Master Class

MILWAUKEE — Irritable bowel syndrome did not result from elective gynecologic surgery in a large prospective binational study of 255 women.

There was no significant difference in the development of irritable bowel syndrome (IBS) at 3 and 12 months' follow-up among 132 women who underwent elective gynecologic surgery for disorders not related to pain and 123 age-matched controls who went for consultation at a gynecology clinic but did not undergo surgery. None of the women had IBS at baseline.

However, significantly more surgical patients than controls developed persistent abdominal pain (14% vs. 2%, respectively), Dr. Ami D. Sperber reported at an international symposium sponsored by the International Foundation for Functional Gastrointestinal Disorders.

The development of persistent pain was predicted by psychosocial factors, but not by sociodemographic or clinical variables, according to an analysis that included surgery type (hysterectomy, tubal ligation, cystectomy); laparotomy versus laparoscopy; surgery duration; amount of postoperative analgesia; and surgical complications.

“One might think—and this is still speculative—that the development of persistent pain could be associated more with central registration and amplification of the afferent signal via cognitive and emotional input, rather than with the degree of the actual peripheral injury per se,” said Dr. Sperber, associate professor of medicine, Soroka Medical Center, Ben Gurion University of the Negev, Beer-Sheba, Israel.

Women who anticipated difficulty in recovering from surgery were more than five times as likely (odds ratio [OR] 5.2) to develop persistent abdominal pain, according to results from psychosocial evaluations that included the Implicit Models of Illness Questionnaire, Client Satisfaction (CSQ) scale, and Sense of Coherence (SOC) scale.

Persistent pain also was more likely to occur among women with a strong personal need for control (OR 1.2), those who perceived their disease as being more severe or constant (OR 1.9), and those who had lower coping skills (OR 1.09), reported Dr. Sperber and coinvestigator Dr. Douglas Drossman, professor of medicine and psychiatry and codirector of the Center for Functional GI & Motility Disorders, University of North Carolina at Chapel Hill.

Although the findings are still preliminary, they could be used to identify women with a similar profile and to conduct interventions before surgery that would improve coping skills or reduce catastrophizing, Dr. Sperber said in an interview.

Prior studies show that patients with IBS undergo more gynecologic operations, particularly hysterectomy, than women in the general population. But it's unknown whether women with IBS undergo more surgery or whether gynecologic surgery can cause IBS or new bowel symptoms such as constipation.

Constipation was increased among the women in the study, but did not differ significantly between groups, said Dr. Sperber at the meeting, which was cosponsored by the University of Wisconsin.

MILWAUKEE — Irritable bowel syndrome did not result from elective gynecologic surgery in a large prospective binational study of 255 women.

There was no significant difference in the development of irritable bowel syndrome (IBS) at 3 and 12 months' follow-up among 132 women who underwent elective gynecologic surgery for disorders not related to pain and 123 age-matched controls who went for consultation at a gynecology clinic but did not undergo surgery. None of the women had IBS at baseline.

However, significantly more surgical patients than controls developed persistent abdominal pain (14% vs. 2%, respectively), Dr. Ami D. Sperber reported at an international symposium sponsored by the International Foundation for Functional Gastrointestinal Disorders.

The development of persistent pain was predicted by psychosocial factors, but not by sociodemographic or clinical variables, according to an analysis that included surgery type (hysterectomy, tubal ligation, cystectomy); laparotomy versus laparoscopy; surgery duration; amount of postoperative analgesia; and surgical complications.

“One might think—and this is still speculative—that the development of persistent pain could be associated more with central registration and amplification of the afferent signal via cognitive and emotional input, rather than with the degree of the actual peripheral injury per se,” said Dr. Sperber, associate professor of medicine, Soroka Medical Center, Ben Gurion University of the Negev, Beer-Sheba, Israel.

Women who anticipated difficulty in recovering from surgery were more than five times as likely (odds ratio [OR] 5.2) to develop persistent abdominal pain, according to results from psychosocial evaluations that included the Implicit Models of Illness Questionnaire, Client Satisfaction (CSQ) scale, and Sense of Coherence (SOC) scale.

Persistent pain also was more likely to occur among women with a strong personal need for control (OR 1.2), those who perceived their disease as being more severe or constant (OR 1.9), and those who had lower coping skills (OR 1.09), reported Dr. Sperber and coinvestigator Dr. Douglas Drossman, professor of medicine and psychiatry and codirector of the Center for Functional GI & Motility Disorders, University of North Carolina at Chapel Hill.

Although the findings are still preliminary, they could be used to identify women with a similar profile and to conduct interventions before surgery that would improve coping skills or reduce catastrophizing, Dr. Sperber said in an interview.

Prior studies show that patients with IBS undergo more gynecologic operations, particularly hysterectomy, than women in the general population. But it's unknown whether women with IBS undergo more surgery or whether gynecologic surgery can cause IBS or new bowel symptoms such as constipation.

Constipation was increased among the women in the study, but did not differ significantly between groups, said Dr. Sperber at the meeting, which was cosponsored by the University of Wisconsin.

MILWAUKEE — Irritable bowel syndrome did not result from elective gynecologic surgery in a large prospective binational study of 255 women.

There was no significant difference in the development of irritable bowel syndrome (IBS) at 3 and 12 months' follow-up among 132 women who underwent elective gynecologic surgery for disorders not related to pain and 123 age-matched controls who went for consultation at a gynecology clinic but did not undergo surgery. None of the women had IBS at baseline.

However, significantly more surgical patients than controls developed persistent abdominal pain (14% vs. 2%, respectively), Dr. Ami D. Sperber reported at an international symposium sponsored by the International Foundation for Functional Gastrointestinal Disorders.

The development of persistent pain was predicted by psychosocial factors, but not by sociodemographic or clinical variables, according to an analysis that included surgery type (hysterectomy, tubal ligation, cystectomy); laparotomy versus laparoscopy; surgery duration; amount of postoperative analgesia; and surgical complications.

“One might think—and this is still speculative—that the development of persistent pain could be associated more with central registration and amplification of the afferent signal via cognitive and emotional input, rather than with the degree of the actual peripheral injury per se,” said Dr. Sperber, associate professor of medicine, Soroka Medical Center, Ben Gurion University of the Negev, Beer-Sheba, Israel.

Women who anticipated difficulty in recovering from surgery were more than five times as likely (odds ratio [OR] 5.2) to develop persistent abdominal pain, according to results from psychosocial evaluations that included the Implicit Models of Illness Questionnaire, Client Satisfaction (CSQ) scale, and Sense of Coherence (SOC) scale.

Persistent pain also was more likely to occur among women with a strong personal need for control (OR 1.2), those who perceived their disease as being more severe or constant (OR 1.9), and those who had lower coping skills (OR 1.09), reported Dr. Sperber and coinvestigator Dr. Douglas Drossman, professor of medicine and psychiatry and codirector of the Center for Functional GI & Motility Disorders, University of North Carolina at Chapel Hill.

Although the findings are still preliminary, they could be used to identify women with a similar profile and to conduct interventions before surgery that would improve coping skills or reduce catastrophizing, Dr. Sperber said in an interview.

Prior studies show that patients with IBS undergo more gynecologic operations, particularly hysterectomy, than women in the general population. But it's unknown whether women with IBS undergo more surgery or whether gynecologic surgery can cause IBS or new bowel symptoms such as constipation.

Constipation was increased among the women in the study, but did not differ significantly between groups, said Dr. Sperber at the meeting, which was cosponsored by the University of Wisconsin.

Presacral neurectomy—the resection of the hypogastric nervous plexus that innervates the uterus—is a safe and effective alternative for these women.

It can be done alone or concomitantly with any surgical treatment of coexisting endometriosis or other pelvic pathology.

Presacral neurectomy is not a simple procedure, however, and should not be attempted without appropriate training and preparation, or without careful patient selection.

The procedure does not alleviate adnexal pain or pelvic pain that is more lateral, and is indicated when medical management has failed.

Nonetheless, when patients are carefully selected, and when the procedure is performed by a skilled surgeon who follows the principles and technique described more than 80 years ago by Dr. M.G. Cotte, it can be effectively carried out with good long-term outcomes for the majority of patients who have disabling midline dysmenorrhea and deep central, chronic pelvic pain.

More and more, the procedure is being done laparoscopically with a lower rate of postoperative morbidity. Indeed, advances in minimally invasive surgery have renewed interest in the procedure after a period starting in the 1960s in which the introduction of nonsteroidal anti-inflammatory drugs and various regimens of hormonal suppression caused interest to wane.

Moreover, despite the fact that the data on presacral neurectomy historically have covered women with dysmenorrhea, nonetheless within modern medicine dyspareunia has become an additional indication for the procedure.

Cotte's Technique

Dr. M. Jaboulay first described the severance of sacral sympathetic afferent fibers for serious dysmenorrhea (using a posterior extraperitoneal approach) in 1899, and a variety of other procedures for nerve interruption subsequently evolved.

It took until 1937, however, for a description of presacral neurectomy to emerge.

Dr. M.G. Cotte is credited with performing the first presacral neurectomy in 1924, and 13 years later he reported 98% success after transection of the superior hypogastric plexus in 1,500 patients.

Dr. Cotte emphasized that the only nerve tissue that should be resected is that within what he called the interiliac triangle (now known as the “Triangle of Cotte”), and that resection of all nerve elements in the triangle is essential in order to maximize effectiveness and minimize complications.

This triangle is extremely important. Unfortunately, because of the perilous location of the sensitive plexus, there have been modifications made in the procedure throughout the years.

Results have thus been variable, and some groups have reported recurrence rates of pelvic pain after presacral neurectomy that are significantly higher than the rates achieved by Cotte and the rates that we—and others—are now achieving.

It is difficult to analyze these results and ascertain exactly what the problems were and why the procedures failed.

However, because those surgeons who follow Cotte's principles and technique are indeed achieving good long-term results, I suspect that patient selection in the other studies wasn't optimal, or that the procedure was performed in a manner different from that originally described by Cotte.

The Anatomy

The presacral nerve is actually almost always a plexus of nerves known as the superior hypogastric plexus. It is a direct extension of the aortic plexus below the aortic bifurcation.

The plexus spreads out behind the peritoneum in the loose areolar tissue lying over the fourth and fifth lumbar vertebrae.

Between the vertebrae and the presacral nerve lies the middle sacral artery. On the right of the presacral nerve lie the right ureter and the common iliac vein and artery. On the left lie the sigmoid colon, inferior mesenteric vessels, left iliac vessels, and the left ureter.

Within the Triangle of Cotte, then, the common iliac artery and ureter are on the right, and the common iliac vein is on the left. The inferior mesenteric, superior hemorrhoidal, and midsacral arteries are in the center of the prelumbar space.

The triangle is defined caudally by the sacral promontory and laterally by the common iliac arteries. The superior edge of the triangle is delineated by the aortic bifurcation.

Centrally and to the left, the multiple nerve fibers representing the presacral nerve—sometimes in bundles—run caudally from the aortic plexus above and through the interiliac triangle to form the superior hypogastric plexus. These fibers are buried in loose areolar tissue. They display no particular patterns and vary among individuals.

In fact, surgeons must be prepared to encounter variable anatomical findings, in addition to being prepared for potential bleeding problems that can result from the sensitive proximity to the aortic bifurcation, vena cava, and iliac vessels.

The Procedure

In our Cotte-based procedure, an operating laparoscope is inserted through a 10-mm cannula placed through an umbilical incision.

Two or three suprapubic 5-mm cannulas are inserted at about 5-cm midsuprapubic and at 7 cm to the left and right side for the introduction of a bipolar electrode, suction irrigator, and grasping forceps, respectively.

I place the patient in the steep Trendelenburg's position, tilt her slightly to the left, and hold the sigmoid colon away from the presacral area.

After the Triangle of Cotte is identified, the peritoneum overlying the sacral promontory is elevated with a grasping forceps. I use grasping forceps to elevate the peritoneum overlying the promontory and make a small opening. I have used the CO₂ laser or scissors in the past. Currently, I use harmonic shears.

The suction irrigator is inserted through this opening, and the peritoneum is elevated. The peritoneum is incised horizontally and vertically, and the opening is extended cephalad to the aortic bifurcation. Any bleeding from the peritoneal vessels can be controlled with the bipolar electrocoagulator. If harmonic shears are used, this is rarely necessary.

After removing retroperitoneal lymphatic and fatty tissue, we reach the hypogastric plexus and can identify the presacral tissue.

The nerve plexus is grasped with an atraumatic forceps, and using blunt and sharp dissection, I skeletonize, desiccate, and excise the nerve fibers.

All the nerve fibers that lie within the boundaries of the interiliac triangle must be removed, including any fibers entering the area from under the common iliac artery and over the left common iliac vein.

I then irrigate the retroperitoneal space and coagulate bleeding points, if any. Sutures are not required to approximate the posterior peritoneum. The area heals completely on follow-up, and is covered by the peritoneum.

I send excised tissue for histologic examination to verify removal of nerve elements and ganglion.

The Outcomes

In 1992, we described a laparoscopic method of presacral neurectomy, based on Cotte's principles and technique, as part of a report on 52 patients with disabling midline dysmenorrhea and varying severity of endometriosis, all of whom had been unresponsive to medical treatment.

Of the 52 patients who were followed for more than a year, 48 (92%) reported relief of dysmenorrhea, and 27 (52%) reported complete pain relief (BJOG 1992:99;659–63).

In 1998, we reported even longer-term outcomes (up to 72 months) in 176 women with central pelvic pain who underwent laparoscopic presacral neurectomy and treatment of endometriosis. Pain was reduced substantially in 74% of the women, and just as notably, the degree of pain improvement was not directly related to the stage of endometriosis.

A reduction in pain of more than 50% was reported in 69.8% of women with stage I endometriosis (using the revised classification of the American Fertility Society), 77.3% of those with stage II, 71.4% of those with stage III, and 84.6% of those with stage IV endometriosis (Obstet. Gynecol. 1998;91:701–4).

We were discouraged from offering patients treatment in a blinded manner because a randomized trial conducted not long before this had been stopped in an early stage by a monitoring committee when the efficacy of presacral neurectomy became clear.

In this prematurely halted study, Dr. B. Tjaden, Dr. John A. Rock, and associates at Johns Hopkins University found that of 17 patients undergoing the procedure (all had moderate to severe dysmenorrhea and stage III-IV endometriosis), only two had recurrence of pain and the remainder remained pain free at 42 months of follow-up.

Of the nine patients who underwent resection of endometriosis but not presacral neurectomy, none had relief of midline pain (Obstet. Gynecol. 1990;76:89–91).

Although Dr. Rock and his team found that relief of dyspareunia was variable in both groups, we and others have had success in treating this manifestation of pelvic pain.

In our study published in 1998, a reduction in dyspareunia by more than 50% was seen in 32 of 60 patients followed for 24 months or longer.

More recently, Dr. F. Zullo and associates published the 2-year success of laparoscopic presacral neurectomy, reporting significant reduction in the frequency and severity not only of chronic pelvic pain and dysmenorrhea but of dyspareunia as well (J. Am. Assoc. Gynecol. Laparosc. 2004;11:23–8).

Laparoscopic uterosacral nerve ablation is an easier procedure to perform than laparoscopic presacral neurectomy, but it has been proved to provide only temporary relief and not the longer-term pain reduction that presacral neurectomy can achieve in most cases. I liken it to trimming a weed in your yard versus pulling the weed out by the roots.

The Complications

The most common and urgent intraoperative complication is bleeding, and we must be prepared, in the event of injury, to actively identify the anatomy and determine the feasibility of the repair laparoscopically, or to immediately convert to laparotomy.

We have not had any major complications, but the slight risk of vascular injury and the possible need to convert to laparotomy is something that patients should be informed of.

Long-term complications with presacral neurectomy are uncommon. Urinary urgency, poor bladder emptying, and constipation have been reported occasionally, as has vaginal dryness during sexual arousal.

We have not had any major complications such as vascular injury, gastrointestinal injury, or genitourinary injury in any of our presacral neurectomy procedures. Nor did any of these cases require conversion to laparotomy or transfusion.

Our initial (1992) study revealed no major intraoperative or immediate postoperative complications.

However, of the 52 women followed after 1 year, seven women reported either constipation (three patients), urinary urgency (one), vaginal dryness (one), or “painless labor” (two). These are all among the issues that we routinely cover in our patient counseling.

In conclusion, procedural failure, of course, is an important long-term complication, but the most common reasons for failure—poor patient selection and incomplete neurectomy because of neurologic variability or failure to remove all nerve tissue within the interiliac triangle—can, in most cases, be avoided with proper training and preparation.

Within the Triangle of Cotte, the common iliac artery is on the right; the common iliac vein is on the left. Courtesy Dr. Ceana Nezhat

The presacral tissue is identified, and the nerve plexus is grasped with an atraumatic forceps.

All the nerve fibers that lie within the boundaries of the interiliac triangle have been removed.

Presacral space on second look: The area heals completely on follow-up. Photos courtesy Dr. Ceana Nezhat

Presacral Neurectomy

In previous Master Class articles, we have explored the diagnosis and work-up of chronic pelvic pain (OB.GYN. NEWS, Feb. 1, 2007, p. 28; April 1, 2007, p. 25). Moreover, we presented an excellent technique in surgical extirpation of endometriosis (OB.GYN. NEWS, April 1, 2007, p. 38).

Despite a thorough evaluation and medical and surgical treatment, midline pelvic pain, dysmenorrhea, and/or dyspareunia may persist. Not only can this be caused by conditions such as primary dysmenorrhea or adenomyosis, but it may persist despite adequate surgical treatment of endometriosis and pelvic adhesions.

When midline pelvic pain, dysmenorrhea, and/or dyspareunia are not alleviated with treatment, ancillary surgical procedures should be considered. Unfortunately, the most commonly performed procedure—transection of the uterosacral nerves—has proved to be ineffective over time.

On the other hand, if performed by a skilled surgeon who understands the anatomy below the bifurcation of the aorta at the level of the sacral promontory, presacral neurectomy has proved quite effective long term.

I once performed this technique via laparotomy, but for nearly 20 years now I have used a purely laparoscopic technique. With the same indications, I have noted similar results to those explained here by Dr. Ceana Nezhat, the invited author of this Master Class article.

Dr. Ceana Nezhat is in private practice in Atlanta and is one of three brothers who are extraordinary gynecologic laparoscopic surgeons. Dr. Camran Nezhat, of Stanford (Calif.) University, has been an innovator in the laparoscopic treatment of endometriosis for a quarter of a century. Dr. Farr Nezhat, who is a gynecologist at Mount Sinai School of Medicine, New York, has been a leader in the use of laparoscopy to perform gynecologic oncology procedures. Dr. Ceana Nezhat is known not only for his laparoscopic treatment of endometriosis, but also for pelvic floor reconstruction. He is a prolific author and an international lecturer, and it is with great admiration that we bring you Dr. Ceana Nezhat, discussing the laparoscopic approach to presacral neurectomy.

Presacral neurectomy—the resection of the hypogastric nervous plexus that innervates the uterus—is a safe and effective alternative for these women.

It can be done alone or concomitantly with any surgical treatment of coexisting endometriosis or other pelvic pathology.

Presacral neurectomy is not a simple procedure, however, and should not be attempted without appropriate training and preparation, or without careful patient selection.

The procedure does not alleviate adnexal pain or pelvic pain that is more lateral, and is indicated when medical management has failed.

Nonetheless, when patients are carefully selected, and when the procedure is performed by a skilled surgeon who follows the principles and technique described more than 80 years ago by Dr. M.G. Cotte, it can be effectively carried out with good long-term outcomes for the majority of patients who have disabling midline dysmenorrhea and deep central, chronic pelvic pain.

More and more, the procedure is being done laparoscopically with a lower rate of postoperative morbidity. Indeed, advances in minimally invasive surgery have renewed interest in the procedure after a period starting in the 1960s in which the introduction of nonsteroidal anti-inflammatory drugs and various regimens of hormonal suppression caused interest to wane.

Moreover, despite the fact that the data on presacral neurectomy historically have covered women with dysmenorrhea, nonetheless within modern medicine dyspareunia has become an additional indication for the procedure.

Cotte's Technique

Dr. M. Jaboulay first described the severance of sacral sympathetic afferent fibers for serious dysmenorrhea (using a posterior extraperitoneal approach) in 1899, and a variety of other procedures for nerve interruption subsequently evolved.

It took until 1937, however, for a description of presacral neurectomy to emerge.

Dr. M.G. Cotte is credited with performing the first presacral neurectomy in 1924, and 13 years later he reported 98% success after transection of the superior hypogastric plexus in 1,500 patients.

Dr. Cotte emphasized that the only nerve tissue that should be resected is that within what he called the interiliac triangle (now known as the “Triangle of Cotte”), and that resection of all nerve elements in the triangle is essential in order to maximize effectiveness and minimize complications.

This triangle is extremely important. Unfortunately, because of the perilous location of the sensitive plexus, there have been modifications made in the procedure throughout the years.

Results have thus been variable, and some groups have reported recurrence rates of pelvic pain after presacral neurectomy that are significantly higher than the rates achieved by Cotte and the rates that we—and others—are now achieving.

It is difficult to analyze these results and ascertain exactly what the problems were and why the procedures failed.

However, because those surgeons who follow Cotte's principles and technique are indeed achieving good long-term results, I suspect that patient selection in the other studies wasn't optimal, or that the procedure was performed in a manner different from that originally described by Cotte.

The Anatomy

The presacral nerve is actually almost always a plexus of nerves known as the superior hypogastric plexus. It is a direct extension of the aortic plexus below the aortic bifurcation.

The plexus spreads out behind the peritoneum in the loose areolar tissue lying over the fourth and fifth lumbar vertebrae.

Between the vertebrae and the presacral nerve lies the middle sacral artery. On the right of the presacral nerve lie the right ureter and the common iliac vein and artery. On the left lie the sigmoid colon, inferior mesenteric vessels, left iliac vessels, and the left ureter.

Within the Triangle of Cotte, then, the common iliac artery and ureter are on the right, and the common iliac vein is on the left. The inferior mesenteric, superior hemorrhoidal, and midsacral arteries are in the center of the prelumbar space.

The triangle is defined caudally by the sacral promontory and laterally by the common iliac arteries. The superior edge of the triangle is delineated by the aortic bifurcation.

Centrally and to the left, the multiple nerve fibers representing the presacral nerve—sometimes in bundles—run caudally from the aortic plexus above and through the interiliac triangle to form the superior hypogastric plexus. These fibers are buried in loose areolar tissue. They display no particular patterns and vary among individuals.

In fact, surgeons must be prepared to encounter variable anatomical findings, in addition to being prepared for potential bleeding problems that can result from the sensitive proximity to the aortic bifurcation, vena cava, and iliac vessels.

The Procedure

In our Cotte-based procedure, an operating laparoscope is inserted through a 10-mm cannula placed through an umbilical incision.

Two or three suprapubic 5-mm cannulas are inserted at about 5-cm midsuprapubic and at 7 cm to the left and right side for the introduction of a bipolar electrode, suction irrigator, and grasping forceps, respectively.

I place the patient in the steep Trendelenburg's position, tilt her slightly to the left, and hold the sigmoid colon away from the presacral area.

After the Triangle of Cotte is identified, the peritoneum overlying the sacral promontory is elevated with a grasping forceps. I use grasping forceps to elevate the peritoneum overlying the promontory and make a small opening. I have used the CO₂ laser or scissors in the past. Currently, I use harmonic shears.

The suction irrigator is inserted through this opening, and the peritoneum is elevated. The peritoneum is incised horizontally and vertically, and the opening is extended cephalad to the aortic bifurcation. Any bleeding from the peritoneal vessels can be controlled with the bipolar electrocoagulator. If harmonic shears are used, this is rarely necessary.

After removing retroperitoneal lymphatic and fatty tissue, we reach the hypogastric plexus and can identify the presacral tissue.

The nerve plexus is grasped with an atraumatic forceps, and using blunt and sharp dissection, I skeletonize, desiccate, and excise the nerve fibers.

All the nerve fibers that lie within the boundaries of the interiliac triangle must be removed, including any fibers entering the area from under the common iliac artery and over the left common iliac vein.

I then irrigate the retroperitoneal space and coagulate bleeding points, if any. Sutures are not required to approximate the posterior peritoneum. The area heals completely on follow-up, and is covered by the peritoneum.

I send excised tissue for histologic examination to verify removal of nerve elements and ganglion.

The Outcomes

In 1992, we described a laparoscopic method of presacral neurectomy, based on Cotte's principles and technique, as part of a report on 52 patients with disabling midline dysmenorrhea and varying severity of endometriosis, all of whom had been unresponsive to medical treatment.

Of the 52 patients who were followed for more than a year, 48 (92%) reported relief of dysmenorrhea, and 27 (52%) reported complete pain relief (BJOG 1992:99;659–63).

In 1998, we reported even longer-term outcomes (up to 72 months) in 176 women with central pelvic pain who underwent laparoscopic presacral neurectomy and treatment of endometriosis. Pain was reduced substantially in 74% of the women, and just as notably, the degree of pain improvement was not directly related to the stage of endometriosis.

A reduction in pain of more than 50% was reported in 69.8% of women with stage I endometriosis (using the revised classification of the American Fertility Society), 77.3% of those with stage II, 71.4% of those with stage III, and 84.6% of those with stage IV endometriosis (Obstet. Gynecol. 1998;91:701–4).

We were discouraged from offering patients treatment in a blinded manner because a randomized trial conducted not long before this had been stopped in an early stage by a monitoring committee when the efficacy of presacral neurectomy became clear.

In this prematurely halted study, Dr. B. Tjaden, Dr. John A. Rock, and associates at Johns Hopkins University found that of 17 patients undergoing the procedure (all had moderate to severe dysmenorrhea and stage III-IV endometriosis), only two had recurrence of pain and the remainder remained pain free at 42 months of follow-up.

Of the nine patients who underwent resection of endometriosis but not presacral neurectomy, none had relief of midline pain (Obstet. Gynecol. 1990;76:89–91).

Although Dr. Rock and his team found that relief of dyspareunia was variable in both groups, we and others have had success in treating this manifestation of pelvic pain.

In our study published in 1998, a reduction in dyspareunia by more than 50% was seen in 32 of 60 patients followed for 24 months or longer.

More recently, Dr. F. Zullo and associates published the 2-year success of laparoscopic presacral neurectomy, reporting significant reduction in the frequency and severity not only of chronic pelvic pain and dysmenorrhea but of dyspareunia as well (J. Am. Assoc. Gynecol. Laparosc. 2004;11:23–8).

Laparoscopic uterosacral nerve ablation is an easier procedure to perform than laparoscopic presacral neurectomy, but it has been proved to provide only temporary relief and not the longer-term pain reduction that presacral neurectomy can achieve in most cases. I liken it to trimming a weed in your yard versus pulling the weed out by the roots.

The Complications

The most common and urgent intraoperative complication is bleeding, and we must be prepared, in the event of injury, to actively identify the anatomy and determine the feasibility of the repair laparoscopically, or to immediately convert to laparotomy.

We have not had any major complications, but the slight risk of vascular injury and the possible need to convert to laparotomy is something that patients should be informed of.

Long-term complications with presacral neurectomy are uncommon. Urinary urgency, poor bladder emptying, and constipation have been reported occasionally, as has vaginal dryness during sexual arousal.

We have not had any major complications such as vascular injury, gastrointestinal injury, or genitourinary injury in any of our presacral neurectomy procedures. Nor did any of these cases require conversion to laparotomy or transfusion.

Our initial (1992) study revealed no major intraoperative or immediate postoperative complications.

However, of the 52 women followed after 1 year, seven women reported either constipation (three patients), urinary urgency (one), vaginal dryness (one), or “painless labor” (two). These are all among the issues that we routinely cover in our patient counseling.

In conclusion, procedural failure, of course, is an important long-term complication, but the most common reasons for failure—poor patient selection and incomplete neurectomy because of neurologic variability or failure to remove all nerve tissue within the interiliac triangle—can, in most cases, be avoided with proper training and preparation.

Within the Triangle of Cotte, the common iliac artery is on the right; the common iliac vein is on the left. Courtesy Dr. Ceana Nezhat

The presacral tissue is identified, and the nerve plexus is grasped with an atraumatic forceps.

All the nerve fibers that lie within the boundaries of the interiliac triangle have been removed.

Presacral space on second look: The area heals completely on follow-up. Photos courtesy Dr. Ceana Nezhat

Presacral Neurectomy

In previous Master Class articles, we have explored the diagnosis and work-up of chronic pelvic pain (OB.GYN. NEWS, Feb. 1, 2007, p. 28; April 1, 2007, p. 25). Moreover, we presented an excellent technique in surgical extirpation of endometriosis (OB.GYN. NEWS, April 1, 2007, p. 38).

Despite a thorough evaluation and medical and surgical treatment, midline pelvic pain, dysmenorrhea, and/or dyspareunia may persist. Not only can this be caused by conditions such as primary dysmenorrhea or adenomyosis, but it may persist despite adequate surgical treatment of endometriosis and pelvic adhesions.

When midline pelvic pain, dysmenorrhea, and/or dyspareunia are not alleviated with treatment, ancillary surgical procedures should be considered. Unfortunately, the most commonly performed procedure—transection of the uterosacral nerves—has proved to be ineffective over time.

On the other hand, if performed by a skilled surgeon who understands the anatomy below the bifurcation of the aorta at the level of the sacral promontory, presacral neurectomy has proved quite effective long term.

I once performed this technique via laparotomy, but for nearly 20 years now I have used a purely laparoscopic technique. With the same indications, I have noted similar results to those explained here by Dr. Ceana Nezhat, the invited author of this Master Class article.

Dr. Ceana Nezhat is in private practice in Atlanta and is one of three brothers who are extraordinary gynecologic laparoscopic surgeons. Dr. Camran Nezhat, of Stanford (Calif.) University, has been an innovator in the laparoscopic treatment of endometriosis for a quarter of a century. Dr. Farr Nezhat, who is a gynecologist at Mount Sinai School of Medicine, New York, has been a leader in the use of laparoscopy to perform gynecologic oncology procedures. Dr. Ceana Nezhat is known not only for his laparoscopic treatment of endometriosis, but also for pelvic floor reconstruction. He is a prolific author and an international lecturer, and it is with great admiration that we bring you Dr. Ceana Nezhat, discussing the laparoscopic approach to presacral neurectomy.

Presacral neurectomy—the resection of the hypogastric nervous plexus that innervates the uterus—is a safe and effective alternative for these women.

It can be done alone or concomitantly with any surgical treatment of coexisting endometriosis or other pelvic pathology.

Presacral neurectomy is not a simple procedure, however, and should not be attempted without appropriate training and preparation, or without careful patient selection.

