Ob.Gyn. News

Obese women may benefit from a higher dose of magnesium sulfate to protect against preeclampsia, based on data from a randomized trial.

Pharmacokinetic models have shown that, “in women who received a 4-g intravenous loading dose followed by a 2-g/h IV maintenance dose, obese women took approximately twice as long as women of mean body weight in the sample to achieve these previously accepted therapeutic serum magnesium concentrations,” which suggests the need for alternate dosing based on body mass index, wrote Kathleen F. Brookfield, MD, of Oregon Health & Science University, Portland, and colleagues.

In a study published in Obstetrics & Gynecology, the researchers randomized 37 women aged 15-45 years with a BMI of 35 kg/m² or higher who were at least 32 weeks’ gestation to receive the standard Zuspan regimen of magnesium sulfate (4 g intravenous loading dose, followed by a 1-g/hour infusion) or to higher dosing (6 g IV loading dose, followed by a 2-g/hour infusion).
 

Higher dose increases effectiveness

Serum magnesium concentrations were measured at baseline, and after administration of magnesium sulfate at 1 hour, 4 hours, and delivery; the primary outcome was the proportion of women with subtherapeutic serum magnesium concentrations (less than 4.8 mg/dL) 4 hours after administration.

After 4 hours, the average magnesium sulfate concentrations were significantly higher for women in the high-dose group vs. the standard group (4.41 mg/dL vs. 3.53 mg/dL). In addition, 100% of women in the standard group had subtherapeutic serum magnesium concentrations compared with 63% of the high-dose group.

No significant differences in maternal side effects or neonatal outcomes occurred between the groups. However, rates of nausea and flushing were higher in the higher dose group, compared with the standard group (10.5% vs. 5.5% and 5.2% vs. 0%, respectively).

The study findings were limited by several factors including the lack of statistical power to evaluate clinical outcomes and lack of generalizability to extremely obese patients, as well as to settings in which the higher-dose regimen is already the standard treatment, the researchers noted. However, the results were strengthened by the use of prospective pharmacokinetic data to determine dosing.

The researchers also noted that the study was not powered to examine preeclampsia as an outcome “and there is no evidence to date to suggest women in the United States with higher BMIs are more likely to experience eclampsia,” they said. “Therefore, we caution against universally applying the study findings to obese women without also considering the potential for increased toxicity with higher dosing regimens,” they added.

Current results may not affect practice

The study objectives are unclear, as they do not change the dosing for magnesium sulfate already in use, said Baha M. Sibai, MD, of the University of Texas Health Science Center at Houston, in an interview.

Dr. Sibai said he was not surprised by the findings. “This information has been known for almost 30 years as to serum levels with different dosing irrespective of BMI,” he said. Based on current evidence, Dr. Sibai advised clinicians “not to change your practice, since there are no therapeutic levels for preventing seizures.” In fact, “the largest trial that included 10,000 women showed no difference in the rate of eclampsia between 4 grams loading with 1 g/hour [magnesium sulfate] and 6 g loading and 2 g/hour,” he explained.

Future research should focus on different outcomes, said Dr. Sibai. “The outcome should be eclampsia and not serum levels. This requires studying over 6,000 women,” he emphasized.

The study was supported by the National Institutes of Health Loan Repayment Program and a Mission Support Award from Oregon Health & Science University to Dr. Brookfield and by the Oregon Clinical & Translational Research Institute grant. Dr. Brookfield also disclosed funding from the World Health Organization. Dr. Sibai had no financial conflicts to disclose.

SOURCE: Brookfield KF et al. Obstet Gynecol. 2020 Dec. doi: 10.1097/AOG.0000000000004137.

Obese women may benefit from a higher dose of magnesium sulfate to protect against preeclampsia, based on data from a randomized trial.

Pharmacokinetic models have shown that, “in women who received a 4-g intravenous loading dose followed by a 2-g/h IV maintenance dose, obese women took approximately twice as long as women of mean body weight in the sample to achieve these previously accepted therapeutic serum magnesium concentrations,” which suggests the need for alternate dosing based on body mass index, wrote Kathleen F. Brookfield, MD, of Oregon Health & Science University, Portland, and colleagues.

In a study published in Obstetrics & Gynecology, the researchers randomized 37 women aged 15-45 years with a BMI of 35 kg/m² or higher who were at least 32 weeks’ gestation to receive the standard Zuspan regimen of magnesium sulfate (4 g intravenous loading dose, followed by a 1-g/hour infusion) or to higher dosing (6 g IV loading dose, followed by a 2-g/hour infusion).
 

Higher dose increases effectiveness

Serum magnesium concentrations were measured at baseline, and after administration of magnesium sulfate at 1 hour, 4 hours, and delivery; the primary outcome was the proportion of women with subtherapeutic serum magnesium concentrations (less than 4.8 mg/dL) 4 hours after administration.

After 4 hours, the average magnesium sulfate concentrations were significantly higher for women in the high-dose group vs. the standard group (4.41 mg/dL vs. 3.53 mg/dL). In addition, 100% of women in the standard group had subtherapeutic serum magnesium concentrations compared with 63% of the high-dose group.

No significant differences in maternal side effects or neonatal outcomes occurred between the groups. However, rates of nausea and flushing were higher in the higher dose group, compared with the standard group (10.5% vs. 5.5% and 5.2% vs. 0%, respectively).

The study findings were limited by several factors including the lack of statistical power to evaluate clinical outcomes and lack of generalizability to extremely obese patients, as well as to settings in which the higher-dose regimen is already the standard treatment, the researchers noted. However, the results were strengthened by the use of prospective pharmacokinetic data to determine dosing.

The researchers also noted that the study was not powered to examine preeclampsia as an outcome “and there is no evidence to date to suggest women in the United States with higher BMIs are more likely to experience eclampsia,” they said. “Therefore, we caution against universally applying the study findings to obese women without also considering the potential for increased toxicity with higher dosing regimens,” they added.

Current results may not affect practice

The study objectives are unclear, as they do not change the dosing for magnesium sulfate already in use, said Baha M. Sibai, MD, of the University of Texas Health Science Center at Houston, in an interview.

Dr. Sibai said he was not surprised by the findings. “This information has been known for almost 30 years as to serum levels with different dosing irrespective of BMI,” he said. Based on current evidence, Dr. Sibai advised clinicians “not to change your practice, since there are no therapeutic levels for preventing seizures.” In fact, “the largest trial that included 10,000 women showed no difference in the rate of eclampsia between 4 grams loading with 1 g/hour [magnesium sulfate] and 6 g loading and 2 g/hour,” he explained.

Future research should focus on different outcomes, said Dr. Sibai. “The outcome should be eclampsia and not serum levels. This requires studying over 6,000 women,” he emphasized.

The study was supported by the National Institutes of Health Loan Repayment Program and a Mission Support Award from Oregon Health & Science University to Dr. Brookfield and by the Oregon Clinical & Translational Research Institute grant. Dr. Brookfield also disclosed funding from the World Health Organization. Dr. Sibai had no financial conflicts to disclose.

SOURCE: Brookfield KF et al. Obstet Gynecol. 2020 Dec. doi: 10.1097/AOG.0000000000004137.

Obese women may benefit from a higher dose of magnesium sulfate to protect against preeclampsia, based on data from a randomized trial.

Pharmacokinetic models have shown that, “in women who received a 4-g intravenous loading dose followed by a 2-g/h IV maintenance dose, obese women took approximately twice as long as women of mean body weight in the sample to achieve these previously accepted therapeutic serum magnesium concentrations,” which suggests the need for alternate dosing based on body mass index, wrote Kathleen F. Brookfield, MD, of Oregon Health & Science University, Portland, and colleagues.

In a study published in Obstetrics & Gynecology, the researchers randomized 37 women aged 15-45 years with a BMI of 35 kg/m² or higher who were at least 32 weeks’ gestation to receive the standard Zuspan regimen of magnesium sulfate (4 g intravenous loading dose, followed by a 1-g/hour infusion) or to higher dosing (6 g IV loading dose, followed by a 2-g/hour infusion).
 

Higher dose increases effectiveness

Serum magnesium concentrations were measured at baseline, and after administration of magnesium sulfate at 1 hour, 4 hours, and delivery; the primary outcome was the proportion of women with subtherapeutic serum magnesium concentrations (less than 4.8 mg/dL) 4 hours after administration.

After 4 hours, the average magnesium sulfate concentrations were significantly higher for women in the high-dose group vs. the standard group (4.41 mg/dL vs. 3.53 mg/dL). In addition, 100% of women in the standard group had subtherapeutic serum magnesium concentrations compared with 63% of the high-dose group.

No significant differences in maternal side effects or neonatal outcomes occurred between the groups. However, rates of nausea and flushing were higher in the higher dose group, compared with the standard group (10.5% vs. 5.5% and 5.2% vs. 0%, respectively).

The study findings were limited by several factors including the lack of statistical power to evaluate clinical outcomes and lack of generalizability to extremely obese patients, as well as to settings in which the higher-dose regimen is already the standard treatment, the researchers noted. However, the results were strengthened by the use of prospective pharmacokinetic data to determine dosing.

The researchers also noted that the study was not powered to examine preeclampsia as an outcome “and there is no evidence to date to suggest women in the United States with higher BMIs are more likely to experience eclampsia,” they said. “Therefore, we caution against universally applying the study findings to obese women without also considering the potential for increased toxicity with higher dosing regimens,” they added.

Current results may not affect practice

The study objectives are unclear, as they do not change the dosing for magnesium sulfate already in use, said Baha M. Sibai, MD, of the University of Texas Health Science Center at Houston, in an interview.

Dr. Sibai said he was not surprised by the findings. “This information has been known for almost 30 years as to serum levels with different dosing irrespective of BMI,” he said. Based on current evidence, Dr. Sibai advised clinicians “not to change your practice, since there are no therapeutic levels for preventing seizures.” In fact, “the largest trial that included 10,000 women showed no difference in the rate of eclampsia between 4 grams loading with 1 g/hour [magnesium sulfate] and 6 g loading and 2 g/hour,” he explained.

Future research should focus on different outcomes, said Dr. Sibai. “The outcome should be eclampsia and not serum levels. This requires studying over 6,000 women,” he emphasized.

The study was supported by the National Institutes of Health Loan Repayment Program and a Mission Support Award from Oregon Health & Science University to Dr. Brookfield and by the Oregon Clinical & Translational Research Institute grant. Dr. Brookfield also disclosed funding from the World Health Organization. Dr. Sibai had no financial conflicts to disclose.

SOURCE: Brookfield KF et al. Obstet Gynecol. 2020 Dec. doi: 10.1097/AOG.0000000000004137.

MRI-guided adaptive brachytherapy yields promising long-term outcomes in locally advanced cervical cancer but needs refinement to reduce morbidity and improve efficacy for certain patients, the EMBRACE I study suggests.

At 5 years, the rate of local control was 92%, and overall survival was 74%. However, nodal and systemic control rates were inferior for node-positive and high-risk patients, and nearly 15% of patients experienced grade 3-5 treatment-related morbidity.

These results were reported at the European Society for Radiology and Oncology 2020 Online Congress.

Historically, brachytherapy dose has been fairly rigidly prescribed, based on dose points defined in two dimensions. By performing imaging before each brachytherapy implant, treatment parameters can be adapted to a patient’s anatomy, taking into account the positions of organs at risk and any tumor regression from prior treatment.

Richard Pötter, MD, emeritus professor at Medical University of Vienna, and colleagues tested MRI-guided adaptive brachytherapy in a multicenter cohort study.

The study’s disease outcome analysis included 1,341 women with cervical cancer of International Federation of Gynecology and Obstetrics stage IB–IVB (52% node positive) being treated with curative intent.

The women underwent definitive external beam radiotherapy (45-50 Gy, using either three-dimensional–conformal radiotherapy or intensity-modulated radiotherapy) with concurrent cisplatin chemotherapy, followed by MRI-guided adaptive brachytherapy based on MRI with the applicator in situ.

“There was no fixed dose prescription for brachytherapy, and there were no constraints for organs at risk,” Dr. Pötter explained. “But there was systematic joint reporting and contouring for the target and organs at risk, and also for doses and volumes.”

