In the United States contraception practices are slowly improving, with robust evidence for the increased use of long-acting reversible contraceptives and preliminary data that the unintended pregnancy rate may be decreasing for the first time in many years.¹ There remains a major gap in contraception practice, however: US women with chronic disease who are at high risk for adverse pregnancy outcomes are not receiving adequate contraceptive counseling or adequate contraception.^2,3 In one study, the majority of women with hypertension, diabetes, epilepsy, stroke, heart disease, lupus, or thrombophilia were not using a prescription contraceptive.³

Recently, I have seen women with major medical problems, who have had many visits with specialists and primary care clinicians, but who have not had their contraceptive needs prioritized. Here are but a few examples:

Clearly, there is a major gap between current and optimal contraceptive services for women with chronic medical problems. Women with diabetes and heart disease are affected substantially, as the evidence I present in this editorial indicates. Studies also show that women taking teratogenic medications do not receive the vital counseling that they should regarding contraception. Given the potential detrimental adverse events to both mother and fetus, obstetrician-gynecologists are poised to offer solutions to this concerning inadequacy of care.

DiabetesWomen with diabetes and an abnormally elevated HbA_1c level are at high risk for many adverse pregnancy outcomes, including major congenital malformations and intrauterine fetal demise.⁴ Unfortunately, results of many studies indicate that women with diabetes are not receiving adequate contraceptive services.^5–7 In one review of records at Kaiser Permanente Northern California, investigators reported that 62% of 122,921 healthy women, but only 48% of 8,182 women with diabetes, received contraceptive counseling, a contraceptive prescription, or contraceptive services.⁵

Why is it that so many women with diabetes do not receive contraceptive services? One possibility is that clinicians are reluctant to prescribe oral hormonal contraceptives that contain estrogen to their patients with diabetes because of a perceived increased risk of cardiovascular events.⁸ In the Kaiser study, 31% of the healthy women, and only 13% of the women with diabetes, were using a pill, patch, or ring (most of which contain estrogen).⁵ In this same study, the rate of utilization of an IUD was similar in the healthy (6.5%) and diabetic (5.6%) women. The IUD is known to be safe for use in women with diabetes.⁹

The low rate of utilization of intrauterine contraception by women with diabetes is a gap that gynecologists are well positioned to help solve.

Heart diseaseIn developed countries, a major cause of maternal mortality is pregnancy among women with congenital or acquired heart disease.¹⁰ Misinformation is a common problem in contraceptive counseling. In a recent study of 83 sexually active women with congenital heart disease, 6 women were told that they could not use an IUD or progestin-implant because they were unsafe for those with repaired congenital heart disease.¹¹ In this cohort of women, who were at high risk for adverse pregnancy outcomes, 45% of pregnancies were unplanned, similar to the rate among healthy women.

On a positive note, authors of a small study from Maryland found that, among women with heart disease, the self-reported use of a contraceptive increased from 60% prepregnancy to 93% following delivery.¹²

Clearly, patient interaction with qualified women’s health clinicians can increase contraceptive use in those with high-risk medical issues.

Teratogenic medicationsShould reproductive-age women taking long-term methotrexate for treatment of rheumatoid conditions receive contraceptive counseling? The answer is clearly, “yes.” Methotrexate can cause fetal death or major congenital malformations, such as absence of digits and oxycephaly (premature closure of the skull sutures). All women of reproductive age prescribed known teratogens should receive effective contraception. Unfortunately, data do not indicate this is occurring.

In one study of 1,694 adolescents and young women aged 14 to 25 years who were prescribed a teratogen, only 29% received documented contraception counseling, and only 11% received a contraceptive prescription or were documented to be actively using a contraceptive.¹³ The most commonly prescribed teratogens in this study were topiramate, methotrexate, and isoretinoin. Among the specialists who prescribed the medications, dermatologists documented contraceptive counseling in 47% of visits—likely because of the federally mandated risk mitigation system for prescribing isoretinoin. Neurologists and hematologists were least likely to document contraceptive counseling, at 16% and 28%, respectively.¹³

In a study of 488,175 women aged 15 to 44 years receiving care from clinicians at Kaiser Permanente Northern California, contraceptive counseling documentation was compared among women prescribed US Food and Drug Administration (FDA) category A or B medications (nonteratogenic) versus FDA category D or X medications (teratogenic).¹⁴ The rate at which women had no contraceptive counseling recorded was similar whether a teratogenic (47.6%) or nonteratogenic (46%) medication was prescribed. Clearly, there is a gap between current and optimal practice when teratogens are prescribed to women of reproductive age.

What could improve contraceptive services for women with serious medical problems?One promising approach is to include contraception status as a vital sign for all women and men of reproductive age. Most electronic medical records prioritize assessment of such health vital signs as allergies, smoking status, depression screening, falls prevention, blood pressure, temperature, heart rate, weight, and height. Contraception status is of equal importance to these vital signs in women and men of reproductive age and should be routinely documented.

Another intervention is to create a standard of care in which reproductive-age women with major medical problems are routinely referred to a clinician who has the time and skill to provide a comprehensive contraception visit. Health systems could take greater responsibility for managing the contraception practices of their members. For example, within a given accountable care organization the electronic health record could be used to identify adult women of reproductive age with diabetes and an HbA_1c level greater than 7%. These women could be contacted to ascertain their contraception status and their need for a contraception health visit. Electronic health records could be utilized to identify all reproductive-age women taking a teratogenic medication. A computer-generated alert could be sent to the responsible clinician recommending referral to an obstetrician-gynecologist for a contraceptive services visit.¹⁵

Pharmacists could be more proactive in highlighting the importance of contraception for women prescribed teratogens and in recommending a contraceptive visit. In some states pharmacists can offer an oral hormonal contraceptive to women who are prescribed a teratogen and at risk for becoming pregnant.

How do you propose to address lack of counseling?As an experienced clinician, you likely have ideas about how to improve contraceptive counseling for women with significant medical problems. Please let me know what interventions you think would best improve the use of contraception in this group of high-risk women by emailing me at OBG Management: [email protected].

Tell us…What are your ideas to improve contraception counseling for women with significant medical problems that put them at high risk for adverse pregnancy outcomes?

Send your letter to the editor to [email protected]. Please include the city and state in which you practice

In the United States contraception practices are slowly improving, with robust evidence for the increased use of long-acting reversible contraceptives and preliminary data that the unintended pregnancy rate may be decreasing for the first time in many years.¹ There remains a major gap in contraception practice, however: US women with chronic disease who are at high risk for adverse pregnancy outcomes are not receiving adequate contraceptive counseling or adequate contraception.^2,3 In one study, the majority of women with hypertension, diabetes, epilepsy, stroke, heart disease, lupus, or thrombophilia were not using a prescription contraceptive.³

Recently, I have seen women with major medical problems, who have had many visits with specialists and primary care clinicians, but who have not had their contraceptive needs prioritized. Here are but a few examples:

Clearly, there is a major gap between current and optimal contraceptive services for women with chronic medical problems. Women with diabetes and heart disease are affected substantially, as the evidence I present in this editorial indicates. Studies also show that women taking teratogenic medications do not receive the vital counseling that they should regarding contraception. Given the potential detrimental adverse events to both mother and fetus, obstetrician-gynecologists are poised to offer solutions to this concerning inadequacy of care.

DiabetesWomen with diabetes and an abnormally elevated HbA_1c level are at high risk for many adverse pregnancy outcomes, including major congenital malformations and intrauterine fetal demise.⁴ Unfortunately, results of many studies indicate that women with diabetes are not receiving adequate contraceptive services.^5–7 In one review of records at Kaiser Permanente Northern California, investigators reported that 62% of 122,921 healthy women, but only 48% of 8,182 women with diabetes, received contraceptive counseling, a contraceptive prescription, or contraceptive services.⁵

Why is it that so many women with diabetes do not receive contraceptive services? One possibility is that clinicians are reluctant to prescribe oral hormonal contraceptives that contain estrogen to their patients with diabetes because of a perceived increased risk of cardiovascular events.⁸ In the Kaiser study, 31% of the healthy women, and only 13% of the women with diabetes, were using a pill, patch, or ring (most of which contain estrogen).⁵ In this same study, the rate of utilization of an IUD was similar in the healthy (6.5%) and diabetic (5.6%) women. The IUD is known to be safe for use in women with diabetes.⁹

The low rate of utilization of intrauterine contraception by women with diabetes is a gap that gynecologists are well positioned to help solve.

Heart diseaseIn developed countries, a major cause of maternal mortality is pregnancy among women with congenital or acquired heart disease.¹⁰ Misinformation is a common problem in contraceptive counseling. In a recent study of 83 sexually active women with congenital heart disease, 6 women were told that they could not use an IUD or progestin-implant because they were unsafe for those with repaired congenital heart disease.¹¹ In this cohort of women, who were at high risk for adverse pregnancy outcomes, 45% of pregnancies were unplanned, similar to the rate among healthy women.

On a positive note, authors of a small study from Maryland found that, among women with heart disease, the self-reported use of a contraceptive increased from 60% prepregnancy to 93% following delivery.¹²

Clearly, patient interaction with qualified women’s health clinicians can increase contraceptive use in those with high-risk medical issues.

Teratogenic medicationsShould reproductive-age women taking long-term methotrexate for treatment of rheumatoid conditions receive contraceptive counseling? The answer is clearly, “yes.” Methotrexate can cause fetal death or major congenital malformations, such as absence of digits and oxycephaly (premature closure of the skull sutures). All women of reproductive age prescribed known teratogens should receive effective contraception. Unfortunately, data do not indicate this is occurring.

In one study of 1,694 adolescents and young women aged 14 to 25 years who were prescribed a teratogen, only 29% received documented contraception counseling, and only 11% received a contraceptive prescription or were documented to be actively using a contraceptive.¹³ The most commonly prescribed teratogens in this study were topiramate, methotrexate, and isoretinoin. Among the specialists who prescribed the medications, dermatologists documented contraceptive counseling in 47% of visits—likely because of the federally mandated risk mitigation system for prescribing isoretinoin. Neurologists and hematologists were least likely to document contraceptive counseling, at 16% and 28%, respectively.¹³

In a study of 488,175 women aged 15 to 44 years receiving care from clinicians at Kaiser Permanente Northern California, contraceptive counseling documentation was compared among women prescribed US Food and Drug Administration (FDA) category A or B medications (nonteratogenic) versus FDA category D or X medications (teratogenic).¹⁴ The rate at which women had no contraceptive counseling recorded was similar whether a teratogenic (47.6%) or nonteratogenic (46%) medication was prescribed. Clearly, there is a gap between current and optimal practice when teratogens are prescribed to women of reproductive age.

What could improve contraceptive services for women with serious medical problems?One promising approach is to include contraception status as a vital sign for all women and men of reproductive age. Most electronic medical records prioritize assessment of such health vital signs as allergies, smoking status, depression screening, falls prevention, blood pressure, temperature, heart rate, weight, and height. Contraception status is of equal importance to these vital signs in women and men of reproductive age and should be routinely documented.

Another intervention is to create a standard of care in which reproductive-age women with major medical problems are routinely referred to a clinician who has the time and skill to provide a comprehensive contraception visit. Health systems could take greater responsibility for managing the contraception practices of their members. For example, within a given accountable care organization the electronic health record could be used to identify adult women of reproductive age with diabetes and an HbA_1c level greater than 7%. These women could be contacted to ascertain their contraception status and their need for a contraception health visit. Electronic health records could be utilized to identify all reproductive-age women taking a teratogenic medication. A computer-generated alert could be sent to the responsible clinician recommending referral to an obstetrician-gynecologist for a contraceptive services visit.¹⁵

Pharmacists could be more proactive in highlighting the importance of contraception for women prescribed teratogens and in recommending a contraceptive visit. In some states pharmacists can offer an oral hormonal contraceptive to women who are prescribed a teratogen and at risk for becoming pregnant.

How do you propose to address lack of counseling?As an experienced clinician, you likely have ideas about how to improve contraceptive counseling for women with significant medical problems. Please let me know what interventions you think would best improve the use of contraception in this group of high-risk women by emailing me at OBG Management: [email protected].

Tell us…What are your ideas to improve contraception counseling for women with significant medical problems that put them at high risk for adverse pregnancy outcomes?

