TBD Meeting (3187-20)

About 20% of gestational carriers at one institution did not meet recommended criteria developed by the American Society for Reproductive Medicine, according to a retrospective study of 194 patients.

The University of California, San Francisco, offers additional, stricter recommendations, including that gestational carriers have a body mass index less than 35. Under these stricter criteria, about 30% of the gestational carriers did not meet recommendations, Brett Stark, MD, MPH, reported at the American Society for Reproductive Medicine’s 2020 annual meeting, held virtually this year.

Deviating from BMI or age recommendations may be associated with increased likelihood of spontaneous abortion, the analysis suggested. In addition, elements of a gestational carrier’s obstetric history not described in current guidelines, such as prior preterm birth, may influence gestational surrogacy outcomes.

The study was limited by incomplete information for some patients, the retrospective design, and the reliance on a relatively small cohort at a single center. Nevertheless, the findings potentially could inform discussions with patients, said Dr. Stark, a 3rd-year obstetrics and gynecology resident at the university.

Investigators aim to enroll patients in a longitudinal cohort study to further examine these questions, he said.

Protecting intended parents and carriers

“Gestational surrogacy has become an increasingly common form of third-party reproduction,” Dr. Stark said at the virtual meeting. The number of cases of in vitro fertilization (IVF) with gestational carriers increased from approximately 700 in 1999 to more than 5,500 in 2016, according to data from the Society for Assisted Reproductive Technology. “Despite the increasing prevalence of gestational carrier utilization, there remains limited guidance with regard to optimizing outcomes for both the intended parents and gestational carriers.”

ASRM and UCSF recommendations are based on expert opinion and include surprisingly little discussion about the prior pregnancy outcomes of potential gestational carriers, Dr. Stark said.

“It is important for all parties involved that we generate research and data that can help drive the development of the guidelines,” he said. Such evidence may help intended parents understand characteristics of gestational carriers that may lead to live births. “For the gestational carriers, it is important that we have information on safety so that they know they are making appropriate decisions for their family and their life.”

Gestational carrier characteristics in the present study that deviated from 2017 ASRM recommendations included age less than 21 years or greater than 45 years, mental health conditions, and having more than five prior deliveries.

“ASRM guidelines focused on criteria for gestational carriers are meant to protect infertile couples, the carrier, as well as the supporting agency,” Alan Penzias, MD, chair of ASRM’s Practice Committee who is in private practice in Boston, said in a society news release that highlighted Dr. Stark’s study. “It is important that gestational carriers have a complete medical history and examination, in addition to a psychological session with a mental health professional to ensure there are no reasons for the carrier to not move forward with pregnancy.”

A retrospective study by Kate Swanson, MD, and associates found that nonadherence to ASRM guidelines was associated with increased rates of cesarean delivery, neonatal morbidity, and preterm birth.

To examine how adherence to ASRM and UCSF recommendations relates to pregnancy outcomes and maternal and neonatal morbidity and death, Dr. Stark and colleagues assessed births from gestational carrier pregnancies at UCSF between 2008 and 2019.

Of 194 gestational carriers included in the analysis, 98.9% had a prior term pregnancy, 11.9% had a prior preterm pregnancy, and 17.5% had a prior spontaneous abortion.

Indications for use of gestational surrogates included serious medical condition of intended parent (25%), uterine factor infertility (23%), recurrent pregnancy loss (10%), and same-sex male couples (8%).

When the researchers compared pregnancy outcomes for gestational carriers who met ASRM guidelines with outcomes for 38 gestational carriers who did not meet ASRM guidelines, there were no statistically significant differences. Antepartum, intrapartum, and postpartum complication rates and cesarean delivery rates did not significantly differ based on ASRM guideline adherence.

Nonadherence to the stricter UCSF guidelines, however, was associated with increased likelihood of spontaneous abortion. In all, 23.7% of the 59 gestational carriers who were nonadherent to UCSF guidelines had a pregnancy end in a spontaneous abortion, compared with 6.7% of gestational carriers who were adherent to the UCSF recommendations (odds ratio, 4.35).

An analysis of individual criteria and poor pregnancy outcomes found that BMI greater than 35 was associated with increased likelihood of spontaneous abortion (OR, 4.29), as was age less than 21 years or greater than 45 years (OR, 3.37).

Prior spontaneous abortion was associated with increased likelihood of a biochemical pregnancy (OR, 3.2), and prior preterm birth was associated with increased likelihood of spontaneous abortion (OR, 3.19), previable delivery (OR, 25.2), cesarean delivery (OR, 2.59), and antepartum complications (OR, 3.56).
 

The role of agencies

About 76% of the gestational carriers had pregnancies mediated through a gestational surrogacy agency. Surrogates from agencies were about three times more likely than surrogates who were family, friends, or from private surrogacy arrangements to adhere to ASRM and UCSF guidelines.

Even after hearing about gestational carrier recommendations, patients may prefer to work with someone they know. “We want to provide our patients with evidence-based information if possible, but ultimately it is their decision to make,” Dr. Stark said. “And we just need to make sure that they are making an informed decision.”

Dr. Stark had no relevant disclosures. Dr. Penzias helped develop the ASRM committee opinion. He had no relevant conflicts of interest.

[email protected]

SOURCE: Stark B et al. ASRM 2020, Abstract O-251.

About 20% of gestational carriers at one institution did not meet recommended criteria developed by the American Society for Reproductive Medicine, according to a retrospective study of 194 patients.

The University of California, San Francisco, offers additional, stricter recommendations, including that gestational carriers have a body mass index less than 35. Under these stricter criteria, about 30% of the gestational carriers did not meet recommendations, Brett Stark, MD, MPH, reported at the American Society for Reproductive Medicine’s 2020 annual meeting, held virtually this year.

Deviating from BMI or age recommendations may be associated with increased likelihood of spontaneous abortion, the analysis suggested. In addition, elements of a gestational carrier’s obstetric history not described in current guidelines, such as prior preterm birth, may influence gestational surrogacy outcomes.

The study was limited by incomplete information for some patients, the retrospective design, and the reliance on a relatively small cohort at a single center. Nevertheless, the findings potentially could inform discussions with patients, said Dr. Stark, a 3rd-year obstetrics and gynecology resident at the university.

Investigators aim to enroll patients in a longitudinal cohort study to further examine these questions, he said.

Protecting intended parents and carriers

“Gestational surrogacy has become an increasingly common form of third-party reproduction,” Dr. Stark said at the virtual meeting. The number of cases of in vitro fertilization (IVF) with gestational carriers increased from approximately 700 in 1999 to more than 5,500 in 2016, according to data from the Society for Assisted Reproductive Technology. “Despite the increasing prevalence of gestational carrier utilization, there remains limited guidance with regard to optimizing outcomes for both the intended parents and gestational carriers.”

ASRM and UCSF recommendations are based on expert opinion and include surprisingly little discussion about the prior pregnancy outcomes of potential gestational carriers, Dr. Stark said.

“It is important for all parties involved that we generate research and data that can help drive the development of the guidelines,” he said. Such evidence may help intended parents understand characteristics of gestational carriers that may lead to live births. “For the gestational carriers, it is important that we have information on safety so that they know they are making appropriate decisions for their family and their life.”

Gestational carrier characteristics in the present study that deviated from 2017 ASRM recommendations included age less than 21 years or greater than 45 years, mental health conditions, and having more than five prior deliveries.

“ASRM guidelines focused on criteria for gestational carriers are meant to protect infertile couples, the carrier, as well as the supporting agency,” Alan Penzias, MD, chair of ASRM’s Practice Committee who is in private practice in Boston, said in a society news release that highlighted Dr. Stark’s study. “It is important that gestational carriers have a complete medical history and examination, in addition to a psychological session with a mental health professional to ensure there are no reasons for the carrier to not move forward with pregnancy.”

A retrospective study by Kate Swanson, MD, and associates found that nonadherence to ASRM guidelines was associated with increased rates of cesarean delivery, neonatal morbidity, and preterm birth.

To examine how adherence to ASRM and UCSF recommendations relates to pregnancy outcomes and maternal and neonatal morbidity and death, Dr. Stark and colleagues assessed births from gestational carrier pregnancies at UCSF between 2008 and 2019.

Of 194 gestational carriers included in the analysis, 98.9% had a prior term pregnancy, 11.9% had a prior preterm pregnancy, and 17.5% had a prior spontaneous abortion.

Indications for use of gestational surrogates included serious medical condition of intended parent (25%), uterine factor infertility (23%), recurrent pregnancy loss (10%), and same-sex male couples (8%).

When the researchers compared pregnancy outcomes for gestational carriers who met ASRM guidelines with outcomes for 38 gestational carriers who did not meet ASRM guidelines, there were no statistically significant differences. Antepartum, intrapartum, and postpartum complication rates and cesarean delivery rates did not significantly differ based on ASRM guideline adherence.

