fetal heart rate testing with biophysical profile scores, in managing the IUGR fetus. Current management should include detailed Doppler evaluation of multiple vessels in the fetal circulation.

Corresponding intrauterine treatment for placental insufficiency is less than optimal, but its development is positive. Work is underway, for example, on ways to alter maternal blood flow, address nutritional aspects, and deliver oxygen, and all these approaches are showing promise in assisting placental development once problems are detected. If these measures prove effective, the role of Doppler will continue to expand.

Doppler technology embraces a common phenomenon and a familiar part of our world. We all come to appreciate its principles when we are stopped at a train crossing: We hear the train's horn at one tonal pitch as the train approaches, and at a lower tonal pitch as it passes us and moves away. The change in pitch is a manifestation of the change in sound-wave frequency that our ears can detect, and—when it is transformed into mathematical equations and scientific formulas—the change in frequency is what forms the basis of Doppler technology.

Blood flow is like the moving train that passes a particular point, which in a clinical context is an ultrasound transducer. As blood rushes past it, the transducer detects changes in frequency.

The speed of blood flow, or the resistance the blood encounters downstream, can thus be assessed using these universal Doppler principles.

Doppler technology has been used quite effectively in medicine for a variety of clinical circumstances, from the assessment of thrombi to the assessment of blood flow to the fetus or resistance in the placenta.

Over the past few decades, this technique has been applied to both normal and problem pregnancies with the expectation that as blood-flow changes are detected by Doppler techniques, such detection might be effective in the assessment of fetal well-being and, more importantly, the loss of fetal well-being. The question, however, is how we can best apply Doppler technology in our general practice.

This month's guest professor is Dr. Christopher Harman, who is a well-known international expert in the area of ultrasound and Doppler technology.

Dr. Harman is professor and vice chairman of the department of obstetrics, gynecology, and reproductive sciences at the University of Maryland, Baltimore, as well as director of the school's maternal-fetal medicine division. He will discuss the application of Doppler in general obstetric practice.

Roles and Limitations of Doppler Ultrasound

What is Doppler good for, many of us wonder. And how might it be useful in routine obstetric care and the general, uncomplicated pregnancy?

To answer these questions, it's helpful to understand the basis for Doppler abnormalities, as well as the ways in which this technology is useful in detecting and managing specific clinical problems.

The evolution of Doppler has significantly expanded our understanding of many fetal disease processes, and it is now clear that Doppler is a useful tool for both evaluation and diagnosis. As part of an integrative, contextual approach to evaluation, it has earned a broad role that is not limited to application in intrauterine growth restriction.

Underlying Principles

The Doppler parameters that are used to evaluate pregnancies at risk for placental problems focus on the relationship between resistance in the blood vessels and its effect on blood flow. Especially important is Doppler's depiction of resistance and flow through the maternal uterine arteries and the fetal umbilical arteries.

When the placenta is developing properly, blood-flow resistance on both sides of this exchange surface falls significantly with advancing gestational age. In the uterine arteries, this phenomenon involves both direct mechanical change in the arteries themselves—the vessels lose their muscular coats and their reactive capability—and a change in the volume of blood that's able to run through them into a low-resistance placental bed.

These changes, signifying normal development of the uterine artery circulation, are easily depicted by Doppler ultrasound. The technology shows progressively lower speeds required to perfuse the uterine arteries, as well as significantly more blood flow during diastole. (See

Blood-flow resistance on the other side of the placenta—that is, in the fetal umbilical arteries—begins its progressive drop a little later than does resistance in the maternal uterine arteries. High resistance on the fetal side is a normal feature of first-trimester fetal circulation. (See

Ultimately, however, the development of successive generations of villous vessel branching offers more area for blood to run through, and resistance in the fetal umbilical arteries drops progressively. Much work has been done correlating the anatomical and structural elements of placental development with blood-flow resistance, and Doppler has been shown again and again to be an excellent method of evaluating the function of the placenta.

Specific Clinical Roles

Elevated resistance and persistence of notching in the uterine arteries throughout pregnancy signify a placenta that is not developing well—and often, an intrauterine growth-restricted fetus that has to cope with and invoke compensations for this placental insufficiency.

These compensations can at least in part be depicted by Doppler ultrasound through a more detailed evaluation of the fetal circulation. Here we must examine two additional vascular beds: the middle cerebral artery (MCA), which is used to evaluate brain blood flow, and the ductus venosus (DV), a unique fetal vessel that funnels a proportion of nutrient-rich umbilical venous return directly into the right atrium. Because this direct connection allows reflection of the atrial impulse, we can use the DV to evaluate cardiac status. Because the DV is very sensitive to fetal oxygen status, we can also use it to evaluate fetoplacental respiratory status.

In combination, Doppler assessment of these four vessels—the maternal uterine arteries, the fetal umbilical arteries, the MCA, and the DV—is key to evaluating maternal responses, placental responses, and fetal responses to altered resistance and subsequent intrauterine growth restriction (IUGR). It also can guide us in the timing of intervention for IUGR, mainly in decisions about when the baby should be delivered and when we should wait a few more days. In a critical sense, then, Doppler is useful in managing the pregnancy.