Send your letter to the editor to [email protected]. Please include the city and state in which you practice

In the United States contraception practices are slowly improving, with robust evidence for the increased use of long-acting reversible contraceptives and preliminary data that the unintended pregnancy rate may be decreasing for the first time in many years.¹ There remains a major gap in contraception practice, however: US women with chronic disease who are at high risk for adverse pregnancy outcomes are not receiving adequate contraceptive counseling or adequate contraception.^2,3 In one study, the majority of women with hypertension, diabetes, epilepsy, stroke, heart disease, lupus, or thrombophilia were not using a prescription contraceptive.³

Recently, I have seen women with major medical problems, who have had many visits with specialists and primary care clinicians, but who have not had their contraceptive needs prioritized. Here are but a few examples:

Clearly, there is a major gap between current and optimal contraceptive services for women with chronic medical problems. Women with diabetes and heart disease are affected substantially, as the evidence I present in this editorial indicates. Studies also show that women taking teratogenic medications do not receive the vital counseling that they should regarding contraception. Given the potential detrimental adverse events to both mother and fetus, obstetrician-gynecologists are poised to offer solutions to this concerning inadequacy of care.

DiabetesWomen with diabetes and an abnormally elevated HbA_1c level are at high risk for many adverse pregnancy outcomes, including major congenital malformations and intrauterine fetal demise.⁴ Unfortunately, results of many studies indicate that women with diabetes are not receiving adequate contraceptive services.^5–7 In one review of records at Kaiser Permanente Northern California, investigators reported that 62% of 122,921 healthy women, but only 48% of 8,182 women with diabetes, received contraceptive counseling, a contraceptive prescription, or contraceptive services.⁵

Why is it that so many women with diabetes do not receive contraceptive services? One possibility is that clinicians are reluctant to prescribe oral hormonal contraceptives that contain estrogen to their patients with diabetes because of a perceived increased risk of cardiovascular events.⁸ In the Kaiser study, 31% of the healthy women, and only 13% of the women with diabetes, were using a pill, patch, or ring (most of which contain estrogen).⁵ In this same study, the rate of utilization of an IUD was similar in the healthy (6.5%) and diabetic (5.6%) women. The IUD is known to be safe for use in women with diabetes.⁹

The low rate of utilization of intrauterine contraception by women with diabetes is a gap that gynecologists are well positioned to help solve.

Heart diseaseIn developed countries, a major cause of maternal mortality is pregnancy among women with congenital or acquired heart disease.¹⁰ Misinformation is a common problem in contraceptive counseling. In a recent study of 83 sexually active women with congenital heart disease, 6 women were told that they could not use an IUD or progestin-implant because they were unsafe for those with repaired congenital heart disease.¹¹ In this cohort of women, who were at high risk for adverse pregnancy outcomes, 45% of pregnancies were unplanned, similar to the rate among healthy women.

On a positive note, authors of a small study from Maryland found that, among women with heart disease, the self-reported use of a contraceptive increased from 60% prepregnancy to 93% following delivery.¹²

Clearly, patient interaction with qualified women’s health clinicians can increase contraceptive use in those with high-risk medical issues.

Teratogenic medicationsShould reproductive-age women taking long-term methotrexate for treatment of rheumatoid conditions receive contraceptive counseling? The answer is clearly, “yes.” Methotrexate can cause fetal death or major congenital malformations, such as absence of digits and oxycephaly (premature closure of the skull sutures). All women of reproductive age prescribed known teratogens should receive effective contraception. Unfortunately, data do not indicate this is occurring.

In one study of 1,694 adolescents and young women aged 14 to 25 years who were prescribed a teratogen, only 29% received documented contraception counseling, and only 11% received a contraceptive prescription or were documented to be actively using a contraceptive.¹³ The most commonly prescribed teratogens in this study were topiramate, methotrexate, and isoretinoin. Among the specialists who prescribed the medications, dermatologists documented contraceptive counseling in 47% of visits—likely because of the federally mandated risk mitigation system for prescribing isoretinoin. Neurologists and hematologists were least likely to document contraceptive counseling, at 16% and 28%, respectively.¹³

In a study of 488,175 women aged 15 to 44 years receiving care from clinicians at Kaiser Permanente Northern California, contraceptive counseling documentation was compared among women prescribed US Food and Drug Administration (FDA) category A or B medications (nonteratogenic) versus FDA category D or X medications (teratogenic).¹⁴ The rate at which women had no contraceptive counseling recorded was similar whether a teratogenic (47.6%) or nonteratogenic (46%) medication was prescribed. Clearly, there is a gap between current and optimal practice when teratogens are prescribed to women of reproductive age.

What could improve contraceptive services for women with serious medical problems?One promising approach is to include contraception status as a vital sign for all women and men of reproductive age. Most electronic medical records prioritize assessment of such health vital signs as allergies, smoking status, depression screening, falls prevention, blood pressure, temperature, heart rate, weight, and height. Contraception status is of equal importance to these vital signs in women and men of reproductive age and should be routinely documented.

Another intervention is to create a standard of care in which reproductive-age women with major medical problems are routinely referred to a clinician who has the time and skill to provide a comprehensive contraception visit. Health systems could take greater responsibility for managing the contraception practices of their members. For example, within a given accountable care organization the electronic health record could be used to identify adult women of reproductive age with diabetes and an HbA_1c level greater than 7%. These women could be contacted to ascertain their contraception status and their need for a contraception health visit. Electronic health records could be utilized to identify all reproductive-age women taking a teratogenic medication. A computer-generated alert could be sent to the responsible clinician recommending referral to an obstetrician-gynecologist for a contraceptive services visit.¹⁵

Pharmacists could be more proactive in highlighting the importance of contraception for women prescribed teratogens and in recommending a contraceptive visit. In some states pharmacists can offer an oral hormonal contraceptive to women who are prescribed a teratogen and at risk for becoming pregnant.

How do you propose to address lack of counseling?As an experienced clinician, you likely have ideas about how to improve contraceptive counseling for women with significant medical problems. Please let me know what interventions you think would best improve the use of contraception in this group of high-risk women by emailing me at OBG Management: [email protected].

Tell us…What are your ideas to improve contraception counseling for women with significant medical problems that put them at high risk for adverse pregnancy outcomes?

Send your letter to the editor to [email protected]. Please include the city and state in which you practice

After previous attempts in Turkey and Saudi Arabia, the first successful uterine transplantation occurred in 2013. The team of successful surgeons was located in Gothenburg, Sweden, led by Mats Brännström, MD. The team performed 9 transplants in all, and the first birth of a healthy baby boy in October 2014 marked a medical breakthrough.¹ The woman who received the transplanted uterus was born without one, a condition known as Mayer-Rokitanksy-Küster-Hauser syndrome, a cause of uterine factor infertility (UFI).

The previous options for having a child for women with UFI (which is the absence of a functional uterus, either congenital or acquired) were adoption or a gestational carrier/surrogacy.² Surrogacy is not an option for many women, however, as in many countries, including Sweden, the use of gestational carriers and its associated contracts is illegal. All Muslim countries prohibit gestational carriers. Surrogacy also is prohibited in 3 US states, including New York, Michigan, and Arizona. Laws in other US states vary widely.³

Tommaso Falcone, MD, professor and chair, Department of Obstetrics and Gynecology, at the Cleveland Clinic in Cleveland, Ohio, is now co–Principal Investigator on a clinical trial assessing uterine transplantation at his institution, the first such surgeries to be performed in the United States. There will be 7 phases involved in the study: primary and secondary screening, medical evaluation, in vitro fertilization (IVF) with cryopreservation of sufficient number of embryos, transplantation and use of antirejection drugs, embryo transfer, pregnancy/delivery, and ultimately removal of the transplanted uterus. The study team is approved to enroll 10 women.⁴

OBG Management recently caught up with Dr. Falcone on his groundbreaking, and controversial, endeavor.
 

OBG Management: When did the thought of performing uterus transplantation enter your mind?
Tommaso Falcone, MD: The idea for uterus transplants was brought to my attention for the first time in Boston in 2007, at an annual meeting of the International Society for Fertility Preservation (ISFP). It was the inaugural meeting for ISFP, a society focused on helping women with cancer to protect their fertility. In 2007, we talked about the standard topics regarding fertility preservation: IVF and ovarian tissue cryopreservation. Then, right at the end of the meeting, was a presentation on uterus transplantation. Upon hearing the presenter, my thought was, “This will never happen in America, for many reasons.”

As time went on, I concentrated my energy more on ovarian tissue transplants for fertility preservation. Then a couple of years ago Andreas G. Tzakis, MD, a transplant surgeon from the University of Miami joined the Cleveland Clinic Florida. Dr. Tzakis was involved with the Swedish Group, including Mats Brännström’s transplant work in humans.

Of course, Dr. Tzakis had had a completely different journey to lead him to uterus transplantation. But as the director of solid organ transplant surgery at the Cleveland Clinic hospital in Florida, he said to me, “I think we should do this. There are many women who have asked for this procedure.” I was not sure at first, but I was interested in going to Sweden to see Dr. Brännström perform his last of 9 uterus transplants.

In Sweden, I asked Dr. Brännström if I could meet the women he already had performed the transplants on. I had certain preconceived notions on which types of women would accept this kind of major surgery to treat their infertility due to absence of a uterus. I expected perhaps that these women could have been coerced into accepting this surgery as a plausible option since surrogacy was not possible for them. I found out, as people usually do, that my preconceived notions were wrong. The women that I met said, “No, we’ve done this because we wanted to.” The women had independently come to a decision that experiencing pregnancy was important in their lives. There was no coercion. They understood the risks. However, I did not meet the uterus donors.

When I got on the plane to return home, I said to myself, we have to offer this service because it is part of the choices that women have to treat their reproductive infertility.

OBG Management: What are the hurdles you have had to overcome to bring this groundbreaking surgery to the Cleveland Clinic?
Dr. Falcone, MD: As soon as I returned from Sweden, we began the internal review board (IRB) approval process, which was extremely long. The first decision was: Do we use a live donor, as they do in Sweden, in America?

We analyzed the data from the Swedes and found that the surgery is very long for the donor and it put some of the donors, especially those who were older and placed on hormones, at risk for venous thromboembolism. (No blood clots had occurred in the Swedish trial.) In addition, there were some complications for patients. Although not major complications, we felt that these could be limited.

To remove the variable of risks for the donor, we decided that we would go in another direction and use the typical approach to donor transplants that is taken in this country, which is to use cadaveric, or brain dead, donors. The use of deceased donors allows us to isolate larger vascular pedicles for transplantation. Although we do not have IRB approval for live donors we are working in animal models to come up with an alternative technique to obtain vessels appropriate for anastomosis.

To address complications for the recipient, including the necessity to continually take antirejection, or immunosuppressive, medications, our recommendation to patients who undergo uterus transplantation surgery is to remove the uterus after delivery of 2 babies. Our plan at that time will be to perform a cesarean delivery and remove the uterus.

Right now in the process we are going through the screening phase and beginning IVF. We are approved for 10 women, and all potential recipients went through the necessary criteria, including psychological counseling. During IVF, each woman needs to have between 6 and 10 embryos (blastocysts).

OBG Management: Do you think that organ transplant pioneers foresaw successful transplantation of a uterus?
Dr. Falcone, MD: I do not think Dr. Tzakis, who is a transplant pioneer and has been doing this his entire career of 25 years or so, even foresaw this. This is something that has evolved over time. The first transplants (of kidney, heart, and liver) were to save lives. Subsequently, quality-of- life transplants have occurred, such as the face transplant and the larynx transplant. Uterus transplants are not to save lives, but they do improve quality of life, and I think that is what is important.

There is a lot of controversy surrounding this procedure—just like many aspects of reproductive medicine. A lot of what we do is full of controversy: IVF, gestational carriers, and genetic screening in utero. But we are in the quality-of-life era with transplantation medicine. If women have a strong desire to carry their own child, and surrogacy is not an option, then this may be one.