Nearly all patients were treated with adaptive MRI-based target and dose-volume and point parameters (99.1%), as well as with individualized multiparametric dose optimization (98.2%). The application technique was adapted, with intracavitary application alone used in 57% of patients, and both intracavitary and interstitial application in 43%.
 

Efficacy and toxicity

At a median follow-up of 51 months, 7.3% of patients had experienced a local failure, with 3.8% having an isolated local failure and 3.5% having synchronous nodal or systemic failure, Dr. Pötter reported.

The local failure rate was similar going from disease stage IB2 to IVA (8%-9%), even though the target volume more than doubled.

“This favorable result was due to an adaptation of dose, which was quite similar for the different stages and volumes. This is a major message of EMBRACE I,” Dr. Pötter commented.

The Kaplan-Meier–estimated 5-year rate of local control was 92% for the whole cohort. It was 98% in patients with stage IB1 disease and 91%-92% in patients with stage IB2–IVA disease.

The 5-year rate of overall survival was 74% for the entire cohort. It fell with stage, from 83% in patients with stage IB1 disease to 52% in patients with stage IVA disease.

For the entire population, the 5-year pelvic control rate was 87%, the 5-year cancer-specific survival was 79%, and the 5-year disease-free survival was 68%.

Overall, 14.6% of patients experienced grade 3-5 treatment-related morbidity at 5 years: 2.7% developed fistulas, 6.1% had vaginal toxicity, 6.5% had genitourinary toxicity, and 7.6% had gastrointestinal toxicity.
 

Room for improvement

“MRI-guided adaptive brachytherapy in locally advanced cervical cancer works in multicenter clinical practice, within such a study, with adaptation of the target and application technique, and multiparametric treatment planning and dose prescription,” Dr. Pötter summarized.

However, “the mature clinical outcomes appear challenging,” he added. Specifically, although the rate of local control was high, the rate of nodal control left room for improvement in node-positive patients, and the rates of systemic control and overall survival left room for improvement in high-risk patients.

In addition, “the grade 3-5 morbidity was limited per organ and per endpoint, but was considerable overall, and this asks for a reduction,” Dr. Pötter said.

Two of the areas needing improvement are being addressed in ongoing and planned research, according to Dr. Pötter. “The nodal part is already being addressed in EMBRACE II, intensifying treatment for node-positive patients through a simultaneous integrated boost and a very sophisticated probability planning concept, and also including more patients for paraaortic radiotherapy,” he elaborated. “For the systemic part, we have thought about [a study testing an] additional drug ... and there are thoughts for EMBRACE III to investigate such effect.”
 

A benchmark for brachytherapy

“This is the largest prospective cohort of patients treated with image-guided brachytherapy. The high rates of local control with long-term follow-up are impressive and speak to the clear value of high-quality brachytherapy,” commented Ann H. Klopp, MD, PhD, of the University of Texas MD Anderson Cancer Center, Houston, who was not involved in this study.

With its consistent reporting of detailed dose and toxicity data, the study establishes a benchmark for brachytherapy worldwide, Dr. Klopp said. It also better informs treatment decision-making in cases where replacing brachytherapy with external beam techniques is being considered.

Although MRI guidance is increasingly being used in brachytherapy, the latest studies on patterns of care suggest that overall use is still low, according to Dr. Klopp.

“The challenges are primarily logistical,” she elaborated. “MRI-compatible applicators must be placed, and patients need to wait for the scans to be performed, which can take an hour or more. In addition, the times that patients get scanned can be unpredictable based on procedure times, which can create practical challenges for scheduling. In some cases, cost may also be a deterrent.

“The bar is high for brachytherapy. It’s an excellent treatment modality that provides very high rates of local control with very low toxicity when done optimally,” Dr. Klopp concluded. “I do think that this experience provides very convincing evidence that the best brachytherapy is image-guided and requires care to monitor normal tissue doses in order to reduce the risk of long-term toxicity.”

The study was supported by unrestricted grants from Elekta and Varian. Dr. Pötter and Dr. Klopp disclosed no conflicts of interest.

SOURCE: Pötter R et al. ESTRO 2020, Abstract OC-0437.

MRI-guided adaptive brachytherapy yields promising long-term outcomes in locally advanced cervical cancer but needs refinement to reduce morbidity and improve efficacy for certain patients, the EMBRACE I study suggests.

At 5 years, the rate of local control was 92%, and overall survival was 74%. However, nodal and systemic control rates were inferior for node-positive and high-risk patients, and nearly 15% of patients experienced grade 3-5 treatment-related morbidity.

These results were reported at the European Society for Radiology and Oncology 2020 Online Congress.

Historically, brachytherapy dose has been fairly rigidly prescribed, based on dose points defined in two dimensions. By performing imaging before each brachytherapy implant, treatment parameters can be adapted to a patient’s anatomy, taking into account the positions of organs at risk and any tumor regression from prior treatment.

Richard Pötter, MD, emeritus professor at Medical University of Vienna, and colleagues tested MRI-guided adaptive brachytherapy in a multicenter cohort study.

The study’s disease outcome analysis included 1,341 women with cervical cancer of International Federation of Gynecology and Obstetrics stage IB–IVB (52% node positive) being treated with curative intent.

The women underwent definitive external beam radiotherapy (45-50 Gy, using either three-dimensional–conformal radiotherapy or intensity-modulated radiotherapy) with concurrent cisplatin chemotherapy, followed by MRI-guided adaptive brachytherapy based on MRI with the applicator in situ.

“There was no fixed dose prescription for brachytherapy, and there were no constraints for organs at risk,” Dr. Pötter explained. “But there was systematic joint reporting and contouring for the target and organs at risk, and also for doses and volumes.”

Nearly all patients were treated with adaptive MRI-based target and dose-volume and point parameters (99.1%), as well as with individualized multiparametric dose optimization (98.2%). The application technique was adapted, with intracavitary application alone used in 57% of patients, and both intracavitary and interstitial application in 43%.
 

Efficacy and toxicity

At a median follow-up of 51 months, 7.3% of patients had experienced a local failure, with 3.8% having an isolated local failure and 3.5% having synchronous nodal or systemic failure, Dr. Pötter reported.

The local failure rate was similar going from disease stage IB2 to IVA (8%-9%), even though the target volume more than doubled.

“This favorable result was due to an adaptation of dose, which was quite similar for the different stages and volumes. This is a major message of EMBRACE I,” Dr. Pötter commented.

The Kaplan-Meier–estimated 5-year rate of local control was 92% for the whole cohort. It was 98% in patients with stage IB1 disease and 91%-92% in patients with stage IB2–IVA disease.

The 5-year rate of overall survival was 74% for the entire cohort. It fell with stage, from 83% in patients with stage IB1 disease to 52% in patients with stage IVA disease.

For the entire population, the 5-year pelvic control rate was 87%, the 5-year cancer-specific survival was 79%, and the 5-year disease-free survival was 68%.

Overall, 14.6% of patients experienced grade 3-5 treatment-related morbidity at 5 years: 2.7% developed fistulas, 6.1% had vaginal toxicity, 6.5% had genitourinary toxicity, and 7.6% had gastrointestinal toxicity.
 

Room for improvement

“MRI-guided adaptive brachytherapy in locally advanced cervical cancer works in multicenter clinical practice, within such a study, with adaptation of the target and application technique, and multiparametric treatment planning and dose prescription,” Dr. Pötter summarized.

However, “the mature clinical outcomes appear challenging,” he added. Specifically, although the rate of local control was high, the rate of nodal control left room for improvement in node-positive patients, and the rates of systemic control and overall survival left room for improvement in high-risk patients.

In addition, “the grade 3-5 morbidity was limited per organ and per endpoint, but was considerable overall, and this asks for a reduction,” Dr. Pötter said.

Two of the areas needing improvement are being addressed in ongoing and planned research, according to Dr. Pötter. “The nodal part is already being addressed in EMBRACE II, intensifying treatment for node-positive patients through a simultaneous integrated boost and a very sophisticated probability planning concept, and also including more patients for paraaortic radiotherapy,” he elaborated. “For the systemic part, we have thought about [a study testing an] additional drug ... and there are thoughts for EMBRACE III to investigate such effect.”
 

A benchmark for brachytherapy

“This is the largest prospective cohort of patients treated with image-guided brachytherapy. The high rates of local control with long-term follow-up are impressive and speak to the clear value of high-quality brachytherapy,” commented Ann H. Klopp, MD, PhD, of the University of Texas MD Anderson Cancer Center, Houston, who was not involved in this study.

With its consistent reporting of detailed dose and toxicity data, the study establishes a benchmark for brachytherapy worldwide, Dr. Klopp said. It also better informs treatment decision-making in cases where replacing brachytherapy with external beam techniques is being considered.

Although MRI guidance is increasingly being used in brachytherapy, the latest studies on patterns of care suggest that overall use is still low, according to Dr. Klopp.

“The challenges are primarily logistical,” she elaborated. “MRI-compatible applicators must be placed, and patients need to wait for the scans to be performed, which can take an hour or more. In addition, the times that patients get scanned can be unpredictable based on procedure times, which can create practical challenges for scheduling. In some cases, cost may also be a deterrent.

“The bar is high for brachytherapy. It’s an excellent treatment modality that provides very high rates of local control with very low toxicity when done optimally,” Dr. Klopp concluded. “I do think that this experience provides very convincing evidence that the best brachytherapy is image-guided and requires care to monitor normal tissue doses in order to reduce the risk of long-term toxicity.”

The study was supported by unrestricted grants from Elekta and Varian. Dr. Pötter and Dr. Klopp disclosed no conflicts of interest.

SOURCE: Pötter R et al. ESTRO 2020, Abstract OC-0437.

MRI-guided adaptive brachytherapy yields promising long-term outcomes in locally advanced cervical cancer but needs refinement to reduce morbidity and improve efficacy for certain patients, the EMBRACE I study suggests.

At 5 years, the rate of local control was 92%, and overall survival was 74%. However, nodal and systemic control rates were inferior for node-positive and high-risk patients, and nearly 15% of patients experienced grade 3-5 treatment-related morbidity.

These results were reported at the European Society for Radiology and Oncology 2020 Online Congress.

Historically, brachytherapy dose has been fairly rigidly prescribed, based on dose points defined in two dimensions. By performing imaging before each brachytherapy implant, treatment parameters can be adapted to a patient’s anatomy, taking into account the positions of organs at risk and any tumor regression from prior treatment.

Richard Pötter, MD, emeritus professor at Medical University of Vienna, and colleagues tested MRI-guided adaptive brachytherapy in a multicenter cohort study.

The study’s disease outcome analysis included 1,341 women with cervical cancer of International Federation of Gynecology and Obstetrics stage IB–IVB (52% node positive) being treated with curative intent.

The women underwent definitive external beam radiotherapy (45-50 Gy, using either three-dimensional–conformal radiotherapy or intensity-modulated radiotherapy) with concurrent cisplatin chemotherapy, followed by MRI-guided adaptive brachytherapy based on MRI with the applicator in situ.

“There was no fixed dose prescription for brachytherapy, and there were no constraints for organs at risk,” Dr. Pötter explained. “But there was systematic joint reporting and contouring for the target and organs at risk, and also for doses and volumes.”

Nearly all patients were treated with adaptive MRI-based target and dose-volume and point parameters (99.1%), as well as with individualized multiparametric dose optimization (98.2%). The application technique was adapted, with intracavitary application alone used in 57% of patients, and both intracavitary and interstitial application in 43%.
 

Efficacy and toxicity

At a median follow-up of 51 months, 7.3% of patients had experienced a local failure, with 3.8% having an isolated local failure and 3.5% having synchronous nodal or systemic failure, Dr. Pötter reported.

The local failure rate was similar going from disease stage IB2 to IVA (8%-9%), even though the target volume more than doubled.

“This favorable result was due to an adaptation of dose, which was quite similar for the different stages and volumes. This is a major message of EMBRACE I,” Dr. Pötter commented.