The procedure does not alleviate adnexal pain or pelvic pain that is more lateral, and is indicated when medical management has failed.

Nonetheless, when patients are carefully selected, and when the procedure is performed by a skilled surgeon who follows the principles and technique described more than 80 years ago by Dr. M.G. Cotte, it can be effectively carried out with good long-term outcomes for the majority of patients who have disabling midline dysmenorrhea and deep central, chronic pelvic pain.

More and more, the procedure is being done laparoscopically with a lower rate of postoperative morbidity. Indeed, advances in minimally invasive surgery have renewed interest in the procedure after a period starting in the 1960s in which the introduction of nonsteroidal anti-inflammatory drugs and various regimens of hormonal suppression caused interest to wane.

Moreover, despite the fact that the data on presacral neurectomy historically have covered women with dysmenorrhea, nonetheless within modern medicine dyspareunia has become an additional indication for the procedure.

Cotte's Technique

Dr. M. Jaboulay first described the severance of sacral sympathetic afferent fibers for serious dysmenorrhea (using a posterior extraperitoneal approach) in 1899, and a variety of other procedures for nerve interruption subsequently evolved.

It took until 1937, however, for a description of presacral neurectomy to emerge.

Dr. M.G. Cotte is credited with performing the first presacral neurectomy in 1924, and 13 years later he reported 98% success after transection of the superior hypogastric plexus in 1,500 patients.

Dr. Cotte emphasized that the only nerve tissue that should be resected is that within what he called the interiliac triangle (now known as the “Triangle of Cotte”), and that resection of all nerve elements in the triangle is essential in order to maximize effectiveness and minimize complications.

This triangle is extremely important. Unfortunately, because of the perilous location of the sensitive plexus, there have been modifications made in the procedure throughout the years.

Results have thus been variable, and some groups have reported recurrence rates of pelvic pain after presacral neurectomy that are significantly higher than the rates achieved by Cotte and the rates that we—and others—are now achieving.

It is difficult to analyze these results and ascertain exactly what the problems were and why the procedures failed.

However, because those surgeons who follow Cotte's principles and technique are indeed achieving good long-term results, I suspect that patient selection in the other studies wasn't optimal, or that the procedure was performed in a manner different from that originally described by Cotte.

The Anatomy

The presacral nerve is actually almost always a plexus of nerves known as the superior hypogastric plexus. It is a direct extension of the aortic plexus below the aortic bifurcation.

The plexus spreads out behind the peritoneum in the loose areolar tissue lying over the fourth and fifth lumbar vertebrae.

Between the vertebrae and the presacral nerve lies the middle sacral artery. On the right of the presacral nerve lie the right ureter and the common iliac vein and artery. On the left lie the sigmoid colon, inferior mesenteric vessels, left iliac vessels, and the left ureter.

Within the Triangle of Cotte, then, the common iliac artery and ureter are on the right, and the common iliac vein is on the left. The inferior mesenteric, superior hemorrhoidal, and midsacral arteries are in the center of the prelumbar space.

The triangle is defined caudally by the sacral promontory and laterally by the common iliac arteries. The superior edge of the triangle is delineated by the aortic bifurcation.

Centrally and to the left, the multiple nerve fibers representing the presacral nerve—sometimes in bundles—run caudally from the aortic plexus above and through the interiliac triangle to form the superior hypogastric plexus. These fibers are buried in loose areolar tissue. They display no particular patterns and vary among individuals.

In fact, surgeons must be prepared to encounter variable anatomical findings, in addition to being prepared for potential bleeding problems that can result from the sensitive proximity to the aortic bifurcation, vena cava, and iliac vessels.

The Procedure

In our Cotte-based procedure, an operating laparoscope is inserted through a 10-mm cannula placed through an umbilical incision.

Two or three suprapubic 5-mm cannulas are inserted at about 5-cm midsuprapubic and at 7 cm to the left and right side for the introduction of a bipolar electrode, suction irrigator, and grasping forceps, respectively.

I place the patient in the steep Trendelenburg's position, tilt her slightly to the left, and hold the sigmoid colon away from the presacral area.

After the Triangle of Cotte is identified, the peritoneum overlying the sacral promontory is elevated with a grasping forceps. I use grasping forceps to elevate the peritoneum overlying the promontory and make a small opening. I have used the CO₂ laser or scissors in the past. Currently, I use harmonic shears.

The suction irrigator is inserted through this opening, and the peritoneum is elevated. The peritoneum is incised horizontally and vertically, and the opening is extended cephalad to the aortic bifurcation. Any bleeding from the peritoneal vessels can be controlled with the bipolar electrocoagulator. If harmonic shears are used, this is rarely necessary.

After removing retroperitoneal lymphatic and fatty tissue, we reach the hypogastric plexus and can identify the presacral tissue.

The nerve plexus is grasped with an atraumatic forceps, and using blunt and sharp dissection, I skeletonize, desiccate, and excise the nerve fibers.

All the nerve fibers that lie within the boundaries of the interiliac triangle must be removed, including any fibers entering the area from under the common iliac artery and over the left common iliac vein.

I then irrigate the retroperitoneal space and coagulate bleeding points, if any. Sutures are not required to approximate the posterior peritoneum. The area heals completely on follow-up, and is covered by the peritoneum.

I send excised tissue for histologic examination to verify removal of nerve elements and ganglion.

The Outcomes

In 1992, we described a laparoscopic method of presacral neurectomy, based on Cotte's principles and technique, as part of a report on 52 patients with disabling midline dysmenorrhea and varying severity of endometriosis, all of whom had been unresponsive to medical treatment.

Of the 52 patients who were followed for more than a year, 48 (92%) reported relief of dysmenorrhea, and 27 (52%) reported complete pain relief (BJOG 1992:99;659–63).

In 1998, we reported even longer-term outcomes (up to 72 months) in 176 women with central pelvic pain who underwent laparoscopic presacral neurectomy and treatment of endometriosis. Pain was reduced substantially in 74% of the women, and just as notably, the degree of pain improvement was not directly related to the stage of endometriosis.

A reduction in pain of more than 50% was reported in 69.8% of women with stage I endometriosis (using the revised classification of the American Fertility Society), 77.3% of those with stage II, 71.4% of those with stage III, and 84.6% of those with stage IV endometriosis (Obstet. Gynecol. 1998;91:701–4).

We were discouraged from offering patients treatment in a blinded manner because a randomized trial conducted not long before this had been stopped in an early stage by a monitoring committee when the efficacy of presacral neurectomy became clear.

In this prematurely halted study, Dr. B. Tjaden, Dr. John A. Rock, and associates at Johns Hopkins University found that of 17 patients undergoing the procedure (all had moderate to severe dysmenorrhea and stage III-IV endometriosis), only two had recurrence of pain and the remainder remained pain free at 42 months of follow-up.

Of the nine patients who underwent resection of endometriosis but not presacral neurectomy, none had relief of midline pain (Obstet. Gynecol. 1990;76:89–91).

Although Dr. Rock and his team found that relief of dyspareunia was variable in both groups, we and others have had success in treating this manifestation of pelvic pain.

In our study published in 1998, a reduction in dyspareunia by more than 50% was seen in 32 of 60 patients followed for 24 months or longer.

More recently, Dr. F. Zullo and associates published the 2-year success of laparoscopic presacral neurectomy, reporting significant reduction in the frequency and severity not only of chronic pelvic pain and dysmenorrhea but of dyspareunia as well (J. Am. Assoc. Gynecol. Laparosc. 2004;11:23–8).

Laparoscopic uterosacral nerve ablation is an easier procedure to perform than laparoscopic presacral neurectomy, but it has been proved to provide only temporary relief and not the longer-term pain reduction that presacral neurectomy can achieve in most cases. I liken it to trimming a weed in your yard versus pulling the weed out by the roots.

The Complications

The most common and urgent intraoperative complication is bleeding, and we must be prepared, in the event of injury, to actively identify the anatomy and determine the feasibility of the repair laparoscopically, or to immediately convert to laparotomy.

We have not had any major complications, but the slight risk of vascular injury and the possible need to convert to laparotomy is something that patients should be informed of.

Long-term complications with presacral neurectomy are uncommon. Urinary urgency, poor bladder emptying, and constipation have been reported occasionally, as has vaginal dryness during sexual arousal.

We have not had any major complications such as vascular injury, gastrointestinal injury, or genitourinary injury in any of our presacral neurectomy procedures. Nor did any of these cases require conversion to laparotomy or transfusion.

Our initial (1992) study revealed no major intraoperative or immediate postoperative complications.

However, of the 52 women followed after 1 year, seven women reported either constipation (three patients), urinary urgency (one), vaginal dryness (one), or “painless labor” (two). These are all among the issues that we routinely cover in our patient counseling.

In conclusion, procedural failure, of course, is an important long-term complication, but the most common reasons for failure—poor patient selection and incomplete neurectomy because of neurologic variability or failure to remove all nerve tissue within the interiliac triangle—can, in most cases, be avoided with proper training and preparation.

Within the Triangle of Cotte, the common iliac artery is on the right; the common iliac vein is on the left. Courtesy Dr. Ceana Nezhat

The presacral tissue is identified, and the nerve plexus is grasped with an atraumatic forceps.

All the nerve fibers that lie within the boundaries of the interiliac triangle have been removed.

Presacral space on second look: The area heals completely on follow-up. Photos courtesy Dr. Ceana Nezhat

Presacral Neurectomy

In previous Master Class articles, we have explored the diagnosis and work-up of chronic pelvic pain (OB.GYN. NEWS, Feb. 1, 2007, p. 28; April 1, 2007, p. 25). Moreover, we presented an excellent technique in surgical extirpation of endometriosis (OB.GYN. NEWS, April 1, 2007, p. 38).

Despite a thorough evaluation and medical and surgical treatment, midline pelvic pain, dysmenorrhea, and/or dyspareunia may persist. Not only can this be caused by conditions such as primary dysmenorrhea or adenomyosis, but it may persist despite adequate surgical treatment of endometriosis and pelvic adhesions.

When midline pelvic pain, dysmenorrhea, and/or dyspareunia are not alleviated with treatment, ancillary surgical procedures should be considered. Unfortunately, the most commonly performed procedure—transection of the uterosacral nerves—has proved to be ineffective over time.

On the other hand, if performed by a skilled surgeon who understands the anatomy below the bifurcation of the aorta at the level of the sacral promontory, presacral neurectomy has proved quite effective long term.

I once performed this technique via laparotomy, but for nearly 20 years now I have used a purely laparoscopic technique. With the same indications, I have noted similar results to those explained here by Dr. Ceana Nezhat, the invited author of this Master Class article.

Dr. Ceana Nezhat is in private practice in Atlanta and is one of three brothers who are extraordinary gynecologic laparoscopic surgeons. Dr. Camran Nezhat, of Stanford (Calif.) University, has been an innovator in the laparoscopic treatment of endometriosis for a quarter of a century. Dr. Farr Nezhat, who is a gynecologist at Mount Sinai School of Medicine, New York, has been a leader in the use of laparoscopy to perform gynecologic oncology procedures. Dr. Ceana Nezhat is known not only for his laparoscopic treatment of endometriosis, but also for pelvic floor reconstruction. He is a prolific author and an international lecturer, and it is with great admiration that we bring you Dr. Ceana Nezhat, discussing the laparoscopic approach to presacral neurectomy.

BARCELONA — Complications occurred in nearly three-quarters of completed pregnancies in the largest-ever reported patient series involving women with congenital aortic stenosis, Dr. Sing-Chien Yap said at the joint congress of the European Society of Cardiology and the World Heart Federation.

Cardiac complications were common but for the most part nonsevere and readily manageable.

However, there were also high rates of general medical, obstetric, and neonatal complications. This underscores the merits of a team approach to management of pregnancy in adults with congenital aortic stenosis, with involvement of a cardiologist, neonatologist, and obstetrician, stressed Dr. Yap, a cardiologist at Erasmus University, Rotterdam, the Netherlands.

He reported on 48 women with congenital aortic stenosis who collectively had 70 completed pregnancies, defined as being of more than 20 weeks' duration. The women were part of the larger ZAHARA study, a Dutch nationwide retrospective study investigating pregnancy outcomes in women with all forms of congenital heart disease.

ZAHARA was undertaken with funding from the Netherlands Heart Foundation because treatment advances have resulted in far more women with congenital heart disease surviving into their childbearing years than was historically the case. Few data exist on the risk factors for and nature and frequency of pregnancy complications in these women, Dr. Yap explained.

Thirty-five of the women had valvular aortic stenosis, 11 had subvalvular disease, and the remainder had supravalvular aortic stenosis. Prepregnancy, 9 had severe aortic stenosis as defined by a valvular gradient in excess of 64 mm Hg, 17 had moderate aortic stenosis with a gradient of 36-44 mm Hg, and the rest had mild aortic stenosis. Mean gradients were unchanged after pregnancy.

The most common cardiac complication of pregnancy was deterioration in New York Heart Association functional class. It occurred during 19 of 70 pregnancies and persisted for longer than 1 year postpartum in 3. Heart failure occurred in two patients, both with severe aortic stenosis. Angina occurred in two patients. Four patients developed arrhythmias, mainly supraventricular arrhythmias treated with ?-blockers.

Seventeen women required hospitalization for general pregnancy disorders, most of which were hypertension related. There were six cases of isolated pregnancy-induced hypertension, three of preeclampsia, and one of eclampsia. Three women were hospitalized for dyspnea. One woman experienced a transient ischemic attack despite being on warfarin for atrial fibrillation.

Eight women had elective cesarean deliveries, and 11 had emergency cesarean sections. There were three cases of placental abruption and two of postpartum hemorrhage.

Mean pregnancy duration was 38.2 weeks. Eleven babies were born small for gestational age. There were 10 preterm deliveries. One neonate died as a consequence of prematurity. Two children were born with congenital heart disease.

Most of these complications occurred at significantly higher rates than in the general Dutch pregnant population. Complication rates were highest in women with severe aortic stenosis.

Because of the limitations inherent in a retrospective study, the investigators have launched a prospective nationwide study of pregnancy in congenital heart disease, according to Dr. Yap.

BARCELONA — Complications occurred in nearly three-quarters of completed pregnancies in the largest-ever reported patient series involving women with congenital aortic stenosis, Dr. Sing-Chien Yap said at the joint congress of the European Society of Cardiology and the World Heart Federation.

Cardiac complications were common but for the most part nonsevere and readily manageable.

However, there were also high rates of general medical, obstetric, and neonatal complications. This underscores the merits of a team approach to management of pregnancy in adults with congenital aortic stenosis, with involvement of a cardiologist, neonatologist, and obstetrician, stressed Dr. Yap, a cardiologist at Erasmus University, Rotterdam, the Netherlands.

He reported on 48 women with congenital aortic stenosis who collectively had 70 completed pregnancies, defined as being of more than 20 weeks' duration. The women were part of the larger ZAHARA study, a Dutch nationwide retrospective study investigating pregnancy outcomes in women with all forms of congenital heart disease.

ZAHARA was undertaken with funding from the Netherlands Heart Foundation because treatment advances have resulted in far more women with congenital heart disease surviving into their childbearing years than was historically the case. Few data exist on the risk factors for and nature and frequency of pregnancy complications in these women, Dr. Yap explained.

Thirty-five of the women had valvular aortic stenosis, 11 had subvalvular disease, and the remainder had supravalvular aortic stenosis. Prepregnancy, 9 had severe aortic stenosis as defined by a valvular gradient in excess of 64 mm Hg, 17 had moderate aortic stenosis with a gradient of 36-44 mm Hg, and the rest had mild aortic stenosis. Mean gradients were unchanged after pregnancy.

The most common cardiac complication of pregnancy was deterioration in New York Heart Association functional class. It occurred during 19 of 70 pregnancies and persisted for longer than 1 year postpartum in 3. Heart failure occurred in two patients, both with severe aortic stenosis. Angina occurred in two patients. Four patients developed arrhythmias, mainly supraventricular arrhythmias treated with ?-blockers.

Seventeen women required hospitalization for general pregnancy disorders, most of which were hypertension related. There were six cases of isolated pregnancy-induced hypertension, three of preeclampsia, and one of eclampsia. Three women were hospitalized for dyspnea. One woman experienced a transient ischemic attack despite being on warfarin for atrial fibrillation.

Eight women had elective cesarean deliveries, and 11 had emergency cesarean sections. There were three cases of placental abruption and two of postpartum hemorrhage.

Mean pregnancy duration was 38.2 weeks. Eleven babies were born small for gestational age. There were 10 preterm deliveries. One neonate died as a consequence of prematurity. Two children were born with congenital heart disease.

Most of these complications occurred at significantly higher rates than in the general Dutch pregnant population. Complication rates were highest in women with severe aortic stenosis.

Because of the limitations inherent in a retrospective study, the investigators have launched a prospective nationwide study of pregnancy in congenital heart disease, according to Dr. Yap.

BARCELONA — Complications occurred in nearly three-quarters of completed pregnancies in the largest-ever reported patient series involving women with congenital aortic stenosis, Dr. Sing-Chien Yap said at the joint congress of the European Society of Cardiology and the World Heart Federation.

Cardiac complications were common but for the most part nonsevere and readily manageable.

However, there were also high rates of general medical, obstetric, and neonatal complications. This underscores the merits of a team approach to management of pregnancy in adults with congenital aortic stenosis, with involvement of a cardiologist, neonatologist, and obstetrician, stressed Dr. Yap, a cardiologist at Erasmus University, Rotterdam, the Netherlands.

He reported on 48 women with congenital aortic stenosis who collectively had 70 completed pregnancies, defined as being of more than 20 weeks' duration. The women were part of the larger ZAHARA study, a Dutch nationwide retrospective study investigating pregnancy outcomes in women with all forms of congenital heart disease.

ZAHARA was undertaken with funding from the Netherlands Heart Foundation because treatment advances have resulted in far more women with congenital heart disease surviving into their childbearing years than was historically the case. Few data exist on the risk factors for and nature and frequency of pregnancy complications in these women, Dr. Yap explained.

Thirty-five of the women had valvular aortic stenosis, 11 had subvalvular disease, and the remainder had supravalvular aortic stenosis. Prepregnancy, 9 had severe aortic stenosis as defined by a valvular gradient in excess of 64 mm Hg, 17 had moderate aortic stenosis with a gradient of 36-44 mm Hg, and the rest had mild aortic stenosis. Mean gradients were unchanged after pregnancy.

The most common cardiac complication of pregnancy was deterioration in New York Heart Association functional class. It occurred during 19 of 70 pregnancies and persisted for longer than 1 year postpartum in 3. Heart failure occurred in two patients, both with severe aortic stenosis. Angina occurred in two patients. Four patients developed arrhythmias, mainly supraventricular arrhythmias treated with ?-blockers.

Seventeen women required hospitalization for general pregnancy disorders, most of which were hypertension related. There were six cases of isolated pregnancy-induced hypertension, three of preeclampsia, and one of eclampsia. Three women were hospitalized for dyspnea. One woman experienced a transient ischemic attack despite being on warfarin for atrial fibrillation.

Eight women had elective cesarean deliveries, and 11 had emergency cesarean sections. There were three cases of placental abruption and two of postpartum hemorrhage.

Mean pregnancy duration was 38.2 weeks. Eleven babies were born small for gestational age. There were 10 preterm deliveries. One neonate died as a consequence of prematurity. Two children were born with congenital heart disease.

Most of these complications occurred at significantly higher rates than in the general Dutch pregnant population. Complication rates were highest in women with severe aortic stenosis.

Because of the limitations inherent in a retrospective study, the investigators have launched a prospective nationwide study of pregnancy in congenital heart disease, according to Dr. Yap.

Patients are bearing children at older ages and are more active than the obstetric populations of generations ago. They are in the workplace, out on the roads, and exposed to common causes of trauma, such as motor vehicle accidents and falls.

It is helpful to know the numbers and be aware of the significance of the problem. Trauma in pregnancy is significantly more frequent, for instance, than the genetic problems we encounter and screen for in our practices.

As ob.gyns., we are bound to be called to treat trauma in pregnancy at some point, and it is important that we be prepared to optimally manage the seriously injured pregnant woman as either a primary manager or as an advisor or consultant, whatever the situation and phase of evaluation and treatment demand.

The Causes

The vast majority of women who experience trauma (95%–96%) suffer injuries from blunt, rather than penetrating, types of trauma. Most of these injuries, in turn, are a result of motor vehicle accidents.

Motor vehicle accidents are the leading cause of death in women aged 12-51 years and the leading cause of trauma in women of childbearing age, accounting for well over half of the major injuries experienced by pregnant women.

Falls are the second most common cause of blunt trauma.

Although relatively infrequent, penetrating trauma—often caused by gunshot wounds—is still a reality. Penetrating trauma leads to significant injury to the fetus more often than to the mother, because the mother's abdominal organs are shielded by the gravid uterus.

As ob.gyns., we can help our patients decrease injury in motor vehicle accidents by urging them to use seat belts. When worn correctly—with the lap belt fitting under the belly and close to the hips, and the shoulder belt resting between the breasts and over the shoulder—seat belts with shoulder restraints can definitively reduce the risk of death and injury for both the mother and fetus.

It is also important to remember that domestic or interpersonal violence may be more frequent during pregnancy than at other times. Such abuse is a less evident cause of blunt trauma, but a very real one. The incidence of interpersonal violence can be as high as 14%–20% in pregnant teenagers, and probably averages about 10%–11% in pregnant women overall.

When taking care of women who report injuries from falls and other events that do not correlate with the overall history or physical exam, we must—in a private and safe environment—address the possibility of partner abuse. We should also remind ourselves that women who are physically abused have a higher incidence of infection, low maternal weight gain, maternal alcohol and drug abuse, and low-birth-weight babies.

Physiologic Changes

Ob.gyns. will sometimes serve as consultants or advisors in managing trauma during pregnancy, and at other times will serve as primary managers. In any case, optimal evaluation and management require both teamwork (an integrated effort of multiple specialties) and a central role for the ob.gyn., whose understanding of the physiologic changes of pregnancy is vital to management decisions.

Key changes that occur secondary to pregnancy most often alter the patient's cardiovascular, hematologic, respiratory, urinary, gastrointestinal, and endocrine systems.

Cardiac output increases during pregnancy by 1-1.5 L/min, with a dramatic increase in the percentage of cardiac output that goes to the uterus. By week 36, the uterus receives up to 600 mL/min of blood—which represents about a tenth of the mother's cardiac output—compared with 60 mL/min in the nonpregnant state. Consequently, trauma to the uterus can result in significant hemorrhage and shock.

Blood volume increases by 45%–50% during pregnancy, and can be instrumental in concealing signs of shock from hypovolemia. Along with this, however, the amount of all clotting factors also increases, which predisposes the pregnant patient to embolic risks as well as coagulopathy from disseminated intravascular coagulation (DIC).

The respiratory system adapts for its role of oxygen delivery to the fetus. Tidal volume increases, with an overall increase in minute ventilation. Changes that result from this adaptation are a lowering of the maternal CO2 level and a decrease in alveolar residual volume. This can further result in a respiratory alkalotic state, which is corrected with a renal decrease in bicarbonate (a compensated respiratory alkalosis). The decreased residual volumes render the pregnant patient more susceptible to alveolar collapse and respiratory compromise.

Under these circumstances, it may be prudent to consider early intubation of the pregnant patient with respiratory compromise in order to preserve the exchange of gases across the fetoplacental unit.

Renal blood flow is increased in pregnancy, with a concomitant increase in creatinine clearance and a tendency to more rapidly clear drugs that are renal dependent.

Standard lab values must be seen in the context of the changes in maternal physiology. For example, blood gas values in pregnancy may reveal lower CO2 values, and hematocrits may be lower secondary to the hemodilution seen in blood volume expansion.

During evaluation or resuscitation, it is important for ob.gyns. to remind the team of the mass of the gravid uterus and its ability—when the woman is in the supine position—to compromise the return of blood flow to the heart by compressing the vena cava.

Beyond the second trimester, the patient should be tilted to the left by approximately 35 degrees, and when a full-body tilt is not possible, left lateral displacement of the uterus must be maintained. When spinal injury is suspected, care must be taken to keep the spine and neck aligned during tilting.

Questions About Imaging

The obstetrician often will be asked whether the imaging needed to diagnose various injuries is safe for the fetus. Doses of radiation used during trauma care and evaluation—for example, CT scans of the pelvis or chest, and chest x-rays—are usually in the range of less than 250 mGy, which is considered to be the intermediate range of exposure and reasonably safe for the fetus.

Whenever possible, the pelvis of a pregnant woman should be shielded, especially in the first trimester. It is important to know, however, that much of today's imaging equipment is faster than previous technology and therefore delivers much lower radiation exposure with more information in a single pass. Additionally, MRI has been shown to be a safe modality in pregnancy.

The bottom line is that imaging studies that are needed for the care of the critically injured patient should not be withheld because she may be pregnant.

Primary Assessment

On initial presentation, all efforts for the pregnant trauma patient must first be directed toward stabilizing the mother and maintaining oxygen delivery, with the ABCs (airway, breathing, and circulation) of trauma care being the first priority.

Women who are pregnant have a reduced ability to compensate for respiratory compromise. Maintaining a patent airway is critical for both maternal and fetal oxygenation, and this very well may require early intubation. We must make sure that the patient is moving oxygen in, with oxygen saturation levels better than 90%.

The fetus's oxygen uptake depends directly on oxygen delivery via uterine blood flow, so circulation—both to the mother's vital organs and to the uterus—is also key. Because of shunting and vasospasm, significant uterine blood flow compromise may exist even with normal-appearing blood pressure. Thus, it is important to control any significant bleeding and pursue vigorous volume replacement.

Only after the ABCs are addressed—and readdressed for effectiveness—can we turn our attention elsewhere. If we were to add a “D” to the trauma protocol, it would stand for “disability” and would involve a rapid neurologic evaluation to assess for any neurologic injury. It is worth considering that neurologic impairment in late pregnancy may be secondary to an eclamptic seizure that may have led to the trauma event.

Other often critical components of trauma injuries, such as fractures and intraperitoneal hemorrhage, are usually evaluated almost simultaneously by the trauma team.

Patients with pelvic fractures (common in motor vehicle accidents) are at risk of having retroperitoneal hemorrhage, which is not always obvious and requires careful diagnosis. A pelvic exam can reveal signs of lower pelvic fracture and possible vaginal lacerations from protruding bone fragments.

The Secondary Survey

Once we have stabilized the mother and evaluated her for other critical signs of trauma, we can turn our attention to fetal assessment. First, we should assess gestational age, either by taking a history if someone close to the mother is present, or through ultrasonography.

Ultrasonography is an important tool at this point for assessing several factors in short order. In addition to assessing the viability of the fetus, we can evaluate the intrauterine fluid volume and the placental location. (The question of viability, of course, depends on the level of neonatal intensive care services available).

A low amount of amniotic fluid should lead us to suspect rupture of the amniotic membranes or, in some cases, uterine rupture secondary to trauma. Although with expert hands it is possible to detect relatively small placental abruptions, abruptions are usually apparent only with larger separations.

Ultrasonography can also be used in determining intra-abdominal free fluid which is consistent with intraperitoneal hemorrhage.

When the woman is severely injured and needs surgery and if delivery of the fetus is unnecessary, we should focus on monitoring the fetus in the operating room. We can do so with an ultrasound probe or a fetal Doppler encased in a sterile sleeve.

After surgery—or when the woman does not need surgery and is considered stable enough to undergo observation—continuous monitoring of the viable fetus, with a longer-term view, should be done using external monitoring of fetal heart rate and uterine monitoring for signs of preterm labor. Frequent uterine contractions should be followed closely, and cervical dilatation should be evaluated.

The ob.gyn. becomes the primary provider when a viable fetus shows signs of fetal compromise that necessitate delivery, or when uterine rupture occurs, in which case urgent intervention is necessary for the mother.

Many studies have attempted to address the question of how long trauma patients should be monitored, and many guidelines have been proposed. In general, we can conclude that 12 hours of observation is adequate for stable patients who are not contracting and have reassuring fetal tracings and no signs of bleeding.

On the other hand, patients who are contracting, who have a nonreassuring fetal tracing, or who have had any form of vaginal bleeding should be observed for a minimum of 24 hours. The more severe the injury to the mother, the more likely there is to be an injury to the fetus, and the higher the risk that a placental abruption or other serious complication may surface.

If a patient is discharged after observation, regardless of the severity of trauma, she must be given precautions regarding any changes in fetal movement or the development of abdominal pain, vaginal bleeding, or fluid loss. Any one of these changes should prompt her to return for evaluation immediately.

The Kleihauer-Betke test may be useful in evaluating the degree of fetal-maternal hemorrhage and the amount of Rh immune globulin that may be needed in the Rh-negative mother. In general, Rh-negative mothers who are involved in trauma should be given a single dose of Rh immune globulin unless it is known that the fetus is Rh negative.

Cardiac arrest is sometimes the tragic outcome for a posttrauma victim. Maternal resuscitation should be undertaken immediately. If maternal resuscitation is not thought likely to be effective, and the fetus is considered viable, the best outcome for fetal survival occurs if delivery can be accomplished within approximately 5 minutes from arrest. Beyond this time, there is diminishing return for fetal survival.

Organized, rapid assessment and intervention hold the key to the best outcomes for the pregnant patient involved in a trauma. Following the rules of trauma resuscitation (those ABCs) provides the best chance of successful treatment of the mother, which in turn provides the best chance of a favorable fetal outcome.

Motor vehicle accidents are the leading cause of trauma and death in women of childbearing age. Courtesy Dr. Hugh Mighty

One situation in which the ob.gyn. becomes the primary provider is when delivery is necessary. Courtesy Dr. Hugh Mighty

Trauma in Pregnancy

High-risk obstetrics by its very nature involves a wide spectrum of diseases and events that complicate pregnancies and preclude or prevent their normal progression. Sometimes, high-risk obstetrics involves physical trauma that is inflicted externally upon an otherwise normal pregnancy.

Physical trauma is, in fact, one of the leading causes of morbidity and mortality during pregnancy. It has been estimated that physical trauma complicates approximately 1 in every 12 pregnancies—a staggering figure and one that we may not fully appreciate or think about often enough.

According to the American College of Obstetricians and Gynecologists, approximately two-thirds of all trauma during pregnancy in industrialized nations results from motor vehicle crashes.

Women not only are more likely to be involved in automobile accidents than are male drivers; they also are increasingly more likely to be victims of violence. In 1994, women were about six times more likely than men to be victims of violence—a significant increase from more than a decade before, when women were half as likely as men to be victims of violence.

Trauma in pregnant women has to be dealt with by a variety of specialists. Very often, these patients will present to emergency departments or urgent care centers, and will have to be seen by emergency physicians, surgeons, or general practitioners. This is a challenging situation and one that presents unusual challenges for obstetric staff.