Tommasso Falcone, MD, was co-director of the Pelvic Anatomy and Gynecologic Surgery (PAGS) Symposium held in Las Vegas, Nevada, December 10–12, 2015. He offered workshops and seminars during the Scientific Program on diverse topics, including: hysteroscopy; ultrasonography; pelvic and abdominal anatomy; myometomy; hysterectomy; endometriosis; avoiding laparoscopic complications; medicolegal considerations; and surgical tips and techniques.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

After previous attempts in Turkey and Saudi Arabia, the first successful uterine transplantation occurred in 2013. The team of successful surgeons was located in Gothenburg, Sweden, led by Mats Brännström, MD. The team performed 9 transplants in all, and the first birth of a healthy baby boy in October 2014 marked a medical breakthrough.¹ The woman who received the transplanted uterus was born without one, a condition known as Mayer-Rokitanksy-Küster-Hauser syndrome, a cause of uterine factor infertility (UFI).

The previous options for having a child for women with UFI (which is the absence of a functional uterus, either congenital or acquired) were adoption or a gestational carrier/surrogacy.² Surrogacy is not an option for many women, however, as in many countries, including Sweden, the use of gestational carriers and its associated contracts is illegal. All Muslim countries prohibit gestational carriers. Surrogacy also is prohibited in 3 US states, including New York, Michigan, and Arizona. Laws in other US states vary widely.³

Tommaso Falcone, MD, professor and chair, Department of Obstetrics and Gynecology, at the Cleveland Clinic in Cleveland, Ohio, is now co–Principal Investigator on a clinical trial assessing uterine transplantation at his institution, the first such surgeries to be performed in the United States. There will be 7 phases involved in the study: primary and secondary screening, medical evaluation, in vitro fertilization (IVF) with cryopreservation of sufficient number of embryos, transplantation and use of antirejection drugs, embryo transfer, pregnancy/delivery, and ultimately removal of the transplanted uterus. The study team is approved to enroll 10 women.⁴

OBG Management recently caught up with Dr. Falcone on his groundbreaking, and controversial, endeavor.
 

OBG Management: When did the thought of performing uterus transplantation enter your mind?
Tommaso Falcone, MD: The idea for uterus transplants was brought to my attention for the first time in Boston in 2007, at an annual meeting of the International Society for Fertility Preservation (ISFP). It was the inaugural meeting for ISFP, a society focused on helping women with cancer to protect their fertility. In 2007, we talked about the standard topics regarding fertility preservation: IVF and ovarian tissue cryopreservation. Then, right at the end of the meeting, was a presentation on uterus transplantation. Upon hearing the presenter, my thought was, “This will never happen in America, for many reasons.”

As time went on, I concentrated my energy more on ovarian tissue transplants for fertility preservation. Then a couple of years ago Andreas G. Tzakis, MD, a transplant surgeon from the University of Miami joined the Cleveland Clinic Florida. Dr. Tzakis was involved with the Swedish Group, including Mats Brännström’s transplant work in humans.

Of course, Dr. Tzakis had had a completely different journey to lead him to uterus transplantation. But as the director of solid organ transplant surgery at the Cleveland Clinic hospital in Florida, he said to me, “I think we should do this. There are many women who have asked for this procedure.” I was not sure at first, but I was interested in going to Sweden to see Dr. Brännström perform his last of 9 uterus transplants.

In Sweden, I asked Dr. Brännström if I could meet the women he already had performed the transplants on. I had certain preconceived notions on which types of women would accept this kind of major surgery to treat their infertility due to absence of a uterus. I expected perhaps that these women could have been coerced into accepting this surgery as a plausible option since surrogacy was not possible for them. I found out, as people usually do, that my preconceived notions were wrong. The women that I met said, “No, we’ve done this because we wanted to.” The women had independently come to a decision that experiencing pregnancy was important in their lives. There was no coercion. They understood the risks. However, I did not meet the uterus donors.

When I got on the plane to return home, I said to myself, we have to offer this service because it is part of the choices that women have to treat their reproductive infertility.

OBG Management: What are the hurdles you have had to overcome to bring this groundbreaking surgery to the Cleveland Clinic?
Dr. Falcone, MD: As soon as I returned from Sweden, we began the internal review board (IRB) approval process, which was extremely long. The first decision was: Do we use a live donor, as they do in Sweden, in America?

We analyzed the data from the Swedes and found that the surgery is very long for the donor and it put some of the donors, especially those who were older and placed on hormones, at risk for venous thromboembolism. (No blood clots had occurred in the Swedish trial.) In addition, there were some complications for patients. Although not major complications, we felt that these could be limited.

To remove the variable of risks for the donor, we decided that we would go in another direction and use the typical approach to donor transplants that is taken in this country, which is to use cadaveric, or brain dead, donors. The use of deceased donors allows us to isolate larger vascular pedicles for transplantation. Although we do not have IRB approval for live donors we are working in animal models to come up with an alternative technique to obtain vessels appropriate for anastomosis.

To address complications for the recipient, including the necessity to continually take antirejection, or immunosuppressive, medications, our recommendation to patients who undergo uterus transplantation surgery is to remove the uterus after delivery of 2 babies. Our plan at that time will be to perform a cesarean delivery and remove the uterus.

Right now in the process we are going through the screening phase and beginning IVF. We are approved for 10 women, and all potential recipients went through the necessary criteria, including psychological counseling. During IVF, each woman needs to have between 6 and 10 embryos (blastocysts).

OBG Management: Do you think that organ transplant pioneers foresaw successful transplantation of a uterus?
Dr. Falcone, MD: I do not think Dr. Tzakis, who is a transplant pioneer and has been doing this his entire career of 25 years or so, even foresaw this. This is something that has evolved over time. The first transplants (of kidney, heart, and liver) were to save lives. Subsequently, quality-of- life transplants have occurred, such as the face transplant and the larynx transplant. Uterus transplants are not to save lives, but they do improve quality of life, and I think that is what is important.

There is a lot of controversy surrounding this procedure—just like many aspects of reproductive medicine. A lot of what we do is full of controversy: IVF, gestational carriers, and genetic screening in utero. But we are in the quality-of-life era with transplantation medicine. If women have a strong desire to carry their own child, and surrogacy is not an option, then this may be one.

Tommasso Falcone, MD, was co-director of the Pelvic Anatomy and Gynecologic Surgery (PAGS) Symposium held in Las Vegas, Nevada, December 10–12, 2015. He offered workshops and seminars during the Scientific Program on diverse topics, including: hysteroscopy; ultrasonography; pelvic and abdominal anatomy; myometomy; hysterectomy; endometriosis; avoiding laparoscopic complications; medicolegal considerations; and surgical tips and techniques.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

After previous attempts in Turkey and Saudi Arabia, the first successful uterine transplantation occurred in 2013. The team of successful surgeons was located in Gothenburg, Sweden, led by Mats Brännström, MD. The team performed 9 transplants in all, and the first birth of a healthy baby boy in October 2014 marked a medical breakthrough.¹ The woman who received the transplanted uterus was born without one, a condition known as Mayer-Rokitanksy-Küster-Hauser syndrome, a cause of uterine factor infertility (UFI).

The previous options for having a child for women with UFI (which is the absence of a functional uterus, either congenital or acquired) were adoption or a gestational carrier/surrogacy.² Surrogacy is not an option for many women, however, as in many countries, including Sweden, the use of gestational carriers and its associated contracts is illegal. All Muslim countries prohibit gestational carriers. Surrogacy also is prohibited in 3 US states, including New York, Michigan, and Arizona. Laws in other US states vary widely.³

Tommaso Falcone, MD, professor and chair, Department of Obstetrics and Gynecology, at the Cleveland Clinic in Cleveland, Ohio, is now co–Principal Investigator on a clinical trial assessing uterine transplantation at his institution, the first such surgeries to be performed in the United States. There will be 7 phases involved in the study: primary and secondary screening, medical evaluation, in vitro fertilization (IVF) with cryopreservation of sufficient number of embryos, transplantation and use of antirejection drugs, embryo transfer, pregnancy/delivery, and ultimately removal of the transplanted uterus. The study team is approved to enroll 10 women.⁴

OBG Management recently caught up with Dr. Falcone on his groundbreaking, and controversial, endeavor.
 

OBG Management: When did the thought of performing uterus transplantation enter your mind?
Tommaso Falcone, MD: The idea for uterus transplants was brought to my attention for the first time in Boston in 2007, at an annual meeting of the International Society for Fertility Preservation (ISFP). It was the inaugural meeting for ISFP, a society focused on helping women with cancer to protect their fertility. In 2007, we talked about the standard topics regarding fertility preservation: IVF and ovarian tissue cryopreservation. Then, right at the end of the meeting, was a presentation on uterus transplantation. Upon hearing the presenter, my thought was, “This will never happen in America, for many reasons.”

As time went on, I concentrated my energy more on ovarian tissue transplants for fertility preservation. Then a couple of years ago Andreas G. Tzakis, MD, a transplant surgeon from the University of Miami joined the Cleveland Clinic Florida. Dr. Tzakis was involved with the Swedish Group, including Mats Brännström’s transplant work in humans.

Of course, Dr. Tzakis had had a completely different journey to lead him to uterus transplantation. But as the director of solid organ transplant surgery at the Cleveland Clinic hospital in Florida, he said to me, “I think we should do this. There are many women who have asked for this procedure.” I was not sure at first, but I was interested in going to Sweden to see Dr. Brännström perform his last of 9 uterus transplants.

In Sweden, I asked Dr. Brännström if I could meet the women he already had performed the transplants on. I had certain preconceived notions on which types of women would accept this kind of major surgery to treat their infertility due to absence of a uterus. I expected perhaps that these women could have been coerced into accepting this surgery as a plausible option since surrogacy was not possible for them. I found out, as people usually do, that my preconceived notions were wrong. The women that I met said, “No, we’ve done this because we wanted to.” The women had independently come to a decision that experiencing pregnancy was important in their lives. There was no coercion. They understood the risks. However, I did not meet the uterus donors.

When I got on the plane to return home, I said to myself, we have to offer this service because it is part of the choices that women have to treat their reproductive infertility.

OBG Management: What are the hurdles you have had to overcome to bring this groundbreaking surgery to the Cleveland Clinic?
Dr. Falcone, MD: As soon as I returned from Sweden, we began the internal review board (IRB) approval process, which was extremely long. The first decision was: Do we use a live donor, as they do in Sweden, in America?

We analyzed the data from the Swedes and found that the surgery is very long for the donor and it put some of the donors, especially those who were older and placed on hormones, at risk for venous thromboembolism. (No blood clots had occurred in the Swedish trial.) In addition, there were some complications for patients. Although not major complications, we felt that these could be limited.

To remove the variable of risks for the donor, we decided that we would go in another direction and use the typical approach to donor transplants that is taken in this country, which is to use cadaveric, or brain dead, donors. The use of deceased donors allows us to isolate larger vascular pedicles for transplantation. Although we do not have IRB approval for live donors we are working in animal models to come up with an alternative technique to obtain vessels appropriate for anastomosis.

To address complications for the recipient, including the necessity to continually take antirejection, or immunosuppressive, medications, our recommendation to patients who undergo uterus transplantation surgery is to remove the uterus after delivery of 2 babies. Our plan at that time will be to perform a cesarean delivery and remove the uterus.

Right now in the process we are going through the screening phase and beginning IVF. We are approved for 10 women, and all potential recipients went through the necessary criteria, including psychological counseling. During IVF, each woman needs to have between 6 and 10 embryos (blastocysts).

OBG Management: Do you think that organ transplant pioneers foresaw successful transplantation of a uterus?
Dr. Falcone, MD: I do not think Dr. Tzakis, who is a transplant pioneer and has been doing this his entire career of 25 years or so, even foresaw this. This is something that has evolved over time. The first transplants (of kidney, heart, and liver) were to save lives. Subsequently, quality-of- life transplants have occurred, such as the face transplant and the larynx transplant. Uterus transplants are not to save lives, but they do improve quality of life, and I think that is what is important.

There is a lot of controversy surrounding this procedure—just like many aspects of reproductive medicine. A lot of what we do is full of controversy: IVF, gestational carriers, and genetic screening in utero. But we are in the quality-of-life era with transplantation medicine. If women have a strong desire to carry their own child, and surrogacy is not an option, then this may be one.