The Kaplan-Meier–estimated 5-year rate of local control was 92% for the whole cohort. It was 98% in patients with stage IB1 disease and 91%-92% in patients with stage IB2–IVA disease.

The 5-year rate of overall survival was 74% for the entire cohort. It fell with stage, from 83% in patients with stage IB1 disease to 52% in patients with stage IVA disease.

For the entire population, the 5-year pelvic control rate was 87%, the 5-year cancer-specific survival was 79%, and the 5-year disease-free survival was 68%.

Overall, 14.6% of patients experienced grade 3-5 treatment-related morbidity at 5 years: 2.7% developed fistulas, 6.1% had vaginal toxicity, 6.5% had genitourinary toxicity, and 7.6% had gastrointestinal toxicity.
 

Room for improvement

“MRI-guided adaptive brachytherapy in locally advanced cervical cancer works in multicenter clinical practice, within such a study, with adaptation of the target and application technique, and multiparametric treatment planning and dose prescription,” Dr. Pötter summarized.

However, “the mature clinical outcomes appear challenging,” he added. Specifically, although the rate of local control was high, the rate of nodal control left room for improvement in node-positive patients, and the rates of systemic control and overall survival left room for improvement in high-risk patients.

In addition, “the grade 3-5 morbidity was limited per organ and per endpoint, but was considerable overall, and this asks for a reduction,” Dr. Pötter said.

Two of the areas needing improvement are being addressed in ongoing and planned research, according to Dr. Pötter. “The nodal part is already being addressed in EMBRACE II, intensifying treatment for node-positive patients through a simultaneous integrated boost and a very sophisticated probability planning concept, and also including more patients for paraaortic radiotherapy,” he elaborated. “For the systemic part, we have thought about [a study testing an] additional drug ... and there are thoughts for EMBRACE III to investigate such effect.”
 

A benchmark for brachytherapy

“This is the largest prospective cohort of patients treated with image-guided brachytherapy. The high rates of local control with long-term follow-up are impressive and speak to the clear value of high-quality brachytherapy,” commented Ann H. Klopp, MD, PhD, of the University of Texas MD Anderson Cancer Center, Houston, who was not involved in this study.

With its consistent reporting of detailed dose and toxicity data, the study establishes a benchmark for brachytherapy worldwide, Dr. Klopp said. It also better informs treatment decision-making in cases where replacing brachytherapy with external beam techniques is being considered.

Although MRI guidance is increasingly being used in brachytherapy, the latest studies on patterns of care suggest that overall use is still low, according to Dr. Klopp.

“The challenges are primarily logistical,” she elaborated. “MRI-compatible applicators must be placed, and patients need to wait for the scans to be performed, which can take an hour or more. In addition, the times that patients get scanned can be unpredictable based on procedure times, which can create practical challenges for scheduling. In some cases, cost may also be a deterrent.

“The bar is high for brachytherapy. It’s an excellent treatment modality that provides very high rates of local control with very low toxicity when done optimally,” Dr. Klopp concluded. “I do think that this experience provides very convincing evidence that the best brachytherapy is image-guided and requires care to monitor normal tissue doses in order to reduce the risk of long-term toxicity.”

The study was supported by unrestricted grants from Elekta and Varian. Dr. Pötter and Dr. Klopp disclosed no conflicts of interest.

SOURCE: Pötter R et al. ESTRO 2020, Abstract OC-0437.

The majority of women in the United States remain unaware of the benefits breastfeeding offers in reducing the risk of breast cancer, reported Adrienne Hoyt-Austin, DO, and colleagues at University of California, Davis.

oksun70/ThinkStock

Using nationally representative data collected from the 2015-2017 National Survey of Family Growth, Dr. Hoyt-Austin and colleagues analyzed responses to the question: “Do you think that breastfeeding decreases a woman’s chances of getting breast cancer a lot, a little, or not at all, no opinion, or don’t know?” A total of 5,554 female respondents aged 15-49 years participated. The response rate was 66.7%.
 

Multiparous status and education play a role in decreased awareness

Those who had given birth more than once, who had no more than a high school education, or who were U.S.-born Hispanic had the lowest level of awareness, believing that breastfeeding offers only “a little” protection. Of those who were aware of the link, 44% reported that breastfeeding provides “a lot” of protection, and foreign-born participants as well as those who breastfed for more than a year were more likely to conclude that breastfeeding offers “a lot” of protection. The researchers found that neither mammogram or personal family history of breast cancer had any bearing on awareness.

Although multiple studies have found breastfeeding to confer a lower rate of cancer risk, morbidity and mortality, with a 26% lower lifetime risk for those mothers who breastfeed for 12 months or longer, only 36% of women in the United States actually breastfeed.
 

Limited data indicate whether respondents were breastfed themselves

“Public health initiatives must consider the complex roots of disparities in breastfeeding,” noted Dr. Hoyt-Austin and colleagues. They acknowledged the subjectivity of perceptions of “a lot” versus “a little” and noted that the study was limited by a lack of data on whether participants were breastfed themselves.

Clinicians have an opportunity to play a key role in better educating families concerning the benefits of breastfeeding, both for mother and child, they advised. According to one recent study, just 5 minutes of counseling on the benefits of breastfeeding “significantly strengthened women’s intentions to breastfeed.

In a separate interview, Amy E. Cyr, MD, FACS, section of surgical oncology at Washington University, St. Louis, noted that “many breast cancer risk factors – age, sex, family history, and age of menopause – are nonmodifiable.” And while other risk factors, including alcohol use, diet, and exercise are controllable, “pregnancies and breastfeeding don’t always go as planned,” Dr. Cyr added.

“Although Dr. Hoyt-Austin et al. observed that many women aren’t aware that breastfeeding decreases breast cancer risk – or to what extent (they cite a 26% cancer risk reduction after 12 or more months of breastfeeding) – most studies haven’t shown that large a drop in breast cancer risk,“ she pointed out, adding that “I think it’s an overstatement to suggest that breastfeeding reduces cancer risk by ‘a lot,’ as one of the survey choices offered in the study suggests.”

Whether or not a woman breastfeeds depends not only on desire but on social and economic support and biology; for some, breastfeeding simply isn’t an option. “I agree that we should educate women about the benefits of breastfeeding so they can make an informed decision for themselves and their infants, but we also need to acknowledge the complexity of this issue,” she cautioned.

One coauthor reported a travel stipend by the Human Milk Banking Association of North America; Dr. Hoyt-Austin and the other authors had no conflicts of interest to report. Dr. Cyr had no conflicts of interest to report.

SOURCE: Hoyt-Austin A et al. Obstet Gynecol. 2020 Dec. doi: 10.1097/AOG.0000000000004162.

The majority of women in the United States remain unaware of the benefits breastfeeding offers in reducing the risk of breast cancer, reported Adrienne Hoyt-Austin, DO, and colleagues at University of California, Davis.

oksun70/ThinkStock

Using nationally representative data collected from the 2015-2017 National Survey of Family Growth, Dr. Hoyt-Austin and colleagues analyzed responses to the question: “Do you think that breastfeeding decreases a woman’s chances of getting breast cancer a lot, a little, or not at all, no opinion, or don’t know?” A total of 5,554 female respondents aged 15-49 years participated. The response rate was 66.7%.
 

Multiparous status and education play a role in decreased awareness

Those who had given birth more than once, who had no more than a high school education, or who were U.S.-born Hispanic had the lowest level of awareness, believing that breastfeeding offers only “a little” protection. Of those who were aware of the link, 44% reported that breastfeeding provides “a lot” of protection, and foreign-born participants as well as those who breastfed for more than a year were more likely to conclude that breastfeeding offers “a lot” of protection. The researchers found that neither mammogram or personal family history of breast cancer had any bearing on awareness.

Although multiple studies have found breastfeeding to confer a lower rate of cancer risk, morbidity and mortality, with a 26% lower lifetime risk for those mothers who breastfeed for 12 months or longer, only 36% of women in the United States actually breastfeed.
 

Limited data indicate whether respondents were breastfed themselves

“Public health initiatives must consider the complex roots of disparities in breastfeeding,” noted Dr. Hoyt-Austin and colleagues. They acknowledged the subjectivity of perceptions of “a lot” versus “a little” and noted that the study was limited by a lack of data on whether participants were breastfed themselves.

Clinicians have an opportunity to play a key role in better educating families concerning the benefits of breastfeeding, both for mother and child, they advised. According to one recent study, just 5 minutes of counseling on the benefits of breastfeeding “significantly strengthened women’s intentions to breastfeed.

In a separate interview, Amy E. Cyr, MD, FACS, section of surgical oncology at Washington University, St. Louis, noted that “many breast cancer risk factors – age, sex, family history, and age of menopause – are nonmodifiable.” And while other risk factors, including alcohol use, diet, and exercise are controllable, “pregnancies and breastfeeding don’t always go as planned,” Dr. Cyr added.

“Although Dr. Hoyt-Austin et al. observed that many women aren’t aware that breastfeeding decreases breast cancer risk – or to what extent (they cite a 26% cancer risk reduction after 12 or more months of breastfeeding) – most studies haven’t shown that large a drop in breast cancer risk,“ she pointed out, adding that “I think it’s an overstatement to suggest that breastfeeding reduces cancer risk by ‘a lot,’ as one of the survey choices offered in the study suggests.”

Whether or not a woman breastfeeds depends not only on desire but on social and economic support and biology; for some, breastfeeding simply isn’t an option. “I agree that we should educate women about the benefits of breastfeeding so they can make an informed decision for themselves and their infants, but we also need to acknowledge the complexity of this issue,” she cautioned.

One coauthor reported a travel stipend by the Human Milk Banking Association of North America; Dr. Hoyt-Austin and the other authors had no conflicts of interest to report. Dr. Cyr had no conflicts of interest to report.

SOURCE: Hoyt-Austin A et al. Obstet Gynecol. 2020 Dec. doi: 10.1097/AOG.0000000000004162.

The majority of women in the United States remain unaware of the benefits breastfeeding offers in reducing the risk of breast cancer, reported Adrienne Hoyt-Austin, DO, and colleagues at University of California, Davis.

oksun70/ThinkStock

Using nationally representative data collected from the 2015-2017 National Survey of Family Growth, Dr. Hoyt-Austin and colleagues analyzed responses to the question: “Do you think that breastfeeding decreases a woman’s chances of getting breast cancer a lot, a little, or not at all, no opinion, or don’t know?” A total of 5,554 female respondents aged 15-49 years participated. The response rate was 66.7%.
 

Multiparous status and education play a role in decreased awareness

Those who had given birth more than once, who had no more than a high school education, or who were U.S.-born Hispanic had the lowest level of awareness, believing that breastfeeding offers only “a little” protection. Of those who were aware of the link, 44% reported that breastfeeding provides “a lot” of protection, and foreign-born participants as well as those who breastfed for more than a year were more likely to conclude that breastfeeding offers “a lot” of protection. The researchers found that neither mammogram or personal family history of breast cancer had any bearing on awareness.

Although multiple studies have found breastfeeding to confer a lower rate of cancer risk, morbidity and mortality, with a 26% lower lifetime risk for those mothers who breastfeed for 12 months or longer, only 36% of women in the United States actually breastfeed.
 

Limited data indicate whether respondents were breastfed themselves

“Public health initiatives must consider the complex roots of disparities in breastfeeding,” noted Dr. Hoyt-Austin and colleagues. They acknowledged the subjectivity of perceptions of “a lot” versus “a little” and noted that the study was limited by a lack of data on whether participants were breastfed themselves.

Clinicians have an opportunity to play a key role in better educating families concerning the benefits of breastfeeding, both for mother and child, they advised. According to one recent study, just 5 minutes of counseling on the benefits of breastfeeding “significantly strengthened women’s intentions to breastfeed.

In a separate interview, Amy E. Cyr, MD, FACS, section of surgical oncology at Washington University, St. Louis, noted that “many breast cancer risk factors – age, sex, family history, and age of menopause – are nonmodifiable.” And while other risk factors, including alcohol use, diet, and exercise are controllable, “pregnancies and breastfeeding don’t always go as planned,” Dr. Cyr added.