Nonadherence to the stricter UCSF guidelines, however, was associated with increased likelihood of spontaneous abortion. In all, 23.7% of the 59 gestational carriers who were nonadherent to UCSF guidelines had a pregnancy end in a spontaneous abortion, compared with 6.7% of gestational carriers who were adherent to the UCSF recommendations (odds ratio, 4.35).

An analysis of individual criteria and poor pregnancy outcomes found that BMI greater than 35 was associated with increased likelihood of spontaneous abortion (OR, 4.29), as was age less than 21 years or greater than 45 years (OR, 3.37).

Prior spontaneous abortion was associated with increased likelihood of a biochemical pregnancy (OR, 3.2), and prior preterm birth was associated with increased likelihood of spontaneous abortion (OR, 3.19), previable delivery (OR, 25.2), cesarean delivery (OR, 2.59), and antepartum complications (OR, 3.56).
 

The role of agencies

About 76% of the gestational carriers had pregnancies mediated through a gestational surrogacy agency. Surrogates from agencies were about three times more likely than surrogates who were family, friends, or from private surrogacy arrangements to adhere to ASRM and UCSF guidelines.

Even after hearing about gestational carrier recommendations, patients may prefer to work with someone they know. “We want to provide our patients with evidence-based information if possible, but ultimately it is their decision to make,” Dr. Stark said. “And we just need to make sure that they are making an informed decision.”

Dr. Stark had no relevant disclosures. Dr. Penzias helped develop the ASRM committee opinion. He had no relevant conflicts of interest.

[email protected]

SOURCE: Stark B et al. ASRM 2020, Abstract O-251.

About 20% of gestational carriers at one institution did not meet recommended criteria developed by the American Society for Reproductive Medicine, according to a retrospective study of 194 patients.

The University of California, San Francisco, offers additional, stricter recommendations, including that gestational carriers have a body mass index less than 35. Under these stricter criteria, about 30% of the gestational carriers did not meet recommendations, Brett Stark, MD, MPH, reported at the American Society for Reproductive Medicine’s 2020 annual meeting, held virtually this year.

Deviating from BMI or age recommendations may be associated with increased likelihood of spontaneous abortion, the analysis suggested. In addition, elements of a gestational carrier’s obstetric history not described in current guidelines, such as prior preterm birth, may influence gestational surrogacy outcomes.

The study was limited by incomplete information for some patients, the retrospective design, and the reliance on a relatively small cohort at a single center. Nevertheless, the findings potentially could inform discussions with patients, said Dr. Stark, a 3rd-year obstetrics and gynecology resident at the university.

Investigators aim to enroll patients in a longitudinal cohort study to further examine these questions, he said.

Protecting intended parents and carriers

“Gestational surrogacy has become an increasingly common form of third-party reproduction,” Dr. Stark said at the virtual meeting. The number of cases of in vitro fertilization (IVF) with gestational carriers increased from approximately 700 in 1999 to more than 5,500 in 2016, according to data from the Society for Assisted Reproductive Technology. “Despite the increasing prevalence of gestational carrier utilization, there remains limited guidance with regard to optimizing outcomes for both the intended parents and gestational carriers.”

ASRM and UCSF recommendations are based on expert opinion and include surprisingly little discussion about the prior pregnancy outcomes of potential gestational carriers, Dr. Stark said.

“It is important for all parties involved that we generate research and data that can help drive the development of the guidelines,” he said. Such evidence may help intended parents understand characteristics of gestational carriers that may lead to live births. “For the gestational carriers, it is important that we have information on safety so that they know they are making appropriate decisions for their family and their life.”

Gestational carrier characteristics in the present study that deviated from 2017 ASRM recommendations included age less than 21 years or greater than 45 years, mental health conditions, and having more than five prior deliveries.

“ASRM guidelines focused on criteria for gestational carriers are meant to protect infertile couples, the carrier, as well as the supporting agency,” Alan Penzias, MD, chair of ASRM’s Practice Committee who is in private practice in Boston, said in a society news release that highlighted Dr. Stark’s study. “It is important that gestational carriers have a complete medical history and examination, in addition to a psychological session with a mental health professional to ensure there are no reasons for the carrier to not move forward with pregnancy.”

A retrospective study by Kate Swanson, MD, and associates found that nonadherence to ASRM guidelines was associated with increased rates of cesarean delivery, neonatal morbidity, and preterm birth.

To examine how adherence to ASRM and UCSF recommendations relates to pregnancy outcomes and maternal and neonatal morbidity and death, Dr. Stark and colleagues assessed births from gestational carrier pregnancies at UCSF between 2008 and 2019.

Of 194 gestational carriers included in the analysis, 98.9% had a prior term pregnancy, 11.9% had a prior preterm pregnancy, and 17.5% had a prior spontaneous abortion.

Indications for use of gestational surrogates included serious medical condition of intended parent (25%), uterine factor infertility (23%), recurrent pregnancy loss (10%), and same-sex male couples (8%).

When the researchers compared pregnancy outcomes for gestational carriers who met ASRM guidelines with outcomes for 38 gestational carriers who did not meet ASRM guidelines, there were no statistically significant differences. Antepartum, intrapartum, and postpartum complication rates and cesarean delivery rates did not significantly differ based on ASRM guideline adherence.

Nonadherence to the stricter UCSF guidelines, however, was associated with increased likelihood of spontaneous abortion. In all, 23.7% of the 59 gestational carriers who were nonadherent to UCSF guidelines had a pregnancy end in a spontaneous abortion, compared with 6.7% of gestational carriers who were adherent to the UCSF recommendations (odds ratio, 4.35).

An analysis of individual criteria and poor pregnancy outcomes found that BMI greater than 35 was associated with increased likelihood of spontaneous abortion (OR, 4.29), as was age less than 21 years or greater than 45 years (OR, 3.37).

Prior spontaneous abortion was associated with increased likelihood of a biochemical pregnancy (OR, 3.2), and prior preterm birth was associated with increased likelihood of spontaneous abortion (OR, 3.19), previable delivery (OR, 25.2), cesarean delivery (OR, 2.59), and antepartum complications (OR, 3.56).
 

The role of agencies

About 76% of the gestational carriers had pregnancies mediated through a gestational surrogacy agency. Surrogates from agencies were about three times more likely than surrogates who were family, friends, or from private surrogacy arrangements to adhere to ASRM and UCSF guidelines.

Even after hearing about gestational carrier recommendations, patients may prefer to work with someone they know. “We want to provide our patients with evidence-based information if possible, but ultimately it is their decision to make,” Dr. Stark said. “And we just need to make sure that they are making an informed decision.”

Dr. Stark had no relevant disclosures. Dr. Penzias helped develop the ASRM committee opinion. He had no relevant conflicts of interest.

[email protected]

SOURCE: Stark B et al. ASRM 2020, Abstract O-251.

Among patients with polycystic ovary syndrome (PCOS), those with obstructive sleep apnea (OSA) are more likely to have moderate to severe depression or anxiety, a study suggests.

This finding could have implications for screening and treatment, Diana Xiaojie Zhou, MD, said at the American Society for Reproductive Medicine’s 2020 annual meeting, held virtually this year.

“Routine OSA screening in women with PCOS should be considered in the setting of existing depression and anxiety,” said Dr. Zhou, a reproductive endocrinology and infertility fellow at the University of California, San Francisco. “Referral for OSA diagnosis and treatment in those who screen positive may have added psychological benefits in this population, as has been seen in the general population.”

Patients with PCOS experience a range of comorbidities, including higher rates of psychological disorders and OSA, she said.

OSA has been associated with depression and anxiety in the general population, and research indicates that treatment, such as with continuous positive airway pressure (CPAP), may have psychological benefits, such as reduced depression symptoms.

PCOS guidelines recommend screening for OSA to identify and alleviate symptoms such as fatigue that may to contribute to mood disorders. “However, there is a lack of studies assessing the relationship between OSA and depression and anxiety specifically in women with PCOS,” Dr. Zhou said.
 

A cross-sectional study

To evaluate whether OSA is associated with depression and anxiety in women with PCOS, Dr. Zhou and colleagues conducted a cross-sectional study of all women seen at a multidisciplinary PCOS clinic at university between June 2017 and June 2020.

Participants had a diagnosis of PCOS clinically confirmed by the Rotterdam criteria. Researchers determined OSA risk using the Berlin questionnaire, which is divided into three domains. A positive score in two or more domains indicates a high risk of OSA.

The investigators used the Patient Health Questionnaire-9 (PHQ-9) to assess depression symptoms, and they used the Generalized Anxiety Disorder-7 (GAD-7) to assess anxiety symptoms.