Doppler can be useful in several other specific instances as well. When assessing and monitoring a fetus for a heart problem—sustained tachycardia, for instance—a look at the DV can be key to understanding the effects of medication given to the mother to alter the fetal heart rate.

Doppler evaluation of the MCA, on the other hand, can be used to assess the anemic fetus. Thin blood moves rapidly, and the absolute velocity of blood flow through the MCA can be analyzed with confidence and used to assess the likelihood that the fetus has anemia—as sometimes occurs with Rh disease, maternal infection, or trauma, for instance—and whether the fetus needs intrauterine transfusions.

Screening Potential

In the regular ob.gyn. practice, then, Doppler ultrasound can certainly be employed in cases of inadequate fetal growth and in cases in which we want to know directly how the placenta is doing—in a patient who had a previous stillbirth or previous IUGR baby, for instance, or in patients for whom we have reason to suspect fetal anemia.

We can extrapolate this further, and ask whether there is a role for Doppler screening. Should everyone receive a Doppler evaluation to detect IUGR and other problems?

A significant amount of research has been done, and is ongoing, to determine Doppler's screening roles. In this context, it is important to consider individual vessels separately. There probably is no role for screening with MCA Doppler (

Ductus venosus Doppler can easily be done, in fact, in the context of the first-trimester ultrasound examination. In a study we recently completed at the University of Maryland, abnormal first-trimester DV Doppler findings were predictive of adverse outcomes—including cardiovascular defects, fetal growth restriction, and aneuploidy—in fetuses with normal nuchal translucency. (See

(Doppler assessment had been known previously to increase the predictive accuracy for Down syndrome when NT is increased. In this study we looked at cases with normal NT.) With respect to the uterine artery and umbilical artery, Doppler's screening applications (in the first half of pregnancy) is not as reliable as its diagnostic role. Patients showing abnormal placental blood-flow resistance before 20–22 weeks may still show normal blood -low patterns in the third trimester, with a normal mother and normal fetus, so we should not base major clinical management decisions or therapies on early Doppler screening.

Although there is not perfect correlation, there does appear to be potential value in Doppler screening in the first half of pregnancy. Uterine artery screening has been used in the first and second trimesters to detect cases in which placental development is deficient enough to put mothers at high risk for developing preeclampsia or isolated hypertension, and it turns out that elevated resistance and persistent notching are significantly predictive of the onset—and even, in some trials, the severity—of hypertensive complications.

Evidence has also suggested that detection of these abnormalities at 11–12 weeks, followed by the administration of low-dose aspirin (ranging in trials from 81 mg to 120 mg daily), may be effective in reducing the incidence of hypertension and preeclampsia.

Although larger trials are underway, they have not yet substantiated the benefits of low-dose aspirin that were seen in the small, original trials; nevertheless, at this point the potential of reducing the incidence and severity of hypertensive complications makes Doppler screening a worthwhile consideration.

Ultimately, I believe, trials will prove that uterine artery Doppler by itself is not the only answer for the detection of hypertensive complications, but is a valuable tool to be used in the context of other forms of evaluation—a conclusion that reflects a broader axiom of Doppler technology.

This principle may be even better illustrated when we consider umbilical artery Doppler screening. We might think that the inability of the fetus to properly develop umbilical arterial perfusion of the placenta would be virtually guaranteed to predict poor placental development and subsequent IUGR. Although that is largely true, studies have shown that it can be up to 24–28 weeks before Doppler predicts with optimal precision the likelihood of severe IUGR.

At this point in time, other factors—such as lack of fetal growth and changes in amniotic fluid volume—are also usually apparent, leaving umbilical artery Doppler without singular, populationwide benefit.

On the other hand, when umbilical artery Doppler, uterine artery Doppler, maternal blood pressure, and biochemical markers are combined, we have the ability to more precisely predict the maternal and fetal ramifications of placental insufficiency. In other words, Doppler by itself is not sufficient, but it will likely be a key component in a multifactorial assessment.

Doppler in 2007

We are on the verge, I believe, of accepting first- and early-second-trimester Doppler—DV Doppler in the context of NT screening, uterine and umbilical artery Doppler screening for placental disease—and putting them into practice.

Every ultrasound machine capable of doing fetal measurements and assessing fetal anatomy comes with Doppler capabilities, so access to technology is no longer a pertinent issue. The last 5 years have brought dramatic change in the application of Doppler ultrasound within ob.gyn. residencies as well.

Methodologies need to be standardized, and the issues of advanced training, certification, and quality control will be an ongoing focus of discussion and debate. Within the next 10 years, however, Doppler assessment will be not only an established tool but also a routine part of the first-trimester evaluation, even in low-risk populations.

Right now, it is no longer acceptable to use fetal heart rate testing alone, or fetal heart rate testing with biophysical profile scores, in managing the IUGR fetus. Current management should include detailed Doppler evaluation of multiple vessels in the fetal circulation.

Corresponding intrauterine treatment for placental insufficiency is less than optimal, but its development is positive. Work is underway, for example, on ways to alter maternal blood flow, address nutritional aspects, and deliver oxygen, and all these approaches are showing promise in assisting placental development once problems are detected. If these measures prove effective, the role of Doppler will continue to expand.