“Although Dr. Hoyt-Austin et al. observed that many women aren’t aware that breastfeeding decreases breast cancer risk – or to what extent (they cite a 26% cancer risk reduction after 12 or more months of breastfeeding) – most studies haven’t shown that large a drop in breast cancer risk,“ she pointed out, adding that “I think it’s an overstatement to suggest that breastfeeding reduces cancer risk by ‘a lot,’ as one of the survey choices offered in the study suggests.”

Whether or not a woman breastfeeds depends not only on desire but on social and economic support and biology; for some, breastfeeding simply isn’t an option. “I agree that we should educate women about the benefits of breastfeeding so they can make an informed decision for themselves and their infants, but we also need to acknowledge the complexity of this issue,” she cautioned.

One coauthor reported a travel stipend by the Human Milk Banking Association of North America; Dr. Hoyt-Austin and the other authors had no conflicts of interest to report. Dr. Cyr had no conflicts of interest to report.

SOURCE: Hoyt-Austin A et al. Obstet Gynecol. 2020 Dec. doi: 10.1097/AOG.0000000000004162.

Racial and ethnic disparities in maternal and infant outcomes persist in the United States, with Black women being 3-4 times more likely to die of pregnancy-related causes, compared with Latina and non-Latina white women, Elizabeth Howell, MD, said in a presentation at the 2020 virtual meeting of the American College of Obstetricians and Gynecologists. 

Location matters, too, and ethnic disparities appear to transcend class, said Dr. Howell of Penn Medicine, Philadelphia. In New York City, for example, Black women are 8-12 times more likely to die than white women regardless of educational attainment.

Dr. Howell cited the definitions of health equity and health disparities as defined by Paula Braveman, MD, in 2014 in the journal Public Health Reports, as follows: “Health equity means social justice in health (i.e., no one is denied the possibility to be healthy for belonging to a group that has historically been economically/socially disadvantaged. Health disparities are the metric we use to measure progress toward achieving health equity.”

Structural racism and discrimination contribute to disparities in maternal and infant morbidity and mortality in several ways, she said. Patient factors include sociodemographics, age, education, poverty, insurance, marital status, language, and literacy. In addition, a patient’s knowledge, beliefs, and health behaviors, as well as stress and self-efficacy are involved. Community factors such as crime, poverty, and community support play a role.

“These factors contribute to the health status of a woman when she becomes pregnant,” Dr. Howell said. “These factors contribute as the woman goes through the health system.”

Then provider factors that impact maternal and infant morbidity and mortality include knowledge, experience, implicit bias, cultural humility, and communication; these factors affect the quality and delivery of neonatal care, and can impact outcomes, Dr. Howell said.

“It is really important to note that many of these pregnancy-related deaths are thought to be preventable,” she said. “They are often caused by delays in diagnosis, problems with communication, and other system failures. Site care has received a great deal of attention” in recent years, the ob.gyn. noted.
 

How hospital quality contributes to health disparities

Dr. Howell shared data from a pair of National Institutes of Health–funded parallel group studies she conducted at New York City hospitals to investigate the contribution of hospital quality to health disparities in severe maternal morbidity and very preterm birth (prior to 32 weeks).

The researchers used vital statistics linked with discharge abstracts for all New York City deliveries between 2011-2013 and 2010-2014. They conducted a logistic regression analysis and ranked hospitals based on metrics of severe maternal morbidity and very preterm birth, and assessed differences by race in each delivery location.

Overall, Black women were almost three times as likely and Latina women were almost twice as likely as White women to experience some type of severe maternal morbidity, with rates of 4.2%, 2.7%, and 1.5%, respectively.

The researchers also ranked hospitals, and found a wide variation; women delivering in the lowest-ranked hospitals had six times the rate of severe maternal morbidity. They also conducted a simulation/thought exercise and determined that the hospital of delivery accounted for approximately 48% of the disparity in severe maternal morbidity between Black and White women.

Results were similar in the parallel study of very preterm birth rates in New York City hospitals, which were 32%, 28%, and 23% for Black, Latina, and White women, respectively.

The researchers also conducted interviews with personnel including chief medical officers, neonatal ICU directors, nurses, and respiratory therapists. The final phase of the research, which is ongoing, is the dissemination of the information, said Dr. Howell.

Overall, the high-performing hospitals were more likely to focus on standards and standardized care, stronger nurse/physician communication, greater awareness of the potential impact of racism on care, and greater sharing of performance data.

Women who participated in focus groups reported a range of experiences, but women of color were likely to report poor communication, feeling traumatized, and not being heard.
 

Study implications

Dr. Howell discussed the implications of her study in a question and answer session. “It is incredibly important for us to think about all the levers that we have to address disparities.”

“It is a complex web of factors, but quality of care is one of those mechanisms, and it is something we can do something about,” she noted.

In response to a question about whether women should know the rates of adverse outcomes at various hospitals, she said, “I think we have a responsibility to come up with quality of care measures that are informative to the women we care for.”

Much of obstetric quality issues focus on overuse of resources, “but that doesn’t help us reduce disparities,” she said.

Dr. Howell had no financial conflicts to disclose.

Racial and ethnic disparities in maternal and infant outcomes persist in the United States, with Black women being 3-4 times more likely to die of pregnancy-related causes, compared with Latina and non-Latina white women, Elizabeth Howell, MD, said in a presentation at the 2020 virtual meeting of the American College of Obstetricians and Gynecologists. 

Location matters, too, and ethnic disparities appear to transcend class, said Dr. Howell of Penn Medicine, Philadelphia. In New York City, for example, Black women are 8-12 times more likely to die than white women regardless of educational attainment.

Dr. Howell cited the definitions of health equity and health disparities as defined by Paula Braveman, MD, in 2014 in the journal Public Health Reports, as follows: “Health equity means social justice in health (i.e., no one is denied the possibility to be healthy for belonging to a group that has historically been economically/socially disadvantaged. Health disparities are the metric we use to measure progress toward achieving health equity.”

Structural racism and discrimination contribute to disparities in maternal and infant morbidity and mortality in several ways, she said. Patient factors include sociodemographics, age, education, poverty, insurance, marital status, language, and literacy. In addition, a patient’s knowledge, beliefs, and health behaviors, as well as stress and self-efficacy are involved. Community factors such as crime, poverty, and community support play a role.

“These factors contribute to the health status of a woman when she becomes pregnant,” Dr. Howell said. “These factors contribute as the woman goes through the health system.”

Then provider factors that impact maternal and infant morbidity and mortality include knowledge, experience, implicit bias, cultural humility, and communication; these factors affect the quality and delivery of neonatal care, and can impact outcomes, Dr. Howell said.

“It is really important to note that many of these pregnancy-related deaths are thought to be preventable,” she said. “They are often caused by delays in diagnosis, problems with communication, and other system failures. Site care has received a great deal of attention” in recent years, the ob.gyn. noted.
 

How hospital quality contributes to health disparities

Dr. Howell shared data from a pair of National Institutes of Health–funded parallel group studies she conducted at New York City hospitals to investigate the contribution of hospital quality to health disparities in severe maternal morbidity and very preterm birth (prior to 32 weeks).

The researchers used vital statistics linked with discharge abstracts for all New York City deliveries between 2011-2013 and 2010-2014. They conducted a logistic regression analysis and ranked hospitals based on metrics of severe maternal morbidity and very preterm birth, and assessed differences by race in each delivery location.

Overall, Black women were almost three times as likely and Latina women were almost twice as likely as White women to experience some type of severe maternal morbidity, with rates of 4.2%, 2.7%, and 1.5%, respectively.

The researchers also ranked hospitals, and found a wide variation; women delivering in the lowest-ranked hospitals had six times the rate of severe maternal morbidity. They also conducted a simulation/thought exercise and determined that the hospital of delivery accounted for approximately 48% of the disparity in severe maternal morbidity between Black and White women.

Results were similar in the parallel study of very preterm birth rates in New York City hospitals, which were 32%, 28%, and 23% for Black, Latina, and White women, respectively.

The researchers also conducted interviews with personnel including chief medical officers, neonatal ICU directors, nurses, and respiratory therapists. The final phase of the research, which is ongoing, is the dissemination of the information, said Dr. Howell.

Overall, the high-performing hospitals were more likely to focus on standards and standardized care, stronger nurse/physician communication, greater awareness of the potential impact of racism on care, and greater sharing of performance data.

Women who participated in focus groups reported a range of experiences, but women of color were likely to report poor communication, feeling traumatized, and not being heard.
 

Study implications

Dr. Howell discussed the implications of her study in a question and answer session. “It is incredibly important for us to think about all the levers that we have to address disparities.”

“It is a complex web of factors, but quality of care is one of those mechanisms, and it is something we can do something about,” she noted.

In response to a question about whether women should know the rates of adverse outcomes at various hospitals, she said, “I think we have a responsibility to come up with quality of care measures that are informative to the women we care for.”

Much of obstetric quality issues focus on overuse of resources, “but that doesn’t help us reduce disparities,” she said.

Dr. Howell had no financial conflicts to disclose.

Racial and ethnic disparities in maternal and infant outcomes persist in the United States, with Black women being 3-4 times more likely to die of pregnancy-related causes, compared with Latina and non-Latina white women, Elizabeth Howell, MD, said in a presentation at the 2020 virtual meeting of the American College of Obstetricians and Gynecologists. 

Location matters, too, and ethnic disparities appear to transcend class, said Dr. Howell of Penn Medicine, Philadelphia. In New York City, for example, Black women are 8-12 times more likely to die than white women regardless of educational attainment.

Dr. Howell cited the definitions of health equity and health disparities as defined by Paula Braveman, MD, in 2014 in the journal Public Health Reports, as follows: “Health equity means social justice in health (i.e., no one is denied the possibility to be healthy for belonging to a group that has historically been economically/socially disadvantaged. Health disparities are the metric we use to measure progress toward achieving health equity.”

Structural racism and discrimination contribute to disparities in maternal and infant morbidity and mortality in several ways, she said. Patient factors include sociodemographics, age, education, poverty, insurance, marital status, language, and literacy. In addition, a patient’s knowledge, beliefs, and health behaviors, as well as stress and self-efficacy are involved. Community factors such as crime, poverty, and community support play a role.

“These factors contribute to the health status of a woman when she becomes pregnant,” Dr. Howell said. “These factors contribute as the woman goes through the health system.”

Then provider factors that impact maternal and infant morbidity and mortality include knowledge, experience, implicit bias, cultural humility, and communication; these factors affect the quality and delivery of neonatal care, and can impact outcomes, Dr. Howell said.

“It is really important to note that many of these pregnancy-related deaths are thought to be preventable,” she said. “They are often caused by delays in diagnosis, problems with communication, and other system failures. Site care has received a great deal of attention” in recent years, the ob.gyn. noted.
 

How hospital quality contributes to health disparities

Dr. Howell shared data from a pair of National Institutes of Health–funded parallel group studies she conducted at New York City hospitals to investigate the contribution of hospital quality to health disparities in severe maternal morbidity and very preterm birth (prior to 32 weeks).

The researchers used vital statistics linked with discharge abstracts for all New York City deliveries between 2011-2013 and 2010-2014. They conducted a logistic regression analysis and ranked hospitals based on metrics of severe maternal morbidity and very preterm birth, and assessed differences by race in each delivery location.

Overall, Black women were almost three times as likely and Latina women were almost twice as likely as White women to experience some type of severe maternal morbidity, with rates of 4.2%, 2.7%, and 1.5%, respectively.

The researchers also ranked hospitals, and found a wide variation; women delivering in the lowest-ranked hospitals had six times the rate of severe maternal morbidity. They also conducted a simulation/thought exercise and determined that the hospital of delivery accounted for approximately 48% of the disparity in severe maternal morbidity between Black and White women.

Results were similar in the parallel study of very preterm birth rates in New York City hospitals, which were 32%, 28%, and 23% for Black, Latina, and White women, respectively.

The researchers also conducted interviews with personnel including chief medical officers, neonatal ICU directors, nurses, and respiratory therapists. The final phase of the research, which is ongoing, is the dissemination of the information, said Dr. Howell.