Researchers used two-sided t-test, chi-square test, and Fisher’s exact test to evaluate for differences in patient characteristics. They performed multivariate logistic regression analyses to determine the odds of moderate to severe symptoms of depression (that is, a PHQ-9 score of 10 or greater) and anxiety (a GAD-7 score of 10 or greater) among patients with a high risk of OSA, compared with patients with a low risk of OSA. They adjusted for age, body mass index, free testosterone level, and insulin resistance using the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR).

The researchers examined data from 201 patients: 125 with a low risk of OSA and 76 with a high risk of OSA. The average age of the patients was 28 years.

On average, patients in the high-risk OSA group had a greater body mass index (37.9 vs. 26.5), a higher level of free testosterone (6.5 ng/dL vs. 4.5 ng/dL), and a higher HOMA-IR score (7 vs. 3.1), relative to those with a low risk of OSA. In addition, a greater percentage of patients with a high risk of OSA experienced oligomenorrhea (84.9% vs. 70.5%).

The average PHQ-9 score was significantly higher in the high-risk OSA group (12 vs. 8.3), as was the average GAD-7 score (8.9 vs. 6.1).

In univariate analyses, having a high risk of OSA increased the likelihood of moderate or severe depression or anxiety approximately threefold.

In multivariate analyses, a high risk of OSA remained significantly associated with moderate or severe depression or anxiety, with an odds ratio of about 2.5. “Of note, BMI was a statistically significant predictor in the univariate analyses, but not so in the multivariate analyses,” Dr. Zhou said.

Although the investigators assessed OSA, depression, and anxiety using validated questionnaires, a study with clinically confirmed diagnoses of those conditions would strengthen these findings, she said.
 

Various possible links

Investigators have proposed various links between PCOS, OSA, and depression and anxiety, Dr. Zhou noted. Features of PCOS such as insulin resistance, obesity, and hyperandrogenemia increase the risk of OSA. “The sleep loss and fragmentation and hypoxia that define OSA then serve to increase sympathetic tone and oxidative stress, which then potentially can lead to an increase in depression and anxiety,” Dr. Zhou said.

The results suggests that treating OSA “may have added psychological benefits for women with PCOS and highlights the broad health implications of this condition,” Marla Lujan, PhD, chair of the ASRM’s androgen excess special interest group, said in a society news release.

“The cause of PCOS is still not well understood, but we do know that 1 in 10 women in their childbearing years suffer from PCOS,” said Dr. Lujan, of Cornell University, Ithaca, N.Y. “In addition to infertility, PCOS is also associated with type 2 diabetes and cardiovascular complications such as hypertension and abnormal blood lipids.”

In a discussion following Dr. Zhou’s presentation, Alice D. Domar, PhD, said the study was eye opening.

Dr. Domar, director of integrative care at Boston IVF and associate professor of obstetrics, gynecology, and reproductive biology at Harvard Medical School, Boston, said that she does not typically discuss sleep apnea with patients. “For those of us who routinely work with PCOS patients, we are always looking for more information.”

Although PCOS guidelines mention screening for OSA, Dr. Zhou expects that few generalists who see PCOS patients or even subspecialists actually do.

Nevertheless, the potential for intervention is fascinating, she said. And if treating OSA also reduced a patient’s need for psychiatric medications, there could be added benefit in PCOS due to the metabolic side effects that accompany some of the drugs.

Dr. Zhou and Dr. Lujan had no relevant disclosures. Dr. Domar is a co-owner of FertiCalm, FertiStrong, and Aliz Health Apps, and a speaker for Ferring, EMD Serono, Merck, and Abbott.

[email protected]

SOURCE: Zhou DX et al. ASRM 2020. Abstract O-146.

Among patients with polycystic ovary syndrome (PCOS), those with obstructive sleep apnea (OSA) are more likely to have moderate to severe depression or anxiety, a study suggests.

This finding could have implications for screening and treatment, Diana Xiaojie Zhou, MD, said at the American Society for Reproductive Medicine’s 2020 annual meeting, held virtually this year.

“Routine OSA screening in women with PCOS should be considered in the setting of existing depression and anxiety,” said Dr. Zhou, a reproductive endocrinology and infertility fellow at the University of California, San Francisco. “Referral for OSA diagnosis and treatment in those who screen positive may have added psychological benefits in this population, as has been seen in the general population.”

Patients with PCOS experience a range of comorbidities, including higher rates of psychological disorders and OSA, she said.

OSA has been associated with depression and anxiety in the general population, and research indicates that treatment, such as with continuous positive airway pressure (CPAP), may have psychological benefits, such as reduced depression symptoms.

PCOS guidelines recommend screening for OSA to identify and alleviate symptoms such as fatigue that may to contribute to mood disorders. “However, there is a lack of studies assessing the relationship between OSA and depression and anxiety specifically in women with PCOS,” Dr. Zhou said.
 

A cross-sectional study

To evaluate whether OSA is associated with depression and anxiety in women with PCOS, Dr. Zhou and colleagues conducted a cross-sectional study of all women seen at a multidisciplinary PCOS clinic at university between June 2017 and June 2020.

Participants had a diagnosis of PCOS clinically confirmed by the Rotterdam criteria. Researchers determined OSA risk using the Berlin questionnaire, which is divided into three domains. A positive score in two or more domains indicates a high risk of OSA.

The investigators used the Patient Health Questionnaire-9 (PHQ-9) to assess depression symptoms, and they used the Generalized Anxiety Disorder-7 (GAD-7) to assess anxiety symptoms.

Researchers used two-sided t-test, chi-square test, and Fisher’s exact test to evaluate for differences in patient characteristics. They performed multivariate logistic regression analyses to determine the odds of moderate to severe symptoms of depression (that is, a PHQ-9 score of 10 or greater) and anxiety (a GAD-7 score of 10 or greater) among patients with a high risk of OSA, compared with patients with a low risk of OSA. They adjusted for age, body mass index, free testosterone level, and insulin resistance using the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR).

The researchers examined data from 201 patients: 125 with a low risk of OSA and 76 with a high risk of OSA. The average age of the patients was 28 years.

On average, patients in the high-risk OSA group had a greater body mass index (37.9 vs. 26.5), a higher level of free testosterone (6.5 ng/dL vs. 4.5 ng/dL), and a higher HOMA-IR score (7 vs. 3.1), relative to those with a low risk of OSA. In addition, a greater percentage of patients with a high risk of OSA experienced oligomenorrhea (84.9% vs. 70.5%).

The average PHQ-9 score was significantly higher in the high-risk OSA group (12 vs. 8.3), as was the average GAD-7 score (8.9 vs. 6.1).

In univariate analyses, having a high risk of OSA increased the likelihood of moderate or severe depression or anxiety approximately threefold.

In multivariate analyses, a high risk of OSA remained significantly associated with moderate or severe depression or anxiety, with an odds ratio of about 2.5. “Of note, BMI was a statistically significant predictor in the univariate analyses, but not so in the multivariate analyses,” Dr. Zhou said.

Although the investigators assessed OSA, depression, and anxiety using validated questionnaires, a study with clinically confirmed diagnoses of those conditions would strengthen these findings, she said.
 

Various possible links

Investigators have proposed various links between PCOS, OSA, and depression and anxiety, Dr. Zhou noted. Features of PCOS such as insulin resistance, obesity, and hyperandrogenemia increase the risk of OSA. “The sleep loss and fragmentation and hypoxia that define OSA then serve to increase sympathetic tone and oxidative stress, which then potentially can lead to an increase in depression and anxiety,” Dr. Zhou said.

The results suggests that treating OSA “may have added psychological benefits for women with PCOS and highlights the broad health implications of this condition,” Marla Lujan, PhD, chair of the ASRM’s androgen excess special interest group, said in a society news release.

“The cause of PCOS is still not well understood, but we do know that 1 in 10 women in their childbearing years suffer from PCOS,” said Dr. Lujan, of Cornell University, Ithaca, N.Y. “In addition to infertility, PCOS is also associated with type 2 diabetes and cardiovascular complications such as hypertension and abnormal blood lipids.”

In a discussion following Dr. Zhou’s presentation, Alice D. Domar, PhD, said the study was eye opening.

Dr. Domar, director of integrative care at Boston IVF and associate professor of obstetrics, gynecology, and reproductive biology at Harvard Medical School, Boston, said that she does not typically discuss sleep apnea with patients. “For those of us who routinely work with PCOS patients, we are always looking for more information.”

Although PCOS guidelines mention screening for OSA, Dr. Zhou expects that few generalists who see PCOS patients or even subspecialists actually do.

Nevertheless, the potential for intervention is fascinating, she said. And if treating OSA also reduced a patient’s need for psychiatric medications, there could be added benefit in PCOS due to the metabolic side effects that accompany some of the drugs.