Tommasso Falcone, MD, was co-director of the Pelvic Anatomy and Gynecologic Surgery (PAGS) Symposium held in Las Vegas, Nevada, December 10–12, 2015. He offered workshops and seminars during the Scientific Program on diverse topics, including: hysteroscopy; ultrasonography; pelvic and abdominal anatomy; myometomy; hysterectomy; endometriosis; avoiding laparoscopic complications; medicolegal considerations; and surgical tips and techniques.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

FemTouch is designed for use with the Lumenis AcuPulse™ MultiMode™ SuperPulse™ CO₂ Laser System, offering 10 built-in treatment modes.

FOR MORE INFORMATION, VISIT: www.lumenis.com

According to the manufacturer’s instructions, a woman folds and inserts the cup in the lower vagina above the pelvic bone. She empties the cup 2 to 4 times per day and can use it overnight. Between uses, she rinses the cup with water and washes it with warm soapy water before reinsertion. When water is not available, toilet paper can be used for cleaning. For thorough cleaning, a woman can place the cup in boiling water then disinfect it with alcohol. Lunette should be cleaned after menses and stored in its own bag. The FDA recommends replacing the cup every 2 to 3 years.

Lunette is designed for all women, including those who have not had sexual intercourse and those who use an IUD or contraceptive ring (consult a physician). Lunette is available in 2 sizes: Model 1 is generally for those with light to moderate flow; Model 2 is recommended for normal or heavier flow. A detailed sizing guide is found on the website.

FOR MORE INFORMATION, VISIT: www.lunette.com/us
 

The ROCA Test uses a woman’s age, menopausal status, risk status, and serial blood measurements of CA 125 to produce a score that indicates current likelihood of having ovarian cancer. The initial risk assessment is then modified based on how closely a patient’s CA 125 profile matches the profiles seen in healthy women and women with ovarian cancer.

The test is intended for postmenopausal women between the ages of 50 and 85 years with no known risk factors other than age and for women between the ages of 35 and 85 years who are considered high risk due to family history of ovarian or breast cancer, have BRCA1 or BRCA2 gene mutations, or have Lynch Syndrome. The ROCA Test is now available in 15 states and the District of Columbia, and will be offered to additional areas of the United States in 2016.

After purchasing a ROCA Test online, the patient will receive an instructional kit, which she will take to her physician to review her medical history and sign a consent form. A blood sample will be drawn and sent to the ROCA Test laboratory. The physician will receive and share the test results with the patient. High-risk patients are encouraged to complete 3 tests per year.

FOR MORE INFORMATION, VISIT: www.rocatest.com
 

A semen sample can be collected at home and then shipped to the sperm banking facilities at Cleveland Clinic’s Andrology Center in Cleveland,Ohio. There, the sperm will be cryopreserved for as long as desired; an annual storage fee will be charged.

FOR MORE INFORMATION, VISIT: www.fairhavenhealth.com/nextgen-home-sperm-banking-kit.html

FemTouch is designed for use with the Lumenis AcuPulse™ MultiMode™ SuperPulse™ CO₂ Laser System, offering 10 built-in treatment modes.

FOR MORE INFORMATION, VISIT: www.lumenis.com

According to the manufacturer’s instructions, a woman folds and inserts the cup in the lower vagina above the pelvic bone. She empties the cup 2 to 4 times per day and can use it overnight. Between uses, she rinses the cup with water and washes it with warm soapy water before reinsertion. When water is not available, toilet paper can be used for cleaning. For thorough cleaning, a woman can place the cup in boiling water then disinfect it with alcohol. Lunette should be cleaned after menses and stored in its own bag. The FDA recommends replacing the cup every 2 to 3 years.

Lunette is designed for all women, including those who have not had sexual intercourse and those who use an IUD or contraceptive ring (consult a physician). Lunette is available in 2 sizes: Model 1 is generally for those with light to moderate flow; Model 2 is recommended for normal or heavier flow. A detailed sizing guide is found on the website.

FOR MORE INFORMATION, VISIT: www.lunette.com/us
 

The ROCA Test uses a woman’s age, menopausal status, risk status, and serial blood measurements of CA 125 to produce a score that indicates current likelihood of having ovarian cancer. The initial risk assessment is then modified based on how closely a patient’s CA 125 profile matches the profiles seen in healthy women and women with ovarian cancer.

The test is intended for postmenopausal women between the ages of 50 and 85 years with no known risk factors other than age and for women between the ages of 35 and 85 years who are considered high risk due to family history of ovarian or breast cancer, have BRCA1 or BRCA2 gene mutations, or have Lynch Syndrome. The ROCA Test is now available in 15 states and the District of Columbia, and will be offered to additional areas of the United States in 2016.

After purchasing a ROCA Test online, the patient will receive an instructional kit, which she will take to her physician to review her medical history and sign a consent form. A blood sample will be drawn and sent to the ROCA Test laboratory. The physician will receive and share the test results with the patient. High-risk patients are encouraged to complete 3 tests per year.

FOR MORE INFORMATION, VISIT: www.rocatest.com
 

A semen sample can be collected at home and then shipped to the sperm banking facilities at Cleveland Clinic’s Andrology Center in Cleveland,Ohio. There, the sperm will be cryopreserved for as long as desired; an annual storage fee will be charged.

FOR MORE INFORMATION, VISIT: www.fairhavenhealth.com/nextgen-home-sperm-banking-kit.html

FemTouch is designed for use with the Lumenis AcuPulse™ MultiMode™ SuperPulse™ CO₂ Laser System, offering 10 built-in treatment modes.

FOR MORE INFORMATION, VISIT: www.lumenis.com

According to the manufacturer’s instructions, a woman folds and inserts the cup in the lower vagina above the pelvic bone. She empties the cup 2 to 4 times per day and can use it overnight. Between uses, she rinses the cup with water and washes it with warm soapy water before reinsertion. When water is not available, toilet paper can be used for cleaning. For thorough cleaning, a woman can place the cup in boiling water then disinfect it with alcohol. Lunette should be cleaned after menses and stored in its own bag. The FDA recommends replacing the cup every 2 to 3 years.

Lunette is designed for all women, including those who have not had sexual intercourse and those who use an IUD or contraceptive ring (consult a physician). Lunette is available in 2 sizes: Model 1 is generally for those with light to moderate flow; Model 2 is recommended for normal or heavier flow. A detailed sizing guide is found on the website.

FOR MORE INFORMATION, VISIT: www.lunette.com/us
 

The ROCA Test uses a woman’s age, menopausal status, risk status, and serial blood measurements of CA 125 to produce a score that indicates current likelihood of having ovarian cancer. The initial risk assessment is then modified based on how closely a patient’s CA 125 profile matches the profiles seen in healthy women and women with ovarian cancer.

The test is intended for postmenopausal women between the ages of 50 and 85 years with no known risk factors other than age and for women between the ages of 35 and 85 years who are considered high risk due to family history of ovarian or breast cancer, have BRCA1 or BRCA2 gene mutations, or have Lynch Syndrome. The ROCA Test is now available in 15 states and the District of Columbia, and will be offered to additional areas of the United States in 2016.

After purchasing a ROCA Test online, the patient will receive an instructional kit, which she will take to her physician to review her medical history and sign a consent form. A blood sample will be drawn and sent to the ROCA Test laboratory. The physician will receive and share the test results with the patient. High-risk patients are encouraged to complete 3 tests per year.

FOR MORE INFORMATION, VISIT: www.rocatest.com
 

A semen sample can be collected at home and then shipped to the sperm banking facilities at Cleveland Clinic’s Andrology Center in Cleveland,Ohio. There, the sperm will be cryopreserved for as long as desired; an annual storage fee will be charged.

FOR MORE INFORMATION, VISIT: www.fairhavenhealth.com/nextgen-home-sperm-banking-kit.html

Cesarean delivery (CD), the most common surgery performed worldwide, is associated with increased morbidity and mortality compared with vaginal delivery. More than 230 randomized controlled trials (RCTs) have been published on varying technical aspects of CD, yet uncertainty remains regarding the optimal approach(es) to minimize perinatal morbidity.

Previous trials of one such technique, uterine closure, have not demonstrated short-term outcome differences among those randomized to single- versus double-layer closure. Results of long-term outcomes such as uterine rupture remain unclear. Emerging evidence also has associated cesarean scar defects with gynecologic problems like dysmenorrhea, pelvic pain, and postmenstrual spotting, further highlighting the importance of identifying surgical techniques that optimize uterine scar healing after CD.

Details of the study
In their recent RCT, Roberge and colleagues randomly assigned 81 women with singleton pregnancies undergoing elective primary CD (at ≥38 0/7 weeks) and compared the following uterine closure types on residual myometrial thickness during postpartum transvaginal ultrasound at 6 months:

In addition to addressing the single- versus double-layer debate, this study highlights another important aspect of closure technique: locked versus unlocked first-layer suture closure. The residual myometrial thickness, a surrogate measure of uterine scar healing, was significantly greater in those women randomly assigned to double-layer (locked or unlocked) closure compared with controls. Additionally, total myometrial thickness significantly increased in the double- layer unlocked closure group. There were no differences in the short-term outcomes of operative time or estimated blood loss among any of the groups.

Based on these findings, the authors advocate for double-layer unlocked uterine closure during CD to maximize uterine scar healing.

Bottom line
Double-layer uterine closure with unlocked first-layer at CD appears to maximize postpartum uterine scar thickness compared with other techniques; it remains unclear, however, if this improves short- or long-term outcomes. What this evidence means for practice
While residual and total myometrial thickness presents a feasible, albeit indirect, assessment of uterine scar healing, it remains unclear if double-layer unlocked first-layer closure decreases long-term adverse outcomes, such as subsequent uterine rupture, cesarean scar defects, or gynecologic morbidity compared with other techniques. Nevertheless, this study highlights the importance of future research specifying both single- or double-layer and locked or unlocked uterine closure techniques.
— Joshua D. Dahlke, MD

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Cesarean delivery (CD), the most common surgery performed worldwide, is associated with increased morbidity and mortality compared with vaginal delivery. More than 230 randomized controlled trials (RCTs) have been published on varying technical aspects of CD, yet uncertainty remains regarding the optimal approach(es) to minimize perinatal morbidity.

Previous trials of one such technique, uterine closure, have not demonstrated short-term outcome differences among those randomized to single- versus double-layer closure. Results of long-term outcomes such as uterine rupture remain unclear. Emerging evidence also has associated cesarean scar defects with gynecologic problems like dysmenorrhea, pelvic pain, and postmenstrual spotting, further highlighting the importance of identifying surgical techniques that optimize uterine scar healing after CD.

Details of the study
In their recent RCT, Roberge and colleagues randomly assigned 81 women with singleton pregnancies undergoing elective primary CD (at ≥38 0/7 weeks) and compared the following uterine closure types on residual myometrial thickness during postpartum transvaginal ultrasound at 6 months:

In addition to addressing the single- versus double-layer debate, this study highlights another important aspect of closure technique: locked versus unlocked first-layer suture closure. The residual myometrial thickness, a surrogate measure of uterine scar healing, was significantly greater in those women randomly assigned to double-layer (locked or unlocked) closure compared with controls. Additionally, total myometrial thickness significantly increased in the double- layer unlocked closure group. There were no differences in the short-term outcomes of operative time or estimated blood loss among any of the groups.

Based on these findings, the authors advocate for double-layer unlocked uterine closure during CD to maximize uterine scar healing.

Bottom line
Double-layer uterine closure with unlocked first-layer at CD appears to maximize postpartum uterine scar thickness compared with other techniques; it remains unclear, however, if this improves short- or long-term outcomes. What this evidence means for practice
While residual and total myometrial thickness presents a feasible, albeit indirect, assessment of uterine scar healing, it remains unclear if double-layer unlocked first-layer closure decreases long-term adverse outcomes, such as subsequent uterine rupture, cesarean scar defects, or gynecologic morbidity compared with other techniques. Nevertheless, this study highlights the importance of future research specifying both single- or double-layer and locked or unlocked uterine closure techniques.
— Joshua D. Dahlke, MD

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Cesarean delivery (CD), the most common surgery performed worldwide, is associated with increased morbidity and mortality compared with vaginal delivery. More than 230 randomized controlled trials (RCTs) have been published on varying technical aspects of CD, yet uncertainty remains regarding the optimal approach(es) to minimize perinatal morbidity.