Overall, the high-performing hospitals were more likely to focus on standards and standardized care, stronger nurse/physician communication, greater awareness of the potential impact of racism on care, and greater sharing of performance data.

Women who participated in focus groups reported a range of experiences, but women of color were likely to report poor communication, feeling traumatized, and not being heard.
 

Study implications

Dr. Howell discussed the implications of her study in a question and answer session. “It is incredibly important for us to think about all the levers that we have to address disparities.”

“It is a complex web of factors, but quality of care is one of those mechanisms, and it is something we can do something about,” she noted.

In response to a question about whether women should know the rates of adverse outcomes at various hospitals, she said, “I think we have a responsibility to come up with quality of care measures that are informative to the women we care for.”

Much of obstetric quality issues focus on overuse of resources, “but that doesn’t help us reduce disparities,” she said.

Dr. Howell had no financial conflicts to disclose.

Incorporating gender-nonconforming patients into practice can seem like a daunting task at first. However, obstetricians/gynecologists, midwives, and other advanced women’s health care practitioners can provide quality care for both transgender men and women. Basic preventative services such as routine health and cancer screening and testing for sexually transmitted infections does not require specialized training in transgender health. In fact, administration of hormonal therapy and some surgical interventions are well within the scope of practice of the general obstetrician/gynecologist, as long as the provider has undergone appropriate training to achieve expertise. For example, organizations such as the World Professional Association for Transgender Health (WPATH) not only provides standards of care regarding the treatment of transgender individuals, but they also have training and educational opportunities targeted at providers who wish to become certified in more advanced care of the transgender patient. If an obstetrician/gynecologist is interested in prescribing hormone therapy, seeking further training within the field is a must.

It is important to remember that the process by which transgender individuals express their gender is a spectrum. Not all patients who identify as transgender will seek hormone therapy or surgical procedures. However, even if a provider has not undergone more specific training to administer hormone therapy, it is still very important to have a basic understanding of the hormones, routes of administration, and side effects.

While cross-sex hormone therapy does differ in practice, compared with hormone replacement therapy in cisgender counterparts, the principles are relatively similar. Testosterone therapy is the mainstay treatment for transgender men who desire medical transition.^1,2 The overall goal of therapy is to achieve testosterone levels within the cisgender male physiologic range (300-1000 ng/dL). While the most common route of administration is subcutaneous or intramuscular injections in weekly, biweekly, or quarterly intervals, other routes may include daily transdermal patches and gels or oral formulations.1 Within the first few months of use, patients will notice signs of masculinization such as increased facial and body hair, increased muscle mass, increased libido, and amenorrhea. Other changes include male-pattern hair loss, clitoromegaly, redistribution of fat, voice deepening, and mood changes.¹

Hormone therapy for transgender women is a bit more complicated as estrogen alone will often not achieve feminizing characteristics that are satisfying for patients.³ Estrogen therapy can include oral formulations of 17-beta estradiol or conjugated estrogens, although the latter is typically avoided because of the marked increase in thromboembolic events. Estrogens can also be administered in sublingual, intramuscular, or transdermal forms. Antiandrogens are often required to help decrease endogenous testosterone levels to cisgender female levels (30-100 ng/dL).³ Spironolactone is most commonly prescribed as an adjunct to estrogen therapy. Finasteride and GnRH agonists like leuprolide acetate can also be added if spironolactone is not effective or not tolerated by the patient. Feminizing effects of estrogen can take several months and most commonly include decreased spontaneous erections, decreased libido, breast growth, redistribution of fat to the waist and hips, decreased skin oiliness, and softening of the skin.³

Overall, hormone therapy for both transgender men and women is considered effective, safe, and well tolerated.⁴ Monitoring is typically performed every 3 months within the first year after initiating hormone therapy, and then continued every 6-12 months thereafter. Routine screening for all organs and tissues present (e.g. prostate, breast) should be undertaken.³ While this simply highlights the therapy and surveillance for patients, it is important to remember that many transgender men and women will see an obstetrician/gynecologist at some interval during their transition. Ultimately, it is paramount that we as obstetricians/gynecologists have a basic understanding of the treatments available so we can provide our patients with competent and compassionate care.
 

Dr. Brandt is an obstetrician/gynecologist and a plastic surgeon at Reading Hospital/Tower Health System in West Reading, Pa., where she has developed a gender-affirming medical and surgical clinic for ob.gyn. residents and plastic surgeon fellows.

References

1. World Professional Association for Transgender Health. Standards of care for the health of transsexual, transgender, and gender nonconforming people. 7th version. Accessed 10/15/20.

2. Joint meeting of the International Society of Endocrinology and the Endocrine Society 2014; ICE/ENDO 2014, Paper 14354. Accessed 01/08/16.

3. Qian R, Safer JD. Hormone treatment for the adult transgender patient, in “Comprehensive Care of the Transgender Patient,” 1st ed. Philadelphia: Elsevier, 2020, pp. 34-6.

4. Weinand JD and Safer JD. Hormone therapy in transgender adults is safe with provider supervision: A review of hormone therapy sequelae for transgender individuals. J Clin Transl Endocrinol. 2015;2(2):55-60.
 

Incorporating gender-nonconforming patients into practice can seem like a daunting task at first. However, obstetricians/gynecologists, midwives, and other advanced women’s health care practitioners can provide quality care for both transgender men and women. Basic preventative services such as routine health and cancer screening and testing for sexually transmitted infections does not require specialized training in transgender health. In fact, administration of hormonal therapy and some surgical interventions are well within the scope of practice of the general obstetrician/gynecologist, as long as the provider has undergone appropriate training to achieve expertise. For example, organizations such as the World Professional Association for Transgender Health (WPATH) not only provides standards of care regarding the treatment of transgender individuals, but they also have training and educational opportunities targeted at providers who wish to become certified in more advanced care of the transgender patient. If an obstetrician/gynecologist is interested in prescribing hormone therapy, seeking further training within the field is a must.

It is important to remember that the process by which transgender individuals express their gender is a spectrum. Not all patients who identify as transgender will seek hormone therapy or surgical procedures. However, even if a provider has not undergone more specific training to administer hormone therapy, it is still very important to have a basic understanding of the hormones, routes of administration, and side effects.

While cross-sex hormone therapy does differ in practice, compared with hormone replacement therapy in cisgender counterparts, the principles are relatively similar. Testosterone therapy is the mainstay treatment for transgender men who desire medical transition.^1,2 The overall goal of therapy is to achieve testosterone levels within the cisgender male physiologic range (300-1000 ng/dL). While the most common route of administration is subcutaneous or intramuscular injections in weekly, biweekly, or quarterly intervals, other routes may include daily transdermal patches and gels or oral formulations.1 Within the first few months of use, patients will notice signs of masculinization such as increased facial and body hair, increased muscle mass, increased libido, and amenorrhea. Other changes include male-pattern hair loss, clitoromegaly, redistribution of fat, voice deepening, and mood changes.¹

Hormone therapy for transgender women is a bit more complicated as estrogen alone will often not achieve feminizing characteristics that are satisfying for patients.³ Estrogen therapy can include oral formulations of 17-beta estradiol or conjugated estrogens, although the latter is typically avoided because of the marked increase in thromboembolic events. Estrogens can also be administered in sublingual, intramuscular, or transdermal forms. Antiandrogens are often required to help decrease endogenous testosterone levels to cisgender female levels (30-100 ng/dL).³ Spironolactone is most commonly prescribed as an adjunct to estrogen therapy. Finasteride and GnRH agonists like leuprolide acetate can also be added if spironolactone is not effective or not tolerated by the patient. Feminizing effects of estrogen can take several months and most commonly include decreased spontaneous erections, decreased libido, breast growth, redistribution of fat to the waist and hips, decreased skin oiliness, and softening of the skin.³

Overall, hormone therapy for both transgender men and women is considered effective, safe, and well tolerated.⁴ Monitoring is typically performed every 3 months within the first year after initiating hormone therapy, and then continued every 6-12 months thereafter. Routine screening for all organs and tissues present (e.g. prostate, breast) should be undertaken.³ While this simply highlights the therapy and surveillance for patients, it is important to remember that many transgender men and women will see an obstetrician/gynecologist at some interval during their transition. Ultimately, it is paramount that we as obstetricians/gynecologists have a basic understanding of the treatments available so we can provide our patients with competent and compassionate care.
 

Dr. Brandt is an obstetrician/gynecologist and a plastic surgeon at Reading Hospital/Tower Health System in West Reading, Pa., where she has developed a gender-affirming medical and surgical clinic for ob.gyn. residents and plastic surgeon fellows.

References

1. World Professional Association for Transgender Health. Standards of care for the health of transsexual, transgender, and gender nonconforming people. 7th version. Accessed 10/15/20.

2. Joint meeting of the International Society of Endocrinology and the Endocrine Society 2014; ICE/ENDO 2014, Paper 14354. Accessed 01/08/16.

3. Qian R, Safer JD. Hormone treatment for the adult transgender patient, in “Comprehensive Care of the Transgender Patient,” 1st ed. Philadelphia: Elsevier, 2020, pp. 34-6.

4. Weinand JD and Safer JD. Hormone therapy in transgender adults is safe with provider supervision: A review of hormone therapy sequelae for transgender individuals. J Clin Transl Endocrinol. 2015;2(2):55-60.
 

Incorporating gender-nonconforming patients into practice can seem like a daunting task at first. However, obstetricians/gynecologists, midwives, and other advanced women’s health care practitioners can provide quality care for both transgender men and women. Basic preventative services such as routine health and cancer screening and testing for sexually transmitted infections does not require specialized training in transgender health. In fact, administration of hormonal therapy and some surgical interventions are well within the scope of practice of the general obstetrician/gynecologist, as long as the provider has undergone appropriate training to achieve expertise. For example, organizations such as the World Professional Association for Transgender Health (WPATH) not only provides standards of care regarding the treatment of transgender individuals, but they also have training and educational opportunities targeted at providers who wish to become certified in more advanced care of the transgender patient. If an obstetrician/gynecologist is interested in prescribing hormone therapy, seeking further training within the field is a must.

It is important to remember that the process by which transgender individuals express their gender is a spectrum. Not all patients who identify as transgender will seek hormone therapy or surgical procedures. However, even if a provider has not undergone more specific training to administer hormone therapy, it is still very important to have a basic understanding of the hormones, routes of administration, and side effects.

While cross-sex hormone therapy does differ in practice, compared with hormone replacement therapy in cisgender counterparts, the principles are relatively similar. Testosterone therapy is the mainstay treatment for transgender men who desire medical transition.^1,2 The overall goal of therapy is to achieve testosterone levels within the cisgender male physiologic range (300-1000 ng/dL). While the most common route of administration is subcutaneous or intramuscular injections in weekly, biweekly, or quarterly intervals, other routes may include daily transdermal patches and gels or oral formulations.1 Within the first few months of use, patients will notice signs of masculinization such as increased facial and body hair, increased muscle mass, increased libido, and amenorrhea. Other changes include male-pattern hair loss, clitoromegaly, redistribution of fat, voice deepening, and mood changes.¹

Hormone therapy for transgender women is a bit more complicated as estrogen alone will often not achieve feminizing characteristics that are satisfying for patients.³ Estrogen therapy can include oral formulations of 17-beta estradiol or conjugated estrogens, although the latter is typically avoided because of the marked increase in thromboembolic events. Estrogens can also be administered in sublingual, intramuscular, or transdermal forms. Antiandrogens are often required to help decrease endogenous testosterone levels to cisgender female levels (30-100 ng/dL).³ Spironolactone is most commonly prescribed as an adjunct to estrogen therapy. Finasteride and GnRH agonists like leuprolide acetate can also be added if spironolactone is not effective or not tolerated by the patient. Feminizing effects of estrogen can take several months and most commonly include decreased spontaneous erections, decreased libido, breast growth, redistribution of fat to the waist and hips, decreased skin oiliness, and softening of the skin.³

Overall, hormone therapy for both transgender men and women is considered effective, safe, and well tolerated.⁴ Monitoring is typically performed every 3 months within the first year after initiating hormone therapy, and then continued every 6-12 months thereafter. Routine screening for all organs and tissues present (e.g. prostate, breast) should be undertaken.³ While this simply highlights the therapy and surveillance for patients, it is important to remember that many transgender men and women will see an obstetrician/gynecologist at some interval during their transition. Ultimately, it is paramount that we as obstetricians/gynecologists have a basic understanding of the treatments available so we can provide our patients with competent and compassionate care.
 