Especially as the number of patients with traumatic injuries and complications increases, it is important that we review some of the key types of presentations and complications of trauma in pregnancy, and discuss how we may best develop therapeutic algorithms for dealing with them.

It is in this light that we have invited Dr. Hugh E. Mighty, chairman of the department of obstetrics, gynecology, and reproductive sciences at the University of Maryland, Baltimore, to discuss the management of seriously injured pregnant women.

Dr. Mighty is not only a maternal-fetal medicine specialist, but is certified in critical care medicine as well. We are pleased to welcome him as an expert on trauma in pregnancy and as this month's guest professor on the subject.

Patients are bearing children at older ages and are more active than the obstetric populations of generations ago. They are in the workplace, out on the roads, and exposed to common causes of trauma, such as motor vehicle accidents and falls.

It is helpful to know the numbers and be aware of the significance of the problem. Trauma in pregnancy is significantly more frequent, for instance, than the genetic problems we encounter and screen for in our practices.

As ob.gyns., we are bound to be called to treat trauma in pregnancy at some point, and it is important that we be prepared to optimally manage the seriously injured pregnant woman as either a primary manager or as an advisor or consultant, whatever the situation and phase of evaluation and treatment demand.

The Causes

The vast majority of women who experience trauma (95%–96%) suffer injuries from blunt, rather than penetrating, types of trauma. Most of these injuries, in turn, are a result of motor vehicle accidents.

Motor vehicle accidents are the leading cause of death in women aged 12-51 years and the leading cause of trauma in women of childbearing age, accounting for well over half of the major injuries experienced by pregnant women.

Falls are the second most common cause of blunt trauma.

Although relatively infrequent, penetrating trauma—often caused by gunshot wounds—is still a reality. Penetrating trauma leads to significant injury to the fetus more often than to the mother, because the mother's abdominal organs are shielded by the gravid uterus.

As ob.gyns., we can help our patients decrease injury in motor vehicle accidents by urging them to use seat belts. When worn correctly—with the lap belt fitting under the belly and close to the hips, and the shoulder belt resting between the breasts and over the shoulder—seat belts with shoulder restraints can definitively reduce the risk of death and injury for both the mother and fetus.

It is also important to remember that domestic or interpersonal violence may be more frequent during pregnancy than at other times. Such abuse is a less evident cause of blunt trauma, but a very real one. The incidence of interpersonal violence can be as high as 14%–20% in pregnant teenagers, and probably averages about 10%–11% in pregnant women overall.

When taking care of women who report injuries from falls and other events that do not correlate with the overall history or physical exam, we must—in a private and safe environment—address the possibility of partner abuse. We should also remind ourselves that women who are physically abused have a higher incidence of infection, low maternal weight gain, maternal alcohol and drug abuse, and low-birth-weight babies.

Physiologic Changes

Ob.gyns. will sometimes serve as consultants or advisors in managing trauma during pregnancy, and at other times will serve as primary managers. In any case, optimal evaluation and management require both teamwork (an integrated effort of multiple specialties) and a central role for the ob.gyn., whose understanding of the physiologic changes of pregnancy is vital to management decisions.

Key changes that occur secondary to pregnancy most often alter the patient's cardiovascular, hematologic, respiratory, urinary, gastrointestinal, and endocrine systems.

Cardiac output increases during pregnancy by 1-1.5 L/min, with a dramatic increase in the percentage of cardiac output that goes to the uterus. By week 36, the uterus receives up to 600 mL/min of blood—which represents about a tenth of the mother's cardiac output—compared with 60 mL/min in the nonpregnant state. Consequently, trauma to the uterus can result in significant hemorrhage and shock.

Blood volume increases by 45%–50% during pregnancy, and can be instrumental in concealing signs of shock from hypovolemia. Along with this, however, the amount of all clotting factors also increases, which predisposes the pregnant patient to embolic risks as well as coagulopathy from disseminated intravascular coagulation (DIC).

The respiratory system adapts for its role of oxygen delivery to the fetus. Tidal volume increases, with an overall increase in minute ventilation. Changes that result from this adaptation are a lowering of the maternal CO2 level and a decrease in alveolar residual volume. This can further result in a respiratory alkalotic state, which is corrected with a renal decrease in bicarbonate (a compensated respiratory alkalosis). The decreased residual volumes render the pregnant patient more susceptible to alveolar collapse and respiratory compromise.

Under these circumstances, it may be prudent to consider early intubation of the pregnant patient with respiratory compromise in order to preserve the exchange of gases across the fetoplacental unit.

Renal blood flow is increased in pregnancy, with a concomitant increase in creatinine clearance and a tendency to more rapidly clear drugs that are renal dependent.

Standard lab values must be seen in the context of the changes in maternal physiology. For example, blood gas values in pregnancy may reveal lower CO2 values, and hematocrits may be lower secondary to the hemodilution seen in blood volume expansion.

During evaluation or resuscitation, it is important for ob.gyns. to remind the team of the mass of the gravid uterus and its ability—when the woman is in the supine position—to compromise the return of blood flow to the heart by compressing the vena cava.

Beyond the second trimester, the patient should be tilted to the left by approximately 35 degrees, and when a full-body tilt is not possible, left lateral displacement of the uterus must be maintained. When spinal injury is suspected, care must be taken to keep the spine and neck aligned during tilting.

Questions About Imaging

The obstetrician often will be asked whether the imaging needed to diagnose various injuries is safe for the fetus. Doses of radiation used during trauma care and evaluation—for example, CT scans of the pelvis or chest, and chest x-rays—are usually in the range of less than 250 mGy, which is considered to be the intermediate range of exposure and reasonably safe for the fetus.

Whenever possible, the pelvis of a pregnant woman should be shielded, especially in the first trimester. It is important to know, however, that much of today's imaging equipment is faster than previous technology and therefore delivers much lower radiation exposure with more information in a single pass. Additionally, MRI has been shown to be a safe modality in pregnancy.

The bottom line is that imaging studies that are needed for the care of the critically injured patient should not be withheld because she may be pregnant.

Primary Assessment

On initial presentation, all efforts for the pregnant trauma patient must first be directed toward stabilizing the mother and maintaining oxygen delivery, with the ABCs (airway, breathing, and circulation) of trauma care being the first priority.

Women who are pregnant have a reduced ability to compensate for respiratory compromise. Maintaining a patent airway is critical for both maternal and fetal oxygenation, and this very well may require early intubation. We must make sure that the patient is moving oxygen in, with oxygen saturation levels better than 90%.

The fetus's oxygen uptake depends directly on oxygen delivery via uterine blood flow, so circulation—both to the mother's vital organs and to the uterus—is also key. Because of shunting and vasospasm, significant uterine blood flow compromise may exist even with normal-appearing blood pressure. Thus, it is important to control any significant bleeding and pursue vigorous volume replacement.

Only after the ABCs are addressed—and readdressed for effectiveness—can we turn our attention elsewhere. If we were to add a “D” to the trauma protocol, it would stand for “disability” and would involve a rapid neurologic evaluation to assess for any neurologic injury. It is worth considering that neurologic impairment in late pregnancy may be secondary to an eclamptic seizure that may have led to the trauma event.

Other often critical components of trauma injuries, such as fractures and intraperitoneal hemorrhage, are usually evaluated almost simultaneously by the trauma team.

Patients with pelvic fractures (common in motor vehicle accidents) are at risk of having retroperitoneal hemorrhage, which is not always obvious and requires careful diagnosis. A pelvic exam can reveal signs of lower pelvic fracture and possible vaginal lacerations from protruding bone fragments.

The Secondary Survey

Once we have stabilized the mother and evaluated her for other critical signs of trauma, we can turn our attention to fetal assessment. First, we should assess gestational age, either by taking a history if someone close to the mother is present, or through ultrasonography.

Ultrasonography is an important tool at this point for assessing several factors in short order. In addition to assessing the viability of the fetus, we can evaluate the intrauterine fluid volume and the placental location. (The question of viability, of course, depends on the level of neonatal intensive care services available).

A low amount of amniotic fluid should lead us to suspect rupture of the amniotic membranes or, in some cases, uterine rupture secondary to trauma. Although with expert hands it is possible to detect relatively small placental abruptions, abruptions are usually apparent only with larger separations.

Ultrasonography can also be used in determining intra-abdominal free fluid which is consistent with intraperitoneal hemorrhage.

When the woman is severely injured and needs surgery and if delivery of the fetus is unnecessary, we should focus on monitoring the fetus in the operating room. We can do so with an ultrasound probe or a fetal Doppler encased in a sterile sleeve.

After surgery—or when the woman does not need surgery and is considered stable enough to undergo observation—continuous monitoring of the viable fetus, with a longer-term view, should be done using external monitoring of fetal heart rate and uterine monitoring for signs of preterm labor. Frequent uterine contractions should be followed closely, and cervical dilatation should be evaluated.

The ob.gyn. becomes the primary provider when a viable fetus shows signs of fetal compromise that necessitate delivery, or when uterine rupture occurs, in which case urgent intervention is necessary for the mother.

Many studies have attempted to address the question of how long trauma patients should be monitored, and many guidelines have been proposed. In general, we can conclude that 12 hours of observation is adequate for stable patients who are not contracting and have reassuring fetal tracings and no signs of bleeding.

On the other hand, patients who are contracting, who have a nonreassuring fetal tracing, or who have had any form of vaginal bleeding should be observed for a minimum of 24 hours. The more severe the injury to the mother, the more likely there is to be an injury to the fetus, and the higher the risk that a placental abruption or other serious complication may surface.

If a patient is discharged after observation, regardless of the severity of trauma, she must be given precautions regarding any changes in fetal movement or the development of abdominal pain, vaginal bleeding, or fluid loss. Any one of these changes should prompt her to return for evaluation immediately.

The Kleihauer-Betke test may be useful in evaluating the degree of fetal-maternal hemorrhage and the amount of Rh immune globulin that may be needed in the Rh-negative mother. In general, Rh-negative mothers who are involved in trauma should be given a single dose of Rh immune globulin unless it is known that the fetus is Rh negative.

Cardiac arrest is sometimes the tragic outcome for a posttrauma victim. Maternal resuscitation should be undertaken immediately. If maternal resuscitation is not thought likely to be effective, and the fetus is considered viable, the best outcome for fetal survival occurs if delivery can be accomplished within approximately 5 minutes from arrest. Beyond this time, there is diminishing return for fetal survival.

Organized, rapid assessment and intervention hold the key to the best outcomes for the pregnant patient involved in a trauma. Following the rules of trauma resuscitation (those ABCs) provides the best chance of successful treatment of the mother, which in turn provides the best chance of a favorable fetal outcome.

Motor vehicle accidents are the leading cause of trauma and death in women of childbearing age. Courtesy Dr. Hugh Mighty

One situation in which the ob.gyn. becomes the primary provider is when delivery is necessary. Courtesy Dr. Hugh Mighty

Trauma in Pregnancy

High-risk obstetrics by its very nature involves a wide spectrum of diseases and events that complicate pregnancies and preclude or prevent their normal progression. Sometimes, high-risk obstetrics involves physical trauma that is inflicted externally upon an otherwise normal pregnancy.

Physical trauma is, in fact, one of the leading causes of morbidity and mortality during pregnancy. It has been estimated that physical trauma complicates approximately 1 in every 12 pregnancies—a staggering figure and one that we may not fully appreciate or think about often enough.

According to the American College of Obstetricians and Gynecologists, approximately two-thirds of all trauma during pregnancy in industrialized nations results from motor vehicle crashes.

Women not only are more likely to be involved in automobile accidents than are male drivers; they also are increasingly more likely to be victims of violence. In 1994, women were about six times more likely than men to be victims of violence—a significant increase from more than a decade before, when women were half as likely as men to be victims of violence.

Trauma in pregnant women has to be dealt with by a variety of specialists. Very often, these patients will present to emergency departments or urgent care centers, and will have to be seen by emergency physicians, surgeons, or general practitioners. This is a challenging situation and one that presents unusual challenges for obstetric staff.

Especially as the number of patients with traumatic injuries and complications increases, it is important that we review some of the key types of presentations and complications of trauma in pregnancy, and discuss how we may best develop therapeutic algorithms for dealing with them.

It is in this light that we have invited Dr. Hugh E. Mighty, chairman of the department of obstetrics, gynecology, and reproductive sciences at the University of Maryland, Baltimore, to discuss the management of seriously injured pregnant women.

Dr. Mighty is not only a maternal-fetal medicine specialist, but is certified in critical care medicine as well. We are pleased to welcome him as an expert on trauma in pregnancy and as this month's guest professor on the subject.

Patients are bearing children at older ages and are more active than the obstetric populations of generations ago. They are in the workplace, out on the roads, and exposed to common causes of trauma, such as motor vehicle accidents and falls.

It is helpful to know the numbers and be aware of the significance of the problem. Trauma in pregnancy is significantly more frequent, for instance, than the genetic problems we encounter and screen for in our practices.

As ob.gyns., we are bound to be called to treat trauma in pregnancy at some point, and it is important that we be prepared to optimally manage the seriously injured pregnant woman as either a primary manager or as an advisor or consultant, whatever the situation and phase of evaluation and treatment demand.

The Causes

The vast majority of women who experience trauma (95%–96%) suffer injuries from blunt, rather than penetrating, types of trauma. Most of these injuries, in turn, are a result of motor vehicle accidents.

Motor vehicle accidents are the leading cause of death in women aged 12-51 years and the leading cause of trauma in women of childbearing age, accounting for well over half of the major injuries experienced by pregnant women.

Falls are the second most common cause of blunt trauma.

Although relatively infrequent, penetrating trauma—often caused by gunshot wounds—is still a reality. Penetrating trauma leads to significant injury to the fetus more often than to the mother, because the mother's abdominal organs are shielded by the gravid uterus.

As ob.gyns., we can help our patients decrease injury in motor vehicle accidents by urging them to use seat belts. When worn correctly—with the lap belt fitting under the belly and close to the hips, and the shoulder belt resting between the breasts and over the shoulder—seat belts with shoulder restraints can definitively reduce the risk of death and injury for both the mother and fetus.

It is also important to remember that domestic or interpersonal violence may be more frequent during pregnancy than at other times. Such abuse is a less evident cause of blunt trauma, but a very real one. The incidence of interpersonal violence can be as high as 14%–20% in pregnant teenagers, and probably averages about 10%–11% in pregnant women overall.

When taking care of women who report injuries from falls and other events that do not correlate with the overall history or physical exam, we must—in a private and safe environment—address the possibility of partner abuse. We should also remind ourselves that women who are physically abused have a higher incidence of infection, low maternal weight gain, maternal alcohol and drug abuse, and low-birth-weight babies.

Physiologic Changes

Ob.gyns. will sometimes serve as consultants or advisors in managing trauma during pregnancy, and at other times will serve as primary managers. In any case, optimal evaluation and management require both teamwork (an integrated effort of multiple specialties) and a central role for the ob.gyn., whose understanding of the physiologic changes of pregnancy is vital to management decisions.

Key changes that occur secondary to pregnancy most often alter the patient's cardiovascular, hematologic, respiratory, urinary, gastrointestinal, and endocrine systems.

Cardiac output increases during pregnancy by 1-1.5 L/min, with a dramatic increase in the percentage of cardiac output that goes to the uterus. By week 36, the uterus receives up to 600 mL/min of blood—which represents about a tenth of the mother's cardiac output—compared with 60 mL/min in the nonpregnant state. Consequently, trauma to the uterus can result in significant hemorrhage and shock.

Blood volume increases by 45%–50% during pregnancy, and can be instrumental in concealing signs of shock from hypovolemia. Along with this, however, the amount of all clotting factors also increases, which predisposes the pregnant patient to embolic risks as well as coagulopathy from disseminated intravascular coagulation (DIC).

The respiratory system adapts for its role of oxygen delivery to the fetus. Tidal volume increases, with an overall increase in minute ventilation. Changes that result from this adaptation are a lowering of the maternal CO2 level and a decrease in alveolar residual volume. This can further result in a respiratory alkalotic state, which is corrected with a renal decrease in bicarbonate (a compensated respiratory alkalosis). The decreased residual volumes render the pregnant patient more susceptible to alveolar collapse and respiratory compromise.

Under these circumstances, it may be prudent to consider early intubation of the pregnant patient with respiratory compromise in order to preserve the exchange of gases across the fetoplacental unit.

Renal blood flow is increased in pregnancy, with a concomitant increase in creatinine clearance and a tendency to more rapidly clear drugs that are renal dependent.

Standard lab values must be seen in the context of the changes in maternal physiology. For example, blood gas values in pregnancy may reveal lower CO2 values, and hematocrits may be lower secondary to the hemodilution seen in blood volume expansion.

During evaluation or resuscitation, it is important for ob.gyns. to remind the team of the mass of the gravid uterus and its ability—when the woman is in the supine position—to compromise the return of blood flow to the heart by compressing the vena cava.

Beyond the second trimester, the patient should be tilted to the left by approximately 35 degrees, and when a full-body tilt is not possible, left lateral displacement of the uterus must be maintained. When spinal injury is suspected, care must be taken to keep the spine and neck aligned during tilting.

Questions About Imaging

The obstetrician often will be asked whether the imaging needed to diagnose various injuries is safe for the fetus. Doses of radiation used during trauma care and evaluation—for example, CT scans of the pelvis or chest, and chest x-rays—are usually in the range of less than 250 mGy, which is considered to be the intermediate range of exposure and reasonably safe for the fetus.

Whenever possible, the pelvis of a pregnant woman should be shielded, especially in the first trimester. It is important to know, however, that much of today's imaging equipment is faster than previous technology and therefore delivers much lower radiation exposure with more information in a single pass. Additionally, MRI has been shown to be a safe modality in pregnancy.

The bottom line is that imaging studies that are needed for the care of the critically injured patient should not be withheld because she may be pregnant.

Primary Assessment

On initial presentation, all efforts for the pregnant trauma patient must first be directed toward stabilizing the mother and maintaining oxygen delivery, with the ABCs (airway, breathing, and circulation) of trauma care being the first priority.

Women who are pregnant have a reduced ability to compensate for respiratory compromise. Maintaining a patent airway is critical for both maternal and fetal oxygenation, and this very well may require early intubation. We must make sure that the patient is moving oxygen in, with oxygen saturation levels better than 90%.

The fetus's oxygen uptake depends directly on oxygen delivery via uterine blood flow, so circulation—both to the mother's vital organs and to the uterus—is also key. Because of shunting and vasospasm, significant uterine blood flow compromise may exist even with normal-appearing blood pressure. Thus, it is important to control any significant bleeding and pursue vigorous volume replacement.

Only after the ABCs are addressed—and readdressed for effectiveness—can we turn our attention elsewhere. If we were to add a “D” to the trauma protocol, it would stand for “disability” and would involve a rapid neurologic evaluation to assess for any neurologic injury. It is worth considering that neurologic impairment in late pregnancy may be secondary to an eclamptic seizure that may have led to the trauma event.

Other often critical components of trauma injuries, such as fractures and intraperitoneal hemorrhage, are usually evaluated almost simultaneously by the trauma team.

Patients with pelvic fractures (common in motor vehicle accidents) are at risk of having retroperitoneal hemorrhage, which is not always obvious and requires careful diagnosis. A pelvic exam can reveal signs of lower pelvic fracture and possible vaginal lacerations from protruding bone fragments.

The Secondary Survey

Once we have stabilized the mother and evaluated her for other critical signs of trauma, we can turn our attention to fetal assessment. First, we should assess gestational age, either by taking a history if someone close to the mother is present, or through ultrasonography.

Ultrasonography is an important tool at this point for assessing several factors in short order. In addition to assessing the viability of the fetus, we can evaluate the intrauterine fluid volume and the placental location. (The question of viability, of course, depends on the level of neonatal intensive care services available).

A low amount of amniotic fluid should lead us to suspect rupture of the amniotic membranes or, in some cases, uterine rupture secondary to trauma. Although with expert hands it is possible to detect relatively small placental abruptions, abruptions are usually apparent only with larger separations.

Ultrasonography can also be used in determining intra-abdominal free fluid which is consistent with intraperitoneal hemorrhage.

When the woman is severely injured and needs surgery and if delivery of the fetus is unnecessary, we should focus on monitoring the fetus in the operating room. We can do so with an ultrasound probe or a fetal Doppler encased in a sterile sleeve.

After surgery—or when the woman does not need surgery and is considered stable enough to undergo observation—continuous monitoring of the viable fetus, with a longer-term view, should be done using external monitoring of fetal heart rate and uterine monitoring for signs of preterm labor. Frequent uterine contractions should be followed closely, and cervical dilatation should be evaluated.

The ob.gyn. becomes the primary provider when a viable fetus shows signs of fetal compromise that necessitate delivery, or when uterine rupture occurs, in which case urgent intervention is necessary for the mother.

Many studies have attempted to address the question of how long trauma patients should be monitored, and many guidelines have been proposed. In general, we can conclude that 12 hours of observation is adequate for stable patients who are not contracting and have reassuring fetal tracings and no signs of bleeding.

On the other hand, patients who are contracting, who have a nonreassuring fetal tracing, or who have had any form of vaginal bleeding should be observed for a minimum of 24 hours. The more severe the injury to the mother, the more likely there is to be an injury to the fetus, and the higher the risk that a placental abruption or other serious complication may surface.

If a patient is discharged after observation, regardless of the severity of trauma, she must be given precautions regarding any changes in fetal movement or the development of abdominal pain, vaginal bleeding, or fluid loss. Any one of these changes should prompt her to return for evaluation immediately.

The Kleihauer-Betke test may be useful in evaluating the degree of fetal-maternal hemorrhage and the amount of Rh immune globulin that may be needed in the Rh-negative mother. In general, Rh-negative mothers who are involved in trauma should be given a single dose of Rh immune globulin unless it is known that the fetus is Rh negative.

Cardiac arrest is sometimes the tragic outcome for a posttrauma victim. Maternal resuscitation should be undertaken immediately. If maternal resuscitation is not thought likely to be effective, and the fetus is considered viable, the best outcome for fetal survival occurs if delivery can be accomplished within approximately 5 minutes from arrest. Beyond this time, there is diminishing return for fetal survival.

Organized, rapid assessment and intervention hold the key to the best outcomes for the pregnant patient involved in a trauma. Following the rules of trauma resuscitation (those ABCs) provides the best chance of successful treatment of the mother, which in turn provides the best chance of a favorable fetal outcome.

Motor vehicle accidents are the leading cause of trauma and death in women of childbearing age. Courtesy Dr. Hugh Mighty

One situation in which the ob.gyn. becomes the primary provider is when delivery is necessary. Courtesy Dr. Hugh Mighty

Trauma in Pregnancy

High-risk obstetrics by its very nature involves a wide spectrum of diseases and events that complicate pregnancies and preclude or prevent their normal progression. Sometimes, high-risk obstetrics involves physical trauma that is inflicted externally upon an otherwise normal pregnancy.

Physical trauma is, in fact, one of the leading causes of morbidity and mortality during pregnancy. It has been estimated that physical trauma complicates approximately 1 in every 12 pregnancies—a staggering figure and one that we may not fully appreciate or think about often enough.

According to the American College of Obstetricians and Gynecologists, approximately two-thirds of all trauma during pregnancy in industrialized nations results from motor vehicle crashes.

Women not only are more likely to be involved in automobile accidents than are male drivers; they also are increasingly more likely to be victims of violence. In 1994, women were about six times more likely than men to be victims of violence—a significant increase from more than a decade before, when women were half as likely as men to be victims of violence.

Trauma in pregnant women has to be dealt with by a variety of specialists. Very often, these patients will present to emergency departments or urgent care centers, and will have to be seen by emergency physicians, surgeons, or general practitioners. This is a challenging situation and one that presents unusual challenges for obstetric staff.

Especially as the number of patients with traumatic injuries and complications increases, it is important that we review some of the key types of presentations and complications of trauma in pregnancy, and discuss how we may best develop therapeutic algorithms for dealing with them.

It is in this light that we have invited Dr. Hugh E. Mighty, chairman of the department of obstetrics, gynecology, and reproductive sciences at the University of Maryland, Baltimore, to discuss the management of seriously injured pregnant women.

Dr. Mighty is not only a maternal-fetal medicine specialist, but is certified in critical care medicine as well. We are pleased to welcome him as an expert on trauma in pregnancy and as this month's guest professor on the subject.

This combination of disease-specific and pain-specific therapies reflects the complexity of chronic pelvic pain and the fact that there most often will be more than one diagnosis, as well as the fact that pain itself will more often than not be one of the diagnoses and not only a symptom.

Just as we should be guided in our differential diagnosis by seeking diagnoses for which we have the best evidence of casual or associative roles in chronic pelvic pain, we should begin with treatments for which there is good level I evidence of efficacy.

Surgery will help a subgroup of women with chronic pelvic pain, especially those with endometriosis and other reproductive tract disorders, but the majority of women with chronic pelvic pain will benefit most from medical, psychological, and physical therapy.

There are strong data from studies of the treatment of irritable bowel syndrome (IBS) and pelvic congestion syndrome that show that adding psychological treatment to medical treatment is more effective than providing either by itself. Physical therapy, moreover, can be helpful for the secondary pelvic floor muscle pain that many women develop regardless of what problems were pain generators in the first place.

Disease-Specific Therapy

In trying to help women with chronic pelvic pain, we will most often find ourselves treating the common diagnoses that have level A evidence of association with the pain: IBS, endometriosis, interstitial cystitis, myofascial trigger points, depression, and chronic pain syndrome.

Endometriosis and interstitial cystitis are particularly common in women with chronic pelvic pain, and there is good evidence that the disorders not only cause the pain but also tend to occur together. The literature suggests that 30%–80% of women with endometriosis also have interstitial cystitis, and we know that treating one but not the other will significantly lessen our chances of success in treating pelvic pain.

For endometriosis, there is good level I evidence of efficacy for the use of hormonal treatments like GnRH agonists, progestins, and continuous oral contraceptives. Additionally, two randomized trials have confirmed that conservative—or organ-sparing—surgical removal of endometriosis lesions is effective in decreasing pain.

Combining surgery and medical treatment for endometriosis may be more efficacious than providing either by itself. We don't yet have level I evidence to support this approach—just as we don't yet have any published studies directly comparing medical and surgical treatments—but some of the completed clinical studies suggest that we should consider a combined approach in patients who are not trying to conceive.

For interstitial cystitis, randomized trials have demonstrated the efficacy of intravesical dimethyl sulfoxide and of oral pentosan polysulfate sodium.

Symptoms of IBS are present in a majority of women with chronic pelvic pain, and treatment tends to be based on which symptoms are predominant. For example, a number of good randomized trials have shown efficacy for the use of antispasmodics in patients whose symptomatology is predominantly abdominal pain, and for loperamide (Imodium) in patients with diarrhea-predominant symptomatology. Interestingly, tricyclic antidepressants, which often are prescribed to control chronic pelvic pain, can be useful for diarrhea-predominant IBS because constipation tends to be a side effect of the drugs. For constipation-predominant IBS, the newer drug tegaserod (Zelnorm) is frequently used.

In general, for our patients clearly troubled by IBS, evaluation and treatment with a gastroenterologist who is well versed in IBS are definitely worthwhile.

When it comes to myofascial and musculoskeletal pain, we don't have as much good data from randomized clinical trials to help direct our treatment decisions, but it certainly appears, based on clinical experience, that physical therapy—and, when indicated, trigger-point injections—is effective.

It is important to realize that physical therapy is often an important adjunct to the treatment of chronic pelvic pain, as well as a specific treatment. Regardless of what the pain generators or specific diagnoses are, many of these women develop secondary pelvic floor muscle pain, or pelvic floor tension myalgia.

Secondary pelvic floor muscle pain often does not respond to treatments for the specific diagnoses we make in women with chronic pelvic pain, and evaluation and treatment by a women's health physical therapist can thus be most useful. For this, contact the women's health section of the American Physical Therapy Association.

When it comes to the issue of surgery for chronic pelvic pain, endometriosis is one of the few diagnoses for which surgery has a clear role.

The treatment of adhesions, which are diagnosed in about one-quarter of women with chronic pelvic pain, is still controversial. It is not clear whether lysis of adhesions is effective in reducing pelvic pain, and it appears that the majority of adhesions that are surgically lysed do reform. The role of adhesions as a cause of pelvic pain, of course, is also controversial.

Pain-Specific Therapy

Here we have many different treatments— pharmacologic, psychological, and neuroablative—that rest, to some extent, on acceptance of the notions that pain may not necessarily be cured but can be managed, and that patients can progress toward more normal lives that are not dominated by pain.

It is important that we not use psychological treatment as a last resort. If we do everything else, and then tell a patient that everything else has failed and we are recommending psychological treatment, we are in essence sending her the message that we think her pain is not real. There are two errors here that warrant correction: First, psychological pain is indeed real. Second, most of the time, the etiology of chronic pelvic pain is not psychological.

What we should do right away, with all of our patients, is explain that cognitive-behavioral therapy, relaxation therapy, and other psychological techniques are extremely useful in helping patients decrease and cope with pain.

I sometimes use the analogy of how our emotions and mind can cause us to turn beet red and make us sweat and become tachycardic when we are embarrassed about something we have said or done. If our emotions can cause that kind of physical reaction, might not relaxation therapy, for instance, cause physiologic changes that help decrease our pain? More often than not, it is financial issues and the relatively poor coverage of mental health care in this country—and not patient acceptance—that is the major impediment to including psychotherapy in the treatment of chronic pelvic pain.

In the neuroablative arena, there is some evidence that adding presacral neurectomy (excision of the superior hypogastric plexus, or presacral nerve) to other treatments for endometriosis is sometimes indicated, although it's not perfectly clear what those indications are. I tend to use the therapy in patients who have previously failed medical or surgical therapy. It is one of the neurolytic therapies that may be useful in decreasing pain centrally even when there is no specific nerve dysfunction.

Tricyclic antidepressants, particularly amitriptyline, have been shown to be effective in treating chronic pelvic pain and other chronic pain syndromes, and therefore are a part of the pharmacologic arm of pain-specific therapy. In addition to reducing depressive symptoms—which is often an aim anyway in patients with chronic pelvic pain, as depression occurs with increased frequency in these women—it is generally thought that the tricyclic antidepressants improve pain tolerance.

Analgesics, of course, are a mainstay of pharmacologic pain-specific treatment of chronic pelvic pain, and there is little controversy about the use of analgesics like acetaminophen, NSAIDs, tricyclic antidepressants, and other neuropathic medications, such as gabapentin and other anticonvulsants used for chronic pain.

The use of opioids in the treatment of chronic pain remains controversial, however. Several studies, as well as clinical experience in pain centers, suggest that opioids are effective for chronic—and not only acute—pain: that the analgesics improve function and quality of life in patients who have failed other treatments. There is, however, the well-known risk of addiction, which is estimated to occur in anywhere from 3% to 15% of chronic pain patients.