Dr. Zhou and Dr. Lujan had no relevant disclosures. Dr. Domar is a co-owner of FertiCalm, FertiStrong, and Aliz Health Apps, and a speaker for Ferring, EMD Serono, Merck, and Abbott.

[email protected]

SOURCE: Zhou DX et al. ASRM 2020. Abstract O-146.

Among patients with polycystic ovary syndrome (PCOS), those with obstructive sleep apnea (OSA) are more likely to have moderate to severe depression or anxiety, a study suggests.

This finding could have implications for screening and treatment, Diana Xiaojie Zhou, MD, said at the American Society for Reproductive Medicine’s 2020 annual meeting, held virtually this year.

“Routine OSA screening in women with PCOS should be considered in the setting of existing depression and anxiety,” said Dr. Zhou, a reproductive endocrinology and infertility fellow at the University of California, San Francisco. “Referral for OSA diagnosis and treatment in those who screen positive may have added psychological benefits in this population, as has been seen in the general population.”

Patients with PCOS experience a range of comorbidities, including higher rates of psychological disorders and OSA, she said.

OSA has been associated with depression and anxiety in the general population, and research indicates that treatment, such as with continuous positive airway pressure (CPAP), may have psychological benefits, such as reduced depression symptoms.

PCOS guidelines recommend screening for OSA to identify and alleviate symptoms such as fatigue that may to contribute to mood disorders. “However, there is a lack of studies assessing the relationship between OSA and depression and anxiety specifically in women with PCOS,” Dr. Zhou said.
 

A cross-sectional study

To evaluate whether OSA is associated with depression and anxiety in women with PCOS, Dr. Zhou and colleagues conducted a cross-sectional study of all women seen at a multidisciplinary PCOS clinic at university between June 2017 and June 2020.

Participants had a diagnosis of PCOS clinically confirmed by the Rotterdam criteria. Researchers determined OSA risk using the Berlin questionnaire, which is divided into three domains. A positive score in two or more domains indicates a high risk of OSA.

The investigators used the Patient Health Questionnaire-9 (PHQ-9) to assess depression symptoms, and they used the Generalized Anxiety Disorder-7 (GAD-7) to assess anxiety symptoms.

Researchers used two-sided t-test, chi-square test, and Fisher’s exact test to evaluate for differences in patient characteristics. They performed multivariate logistic regression analyses to determine the odds of moderate to severe symptoms of depression (that is, a PHQ-9 score of 10 or greater) and anxiety (a GAD-7 score of 10 or greater) among patients with a high risk of OSA, compared with patients with a low risk of OSA. They adjusted for age, body mass index, free testosterone level, and insulin resistance using the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR).

The researchers examined data from 201 patients: 125 with a low risk of OSA and 76 with a high risk of OSA. The average age of the patients was 28 years.

On average, patients in the high-risk OSA group had a greater body mass index (37.9 vs. 26.5), a higher level of free testosterone (6.5 ng/dL vs. 4.5 ng/dL), and a higher HOMA-IR score (7 vs. 3.1), relative to those with a low risk of OSA. In addition, a greater percentage of patients with a high risk of OSA experienced oligomenorrhea (84.9% vs. 70.5%).

The average PHQ-9 score was significantly higher in the high-risk OSA group (12 vs. 8.3), as was the average GAD-7 score (8.9 vs. 6.1).

In univariate analyses, having a high risk of OSA increased the likelihood of moderate or severe depression or anxiety approximately threefold.

In multivariate analyses, a high risk of OSA remained significantly associated with moderate or severe depression or anxiety, with an odds ratio of about 2.5. “Of note, BMI was a statistically significant predictor in the univariate analyses, but not so in the multivariate analyses,” Dr. Zhou said.

Although the investigators assessed OSA, depression, and anxiety using validated questionnaires, a study with clinically confirmed diagnoses of those conditions would strengthen these findings, she said.
 

Various possible links

Investigators have proposed various links between PCOS, OSA, and depression and anxiety, Dr. Zhou noted. Features of PCOS such as insulin resistance, obesity, and hyperandrogenemia increase the risk of OSA. “The sleep loss and fragmentation and hypoxia that define OSA then serve to increase sympathetic tone and oxidative stress, which then potentially can lead to an increase in depression and anxiety,” Dr. Zhou said.

The results suggests that treating OSA “may have added psychological benefits for women with PCOS and highlights the broad health implications of this condition,” Marla Lujan, PhD, chair of the ASRM’s androgen excess special interest group, said in a society news release.

“The cause of PCOS is still not well understood, but we do know that 1 in 10 women in their childbearing years suffer from PCOS,” said Dr. Lujan, of Cornell University, Ithaca, N.Y. “In addition to infertility, PCOS is also associated with type 2 diabetes and cardiovascular complications such as hypertension and abnormal blood lipids.”

In a discussion following Dr. Zhou’s presentation, Alice D. Domar, PhD, said the study was eye opening.

Dr. Domar, director of integrative care at Boston IVF and associate professor of obstetrics, gynecology, and reproductive biology at Harvard Medical School, Boston, said that she does not typically discuss sleep apnea with patients. “For those of us who routinely work with PCOS patients, we are always looking for more information.”

Although PCOS guidelines mention screening for OSA, Dr. Zhou expects that few generalists who see PCOS patients or even subspecialists actually do.

Nevertheless, the potential for intervention is fascinating, she said. And if treating OSA also reduced a patient’s need for psychiatric medications, there could be added benefit in PCOS due to the metabolic side effects that accompany some of the drugs.

Dr. Zhou and Dr. Lujan had no relevant disclosures. Dr. Domar is a co-owner of FertiCalm, FertiStrong, and Aliz Health Apps, and a speaker for Ferring, EMD Serono, Merck, and Abbott.

[email protected]

SOURCE: Zhou DX et al. ASRM 2020. Abstract O-146.

More than 60% of patients at a center for reproductive medicine in Utah who had fertility treatments canceled because of the COVID-19 pandemic opted to resume treatment once the suspension was lifted about 7 weeks later.

At another fertility center in New York, a survey found that 96% of respondents who had a cycle canceled because of the pandemic found it upsetting, and 22% found it extremely upsetting, with extremely upsetting defined as equivalent to the loss of a child.

The indefinite time frame for resuming treatment when the New York survey was conducted may have been a major source of distress for patients, one of the researchers said at the American Society for Reproductive Medicine’s 2020 annual meeting, held virtually this year.

“They don’t know when they might have that chance again,” said Jenna M. Turocy, MD, of Columbia University Fertility Center, New York.

COVID-19 guidelines published by ASRM on March 17 recommended the suspension of new treatment cycles, including ovulation induction, intrauterine inseminations, and in vitro fertilization (IVF).

An ASRM COVID-19 task force has since supported “the measured resumption of fertility care following the easing of restrictions,” said Paul C. Lin, MD, president of the Society for Assisted Reproductive Technology and a member of the task force.

“Over the past several months, significant knowledge has been gained regarding the COVID-19 virus and its impact on patients and the medical system,” he said in a news release about the two studies that assessed the pandemic’s effects.

Certain precautions remain. “It has become clear that we will need to be practicing COVID-19 protocols at least until an effective and safe vaccine or broadly effective treatment becomes widely available,” Dr. Lin said.
 

Desire to proceed during a pandemic

The Utah Center for Reproductive Medicine on March 15 suspended new IVF cycles and frozen embryo transfers. The center continued to offer IVF cycles for oncofertility patients on an urgent basis.

In early May, patients whose cycles had been suspended had the option to receive treatment.

“Upon reopening, every patient received standardized counseling from their primary IVF physician,” Lauren Verrilli, MD, a reproductive endocrinology and infertility fellow at the University of Utah, Salt Lake City, said at the virtual meeting.

Doctors explained that much remained unknown about COVID-19 in pregnancy, and that it was unclear whether the clinic would need to shut down again. In addition, patients had to undergo COVID-19 testing.

To identify factors associated with proceeding with treatment after the suspension, the researchers compared patients who resumed treatment with patients who did not.

Their analysis included 278 patients who had planned an IVF cycle or frozen embryo transfer (FET) prior to the shutdown. The researchers examined factors such as age, parity, anti-Müllerian hormone, antral follicle count, history of prior IVF cycles or FET, number of frozen blastocysts, gamete source, and use of a gestational carrier.

In all, 62% of patients opted to receive treatment once restrictions were lifted, including 69 of the 133 (52%) patients with planned fresh cycles and 104 of the 145 (72%) patients with planned FET cycles.

Among those with planned fresh cycles, those who opted to resume treatment tended to be older than those who did not resume treatment, with a median age of 37 years versus 35 years, but the difference was not statistically significant.

Among patients with planned FET cycles, those who did not resume treatment were more likely to have a gestational carrier, compared with those who resumed treatment (7% vs. 1%). In some cases, gestational carriers lived in another state and the pandemic complicated travel arrangements, which contributed to delays, Dr. Verrilli said.