Dr. Brandt is an obstetrician/gynecologist and a plastic surgeon at Reading Hospital/Tower Health System in West Reading, Pa., where she has developed a gender-affirming medical and surgical clinic for ob.gyn. residents and plastic surgeon fellows.

References

1. World Professional Association for Transgender Health. Standards of care for the health of transsexual, transgender, and gender nonconforming people. 7th version. Accessed 10/15/20.

2. Joint meeting of the International Society of Endocrinology and the Endocrine Society 2014; ICE/ENDO 2014, Paper 14354. Accessed 01/08/16.

3. Qian R, Safer JD. Hormone treatment for the adult transgender patient, in “Comprehensive Care of the Transgender Patient,” 1st ed. Philadelphia: Elsevier, 2020, pp. 34-6.

4. Weinand JD and Safer JD. Hormone therapy in transgender adults is safe with provider supervision: A review of hormone therapy sequelae for transgender individuals. J Clin Transl Endocrinol. 2015;2(2):55-60.
 

In reproductive medicine, there are few, if any, more pressing concerns from our patients than the biological clock, i.e., ovarian aging. While addressing this issue with women can be challenging, particularly for those who are anxious regarding their advanced maternal age, gynecologists must possess a thorough understanding of available diagnostic testing. This article will review the various methods to assess ovarian age and appropriate clinical management.

Ovarian reserve tests

Ovarian reserve represents the quality and quantity of oocytes. The former is defined by the woman’s chronologic age, which is the greatest predictor of fertility. From a peak monthly fecundity rate at age 30 of approximately 20%, the slow and steady decline of fertility ensues. Quantity represents the number of oocytes remaining from the original cohort.

Ovarian reserve is most provocatively gauged by the follicle response to gonadotropin stimulation, typically during an in vitro fertilization (IVF) cycle.

Several biomarkers have been used to assess ovarian age. These include FSH, estradiol, and inhibin B. In general, these tests are more specific than sensitive, i.e., “normal” results do not necessarily exclude decreased ovarian reserve. But as a screening tool for decreased ovarian reserve, the most important factor is the positive predictive value (PPV). Statistically, in a population of women at low risk for decreased ovarian reserve, the PPV will be low despite sensitivity and specificity.

While inhibin B is a more direct and earlier reflection of ovarian function produced by granulose cells, assays lacked consistent results and a standardized cut-off value. FSH is the last biomarker to be affected by decreased ovarian reserve so elevations reflect more “end-stage” ovarian aging.

Additional tests for decreased ovarian reserve include antral follicle count (AFC) and the clomiphene citrate challenge test (CCCT). AFC is determined by using transvaginal ultrasound to count the number of follicular cysts in the 2- to 9-mm range. While AFC can be performed on any day of the cycle, the ovary is most optimally measured on menses because of less cystic activity. A combined AFC of 3-6 is considered severe decreased ovarian reserve. The CCCT involves prescribing clomiphene citrate 100 mg daily from cycle day 5-9 to measure FSH on cycle days 3 and 10. An FSH level greater than 10 IU/L or any elevation in FSH following CCCT is considered decreased ovarian reserve.

FSH had been the standard but levels may dramatically change monthly, making testing only valuable if it is elevated. Consequently, antimüllerian hormone (AMH) and AFC are considered the most useful tools to determine decreased ovarian reserve because of less variability. The other distinct advantage is the ability to obtain AMH any day in the menstrual cycle. Recently, in women undergoing IVF, AMH was superior to FSH in predicting live birth, particularly when their values were discordant (J Ovarian Res. 2018;11:60). While there is no established consensus, the ideal interval for repeating AMH appears to be approximately 3 months (Obstet Gynecol 2016;127:65S-6S).
 

AMH

AMH is expressed in the embryo at 8 weeks by the Sertoli cells of the testis causing the female reproductive internal system (müllerian) to regress. Without AMH expression, the müllerian system remains and the male (woffian duct system) regresses. The discovery of AMH production by the granulosa cells of the ovary launched a new era in the evaluation and management of infertile women. First reported in Fertility & Sterility in 2002 as a much earlier potential marker of ovarian aging, low levels of AMH predict a lower number of eggs in IVF.

AMH levels are produced in the embryo at 36 weeks’ gestation and increase up to the age of 24.5 years, decreasing thereafter. AMH reflects primordial (early) follicles that are FSH independent. The median AMH level decreases per year according to age groups are: 0.25 ng/mL in ages 26-30; 0.2 ng/mL in ages 31-36 years; and 0.1 ng/mL above age 36. (PLOS ONE 2015 doi: 10.1371/journal.pone.0125216).

AMH has also been studied as a potential biomarker to diagnose PCOS. While many women with PCOS have elevated AMH levels (typically greater than 3 ng/mL), there is no consensus on an AMH value that would be a criterion.

Many women, particularly those electing to defer fertility, express interest in obtaining their AMH level to consider planned oocyte cryopreservation, AKA, social egg freezing. While it is possible the results of AMH screening may compel women to electively freeze their eggs, extensive counseling on the implications and pitfalls of AMH levels is essential. Further, AMH cannot be used to accurately predict menopause.
 

Predicting outcomes

No biomarker is necessarily predictive of pregnancy but more a gauge of gonadotropin dosage to induce multifollicular development. AMH is a great predictor of oocyte yield with IVF (J Assist Reprod Genet. 2009;26[7]:383-9). However, in women older than 35 undergoing IVF, low AMH levels have been shown to reduce pregnancy rates (J Hum Reprod Sci. 2017;10:24–30). During IVF cycle attempts, an ultra-low AMH (≤0.4) resulted in high cancellation rates, reduced the number of oocytes retrieved and embryos developed, and lowered pregnancy rates in women of advanced reproductive age.

Alternatively, a study of 750 women who were not infertile and were actively trying to conceive demonstrated no difference in natural pregnancy rates in women aged 30-44 irrespective of AMH levels (JAMA. 2017;318[14]:1367-76).

A special consideration is for cancer patients who are status postgonadotoxic chemotherapy. Their oocyte attrition can be accelerated and AMH levels can become profoundly low. In those patients, current data suggest there is a modest recovery of postchemotherapy AMH levels up to 1 year. Further, oocyte yield following stimulation may be higher than expected despite a poor AMH level.
 

Conclusion

Ovarian aging is currently best measured by combining chronologic age, AFC, and AMH. There is no current evidence that AMH levels should be used to exclude patients from undergoing IVF or to recommend egg donation. Random screening of AMH levels in a low-risk population for decreased ovarian reserve may result in unnecessary alarm.

Dr. Trolice is director of Fertility CARE - The IVF Center in Winter Park, Fla., and associate professor of obstetrics and gynecology at the University of Central Florida, Orlando.

In reproductive medicine, there are few, if any, more pressing concerns from our patients than the biological clock, i.e., ovarian aging. While addressing this issue with women can be challenging, particularly for those who are anxious regarding their advanced maternal age, gynecologists must possess a thorough understanding of available diagnostic testing. This article will review the various methods to assess ovarian age and appropriate clinical management.

Ovarian reserve tests

Ovarian reserve represents the quality and quantity of oocytes. The former is defined by the woman’s chronologic age, which is the greatest predictor of fertility. From a peak monthly fecundity rate at age 30 of approximately 20%, the slow and steady decline of fertility ensues. Quantity represents the number of oocytes remaining from the original cohort.

Ovarian reserve is most provocatively gauged by the follicle response to gonadotropin stimulation, typically during an in vitro fertilization (IVF) cycle.

Several biomarkers have been used to assess ovarian age. These include FSH, estradiol, and inhibin B. In general, these tests are more specific than sensitive, i.e., “normal” results do not necessarily exclude decreased ovarian reserve. But as a screening tool for decreased ovarian reserve, the most important factor is the positive predictive value (PPV). Statistically, in a population of women at low risk for decreased ovarian reserve, the PPV will be low despite sensitivity and specificity.

While inhibin B is a more direct and earlier reflection of ovarian function produced by granulose cells, assays lacked consistent results and a standardized cut-off value. FSH is the last biomarker to be affected by decreased ovarian reserve so elevations reflect more “end-stage” ovarian aging.

Additional tests for decreased ovarian reserve include antral follicle count (AFC) and the clomiphene citrate challenge test (CCCT). AFC is determined by using transvaginal ultrasound to count the number of follicular cysts in the 2- to 9-mm range. While AFC can be performed on any day of the cycle, the ovary is most optimally measured on menses because of less cystic activity. A combined AFC of 3-6 is considered severe decreased ovarian reserve. The CCCT involves prescribing clomiphene citrate 100 mg daily from cycle day 5-9 to measure FSH on cycle days 3 and 10. An FSH level greater than 10 IU/L or any elevation in FSH following CCCT is considered decreased ovarian reserve.

FSH had been the standard but levels may dramatically change monthly, making testing only valuable if it is elevated. Consequently, antimüllerian hormone (AMH) and AFC are considered the most useful tools to determine decreased ovarian reserve because of less variability. The other distinct advantage is the ability to obtain AMH any day in the menstrual cycle. Recently, in women undergoing IVF, AMH was superior to FSH in predicting live birth, particularly when their values were discordant (J Ovarian Res. 2018;11:60). While there is no established consensus, the ideal interval for repeating AMH appears to be approximately 3 months (Obstet Gynecol 2016;127:65S-6S).
 

AMH

AMH is expressed in the embryo at 8 weeks by the Sertoli cells of the testis causing the female reproductive internal system (müllerian) to regress. Without AMH expression, the müllerian system remains and the male (woffian duct system) regresses. The discovery of AMH production by the granulosa cells of the ovary launched a new era in the evaluation and management of infertile women. First reported in Fertility & Sterility in 2002 as a much earlier potential marker of ovarian aging, low levels of AMH predict a lower number of eggs in IVF.

AMH levels are produced in the embryo at 36 weeks’ gestation and increase up to the age of 24.5 years, decreasing thereafter. AMH reflects primordial (early) follicles that are FSH independent. The median AMH level decreases per year according to age groups are: 0.25 ng/mL in ages 26-30; 0.2 ng/mL in ages 31-36 years; and 0.1 ng/mL above age 36. (PLOS ONE 2015 doi: 10.1371/journal.pone.0125216).

AMH has also been studied as a potential biomarker to diagnose PCOS. While many women with PCOS have elevated AMH levels (typically greater than 3 ng/mL), there is no consensus on an AMH value that would be a criterion.

Many women, particularly those electing to defer fertility, express interest in obtaining their AMH level to consider planned oocyte cryopreservation, AKA, social egg freezing. While it is possible the results of AMH screening may compel women to electively freeze their eggs, extensive counseling on the implications and pitfalls of AMH levels is essential. Further, AMH cannot be used to accurately predict menopause.
 

Predicting outcomes

No biomarker is necessarily predictive of pregnancy but more a gauge of gonadotropin dosage to induce multifollicular development. AMH is a great predictor of oocyte yield with IVF (J Assist Reprod Genet. 2009;26[7]:383-9). However, in women older than 35 undergoing IVF, low AMH levels have been shown to reduce pregnancy rates (J Hum Reprod Sci. 2017;10:24–30). During IVF cycle attempts, an ultra-low AMH (≤0.4) resulted in high cancellation rates, reduced the number of oocytes retrieved and embryos developed, and lowered pregnancy rates in women of advanced reproductive age.

Alternatively, a study of 750 women who were not infertile and were actively trying to conceive demonstrated no difference in natural pregnancy rates in women aged 30-44 irrespective of AMH levels (JAMA. 2017;318[14]:1367-76).

A special consideration is for cancer patients who are status postgonadotoxic chemotherapy. Their oocyte attrition can be accelerated and AMH levels can become profoundly low. In those patients, current data suggest there is a modest recovery of postchemotherapy AMH levels up to 1 year. Further, oocyte yield following stimulation may be higher than expected despite a poor AMH level.
 