As gynecologists, we can consider providing opioid treatment ourselves, but only if we are attuned to looking for addictive behaviors and only if we are familiar with state regulations that address chronic opioid use. Federal codes are quite clear in stating that the federal government has no intention of preventing physicians from treating chronic pain with opioids if such treatment is indicated, but state regulations vary.

Treatment of Chronic Pelvic Pain

This is the second installment of the Master Class in Gynecologic Surgery on pelvic pain. In part 1, I drafted Dr. Fred Howard, who serves as associate chair for academic affairs, director of the division of gynecologic specialists, and professor of obstetrics and gynecology at the University of Rochester (N.Y.), to discuss the differential diagnosis and work-up of chronic pelvic pain. In part 2, he will turn from the diagnosis to the treatment of chronic pelvic pain.

I am certain that the reader will be immediately drawn to Dr. Howard's double-armed treatment regimen of both disease-specific therapy and pain-specific therapy. Although he recognizes the importance of surgical treatment—especially in cases of endometriosis, uterine fibroids, ovarian cysts, and other reproductive tract disorders—he is quick to point out that medical, psychological, or physical therapy will suffice in most women's cases. Moreover, as Dr. Howard recognizes, physicians as well as their patients must realize and accept that although a cure is the ultimate goal of treatment, pain management may be the reality.

This combination of disease-specific and pain-specific therapies reflects the complexity of chronic pelvic pain and the fact that there most often will be more than one diagnosis, as well as the fact that pain itself will more often than not be one of the diagnoses and not only a symptom.

Just as we should be guided in our differential diagnosis by seeking diagnoses for which we have the best evidence of casual or associative roles in chronic pelvic pain, we should begin with treatments for which there is good level I evidence of efficacy.

Surgery will help a subgroup of women with chronic pelvic pain, especially those with endometriosis and other reproductive tract disorders, but the majority of women with chronic pelvic pain will benefit most from medical, psychological, and physical therapy.

There are strong data from studies of the treatment of irritable bowel syndrome (IBS) and pelvic congestion syndrome that show that adding psychological treatment to medical treatment is more effective than providing either by itself. Physical therapy, moreover, can be helpful for the secondary pelvic floor muscle pain that many women develop regardless of what problems were pain generators in the first place.

Disease-Specific Therapy

In trying to help women with chronic pelvic pain, we will most often find ourselves treating the common diagnoses that have level A evidence of association with the pain: IBS, endometriosis, interstitial cystitis, myofascial trigger points, depression, and chronic pain syndrome.

Endometriosis and interstitial cystitis are particularly common in women with chronic pelvic pain, and there is good evidence that the disorders not only cause the pain but also tend to occur together. The literature suggests that 30%–80% of women with endometriosis also have interstitial cystitis, and we know that treating one but not the other will significantly lessen our chances of success in treating pelvic pain.

For endometriosis, there is good level I evidence of efficacy for the use of hormonal treatments like GnRH agonists, progestins, and continuous oral contraceptives. Additionally, two randomized trials have confirmed that conservative—or organ-sparing—surgical removal of endometriosis lesions is effective in decreasing pain.

Combining surgery and medical treatment for endometriosis may be more efficacious than providing either by itself. We don't yet have level I evidence to support this approach—just as we don't yet have any published studies directly comparing medical and surgical treatments—but some of the completed clinical studies suggest that we should consider a combined approach in patients who are not trying to conceive.

For interstitial cystitis, randomized trials have demonstrated the efficacy of intravesical dimethyl sulfoxide and of oral pentosan polysulfate sodium.

Symptoms of IBS are present in a majority of women with chronic pelvic pain, and treatment tends to be based on which symptoms are predominant. For example, a number of good randomized trials have shown efficacy for the use of antispasmodics in patients whose symptomatology is predominantly abdominal pain, and for loperamide (Imodium) in patients with diarrhea-predominant symptomatology. Interestingly, tricyclic antidepressants, which often are prescribed to control chronic pelvic pain, can be useful for diarrhea-predominant IBS because constipation tends to be a side effect of the drugs. For constipation-predominant IBS, the newer drug tegaserod (Zelnorm) is frequently used.

In general, for our patients clearly troubled by IBS, evaluation and treatment with a gastroenterologist who is well versed in IBS are definitely worthwhile.

When it comes to myofascial and musculoskeletal pain, we don't have as much good data from randomized clinical trials to help direct our treatment decisions, but it certainly appears, based on clinical experience, that physical therapy—and, when indicated, trigger-point injections—is effective.

It is important to realize that physical therapy is often an important adjunct to the treatment of chronic pelvic pain, as well as a specific treatment. Regardless of what the pain generators or specific diagnoses are, many of these women develop secondary pelvic floor muscle pain, or pelvic floor tension myalgia.

Secondary pelvic floor muscle pain often does not respond to treatments for the specific diagnoses we make in women with chronic pelvic pain, and evaluation and treatment by a women's health physical therapist can thus be most useful. For this, contact the women's health section of the American Physical Therapy Association.

When it comes to the issue of surgery for chronic pelvic pain, endometriosis is one of the few diagnoses for which surgery has a clear role.

The treatment of adhesions, which are diagnosed in about one-quarter of women with chronic pelvic pain, is still controversial. It is not clear whether lysis of adhesions is effective in reducing pelvic pain, and it appears that the majority of adhesions that are surgically lysed do reform. The role of adhesions as a cause of pelvic pain, of course, is also controversial.

Pain-Specific Therapy

Here we have many different treatments— pharmacologic, psychological, and neuroablative—that rest, to some extent, on acceptance of the notions that pain may not necessarily be cured but can be managed, and that patients can progress toward more normal lives that are not dominated by pain.

It is important that we not use psychological treatment as a last resort. If we do everything else, and then tell a patient that everything else has failed and we are recommending psychological treatment, we are in essence sending her the message that we think her pain is not real. There are two errors here that warrant correction: First, psychological pain is indeed real. Second, most of the time, the etiology of chronic pelvic pain is not psychological.

What we should do right away, with all of our patients, is explain that cognitive-behavioral therapy, relaxation therapy, and other psychological techniques are extremely useful in helping patients decrease and cope with pain.

I sometimes use the analogy of how our emotions and mind can cause us to turn beet red and make us sweat and become tachycardic when we are embarrassed about something we have said or done. If our emotions can cause that kind of physical reaction, might not relaxation therapy, for instance, cause physiologic changes that help decrease our pain? More often than not, it is financial issues and the relatively poor coverage of mental health care in this country—and not patient acceptance—that is the major impediment to including psychotherapy in the treatment of chronic pelvic pain.

In the neuroablative arena, there is some evidence that adding presacral neurectomy (excision of the superior hypogastric plexus, or presacral nerve) to other treatments for endometriosis is sometimes indicated, although it's not perfectly clear what those indications are. I tend to use the therapy in patients who have previously failed medical or surgical therapy. It is one of the neurolytic therapies that may be useful in decreasing pain centrally even when there is no specific nerve dysfunction.

Tricyclic antidepressants, particularly amitriptyline, have been shown to be effective in treating chronic pelvic pain and other chronic pain syndromes, and therefore are a part of the pharmacologic arm of pain-specific therapy. In addition to reducing depressive symptoms—which is often an aim anyway in patients with chronic pelvic pain, as depression occurs with increased frequency in these women—it is generally thought that the tricyclic antidepressants improve pain tolerance.

Analgesics, of course, are a mainstay of pharmacologic pain-specific treatment of chronic pelvic pain, and there is little controversy about the use of analgesics like acetaminophen, NSAIDs, tricyclic antidepressants, and other neuropathic medications, such as gabapentin and other anticonvulsants used for chronic pain.

The use of opioids in the treatment of chronic pain remains controversial, however. Several studies, as well as clinical experience in pain centers, suggest that opioids are effective for chronic—and not only acute—pain: that the analgesics improve function and quality of life in patients who have failed other treatments. There is, however, the well-known risk of addiction, which is estimated to occur in anywhere from 3% to 15% of chronic pain patients.

As gynecologists, we can consider providing opioid treatment ourselves, but only if we are attuned to looking for addictive behaviors and only if we are familiar with state regulations that address chronic opioid use. Federal codes are quite clear in stating that the federal government has no intention of preventing physicians from treating chronic pain with opioids if such treatment is indicated, but state regulations vary.

Treatment of Chronic Pelvic Pain

This is the second installment of the Master Class in Gynecologic Surgery on pelvic pain. In part 1, I drafted Dr. Fred Howard, who serves as associate chair for academic affairs, director of the division of gynecologic specialists, and professor of obstetrics and gynecology at the University of Rochester (N.Y.), to discuss the differential diagnosis and work-up of chronic pelvic pain. In part 2, he will turn from the diagnosis to the treatment of chronic pelvic pain.

I am certain that the reader will be immediately drawn to Dr. Howard's double-armed treatment regimen of both disease-specific therapy and pain-specific therapy. Although he recognizes the importance of surgical treatment—especially in cases of endometriosis, uterine fibroids, ovarian cysts, and other reproductive tract disorders—he is quick to point out that medical, psychological, or physical therapy will suffice in most women's cases. Moreover, as Dr. Howard recognizes, physicians as well as their patients must realize and accept that although a cure is the ultimate goal of treatment, pain management may be the reality.

This combination of disease-specific and pain-specific therapies reflects the complexity of chronic pelvic pain and the fact that there most often will be more than one diagnosis, as well as the fact that pain itself will more often than not be one of the diagnoses and not only a symptom.

Just as we should be guided in our differential diagnosis by seeking diagnoses for which we have the best evidence of casual or associative roles in chronic pelvic pain, we should begin with treatments for which there is good level I evidence of efficacy.

Surgery will help a subgroup of women with chronic pelvic pain, especially those with endometriosis and other reproductive tract disorders, but the majority of women with chronic pelvic pain will benefit most from medical, psychological, and physical therapy.

There are strong data from studies of the treatment of irritable bowel syndrome (IBS) and pelvic congestion syndrome that show that adding psychological treatment to medical treatment is more effective than providing either by itself. Physical therapy, moreover, can be helpful for the secondary pelvic floor muscle pain that many women develop regardless of what problems were pain generators in the first place.

Disease-Specific Therapy

In trying to help women with chronic pelvic pain, we will most often find ourselves treating the common diagnoses that have level A evidence of association with the pain: IBS, endometriosis, interstitial cystitis, myofascial trigger points, depression, and chronic pain syndrome.

Endometriosis and interstitial cystitis are particularly common in women with chronic pelvic pain, and there is good evidence that the disorders not only cause the pain but also tend to occur together. The literature suggests that 30%–80% of women with endometriosis also have interstitial cystitis, and we know that treating one but not the other will significantly lessen our chances of success in treating pelvic pain.

For endometriosis, there is good level I evidence of efficacy for the use of hormonal treatments like GnRH agonists, progestins, and continuous oral contraceptives. Additionally, two randomized trials have confirmed that conservative—or organ-sparing—surgical removal of endometriosis lesions is effective in decreasing pain.

Combining surgery and medical treatment for endometriosis may be more efficacious than providing either by itself. We don't yet have level I evidence to support this approach—just as we don't yet have any published studies directly comparing medical and surgical treatments—but some of the completed clinical studies suggest that we should consider a combined approach in patients who are not trying to conceive.

For interstitial cystitis, randomized trials have demonstrated the efficacy of intravesical dimethyl sulfoxide and of oral pentosan polysulfate sodium.

Symptoms of IBS are present in a majority of women with chronic pelvic pain, and treatment tends to be based on which symptoms are predominant. For example, a number of good randomized trials have shown efficacy for the use of antispasmodics in patients whose symptomatology is predominantly abdominal pain, and for loperamide (Imodium) in patients with diarrhea-predominant symptomatology. Interestingly, tricyclic antidepressants, which often are prescribed to control chronic pelvic pain, can be useful for diarrhea-predominant IBS because constipation tends to be a side effect of the drugs. For constipation-predominant IBS, the newer drug tegaserod (Zelnorm) is frequently used.

In general, for our patients clearly troubled by IBS, evaluation and treatment with a gastroenterologist who is well versed in IBS are definitely worthwhile.

When it comes to myofascial and musculoskeletal pain, we don't have as much good data from randomized clinical trials to help direct our treatment decisions, but it certainly appears, based on clinical experience, that physical therapy—and, when indicated, trigger-point injections—is effective.

It is important to realize that physical therapy is often an important adjunct to the treatment of chronic pelvic pain, as well as a specific treatment. Regardless of what the pain generators or specific diagnoses are, many of these women develop secondary pelvic floor muscle pain, or pelvic floor tension myalgia.

Secondary pelvic floor muscle pain often does not respond to treatments for the specific diagnoses we make in women with chronic pelvic pain, and evaluation and treatment by a women's health physical therapist can thus be most useful. For this, contact the women's health section of the American Physical Therapy Association.

When it comes to the issue of surgery for chronic pelvic pain, endometriosis is one of the few diagnoses for which surgery has a clear role.

The treatment of adhesions, which are diagnosed in about one-quarter of women with chronic pelvic pain, is still controversial. It is not clear whether lysis of adhesions is effective in reducing pelvic pain, and it appears that the majority of adhesions that are surgically lysed do reform. The role of adhesions as a cause of pelvic pain, of course, is also controversial.

Pain-Specific Therapy

Here we have many different treatments— pharmacologic, psychological, and neuroablative—that rest, to some extent, on acceptance of the notions that pain may not necessarily be cured but can be managed, and that patients can progress toward more normal lives that are not dominated by pain.

It is important that we not use psychological treatment as a last resort. If we do everything else, and then tell a patient that everything else has failed and we are recommending psychological treatment, we are in essence sending her the message that we think her pain is not real. There are two errors here that warrant correction: First, psychological pain is indeed real. Second, most of the time, the etiology of chronic pelvic pain is not psychological.

What we should do right away, with all of our patients, is explain that cognitive-behavioral therapy, relaxation therapy, and other psychological techniques are extremely useful in helping patients decrease and cope with pain.

I sometimes use the analogy of how our emotions and mind can cause us to turn beet red and make us sweat and become tachycardic when we are embarrassed about something we have said or done. If our emotions can cause that kind of physical reaction, might not relaxation therapy, for instance, cause physiologic changes that help decrease our pain? More often than not, it is financial issues and the relatively poor coverage of mental health care in this country—and not patient acceptance—that is the major impediment to including psychotherapy in the treatment of chronic pelvic pain.

In the neuroablative arena, there is some evidence that adding presacral neurectomy (excision of the superior hypogastric plexus, or presacral nerve) to other treatments for endometriosis is sometimes indicated, although it's not perfectly clear what those indications are. I tend to use the therapy in patients who have previously failed medical or surgical therapy. It is one of the neurolytic therapies that may be useful in decreasing pain centrally even when there is no specific nerve dysfunction.

Tricyclic antidepressants, particularly amitriptyline, have been shown to be effective in treating chronic pelvic pain and other chronic pain syndromes, and therefore are a part of the pharmacologic arm of pain-specific therapy. In addition to reducing depressive symptoms—which is often an aim anyway in patients with chronic pelvic pain, as depression occurs with increased frequency in these women—it is generally thought that the tricyclic antidepressants improve pain tolerance.

Analgesics, of course, are a mainstay of pharmacologic pain-specific treatment of chronic pelvic pain, and there is little controversy about the use of analgesics like acetaminophen, NSAIDs, tricyclic antidepressants, and other neuropathic medications, such as gabapentin and other anticonvulsants used for chronic pain.

The use of opioids in the treatment of chronic pain remains controversial, however. Several studies, as well as clinical experience in pain centers, suggest that opioids are effective for chronic—and not only acute—pain: that the analgesics improve function and quality of life in patients who have failed other treatments. There is, however, the well-known risk of addiction, which is estimated to occur in anywhere from 3% to 15% of chronic pain patients.

As gynecologists, we can consider providing opioid treatment ourselves, but only if we are attuned to looking for addictive behaviors and only if we are familiar with state regulations that address chronic opioid use. Federal codes are quite clear in stating that the federal government has no intention of preventing physicians from treating chronic pain with opioids if such treatment is indicated, but state regulations vary.

Treatment of Chronic Pelvic Pain

This is the second installment of the Master Class in Gynecologic Surgery on pelvic pain. In part 1, I drafted Dr. Fred Howard, who serves as associate chair for academic affairs, director of the division of gynecologic specialists, and professor of obstetrics and gynecology at the University of Rochester (N.Y.), to discuss the differential diagnosis and work-up of chronic pelvic pain. In part 2, he will turn from the diagnosis to the treatment of chronic pelvic pain.

I am certain that the reader will be immediately drawn to Dr. Howard's double-armed treatment regimen of both disease-specific therapy and pain-specific therapy. Although he recognizes the importance of surgical treatment—especially in cases of endometriosis, uterine fibroids, ovarian cysts, and other reproductive tract disorders—he is quick to point out that medical, psychological, or physical therapy will suffice in most women's cases. Moreover, as Dr. Howard recognizes, physicians as well as their patients must realize and accept that although a cure is the ultimate goal of treatment, pain management may be the reality.

It was my job to explain to the baby's parents what the disorder was and how it happened. Many of the babies I saw had an autosomal recessive disorder, and it was necessary to explain to the baby's mother and father how this awful disease suddenly appeared in their child, and tell them that they faced a 25% risk of its happening again should they decide to have more children. Their options for the future, I would tell them, would be to adopt, to elect not have any more children, to use an anonymous donor for eggs or sperm, or—as many couples do—to carefully roll the genetic dice again with hopes of a better outcome.

In the last scenario, I would explain, the parents would have the opportunity to have a chorionic villus sampling or amniocentesis. But it goes without saying that the 12–15 weeks that unfold before such testing is done are often filled with anxiety: first, about having the test, and second, about the decision to be made if the results are not favorable.

Today, obstetricians have good reason to present such parents with another option—preimplantation genetic diagnosis (PGD)–and to be aware of its capabilities and limitations. Developments in PGD mean that we, also, in all of our preconceptual obstetrical work, have good reason to be cognizant of ethnicity-based risks for genetic disorders and to advise patients, when indicated, to have genetic screening themselves.

We can use PGD today, in conjunction with in vitro fertilization, to test for over 250 serious diseases and conditions caused by mutations or chromosomal abnormalities. Parents who choose the technology—usually couples who know they carry mutations or who have had another baby or a family member with a serious inherited illness—can learn that an embryo is free of the disease that their family is prone to, and can thus start a pregnancy with a commitment to continuing it.

The Genetics, the Process

As obstetricians, we are not trained geneticists. Therefore, it is helpful for us and for our patients if we understand the basic genetics behind PGD, and appreciate how PGD pushes diagnostic technology to its absolute limits—both its theoretical limits and its practical limits.

Every cell taken from an embryo (or any cell in our body) contains all the genes needed to make a new, complete individual. Each cell's DNA contains just four letters of the genetic alphabet: A, T, G, and C. The way in which these letters are strung together, just as letters are put together to make a book, will tell that cell what to do.

We can think of chromosomes as books of the gigantic encyclopedia of life, and genes as paragraphs within these chromosome books. Each chromosome has thousands of genes, most of which contribute something unique to the story of who we are, just as most paragraphs in a novel or encyclopedia contribute a unique element to the story or knowledge base. Some genes do not appear to be as important to our health as others, just as some paragraphs seem like “filler” in a story.

All genes have a defined beginning and a defined end, and just as a paragraph has an indentation, a gene has a promoter. Genes are made up of little bits called exons, just as paragraphs are made up of sentences. Some genes are gigantic; the gene whose mutation causes muscular dystrophy, for instance, would be equivalent to a paragraph about 158 pages long. Other genes are tiny, similar to a short phrase.

We all carry hundreds and hundreds of typographical errors in our personal encyclopedia, some of them inactivating the gene paragraph that contains them. Fortunately, the errors we inherit from our mothers are generally not matched by the errors we inherit from our fathers. Every once in a while, though, we choose a mate with a gene mutation in the same paragraph. When this occurs, the baby does not have a “backup” copy of the intact gene paragraph, and a recessive disease can occur.

Such unfortunate pairings happen more often in couples of similar ethnicity because many gene mutations are ancestral in a given ethnic population. Thus, one of our roles in preconceptual counseling is to think about the possibility that a patient who wants to discontinue birth control and start a family might carry a gene mutation for an inherited disorder common to his or her ethnic background.

In couples of Northern European ancestry, we think first of cystic fibrosis (with a carrier frequency of about 1 in 29 in the United States) and spinal muscular atrophy (1 in 5). In African Americans, we worry about sickle cell anemia (1 in 22).

If our patients have Southeast Asian ancestry, we should consider α-thalassemia (1 in 30), and for patients with Mediterranean ancestry, β-thalassemia. For patients of Ashkenazi Jewish ancestry, genetic screening is performed routinely for the ancestral mutations causing Tay-Sachs disease, familial dysautonomia, Gaucher's disease type 1, Niemann-Pick disease, Bloom syndrome, Canavan disease, and cystic fibrosis.

When we perform PGD, the testing is done overnight. Couples follow the same process that any infertile couple undergoing in vitro fertilization (IVF) would follow, but before implantation, a single cell is taken for analysis from each embryo in its day-3, eight-cell stage. The single-cell samples are sent by courier to a reference laboratory for overnight testing, and a report is electronically sent to the reproductive endocrinologist. Couples are notified of the results in time for embryo transfer on day 5.

In the future, we may be able to relax the timeline and allow more time for embryo transfer by performing the biopsies when the embryo is 5 days old. In this procedure, cells would be taken from the trophectoderm—the outer layer of the embryo that ultimately develops into the placenta—and the embryos would be frozen via a rapid freezing process called vitrification.

Ice crystals do not form in this method, so concerns about damage to the cells is alleviated. Women could then undergo embryo transfer the next month. For now, however, we follow a 5-day deadline for embryo transfer.

Regardless of what advances are made, we must appreciate the fact that this technology pushes medical diagnostics to its limits. PGD involves the testing of one single cell (the smallest unit of life) and one gene (the smallest unit of inheritance), for one typographical error in 3.3 billion DNA letters, and all of this occurs overnight.

Its Value and Accuracy

The nomenclature of what we have simply and rather loosely called PGD is actually changing a bit. Following Europe's lead, U.S. experts are beginning to use the term PGD to refer specifically to the actual diagnosis of a particular disease. PGS (preimplantation genetic screening) is exactly what its name implies as well—screening, largely for abnormal numbers of chromosomes—and not the actual disease diagnosis. Together, the terms fall under the general rubric of preimplantation genetics.

The differentiation is being made because everything about the two procedures—the technology; the people and issues involved; the risks and benefits; and importantly, the accuracy of the procedure—is different. All told, the error rate for preimplantation genetics is in the range of about 2%–4%. Analyzing chromosomes, however, is quite different from analyzing genes, just as counting books of the encyclopedia is quite different from opening a book and finding a letter error.

In analyzing chromosomes, we have to worry about the possibility of complex chromosomal mosaicism having occurred. This is a process by which chromosomes segregate unevenly to cells as the cells are dividing, and if it has occurred, some of the cells we biopsy may appear normal even though the rest of the cells are not.

Experts are increasingly concerned that the chromosome analysis component of preimplantation screening may not really be improving parents' chances of having a healthy baby. However, although the prognostic value of what we now should call PGS is unclear and confusing, there are no such doubts associated with PGD. Telling parents that their baby has a clear 25% chance of having a serious disease is quite different from telling parents that their baby may—or may not—have a chromosomal abnormality.

This is not to say, however, that PGS is without value. I would advise it in cases in which the woman already needs IVF and if she has had recurrent miscarriages.

Ethical Issues and the Future

The real issue with preimplantation genetics, I believe, is whether there are limits to when the technology can and should be used. We must continue, of course, to consider and address the questions associated with PGS and its value. But beyond this, we face numerous questions emanating not as much from a scientific or technologic perspective as from an ethical perspective.

For instance, couples who already have a child with a genetic disease and do not want it to happen again can test their embryos not only to learn which ones carry the genetic defect, but also to learn whether any of their embryos are an identical stem-cell match with their child who is ill.

At the time of delivery, then, they will have not only a healthy baby, but also a baby who can donate identically human leukocyte antigen (HLA)-matched cord blood for stem-cell transplantation to the sibling. Such testing for HLA matching happens daily in the United States.

It is also possible to screen embryos for genes that raise the risk of cancer—primarily breast, ovarian, and colon—in adulthood. We know this is being done in England today, where regulators ruled last year to allow it. The questions are a bit different with this issue, as I see it, because genotype in this case does not accurately predict phenotype. Having the BRCA1 or BRCA2 gene mutation does not mean, for instance, that a person will develop breast or ovarian cancer. So the question really is whether we should be testing embryos for a disease that may never occur.

As in other ethical debates, we must listen to all points of view. Many couples have watched multiple family members die from colon cancer or breast cancer and have decided that enough is enough, whereas other couples who are testing for HLA matching have a child with an incurable, often fatal disease. These couples know there is no such thing as a perfect baby. All they want is to have the A and the G and the T and the C in the right places, or to save their child while having the chance to have another healthy baby to love as well.

Most clinics have ethics teams to develop policies that address these issues and to describe which indications for preimplantation genetics are acceptable and which are not. Most clinics allow the use of technology for finding cancer genes and for HLA matching, for instance, but not for selecting gender.

Studies following children after IVF and preimplantation genetics that have been done in Europe—where the type of medical system allows investigators to effectively track patients for longer-term outcomes—are better than those done in the United States. Clearly, safety and good outcomes have been demonstrated. Thousands and thousands of babies have been born after having undergone IVF and PGS or PGS, with no evidence of birth defects.

Still, experts in the United States have been designing a database—a prospective registry of sorts—that, when implemented, will collect data on the use of preimplantation genetics, primarily regarding how much is being done and for what ends the technology is being used. Such data will help us to further understand and guide this fast-growing facet of reproductive medicine.

A human 8-cell embryo produced routinely in an IVF laboratory is undergoing the biopsy of one blastomere (cell) for testing. Courtesy Dr. Mark R. Hughes

The Quest for Prenatal Evaluation

The quest for fetal and embryonic evaluation has been of great interest to many scientists, physicians, parents, and members of the lay public. It has eventuated into the well-established field of prenatal diagnosis.

The focus, for the most part, has been on gleaning information during the early and midtrimester periods of pregnancy. Such evaluation has been found most useful in providing reassurance to parents when anomalies are excluded, or—under those uncommon circumstances when a diagnosis is made prenatally—in allowing parents and physicians to create appropriate medical and social strategies to deal with these diagnoses.

Despite the benefits afforded by prenatal diagnosis, there remains a subset of the potentially reproductive population for whom conceiving and delivering an abnormal child is not a rare event, but may in fact have a high degree of predictability. These aspiring parents have had to choose among high-risk pregnancy, nonconception, adoption, or egg or sperm donors.

Most recently, however, these patients and their physicians have been able to exploit the new technology of preimplantation genetic diagnosis. This is a rapidly expanding field that has the potential to make a significant difference in the lives of patients who could not otherwise be anywhere near certain that they would deliver a healthy, normal child.

The technology affords us a wide range of possibilities, both now and in the future, but it also presents a number of challenges, including ethical issues, financial coverage issues, and issues concerning the actual availability of the services to select populations and individuals.

This all makes preimplantation genetics quite a complex topic, with great positive potential and a great many implications and potential hurdles and obstacles, all of which must be discussed and deliberated.

It is for this reason that we have invited Dr. Mark R. Hughes, a leading international scholar in the area of preimplantation diagnosis and one of the pioneers of this technology, to serve as the guest author of this month's Master Class.

Currently, Dr. Hughes is the director of the Genesis Genetics Institute in Detroit. He previously served on the faculty of the schools of medicine at Baylor College of Medicine, Georgetown University, and Wayne State University, and was a member of the founding group of the Human Genome Institute at the National Institutes of Health.

It was my job to explain to the baby's parents what the disorder was and how it happened. Many of the babies I saw had an autosomal recessive disorder, and it was necessary to explain to the baby's mother and father how this awful disease suddenly appeared in their child, and tell them that they faced a 25% risk of its happening again should they decide to have more children. Their options for the future, I would tell them, would be to adopt, to elect not have any more children, to use an anonymous donor for eggs or sperm, or—as many couples do—to carefully roll the genetic dice again with hopes of a better outcome.

In the last scenario, I would explain, the parents would have the opportunity to have a chorionic villus sampling or amniocentesis. But it goes without saying that the 12–15 weeks that unfold before such testing is done are often filled with anxiety: first, about having the test, and second, about the decision to be made if the results are not favorable.

Today, obstetricians have good reason to present such parents with another option—preimplantation genetic diagnosis (PGD)–and to be aware of its capabilities and limitations. Developments in PGD mean that we, also, in all of our preconceptual obstetrical work, have good reason to be cognizant of ethnicity-based risks for genetic disorders and to advise patients, when indicated, to have genetic screening themselves.

We can use PGD today, in conjunction with in vitro fertilization, to test for over 250 serious diseases and conditions caused by mutations or chromosomal abnormalities. Parents who choose the technology—usually couples who know they carry mutations or who have had another baby or a family member with a serious inherited illness—can learn that an embryo is free of the disease that their family is prone to, and can thus start a pregnancy with a commitment to continuing it.

The Genetics, the Process

As obstetricians, we are not trained geneticists. Therefore, it is helpful for us and for our patients if we understand the basic genetics behind PGD, and appreciate how PGD pushes diagnostic technology to its absolute limits—both its theoretical limits and its practical limits.

Every cell taken from an embryo (or any cell in our body) contains all the genes needed to make a new, complete individual. Each cell's DNA contains just four letters of the genetic alphabet: A, T, G, and C. The way in which these letters are strung together, just as letters are put together to make a book, will tell that cell what to do.

We can think of chromosomes as books of the gigantic encyclopedia of life, and genes as paragraphs within these chromosome books. Each chromosome has thousands of genes, most of which contribute something unique to the story of who we are, just as most paragraphs in a novel or encyclopedia contribute a unique element to the story or knowledge base. Some genes do not appear to be as important to our health as others, just as some paragraphs seem like “filler” in a story.

All genes have a defined beginning and a defined end, and just as a paragraph has an indentation, a gene has a promoter. Genes are made up of little bits called exons, just as paragraphs are made up of sentences. Some genes are gigantic; the gene whose mutation causes muscular dystrophy, for instance, would be equivalent to a paragraph about 158 pages long. Other genes are tiny, similar to a short phrase.