Previous trials of one such technique, uterine closure, have not demonstrated short-term outcome differences among those randomized to single- versus double-layer closure. Results of long-term outcomes such as uterine rupture remain unclear. Emerging evidence also has associated cesarean scar defects with gynecologic problems like dysmenorrhea, pelvic pain, and postmenstrual spotting, further highlighting the importance of identifying surgical techniques that optimize uterine scar healing after CD.

Details of the study
In their recent RCT, Roberge and colleagues randomly assigned 81 women with singleton pregnancies undergoing elective primary CD (at ≥38 0/7 weeks) and compared the following uterine closure types on residual myometrial thickness during postpartum transvaginal ultrasound at 6 months:

In addition to addressing the single- versus double-layer debate, this study highlights another important aspect of closure technique: locked versus unlocked first-layer suture closure. The residual myometrial thickness, a surrogate measure of uterine scar healing, was significantly greater in those women randomly assigned to double-layer (locked or unlocked) closure compared with controls. Additionally, total myometrial thickness significantly increased in the double- layer unlocked closure group. There were no differences in the short-term outcomes of operative time or estimated blood loss among any of the groups.

Based on these findings, the authors advocate for double-layer unlocked uterine closure during CD to maximize uterine scar healing.

Bottom line
Double-layer uterine closure with unlocked first-layer at CD appears to maximize postpartum uterine scar thickness compared with other techniques; it remains unclear, however, if this improves short- or long-term outcomes. What this evidence means for practice
While residual and total myometrial thickness presents a feasible, albeit indirect, assessment of uterine scar healing, it remains unclear if double-layer unlocked first-layer closure decreases long-term adverse outcomes, such as subsequent uterine rupture, cesarean scar defects, or gynecologic morbidity compared with other techniques. Nevertheless, this study highlights the importance of future research specifying both single- or double-layer and locked or unlocked uterine closure techniques.
— Joshua D. Dahlke, MD

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Stroke during delivery: $35.4M verdict
During delivery, a 25-year-old woman had a hemorrhagic stroke that left her unable to care for herself or her child.

Patient’s claim The patient’s neurologist failed to advise the ObGyn that the patient had a history of brain aneurysm and a venous varix, which increased the risk for stroke during labor and delivery. The patient had shared her history with the ObGyn, and she requested that her neurologist contact the ObGyn.

Neurologist’s defense There was no negligence. The entire medical file had been delivered to the ObGyn. Any negligence was on the part of the ObGyn for failure to educate herself as to the patient’s condition.

Verdict A $35.4 million Massachusetts verdict was returned against the neurologist, including $12.9 million for past and future pain and suffering, $4 million for past medical care, $11 million for future medical care, $4.5 million for the husband’s loss of consortium, $1.5 million for lost wages, and $1.5 million for the child’s loss of consortium.
 

IUGR detected but not immediately treated: $15.5M settlement
During a prenatal visit at 38 weeks’ gestation, a mother’s ObGyn saw signs of intrauterine growth restriction (IUGR) but did not order ultrasono- graphy to confirm the diagnosis or induce labor. When born 15 days later, the baby had a low birth weight and low Apgar scores. The child has permanent brain injury due to hypoxia.

Parents’ claim The ObGyn should have confirmed the presence of IUGR and appropriately managed the mother’s prenatal care. The child’s injuries could have been prevented if an earlier delivery had occurred.

Physician’s defense The case was settled during the trial.

Verdict A $15.5 million Illinois settlement was reached.
 

Ureter injured during total abdominal hysterectomy
A 40-year-old woman with uterine fibroids, excessive bleeding, and pelvic pain underwent total abdominal hysterectomy performed by her ObGyn.

Postoperatively, the patient reported abdominal pain, but she was discharged from the hospital. Two days later, she returned to the emergency department reporting continued and increasing abdominal pain and urine leakage. The ObGyn referred her to a urologist who diagnosed stricture of the left ureter with a ureterovaginal fistula. A nephrostomy procedure was performed. Three months later, left ureter reimplantation surgery was completed.

Patient’s claim The ObGyn was negligent in injuring the ureter during hysterectomy, in not identifying the injury during surgery, and in not diagnosing and treating the injury in a timely manner, despite the patient’s reports of increasing pain.

Physician’s defense The case was settled during the trial.

Verdict A $350,000 Virginia settlement was reached.
 

Breech presentation but cesarean not performed
When her water broke, a mother was admitted to the hospital. The ObGyn ordered induction of labor but deferred vaginal examination to avoid infection. After labor was induced, a nurse noticed the presence of meconium. She performed a vaginal examination and found that the baby was in breech position; she did not immediately contact the ObGyn. After several hours of labor, the baby was born limp and not breathing with a heart rate of 50 bpm. The baby was resuscitated but sustained severe brain damage.

Parents’ claim The mother should have been examined before induction of labor. When it was determined that the baby was in breech position, a cesarean delivery should have been ordered. Communication between the nurse and ObGyn was poor.

Defendants' defense There was no negligence; labor was managed according to the standard of care.

Verdict A New Jersey defense verdict was returned.
 

Stroke during delivery: $35.4M verdict
During delivery, a 25-year-old woman had a hemorrhagic stroke that left her unable to care for herself or her child.

Patient’s claim The patient’s neurologist failed to advise the ObGyn that the patient had a history of brain aneurysm and a venous varix, which increased the risk for stroke during labor and delivery. The patient had shared her history with the ObGyn, and she requested that her neurologist contact the ObGyn.

Neurologist’s defense There was no negligence. The entire medical file had been delivered to the ObGyn. Any negligence was on the part of the ObGyn for failure to educate herself as to the patient’s condition.

Verdict A $35.4 million Massachusetts verdict was returned against the neurologist, including $12.9 million for past and future pain and suffering, $4 million for past medical care, $11 million for future medical care, $4.5 million for the husband’s loss of consortium, $1.5 million for lost wages, and $1.5 million for the child’s loss of consortium.
 

IUGR detected but not immediately treated: $15.5M settlement
During a prenatal visit at 38 weeks’ gestation, a mother’s ObGyn saw signs of intrauterine growth restriction (IUGR) but did not order ultrasono- graphy to confirm the diagnosis or induce labor. When born 15 days later, the baby had a low birth weight and low Apgar scores. The child has permanent brain injury due to hypoxia.

Parents’ claim The ObGyn should have confirmed the presence of IUGR and appropriately managed the mother’s prenatal care. The child’s injuries could have been prevented if an earlier delivery had occurred.

Physician’s defense The case was settled during the trial.

Verdict A $15.5 million Illinois settlement was reached.
 

Ureter injured during total abdominal hysterectomy
A 40-year-old woman with uterine fibroids, excessive bleeding, and pelvic pain underwent total abdominal hysterectomy performed by her ObGyn.

Postoperatively, the patient reported abdominal pain, but she was discharged from the hospital. Two days later, she returned to the emergency department reporting continued and increasing abdominal pain and urine leakage. The ObGyn referred her to a urologist who diagnosed stricture of the left ureter with a ureterovaginal fistula. A nephrostomy procedure was performed. Three months later, left ureter reimplantation surgery was completed.

Patient’s claim The ObGyn was negligent in injuring the ureter during hysterectomy, in not identifying the injury during surgery, and in not diagnosing and treating the injury in a timely manner, despite the patient’s reports of increasing pain.

Physician’s defense The case was settled during the trial.

Verdict A $350,000 Virginia settlement was reached.
 

Breech presentation but cesarean not performed
When her water broke, a mother was admitted to the hospital. The ObGyn ordered induction of labor but deferred vaginal examination to avoid infection. After labor was induced, a nurse noticed the presence of meconium. She performed a vaginal examination and found that the baby was in breech position; she did not immediately contact the ObGyn. After several hours of labor, the baby was born limp and not breathing with a heart rate of 50 bpm. The baby was resuscitated but sustained severe brain damage.

Parents’ claim The mother should have been examined before induction of labor. When it was determined that the baby was in breech position, a cesarean delivery should have been ordered. Communication between the nurse and ObGyn was poor.

Defendants' defense There was no negligence; labor was managed according to the standard of care.

Verdict A New Jersey defense verdict was returned.
 

Stroke during delivery: $35.4M verdict
During delivery, a 25-year-old woman had a hemorrhagic stroke that left her unable to care for herself or her child.

Patient’s claim The patient’s neurologist failed to advise the ObGyn that the patient had a history of brain aneurysm and a venous varix, which increased the risk for stroke during labor and delivery. The patient had shared her history with the ObGyn, and she requested that her neurologist contact the ObGyn.

Neurologist’s defense There was no negligence. The entire medical file had been delivered to the ObGyn. Any negligence was on the part of the ObGyn for failure to educate herself as to the patient’s condition.

Verdict A $35.4 million Massachusetts verdict was returned against the neurologist, including $12.9 million for past and future pain and suffering, $4 million for past medical care, $11 million for future medical care, $4.5 million for the husband’s loss of consortium, $1.5 million for lost wages, and $1.5 million for the child’s loss of consortium.
 

IUGR detected but not immediately treated: $15.5M settlement
During a prenatal visit at 38 weeks’ gestation, a mother’s ObGyn saw signs of intrauterine growth restriction (IUGR) but did not order ultrasono- graphy to confirm the diagnosis or induce labor. When born 15 days later, the baby had a low birth weight and low Apgar scores. The child has permanent brain injury due to hypoxia.

Parents’ claim The ObGyn should have confirmed the presence of IUGR and appropriately managed the mother’s prenatal care. The child’s injuries could have been prevented if an earlier delivery had occurred.

Physician’s defense The case was settled during the trial.

Verdict A $15.5 million Illinois settlement was reached.
 

Ureter injured during total abdominal hysterectomy
A 40-year-old woman with uterine fibroids, excessive bleeding, and pelvic pain underwent total abdominal hysterectomy performed by her ObGyn.

Postoperatively, the patient reported abdominal pain, but she was discharged from the hospital. Two days later, she returned to the emergency department reporting continued and increasing abdominal pain and urine leakage. The ObGyn referred her to a urologist who diagnosed stricture of the left ureter with a ureterovaginal fistula. A nephrostomy procedure was performed. Three months later, left ureter reimplantation surgery was completed.

Patient’s claim The ObGyn was negligent in injuring the ureter during hysterectomy, in not identifying the injury during surgery, and in not diagnosing and treating the injury in a timely manner, despite the patient’s reports of increasing pain.

Physician’s defense The case was settled during the trial.

Verdict A $350,000 Virginia settlement was reached.
 

Breech presentation but cesarean not performed
When her water broke, a mother was admitted to the hospital. The ObGyn ordered induction of labor but deferred vaginal examination to avoid infection. After labor was induced, a nurse noticed the presence of meconium. She performed a vaginal examination and found that the baby was in breech position; she did not immediately contact the ObGyn. After several hours of labor, the baby was born limp and not breathing with a heart rate of 50 bpm. The baby was resuscitated but sustained severe brain damage.

Parents’ claim The mother should have been examined before induction of labor. When it was determined that the baby was in breech position, a cesarean delivery should have been ordered. Communication between the nurse and ObGyn was poor.

Defendants' defense There was no negligence; labor was managed according to the standard of care.

Verdict A New Jersey defense verdict was returned.
 

NEW YORK – Of psychiatric issues affecting child development, generalized anxiety is not getting the attention it deserves and is frequently mistaken for attention-deficit/hyperactivity disorder (ADHD), according to a review of key diagnostic signs and evidence-based therapies presented at a psychopharmacology update held by the American Academy of Child and Adolescent Psychiatry.

“Pediatricians have an ASD [autism spectrum disorder] toolkit, they have an ADHD toolkit, and they now have a postpartum depression toolkit for moms, but they do not have an anxiety tool kit,” reported Dr. John T. Walkup, director of the division of child and adolescent psychiatry, Cornell University, New York. “So if a kid is 7 or 8 and is inattentive, they have two choices: Either he has ASD or he has ADHD.”

Confusion with ASD is less likely, because there is less symptom crossover, but the differential diagnosis with ADHD is more challenging. For anxiety, symptoms typically peak between the ages of 6 and 12 years. Although the onset of ADHD symptoms, like symptoms of ASD, generally occurs earlier, children with anxiety and ADHD often are brought to the attention of a physician within the same general window of time.