Conclusion

Ovarian aging is currently best measured by combining chronologic age, AFC, and AMH. There is no current evidence that AMH levels should be used to exclude patients from undergoing IVF or to recommend egg donation. Random screening of AMH levels in a low-risk population for decreased ovarian reserve may result in unnecessary alarm.

Dr. Trolice is director of Fertility CARE - The IVF Center in Winter Park, Fla., and associate professor of obstetrics and gynecology at the University of Central Florida, Orlando.

In reproductive medicine, there are few, if any, more pressing concerns from our patients than the biological clock, i.e., ovarian aging. While addressing this issue with women can be challenging, particularly for those who are anxious regarding their advanced maternal age, gynecologists must possess a thorough understanding of available diagnostic testing. This article will review the various methods to assess ovarian age and appropriate clinical management.

Ovarian reserve tests

Ovarian reserve represents the quality and quantity of oocytes. The former is defined by the woman’s chronologic age, which is the greatest predictor of fertility. From a peak monthly fecundity rate at age 30 of approximately 20%, the slow and steady decline of fertility ensues. Quantity represents the number of oocytes remaining from the original cohort.

Ovarian reserve is most provocatively gauged by the follicle response to gonadotropin stimulation, typically during an in vitro fertilization (IVF) cycle.

Several biomarkers have been used to assess ovarian age. These include FSH, estradiol, and inhibin B. In general, these tests are more specific than sensitive, i.e., “normal” results do not necessarily exclude decreased ovarian reserve. But as a screening tool for decreased ovarian reserve, the most important factor is the positive predictive value (PPV). Statistically, in a population of women at low risk for decreased ovarian reserve, the PPV will be low despite sensitivity and specificity.

While inhibin B is a more direct and earlier reflection of ovarian function produced by granulose cells, assays lacked consistent results and a standardized cut-off value. FSH is the last biomarker to be affected by decreased ovarian reserve so elevations reflect more “end-stage” ovarian aging.

Additional tests for decreased ovarian reserve include antral follicle count (AFC) and the clomiphene citrate challenge test (CCCT). AFC is determined by using transvaginal ultrasound to count the number of follicular cysts in the 2- to 9-mm range. While AFC can be performed on any day of the cycle, the ovary is most optimally measured on menses because of less cystic activity. A combined AFC of 3-6 is considered severe decreased ovarian reserve. The CCCT involves prescribing clomiphene citrate 100 mg daily from cycle day 5-9 to measure FSH on cycle days 3 and 10. An FSH level greater than 10 IU/L or any elevation in FSH following CCCT is considered decreased ovarian reserve.

FSH had been the standard but levels may dramatically change monthly, making testing only valuable if it is elevated. Consequently, antimüllerian hormone (AMH) and AFC are considered the most useful tools to determine decreased ovarian reserve because of less variability. The other distinct advantage is the ability to obtain AMH any day in the menstrual cycle. Recently, in women undergoing IVF, AMH was superior to FSH in predicting live birth, particularly when their values were discordant (J Ovarian Res. 2018;11:60). While there is no established consensus, the ideal interval for repeating AMH appears to be approximately 3 months (Obstet Gynecol 2016;127:65S-6S).
 

AMH

AMH is expressed in the embryo at 8 weeks by the Sertoli cells of the testis causing the female reproductive internal system (müllerian) to regress. Without AMH expression, the müllerian system remains and the male (woffian duct system) regresses. The discovery of AMH production by the granulosa cells of the ovary launched a new era in the evaluation and management of infertile women. First reported in Fertility & Sterility in 2002 as a much earlier potential marker of ovarian aging, low levels of AMH predict a lower number of eggs in IVF.

AMH levels are produced in the embryo at 36 weeks’ gestation and increase up to the age of 24.5 years, decreasing thereafter. AMH reflects primordial (early) follicles that are FSH independent. The median AMH level decreases per year according to age groups are: 0.25 ng/mL in ages 26-30; 0.2 ng/mL in ages 31-36 years; and 0.1 ng/mL above age 36. (PLOS ONE 2015 doi: 10.1371/journal.pone.0125216).

AMH has also been studied as a potential biomarker to diagnose PCOS. While many women with PCOS have elevated AMH levels (typically greater than 3 ng/mL), there is no consensus on an AMH value that would be a criterion.

Many women, particularly those electing to defer fertility, express interest in obtaining their AMH level to consider planned oocyte cryopreservation, AKA, social egg freezing. While it is possible the results of AMH screening may compel women to electively freeze their eggs, extensive counseling on the implications and pitfalls of AMH levels is essential. Further, AMH cannot be used to accurately predict menopause.
 

Predicting outcomes

No biomarker is necessarily predictive of pregnancy but more a gauge of gonadotropin dosage to induce multifollicular development. AMH is a great predictor of oocyte yield with IVF (J Assist Reprod Genet. 2009;26[7]:383-9). However, in women older than 35 undergoing IVF, low AMH levels have been shown to reduce pregnancy rates (J Hum Reprod Sci. 2017;10:24–30). During IVF cycle attempts, an ultra-low AMH (≤0.4) resulted in high cancellation rates, reduced the number of oocytes retrieved and embryos developed, and lowered pregnancy rates in women of advanced reproductive age.

Alternatively, a study of 750 women who were not infertile and were actively trying to conceive demonstrated no difference in natural pregnancy rates in women aged 30-44 irrespective of AMH levels (JAMA. 2017;318[14]:1367-76).

A special consideration is for cancer patients who are status postgonadotoxic chemotherapy. Their oocyte attrition can be accelerated and AMH levels can become profoundly low. In those patients, current data suggest there is a modest recovery of postchemotherapy AMH levels up to 1 year. Further, oocyte yield following stimulation may be higher than expected despite a poor AMH level.
 

Conclusion

Ovarian aging is currently best measured by combining chronologic age, AFC, and AMH. There is no current evidence that AMH levels should be used to exclude patients from undergoing IVF or to recommend egg donation. Random screening of AMH levels in a low-risk population for decreased ovarian reserve may result in unnecessary alarm.

Dr. Trolice is director of Fertility CARE - The IVF Center in Winter Park, Fla., and associate professor of obstetrics and gynecology at the University of Central Florida, Orlando.

Researchers in Italy have identified microplastic (MP) fragments in four human placentas that were donated for study after delivery.

curtoicurto/Getty Images

“The presence of MPs in the placenta tissue requires the reconsideration of the immunological mechanism of self-tolerance,” wrote Antonio Ragusa, MD, of San Giovanni Calibita Fatebenefratelli Hospital, Rome, and colleagues. “Placenta represents the interface between the fetus and the environment.”

In a pilot observational study published in Environment International, the researchers used Raman microspectroscopy to analyze placentas from six women with physiological pregnancies for the presence of MPs. MPs were defined as particles smaller than 5 mm resulting from the degradation of plastic in the environment, such as plastic objects, coatings, adhesives, paints, and personal care products. Data from previous studies have shown that MPs can move into living organisms, but this study is the first to identify MPs in human placentas, the researchers said.
 

Polypropylene and pigments identified

A total of 12 microplastic fragments were identified in tissue from the placentas of four women; 5 in the fetal side, 4 in the maternal side, and 3 in the chorioamniotic membranes, which suggests that MPs can reach all levels of placental tissue, the researchers said. Most of the MPs were approximately 10 mcm in size, but two were roughly 5 mcm.

All 12 of the MPs were pigmented; of these, 3 were identified as stained polypropylene and the other 9 contained pigments used in a variety of items including coatings, paints, adhesives, plasters, finger paints, polymers and cosmetics, and personal care products. The researchers used a software program to analyze the pigments and matched them with information from the European Chemical Agency for identification of the commercial name, chemical formula, International Union of Pure and Applied Chemistry name, and Color Index Constitution Number.

The mechanism by which MPs may enter the bloodstream and access the placenta remains unclear, the researchers said. “The most probable transport route for MPs is a mechanism of particle uptake and translocation, already described for the internalization from the gastrointestinal tract. Once MPs have reached the maternal surface of the placenta, as other exogenous materials, they can invade the tissue in depth by several transport mechanisms, both active and passive, that are not clearly understood yet.”

The range in location and characteristics of the particles found in the study suggest that passage of MPs into the placenta may be affected by physiological conditions and genetics, as well as food and lifestyle habits of the patients, the researchers said.

The study findings were limited by several factors including the small sample size and observational study design.

However, the presence of MPs in the placenta could affect the pregnancy in various ways, including immunity, growth factor signaling, maternal-fetal communication, and trafficking of various cell types and macrophages, the researchers wrote. In addition, MPs could have a transgenerational effect on metabolism and reproduction.

“Further studies need to be performed to assess if the presence of MPs in human placenta may trigger immune responses or may lead to the release of toxic contaminants, resulting harmful for pregnancy,” they concluded.
 

Cause for concern, but research gaps remain

“Microplastics are ubiquitous in the environment and are detectable in tissues of humans and wildlife,” Andrea C. Gore, PhD, of the University of Texas, Austin, said in an interview. “To my knowledge, this was never previously shown in the placenta.

“There are two reasons why detection of microplastics in placenta would be concerning,” Dr. Gore explained. “First, microplastics may be endocrine-disrupting chemicals (EDCs), or they may concentrate other chemicals that are EDCs. Second, the developing fetus is exquisitely sensitive to natural hormones, and disruptions by EDCs may lead to both immediate as well as latent health problems.

“Clinicians should be concerned about particulate matter in the placenta, “although the number of particles was very small,” said Dr. Gore. “Out of six women, four had particles in their placentas (total of 12) of which one was confirmed to be a plastic (polypropylene). For the other 11 particles, only the pigments could be identified, so more work is needed to confirm whether they were plastics.

“If I were a clinician discussing this article with my patients, I would point out that, although it is concerning that microparticles are present in placenta, few of them were found, and it is not known whether any chemical is released from the particles or actually reaches the fetal circulation,” Dr. Gore said. “I would use it as a starting point for a conversation about lifestyle during pregnancy and encouraging pregnant women to avoid eating foods stored and/or prepared in plastics.”

The limitations of the study include not only the small sample size, but also that “the type of chemicals in the microplastics is for the most part unknown, making it difficult to assess which (if any) might be EDCs,” Dr. Gore emphasized. In addition, “lifestyle and diet can greatly affect exposures to chemicals, so this needs to be carefully factored into the analysis.” Also, “most of the detected particles are pigments, so connections to plastics (other than the one polypropylene particle) need to be strengthened,” she explained.

“The pathways by which microplastics might get into tissues are still rather speculative, and the mechanisms proposed by the authors (endocytosis, paracellular diffusion, entry via airways) need to be demonstrated,” Dr. Gore concluded.

The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Gore had no conflicts to disclose.

SOURCE: Ragusa A et al. Environ Int. 2020 Dec 2. doi: 10.1016/j.envint.2020.106274.

Researchers in Italy have identified microplastic (MP) fragments in four human placentas that were donated for study after delivery.

curtoicurto/Getty Images

“The presence of MPs in the placenta tissue requires the reconsideration of the immunological mechanism of self-tolerance,” wrote Antonio Ragusa, MD, of San Giovanni Calibita Fatebenefratelli Hospital, Rome, and colleagues. “Placenta represents the interface between the fetus and the environment.”

In a pilot observational study published in Environment International, the researchers used Raman microspectroscopy to analyze placentas from six women with physiological pregnancies for the presence of MPs. MPs were defined as particles smaller than 5 mm resulting from the degradation of plastic in the environment, such as plastic objects, coatings, adhesives, paints, and personal care products. Data from previous studies have shown that MPs can move into living organisms, but this study is the first to identify MPs in human placentas, the researchers said.
 

Polypropylene and pigments identified

A total of 12 microplastic fragments were identified in tissue from the placentas of four women; 5 in the fetal side, 4 in the maternal side, and 3 in the chorioamniotic membranes, which suggests that MPs can reach all levels of placental tissue, the researchers said. Most of the MPs were approximately 10 mcm in size, but two were roughly 5 mcm.