The analysis did not include information about income or socioeconomic status, which may play a role in patients’ decisions, Dr. Verrilli said.
 

Emotional impact of indefinite delay

Fertility treatment is often time sensitive, particularly for patients with advanced reproductive age or diminished ovarian reserve, and indefinite postponement of fertility treatment potentially could lead some patients to lose the ability to conceive with their own gametes, Dr. Turocy said.

In early April, Dr. Turocy and colleagues surveyed patients at their academic fertility center in New York City to assess patients’ reactions to the ASRM recommendations. They decided to conduct the study after they realized that treatment cancellations were having a significant emotional effect.

Investigators emailed an 18-item survey to more than 3,000 patients.

In all, 518 patients completed the survey, a response rate of 17%. Patients had an average age of 37 years (range, 23-52 years), and 92% were female. About 24% had children, and 66% had received at least one fertility treatment.

Half had a cycle canceled because of the COVID-19 pandemic, including timed intercourse cycles (5%), intrauterine insemination cycles (23%), IVF cycles with a planned fresh embryo transfer (10%), IVF with all frozen embryos (27%), egg freeze cycles (3%), and FET cycles (30%).

In response to survey questions about whether they agreed with ASRM recommendations, “the reactions were mixed,” Dr. Turocy said.

About 36% of patients agreed all fertility cycles should be canceled, 22% were unsure, and 43% disagreed with the recommendation. Patients who had a cycle canceled were slightly more likely to agree with the cancellations (40% agreed) than those who did not have a cycle canceled (30% agreed), Dr. Turocy said.

Most respondents would have preferred an option to start a treatment cycle in consultation with their doctor. Half “would have chosen to start a new cycle during the height of the pandemic in New York City,” Dr. Turocy said.

Patient opinions may vary by region and depend on the severity of COVID-19 outbreaks there, and they also might change over time, Dr. Turocy suggested. In addition, the opinions and characteristics of patients who responded to the anonymous survey may differ from those of patients who did not respond.

Dr. Verrilli, Dr. Turocy, and Dr. Lin had no relevant financial disclosures.

[email protected]

More than 60% of patients at a center for reproductive medicine in Utah who had fertility treatments canceled because of the COVID-19 pandemic opted to resume treatment once the suspension was lifted about 7 weeks later.

At another fertility center in New York, a survey found that 96% of respondents who had a cycle canceled because of the pandemic found it upsetting, and 22% found it extremely upsetting, with extremely upsetting defined as equivalent to the loss of a child.

The indefinite time frame for resuming treatment when the New York survey was conducted may have been a major source of distress for patients, one of the researchers said at the American Society for Reproductive Medicine’s 2020 annual meeting, held virtually this year.

“They don’t know when they might have that chance again,” said Jenna M. Turocy, MD, of Columbia University Fertility Center, New York.

COVID-19 guidelines published by ASRM on March 17 recommended the suspension of new treatment cycles, including ovulation induction, intrauterine inseminations, and in vitro fertilization (IVF).

An ASRM COVID-19 task force has since supported “the measured resumption of fertility care following the easing of restrictions,” said Paul C. Lin, MD, president of the Society for Assisted Reproductive Technology and a member of the task force.

“Over the past several months, significant knowledge has been gained regarding the COVID-19 virus and its impact on patients and the medical system,” he said in a news release about the two studies that assessed the pandemic’s effects.

Certain precautions remain. “It has become clear that we will need to be practicing COVID-19 protocols at least until an effective and safe vaccine or broadly effective treatment becomes widely available,” Dr. Lin said.
 

Desire to proceed during a pandemic

The Utah Center for Reproductive Medicine on March 15 suspended new IVF cycles and frozen embryo transfers. The center continued to offer IVF cycles for oncofertility patients on an urgent basis.

In early May, patients whose cycles had been suspended had the option to receive treatment.

“Upon reopening, every patient received standardized counseling from their primary IVF physician,” Lauren Verrilli, MD, a reproductive endocrinology and infertility fellow at the University of Utah, Salt Lake City, said at the virtual meeting.

Doctors explained that much remained unknown about COVID-19 in pregnancy, and that it was unclear whether the clinic would need to shut down again. In addition, patients had to undergo COVID-19 testing.

To identify factors associated with proceeding with treatment after the suspension, the researchers compared patients who resumed treatment with patients who did not.

Their analysis included 278 patients who had planned an IVF cycle or frozen embryo transfer (FET) prior to the shutdown. The researchers examined factors such as age, parity, anti-Müllerian hormone, antral follicle count, history of prior IVF cycles or FET, number of frozen blastocysts, gamete source, and use of a gestational carrier.

In all, 62% of patients opted to receive treatment once restrictions were lifted, including 69 of the 133 (52%) patients with planned fresh cycles and 104 of the 145 (72%) patients with planned FET cycles.

Among those with planned fresh cycles, those who opted to resume treatment tended to be older than those who did not resume treatment, with a median age of 37 years versus 35 years, but the difference was not statistically significant.

Among patients with planned FET cycles, those who did not resume treatment were more likely to have a gestational carrier, compared with those who resumed treatment (7% vs. 1%). In some cases, gestational carriers lived in another state and the pandemic complicated travel arrangements, which contributed to delays, Dr. Verrilli said.

The analysis did not include information about income or socioeconomic status, which may play a role in patients’ decisions, Dr. Verrilli said.
 

Emotional impact of indefinite delay

Fertility treatment is often time sensitive, particularly for patients with advanced reproductive age or diminished ovarian reserve, and indefinite postponement of fertility treatment potentially could lead some patients to lose the ability to conceive with their own gametes, Dr. Turocy said.

In early April, Dr. Turocy and colleagues surveyed patients at their academic fertility center in New York City to assess patients’ reactions to the ASRM recommendations. They decided to conduct the study after they realized that treatment cancellations were having a significant emotional effect.

Investigators emailed an 18-item survey to more than 3,000 patients.

In all, 518 patients completed the survey, a response rate of 17%. Patients had an average age of 37 years (range, 23-52 years), and 92% were female. About 24% had children, and 66% had received at least one fertility treatment.

Half had a cycle canceled because of the COVID-19 pandemic, including timed intercourse cycles (5%), intrauterine insemination cycles (23%), IVF cycles with a planned fresh embryo transfer (10%), IVF with all frozen embryos (27%), egg freeze cycles (3%), and FET cycles (30%).

In response to survey questions about whether they agreed with ASRM recommendations, “the reactions were mixed,” Dr. Turocy said.

About 36% of patients agreed all fertility cycles should be canceled, 22% were unsure, and 43% disagreed with the recommendation. Patients who had a cycle canceled were slightly more likely to agree with the cancellations (40% agreed) than those who did not have a cycle canceled (30% agreed), Dr. Turocy said.

Most respondents would have preferred an option to start a treatment cycle in consultation with their doctor. Half “would have chosen to start a new cycle during the height of the pandemic in New York City,” Dr. Turocy said.

Patient opinions may vary by region and depend on the severity of COVID-19 outbreaks there, and they also might change over time, Dr. Turocy suggested. In addition, the opinions and characteristics of patients who responded to the anonymous survey may differ from those of patients who did not respond.

Dr. Verrilli, Dr. Turocy, and Dr. Lin had no relevant financial disclosures.

[email protected]

More than 60% of patients at a center for reproductive medicine in Utah who had fertility treatments canceled because of the COVID-19 pandemic opted to resume treatment once the suspension was lifted about 7 weeks later.

At another fertility center in New York, a survey found that 96% of respondents who had a cycle canceled because of the pandemic found it upsetting, and 22% found it extremely upsetting, with extremely upsetting defined as equivalent to the loss of a child.

The indefinite time frame for resuming treatment when the New York survey was conducted may have been a major source of distress for patients, one of the researchers said at the American Society for Reproductive Medicine’s 2020 annual meeting, held virtually this year.

“They don’t know when they might have that chance again,” said Jenna M. Turocy, MD, of Columbia University Fertility Center, New York.

COVID-19 guidelines published by ASRM on March 17 recommended the suspension of new treatment cycles, including ovulation induction, intrauterine inseminations, and in vitro fertilization (IVF).

An ASRM COVID-19 task force has since supported “the measured resumption of fertility care following the easing of restrictions,” said Paul C. Lin, MD, president of the Society for Assisted Reproductive Technology and a member of the task force.

“Over the past several months, significant knowledge has been gained regarding the COVID-19 virus and its impact on patients and the medical system,” he said in a news release about the two studies that assessed the pandemic’s effects.

Certain precautions remain. “It has become clear that we will need to be practicing COVID-19 protocols at least until an effective and safe vaccine or broadly effective treatment becomes widely available,” Dr. Lin said.
 