From the point of view of the complaints that initiated an evaluation, “generalized anxiety disorder and the inattentive subtype of ADHD are almost indistinguishable,” Dr. Walkup asserted. He suggested that children who are anxious have difficulty concentrating in class because their minds are “full of ideas, worries, and concerns.” Children with ADHD have difficulty concentrating in class because their minds are “susceptible to distraction,” but the result is the same.

Some children, even those who are only 7 or 8 years old, “can really describe to you that difference,” Dr. Walkup observed, although he said other features can be useful for distinguishing anxiety from other psychiatric disorders, including depression. In taking the history of a child with potential anxiety, key signs include difficulty coping with novel situations, excessive sensitivity to perceived threats, and shyness. These features are less likely to be in children with ADHD or depression.

Once children reach adolescence, social insecurity is more ubiquitous, making this complaint less useful for identifying a child with pathologic anxiety, but here there is also room for confusion without a careful history.

“We see a lot of kids who have social anxiety who get mislabeled as depressed. Socially anxious kids become demoralized, but they do not become anhedonic,” Dr. Walkup reported. In patients who are inhibited with their peers but who do not otherwise report disturbances in mood, generalized anxiety rather than depression may be driving the psychopathology, according to Dr. Walkup, who said this set of circumstances is common.

Once the diagnosis of anxiety is made, both SSRIs and cognitive-behavioral therapy are effective, with response rates of about 55%-60%, Dr. Walkup said. The response rates can climb as high as 80% when the two are combined, particularly when CBT is performed at experienced centers.

With SSRIs, one of the biggest concerns is activation, an adverse event that occurs in up to 10% of patients, Dr. Walkup said. If activation occurs, he advised switching patients to a nonactivating antidepressant, such as duloxetine, nefazodone, or a tricyclic agent, rather than rechallenging them with another SSRI. In his experience, activation on one agent predicts activation on another, but he cautioned against confusing activation with SSRI-induced mania.

“We do see so many kids who get activated on an SSRI and never see another antidepressant again, simply because the doc is afraid of precipitating mania,” Dr. Walkup said. He said mania is a very uncommon adverse event not typically observed, like activation, relatively quickly after initiating therapy. Because of the efficacy of SSRIs for pediatric anxiety, Dr. Walkup advised being slow in abandoning this drug class.

“Antidepressants work extremely well, and SSRIs are the medications of choice,” emphasized Dr. Walkup, who identified atypical antidepressants as a second-line choice in children and benzodiazepines, for which pediatric data are “limited,” as an option further down the list.

However, therapy first requires a diagnosis.

“Identifying anxiety is key,” Dr. Walkup said. “With evidence-based treatments available, there is a need to enhance public awareness and advocacy.”

Dr. Walkup reported no financial relationships.

NEW YORK – Of psychiatric issues affecting child development, generalized anxiety is not getting the attention it deserves and is frequently mistaken for attention-deficit/hyperactivity disorder (ADHD), according to a review of key diagnostic signs and evidence-based therapies presented at a psychopharmacology update held by the American Academy of Child and Adolescent Psychiatry.

“Pediatricians have an ASD [autism spectrum disorder] toolkit, they have an ADHD toolkit, and they now have a postpartum depression toolkit for moms, but they do not have an anxiety tool kit,” reported Dr. John T. Walkup, director of the division of child and adolescent psychiatry, Cornell University, New York. “So if a kid is 7 or 8 and is inattentive, they have two choices: Either he has ASD or he has ADHD.”

Confusion with ASD is less likely, because there is less symptom crossover, but the differential diagnosis with ADHD is more challenging. For anxiety, symptoms typically peak between the ages of 6 and 12 years. Although the onset of ADHD symptoms, like symptoms of ASD, generally occurs earlier, children with anxiety and ADHD often are brought to the attention of a physician within the same general window of time.

From the point of view of the complaints that initiated an evaluation, “generalized anxiety disorder and the inattentive subtype of ADHD are almost indistinguishable,” Dr. Walkup asserted. He suggested that children who are anxious have difficulty concentrating in class because their minds are “full of ideas, worries, and concerns.” Children with ADHD have difficulty concentrating in class because their minds are “susceptible to distraction,” but the result is the same.

Some children, even those who are only 7 or 8 years old, “can really describe to you that difference,” Dr. Walkup observed, although he said other features can be useful for distinguishing anxiety from other psychiatric disorders, including depression. In taking the history of a child with potential anxiety, key signs include difficulty coping with novel situations, excessive sensitivity to perceived threats, and shyness. These features are less likely to be in children with ADHD or depression.

Once children reach adolescence, social insecurity is more ubiquitous, making this complaint less useful for identifying a child with pathologic anxiety, but here there is also room for confusion without a careful history.

“We see a lot of kids who have social anxiety who get mislabeled as depressed. Socially anxious kids become demoralized, but they do not become anhedonic,” Dr. Walkup reported. In patients who are inhibited with their peers but who do not otherwise report disturbances in mood, generalized anxiety rather than depression may be driving the psychopathology, according to Dr. Walkup, who said this set of circumstances is common.

Once the diagnosis of anxiety is made, both SSRIs and cognitive-behavioral therapy are effective, with response rates of about 55%-60%, Dr. Walkup said. The response rates can climb as high as 80% when the two are combined, particularly when CBT is performed at experienced centers.

With SSRIs, one of the biggest concerns is activation, an adverse event that occurs in up to 10% of patients, Dr. Walkup said. If activation occurs, he advised switching patients to a nonactivating antidepressant, such as duloxetine, nefazodone, or a tricyclic agent, rather than rechallenging them with another SSRI. In his experience, activation on one agent predicts activation on another, but he cautioned against confusing activation with SSRI-induced mania.

“We do see so many kids who get activated on an SSRI and never see another antidepressant again, simply because the doc is afraid of precipitating mania,” Dr. Walkup said. He said mania is a very uncommon adverse event not typically observed, like activation, relatively quickly after initiating therapy. Because of the efficacy of SSRIs for pediatric anxiety, Dr. Walkup advised being slow in abandoning this drug class.

“Antidepressants work extremely well, and SSRIs are the medications of choice,” emphasized Dr. Walkup, who identified atypical antidepressants as a second-line choice in children and benzodiazepines, for which pediatric data are “limited,” as an option further down the list.

However, therapy first requires a diagnosis.

“Identifying anxiety is key,” Dr. Walkup said. “With evidence-based treatments available, there is a need to enhance public awareness and advocacy.”

Dr. Walkup reported no financial relationships.

NEW YORK – Of psychiatric issues affecting child development, generalized anxiety is not getting the attention it deserves and is frequently mistaken for attention-deficit/hyperactivity disorder (ADHD), according to a review of key diagnostic signs and evidence-based therapies presented at a psychopharmacology update held by the American Academy of Child and Adolescent Psychiatry.

“Pediatricians have an ASD [autism spectrum disorder] toolkit, they have an ADHD toolkit, and they now have a postpartum depression toolkit for moms, but they do not have an anxiety tool kit,” reported Dr. John T. Walkup, director of the division of child and adolescent psychiatry, Cornell University, New York. “So if a kid is 7 or 8 and is inattentive, they have two choices: Either he has ASD or he has ADHD.”

Confusion with ASD is less likely, because there is less symptom crossover, but the differential diagnosis with ADHD is more challenging. For anxiety, symptoms typically peak between the ages of 6 and 12 years. Although the onset of ADHD symptoms, like symptoms of ASD, generally occurs earlier, children with anxiety and ADHD often are brought to the attention of a physician within the same general window of time.

From the point of view of the complaints that initiated an evaluation, “generalized anxiety disorder and the inattentive subtype of ADHD are almost indistinguishable,” Dr. Walkup asserted. He suggested that children who are anxious have difficulty concentrating in class because their minds are “full of ideas, worries, and concerns.” Children with ADHD have difficulty concentrating in class because their minds are “susceptible to distraction,” but the result is the same.

Some children, even those who are only 7 or 8 years old, “can really describe to you that difference,” Dr. Walkup observed, although he said other features can be useful for distinguishing anxiety from other psychiatric disorders, including depression. In taking the history of a child with potential anxiety, key signs include difficulty coping with novel situations, excessive sensitivity to perceived threats, and shyness. These features are less likely to be in children with ADHD or depression.

Once children reach adolescence, social insecurity is more ubiquitous, making this complaint less useful for identifying a child with pathologic anxiety, but here there is also room for confusion without a careful history.

“We see a lot of kids who have social anxiety who get mislabeled as depressed. Socially anxious kids become demoralized, but they do not become anhedonic,” Dr. Walkup reported. In patients who are inhibited with their peers but who do not otherwise report disturbances in mood, generalized anxiety rather than depression may be driving the psychopathology, according to Dr. Walkup, who said this set of circumstances is common.

Once the diagnosis of anxiety is made, both SSRIs and cognitive-behavioral therapy are effective, with response rates of about 55%-60%, Dr. Walkup said. The response rates can climb as high as 80% when the two are combined, particularly when CBT is performed at experienced centers.

With SSRIs, one of the biggest concerns is activation, an adverse event that occurs in up to 10% of patients, Dr. Walkup said. If activation occurs, he advised switching patients to a nonactivating antidepressant, such as duloxetine, nefazodone, or a tricyclic agent, rather than rechallenging them with another SSRI. In his experience, activation on one agent predicts activation on another, but he cautioned against confusing activation with SSRI-induced mania.

“We do see so many kids who get activated on an SSRI and never see another antidepressant again, simply because the doc is afraid of precipitating mania,” Dr. Walkup said. He said mania is a very uncommon adverse event not typically observed, like activation, relatively quickly after initiating therapy. Because of the efficacy of SSRIs for pediatric anxiety, Dr. Walkup advised being slow in abandoning this drug class.

“Antidepressants work extremely well, and SSRIs are the medications of choice,” emphasized Dr. Walkup, who identified atypical antidepressants as a second-line choice in children and benzodiazepines, for which pediatric data are “limited,” as an option further down the list.

However, therapy first requires a diagnosis.

“Identifying anxiety is key,” Dr. Walkup said. “With evidence-based treatments available, there is a need to enhance public awareness and advocacy.”

Dr. Walkup reported no financial relationships.

SAN ANTONIO – Initiation of venous thromboembolism prophylaxis within 72 hours of severe traumatic brain injury (TBI) reduced the odds of venous thromboembolism by 50% without increasing subsequent intracranial complications or death in a large, propensity-matched cohort study from the University of Toronto.

The investigators matched 1,234 adult patients given prophylaxis before 72 hours – the early-prophylaxis (EP) group – to 1,234 given prophylaxis at 72 hours or later – the late-prophylaxis (LP) group – based on demographics, injury characteristics, intracranial lesions, early neurosurgical procedures, and prophylaxis type.

EP patients had a significantly lower rate of pulmonary embolism (1.1% vs. 2.4%; odds ratio, 0.48; 95% confidence interval, 0.25-0.91) and deep vein thrombosis (4.2% vs. 7.9%; OR, 0.51; 95% CI, 0.36-0.72), with no significant increase in the risk of death (9.8% EP vs. 9% LP; OR, 1.1; 95% CI 0.84-1.4) or late secondary craniotomy/-ectomy (EP 2.5% vs. LP 2.9%; OR, 0.86; 95% CI 0.53-1.4) or intracranial monitoring/drainage (EP 1.1% vs. LP 1.4%; OR, 0.76; 95% CI 0.37-1.6) from VTE complications or other reasons.

“Practice guidelines say we should initiate VTE [venous thromboembolism] prophylaxis” in severe TBI “as early as possible. It’s a very loose recommendation,” so some centers wait 72 hours or longer for fear of extending intracranial hemorrhages. Pending results from prospective trials, “our study lends evidence that early prophylaxis in this population may be safe,” said investigator and University of Toronto general surgery resident, Dr. James Byrne.

The study included 3,634 severe, adult TBI patients in the American College of Surgeons Trauma Quality Improvement Program database from 2012-2014. The subjects had head Abbreviated Injury Scale (AIS) scores of at least 3, Glasgow Coma Scale scores of no more than 8, and, in almost all cases, initial surgeries within 48 hours. Injury was due to blunt trauma. Patients who died or were discharged within 5 days of their injury and those with severe injuries to other body areas were excluded from the analysis.