We all carry hundreds and hundreds of typographical errors in our personal encyclopedia, some of them inactivating the gene paragraph that contains them. Fortunately, the errors we inherit from our mothers are generally not matched by the errors we inherit from our fathers. Every once in a while, though, we choose a mate with a gene mutation in the same paragraph. When this occurs, the baby does not have a “backup” copy of the intact gene paragraph, and a recessive disease can occur.

Such unfortunate pairings happen more often in couples of similar ethnicity because many gene mutations are ancestral in a given ethnic population. Thus, one of our roles in preconceptual counseling is to think about the possibility that a patient who wants to discontinue birth control and start a family might carry a gene mutation for an inherited disorder common to his or her ethnic background.

In couples of Northern European ancestry, we think first of cystic fibrosis (with a carrier frequency of about 1 in 29 in the United States) and spinal muscular atrophy (1 in 5). In African Americans, we worry about sickle cell anemia (1 in 22).

If our patients have Southeast Asian ancestry, we should consider α-thalassemia (1 in 30), and for patients with Mediterranean ancestry, β-thalassemia. For patients of Ashkenazi Jewish ancestry, genetic screening is performed routinely for the ancestral mutations causing Tay-Sachs disease, familial dysautonomia, Gaucher's disease type 1, Niemann-Pick disease, Bloom syndrome, Canavan disease, and cystic fibrosis.

When we perform PGD, the testing is done overnight. Couples follow the same process that any infertile couple undergoing in vitro fertilization (IVF) would follow, but before implantation, a single cell is taken for analysis from each embryo in its day-3, eight-cell stage. The single-cell samples are sent by courier to a reference laboratory for overnight testing, and a report is electronically sent to the reproductive endocrinologist. Couples are notified of the results in time for embryo transfer on day 5.

In the future, we may be able to relax the timeline and allow more time for embryo transfer by performing the biopsies when the embryo is 5 days old. In this procedure, cells would be taken from the trophectoderm—the outer layer of the embryo that ultimately develops into the placenta—and the embryos would be frozen via a rapid freezing process called vitrification.

Ice crystals do not form in this method, so concerns about damage to the cells is alleviated. Women could then undergo embryo transfer the next month. For now, however, we follow a 5-day deadline for embryo transfer.

Regardless of what advances are made, we must appreciate the fact that this technology pushes medical diagnostics to its limits. PGD involves the testing of one single cell (the smallest unit of life) and one gene (the smallest unit of inheritance), for one typographical error in 3.3 billion DNA letters, and all of this occurs overnight.

Its Value and Accuracy

The nomenclature of what we have simply and rather loosely called PGD is actually changing a bit. Following Europe's lead, U.S. experts are beginning to use the term PGD to refer specifically to the actual diagnosis of a particular disease. PGS (preimplantation genetic screening) is exactly what its name implies as well—screening, largely for abnormal numbers of chromosomes—and not the actual disease diagnosis. Together, the terms fall under the general rubric of preimplantation genetics.

The differentiation is being made because everything about the two procedures—the technology; the people and issues involved; the risks and benefits; and importantly, the accuracy of the procedure—is different. All told, the error rate for preimplantation genetics is in the range of about 2%–4%. Analyzing chromosomes, however, is quite different from analyzing genes, just as counting books of the encyclopedia is quite different from opening a book and finding a letter error.

In analyzing chromosomes, we have to worry about the possibility of complex chromosomal mosaicism having occurred. This is a process by which chromosomes segregate unevenly to cells as the cells are dividing, and if it has occurred, some of the cells we biopsy may appear normal even though the rest of the cells are not.

Experts are increasingly concerned that the chromosome analysis component of preimplantation screening may not really be improving parents' chances of having a healthy baby. However, although the prognostic value of what we now should call PGS is unclear and confusing, there are no such doubts associated with PGD. Telling parents that their baby has a clear 25% chance of having a serious disease is quite different from telling parents that their baby may—or may not—have a chromosomal abnormality.

This is not to say, however, that PGS is without value. I would advise it in cases in which the woman already needs IVF and if she has had recurrent miscarriages.

Ethical Issues and the Future

The real issue with preimplantation genetics, I believe, is whether there are limits to when the technology can and should be used. We must continue, of course, to consider and address the questions associated with PGS and its value. But beyond this, we face numerous questions emanating not as much from a scientific or technologic perspective as from an ethical perspective.

For instance, couples who already have a child with a genetic disease and do not want it to happen again can test their embryos not only to learn which ones carry the genetic defect, but also to learn whether any of their embryos are an identical stem-cell match with their child who is ill.

At the time of delivery, then, they will have not only a healthy baby, but also a baby who can donate identically human leukocyte antigen (HLA)-matched cord blood for stem-cell transplantation to the sibling. Such testing for HLA matching happens daily in the United States.

It is also possible to screen embryos for genes that raise the risk of cancer—primarily breast, ovarian, and colon—in adulthood. We know this is being done in England today, where regulators ruled last year to allow it. The questions are a bit different with this issue, as I see it, because genotype in this case does not accurately predict phenotype. Having the BRCA1 or BRCA2 gene mutation does not mean, for instance, that a person will develop breast or ovarian cancer. So the question really is whether we should be testing embryos for a disease that may never occur.

As in other ethical debates, we must listen to all points of view. Many couples have watched multiple family members die from colon cancer or breast cancer and have decided that enough is enough, whereas other couples who are testing for HLA matching have a child with an incurable, often fatal disease. These couples know there is no such thing as a perfect baby. All they want is to have the A and the G and the T and the C in the right places, or to save their child while having the chance to have another healthy baby to love as well.

Most clinics have ethics teams to develop policies that address these issues and to describe which indications for preimplantation genetics are acceptable and which are not. Most clinics allow the use of technology for finding cancer genes and for HLA matching, for instance, but not for selecting gender.

Studies following children after IVF and preimplantation genetics that have been done in Europe—where the type of medical system allows investigators to effectively track patients for longer-term outcomes—are better than those done in the United States. Clearly, safety and good outcomes have been demonstrated. Thousands and thousands of babies have been born after having undergone IVF and PGS or PGS, with no evidence of birth defects.

Still, experts in the United States have been designing a database—a prospective registry of sorts—that, when implemented, will collect data on the use of preimplantation genetics, primarily regarding how much is being done and for what ends the technology is being used. Such data will help us to further understand and guide this fast-growing facet of reproductive medicine.

A human 8-cell embryo produced routinely in an IVF laboratory is undergoing the biopsy of one blastomere (cell) for testing. Courtesy Dr. Mark R. Hughes

The Quest for Prenatal Evaluation

The quest for fetal and embryonic evaluation has been of great interest to many scientists, physicians, parents, and members of the lay public. It has eventuated into the well-established field of prenatal diagnosis.

The focus, for the most part, has been on gleaning information during the early and midtrimester periods of pregnancy. Such evaluation has been found most useful in providing reassurance to parents when anomalies are excluded, or—under those uncommon circumstances when a diagnosis is made prenatally—in allowing parents and physicians to create appropriate medical and social strategies to deal with these diagnoses.

Despite the benefits afforded by prenatal diagnosis, there remains a subset of the potentially reproductive population for whom conceiving and delivering an abnormal child is not a rare event, but may in fact have a high degree of predictability. These aspiring parents have had to choose among high-risk pregnancy, nonconception, adoption, or egg or sperm donors.

Most recently, however, these patients and their physicians have been able to exploit the new technology of preimplantation genetic diagnosis. This is a rapidly expanding field that has the potential to make a significant difference in the lives of patients who could not otherwise be anywhere near certain that they would deliver a healthy, normal child.

The technology affords us a wide range of possibilities, both now and in the future, but it also presents a number of challenges, including ethical issues, financial coverage issues, and issues concerning the actual availability of the services to select populations and individuals.

This all makes preimplantation genetics quite a complex topic, with great positive potential and a great many implications and potential hurdles and obstacles, all of which must be discussed and deliberated.

It is for this reason that we have invited Dr. Mark R. Hughes, a leading international scholar in the area of preimplantation diagnosis and one of the pioneers of this technology, to serve as the guest author of this month's Master Class.

Currently, Dr. Hughes is the director of the Genesis Genetics Institute in Detroit. He previously served on the faculty of the schools of medicine at Baylor College of Medicine, Georgetown University, and Wayne State University, and was a member of the founding group of the Human Genome Institute at the National Institutes of Health.

It was my job to explain to the baby's parents what the disorder was and how it happened. Many of the babies I saw had an autosomal recessive disorder, and it was necessary to explain to the baby's mother and father how this awful disease suddenly appeared in their child, and tell them that they faced a 25% risk of its happening again should they decide to have more children. Their options for the future, I would tell them, would be to adopt, to elect not have any more children, to use an anonymous donor for eggs or sperm, or—as many couples do—to carefully roll the genetic dice again with hopes of a better outcome.

In the last scenario, I would explain, the parents would have the opportunity to have a chorionic villus sampling or amniocentesis. But it goes without saying that the 12–15 weeks that unfold before such testing is done are often filled with anxiety: first, about having the test, and second, about the decision to be made if the results are not favorable.

Today, obstetricians have good reason to present such parents with another option—preimplantation genetic diagnosis (PGD)–and to be aware of its capabilities and limitations. Developments in PGD mean that we, also, in all of our preconceptual obstetrical work, have good reason to be cognizant of ethnicity-based risks for genetic disorders and to advise patients, when indicated, to have genetic screening themselves.

We can use PGD today, in conjunction with in vitro fertilization, to test for over 250 serious diseases and conditions caused by mutations or chromosomal abnormalities. Parents who choose the technology—usually couples who know they carry mutations or who have had another baby or a family member with a serious inherited illness—can learn that an embryo is free of the disease that their family is prone to, and can thus start a pregnancy with a commitment to continuing it.

The Genetics, the Process

As obstetricians, we are not trained geneticists. Therefore, it is helpful for us and for our patients if we understand the basic genetics behind PGD, and appreciate how PGD pushes diagnostic technology to its absolute limits—both its theoretical limits and its practical limits.

Every cell taken from an embryo (or any cell in our body) contains all the genes needed to make a new, complete individual. Each cell's DNA contains just four letters of the genetic alphabet: A, T, G, and C. The way in which these letters are strung together, just as letters are put together to make a book, will tell that cell what to do.

We can think of chromosomes as books of the gigantic encyclopedia of life, and genes as paragraphs within these chromosome books. Each chromosome has thousands of genes, most of which contribute something unique to the story of who we are, just as most paragraphs in a novel or encyclopedia contribute a unique element to the story or knowledge base. Some genes do not appear to be as important to our health as others, just as some paragraphs seem like “filler” in a story.

All genes have a defined beginning and a defined end, and just as a paragraph has an indentation, a gene has a promoter. Genes are made up of little bits called exons, just as paragraphs are made up of sentences. Some genes are gigantic; the gene whose mutation causes muscular dystrophy, for instance, would be equivalent to a paragraph about 158 pages long. Other genes are tiny, similar to a short phrase.

We all carry hundreds and hundreds of typographical errors in our personal encyclopedia, some of them inactivating the gene paragraph that contains them. Fortunately, the errors we inherit from our mothers are generally not matched by the errors we inherit from our fathers. Every once in a while, though, we choose a mate with a gene mutation in the same paragraph. When this occurs, the baby does not have a “backup” copy of the intact gene paragraph, and a recessive disease can occur.

Such unfortunate pairings happen more often in couples of similar ethnicity because many gene mutations are ancestral in a given ethnic population. Thus, one of our roles in preconceptual counseling is to think about the possibility that a patient who wants to discontinue birth control and start a family might carry a gene mutation for an inherited disorder common to his or her ethnic background.

In couples of Northern European ancestry, we think first of cystic fibrosis (with a carrier frequency of about 1 in 29 in the United States) and spinal muscular atrophy (1 in 5). In African Americans, we worry about sickle cell anemia (1 in 22).

If our patients have Southeast Asian ancestry, we should consider α-thalassemia (1 in 30), and for patients with Mediterranean ancestry, β-thalassemia. For patients of Ashkenazi Jewish ancestry, genetic screening is performed routinely for the ancestral mutations causing Tay-Sachs disease, familial dysautonomia, Gaucher's disease type 1, Niemann-Pick disease, Bloom syndrome, Canavan disease, and cystic fibrosis.

When we perform PGD, the testing is done overnight. Couples follow the same process that any infertile couple undergoing in vitro fertilization (IVF) would follow, but before implantation, a single cell is taken for analysis from each embryo in its day-3, eight-cell stage. The single-cell samples are sent by courier to a reference laboratory for overnight testing, and a report is electronically sent to the reproductive endocrinologist. Couples are notified of the results in time for embryo transfer on day 5.

In the future, we may be able to relax the timeline and allow more time for embryo transfer by performing the biopsies when the embryo is 5 days old. In this procedure, cells would be taken from the trophectoderm—the outer layer of the embryo that ultimately develops into the placenta—and the embryos would be frozen via a rapid freezing process called vitrification.

Ice crystals do not form in this method, so concerns about damage to the cells is alleviated. Women could then undergo embryo transfer the next month. For now, however, we follow a 5-day deadline for embryo transfer.

Regardless of what advances are made, we must appreciate the fact that this technology pushes medical diagnostics to its limits. PGD involves the testing of one single cell (the smallest unit of life) and one gene (the smallest unit of inheritance), for one typographical error in 3.3 billion DNA letters, and all of this occurs overnight.

Its Value and Accuracy

The nomenclature of what we have simply and rather loosely called PGD is actually changing a bit. Following Europe's lead, U.S. experts are beginning to use the term PGD to refer specifically to the actual diagnosis of a particular disease. PGS (preimplantation genetic screening) is exactly what its name implies as well—screening, largely for abnormal numbers of chromosomes—and not the actual disease diagnosis. Together, the terms fall under the general rubric of preimplantation genetics.

The differentiation is being made because everything about the two procedures—the technology; the people and issues involved; the risks and benefits; and importantly, the accuracy of the procedure—is different. All told, the error rate for preimplantation genetics is in the range of about 2%–4%. Analyzing chromosomes, however, is quite different from analyzing genes, just as counting books of the encyclopedia is quite different from opening a book and finding a letter error.

In analyzing chromosomes, we have to worry about the possibility of complex chromosomal mosaicism having occurred. This is a process by which chromosomes segregate unevenly to cells as the cells are dividing, and if it has occurred, some of the cells we biopsy may appear normal even though the rest of the cells are not.

Experts are increasingly concerned that the chromosome analysis component of preimplantation screening may not really be improving parents' chances of having a healthy baby. However, although the prognostic value of what we now should call PGS is unclear and confusing, there are no such doubts associated with PGD. Telling parents that their baby has a clear 25% chance of having a serious disease is quite different from telling parents that their baby may—or may not—have a chromosomal abnormality.

This is not to say, however, that PGS is without value. I would advise it in cases in which the woman already needs IVF and if she has had recurrent miscarriages.

Ethical Issues and the Future

The real issue with preimplantation genetics, I believe, is whether there are limits to when the technology can and should be used. We must continue, of course, to consider and address the questions associated with PGS and its value. But beyond this, we face numerous questions emanating not as much from a scientific or technologic perspective as from an ethical perspective.

For instance, couples who already have a child with a genetic disease and do not want it to happen again can test their embryos not only to learn which ones carry the genetic defect, but also to learn whether any of their embryos are an identical stem-cell match with their child who is ill.

At the time of delivery, then, they will have not only a healthy baby, but also a baby who can donate identically human leukocyte antigen (HLA)-matched cord blood for stem-cell transplantation to the sibling. Such testing for HLA matching happens daily in the United States.

It is also possible to screen embryos for genes that raise the risk of cancer—primarily breast, ovarian, and colon—in adulthood. We know this is being done in England today, where regulators ruled last year to allow it. The questions are a bit different with this issue, as I see it, because genotype in this case does not accurately predict phenotype. Having the BRCA1 or BRCA2 gene mutation does not mean, for instance, that a person will develop breast or ovarian cancer. So the question really is whether we should be testing embryos for a disease that may never occur.

As in other ethical debates, we must listen to all points of view. Many couples have watched multiple family members die from colon cancer or breast cancer and have decided that enough is enough, whereas other couples who are testing for HLA matching have a child with an incurable, often fatal disease. These couples know there is no such thing as a perfect baby. All they want is to have the A and the G and the T and the C in the right places, or to save their child while having the chance to have another healthy baby to love as well.

Most clinics have ethics teams to develop policies that address these issues and to describe which indications for preimplantation genetics are acceptable and which are not. Most clinics allow the use of technology for finding cancer genes and for HLA matching, for instance, but not for selecting gender.

Studies following children after IVF and preimplantation genetics that have been done in Europe—where the type of medical system allows investigators to effectively track patients for longer-term outcomes—are better than those done in the United States. Clearly, safety and good outcomes have been demonstrated. Thousands and thousands of babies have been born after having undergone IVF and PGS or PGS, with no evidence of birth defects.

Still, experts in the United States have been designing a database—a prospective registry of sorts—that, when implemented, will collect data on the use of preimplantation genetics, primarily regarding how much is being done and for what ends the technology is being used. Such data will help us to further understand and guide this fast-growing facet of reproductive medicine.

A human 8-cell embryo produced routinely in an IVF laboratory is undergoing the biopsy of one blastomere (cell) for testing. Courtesy Dr. Mark R. Hughes

The Quest for Prenatal Evaluation

The quest for fetal and embryonic evaluation has been of great interest to many scientists, physicians, parents, and members of the lay public. It has eventuated into the well-established field of prenatal diagnosis.

The focus, for the most part, has been on gleaning information during the early and midtrimester periods of pregnancy. Such evaluation has been found most useful in providing reassurance to parents when anomalies are excluded, or—under those uncommon circumstances when a diagnosis is made prenatally—in allowing parents and physicians to create appropriate medical and social strategies to deal with these diagnoses.

Despite the benefits afforded by prenatal diagnosis, there remains a subset of the potentially reproductive population for whom conceiving and delivering an abnormal child is not a rare event, but may in fact have a high degree of predictability. These aspiring parents have had to choose among high-risk pregnancy, nonconception, adoption, or egg or sperm donors.

Most recently, however, these patients and their physicians have been able to exploit the new technology of preimplantation genetic diagnosis. This is a rapidly expanding field that has the potential to make a significant difference in the lives of patients who could not otherwise be anywhere near certain that they would deliver a healthy, normal child.

The technology affords us a wide range of possibilities, both now and in the future, but it also presents a number of challenges, including ethical issues, financial coverage issues, and issues concerning the actual availability of the services to select populations and individuals.

This all makes preimplantation genetics quite a complex topic, with great positive potential and a great many implications and potential hurdles and obstacles, all of which must be discussed and deliberated.

It is for this reason that we have invited Dr. Mark R. Hughes, a leading international scholar in the area of preimplantation diagnosis and one of the pioneers of this technology, to serve as the guest author of this month's Master Class.

Currently, Dr. Hughes is the director of the Genesis Genetics Institute in Detroit. He previously served on the faculty of the schools of medicine at Baylor College of Medicine, Georgetown University, and Wayne State University, and was a member of the founding group of the Human Genome Institute at the National Institutes of Health.

Too often, women with chronic pelvic pain will have a barium enema to rule out a gastrointestinal cause, an intravenous pyelogram to rule out urinary tract disease, and a host of other diagnostic tests that are neither efficient nor effective because they have not been driven specifically by the findings of a history and physical exam. Most gastrointestinal causes of pelvic pain, in fact, cannot be diagnosed by a barium enema, and most urologic causes cannot be determined through an IVP. The same holds true for other tests.

Such a rule-out approach may seem appropriate up front, but it actually is much less efficient—and quite often less accurate—than a stepwise, deliberate approach to history-taking and physical examination.

With the correct approach, we can successfully evaluate most patients with chronic pelvic pain in a 45-minute visit—which is an achievement, considering that many disorders of the reproductive tract, gastrointestinal system, urologic organs, musculoskeletal system, and psychoneurologic system may be associated with the disorder.

Behind the Diagnostic Approach

After years of treating patients with chronic pelvic pain, I still am struck by the fact that among women of reproductive age, the disorder has about the same prevalence as do asthma, migraine headache, and low-back pain. It is a significant cause of all referrals to gynecologists, and the etiology is usually not immediately discernible. More often than not, chronic pelvic pain is caused by or associated with several diagnoses or disorders.

One woman, for instance, might have endometriosis, irritable bowel syndrome, and emotional stresses, all of which could be contributing to her chronic pelvic pain.

We lack a universally accepted definition of chronic pelvic pain, but we come closest, I believe, with a definition described in a practice bulletin published by the American College of Gynecologists and Obstetricians in 2004.

The definition is based primarily on the duration, location, and severity of the pain. It says that chronic pelvic pain is noncyclic pain of 6 or more months' duration that is localized to the true anatomical pelvis; the anterior abdominal wall at or below the umbilicus; the lumbosacral back; or the buttocks. The pain must be severe enough to cause functional disability or require medical care.

Some experts include chronic vulvar pain in their definition of chronic pelvic pain, but many do not—and the latter sentiment is reflected in ACOG's definition. According to the bulletin, approximately 15%–20% of women aged 18–50 years have chronic pelvic pain that lasts longer than 1 year.

It is less clear what proportions of women with chronic pelvic pain have specific diagnoses. We do know, however, that the gastrointestinal tract and urinary tract are just as important—if not more important—than the reproductive tract in its diagnosis. One study using a large, primary care database in the United Kingdom found that diagnoses related to the GI and urinary tracts were significantly more common than gynecologic diagnoses (approximately 38% GI, 31% urinary, and 20% gynecologic).

Again, the message for us is significant: We need to conduct a comprehensive review, through a history and physical exam, of all the systems—not only the reproductive tract—that are potentially involved in chronic pelvic pain.

The History and Exam

One of the fundamental components of the diagnostic approach is a pelvic pain intake questionnaire. Questionnaires are so commonly used in medicine today that they generally are well received by patients, and although they are not at all meant to take the place of listening to the patient tell her story, they can be quite helpful in securing details of your patient's obstetric and other medical and psychosocial history as well as the location, severity, quality, and timing of her pain. The International Pelvic Pain Society offers a useful form that can be downloaded free of charge.

It can also be useful to ask your patient to mark the location of her pain on a pain map, indicating whether it is external or internal, and whether it is sharp, dull, numb, or prickly. Other evaluation instruments, such as the visual analog scale, may also be used to assess pain severity. In addition, it can be useful to ask the patient how long the pain lasts when it occurs, how much it affects her daily life, and how the pain has changed over time.

When it comes to the physical exam of a patient with chronic pelvic pain, we need to think a little differently than we would in other scenarios and with other classic exam techniques. One of our major goals with chronic pelvic pain is to detect exact locations of tenderness and correlate these with areas of pain, so we need to think of our exam as an attempt to map the patient's pain.

This means that we must take a systematic, step-by-step approach to reproducing the pain through gentle palpations and physical positioning and maneuvering.

When I do an examination, I divide it into standing, sitting, supine, and lithotomy exams. The standing exam is mainly an evaluation for musculoskeletal problems, and should specifically seek evidence of abdominal, inguinal, or femoral hernias; fibromyalgia; lumbosacral disk disease; short leg syndrome; and postural abnormalities.

The supine exam consists of a series of maneuvers and tests, from active leg flexion and obturator and psoas sign testing, to abdominal palpation and groin and pubic symphysis evaluation. It is important to initially palpate the abdominal wall with a light touch—almost superficially at first—while you note hyperesthesias or hypersensitivity of the skin and check for superficial abdominal reflexes. Then use single-digit palpation to look for myofascial or trigger-point pain.

An abdominal wall-tenderness test (known as Carnett's test), in which the patient tenses her abdominal muscles while you palpate an area of tenderness, can be used to distinguish myofascial tenderness or trigger points from visceral tenderness. Pain that increases during the test is usually of myofascial origin, or comes from the abdominal wall itself. If the pain is decreased or unchanged, it likely is not myofascial.

Myofascial pain is most often related to trigger points and can be the result of hernias, hematomas, infections, or trauma.

It is important also to specifically evaluate any scars for abnormal tenderness.

Once you have moved through these components, you can finish the supine examination with a more classic approach aimed at detecting distention, masses, ascites, and other irregularities.

The most important thing to consider for the pelvic examination is that it should always be done with a single finger on a single hand. The objective is to identify focal areas of abnormal tenderness in any pelvic structure. This includes the pelvic floor muscles (levators, piriformis, obturators), rectovaginal septum, cul-de-sac, vulvar vestibule, urethra, bladder, Alcock's canal, uterosacral ligaments, cervix, lower uterine segment, uterine fundus, adnexae, pelvic ureters, anus, coccyx, and rectum.

Beyond the Physical Exam

It is then appropriate to perform laboratory and other diagnostic tests as indicated by the history and physical exam. Overall, such tests do not add much to the evaluation. They are important, however, for ruling out potentially life-threatening conditions or for verifying suspected diagnoses.

If you think your patient has interstitial cystitis, for example, you would probably move on to cystoscopy or potassium sensitivity testing. If you think your patient has endometriosis, you may perform a laparoscopy. If colorectal cancer is a concern, then referral for a colonoscopy might be the best option.

In general, we should be guided in our differential diagnosis by seeking those diagnoses for which we have the best evidence of causal or associative roles in chronic pelvic pain. These include interstitial cystitis, irritable bowel syndrome, endometriosis, depression, myofascial pain, and chronic pain syndrome. This does not mean we will never diagnose disorders for which the evidence of association with chronic pelvic pain is weak; it just means that these are not the diagnoses that we should seek initially.

We must not be surprised, moreover, when our patients have more than one diagnosis. In fact, we should anticipate and expect more than one. And more often than not, the pain itself will be a diagnosis and not just a symptom. Although it is frustrating to us and to our patients, in some cases chronic pain syndrome may be the only diagnosis that can be confirmed.

An Individual's Pain, Society's Pain

Chronic pelvic pain is a staggering problem. Medical costs have been estimated at $1–$2 billion per year. Missed work and decreased productivity are believed to affect business negatively at a cost of $15 billion per year. Chronic pelvic pain is responsible for 10% of ambulatory referrals to gynecologists, 20% of all hysterectomies for benign disease, and 40% of all laparoscopies. Moreover, 15% of women have reported chronic pelvic pain within the past 3 months.

Despite this, we as physicians do a poor job of diagnosing and managing chronic pelvic pain. Several reasons, including the following, account for this shortcoming:

▸ Chronic pelvic pain patients require a real time commitment. Because time is our greatest commodity, the lengthy process of reviewing voluminous records, taking a detailed history, and carrying out a meticulous examination can be quite exasperating for a busy practitioner.

▸ Evaluation and treatment generally reflect our training. That is, we tend to make gynecology-related diagnoses and to recommend treatment within our skill set, just as urologists and gastroenterologists would make GU- and GI-related diagnoses and treatment recommendations.

▸ Once a diagnosis has been made, physicians have a tendency to stay with the diagnosis; they do not reinvestigate for other causes. Unfortunately, chronic pelvic pain can have multiple etiologies.

▸ Physicians can be uncomfortable initiating a discussion of abuse issues with their patients, thus omitting the evaluation of a very real aspect of chronic pelvic pain.

I have asked Dr. Fred Howard to present the first of two articles for the Master Class in gynecologic surgery. In this article, he discusses the diagnostic approach to chronic pelvic pain; in April, he will present therapeutic options.

Dr. Howard, who is associate chair for academic affairs, director of the division of gynecologic specialists, and professor of ob.gyn. at the University of Rochester (N.Y.), is a world leader in the arena of chronic pelvic pain. Not only has he authored numerous peer-reviewed journal articles and book chapters on the condition, but he is also the coeditor of one of the essential authoritative resources on the subject, “Pelvic Pain: Diagnosis and Management” (Philadelphia: Lippincott Williams & Wilkins, 2000).

Main Concepts For Evaluations

▸ Obtain a thorough and complete history in the following areas:

Pain

Gynecologic

Gastrointestinal

Urinary

Musculoskeletal

Psychological

Neurologic

Prior evaluations

Prior treatments

▸ Use a questionnaire.

▸ Direct the physical examination to “pain mapping.”

▸ Do not expect laboratory and imaging studies to add much to your evaluation:

Order tests that are needed to rule out life-threatening diseases.

Order tests that will definitively confirm your clinical diagnoses.

▸ Expect common diagnoses that have level A evidence of association with CPP:

Irritable bowel syndrome

Interstitial cystitis

Myofascial trigger points

Depression

Endometriosis

Chronic pain syndrome

▸ Expect more than one diagnosis.

▸ Appreciate that chronic pain syndrome is often a diagnosis.

▸ Do not assume that laparoscopy is essential; it is usually not needed for a diagnosis.

Too often, women with chronic pelvic pain will have a barium enema to rule out a gastrointestinal cause, an intravenous pyelogram to rule out urinary tract disease, and a host of other diagnostic tests that are neither efficient nor effective because they have not been driven specifically by the findings of a history and physical exam. Most gastrointestinal causes of pelvic pain, in fact, cannot be diagnosed by a barium enema, and most urologic causes cannot be determined through an IVP. The same holds true for other tests.

Such a rule-out approach may seem appropriate up front, but it actually is much less efficient—and quite often less accurate—than a stepwise, deliberate approach to history-taking and physical examination.

With the correct approach, we can successfully evaluate most patients with chronic pelvic pain in a 45-minute visit—which is an achievement, considering that many disorders of the reproductive tract, gastrointestinal system, urologic organs, musculoskeletal system, and psychoneurologic system may be associated with the disorder.

Behind the Diagnostic Approach

After years of treating patients with chronic pelvic pain, I still am struck by the fact that among women of reproductive age, the disorder has about the same prevalence as do asthma, migraine headache, and low-back pain. It is a significant cause of all referrals to gynecologists, and the etiology is usually not immediately discernible. More often than not, chronic pelvic pain is caused by or associated with several diagnoses or disorders.

One woman, for instance, might have endometriosis, irritable bowel syndrome, and emotional stresses, all of which could be contributing to her chronic pelvic pain.

We lack a universally accepted definition of chronic pelvic pain, but we come closest, I believe, with a definition described in a practice bulletin published by the American College of Gynecologists and Obstetricians in 2004.

The definition is based primarily on the duration, location, and severity of the pain. It says that chronic pelvic pain is noncyclic pain of 6 or more months' duration that is localized to the true anatomical pelvis; the anterior abdominal wall at or below the umbilicus; the lumbosacral back; or the buttocks. The pain must be severe enough to cause functional disability or require medical care.

Some experts include chronic vulvar pain in their definition of chronic pelvic pain, but many do not—and the latter sentiment is reflected in ACOG's definition. According to the bulletin, approximately 15%–20% of women aged 18–50 years have chronic pelvic pain that lasts longer than 1 year.