Desire to proceed during a pandemic

The Utah Center for Reproductive Medicine on March 15 suspended new IVF cycles and frozen embryo transfers. The center continued to offer IVF cycles for oncofertility patients on an urgent basis.

In early May, patients whose cycles had been suspended had the option to receive treatment.

“Upon reopening, every patient received standardized counseling from their primary IVF physician,” Lauren Verrilli, MD, a reproductive endocrinology and infertility fellow at the University of Utah, Salt Lake City, said at the virtual meeting.

Doctors explained that much remained unknown about COVID-19 in pregnancy, and that it was unclear whether the clinic would need to shut down again. In addition, patients had to undergo COVID-19 testing.

To identify factors associated with proceeding with treatment after the suspension, the researchers compared patients who resumed treatment with patients who did not.

Their analysis included 278 patients who had planned an IVF cycle or frozen embryo transfer (FET) prior to the shutdown. The researchers examined factors such as age, parity, anti-Müllerian hormone, antral follicle count, history of prior IVF cycles or FET, number of frozen blastocysts, gamete source, and use of a gestational carrier.

In all, 62% of patients opted to receive treatment once restrictions were lifted, including 69 of the 133 (52%) patients with planned fresh cycles and 104 of the 145 (72%) patients with planned FET cycles.

Among those with planned fresh cycles, those who opted to resume treatment tended to be older than those who did not resume treatment, with a median age of 37 years versus 35 years, but the difference was not statistically significant.

Among patients with planned FET cycles, those who did not resume treatment were more likely to have a gestational carrier, compared with those who resumed treatment (7% vs. 1%). In some cases, gestational carriers lived in another state and the pandemic complicated travel arrangements, which contributed to delays, Dr. Verrilli said.

The analysis did not include information about income or socioeconomic status, which may play a role in patients’ decisions, Dr. Verrilli said.
 

Emotional impact of indefinite delay

Fertility treatment is often time sensitive, particularly for patients with advanced reproductive age or diminished ovarian reserve, and indefinite postponement of fertility treatment potentially could lead some patients to lose the ability to conceive with their own gametes, Dr. Turocy said.

In early April, Dr. Turocy and colleagues surveyed patients at their academic fertility center in New York City to assess patients’ reactions to the ASRM recommendations. They decided to conduct the study after they realized that treatment cancellations were having a significant emotional effect.

Investigators emailed an 18-item survey to more than 3,000 patients.

In all, 518 patients completed the survey, a response rate of 17%. Patients had an average age of 37 years (range, 23-52 years), and 92% were female. About 24% had children, and 66% had received at least one fertility treatment.

Half had a cycle canceled because of the COVID-19 pandemic, including timed intercourse cycles (5%), intrauterine insemination cycles (23%), IVF cycles with a planned fresh embryo transfer (10%), IVF with all frozen embryos (27%), egg freeze cycles (3%), and FET cycles (30%).

In response to survey questions about whether they agreed with ASRM recommendations, “the reactions were mixed,” Dr. Turocy said.

About 36% of patients agreed all fertility cycles should be canceled, 22% were unsure, and 43% disagreed with the recommendation. Patients who had a cycle canceled were slightly more likely to agree with the cancellations (40% agreed) than those who did not have a cycle canceled (30% agreed), Dr. Turocy said.

Most respondents would have preferred an option to start a treatment cycle in consultation with their doctor. Half “would have chosen to start a new cycle during the height of the pandemic in New York City,” Dr. Turocy said.

Patient opinions may vary by region and depend on the severity of COVID-19 outbreaks there, and they also might change over time, Dr. Turocy suggested. In addition, the opinions and characteristics of patients who responded to the anonymous survey may differ from those of patients who did not respond.

Dr. Verrilli, Dr. Turocy, and Dr. Lin had no relevant financial disclosures.

[email protected]

A combination therapy using the experimental drug relugolix was effective in treating pain and heavy bleeding from uterine fibroids for a full year, according to findings from a long-term extension study of the phase 3, open-label LIBERTY trials.

The drug was also well tolerated, with retention of bone mineral density and no new adverse events, said Ayman Al-Hendy, MD, PhD, who presented the results Oct. 17 at the virtual American Society for Reproductive Medicine 2020 Scientific Congress.

“Relugolix combination therapy represents a potential long-term treatment for women with heavy menstrual bleeding associated with uterine fibroids,” said Al-Hendy, a gynecologist and endoscopic surgeon at the University of Chicago.

Dr. Al-Hendy, who consults for the company that makes the drug, on Oct. 20 presented results showing improvement in quality of life with relugolix therapy.

“The fact that this longer-term study shows continued, persistent results at a year really gives us confidence that we’ll be able to use these drugs as a long-term therapy to treat fibroids,” Hugh S. Taylor, MD, president-elect of ASRM, said in an interview. Dr. Taylor, a professor and chair of ob.gyn. and reproductive sciences at Yale University, New Haven, Conn., was not involved in the study.

“A drug like this is so necessary,” Dr. Taylor continued. “We don’t have any other drugs on the market approved for long-term use.”

Relugolix is an oral gonadotropin-releasing hormone (GnRH) receptor antagonist under investigation for long-term management of uterine fibroids. The once-daily combination therapy includes 40 mg relugolix, 1 mg estradiol, and 0.5 mg norethindrone acetate.
 

Extension study shows prolonged benefits

The extension trial enrolled women aged 18-50 years who were experiencing heavy menstrual bleeding from uterine fibroids and who completed the 24-week phase 3, double-blind, placebo-controlled LIBERTY 1 or 2 trials. Heavy menstrual bleeding was defined as bleeding in which at least 80 mL of blood was lost per cycle for two cycles or 160 mL was lost during one cycle. Ultrasound imaging was used to confirm the presence of fibroids.

In LIBERTY 1 and 2, women were randomly assigned to receive relugolix combination therapy, placebo, or relugolix alone for 12 weeks followed by combination therapy for the remaining 12 weeks (delayed group). Those trials found that relugolix combination therapy was effective through 6 months in reducing menstrual blood loss and pain in women with uterine fibroids without loss of bone mineral density.

LIBERTY 3 extended the trial to 52 weeks, with all participants receiving relugolix combination therapy.

As in the earlier trials, the primary endpoint was reduced menstrual blood loss. By the end of the study, women needed to have at least a 50% reduction in blood loss from the initial study’s baseline while maintaining a blood loss of <80 mL. The investigators also evaluated the mean percentage of menstrual blood loss reduction, amenorrhea rate, and improvements in anemia as secondary endpoints and assessed changes in bone mineral density.

The extension study enrolled 78% (n = 477) of the 610 women who completed the initial study; of those, 363 women completed the extension study.

Among the 163 women who began with relugolix combination therapy in the first two trials, 87.7% met the primary endpoint in a per-protocol analysis through week 52. The proportion of responders in the extension study was 75.6% among the group that formerly received placebo (n = 164) and 79.9% in the delayed group (n = 149).

The overall average reduction in menstrual blood volume was 89.9%. Most of the women experienced amenorrhea at the end of the year: 70.6% in the relugolix group, 57.9% in the group that formerly received placebo, and 68.5% in the delayed group.

Reductions in uterine volume and uterine fibroid volume were also sustained from week 24 to week 52. For the relugolix combination therapy group, the mean loss of uterine fibroid volume from baseline was 13.5% at week 24 and 18.3% at week 52. Similarly, the delayed group’s average loss in fibroid volume was 28.1% at week 24 and 33.9% at week 52. The placebo group, which only had a 7% loss in fibroid volume at week 24, had an 18.4% loss in volume from baseline at week 52.

Among patients with anemia, defined as hemoglobin concentrations of <10.5 g/dL at baseline, 59% of those in the original relugolix group saw an improvement of at least 2 g/dL hemoglobin. The women’s improvement in pain symptoms also continued through week 52, with a 51.3-point reduction in scores on the bleeding pain and discomfort scale from baseline to the end of the study.

Adverse events were the same in the extension study and in the initial study. Those most commonly reported were headache and hot flashes. No serious safety signals occurred. The average reduction in bone mineral density was 0.80% at week 52, indicating no concerning loss.
 

A new drug class to treat uterine fibroids

Relugolix is one of three GnRH antagonists being studied for the long-term treatment of fibroids. The Food and Drug Administration approved the combination of elagolix, estradiol, and norethindrone acetate (Oriahnn) in May. Linzagolix, another GnRH antagonist, is currently in clinical trials.

“We’ll have a whole class of new drugs that are likely to fulfill this long sought-after goal of reducing the need for surgery for fibroids and doing it without a lot of side effects,” Dr. Taylor said. “The quality-of-life improvements seen here, the lack of significant adverse effects – none that were surprising in long term – the relatively low reduction in bone mineral density in a year are all very exciting [and suggest] that this will be a safe and effective long-term treatment.”
 