The median time to starting VTE prophylaxis was 84 hours across the 186 trauma centers in the study, but ranged from 48-150 hours. Centers started prophylaxis within 72 hours in 18%-54% of patients. Fifty-five percent of patients had prophylaxis with low-molecular-weight heparin, and the rest with unfractionated heparin. Overall, 1.7% of patients developed pulmonary emboli, and 6.5% deep vein thromboses. Less than 3% had secondary neurosurgical interventions.

Prophylaxis was more likely to be delayed past 72 hours in patients with higher head AIS scores; subdural hematomas; subarachnoid hemorrhages; blood transfusions within 12 hours of admission; and early neurosurgery. Low-molecular-weight heparin was the more likely option past 72 hours.

Among the 114 centers who treated 10 or more patients, there was a continuous trend toward lower VTE rates with higher EP use, a rate of 9.1% in centers using EP in 18% of patients, but 6.1% in centers using it in 54% (P = .126).

The decision of when to start prophylaxis in severe TBI “still needs to be made at the patient level, but it may be safe to start earlier than 72 hours,” Dr. Byrne said.

The median age in the study was about 43 years, and three-quarters of the subjects were men. Most of the injuries were due to falls or motor vehicle crashes.

Dr. Byrne had no disclosures.

[email protected]

SAN ANTONIO – Initiation of venous thromboembolism prophylaxis within 72 hours of severe traumatic brain injury (TBI) reduced the odds of venous thromboembolism by 50% without increasing subsequent intracranial complications or death in a large, propensity-matched cohort study from the University of Toronto.

The investigators matched 1,234 adult patients given prophylaxis before 72 hours – the early-prophylaxis (EP) group – to 1,234 given prophylaxis at 72 hours or later – the late-prophylaxis (LP) group – based on demographics, injury characteristics, intracranial lesions, early neurosurgical procedures, and prophylaxis type.

EP patients had a significantly lower rate of pulmonary embolism (1.1% vs. 2.4%; odds ratio, 0.48; 95% confidence interval, 0.25-0.91) and deep vein thrombosis (4.2% vs. 7.9%; OR, 0.51; 95% CI, 0.36-0.72), with no significant increase in the risk of death (9.8% EP vs. 9% LP; OR, 1.1; 95% CI 0.84-1.4) or late secondary craniotomy/-ectomy (EP 2.5% vs. LP 2.9%; OR, 0.86; 95% CI 0.53-1.4) or intracranial monitoring/drainage (EP 1.1% vs. LP 1.4%; OR, 0.76; 95% CI 0.37-1.6) from VTE complications or other reasons.

“Practice guidelines say we should initiate VTE [venous thromboembolism] prophylaxis” in severe TBI “as early as possible. It’s a very loose recommendation,” so some centers wait 72 hours or longer for fear of extending intracranial hemorrhages. Pending results from prospective trials, “our study lends evidence that early prophylaxis in this population may be safe,” said investigator and University of Toronto general surgery resident, Dr. James Byrne.

The study included 3,634 severe, adult TBI patients in the American College of Surgeons Trauma Quality Improvement Program database from 2012-2014. The subjects had head Abbreviated Injury Scale (AIS) scores of at least 3, Glasgow Coma Scale scores of no more than 8, and, in almost all cases, initial surgeries within 48 hours. Injury was due to blunt trauma. Patients who died or were discharged within 5 days of their injury and those with severe injuries to other body areas were excluded from the analysis.

The median time to starting VTE prophylaxis was 84 hours across the 186 trauma centers in the study, but ranged from 48-150 hours. Centers started prophylaxis within 72 hours in 18%-54% of patients. Fifty-five percent of patients had prophylaxis with low-molecular-weight heparin, and the rest with unfractionated heparin. Overall, 1.7% of patients developed pulmonary emboli, and 6.5% deep vein thromboses. Less than 3% had secondary neurosurgical interventions.

Prophylaxis was more likely to be delayed past 72 hours in patients with higher head AIS scores; subdural hematomas; subarachnoid hemorrhages; blood transfusions within 12 hours of admission; and early neurosurgery. Low-molecular-weight heparin was the more likely option past 72 hours.

Among the 114 centers who treated 10 or more patients, there was a continuous trend toward lower VTE rates with higher EP use, a rate of 9.1% in centers using EP in 18% of patients, but 6.1% in centers using it in 54% (P = .126).

The decision of when to start prophylaxis in severe TBI “still needs to be made at the patient level, but it may be safe to start earlier than 72 hours,” Dr. Byrne said.

The median age in the study was about 43 years, and three-quarters of the subjects were men. Most of the injuries were due to falls or motor vehicle crashes.

Dr. Byrne had no disclosures.

[email protected]

SAN ANTONIO – Initiation of venous thromboembolism prophylaxis within 72 hours of severe traumatic brain injury (TBI) reduced the odds of venous thromboembolism by 50% without increasing subsequent intracranial complications or death in a large, propensity-matched cohort study from the University of Toronto.

The investigators matched 1,234 adult patients given prophylaxis before 72 hours – the early-prophylaxis (EP) group – to 1,234 given prophylaxis at 72 hours or later – the late-prophylaxis (LP) group – based on demographics, injury characteristics, intracranial lesions, early neurosurgical procedures, and prophylaxis type.

EP patients had a significantly lower rate of pulmonary embolism (1.1% vs. 2.4%; odds ratio, 0.48; 95% confidence interval, 0.25-0.91) and deep vein thrombosis (4.2% vs. 7.9%; OR, 0.51; 95% CI, 0.36-0.72), with no significant increase in the risk of death (9.8% EP vs. 9% LP; OR, 1.1; 95% CI 0.84-1.4) or late secondary craniotomy/-ectomy (EP 2.5% vs. LP 2.9%; OR, 0.86; 95% CI 0.53-1.4) or intracranial monitoring/drainage (EP 1.1% vs. LP 1.4%; OR, 0.76; 95% CI 0.37-1.6) from VTE complications or other reasons.

“Practice guidelines say we should initiate VTE [venous thromboembolism] prophylaxis” in severe TBI “as early as possible. It’s a very loose recommendation,” so some centers wait 72 hours or longer for fear of extending intracranial hemorrhages. Pending results from prospective trials, “our study lends evidence that early prophylaxis in this population may be safe,” said investigator and University of Toronto general surgery resident, Dr. James Byrne.

The study included 3,634 severe, adult TBI patients in the American College of Surgeons Trauma Quality Improvement Program database from 2012-2014. The subjects had head Abbreviated Injury Scale (AIS) scores of at least 3, Glasgow Coma Scale scores of no more than 8, and, in almost all cases, initial surgeries within 48 hours. Injury was due to blunt trauma. Patients who died or were discharged within 5 days of their injury and those with severe injuries to other body areas were excluded from the analysis.

The median time to starting VTE prophylaxis was 84 hours across the 186 trauma centers in the study, but ranged from 48-150 hours. Centers started prophylaxis within 72 hours in 18%-54% of patients. Fifty-five percent of patients had prophylaxis with low-molecular-weight heparin, and the rest with unfractionated heparin. Overall, 1.7% of patients developed pulmonary emboli, and 6.5% deep vein thromboses. Less than 3% had secondary neurosurgical interventions.

Prophylaxis was more likely to be delayed past 72 hours in patients with higher head AIS scores; subdural hematomas; subarachnoid hemorrhages; blood transfusions within 12 hours of admission; and early neurosurgery. Low-molecular-weight heparin was the more likely option past 72 hours.

Among the 114 centers who treated 10 or more patients, there was a continuous trend toward lower VTE rates with higher EP use, a rate of 9.1% in centers using EP in 18% of patients, but 6.1% in centers using it in 54% (P = .126).

The decision of when to start prophylaxis in severe TBI “still needs to be made at the patient level, but it may be safe to start earlier than 72 hours,” Dr. Byrne said.

The median age in the study was about 43 years, and three-quarters of the subjects were men. Most of the injuries were due to falls or motor vehicle crashes.

Dr. Byrne had no disclosures.

[email protected]

SAN ANTONIO – Perioperative risk factors affect postoperative morbidity and mortality differently in emergency and nonemergency surgery, according to an analysis of the ACS National Surgical Quality Improvement Program (ACS NSQIP) database by investigators from Massachusetts General Hospital, Boston.

“Instead of using the same risk-adjustment model for both ... as is currently being done, our findings strongly suggest the need to benchmark emergent and elective surgeries separately,” they concluded.

“Most risk-adjustment models simply have an on/off switch for whether or not the patient underwent emergency surgery and treat comorbidities and other perioperative variables the same.” Those variables, however, “don’t behave the same way in emergency surgery,” said investigator Dr. Jordan Bohnen, a surgical research resident at Mass General.

Because risk adjustment doesn’t take into account variables that have a particularly strong negative impact in emergency settings, acute care surgeons are getting “unnecessarily dinged for having higher complication rates,” he said at the Eastern Association for the Surgery of Trauma scientific assembly.

For example, the team found that preop transfusions and white blood counts (WBC) at or below 4.5 carry a significantly higher risk of 30-day major morbidity or mortality (MMM) in emergency versus nonemergency surgery. Conversely, ascites, preop anemia, and leukocytosis carry a greater MMM risk in nonemergent cases.

The findings come from a comparison of 110,182 nonemergent surgeries to 59,949 emergency cases – generally meaning surgery within 12 hours of emergency department (ED) admission – from the NSQIP database for 2011-2012.

As expected, the overall risk of MMM was significantly higher for emergency cases (16.75% vs. 9.73%; P less than .001), and four procedures – laparoscopic cholecystectomy, exploratory laparotomy, and umbilical and incisional hernia repairs – were relatively riskier when done emergently.

“As surgical quality improvement efforts mature, it’s increasingly important to apply accurate risk-adjustment models to benchmark quality improvement for surgeons, hospitals, and health care systems.” The current “assumption that perioperative variables have an equal impact on outcomes in emergent and nonemergent settings” is incorrect. “Risk factors for bad outcomes change depending on the setting,” Dr. Bohnen said.

Dr. Bohnen has no disclosures.

[email protected]

SAN ANTONIO – Perioperative risk factors affect postoperative morbidity and mortality differently in emergency and nonemergency surgery, according to an analysis of the ACS National Surgical Quality Improvement Program (ACS NSQIP) database by investigators from Massachusetts General Hospital, Boston.

“Instead of using the same risk-adjustment model for both ... as is currently being done, our findings strongly suggest the need to benchmark emergent and elective surgeries separately,” they concluded.

“Most risk-adjustment models simply have an on/off switch for whether or not the patient underwent emergency surgery and treat comorbidities and other perioperative variables the same.” Those variables, however, “don’t behave the same way in emergency surgery,” said investigator Dr. Jordan Bohnen, a surgical research resident at Mass General.

Because risk adjustment doesn’t take into account variables that have a particularly strong negative impact in emergency settings, acute care surgeons are getting “unnecessarily dinged for having higher complication rates,” he said at the Eastern Association for the Surgery of Trauma scientific assembly.

For example, the team found that preop transfusions and white blood counts (WBC) at or below 4.5 carry a significantly higher risk of 30-day major morbidity or mortality (MMM) in emergency versus nonemergency surgery. Conversely, ascites, preop anemia, and leukocytosis carry a greater MMM risk in nonemergent cases.

The findings come from a comparison of 110,182 nonemergent surgeries to 59,949 emergency cases – generally meaning surgery within 12 hours of emergency department (ED) admission – from the NSQIP database for 2011-2012.

As expected, the overall risk of MMM was significantly higher for emergency cases (16.75% vs. 9.73%; P less than .001), and four procedures – laparoscopic cholecystectomy, exploratory laparotomy, and umbilical and incisional hernia repairs – were relatively riskier when done emergently.

“As surgical quality improvement efforts mature, it’s increasingly important to apply accurate risk-adjustment models to benchmark quality improvement for surgeons, hospitals, and health care systems.” The current “assumption that perioperative variables have an equal impact on outcomes in emergent and nonemergent settings” is incorrect. “Risk factors for bad outcomes change depending on the setting,” Dr. Bohnen said.

Dr. Bohnen has no disclosures.

[email protected]

SAN ANTONIO – Perioperative risk factors affect postoperative morbidity and mortality differently in emergency and nonemergency surgery, according to an analysis of the ACS National Surgical Quality Improvement Program (ACS NSQIP) database by investigators from Massachusetts General Hospital, Boston.