It is less clear what proportions of women with chronic pelvic pain have specific diagnoses. We do know, however, that the gastrointestinal tract and urinary tract are just as important—if not more important—than the reproductive tract in its diagnosis. One study using a large, primary care database in the United Kingdom found that diagnoses related to the GI and urinary tracts were significantly more common than gynecologic diagnoses (approximately 38% GI, 31% urinary, and 20% gynecologic).

Again, the message for us is significant: We need to conduct a comprehensive review, through a history and physical exam, of all the systems—not only the reproductive tract—that are potentially involved in chronic pelvic pain.

The History and Exam

One of the fundamental components of the diagnostic approach is a pelvic pain intake questionnaire. Questionnaires are so commonly used in medicine today that they generally are well received by patients, and although they are not at all meant to take the place of listening to the patient tell her story, they can be quite helpful in securing details of your patient's obstetric and other medical and psychosocial history as well as the location, severity, quality, and timing of her pain. The International Pelvic Pain Society offers a useful form that can be downloaded free of charge.

It can also be useful to ask your patient to mark the location of her pain on a pain map, indicating whether it is external or internal, and whether it is sharp, dull, numb, or prickly. Other evaluation instruments, such as the visual analog scale, may also be used to assess pain severity. In addition, it can be useful to ask the patient how long the pain lasts when it occurs, how much it affects her daily life, and how the pain has changed over time.

When it comes to the physical exam of a patient with chronic pelvic pain, we need to think a little differently than we would in other scenarios and with other classic exam techniques. One of our major goals with chronic pelvic pain is to detect exact locations of tenderness and correlate these with areas of pain, so we need to think of our exam as an attempt to map the patient's pain.

This means that we must take a systematic, step-by-step approach to reproducing the pain through gentle palpations and physical positioning and maneuvering.

When I do an examination, I divide it into standing, sitting, supine, and lithotomy exams. The standing exam is mainly an evaluation for musculoskeletal problems, and should specifically seek evidence of abdominal, inguinal, or femoral hernias; fibromyalgia; lumbosacral disk disease; short leg syndrome; and postural abnormalities.

The supine exam consists of a series of maneuvers and tests, from active leg flexion and obturator and psoas sign testing, to abdominal palpation and groin and pubic symphysis evaluation. It is important to initially palpate the abdominal wall with a light touch—almost superficially at first—while you note hyperesthesias or hypersensitivity of the skin and check for superficial abdominal reflexes. Then use single-digit palpation to look for myofascial or trigger-point pain.

An abdominal wall-tenderness test (known as Carnett's test), in which the patient tenses her abdominal muscles while you palpate an area of tenderness, can be used to distinguish myofascial tenderness or trigger points from visceral tenderness. Pain that increases during the test is usually of myofascial origin, or comes from the abdominal wall itself. If the pain is decreased or unchanged, it likely is not myofascial.

Myofascial pain is most often related to trigger points and can be the result of hernias, hematomas, infections, or trauma.

It is important also to specifically evaluate any scars for abnormal tenderness.

Once you have moved through these components, you can finish the supine examination with a more classic approach aimed at detecting distention, masses, ascites, and other irregularities.

The most important thing to consider for the pelvic examination is that it should always be done with a single finger on a single hand. The objective is to identify focal areas of abnormal tenderness in any pelvic structure. This includes the pelvic floor muscles (levators, piriformis, obturators), rectovaginal septum, cul-de-sac, vulvar vestibule, urethra, bladder, Alcock's canal, uterosacral ligaments, cervix, lower uterine segment, uterine fundus, adnexae, pelvic ureters, anus, coccyx, and rectum.

Beyond the Physical Exam

It is then appropriate to perform laboratory and other diagnostic tests as indicated by the history and physical exam. Overall, such tests do not add much to the evaluation. They are important, however, for ruling out potentially life-threatening conditions or for verifying suspected diagnoses.

If you think your patient has interstitial cystitis, for example, you would probably move on to cystoscopy or potassium sensitivity testing. If you think your patient has endometriosis, you may perform a laparoscopy. If colorectal cancer is a concern, then referral for a colonoscopy might be the best option.

In general, we should be guided in our differential diagnosis by seeking those diagnoses for which we have the best evidence of causal or associative roles in chronic pelvic pain. These include interstitial cystitis, irritable bowel syndrome, endometriosis, depression, myofascial pain, and chronic pain syndrome. This does not mean we will never diagnose disorders for which the evidence of association with chronic pelvic pain is weak; it just means that these are not the diagnoses that we should seek initially.

We must not be surprised, moreover, when our patients have more than one diagnosis. In fact, we should anticipate and expect more than one. And more often than not, the pain itself will be a diagnosis and not just a symptom. Although it is frustrating to us and to our patients, in some cases chronic pain syndrome may be the only diagnosis that can be confirmed.

An Individual's Pain, Society's Pain

Chronic pelvic pain is a staggering problem. Medical costs have been estimated at $1–$2 billion per year. Missed work and decreased productivity are believed to affect business negatively at a cost of $15 billion per year. Chronic pelvic pain is responsible for 10% of ambulatory referrals to gynecologists, 20% of all hysterectomies for benign disease, and 40% of all laparoscopies. Moreover, 15% of women have reported chronic pelvic pain within the past 3 months.

Despite this, we as physicians do a poor job of diagnosing and managing chronic pelvic pain. Several reasons, including the following, account for this shortcoming:

▸ Chronic pelvic pain patients require a real time commitment. Because time is our greatest commodity, the lengthy process of reviewing voluminous records, taking a detailed history, and carrying out a meticulous examination can be quite exasperating for a busy practitioner.

▸ Evaluation and treatment generally reflect our training. That is, we tend to make gynecology-related diagnoses and to recommend treatment within our skill set, just as urologists and gastroenterologists would make GU- and GI-related diagnoses and treatment recommendations.

▸ Once a diagnosis has been made, physicians have a tendency to stay with the diagnosis; they do not reinvestigate for other causes. Unfortunately, chronic pelvic pain can have multiple etiologies.

▸ Physicians can be uncomfortable initiating a discussion of abuse issues with their patients, thus omitting the evaluation of a very real aspect of chronic pelvic pain.

I have asked Dr. Fred Howard to present the first of two articles for the Master Class in gynecologic surgery. In this article, he discusses the diagnostic approach to chronic pelvic pain; in April, he will present therapeutic options.

Dr. Howard, who is associate chair for academic affairs, director of the division of gynecologic specialists, and professor of ob.gyn. at the University of Rochester (N.Y.), is a world leader in the arena of chronic pelvic pain. Not only has he authored numerous peer-reviewed journal articles and book chapters on the condition, but he is also the coeditor of one of the essential authoritative resources on the subject, “Pelvic Pain: Diagnosis and Management” (Philadelphia: Lippincott Williams & Wilkins, 2000).

Main Concepts For Evaluations

▸ Obtain a thorough and complete history in the following areas:

Pain

Gynecologic

Gastrointestinal

Urinary

Musculoskeletal

Psychological

Neurologic

Prior evaluations

Prior treatments

▸ Use a questionnaire.

▸ Direct the physical examination to “pain mapping.”

▸ Do not expect laboratory and imaging studies to add much to your evaluation:

Order tests that are needed to rule out life-threatening diseases.

Order tests that will definitively confirm your clinical diagnoses.

▸ Expect common diagnoses that have level A evidence of association with CPP:

Irritable bowel syndrome

Interstitial cystitis

Myofascial trigger points

Depression

Endometriosis

Chronic pain syndrome

▸ Expect more than one diagnosis.

▸ Appreciate that chronic pain syndrome is often a diagnosis.

▸ Do not assume that laparoscopy is essential; it is usually not needed for a diagnosis.

Too often, women with chronic pelvic pain will have a barium enema to rule out a gastrointestinal cause, an intravenous pyelogram to rule out urinary tract disease, and a host of other diagnostic tests that are neither efficient nor effective because they have not been driven specifically by the findings of a history and physical exam. Most gastrointestinal causes of pelvic pain, in fact, cannot be diagnosed by a barium enema, and most urologic causes cannot be determined through an IVP. The same holds true for other tests.

Such a rule-out approach may seem appropriate up front, but it actually is much less efficient—and quite often less accurate—than a stepwise, deliberate approach to history-taking and physical examination.

With the correct approach, we can successfully evaluate most patients with chronic pelvic pain in a 45-minute visit—which is an achievement, considering that many disorders of the reproductive tract, gastrointestinal system, urologic organs, musculoskeletal system, and psychoneurologic system may be associated with the disorder.

Behind the Diagnostic Approach

After years of treating patients with chronic pelvic pain, I still am struck by the fact that among women of reproductive age, the disorder has about the same prevalence as do asthma, migraine headache, and low-back pain. It is a significant cause of all referrals to gynecologists, and the etiology is usually not immediately discernible. More often than not, chronic pelvic pain is caused by or associated with several diagnoses or disorders.

One woman, for instance, might have endometriosis, irritable bowel syndrome, and emotional stresses, all of which could be contributing to her chronic pelvic pain.

We lack a universally accepted definition of chronic pelvic pain, but we come closest, I believe, with a definition described in a practice bulletin published by the American College of Gynecologists and Obstetricians in 2004.

The definition is based primarily on the duration, location, and severity of the pain. It says that chronic pelvic pain is noncyclic pain of 6 or more months' duration that is localized to the true anatomical pelvis; the anterior abdominal wall at or below the umbilicus; the lumbosacral back; or the buttocks. The pain must be severe enough to cause functional disability or require medical care.

Some experts include chronic vulvar pain in their definition of chronic pelvic pain, but many do not—and the latter sentiment is reflected in ACOG's definition. According to the bulletin, approximately 15%–20% of women aged 18–50 years have chronic pelvic pain that lasts longer than 1 year.

It is less clear what proportions of women with chronic pelvic pain have specific diagnoses. We do know, however, that the gastrointestinal tract and urinary tract are just as important—if not more important—than the reproductive tract in its diagnosis. One study using a large, primary care database in the United Kingdom found that diagnoses related to the GI and urinary tracts were significantly more common than gynecologic diagnoses (approximately 38% GI, 31% urinary, and 20% gynecologic).

Again, the message for us is significant: We need to conduct a comprehensive review, through a history and physical exam, of all the systems—not only the reproductive tract—that are potentially involved in chronic pelvic pain.

The History and Exam

One of the fundamental components of the diagnostic approach is a pelvic pain intake questionnaire. Questionnaires are so commonly used in medicine today that they generally are well received by patients, and although they are not at all meant to take the place of listening to the patient tell her story, they can be quite helpful in securing details of your patient's obstetric and other medical and psychosocial history as well as the location, severity, quality, and timing of her pain. The International Pelvic Pain Society offers a useful form that can be downloaded free of charge.

It can also be useful to ask your patient to mark the location of her pain on a pain map, indicating whether it is external or internal, and whether it is sharp, dull, numb, or prickly. Other evaluation instruments, such as the visual analog scale, may also be used to assess pain severity. In addition, it can be useful to ask the patient how long the pain lasts when it occurs, how much it affects her daily life, and how the pain has changed over time.

When it comes to the physical exam of a patient with chronic pelvic pain, we need to think a little differently than we would in other scenarios and with other classic exam techniques. One of our major goals with chronic pelvic pain is to detect exact locations of tenderness and correlate these with areas of pain, so we need to think of our exam as an attempt to map the patient's pain.

This means that we must take a systematic, step-by-step approach to reproducing the pain through gentle palpations and physical positioning and maneuvering.

When I do an examination, I divide it into standing, sitting, supine, and lithotomy exams. The standing exam is mainly an evaluation for musculoskeletal problems, and should specifically seek evidence of abdominal, inguinal, or femoral hernias; fibromyalgia; lumbosacral disk disease; short leg syndrome; and postural abnormalities.

The supine exam consists of a series of maneuvers and tests, from active leg flexion and obturator and psoas sign testing, to abdominal palpation and groin and pubic symphysis evaluation. It is important to initially palpate the abdominal wall with a light touch—almost superficially at first—while you note hyperesthesias or hypersensitivity of the skin and check for superficial abdominal reflexes. Then use single-digit palpation to look for myofascial or trigger-point pain.

An abdominal wall-tenderness test (known as Carnett's test), in which the patient tenses her abdominal muscles while you palpate an area of tenderness, can be used to distinguish myofascial tenderness or trigger points from visceral tenderness. Pain that increases during the test is usually of myofascial origin, or comes from the abdominal wall itself. If the pain is decreased or unchanged, it likely is not myofascial.

Myofascial pain is most often related to trigger points and can be the result of hernias, hematomas, infections, or trauma.

It is important also to specifically evaluate any scars for abnormal tenderness.

Once you have moved through these components, you can finish the supine examination with a more classic approach aimed at detecting distention, masses, ascites, and other irregularities.

The most important thing to consider for the pelvic examination is that it should always be done with a single finger on a single hand. The objective is to identify focal areas of abnormal tenderness in any pelvic structure. This includes the pelvic floor muscles (levators, piriformis, obturators), rectovaginal septum, cul-de-sac, vulvar vestibule, urethra, bladder, Alcock's canal, uterosacral ligaments, cervix, lower uterine segment, uterine fundus, adnexae, pelvic ureters, anus, coccyx, and rectum.

Beyond the Physical Exam

It is then appropriate to perform laboratory and other diagnostic tests as indicated by the history and physical exam. Overall, such tests do not add much to the evaluation. They are important, however, for ruling out potentially life-threatening conditions or for verifying suspected diagnoses.

If you think your patient has interstitial cystitis, for example, you would probably move on to cystoscopy or potassium sensitivity testing. If you think your patient has endometriosis, you may perform a laparoscopy. If colorectal cancer is a concern, then referral for a colonoscopy might be the best option.

In general, we should be guided in our differential diagnosis by seeking those diagnoses for which we have the best evidence of causal or associative roles in chronic pelvic pain. These include interstitial cystitis, irritable bowel syndrome, endometriosis, depression, myofascial pain, and chronic pain syndrome. This does not mean we will never diagnose disorders for which the evidence of association with chronic pelvic pain is weak; it just means that these are not the diagnoses that we should seek initially.

We must not be surprised, moreover, when our patients have more than one diagnosis. In fact, we should anticipate and expect more than one. And more often than not, the pain itself will be a diagnosis and not just a symptom. Although it is frustrating to us and to our patients, in some cases chronic pain syndrome may be the only diagnosis that can be confirmed.

An Individual's Pain, Society's Pain

Chronic pelvic pain is a staggering problem. Medical costs have been estimated at $1–$2 billion per year. Missed work and decreased productivity are believed to affect business negatively at a cost of $15 billion per year. Chronic pelvic pain is responsible for 10% of ambulatory referrals to gynecologists, 20% of all hysterectomies for benign disease, and 40% of all laparoscopies. Moreover, 15% of women have reported chronic pelvic pain within the past 3 months.

Despite this, we as physicians do a poor job of diagnosing and managing chronic pelvic pain. Several reasons, including the following, account for this shortcoming:

▸ Chronic pelvic pain patients require a real time commitment. Because time is our greatest commodity, the lengthy process of reviewing voluminous records, taking a detailed history, and carrying out a meticulous examination can be quite exasperating for a busy practitioner.

▸ Evaluation and treatment generally reflect our training. That is, we tend to make gynecology-related diagnoses and to recommend treatment within our skill set, just as urologists and gastroenterologists would make GU- and GI-related diagnoses and treatment recommendations.

▸ Once a diagnosis has been made, physicians have a tendency to stay with the diagnosis; they do not reinvestigate for other causes. Unfortunately, chronic pelvic pain can have multiple etiologies.

▸ Physicians can be uncomfortable initiating a discussion of abuse issues with their patients, thus omitting the evaluation of a very real aspect of chronic pelvic pain.

I have asked Dr. Fred Howard to present the first of two articles for the Master Class in gynecologic surgery. In this article, he discusses the diagnostic approach to chronic pelvic pain; in April, he will present therapeutic options.

Dr. Howard, who is associate chair for academic affairs, director of the division of gynecologic specialists, and professor of ob.gyn. at the University of Rochester (N.Y.), is a world leader in the arena of chronic pelvic pain. Not only has he authored numerous peer-reviewed journal articles and book chapters on the condition, but he is also the coeditor of one of the essential authoritative resources on the subject, “Pelvic Pain: Diagnosis and Management” (Philadelphia: Lippincott Williams & Wilkins, 2000).

Main Concepts For Evaluations

▸ Obtain a thorough and complete history in the following areas:

Pain

Gynecologic

Gastrointestinal

Urinary

Musculoskeletal

Psychological

Neurologic

Prior evaluations

Prior treatments

▸ Use a questionnaire.

▸ Direct the physical examination to “pain mapping.”

▸ Do not expect laboratory and imaging studies to add much to your evaluation:

Order tests that are needed to rule out life-threatening diseases.

Order tests that will definitively confirm your clinical diagnoses.

▸ Expect common diagnoses that have level A evidence of association with CPP:

Irritable bowel syndrome

Interstitial cystitis

Myofascial trigger points

Depression

Endometriosis

Chronic pain syndrome

▸ Expect more than one diagnosis.

▸ Appreciate that chronic pain syndrome is often a diagnosis.

▸ Do not assume that laparoscopy is essential; it is usually not needed for a diagnosis.

The American College of Obstetricians and Gynecologists (ACOG) has described examples of commonly accepted indications, contraindications, and clinical conditions requiring special attention for an induction of labor. (See box p. 37.) We must remember that indications for labor induction are often not absolute and need to take maternal and fetal conditions, gestational age, and cervical status into account. Many contraindications are the same as those for either spontaneous labor or vaginal delivery; several obstetric conditions are not contraindications, but do necessitate special attention.

In 1988, the National Center for Health Statistics began requiring hospitals to indicate on birth certificates whether labor was induced or not. This requirement has provided us with remarkable insight into labor induction rates—insight that should cause us to pause, to reflect on available data and our own practices, and to demand that the issue receive more widespread attention.

Over a 10-year period beginning in 1989, the rate of labor induction doubled from about 9% to almost 19% of live births. (See chart.) The trend steadily continued into the new millennium, to the point where, in 2003, nearly 23% of all births involved induction of labor. Clearly, labor induction is one of the most common procedures in obstetrics.

Examining the Increase

The reasons for this significant increase over just 15 years relate to the availability of FDA-approved cervical ripening agents; to both the patient's desire and the physician's convenience; to the acceptance of added risks of cesarean delivery; and to increases in marginal or elective inductions for term pregnancies, especially those past 40 weeks. Inductions in which the reason is not evidence based now account for at least half of all term inductions, or up to 10% of all deliveries. The increase in medically indicated inductions was slower than the overall increase, suggesting that inductions for marginal or elective reasons have risen more rapidly.

Also contributing to the rising rate in inductions is our increasing success with cervical ripening and the fact that, in the current era of ultrasound availability and a more accurate dating of gestational age, we have had to worry less about iatrogenic prematurity.

When considering labor induction, we can view “elective” and “marginal” indications as being very similar, or we can differentiate the two, with “elective” meaning there is no plausible medical or obstetric reason for the induction, and “marginal” referring to cases in which obstetricians face or suspect problems but have no data to suggest that the benefits of labor induction outweigh the risks. I believe it is valuable to consider the terms separately as we attempt to understand the changes in induction rates.

Marginal indications include gestational hypertension; unexplained and mild fetal-growth restriction; idiopathic decreased amniotic fluid (which does not pose substantial danger unless it is accompanied by a recognized complication, such as hypertension or a small-for-gestational-age baby); and a pregnancy beyond 40 weeks. Prospective studies to recommend induction for these and other marginal indications are limited in size or design, or are nonexistent.

There is some rationale behind induction for suspected fetal macrosomia in nondiabetic pregnancies. Theoretically, eliminating further fetal growth should reduce the risks of shoulder dystocia and perhaps of cesarean delivery. However, there is no evidence-based justification for labor induction in these patients. Studies have shown, in fact, that the procedure approximately doubles the cesarean delivery risk, does not reduce neonatal morbidity, and does not appear to reduce the risk of shoulder dystocia.

There is also no published evidence to support the induction of labor for preterm mild preeclampsia, prior shoulder dystocia, and prior cephalopelvic disproportion.

ACOG weighed into the issue by approving “logistic reasons” for labor induction, such as a risk of rapid labor, a patient's unacceptable distance from the hospital, and psychosocial indications. This has left ob.gyns. with a substantial amount of latitude. For instance, one could argue that “psychosocial” reasons could include alleviating the concerns of a mother who previously had a stillborn infant, or alleviating the anxiety of a woman whose spouse is scheduled for deployment to Iraq before the delivery date.

In analyzing the increased rate of labor inductions, we can simply and easily make our own justifications for elective and marginal inductions—we are making our patients happy, for one thing—and put on the back burner the lack of evidence favoring non-medically indicated induction. No matter how appealing our justifications might be, however, we cannot ignore the paucity of published data on benefits, nor can we ignore the data that do exist on the risks of labor induction.

Appreciating the Risks

Studies have shown that induced labor is associated with an increase in epidurals, with the greatest risk of uterine rupture in patients with a scarred uterus, with perhaps an increase in instrumental vaginal deliveries, and with an increase in cesarean deliveries, particularly among nulliparas undergoing an induction with an unfavorable cervix.

Investigators of a large study published in 2005 found a 1.5-fold greater risk of diagnosing a nonreassuring fetal heart rate pattern, a twofold increase in the need for epidural anesthesia, and a 1.5-fold increased risk of having a cesarean delivery among women who had elective inductions of labor compared with women who had spontaneous labor.

The risks of oxytocin use are principally dose related. Excess or undesired uterine hyperstimulation and subsequent fetal heart rate decelerations (“hyperstimulation syndrome”) are the most common side effects. In addition, hyperstimulation is associated with a greater risk of abruptio placentae or uterine rupture. There does not appear to be a significant increase in adverse fetal outcomes from uterine tachysystole.

Uterine hyperstimulation is an adverse effect that is also dose-dependent for prostaglandins (misoprostol, dinoprostone) used as cervical-ripening agents. The potential risks associated with amniotomy include prolapse of the umbilical cord, chorioamnionitis, significant umbilical cord compression, and rupture of vasa previa. With close monitoring and proper precaution, these hazards are fortunately uncommon.

Even if no additional risks are found with elective and marginal indications, it is important to consider issues related to personnel and cost. In addition to increasing the primary cesarean rate—and even a small additional risk of cesarean delivery for nulliparous women who have their labor induced translates into a significantly larger number of cesarean deliveries nationally—labor that is induced requires more one-on-one care and thus more nurses or nursing time.

It also independently leads to significantly longer time in labor and delivery, as well as a prolonged maternal length of hospital stay. Investigators have demonstrated significant differences in the admission-to-delivery times and in-hospital costs between patients who have vaginal deliveries after induced labor as compared with those who have spontaneous labor, as well as with patients who have cesarean deliveries in both scenarios.

Other studies have shown that labor inductions can overload the labor and delivery departments of some hospitals during “popular” midweek times. Downstream, labor induction also leads to an excess number of vaginal births after cesarean (VBAC) or repeat cesarean procedures. I am convinced, moreover, that litigation will be a concern in the future, especially with our armamentarium of cervical ripening agents. When there is a negative outcome after induction, I believe we can anticipate an allegation of unnecessary induction due to the lack of a medical indication.

The frequency of elective inductions and inductions for marginal indications appears to be higher in community hospitals than at university hospitals. A study that my colleagues and I published in 2000 found that 5% of all labor inductions at a university hospital were elective or not medically indicated using the ACOG criteria. At two community hospitals, on the other hand, 44% and 57% of inductions were for elective reasons.

Physicians in academic settings—particularly those involved in clinical trials to assess the effectiveness of therapies for labor induction—are more likely to use the Bishop scoring system. The Bishop score, first described in 1964, is based on cervical dilation, effacement, consistency, and position, as well as on fetal station. Although the scale isn't used much outside of academia, the principles should be consistently and universally applied, particularly the assessment of dilation and cervical consistency.

Planning the Future

Investigators have looked and will continue to look for predictors of success and ideal conditions for labor induction, but at this point in time the only known conditions are a favorable cervix and a patient who has had a previous vaginal delivery. Multiparous women at term generally present with a more favorable cervix.

Right now, roughly half of women who have their labor induced—or roughly 10% of the overall pregnancy population—have an unfavorable cervix. Cesarean rates are high for nulliparas who undergo an induction with an unfavorable cervix. This is a picture that needs widespread attention and an awareness of the desirability of evidence-based decisions.

Obstetricians must construct consistent and evidence-based protocols for cervical ripening; formally evaluate physician and patient satisfaction with induction; and design and lead clinical trials to provide answers on the value of marginal indications.

In the meantime, labor induction rates for hospitals and physicians should be monitored, and patients should be educated about the risks of induction so that they can participate in decision making and be better able to balance concerns and benefits. It is quite possible that written consent may become a standard of care before any induction is undertaken.

Until we do so, we should be aware that we may be complicating the uncomplicated.

ELSEVIER GLOBAL MEDICAL NEWS

Induction of Labor

The timing of parturition remains a conundrum in obstetric medicine in that the majority of pregnancies will go to term and enter labor spontaneously, whereas another portion will go post term and often require induction, and still others will enter labor prematurely.

The concept of labor induction, therefore, has become very important in obstetric management, especially in addressing pregnancies that either go post term or pregnancies that require induction because of medical complications in the mother.

Increasingly, however, patients are apt to have labor induced for their own convenience, for personal reasons, for the convenience of the physician, and sometimes for all of these reasons.

This increasingly utilized social option ushers in a whole new perspective on the issue of induction, and the question is raised about whether or not the elective induction of labor brings with it added risk and more complications.

It is for this reason that we decided to develop a Master Class feature on this topic. It gives us the important opportunity to examine and consider the pros and cons of labor induction, the timing of labor induction, and the advisability of the various conditions under which induction can and does occur.

This month's guest professor is Dr. William F. Rayburn, professor and chairman of the department of ob.gyn. at the University of New Mexico, Albuquerque. Dr. Rayburn is a maternal and fetal medicine specialist with a national reputation in this area.

Indications and Contraindications

Indications

Abruptio placentae

Chorioamnionitis

Fetal demise

Pregnancy-induced hypertension

Premature rupture of membranes

Postterm pregnancy

Maternal medical conditions (such as diabetes mellitus, renal disease, chronic pulmonary disease, chronic hypertension)

Fetal compromise (such as severe fetal growth restriction, isoimmunization)

Preeclampsia, eclampsia

Contraindications

Vasa previa or complete placenta previa

Transverse fetal lie

Umbilical cord prolapse

Previous transfundal uterine surgery

Special Attention

One or more previous low-transverse cesarean deliveries

Breech presentation

Maternal heart disease

Multifetal pregnancy

Polyhydramnios

Presenting part above the pelvic inlet

Severe hypertension

Abnormal fetal heart rate patterns not necessitating emergent delivery

Source: Adapted from ACOG Practice Bulletin No. 10, “Induction of Labor” (Nov. 1999).

The American College of Obstetricians and Gynecologists (ACOG) has described examples of commonly accepted indications, contraindications, and clinical conditions requiring special attention for an induction of labor. (See box p. 37.) We must remember that indications for labor induction are often not absolute and need to take maternal and fetal conditions, gestational age, and cervical status into account. Many contraindications are the same as those for either spontaneous labor or vaginal delivery; several obstetric conditions are not contraindications, but do necessitate special attention.

In 1988, the National Center for Health Statistics began requiring hospitals to indicate on birth certificates whether labor was induced or not. This requirement has provided us with remarkable insight into labor induction rates—insight that should cause us to pause, to reflect on available data and our own practices, and to demand that the issue receive more widespread attention.

Over a 10-year period beginning in 1989, the rate of labor induction doubled from about 9% to almost 19% of live births. (See chart.) The trend steadily continued into the new millennium, to the point where, in 2003, nearly 23% of all births involved induction of labor. Clearly, labor induction is one of the most common procedures in obstetrics.

Examining the Increase

The reasons for this significant increase over just 15 years relate to the availability of FDA-approved cervical ripening agents; to both the patient's desire and the physician's convenience; to the acceptance of added risks of cesarean delivery; and to increases in marginal or elective inductions for term pregnancies, especially those past 40 weeks. Inductions in which the reason is not evidence based now account for at least half of all term inductions, or up to 10% of all deliveries. The increase in medically indicated inductions was slower than the overall increase, suggesting that inductions for marginal or elective reasons have risen more rapidly.

Also contributing to the rising rate in inductions is our increasing success with cervical ripening and the fact that, in the current era of ultrasound availability and a more accurate dating of gestational age, we have had to worry less about iatrogenic prematurity.

When considering labor induction, we can view “elective” and “marginal” indications as being very similar, or we can differentiate the two, with “elective” meaning there is no plausible medical or obstetric reason for the induction, and “marginal” referring to cases in which obstetricians face or suspect problems but have no data to suggest that the benefits of labor induction outweigh the risks. I believe it is valuable to consider the terms separately as we attempt to understand the changes in induction rates.

Marginal indications include gestational hypertension; unexplained and mild fetal-growth restriction; idiopathic decreased amniotic fluid (which does not pose substantial danger unless it is accompanied by a recognized complication, such as hypertension or a small-for-gestational-age baby); and a pregnancy beyond 40 weeks. Prospective studies to recommend induction for these and other marginal indications are limited in size or design, or are nonexistent.

There is some rationale behind induction for suspected fetal macrosomia in nondiabetic pregnancies. Theoretically, eliminating further fetal growth should reduce the risks of shoulder dystocia and perhaps of cesarean delivery. However, there is no evidence-based justification for labor induction in these patients. Studies have shown, in fact, that the procedure approximately doubles the cesarean delivery risk, does not reduce neonatal morbidity, and does not appear to reduce the risk of shoulder dystocia.

There is also no published evidence to support the induction of labor for preterm mild preeclampsia, prior shoulder dystocia, and prior cephalopelvic disproportion.

ACOG weighed into the issue by approving “logistic reasons” for labor induction, such as a risk of rapid labor, a patient's unacceptable distance from the hospital, and psychosocial indications. This has left ob.gyns. with a substantial amount of latitude. For instance, one could argue that “psychosocial” reasons could include alleviating the concerns of a mother who previously had a stillborn infant, or alleviating the anxiety of a woman whose spouse is scheduled for deployment to Iraq before the delivery date.

In analyzing the increased rate of labor inductions, we can simply and easily make our own justifications for elective and marginal inductions—we are making our patients happy, for one thing—and put on the back burner the lack of evidence favoring non-medically indicated induction. No matter how appealing our justifications might be, however, we cannot ignore the paucity of published data on benefits, nor can we ignore the data that do exist on the risks of labor induction.

Appreciating the Risks

Studies have shown that induced labor is associated with an increase in epidurals, with the greatest risk of uterine rupture in patients with a scarred uterus, with perhaps an increase in instrumental vaginal deliveries, and with an increase in cesarean deliveries, particularly among nulliparas undergoing an induction with an unfavorable cervix.