Significant improvement in quality of life

In the presentation on quality of life with relugolix therapy, Dr. Al-Hendy shared results regarding the severity of women’s symptoms as well as health-related quality of life, as determined on the basis of the Uterine Fibroid Symptom and Health-Related Quality of Life (UFS-QoL) questionnaire at baseline, week 12, and week 24 in LIBERTY 1 and 2. Higher UFS-QoL scores correlate with more severe symptoms. With the subscale of health-related quality of life, higher scores indicate a better quality of life.

The substudy enrolled 253 patients who received relugolix combination therapy and 256 patients who received placebo. The average menstrual blood loss was 243 mL in the relugolix group and 215 mL in the placebo group at baseline. Mean fibroid volume was the same in both groups at baseline, 73 cm³.

The proportion of Black patients was similar in both groups: 48% of the relugolix group and 54% of the placebo group.

The severity of women’s symptoms dropped from a baseline UFS-QoL score of 57 to 22.4 at 6 months among those who received relugolix combination therapy. In the placebo group, the initial score of 59.6 only dropped to 46.9 (P < .0001, for –21.4 difference in change).

Health-related quality of life increased from 38.3 to 76.6 among those who received relugolix. In the placebo group, it increased from 35.7 to 48.2 (P < .0001, for 24.5 difference). Subscales of health-related quality of life – including concern, control, activities, energy/mood, self-consciousness, and sexual function – also all improved significantly in the relugolix group, compared with the placebo group (P < .0001).

“This is a condition we see all the time that’s easily diagnosed, and we have first-line drugs we’ve been using to treat them, but none are good long-term fixes,” Dr. Taylor said. The current first-line treatments, oral contraceptives, can stabilize bleeding, “but they don’t make the fibroids shrink, they don’t stop the bleeding, women continue to have breakthrough bleeding, and the fibroids can continue to grow.”

He said most of the estimated 600,000 hysterectomies performed in the United States each year are for uterine fibroids.

“It’s a major surgery that no one wants to go through if they don’t have to,” Dr. Taylor said. “Here we have a drug that really has potential to stop the growth of the fibroids, that can stop the bleeding or dramatically improve it, and, really, for the first time, directly impact the fibroids and give us a long-term alternative.”

The studies were funded by Myovant Sciences. Dr. Al-Hendy reported consulting for AbbVie, Bayer, and Myovant Sciences, and he owns a patent for novel diagnostics and therapeutics for uterine sarcoma. Dr. Taylor has disclosed no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

A combination therapy using the experimental drug relugolix was effective in treating pain and heavy bleeding from uterine fibroids for a full year, according to findings from a long-term extension study of the phase 3, open-label LIBERTY trials.

The drug was also well tolerated, with retention of bone mineral density and no new adverse events, said Ayman Al-Hendy, MD, PhD, who presented the results Oct. 17 at the virtual American Society for Reproductive Medicine 2020 Scientific Congress.

“Relugolix combination therapy represents a potential long-term treatment for women with heavy menstrual bleeding associated with uterine fibroids,” said Al-Hendy, a gynecologist and endoscopic surgeon at the University of Chicago.

Dr. Al-Hendy, who consults for the company that makes the drug, on Oct. 20 presented results showing improvement in quality of life with relugolix therapy.

“The fact that this longer-term study shows continued, persistent results at a year really gives us confidence that we’ll be able to use these drugs as a long-term therapy to treat fibroids,” Hugh S. Taylor, MD, president-elect of ASRM, said in an interview. Dr. Taylor, a professor and chair of ob.gyn. and reproductive sciences at Yale University, New Haven, Conn., was not involved in the study.

“A drug like this is so necessary,” Dr. Taylor continued. “We don’t have any other drugs on the market approved for long-term use.”

Relugolix is an oral gonadotropin-releasing hormone (GnRH) receptor antagonist under investigation for long-term management of uterine fibroids. The once-daily combination therapy includes 40 mg relugolix, 1 mg estradiol, and 0.5 mg norethindrone acetate.
 

Extension study shows prolonged benefits

The extension trial enrolled women aged 18-50 years who were experiencing heavy menstrual bleeding from uterine fibroids and who completed the 24-week phase 3, double-blind, placebo-controlled LIBERTY 1 or 2 trials. Heavy menstrual bleeding was defined as bleeding in which at least 80 mL of blood was lost per cycle for two cycles or 160 mL was lost during one cycle. Ultrasound imaging was used to confirm the presence of fibroids.

In LIBERTY 1 and 2, women were randomly assigned to receive relugolix combination therapy, placebo, or relugolix alone for 12 weeks followed by combination therapy for the remaining 12 weeks (delayed group). Those trials found that relugolix combination therapy was effective through 6 months in reducing menstrual blood loss and pain in women with uterine fibroids without loss of bone mineral density.

LIBERTY 3 extended the trial to 52 weeks, with all participants receiving relugolix combination therapy.

As in the earlier trials, the primary endpoint was reduced menstrual blood loss. By the end of the study, women needed to have at least a 50% reduction in blood loss from the initial study’s baseline while maintaining a blood loss of <80 mL. The investigators also evaluated the mean percentage of menstrual blood loss reduction, amenorrhea rate, and improvements in anemia as secondary endpoints and assessed changes in bone mineral density.

The extension study enrolled 78% (n = 477) of the 610 women who completed the initial study; of those, 363 women completed the extension study.

Among the 163 women who began with relugolix combination therapy in the first two trials, 87.7% met the primary endpoint in a per-protocol analysis through week 52. The proportion of responders in the extension study was 75.6% among the group that formerly received placebo (n = 164) and 79.9% in the delayed group (n = 149).

The overall average reduction in menstrual blood volume was 89.9%. Most of the women experienced amenorrhea at the end of the year: 70.6% in the relugolix group, 57.9% in the group that formerly received placebo, and 68.5% in the delayed group.

Reductions in uterine volume and uterine fibroid volume were also sustained from week 24 to week 52. For the relugolix combination therapy group, the mean loss of uterine fibroid volume from baseline was 13.5% at week 24 and 18.3% at week 52. Similarly, the delayed group’s average loss in fibroid volume was 28.1% at week 24 and 33.9% at week 52. The placebo group, which only had a 7% loss in fibroid volume at week 24, had an 18.4% loss in volume from baseline at week 52.

Among patients with anemia, defined as hemoglobin concentrations of <10.5 g/dL at baseline, 59% of those in the original relugolix group saw an improvement of at least 2 g/dL hemoglobin. The women’s improvement in pain symptoms also continued through week 52, with a 51.3-point reduction in scores on the bleeding pain and discomfort scale from baseline to the end of the study.

Adverse events were the same in the extension study and in the initial study. Those most commonly reported were headache and hot flashes. No serious safety signals occurred. The average reduction in bone mineral density was 0.80% at week 52, indicating no concerning loss.
 

A new drug class to treat uterine fibroids

Relugolix is one of three GnRH antagonists being studied for the long-term treatment of fibroids. The Food and Drug Administration approved the combination of elagolix, estradiol, and norethindrone acetate (Oriahnn) in May. Linzagolix, another GnRH antagonist, is currently in clinical trials.

“We’ll have a whole class of new drugs that are likely to fulfill this long sought-after goal of reducing the need for surgery for fibroids and doing it without a lot of side effects,” Dr. Taylor said. “The quality-of-life improvements seen here, the lack of significant adverse effects – none that were surprising in long term – the relatively low reduction in bone mineral density in a year are all very exciting [and suggest] that this will be a safe and effective long-term treatment.”
 

Significant improvement in quality of life

In the presentation on quality of life with relugolix therapy, Dr. Al-Hendy shared results regarding the severity of women’s symptoms as well as health-related quality of life, as determined on the basis of the Uterine Fibroid Symptom and Health-Related Quality of Life (UFS-QoL) questionnaire at baseline, week 12, and week 24 in LIBERTY 1 and 2. Higher UFS-QoL scores correlate with more severe symptoms. With the subscale of health-related quality of life, higher scores indicate a better quality of life.

The substudy enrolled 253 patients who received relugolix combination therapy and 256 patients who received placebo. The average menstrual blood loss was 243 mL in the relugolix group and 215 mL in the placebo group at baseline. Mean fibroid volume was the same in both groups at baseline, 73 cm³.

The proportion of Black patients was similar in both groups: 48% of the relugolix group and 54% of the placebo group.

The severity of women’s symptoms dropped from a baseline UFS-QoL score of 57 to 22.4 at 6 months among those who received relugolix combination therapy. In the placebo group, the initial score of 59.6 only dropped to 46.9 (P < .0001, for –21.4 difference in change).