“Instead of using the same risk-adjustment model for both ... as is currently being done, our findings strongly suggest the need to benchmark emergent and elective surgeries separately,” they concluded.

“Most risk-adjustment models simply have an on/off switch for whether or not the patient underwent emergency surgery and treat comorbidities and other perioperative variables the same.” Those variables, however, “don’t behave the same way in emergency surgery,” said investigator Dr. Jordan Bohnen, a surgical research resident at Mass General.

Because risk adjustment doesn’t take into account variables that have a particularly strong negative impact in emergency settings, acute care surgeons are getting “unnecessarily dinged for having higher complication rates,” he said at the Eastern Association for the Surgery of Trauma scientific assembly.

For example, the team found that preop transfusions and white blood counts (WBC) at or below 4.5 carry a significantly higher risk of 30-day major morbidity or mortality (MMM) in emergency versus nonemergency surgery. Conversely, ascites, preop anemia, and leukocytosis carry a greater MMM risk in nonemergent cases.

The findings come from a comparison of 110,182 nonemergent surgeries to 59,949 emergency cases – generally meaning surgery within 12 hours of emergency department (ED) admission – from the NSQIP database for 2011-2012.

As expected, the overall risk of MMM was significantly higher for emergency cases (16.75% vs. 9.73%; P less than .001), and four procedures – laparoscopic cholecystectomy, exploratory laparotomy, and umbilical and incisional hernia repairs – were relatively riskier when done emergently.

“As surgical quality improvement efforts mature, it’s increasingly important to apply accurate risk-adjustment models to benchmark quality improvement for surgeons, hospitals, and health care systems.” The current “assumption that perioperative variables have an equal impact on outcomes in emergent and nonemergent settings” is incorrect. “Risk factors for bad outcomes change depending on the setting,” Dr. Bohnen said.

Dr. Bohnen has no disclosures.

[email protected]

Kisato Nosaka, MD, PhD

Photo by Larry Young

SAN FRANCISCO—Results of a phase 2 trial suggest lenalidomide may be a treatment option for patients with relapsed adult T-cell leukemia-lymphoma (ATLL).

Lenalidomide produced a 42% overall response rate (ORR) in this trial, and patients had a “favorable” median overall survival, according to Kisato Nosaka, MD, PhD, of the National Center for Global Health and Medicine in Tokyo, Japan.

He noted, however, that the survival data are still immature and may have been confounded by subsequent therapies.

Dr Nosaka presented these results at the 8th Annual T-cell Lymphoma Forum. The study was sponsored by Celgene K.K.

The trial included 26 Japanese patients with relapsed ATLL. Fifty-eight percent of patients had the acute subtype, 27% had the lymphoma subtype, and 15% had the unfavorable chronic subtype.

The patients’ median age was 68.5 (range, 53-81), and 65% of patients were 65 or older. Fifty percent of patients had an ECOG performance status of 0, 35% had a status of 1, and 15% had a status of 2.

Most patients had a low-risk simplified ATL-PI score (65%), but 35% had an intermediate-risk score. Fifteen percent had bone marrow involvement.

The median number of prior treatment regimens was 2 (range, 1-4). Forty-two percent of patients had prior mogamulizumab, and 35% had received LSG15 or modified LSG15.

Patients received lenalidomide at 25 mg per day, given continuously until disease progression or intolerability.

Safety

The median duration of treatment was 3.7 months (range, 0.4 to 18.3 months). There were no deaths during treatment or for 28 days after.

Nine patients (35%) experienced serious adverse events (AEs), but only 1 serious AE occurred in more than 1 patient. Two patients had serious thrombocytopenia.

The most frequent AEs were thrombocytopenia (77%), neutropenia (73%), lymphopenia (69%), and increased C-reactive protein (42%). The most frequent grade 3 or higher AEs were neutropenia (65%), leukopenia (38%), and lymphopenia (38%).

Response and survival

The median follow-up was 3.9 months. The ORR was 42%, including 5 complete responses/unconfirmed complete responses and 6 partial responses. Eight patients (31%) had stable disease, and 7 (27%) progressed.

Dr Nosaka noted that responses occurred in all disease subtypes and at all disease sites. The ORR was 33% (5/15) for the acute subtype, 50% (2/4) for the unfavorable chronic subtype, and 57% (4/7) for the lymphoma subtype.

The ORR was 31% (5/16) at the target lesion, 60% (6/10) in the peripheral blood, and 75% (6/8) for PGA (Physician’s Global Assessment of Clinical Condition, used to assess skin lesions).

Dr Nosaka also pointed out that the ORR was higher in patients who did not receive prior mogamulizumab (60%) than in patients who did (18%). However, he said the number of patients was too small for a definitive conclusion to be reached.

Similarly, the ORR was higher for patients in the low-risk simplified ATL-PI risk group than for those in the intermediate-risk group—53% and 22%, respectively.

Among the 11 responders, the median duration of response was not reached (range, 0.5 months to not reached). The mean duration of response was 5.2 months (range, 0 to 16.6 months).

The median progression-free survival was 3.8 months (range, 1.9 months to not reached). The median overall survival was 20.3 months (range, 9.1 months to not reached).

The overall survival was longer for patients in the low-risk ATL-PI group than the intermediate-risk group—not reached and 10.1 months, respectively (P=0.03).

In closing, Dr Nosaka said these results support lenalidomide as a possible treatment option for patients with relapsed/recurrent ATLL.

Kisato Nosaka, MD, PhD

Photo by Larry Young

SAN FRANCISCO—Results of a phase 2 trial suggest lenalidomide may be a treatment option for patients with relapsed adult T-cell leukemia-lymphoma (ATLL).

Lenalidomide produced a 42% overall response rate (ORR) in this trial, and patients had a “favorable” median overall survival, according to Kisato Nosaka, MD, PhD, of the National Center for Global Health and Medicine in Tokyo, Japan.

He noted, however, that the survival data are still immature and may have been confounded by subsequent therapies.

Dr Nosaka presented these results at the 8th Annual T-cell Lymphoma Forum. The study was sponsored by Celgene K.K.

The trial included 26 Japanese patients with relapsed ATLL. Fifty-eight percent of patients had the acute subtype, 27% had the lymphoma subtype, and 15% had the unfavorable chronic subtype.

The patients’ median age was 68.5 (range, 53-81), and 65% of patients were 65 or older. Fifty percent of patients had an ECOG performance status of 0, 35% had a status of 1, and 15% had a status of 2.

Most patients had a low-risk simplified ATL-PI score (65%), but 35% had an intermediate-risk score. Fifteen percent had bone marrow involvement.

The median number of prior treatment regimens was 2 (range, 1-4). Forty-two percent of patients had prior mogamulizumab, and 35% had received LSG15 or modified LSG15.

Patients received lenalidomide at 25 mg per day, given continuously until disease progression or intolerability.

Safety

The median duration of treatment was 3.7 months (range, 0.4 to 18.3 months). There were no deaths during treatment or for 28 days after.

Nine patients (35%) experienced serious adverse events (AEs), but only 1 serious AE occurred in more than 1 patient. Two patients had serious thrombocytopenia.

The most frequent AEs were thrombocytopenia (77%), neutropenia (73%), lymphopenia (69%), and increased C-reactive protein (42%). The most frequent grade 3 or higher AEs were neutropenia (65%), leukopenia (38%), and lymphopenia (38%).

Response and survival

The median follow-up was 3.9 months. The ORR was 42%, including 5 complete responses/unconfirmed complete responses and 6 partial responses. Eight patients (31%) had stable disease, and 7 (27%) progressed.

Dr Nosaka noted that responses occurred in all disease subtypes and at all disease sites. The ORR was 33% (5/15) for the acute subtype, 50% (2/4) for the unfavorable chronic subtype, and 57% (4/7) for the lymphoma subtype.

The ORR was 31% (5/16) at the target lesion, 60% (6/10) in the peripheral blood, and 75% (6/8) for PGA (Physician’s Global Assessment of Clinical Condition, used to assess skin lesions).

Dr Nosaka also pointed out that the ORR was higher in patients who did not receive prior mogamulizumab (60%) than in patients who did (18%). However, he said the number of patients was too small for a definitive conclusion to be reached.

Similarly, the ORR was higher for patients in the low-risk simplified ATL-PI risk group than for those in the intermediate-risk group—53% and 22%, respectively.

Among the 11 responders, the median duration of response was not reached (range, 0.5 months to not reached). The mean duration of response was 5.2 months (range, 0 to 16.6 months).

The median progression-free survival was 3.8 months (range, 1.9 months to not reached). The median overall survival was 20.3 months (range, 9.1 months to not reached).

The overall survival was longer for patients in the low-risk ATL-PI group than the intermediate-risk group—not reached and 10.1 months, respectively (P=0.03).

In closing, Dr Nosaka said these results support lenalidomide as a possible treatment option for patients with relapsed/recurrent ATLL.

Kisato Nosaka, MD, PhD

Photo by Larry Young

SAN FRANCISCO—Results of a phase 2 trial suggest lenalidomide may be a treatment option for patients with relapsed adult T-cell leukemia-lymphoma (ATLL).

Lenalidomide produced a 42% overall response rate (ORR) in this trial, and patients had a “favorable” median overall survival, according to Kisato Nosaka, MD, PhD, of the National Center for Global Health and Medicine in Tokyo, Japan.

He noted, however, that the survival data are still immature and may have been confounded by subsequent therapies.

Dr Nosaka presented these results at the 8th Annual T-cell Lymphoma Forum. The study was sponsored by Celgene K.K.

The trial included 26 Japanese patients with relapsed ATLL. Fifty-eight percent of patients had the acute subtype, 27% had the lymphoma subtype, and 15% had the unfavorable chronic subtype.

The patients’ median age was 68.5 (range, 53-81), and 65% of patients were 65 or older. Fifty percent of patients had an ECOG performance status of 0, 35% had a status of 1, and 15% had a status of 2.

Most patients had a low-risk simplified ATL-PI score (65%), but 35% had an intermediate-risk score. Fifteen percent had bone marrow involvement.

The median number of prior treatment regimens was 2 (range, 1-4). Forty-two percent of patients had prior mogamulizumab, and 35% had received LSG15 or modified LSG15.

Patients received lenalidomide at 25 mg per day, given continuously until disease progression or intolerability.

Safety

The median duration of treatment was 3.7 months (range, 0.4 to 18.3 months). There were no deaths during treatment or for 28 days after.

Nine patients (35%) experienced serious adverse events (AEs), but only 1 serious AE occurred in more than 1 patient. Two patients had serious thrombocytopenia.

The most frequent AEs were thrombocytopenia (77%), neutropenia (73%), lymphopenia (69%), and increased C-reactive protein (42%). The most frequent grade 3 or higher AEs were neutropenia (65%), leukopenia (38%), and lymphopenia (38%).

Response and survival

The median follow-up was 3.9 months. The ORR was 42%, including 5 complete responses/unconfirmed complete responses and 6 partial responses. Eight patients (31%) had stable disease, and 7 (27%) progressed.

Dr Nosaka noted that responses occurred in all disease subtypes and at all disease sites. The ORR was 33% (5/15) for the acute subtype, 50% (2/4) for the unfavorable chronic subtype, and 57% (4/7) for the lymphoma subtype.

The ORR was 31% (5/16) at the target lesion, 60% (6/10) in the peripheral blood, and 75% (6/8) for PGA (Physician’s Global Assessment of Clinical Condition, used to assess skin lesions).

Dr Nosaka also pointed out that the ORR was higher in patients who did not receive prior mogamulizumab (60%) than in patients who did (18%). However, he said the number of patients was too small for a definitive conclusion to be reached.

Similarly, the ORR was higher for patients in the low-risk simplified ATL-PI risk group than for those in the intermediate-risk group—53% and 22%, respectively.

Among the 11 responders, the median duration of response was not reached (range, 0.5 months to not reached). The mean duration of response was 5.2 months (range, 0 to 16.6 months).

The median progression-free survival was 3.8 months (range, 1.9 months to not reached). The median overall survival was 20.3 months (range, 9.1 months to not reached).

The overall survival was longer for patients in the low-risk ATL-PI group than the intermediate-risk group—not reached and 10.1 months, respectively (P=0.03).

In closing, Dr Nosaka said these results support lenalidomide as a possible treatment option for patients with relapsed/recurrent ATLL.