Investigators of a large study published in 2005 found a 1.5-fold greater risk of diagnosing a nonreassuring fetal heart rate pattern, a twofold increase in the need for epidural anesthesia, and a 1.5-fold increased risk of having a cesarean delivery among women who had elective inductions of labor compared with women who had spontaneous labor.

The risks of oxytocin use are principally dose related. Excess or undesired uterine hyperstimulation and subsequent fetal heart rate decelerations (“hyperstimulation syndrome”) are the most common side effects. In addition, hyperstimulation is associated with a greater risk of abruptio placentae or uterine rupture. There does not appear to be a significant increase in adverse fetal outcomes from uterine tachysystole.

Uterine hyperstimulation is an adverse effect that is also dose-dependent for prostaglandins (misoprostol, dinoprostone) used as cervical-ripening agents. The potential risks associated with amniotomy include prolapse of the umbilical cord, chorioamnionitis, significant umbilical cord compression, and rupture of vasa previa. With close monitoring and proper precaution, these hazards are fortunately uncommon.

Even if no additional risks are found with elective and marginal indications, it is important to consider issues related to personnel and cost. In addition to increasing the primary cesarean rate—and even a small additional risk of cesarean delivery for nulliparous women who have their labor induced translates into a significantly larger number of cesarean deliveries nationally—labor that is induced requires more one-on-one care and thus more nurses or nursing time.

It also independently leads to significantly longer time in labor and delivery, as well as a prolonged maternal length of hospital stay. Investigators have demonstrated significant differences in the admission-to-delivery times and in-hospital costs between patients who have vaginal deliveries after induced labor as compared with those who have spontaneous labor, as well as with patients who have cesarean deliveries in both scenarios.

Other studies have shown that labor inductions can overload the labor and delivery departments of some hospitals during “popular” midweek times. Downstream, labor induction also leads to an excess number of vaginal births after cesarean (VBAC) or repeat cesarean procedures. I am convinced, moreover, that litigation will be a concern in the future, especially with our armamentarium of cervical ripening agents. When there is a negative outcome after induction, I believe we can anticipate an allegation of unnecessary induction due to the lack of a medical indication.

The frequency of elective inductions and inductions for marginal indications appears to be higher in community hospitals than at university hospitals. A study that my colleagues and I published in 2000 found that 5% of all labor inductions at a university hospital were elective or not medically indicated using the ACOG criteria. At two community hospitals, on the other hand, 44% and 57% of inductions were for elective reasons.

Physicians in academic settings—particularly those involved in clinical trials to assess the effectiveness of therapies for labor induction—are more likely to use the Bishop scoring system. The Bishop score, first described in 1964, is based on cervical dilation, effacement, consistency, and position, as well as on fetal station. Although the scale isn't used much outside of academia, the principles should be consistently and universally applied, particularly the assessment of dilation and cervical consistency.

Planning the Future

Investigators have looked and will continue to look for predictors of success and ideal conditions for labor induction, but at this point in time the only known conditions are a favorable cervix and a patient who has had a previous vaginal delivery. Multiparous women at term generally present with a more favorable cervix.

Right now, roughly half of women who have their labor induced—or roughly 10% of the overall pregnancy population—have an unfavorable cervix. Cesarean rates are high for nulliparas who undergo an induction with an unfavorable cervix. This is a picture that needs widespread attention and an awareness of the desirability of evidence-based decisions.

Obstetricians must construct consistent and evidence-based protocols for cervical ripening; formally evaluate physician and patient satisfaction with induction; and design and lead clinical trials to provide answers on the value of marginal indications.

In the meantime, labor induction rates for hospitals and physicians should be monitored, and patients should be educated about the risks of induction so that they can participate in decision making and be better able to balance concerns and benefits. It is quite possible that written consent may become a standard of care before any induction is undertaken.

Until we do so, we should be aware that we may be complicating the uncomplicated.

ELSEVIER GLOBAL MEDICAL NEWS

Induction of Labor

The timing of parturition remains a conundrum in obstetric medicine in that the majority of pregnancies will go to term and enter labor spontaneously, whereas another portion will go post term and often require induction, and still others will enter labor prematurely.

The concept of labor induction, therefore, has become very important in obstetric management, especially in addressing pregnancies that either go post term or pregnancies that require induction because of medical complications in the mother.

Increasingly, however, patients are apt to have labor induced for their own convenience, for personal reasons, for the convenience of the physician, and sometimes for all of these reasons.

This increasingly utilized social option ushers in a whole new perspective on the issue of induction, and the question is raised about whether or not the elective induction of labor brings with it added risk and more complications.

It is for this reason that we decided to develop a Master Class feature on this topic. It gives us the important opportunity to examine and consider the pros and cons of labor induction, the timing of labor induction, and the advisability of the various conditions under which induction can and does occur.

This month's guest professor is Dr. William F. Rayburn, professor and chairman of the department of ob.gyn. at the University of New Mexico, Albuquerque. Dr. Rayburn is a maternal and fetal medicine specialist with a national reputation in this area.

Indications and Contraindications

Indications

Abruptio placentae

Chorioamnionitis

Fetal demise

Pregnancy-induced hypertension

Premature rupture of membranes

Postterm pregnancy

Maternal medical conditions (such as diabetes mellitus, renal disease, chronic pulmonary disease, chronic hypertension)

Fetal compromise (such as severe fetal growth restriction, isoimmunization)

Preeclampsia, eclampsia

Contraindications

Vasa previa or complete placenta previa

Transverse fetal lie

Umbilical cord prolapse

Previous transfundal uterine surgery

Special Attention

One or more previous low-transverse cesarean deliveries

Breech presentation

Maternal heart disease

Multifetal pregnancy

Polyhydramnios

Presenting part above the pelvic inlet

Severe hypertension

Abnormal fetal heart rate patterns not necessitating emergent delivery

Source: Adapted from ACOG Practice Bulletin No. 10, “Induction of Labor” (Nov. 1999).

The American College of Obstetricians and Gynecologists (ACOG) has described examples of commonly accepted indications, contraindications, and clinical conditions requiring special attention for an induction of labor. (See box p. 37.) We must remember that indications for labor induction are often not absolute and need to take maternal and fetal conditions, gestational age, and cervical status into account. Many contraindications are the same as those for either spontaneous labor or vaginal delivery; several obstetric conditions are not contraindications, but do necessitate special attention.

In 1988, the National Center for Health Statistics began requiring hospitals to indicate on birth certificates whether labor was induced or not. This requirement has provided us with remarkable insight into labor induction rates—insight that should cause us to pause, to reflect on available data and our own practices, and to demand that the issue receive more widespread attention.

Over a 10-year period beginning in 1989, the rate of labor induction doubled from about 9% to almost 19% of live births. (See chart.) The trend steadily continued into the new millennium, to the point where, in 2003, nearly 23% of all births involved induction of labor. Clearly, labor induction is one of the most common procedures in obstetrics.

Examining the Increase

The reasons for this significant increase over just 15 years relate to the availability of FDA-approved cervical ripening agents; to both the patient's desire and the physician's convenience; to the acceptance of added risks of cesarean delivery; and to increases in marginal or elective inductions for term pregnancies, especially those past 40 weeks. Inductions in which the reason is not evidence based now account for at least half of all term inductions, or up to 10% of all deliveries. The increase in medically indicated inductions was slower than the overall increase, suggesting that inductions for marginal or elective reasons have risen more rapidly.

Also contributing to the rising rate in inductions is our increasing success with cervical ripening and the fact that, in the current era of ultrasound availability and a more accurate dating of gestational age, we have had to worry less about iatrogenic prematurity.

When considering labor induction, we can view “elective” and “marginal” indications as being very similar, or we can differentiate the two, with “elective” meaning there is no plausible medical or obstetric reason for the induction, and “marginal” referring to cases in which obstetricians face or suspect problems but have no data to suggest that the benefits of labor induction outweigh the risks. I believe it is valuable to consider the terms separately as we attempt to understand the changes in induction rates.

Marginal indications include gestational hypertension; unexplained and mild fetal-growth restriction; idiopathic decreased amniotic fluid (which does not pose substantial danger unless it is accompanied by a recognized complication, such as hypertension or a small-for-gestational-age baby); and a pregnancy beyond 40 weeks. Prospective studies to recommend induction for these and other marginal indications are limited in size or design, or are nonexistent.

There is some rationale behind induction for suspected fetal macrosomia in nondiabetic pregnancies. Theoretically, eliminating further fetal growth should reduce the risks of shoulder dystocia and perhaps of cesarean delivery. However, there is no evidence-based justification for labor induction in these patients. Studies have shown, in fact, that the procedure approximately doubles the cesarean delivery risk, does not reduce neonatal morbidity, and does not appear to reduce the risk of shoulder dystocia.

There is also no published evidence to support the induction of labor for preterm mild preeclampsia, prior shoulder dystocia, and prior cephalopelvic disproportion.

ACOG weighed into the issue by approving “logistic reasons” for labor induction, such as a risk of rapid labor, a patient's unacceptable distance from the hospital, and psychosocial indications. This has left ob.gyns. with a substantial amount of latitude. For instance, one could argue that “psychosocial” reasons could include alleviating the concerns of a mother who previously had a stillborn infant, or alleviating the anxiety of a woman whose spouse is scheduled for deployment to Iraq before the delivery date.

In analyzing the increased rate of labor inductions, we can simply and easily make our own justifications for elective and marginal inductions—we are making our patients happy, for one thing—and put on the back burner the lack of evidence favoring non-medically indicated induction. No matter how appealing our justifications might be, however, we cannot ignore the paucity of published data on benefits, nor can we ignore the data that do exist on the risks of labor induction.

Appreciating the Risks

Studies have shown that induced labor is associated with an increase in epidurals, with the greatest risk of uterine rupture in patients with a scarred uterus, with perhaps an increase in instrumental vaginal deliveries, and with an increase in cesarean deliveries, particularly among nulliparas undergoing an induction with an unfavorable cervix.

Investigators of a large study published in 2005 found a 1.5-fold greater risk of diagnosing a nonreassuring fetal heart rate pattern, a twofold increase in the need for epidural anesthesia, and a 1.5-fold increased risk of having a cesarean delivery among women who had elective inductions of labor compared with women who had spontaneous labor.

The risks of oxytocin use are principally dose related. Excess or undesired uterine hyperstimulation and subsequent fetal heart rate decelerations (“hyperstimulation syndrome”) are the most common side effects. In addition, hyperstimulation is associated with a greater risk of abruptio placentae or uterine rupture. There does not appear to be a significant increase in adverse fetal outcomes from uterine tachysystole.

Uterine hyperstimulation is an adverse effect that is also dose-dependent for prostaglandins (misoprostol, dinoprostone) used as cervical-ripening agents. The potential risks associated with amniotomy include prolapse of the umbilical cord, chorioamnionitis, significant umbilical cord compression, and rupture of vasa previa. With close monitoring and proper precaution, these hazards are fortunately uncommon.

Even if no additional risks are found with elective and marginal indications, it is important to consider issues related to personnel and cost. In addition to increasing the primary cesarean rate—and even a small additional risk of cesarean delivery for nulliparous women who have their labor induced translates into a significantly larger number of cesarean deliveries nationally—labor that is induced requires more one-on-one care and thus more nurses or nursing time.

It also independently leads to significantly longer time in labor and delivery, as well as a prolonged maternal length of hospital stay. Investigators have demonstrated significant differences in the admission-to-delivery times and in-hospital costs between patients who have vaginal deliveries after induced labor as compared with those who have spontaneous labor, as well as with patients who have cesarean deliveries in both scenarios.

Other studies have shown that labor inductions can overload the labor and delivery departments of some hospitals during “popular” midweek times. Downstream, labor induction also leads to an excess number of vaginal births after cesarean (VBAC) or repeat cesarean procedures. I am convinced, moreover, that litigation will be a concern in the future, especially with our armamentarium of cervical ripening agents. When there is a negative outcome after induction, I believe we can anticipate an allegation of unnecessary induction due to the lack of a medical indication.

The frequency of elective inductions and inductions for marginal indications appears to be higher in community hospitals than at university hospitals. A study that my colleagues and I published in 2000 found that 5% of all labor inductions at a university hospital were elective or not medically indicated using the ACOG criteria. At two community hospitals, on the other hand, 44% and 57% of inductions were for elective reasons.

Physicians in academic settings—particularly those involved in clinical trials to assess the effectiveness of therapies for labor induction—are more likely to use the Bishop scoring system. The Bishop score, first described in 1964, is based on cervical dilation, effacement, consistency, and position, as well as on fetal station. Although the scale isn't used much outside of academia, the principles should be consistently and universally applied, particularly the assessment of dilation and cervical consistency.

Planning the Future

Investigators have looked and will continue to look for predictors of success and ideal conditions for labor induction, but at this point in time the only known conditions are a favorable cervix and a patient who has had a previous vaginal delivery. Multiparous women at term generally present with a more favorable cervix.

Right now, roughly half of women who have their labor induced—or roughly 10% of the overall pregnancy population—have an unfavorable cervix. Cesarean rates are high for nulliparas who undergo an induction with an unfavorable cervix. This is a picture that needs widespread attention and an awareness of the desirability of evidence-based decisions.

Obstetricians must construct consistent and evidence-based protocols for cervical ripening; formally evaluate physician and patient satisfaction with induction; and design and lead clinical trials to provide answers on the value of marginal indications.

In the meantime, labor induction rates for hospitals and physicians should be monitored, and patients should be educated about the risks of induction so that they can participate in decision making and be better able to balance concerns and benefits. It is quite possible that written consent may become a standard of care before any induction is undertaken.

Until we do so, we should be aware that we may be complicating the uncomplicated.

ELSEVIER GLOBAL MEDICAL NEWS

Induction of Labor

The timing of parturition remains a conundrum in obstetric medicine in that the majority of pregnancies will go to term and enter labor spontaneously, whereas another portion will go post term and often require induction, and still others will enter labor prematurely.

The concept of labor induction, therefore, has become very important in obstetric management, especially in addressing pregnancies that either go post term or pregnancies that require induction because of medical complications in the mother.

Increasingly, however, patients are apt to have labor induced for their own convenience, for personal reasons, for the convenience of the physician, and sometimes for all of these reasons.

This increasingly utilized social option ushers in a whole new perspective on the issue of induction, and the question is raised about whether or not the elective induction of labor brings with it added risk and more complications.

It is for this reason that we decided to develop a Master Class feature on this topic. It gives us the important opportunity to examine and consider the pros and cons of labor induction, the timing of labor induction, and the advisability of the various conditions under which induction can and does occur.

This month's guest professor is Dr. William F. Rayburn, professor and chairman of the department of ob.gyn. at the University of New Mexico, Albuquerque. Dr. Rayburn is a maternal and fetal medicine specialist with a national reputation in this area.

Indications and Contraindications

Indications

Abruptio placentae

Chorioamnionitis

Fetal demise

Pregnancy-induced hypertension

Premature rupture of membranes

Postterm pregnancy

Maternal medical conditions (such as diabetes mellitus, renal disease, chronic pulmonary disease, chronic hypertension)

Fetal compromise (such as severe fetal growth restriction, isoimmunization)

Preeclampsia, eclampsia

Contraindications

Vasa previa or complete placenta previa

Transverse fetal lie

Umbilical cord prolapse

Previous transfundal uterine surgery

Special Attention

One or more previous low-transverse cesarean deliveries

Breech presentation

Maternal heart disease

Multifetal pregnancy

Polyhydramnios

Presenting part above the pelvic inlet

Severe hypertension

Abnormal fetal heart rate patterns not necessitating emergent delivery

Source: Adapted from ACOG Practice Bulletin No. 10, “Induction of Labor” (Nov. 1999).

Asherman's syndrome can occur after any type of gynecologic surgery, and we must shift our thinking and heighten our index of suspicion to accommodate the growing body of data that supports this claim.

A literature review published in Fertility and Sterility 15 years ago reported that approximately 90% of all cases of Asherman's syndrome occurred after curettage, mainly after D&C for a spontaneous abortion or one performed to control a postpartum hemorrhage. Although these two antecedent factors remain the most common causes, there has been a significant increase in the number of patients who develop endometrial scarring after gynecologic surgery, particularly following abdominal and hysteroscopic myomectomy.

Women who have had myomectomy or other types of uterine surgery make up an increasing proportion of all patients with adhesion formation and a variant of Asherman's syndrome known as endometrial sclerosis.

Endometrial sclerosis, commonly called an “unstuck Asherman's,” is an end-stage disease in which the basalis layer of the endometrium has been severely damaged or even removed. In these women, the hysterosalpingography (HSG) may demonstrate a normal cavity or one of slightly reduced size, but with little or no scarring.

This change presents new challenges because the damage that follows gynecologic surgery other than curettage is a much less curable condition.

Our Index of Suspicion

Key to our role as gynecologists is suspecting the problem. Any change in menstrual flow and pattern—from amenorrhea to any decrease in the duration or amount of bleeding—that follows any type of uterine surgery, irrespective of how minimal that surgery might have been, must prompt us to suspect that this patient may have scarring in her uterus. All patients with a history of intrauterine trauma must be considered at risk.

In addition to endometrial trauma, pregnancy (or recent pregnancy) and hypoestrogenism are important keys. The pregnant or recently pregnant uterus appears to be more vulnerable to scar formation.

Concomitantly, breast-feeding increases the risk of adhesion formation because women who breast-feed remain estrogen deficient. Estrogen has a tremendous effect in promoting the healing of the uterus and regeneration of the endometrium. Women who breast-feed don't have that stimulus.

To a lesser extent, infection also can play a role. Decades ago, infection was viewed as critical, in that it was the “infected abortion” that was thought to cause Asherman's syndrome. Today, infections are an uncommon cause of the problem. I have treated more than 1,000 patients with Asherman's, and fewer than 5 had any clinical evidence of infection around the time of their original surgery. Still, the possibility of Asherman's resulting from infections still exists.

Pelvic tuberculosis by itself, without any surgical trauma, causes scarring in the uterus. Considering the diversity of our society and the rise in antibiotic-resistant TB, we ought to keep it in mind.

It is also important to appreciate the fact that the presence of normal menstrual flow does not rule out the presence of intrauterine adhesions. Approximately three-quarters of women with Asherman's syndrome have amenorrhea or hypomenorrhea, but the remainder have menses of normal flow and duration. Other symptoms of intrauterine adhesions include infertility, recurrent miscarriage, and placenta accreta or its more severe variants.

Methods of Diagnosis

The diagnosis will most frequently be made by either HSG or a saline-infusion sonogram. However, these methods provide us with only a presumptive diagnosis. Both will demonstrate irregular, lacunalike defects spaced throughout the cavity. Access to the oviducts may or may not be blocked. A definitive diagnosis comes only with hysteroscopy.

We should individualize our diagnostic methods depending on the patient's history and symptoms and our own index of suspicion. For instance, a patient who presents with amenorrhea and monthly cramping following a D&C would benefit from a pelvic ultrasound. This study is likely to demonstrate fluid in the uterus. Her hematometra is secondary to outflow tract obstruction. There is no reason in this case to do a saline-infusion sonogram or an HSG. The next appropriate step is hysteroscopy, which will allow the diagnosis to be made with certainty so that treatment can commence.

Consider another patient with postcurettage amenorrhea. She has little or no fluid in the uterus and her endometrium is thin and/or irregular. A pregnancy test is negative and a uterine sound cannot be passed into the cavity. In this case, it is wise to proceed to hysteroscopy because it would not be possible to pass the contrast material for HSG—or the saline for a saline-infusion sonogram—beyond the site that blocked passage of the sound.

Hysteroscopy provides us with absolute proof of intrauterine adhesions. It allows us to directly inspect the uterine cavity and assess the extent, nature, and location of the adhesions. This also allows us to classify the disease, which is critical because classification enables us to make meaningful comparisons among different types of treatment regimens or adjunctive therapies. Finally, adhesiolysis under hysteroscopic guidance is more efficacious and less traumatic to the adjacent normal tissue.

Scissors vs. Heat

Since the introduction of hysteroscopy to treat intrauterine adhesions, the prognosis has gone from dismal to excellent. Hysteroscopic management not only enables us to cut all the scar tissue, but it ensures that we will not damage adjacent normal endometrium. There is no justification today for treating Asherman's syndrome by a technique other than hysteroscopy.

Although comparative studies are not available, we advocate that only scissors be used to cut adhesions, and we use them in our own practice.

Adhesiolysis methods that use a resectoscope, an Nd:YAG laser, or a monopolar or bipolar electrode have their proponents. However, all of these modalities deliver energy to the endometrial surface and can cause further damage to the endometrium. Remember that these same instruments are used to cause endometrial ablation.

Years ago, it was demonstrated that—in contrast to what occurs after a scalpel has been used to make an incision—tissue damage is observed far from the operative site when electrodes or an Nd:YAG laser is used for the same purpose. These energy sources offer no advantage—neither speed nor improved hemostasis (intrauterine scars do not bleed, but myometrium does)—over scissor dissection. In a patient with a damaged endometrium, it is prudent to limit the risk of further injury.

Although I have performed surgery that was not successful, it was not because of the inability of the flexible or semirigid scissors to cut through dense scars.

For women with extensive scarring, we should use simultaneous laparoscopy to reduce the risk of uterine perforation. This group of patients is increasing in relative frequency. The main antecedent factors for severe disease are the postpartum curettage performed 2–4 weeks after delivery, and scarring after myomectomy or metroplasty.

After the cutting of all adhesions under direct vision using hysteroscopy, I advise the placement of a splint into the uterus to help reduce adhesion reformation, and the prescription of 1–2 months of high-dose estrogen treatment to promote healing of the tissue and overgrowth of the endometrium.

We use the Cook balloon uterine stent, which has a triangular shape and therefore conforms to the shape of the normal uterus. (See photo, page 36.) This configuration allows it to reduce the risk of reformation of adhesions that had been along the margins of the cavity.

If the adhesions are limited to the endocervical canal and lower uterine segment, a Foley catheter is used as a stent instead of the Cook device because the former has a much wider diameter.

If a Foley catheter is used, the portion distal to the balloon is removed prior to insertion. After insertion of the Foley and inflation of its balloon, ligatures of No. 1 silk are placed around the catheter close to the cervix. This step keeps the balloon inflated and allows the trailing edge to be removed, thereby reducing patient discomfort.

The stent remains in place for 5 days to 3 weeks, depending on the type of stent used and the location and density of the adhesions. During the time that the stent is in situ, a broad-spectrum antibiotic is prescribed.

Following surgery, high-dose estrogen therapy (usually 3–4 mg of micronized oral estradiol) is prescribed for 30–60 days in order to maximally stimulate the endometrium, especially those areas under and adjacent to the adhesions. On the last 5 days of estrogen treatment, 10 mg of medroxyprogesterone acetate is added.

After the menstrual period that follows cessation of the estrogen-progestin treatment, we must perform HSG, hysteroscopy, or a saline-infusion sonogram to assess thoroughly the structure and configuration of the uterus. The last step in postoperative surveillance is a midcycle ultrasound to check endometrial growth and development.

The importance of verifying the normalcy of the uterine cavity and the complete resolution of adhesions before permitting conception cannot be overemphasized. The prognosis for the patient whose problem has been only partially solved is not good.

Variable Success, Mitigating Risks

The rates of cure of Asherman's syndrome vary dramatically according to the antecedent factors involved. In women with Asherman's syndrome that occurs after a D&C for a first-trimester abortion, whether spontaneous or induced, we can achieve a 98% structural success rate (normal follow-up HSG and ultrasound). This rate drops to 50% for Asherman's that occurs after a D&C for postpartum hemorrhage that is performed 2–4 weeks after delivery. The success rate drops further—to 20%—for treatment of scarring that follows myomectomy.

The low success rate of treatment for Asherman's after myomectomy is especially disconcerting because these cases make up an increasing proportion of all those with intrauterine adhesions that we see today. As women delay childbearing, there are more who will develop myomas prior to seeking their first pregnancy at an age older than 35 years.

If one or more myomas were removed because of symptoms, or to improve the likelihood of a successful pregnancy, then attempts to achieve a successful implantation may be stymied by the resultant scarring.

The key to increasing the cure rates for postmyomectomy Asherman's syndrome—and to reducing the incidence and severity of postmyomectomy scarring—could lie in the approach to fibroid removal.

The best approach for a woman who may want to become pregnant in the future, and who has a myoma that occupies a fair amount of the endometrial surface, may be to extract it abdominally. This approach provides a better chance of sparing the endometrium because the fibroid can often be “peeled” away from the endometrial surface, thereby maintaining the basalis layer within the outer layer of the myoma's capsule.

If the hysteroscopic approach is used, all of the endometrium over the surface of the myoma will be removed in order to extract the tumor.

The European Society of Hysteroscopy's classification of myomas is a helpful guide to plan the ideal route of surgery based on the extent of the intracavitary component. I have found this system—coupled with the size and location of the tumor (or tumors) and the patient's desire for future fertility—to be very useful in planning the ideal surgical approach.

We also should be extremely selective in our use of GnRH agonists. These agents allow anemia to be reversed, cause endometrial atrophy, and can make myomectomy easier to perform. However, the atrophic, estrogen-depleted endometrium may be more prone to adhesion formation.

To prevent intrauterine scarring following a D&C performed for postpartum hemorrhage 2–4 weeks after delivery, when the uterus is most vulnerable to scarring, I would propose to the patient that she not breast-feed, that a splint be placed in her uterus, and that she receive estrogen therapy. Although there are no studies on the efficacy of this prophylactic approach, these measures may help prevent the development of intrauterine adhesions, which are quite difficult to cure.

Administering prophylactic antibiotics at the time of D&C is a common practice and may help prevent subclinical infection. For the pregnancy loss that occurs very early in gestation, medical rather than surgical termination may be considered as a method of reducing the risk of scar formation. If curettage is necessary, it is advisable to perform surgery shortly after the fetal demise has been diagnosed. Curettage performed long after fetal demise is associated with a higher risk of scar formation, probably because some degree of fibrosis has begun.

Subsequent Pregnancy

The overall pregnancy rate after successful treatment for intrauterine adhesions is approximately 75%. (Other causes of infertility prevent us from reaching 100%.) In patients who conceive, approximately 85% of the pregnancies are successful. During pregnancy, there are several potential complications that must be anticipated in patients who have been treated for Asherman's syndrome. One is an incompetent cervix. These patients often have had many cervical dilatations because of curettages and hysteroscopies before becoming pregnant. An ultrasound can be used to assess the shortening of the cervix and any funneling of the membranes.

We must also consider the possibility of placenta accreta, which can be easily diagnosed with either high-resolution ultrasound or MRI in late pregnancy.

The advantages of suspecting the problem are several. For example, a patient can bank her own blood because placenta accreta can be associated with significant blood loss at delivery, and she can plan the timing and/or site of her delivery to optimize hospital resources and ensure access to a large amount of blood products and consultants from various specialties.

Even if the placenta appears to have been delivered complete and intact, uterine exploration is advised to verify that there are no retained fragments. Placenta accreta occurs significantly more often in patients who become pregnant with only partially treated Asherman's syndrome than in patients whose uterine cavity is normal. The successful-pregnancy rate in patients with incompletely resolved intrauterine adhesions is only 20%, and 18%–28% of these patients will have placental complications.

This means that once a diagnosis of intrauterine adhesions has been made, the patient should be offered therapy if she wishes to conceive. The recommendation to “try to conceive and see how it works” is a recipe for a bad outcome.

About 20% of my patients have needed more than one procedure in order to restore the cavity to normalcy. The second—or, rarely, even a fifth—procedure may be considered extreme if the postoperative HSG and ultrasound that followed a prior hysteroscopic adhesiolysis were “pretty normal.” However, the poor outcome in those with partially treated disease speaks volumes, especially in women who are older and are less fertile than in the past.

An important resource for patients with this condition is Asherman's Syndrome International, which is accessible at

http://groups.yahoo.com/group/Ashermans

Intrauterine Adhesions

Intrauterine adhesions continue to plague gynecologists and reproductive endocrinologists. Approximately 70 years ago, Asherman and Toaff came out with their landmark paper on patients who present with intrauterine synechiae and amenorrhea: Asherman's syndrome. The scarring can affect not only menstrual flow, but implantation as well, even in the environment of apparently normal menstruation.

When these adhesions are removed, proper care must be taken to minimize damage to the normal intrauterine cavity. Moreover, strategies must be considered to reduce subsequent postoperative adhesions. This is especially problematic because the intrauterine cavity is a pseudospace. The removal of intrauterine synechiae places traumatized tissue against traumatized tissue. This situation would appear to enable subsequent postoperative adhesion formation.

For this Master Class in gynecologic surgery, I have elicited the help of Dr. Charles March. Dr. March spent 30 years in the department of obstetrics and gynecology at the University of Southern California, Los Angeles, where he became professor in 1987. During his tenure there, Dr. March was a prolific writer, especially in the area of operative hysteroscopy, and was the recipient of numerous awards including many resident-teaching awards. In 2000, Dr. March was given a Pioneer in Hysteroscopy award from the American Association of Gynecologic Laparoscopists.

Since 2003, Dr. March has been in private practice, where he specializes in infertility treatment and sees patients from across the country for operative hysteroscopy secondary to intrauterine synechiae. Even so, Dr. March continues to win teaching awards, now as a voluntary faculty member.

Asherman's syndrome can occur after any type of gynecologic surgery, and we must shift our thinking and heighten our index of suspicion to accommodate the growing body of data that supports this claim.

A literature review published in Fertility and Sterility 15 years ago reported that approximately 90% of all cases of Asherman's syndrome occurred after curettage, mainly after D&C for a spontaneous abortion or one performed to control a postpartum hemorrhage. Although these two antecedent factors remain the most common causes, there has been a significant increase in the number of patients who develop endometrial scarring after gynecologic surgery, particularly following abdominal and hysteroscopic myomectomy.

Women who have had myomectomy or other types of uterine surgery make up an increasing proportion of all patients with adhesion formation and a variant of Asherman's syndrome known as endometrial sclerosis.

Endometrial sclerosis, commonly called an “unstuck Asherman's,” is an end-stage disease in which the basalis layer of the endometrium has been severely damaged or even removed. In these women, the hysterosalpingography (HSG) may demonstrate a normal cavity or one of slightly reduced size, but with little or no scarring.

This change presents new challenges because the damage that follows gynecologic surgery other than curettage is a much less curable condition.

Our Index of Suspicion

Key to our role as gynecologists is suspecting the problem. Any change in menstrual flow and pattern—from amenorrhea to any decrease in the duration or amount of bleeding—that follows any type of uterine surgery, irrespective of how minimal that surgery might have been, must prompt us to suspect that this patient may have scarring in her uterus. All patients with a history of intrauterine trauma must be considered at risk.