Health-related quality of life increased from 38.3 to 76.6 among those who received relugolix. In the placebo group, it increased from 35.7 to 48.2 (P < .0001, for 24.5 difference). Subscales of health-related quality of life – including concern, control, activities, energy/mood, self-consciousness, and sexual function – also all improved significantly in the relugolix group, compared with the placebo group (P < .0001).

“This is a condition we see all the time that’s easily diagnosed, and we have first-line drugs we’ve been using to treat them, but none are good long-term fixes,” Dr. Taylor said. The current first-line treatments, oral contraceptives, can stabilize bleeding, “but they don’t make the fibroids shrink, they don’t stop the bleeding, women continue to have breakthrough bleeding, and the fibroids can continue to grow.”

He said most of the estimated 600,000 hysterectomies performed in the United States each year are for uterine fibroids.

“It’s a major surgery that no one wants to go through if they don’t have to,” Dr. Taylor said. “Here we have a drug that really has potential to stop the growth of the fibroids, that can stop the bleeding or dramatically improve it, and, really, for the first time, directly impact the fibroids and give us a long-term alternative.”

The studies were funded by Myovant Sciences. Dr. Al-Hendy reported consulting for AbbVie, Bayer, and Myovant Sciences, and he owns a patent for novel diagnostics and therapeutics for uterine sarcoma. Dr. Taylor has disclosed no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

A combination therapy using the experimental drug relugolix was effective in treating pain and heavy bleeding from uterine fibroids for a full year, according to findings from a long-term extension study of the phase 3, open-label LIBERTY trials.

The drug was also well tolerated, with retention of bone mineral density and no new adverse events, said Ayman Al-Hendy, MD, PhD, who presented the results Oct. 17 at the virtual American Society for Reproductive Medicine 2020 Scientific Congress.

“Relugolix combination therapy represents a potential long-term treatment for women with heavy menstrual bleeding associated with uterine fibroids,” said Al-Hendy, a gynecologist and endoscopic surgeon at the University of Chicago.

Dr. Al-Hendy, who consults for the company that makes the drug, on Oct. 20 presented results showing improvement in quality of life with relugolix therapy.

“The fact that this longer-term study shows continued, persistent results at a year really gives us confidence that we’ll be able to use these drugs as a long-term therapy to treat fibroids,” Hugh S. Taylor, MD, president-elect of ASRM, said in an interview. Dr. Taylor, a professor and chair of ob.gyn. and reproductive sciences at Yale University, New Haven, Conn., was not involved in the study.

“A drug like this is so necessary,” Dr. Taylor continued. “We don’t have any other drugs on the market approved for long-term use.”

Relugolix is an oral gonadotropin-releasing hormone (GnRH) receptor antagonist under investigation for long-term management of uterine fibroids. The once-daily combination therapy includes 40 mg relugolix, 1 mg estradiol, and 0.5 mg norethindrone acetate.
 

Extension study shows prolonged benefits

The extension trial enrolled women aged 18-50 years who were experiencing heavy menstrual bleeding from uterine fibroids and who completed the 24-week phase 3, double-blind, placebo-controlled LIBERTY 1 or 2 trials. Heavy menstrual bleeding was defined as bleeding in which at least 80 mL of blood was lost per cycle for two cycles or 160 mL was lost during one cycle. Ultrasound imaging was used to confirm the presence of fibroids.

In LIBERTY 1 and 2, women were randomly assigned to receive relugolix combination therapy, placebo, or relugolix alone for 12 weeks followed by combination therapy for the remaining 12 weeks (delayed group). Those trials found that relugolix combination therapy was effective through 6 months in reducing menstrual blood loss and pain in women with uterine fibroids without loss of bone mineral density.

LIBERTY 3 extended the trial to 52 weeks, with all participants receiving relugolix combination therapy.

As in the earlier trials, the primary endpoint was reduced menstrual blood loss. By the end of the study, women needed to have at least a 50% reduction in blood loss from the initial study’s baseline while maintaining a blood loss of <80 mL. The investigators also evaluated the mean percentage of menstrual blood loss reduction, amenorrhea rate, and improvements in anemia as secondary endpoints and assessed changes in bone mineral density.

The extension study enrolled 78% (n = 477) of the 610 women who completed the initial study; of those, 363 women completed the extension study.

Among the 163 women who began with relugolix combination therapy in the first two trials, 87.7% met the primary endpoint in a per-protocol analysis through week 52. The proportion of responders in the extension study was 75.6% among the group that formerly received placebo (n = 164) and 79.9% in the delayed group (n = 149).

The overall average reduction in menstrual blood volume was 89.9%. Most of the women experienced amenorrhea at the end of the year: 70.6% in the relugolix group, 57.9% in the group that formerly received placebo, and 68.5% in the delayed group.

Reductions in uterine volume and uterine fibroid volume were also sustained from week 24 to week 52. For the relugolix combination therapy group, the mean loss of uterine fibroid volume from baseline was 13.5% at week 24 and 18.3% at week 52. Similarly, the delayed group’s average loss in fibroid volume was 28.1% at week 24 and 33.9% at week 52. The placebo group, which only had a 7% loss in fibroid volume at week 24, had an 18.4% loss in volume from baseline at week 52.

Among patients with anemia, defined as hemoglobin concentrations of <10.5 g/dL at baseline, 59% of those in the original relugolix group saw an improvement of at least 2 g/dL hemoglobin. The women’s improvement in pain symptoms also continued through week 52, with a 51.3-point reduction in scores on the bleeding pain and discomfort scale from baseline to the end of the study.

Adverse events were the same in the extension study and in the initial study. Those most commonly reported were headache and hot flashes. No serious safety signals occurred. The average reduction in bone mineral density was 0.80% at week 52, indicating no concerning loss.
 

A new drug class to treat uterine fibroids

Relugolix is one of three GnRH antagonists being studied for the long-term treatment of fibroids. The Food and Drug Administration approved the combination of elagolix, estradiol, and norethindrone acetate (Oriahnn) in May. Linzagolix, another GnRH antagonist, is currently in clinical trials.

“We’ll have a whole class of new drugs that are likely to fulfill this long sought-after goal of reducing the need for surgery for fibroids and doing it without a lot of side effects,” Dr. Taylor said. “The quality-of-life improvements seen here, the lack of significant adverse effects – none that were surprising in long term – the relatively low reduction in bone mineral density in a year are all very exciting [and suggest] that this will be a safe and effective long-term treatment.”
 

Significant improvement in quality of life

In the presentation on quality of life with relugolix therapy, Dr. Al-Hendy shared results regarding the severity of women’s symptoms as well as health-related quality of life, as determined on the basis of the Uterine Fibroid Symptom and Health-Related Quality of Life (UFS-QoL) questionnaire at baseline, week 12, and week 24 in LIBERTY 1 and 2. Higher UFS-QoL scores correlate with more severe symptoms. With the subscale of health-related quality of life, higher scores indicate a better quality of life.

The substudy enrolled 253 patients who received relugolix combination therapy and 256 patients who received placebo. The average menstrual blood loss was 243 mL in the relugolix group and 215 mL in the placebo group at baseline. Mean fibroid volume was the same in both groups at baseline, 73 cm³.

The proportion of Black patients was similar in both groups: 48% of the relugolix group and 54% of the placebo group.

The severity of women’s symptoms dropped from a baseline UFS-QoL score of 57 to 22.4 at 6 months among those who received relugolix combination therapy. In the placebo group, the initial score of 59.6 only dropped to 46.9 (P < .0001, for –21.4 difference in change).

Health-related quality of life increased from 38.3 to 76.6 among those who received relugolix. In the placebo group, it increased from 35.7 to 48.2 (P < .0001, for 24.5 difference). Subscales of health-related quality of life – including concern, control, activities, energy/mood, self-consciousness, and sexual function – also all improved significantly in the relugolix group, compared with the placebo group (P < .0001).

“This is a condition we see all the time that’s easily diagnosed, and we have first-line drugs we’ve been using to treat them, but none are good long-term fixes,” Dr. Taylor said. The current first-line treatments, oral contraceptives, can stabilize bleeding, “but they don’t make the fibroids shrink, they don’t stop the bleeding, women continue to have breakthrough bleeding, and the fibroids can continue to grow.”

He said most of the estimated 600,000 hysterectomies performed in the United States each year are for uterine fibroids.

“It’s a major surgery that no one wants to go through if they don’t have to,” Dr. Taylor said. “Here we have a drug that really has potential to stop the growth of the fibroids, that can stop the bleeding or dramatically improve it, and, really, for the first time, directly impact the fibroids and give us a long-term alternative.”

The studies were funded by Myovant Sciences. Dr. Al-Hendy reported consulting for AbbVie, Bayer, and Myovant Sciences, and he owns a patent for novel diagnostics and therapeutics for uterine sarcoma. Dr. Taylor has disclosed no relevant financial relationships.

A version of this article originally appeared on Medscape.com.