In addition to endometrial trauma, pregnancy (or recent pregnancy) and hypoestrogenism are important keys. The pregnant or recently pregnant uterus appears to be more vulnerable to scar formation.

Concomitantly, breast-feeding increases the risk of adhesion formation because women who breast-feed remain estrogen deficient. Estrogen has a tremendous effect in promoting the healing of the uterus and regeneration of the endometrium. Women who breast-feed don't have that stimulus.

To a lesser extent, infection also can play a role. Decades ago, infection was viewed as critical, in that it was the “infected abortion” that was thought to cause Asherman's syndrome. Today, infections are an uncommon cause of the problem. I have treated more than 1,000 patients with Asherman's, and fewer than 5 had any clinical evidence of infection around the time of their original surgery. Still, the possibility of Asherman's resulting from infections still exists.

Pelvic tuberculosis by itself, without any surgical trauma, causes scarring in the uterus. Considering the diversity of our society and the rise in antibiotic-resistant TB, we ought to keep it in mind.

It is also important to appreciate the fact that the presence of normal menstrual flow does not rule out the presence of intrauterine adhesions. Approximately three-quarters of women with Asherman's syndrome have amenorrhea or hypomenorrhea, but the remainder have menses of normal flow and duration. Other symptoms of intrauterine adhesions include infertility, recurrent miscarriage, and placenta accreta or its more severe variants.

Methods of Diagnosis

The diagnosis will most frequently be made by either HSG or a saline-infusion sonogram. However, these methods provide us with only a presumptive diagnosis. Both will demonstrate irregular, lacunalike defects spaced throughout the cavity. Access to the oviducts may or may not be blocked. A definitive diagnosis comes only with hysteroscopy.

We should individualize our diagnostic methods depending on the patient's history and symptoms and our own index of suspicion. For instance, a patient who presents with amenorrhea and monthly cramping following a D&C would benefit from a pelvic ultrasound. This study is likely to demonstrate fluid in the uterus. Her hematometra is secondary to outflow tract obstruction. There is no reason in this case to do a saline-infusion sonogram or an HSG. The next appropriate step is hysteroscopy, which will allow the diagnosis to be made with certainty so that treatment can commence.

Consider another patient with postcurettage amenorrhea. She has little or no fluid in the uterus and her endometrium is thin and/or irregular. A pregnancy test is negative and a uterine sound cannot be passed into the cavity. In this case, it is wise to proceed to hysteroscopy because it would not be possible to pass the contrast material for HSG—or the saline for a saline-infusion sonogram—beyond the site that blocked passage of the sound.

Hysteroscopy provides us with absolute proof of intrauterine adhesions. It allows us to directly inspect the uterine cavity and assess the extent, nature, and location of the adhesions. This also allows us to classify the disease, which is critical because classification enables us to make meaningful comparisons among different types of treatment regimens or adjunctive therapies. Finally, adhesiolysis under hysteroscopic guidance is more efficacious and less traumatic to the adjacent normal tissue.

Scissors vs. Heat

Since the introduction of hysteroscopy to treat intrauterine adhesions, the prognosis has gone from dismal to excellent. Hysteroscopic management not only enables us to cut all the scar tissue, but it ensures that we will not damage adjacent normal endometrium. There is no justification today for treating Asherman's syndrome by a technique other than hysteroscopy.

Although comparative studies are not available, we advocate that only scissors be used to cut adhesions, and we use them in our own practice.

Adhesiolysis methods that use a resectoscope, an Nd:YAG laser, or a monopolar or bipolar electrode have their proponents. However, all of these modalities deliver energy to the endometrial surface and can cause further damage to the endometrium. Remember that these same instruments are used to cause endometrial ablation.

Years ago, it was demonstrated that—in contrast to what occurs after a scalpel has been used to make an incision—tissue damage is observed far from the operative site when electrodes or an Nd:YAG laser is used for the same purpose. These energy sources offer no advantage—neither speed nor improved hemostasis (intrauterine scars do not bleed, but myometrium does)—over scissor dissection. In a patient with a damaged endometrium, it is prudent to limit the risk of further injury.

Although I have performed surgery that was not successful, it was not because of the inability of the flexible or semirigid scissors to cut through dense scars.

For women with extensive scarring, we should use simultaneous laparoscopy to reduce the risk of uterine perforation. This group of patients is increasing in relative frequency. The main antecedent factors for severe disease are the postpartum curettage performed 2–4 weeks after delivery, and scarring after myomectomy or metroplasty.

After the cutting of all adhesions under direct vision using hysteroscopy, I advise the placement of a splint into the uterus to help reduce adhesion reformation, and the prescription of 1–2 months of high-dose estrogen treatment to promote healing of the tissue and overgrowth of the endometrium.

We use the Cook balloon uterine stent, which has a triangular shape and therefore conforms to the shape of the normal uterus. (See photo, page 36.) This configuration allows it to reduce the risk of reformation of adhesions that had been along the margins of the cavity.

If the adhesions are limited to the endocervical canal and lower uterine segment, a Foley catheter is used as a stent instead of the Cook device because the former has a much wider diameter.

If a Foley catheter is used, the portion distal to the balloon is removed prior to insertion. After insertion of the Foley and inflation of its balloon, ligatures of No. 1 silk are placed around the catheter close to the cervix. This step keeps the balloon inflated and allows the trailing edge to be removed, thereby reducing patient discomfort.

The stent remains in place for 5 days to 3 weeks, depending on the type of stent used and the location and density of the adhesions. During the time that the stent is in situ, a broad-spectrum antibiotic is prescribed.

Following surgery, high-dose estrogen therapy (usually 3–4 mg of micronized oral estradiol) is prescribed for 30–60 days in order to maximally stimulate the endometrium, especially those areas under and adjacent to the adhesions. On the last 5 days of estrogen treatment, 10 mg of medroxyprogesterone acetate is added.

After the menstrual period that follows cessation of the estrogen-progestin treatment, we must perform HSG, hysteroscopy, or a saline-infusion sonogram to assess thoroughly the structure and configuration of the uterus. The last step in postoperative surveillance is a midcycle ultrasound to check endometrial growth and development.

The importance of verifying the normalcy of the uterine cavity and the complete resolution of adhesions before permitting conception cannot be overemphasized. The prognosis for the patient whose problem has been only partially solved is not good.

Variable Success, Mitigating Risks

The rates of cure of Asherman's syndrome vary dramatically according to the antecedent factors involved. In women with Asherman's syndrome that occurs after a D&C for a first-trimester abortion, whether spontaneous or induced, we can achieve a 98% structural success rate (normal follow-up HSG and ultrasound). This rate drops to 50% for Asherman's that occurs after a D&C for postpartum hemorrhage that is performed 2–4 weeks after delivery. The success rate drops further—to 20%—for treatment of scarring that follows myomectomy.

The low success rate of treatment for Asherman's after myomectomy is especially disconcerting because these cases make up an increasing proportion of all those with intrauterine adhesions that we see today. As women delay childbearing, there are more who will develop myomas prior to seeking their first pregnancy at an age older than 35 years.

If one or more myomas were removed because of symptoms, or to improve the likelihood of a successful pregnancy, then attempts to achieve a successful implantation may be stymied by the resultant scarring.

The key to increasing the cure rates for postmyomectomy Asherman's syndrome—and to reducing the incidence and severity of postmyomectomy scarring—could lie in the approach to fibroid removal.

The best approach for a woman who may want to become pregnant in the future, and who has a myoma that occupies a fair amount of the endometrial surface, may be to extract it abdominally. This approach provides a better chance of sparing the endometrium because the fibroid can often be “peeled” away from the endometrial surface, thereby maintaining the basalis layer within the outer layer of the myoma's capsule.

If the hysteroscopic approach is used, all of the endometrium over the surface of the myoma will be removed in order to extract the tumor.

The European Society of Hysteroscopy's classification of myomas is a helpful guide to plan the ideal route of surgery based on the extent of the intracavitary component. I have found this system—coupled with the size and location of the tumor (or tumors) and the patient's desire for future fertility—to be very useful in planning the ideal surgical approach.

We also should be extremely selective in our use of GnRH agonists. These agents allow anemia to be reversed, cause endometrial atrophy, and can make myomectomy easier to perform. However, the atrophic, estrogen-depleted endometrium may be more prone to adhesion formation.

To prevent intrauterine scarring following a D&C performed for postpartum hemorrhage 2–4 weeks after delivery, when the uterus is most vulnerable to scarring, I would propose to the patient that she not breast-feed, that a splint be placed in her uterus, and that she receive estrogen therapy. Although there are no studies on the efficacy of this prophylactic approach, these measures may help prevent the development of intrauterine adhesions, which are quite difficult to cure.

Administering prophylactic antibiotics at the time of D&C is a common practice and may help prevent subclinical infection. For the pregnancy loss that occurs very early in gestation, medical rather than surgical termination may be considered as a method of reducing the risk of scar formation. If curettage is necessary, it is advisable to perform surgery shortly after the fetal demise has been diagnosed. Curettage performed long after fetal demise is associated with a higher risk of scar formation, probably because some degree of fibrosis has begun.

Subsequent Pregnancy

The overall pregnancy rate after successful treatment for intrauterine adhesions is approximately 75%. (Other causes of infertility prevent us from reaching 100%.) In patients who conceive, approximately 85% of the pregnancies are successful. During pregnancy, there are several potential complications that must be anticipated in patients who have been treated for Asherman's syndrome. One is an incompetent cervix. These patients often have had many cervical dilatations because of curettages and hysteroscopies before becoming pregnant. An ultrasound can be used to assess the shortening of the cervix and any funneling of the membranes.

We must also consider the possibility of placenta accreta, which can be easily diagnosed with either high-resolution ultrasound or MRI in late pregnancy.

The advantages of suspecting the problem are several. For example, a patient can bank her own blood because placenta accreta can be associated with significant blood loss at delivery, and she can plan the timing and/or site of her delivery to optimize hospital resources and ensure access to a large amount of blood products and consultants from various specialties.

Even if the placenta appears to have been delivered complete and intact, uterine exploration is advised to verify that there are no retained fragments. Placenta accreta occurs significantly more often in patients who become pregnant with only partially treated Asherman's syndrome than in patients whose uterine cavity is normal. The successful-pregnancy rate in patients with incompletely resolved intrauterine adhesions is only 20%, and 18%–28% of these patients will have placental complications.

This means that once a diagnosis of intrauterine adhesions has been made, the patient should be offered therapy if she wishes to conceive. The recommendation to “try to conceive and see how it works” is a recipe for a bad outcome.

About 20% of my patients have needed more than one procedure in order to restore the cavity to normalcy. The second—or, rarely, even a fifth—procedure may be considered extreme if the postoperative HSG and ultrasound that followed a prior hysteroscopic adhesiolysis were “pretty normal.” However, the poor outcome in those with partially treated disease speaks volumes, especially in women who are older and are less fertile than in the past.

An important resource for patients with this condition is Asherman's Syndrome International, which is accessible at

http://groups.yahoo.com/group/Ashermans

Intrauterine Adhesions

Intrauterine adhesions continue to plague gynecologists and reproductive endocrinologists. Approximately 70 years ago, Asherman and Toaff came out with their landmark paper on patients who present with intrauterine synechiae and amenorrhea: Asherman's syndrome. The scarring can affect not only menstrual flow, but implantation as well, even in the environment of apparently normal menstruation.

When these adhesions are removed, proper care must be taken to minimize damage to the normal intrauterine cavity. Moreover, strategies must be considered to reduce subsequent postoperative adhesions. This is especially problematic because the intrauterine cavity is a pseudospace. The removal of intrauterine synechiae places traumatized tissue against traumatized tissue. This situation would appear to enable subsequent postoperative adhesion formation.

For this Master Class in gynecologic surgery, I have elicited the help of Dr. Charles March. Dr. March spent 30 years in the department of obstetrics and gynecology at the University of Southern California, Los Angeles, where he became professor in 1987. During his tenure there, Dr. March was a prolific writer, especially in the area of operative hysteroscopy, and was the recipient of numerous awards including many resident-teaching awards. In 2000, Dr. March was given a Pioneer in Hysteroscopy award from the American Association of Gynecologic Laparoscopists.

Since 2003, Dr. March has been in private practice, where he specializes in infertility treatment and sees patients from across the country for operative hysteroscopy secondary to intrauterine synechiae. Even so, Dr. March continues to win teaching awards, now as a voluntary faculty member.

Asherman's syndrome can occur after any type of gynecologic surgery, and we must shift our thinking and heighten our index of suspicion to accommodate the growing body of data that supports this claim.

A literature review published in Fertility and Sterility 15 years ago reported that approximately 90% of all cases of Asherman's syndrome occurred after curettage, mainly after D&C for a spontaneous abortion or one performed to control a postpartum hemorrhage. Although these two antecedent factors remain the most common causes, there has been a significant increase in the number of patients who develop endometrial scarring after gynecologic surgery, particularly following abdominal and hysteroscopic myomectomy.

Women who have had myomectomy or other types of uterine surgery make up an increasing proportion of all patients with adhesion formation and a variant of Asherman's syndrome known as endometrial sclerosis.

Endometrial sclerosis, commonly called an “unstuck Asherman's,” is an end-stage disease in which the basalis layer of the endometrium has been severely damaged or even removed. In these women, the hysterosalpingography (HSG) may demonstrate a normal cavity or one of slightly reduced size, but with little or no scarring.

This change presents new challenges because the damage that follows gynecologic surgery other than curettage is a much less curable condition.

Our Index of Suspicion

Key to our role as gynecologists is suspecting the problem. Any change in menstrual flow and pattern—from amenorrhea to any decrease in the duration or amount of bleeding—that follows any type of uterine surgery, irrespective of how minimal that surgery might have been, must prompt us to suspect that this patient may have scarring in her uterus. All patients with a history of intrauterine trauma must be considered at risk.

In addition to endometrial trauma, pregnancy (or recent pregnancy) and hypoestrogenism are important keys. The pregnant or recently pregnant uterus appears to be more vulnerable to scar formation.

Concomitantly, breast-feeding increases the risk of adhesion formation because women who breast-feed remain estrogen deficient. Estrogen has a tremendous effect in promoting the healing of the uterus and regeneration of the endometrium. Women who breast-feed don't have that stimulus.

To a lesser extent, infection also can play a role. Decades ago, infection was viewed as critical, in that it was the “infected abortion” that was thought to cause Asherman's syndrome. Today, infections are an uncommon cause of the problem. I have treated more than 1,000 patients with Asherman's, and fewer than 5 had any clinical evidence of infection around the time of their original surgery. Still, the possibility of Asherman's resulting from infections still exists.

Pelvic tuberculosis by itself, without any surgical trauma, causes scarring in the uterus. Considering the diversity of our society and the rise in antibiotic-resistant TB, we ought to keep it in mind.

It is also important to appreciate the fact that the presence of normal menstrual flow does not rule out the presence of intrauterine adhesions. Approximately three-quarters of women with Asherman's syndrome have amenorrhea or hypomenorrhea, but the remainder have menses of normal flow and duration. Other symptoms of intrauterine adhesions include infertility, recurrent miscarriage, and placenta accreta or its more severe variants.

Methods of Diagnosis

The diagnosis will most frequently be made by either HSG or a saline-infusion sonogram. However, these methods provide us with only a presumptive diagnosis. Both will demonstrate irregular, lacunalike defects spaced throughout the cavity. Access to the oviducts may or may not be blocked. A definitive diagnosis comes only with hysteroscopy.

We should individualize our diagnostic methods depending on the patient's history and symptoms and our own index of suspicion. For instance, a patient who presents with amenorrhea and monthly cramping following a D&C would benefit from a pelvic ultrasound. This study is likely to demonstrate fluid in the uterus. Her hematometra is secondary to outflow tract obstruction. There is no reason in this case to do a saline-infusion sonogram or an HSG. The next appropriate step is hysteroscopy, which will allow the diagnosis to be made with certainty so that treatment can commence.

Consider another patient with postcurettage amenorrhea. She has little or no fluid in the uterus and her endometrium is thin and/or irregular. A pregnancy test is negative and a uterine sound cannot be passed into the cavity. In this case, it is wise to proceed to hysteroscopy because it would not be possible to pass the contrast material for HSG—or the saline for a saline-infusion sonogram—beyond the site that blocked passage of the sound.

Hysteroscopy provides us with absolute proof of intrauterine adhesions. It allows us to directly inspect the uterine cavity and assess the extent, nature, and location of the adhesions. This also allows us to classify the disease, which is critical because classification enables us to make meaningful comparisons among different types of treatment regimens or adjunctive therapies. Finally, adhesiolysis under hysteroscopic guidance is more efficacious and less traumatic to the adjacent normal tissue.

Scissors vs. Heat

Since the introduction of hysteroscopy to treat intrauterine adhesions, the prognosis has gone from dismal to excellent. Hysteroscopic management not only enables us to cut all the scar tissue, but it ensures that we will not damage adjacent normal endometrium. There is no justification today for treating Asherman's syndrome by a technique other than hysteroscopy.

Although comparative studies are not available, we advocate that only scissors be used to cut adhesions, and we use them in our own practice.

Adhesiolysis methods that use a resectoscope, an Nd:YAG laser, or a monopolar or bipolar electrode have their proponents. However, all of these modalities deliver energy to the endometrial surface and can cause further damage to the endometrium. Remember that these same instruments are used to cause endometrial ablation.

Years ago, it was demonstrated that—in contrast to what occurs after a scalpel has been used to make an incision—tissue damage is observed far from the operative site when electrodes or an Nd:YAG laser is used for the same purpose. These energy sources offer no advantage—neither speed nor improved hemostasis (intrauterine scars do not bleed, but myometrium does)—over scissor dissection. In a patient with a damaged endometrium, it is prudent to limit the risk of further injury.

Although I have performed surgery that was not successful, it was not because of the inability of the flexible or semirigid scissors to cut through dense scars.

For women with extensive scarring, we should use simultaneous laparoscopy to reduce the risk of uterine perforation. This group of patients is increasing in relative frequency. The main antecedent factors for severe disease are the postpartum curettage performed 2–4 weeks after delivery, and scarring after myomectomy or metroplasty.

After the cutting of all adhesions under direct vision using hysteroscopy, I advise the placement of a splint into the uterus to help reduce adhesion reformation, and the prescription of 1–2 months of high-dose estrogen treatment to promote healing of the tissue and overgrowth of the endometrium.

We use the Cook balloon uterine stent, which has a triangular shape and therefore conforms to the shape of the normal uterus. (See photo, page 36.) This configuration allows it to reduce the risk of reformation of adhesions that had been along the margins of the cavity.

If the adhesions are limited to the endocervical canal and lower uterine segment, a Foley catheter is used as a stent instead of the Cook device because the former has a much wider diameter.

If a Foley catheter is used, the portion distal to the balloon is removed prior to insertion. After insertion of the Foley and inflation of its balloon, ligatures of No. 1 silk are placed around the catheter close to the cervix. This step keeps the balloon inflated and allows the trailing edge to be removed, thereby reducing patient discomfort.

The stent remains in place for 5 days to 3 weeks, depending on the type of stent used and the location and density of the adhesions. During the time that the stent is in situ, a broad-spectrum antibiotic is prescribed.

Following surgery, high-dose estrogen therapy (usually 3–4 mg of micronized oral estradiol) is prescribed for 30–60 days in order to maximally stimulate the endometrium, especially those areas under and adjacent to the adhesions. On the last 5 days of estrogen treatment, 10 mg of medroxyprogesterone acetate is added.

After the menstrual period that follows cessation of the estrogen-progestin treatment, we must perform HSG, hysteroscopy, or a saline-infusion sonogram to assess thoroughly the structure and configuration of the uterus. The last step in postoperative surveillance is a midcycle ultrasound to check endometrial growth and development.

The importance of verifying the normalcy of the uterine cavity and the complete resolution of adhesions before permitting conception cannot be overemphasized. The prognosis for the patient whose problem has been only partially solved is not good.

Variable Success, Mitigating Risks

The rates of cure of Asherman's syndrome vary dramatically according to the antecedent factors involved. In women with Asherman's syndrome that occurs after a D&C for a first-trimester abortion, whether spontaneous or induced, we can achieve a 98% structural success rate (normal follow-up HSG and ultrasound). This rate drops to 50% for Asherman's that occurs after a D&C for postpartum hemorrhage that is performed 2–4 weeks after delivery. The success rate drops further—to 20%—for treatment of scarring that follows myomectomy.

The low success rate of treatment for Asherman's after myomectomy is especially disconcerting because these cases make up an increasing proportion of all those with intrauterine adhesions that we see today. As women delay childbearing, there are more who will develop myomas prior to seeking their first pregnancy at an age older than 35 years.

If one or more myomas were removed because of symptoms, or to improve the likelihood of a successful pregnancy, then attempts to achieve a successful implantation may be stymied by the resultant scarring.

The key to increasing the cure rates for postmyomectomy Asherman's syndrome—and to reducing the incidence and severity of postmyomectomy scarring—could lie in the approach to fibroid removal.

The best approach for a woman who may want to become pregnant in the future, and who has a myoma that occupies a fair amount of the endometrial surface, may be to extract it abdominally. This approach provides a better chance of sparing the endometrium because the fibroid can often be “peeled” away from the endometrial surface, thereby maintaining the basalis layer within the outer layer of the myoma's capsule.

If the hysteroscopic approach is used, all of the endometrium over the surface of the myoma will be removed in order to extract the tumor.

The European Society of Hysteroscopy's classification of myomas is a helpful guide to plan the ideal route of surgery based on the extent of the intracavitary component. I have found this system—coupled with the size and location of the tumor (or tumors) and the patient's desire for future fertility—to be very useful in planning the ideal surgical approach.

We also should be extremely selective in our use of GnRH agonists. These agents allow anemia to be reversed, cause endometrial atrophy, and can make myomectomy easier to perform. However, the atrophic, estrogen-depleted endometrium may be more prone to adhesion formation.

To prevent intrauterine scarring following a D&C performed for postpartum hemorrhage 2–4 weeks after delivery, when the uterus is most vulnerable to scarring, I would propose to the patient that she not breast-feed, that a splint be placed in her uterus, and that she receive estrogen therapy. Although there are no studies on the efficacy of this prophylactic approach, these measures may help prevent the development of intrauterine adhesions, which are quite difficult to cure.

Administering prophylactic antibiotics at the time of D&C is a common practice and may help prevent subclinical infection. For the pregnancy loss that occurs very early in gestation, medical rather than surgical termination may be considered as a method of reducing the risk of scar formation. If curettage is necessary, it is advisable to perform surgery shortly after the fetal demise has been diagnosed. Curettage performed long after fetal demise is associated with a higher risk of scar formation, probably because some degree of fibrosis has begun.

Subsequent Pregnancy

The overall pregnancy rate after successful treatment for intrauterine adhesions is approximately 75%. (Other causes of infertility prevent us from reaching 100%.) In patients who conceive, approximately 85% of the pregnancies are successful. During pregnancy, there are several potential complications that must be anticipated in patients who have been treated for Asherman's syndrome. One is an incompetent cervix. These patients often have had many cervical dilatations because of curettages and hysteroscopies before becoming pregnant. An ultrasound can be used to assess the shortening of the cervix and any funneling of the membranes.

We must also consider the possibility of placenta accreta, which can be easily diagnosed with either high-resolution ultrasound or MRI in late pregnancy.

The advantages of suspecting the problem are several. For example, a patient can bank her own blood because placenta accreta can be associated with significant blood loss at delivery, and she can plan the timing and/or site of her delivery to optimize hospital resources and ensure access to a large amount of blood products and consultants from various specialties.

Even if the placenta appears to have been delivered complete and intact, uterine exploration is advised to verify that there are no retained fragments. Placenta accreta occurs significantly more often in patients who become pregnant with only partially treated Asherman's syndrome than in patients whose uterine cavity is normal. The successful-pregnancy rate in patients with incompletely resolved intrauterine adhesions is only 20%, and 18%–28% of these patients will have placental complications.

This means that once a diagnosis of intrauterine adhesions has been made, the patient should be offered therapy if she wishes to conceive. The recommendation to “try to conceive and see how it works” is a recipe for a bad outcome.

About 20% of my patients have needed more than one procedure in order to restore the cavity to normalcy. The second—or, rarely, even a fifth—procedure may be considered extreme if the postoperative HSG and ultrasound that followed a prior hysteroscopic adhesiolysis were “pretty normal.” However, the poor outcome in those with partially treated disease speaks volumes, especially in women who are older and are less fertile than in the past.

An important resource for patients with this condition is Asherman's Syndrome International, which is accessible at

http://groups.yahoo.com/group/Ashermans

Intrauterine Adhesions

Intrauterine adhesions continue to plague gynecologists and reproductive endocrinologists. Approximately 70 years ago, Asherman and Toaff came out with their landmark paper on patients who present with intrauterine synechiae and amenorrhea: Asherman's syndrome. The scarring can affect not only menstrual flow, but implantation as well, even in the environment of apparently normal menstruation.

When these adhesions are removed, proper care must be taken to minimize damage to the normal intrauterine cavity. Moreover, strategies must be considered to reduce subsequent postoperative adhesions. This is especially problematic because the intrauterine cavity is a pseudospace. The removal of intrauterine synechiae places traumatized tissue against traumatized tissue. This situation would appear to enable subsequent postoperative adhesion formation.

For this Master Class in gynecologic surgery, I have elicited the help of Dr. Charles March. Dr. March spent 30 years in the department of obstetrics and gynecology at the University of Southern California, Los Angeles, where he became professor in 1987. During his tenure there, Dr. March was a prolific writer, especially in the area of operative hysteroscopy, and was the recipient of numerous awards including many resident-teaching awards. In 2000, Dr. March was given a Pioneer in Hysteroscopy award from the American Association of Gynecologic Laparoscopists.

Since 2003, Dr. March has been in private practice, where he specializes in infertility treatment and sees patients from across the country for operative hysteroscopy secondary to intrauterine synechiae. Even so, Dr. March continues to win teaching awards, now as a voluntary faculty member.

Waiting up to 2 minutes after delivery to cut the umbilical cord led to increased iron status at 6 months, with no adverse associations for mothers or infants, and could be valuable in preventing developmental delays associated with iron deficiencies, according to findings from a large randomized controlled trial.

Dr. Camila M. Chaparro of the University of California, Davis, and colleagues reported results from 358 mother-and-singleton infant pairs delivered at a large obstetric hospital in Mexico City. The primary outcomes were infant blood and iron status at age 6 months—the longest follow-up to date in any trial of delayed cord clamping (Lancet 2006;367:1997–2004).

The investigators randomized mothers to one of two groups: In one group, the umbilical cord was clamped after 10 seconds. In the other group, it was clamped after 2 minutes—coinciding roughly with the usual cessation of cord pulsations—unless the physician determined earlier cord removal was necessary. Ultimately, the mean clamping time for the early-clamping group was roughly 17 seconds, compared with about 94 seconds for the delayed-clamping group—a difference of just over 1 minute.

At 6 months of age, the delayed-clamping infants had significantly higher levels than the early-clamping infants in several measures (adjusted for maternal factors): stored iron (58 mg vs. 31 mg), body iron (343 mg vs. 316 mg), mean corpuscular volume (81.0 fL vs. 79.5 fL), and ferritin (50.7 mcg/L vs. 34.4 mcg/L). Moreover, the incidence of iron deficiency (less than 9 mcg/L) in the early-clamping infants was 7%, compared with 1% in the delayed-clamping group, and unadjusted incidence of iron-deficiency anemia was 4% in early-clamping infants vs. 0% in the delayed-clamping group, the investigators noted.

Waiting up to 2 minutes after delivery to cut the umbilical cord led to increased iron status at 6 months, with no adverse associations for mothers or infants, and could be valuable in preventing developmental delays associated with iron deficiencies, according to findings from a large randomized controlled trial.

Dr. Camila M. Chaparro of the University of California, Davis, and colleagues reported results from 358 mother-and-singleton infant pairs delivered at a large obstetric hospital in Mexico City. The primary outcomes were infant blood and iron status at age 6 months—the longest follow-up to date in any trial of delayed cord clamping (Lancet 2006;367:1997–2004).

The investigators randomized mothers to one of two groups: In one group, the umbilical cord was clamped after 10 seconds. In the other group, it was clamped after 2 minutes—coinciding roughly with the usual cessation of cord pulsations—unless the physician determined earlier cord removal was necessary. Ultimately, the mean clamping time for the early-clamping group was roughly 17 seconds, compared with about 94 seconds for the delayed-clamping group—a difference of just over 1 minute.

At 6 months of age, the delayed-clamping infants had significantly higher levels than the early-clamping infants in several measures (adjusted for maternal factors): stored iron (58 mg vs. 31 mg), body iron (343 mg vs. 316 mg), mean corpuscular volume (81.0 fL vs. 79.5 fL), and ferritin (50.7 mcg/L vs. 34.4 mcg/L). Moreover, the incidence of iron deficiency (less than 9 mcg/L) in the early-clamping infants was 7%, compared with 1% in the delayed-clamping group, and unadjusted incidence of iron-deficiency anemia was 4% in early-clamping infants vs. 0% in the delayed-clamping group, the investigators noted.

Waiting up to 2 minutes after delivery to cut the umbilical cord led to increased iron status at 6 months, with no adverse associations for mothers or infants, and could be valuable in preventing developmental delays associated with iron deficiencies, according to findings from a large randomized controlled trial.

Dr. Camila M. Chaparro of the University of California, Davis, and colleagues reported results from 358 mother-and-singleton infant pairs delivered at a large obstetric hospital in Mexico City. The primary outcomes were infant blood and iron status at age 6 months—the longest follow-up to date in any trial of delayed cord clamping (Lancet 2006;367:1997–2004).

The investigators randomized mothers to one of two groups: In one group, the umbilical cord was clamped after 10 seconds. In the other group, it was clamped after 2 minutes—coinciding roughly with the usual cessation of cord pulsations—unless the physician determined earlier cord removal was necessary. Ultimately, the mean clamping time for the early-clamping group was roughly 17 seconds, compared with about 94 seconds for the delayed-clamping group—a difference of just over 1 minute.

At 6 months of age, the delayed-clamping infants had significantly higher levels than the early-clamping infants in several measures (adjusted for maternal factors): stored iron (58 mg vs. 31 mg), body iron (343 mg vs. 316 mg), mean corpuscular volume (81.0 fL vs. 79.5 fL), and ferritin (50.7 mcg/L vs. 34.4 mcg/L). Moreover, the incidence of iron deficiency (less than 9 mcg/L) in the early-clamping infants was 7%, compared with 1% in the delayed-clamping group, and unadjusted incidence of iron-deficiency anemia was 4% in early-clamping infants vs. 0% in the delayed-clamping group, the investigators noted.