All 12 of the MPs were pigmented; of these, 3 were identified as stained polypropylene and the other 9 contained pigments used in a variety of items including coatings, paints, adhesives, plasters, finger paints, polymers and cosmetics, and personal care products. The researchers used a software program to analyze the pigments and matched them with information from the European Chemical Agency for identification of the commercial name, chemical formula, International Union of Pure and Applied Chemistry name, and Color Index Constitution Number.

The mechanism by which MPs may enter the bloodstream and access the placenta remains unclear, the researchers said. “The most probable transport route for MPs is a mechanism of particle uptake and translocation, already described for the internalization from the gastrointestinal tract. Once MPs have reached the maternal surface of the placenta, as other exogenous materials, they can invade the tissue in depth by several transport mechanisms, both active and passive, that are not clearly understood yet.”

The range in location and characteristics of the particles found in the study suggest that passage of MPs into the placenta may be affected by physiological conditions and genetics, as well as food and lifestyle habits of the patients, the researchers said.

The study findings were limited by several factors including the small sample size and observational study design.

However, the presence of MPs in the placenta could affect the pregnancy in various ways, including immunity, growth factor signaling, maternal-fetal communication, and trafficking of various cell types and macrophages, the researchers wrote. In addition, MPs could have a transgenerational effect on metabolism and reproduction.

“Further studies need to be performed to assess if the presence of MPs in human placenta may trigger immune responses or may lead to the release of toxic contaminants, resulting harmful for pregnancy,” they concluded.
 

Cause for concern, but research gaps remain

“Microplastics are ubiquitous in the environment and are detectable in tissues of humans and wildlife,” Andrea C. Gore, PhD, of the University of Texas, Austin, said in an interview. “To my knowledge, this was never previously shown in the placenta.

“There are two reasons why detection of microplastics in placenta would be concerning,” Dr. Gore explained. “First, microplastics may be endocrine-disrupting chemicals (EDCs), or they may concentrate other chemicals that are EDCs. Second, the developing fetus is exquisitely sensitive to natural hormones, and disruptions by EDCs may lead to both immediate as well as latent health problems.

“Clinicians should be concerned about particulate matter in the placenta, “although the number of particles was very small,” said Dr. Gore. “Out of six women, four had particles in their placentas (total of 12) of which one was confirmed to be a plastic (polypropylene). For the other 11 particles, only the pigments could be identified, so more work is needed to confirm whether they were plastics.

“If I were a clinician discussing this article with my patients, I would point out that, although it is concerning that microparticles are present in placenta, few of them were found, and it is not known whether any chemical is released from the particles or actually reaches the fetal circulation,” Dr. Gore said. “I would use it as a starting point for a conversation about lifestyle during pregnancy and encouraging pregnant women to avoid eating foods stored and/or prepared in plastics.”

The limitations of the study include not only the small sample size, but also that “the type of chemicals in the microplastics is for the most part unknown, making it difficult to assess which (if any) might be EDCs,” Dr. Gore emphasized. In addition, “lifestyle and diet can greatly affect exposures to chemicals, so this needs to be carefully factored into the analysis.” Also, “most of the detected particles are pigments, so connections to plastics (other than the one polypropylene particle) need to be strengthened,” she explained.

“The pathways by which microplastics might get into tissues are still rather speculative, and the mechanisms proposed by the authors (endocytosis, paracellular diffusion, entry via airways) need to be demonstrated,” Dr. Gore concluded.

The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Gore had no conflicts to disclose.

SOURCE: Ragusa A et al. Environ Int. 2020 Dec 2. doi: 10.1016/j.envint.2020.106274.

Researchers in Italy have identified microplastic (MP) fragments in four human placentas that were donated for study after delivery.

curtoicurto/Getty Images

“The presence of MPs in the placenta tissue requires the reconsideration of the immunological mechanism of self-tolerance,” wrote Antonio Ragusa, MD, of San Giovanni Calibita Fatebenefratelli Hospital, Rome, and colleagues. “Placenta represents the interface between the fetus and the environment.”

In a pilot observational study published in Environment International, the researchers used Raman microspectroscopy to analyze placentas from six women with physiological pregnancies for the presence of MPs. MPs were defined as particles smaller than 5 mm resulting from the degradation of plastic in the environment, such as plastic objects, coatings, adhesives, paints, and personal care products. Data from previous studies have shown that MPs can move into living organisms, but this study is the first to identify MPs in human placentas, the researchers said.
 

Polypropylene and pigments identified

A total of 12 microplastic fragments were identified in tissue from the placentas of four women; 5 in the fetal side, 4 in the maternal side, and 3 in the chorioamniotic membranes, which suggests that MPs can reach all levels of placental tissue, the researchers said. Most of the MPs were approximately 10 mcm in size, but two were roughly 5 mcm.

All 12 of the MPs were pigmented; of these, 3 were identified as stained polypropylene and the other 9 contained pigments used in a variety of items including coatings, paints, adhesives, plasters, finger paints, polymers and cosmetics, and personal care products. The researchers used a software program to analyze the pigments and matched them with information from the European Chemical Agency for identification of the commercial name, chemical formula, International Union of Pure and Applied Chemistry name, and Color Index Constitution Number.

The mechanism by which MPs may enter the bloodstream and access the placenta remains unclear, the researchers said. “The most probable transport route for MPs is a mechanism of particle uptake and translocation, already described for the internalization from the gastrointestinal tract. Once MPs have reached the maternal surface of the placenta, as other exogenous materials, they can invade the tissue in depth by several transport mechanisms, both active and passive, that are not clearly understood yet.”

The range in location and characteristics of the particles found in the study suggest that passage of MPs into the placenta may be affected by physiological conditions and genetics, as well as food and lifestyle habits of the patients, the researchers said.

The study findings were limited by several factors including the small sample size and observational study design.

However, the presence of MPs in the placenta could affect the pregnancy in various ways, including immunity, growth factor signaling, maternal-fetal communication, and trafficking of various cell types and macrophages, the researchers wrote. In addition, MPs could have a transgenerational effect on metabolism and reproduction.

“Further studies need to be performed to assess if the presence of MPs in human placenta may trigger immune responses or may lead to the release of toxic contaminants, resulting harmful for pregnancy,” they concluded.
 

Cause for concern, but research gaps remain

“Microplastics are ubiquitous in the environment and are detectable in tissues of humans and wildlife,” Andrea C. Gore, PhD, of the University of Texas, Austin, said in an interview. “To my knowledge, this was never previously shown in the placenta.

“There are two reasons why detection of microplastics in placenta would be concerning,” Dr. Gore explained. “First, microplastics may be endocrine-disrupting chemicals (EDCs), or they may concentrate other chemicals that are EDCs. Second, the developing fetus is exquisitely sensitive to natural hormones, and disruptions by EDCs may lead to both immediate as well as latent health problems.

“Clinicians should be concerned about particulate matter in the placenta, “although the number of particles was very small,” said Dr. Gore. “Out of six women, four had particles in their placentas (total of 12) of which one was confirmed to be a plastic (polypropylene). For the other 11 particles, only the pigments could be identified, so more work is needed to confirm whether they were plastics.

“If I were a clinician discussing this article with my patients, I would point out that, although it is concerning that microparticles are present in placenta, few of them were found, and it is not known whether any chemical is released from the particles or actually reaches the fetal circulation,” Dr. Gore said. “I would use it as a starting point for a conversation about lifestyle during pregnancy and encouraging pregnant women to avoid eating foods stored and/or prepared in plastics.”

The limitations of the study include not only the small sample size, but also that “the type of chemicals in the microplastics is for the most part unknown, making it difficult to assess which (if any) might be EDCs,” Dr. Gore emphasized. In addition, “lifestyle and diet can greatly affect exposures to chemicals, so this needs to be carefully factored into the analysis.” Also, “most of the detected particles are pigments, so connections to plastics (other than the one polypropylene particle) need to be strengthened,” she explained.

“The pathways by which microplastics might get into tissues are still rather speculative, and the mechanisms proposed by the authors (endocytosis, paracellular diffusion, entry via airways) need to be demonstrated,” Dr. Gore concluded.

The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Gore had no conflicts to disclose.

SOURCE: Ragusa A et al. Environ Int. 2020 Dec 2. doi: 10.1016/j.envint.2020.106274.

A proposal to delay administration of the second dose of COVID-19 vaccines – suggested as a strategy to boost the number of people who get some degree of protection from a single immunization with the Pfizer/BioNTech or Moderna vaccines – is inciting a strong debate among clinicians and public health officials.

Proponents argue that getting some degree of protection to a greater number of Americans is worthwhile, particularly as case numbers and hospitalizations continue to rise and with the emergence of a more contagious variant.

Opponents raise concerns about diverting from the two-dose schedule evaluated in clinical trials, including a lack of data on long-term protection from a single dose. They also suggest a longer interval between dosing could increase resistance of SARS-CoV-2 virus.

It is time to consider delaying the second dose, Robert M. Wachter, MD, at the University of California San Francisco, and Ashish Jha, MD, MPH, at Brown University in Providence, R.I., wrote in an opinion piece in The Washington Post Jan. 3. 

The two experts state that supply constraints, distribution bottlenecks, and hundreds of thousands of new infections daily prompted them to change their stance on administering COVID-19 vaccines according to the two-dose clinical trial regimen. Furthermore, they cited a study in the New England Journal of Medicine that suggests 80%-90% efficacy for preventing SARS-CoV-2 infection following one dose of the Moderna vaccine. 

Not everyone agrees one dose is a good idea. “Clinical trials with specific schedules for vaccine dosing – that’s the whole basis of the scientific evidence,” Maria Elena Bottazzi, PhD, associate dean of the National School of Tropical Medicine at Baylor College of Medicine in Houston, said in an interview.

After one dose “the immune system is learning, but it’s not ideal. That’s why you need the second dose,” Dr. Bottazzi said. “I appreciate the urgency and the anxiety ... but the data support [that] clinical efficacy requires two doses.”

Another proposed strategy to extend the current supply of COVID-19 vaccines to more Americans involves splitting the current dosage of the Moderna vaccine in half. Officials in the United States and the United Kingdom are reportedly considering this approach. In the United States, the Food and Drug Administration would have to approve any dosing change.
 

Agreeing to disagree

Dr. Wachter shared a link to his opinion piece on Twitter, stating that “We both came to this view because of the slow rollout & the new variant. But it’s a tough call and reasonable people will disagree.”

As predicted, the tweet elicited a number of strong opinions.

“There are no correct answers but there’s data deficiency, plenty of fodder and need for healthy, intellectual debate. That wouldn’t be occurring if there was an ample supply of vaccines,” Eric Topol, MD, director of the Scripps Translational Science Institute and editor-in-chief of Medscape, tweeted on Jan. 3.

“If the problem were with the supply of the vaccine, one might make an argument for focusing on 1st dose. But the problem is in distribution of the vaccine & giving actual doses,” John Grohol, PsyD, tweeted.

“Right now we don’t have a supply issue, we have a distribution issue,” Angela Shen, ScD, MPH, a research scientist in the Vaccine Education Center at Children’s Hospital of Philadelphia, said in an interview. Emergency use authorization for the Johnson & Johnson and other COVID-19 vaccines in development could further boost available supplies, she added.

“The clinical trials studied two doses,” Dr. Shen said. “We don’t have data that one dose is going to have lasting protection.” 
 

Does new variant change equation?

Dr. Wachter and Dr. Jha, in their editorial, cited a quote from former boxing champion Mike Tyson: “Everybody has a plan until they’ve been punched in the mouth.” ‘Punches’ such as the new variant, the high number of cases and deaths in the United States, and other problems prompted them to advocate for the delayed dosing strategy.

“Appreciate the concern for the new variant – I think it’s worth noting that we’re punching ourselves in the mouth with the slow vaccine rollout, which is the first problem to solve,” Jake Quinton, MD, an internist at UCLA Health in Los Angeles, noted on Twitter.

 

Vaccine and public resistance raised

“I agree with the problem but not with the proposed solution, which is guesswork not based on data,” the Jan Grimm Lab at Memorial Sloan Kettering Cancer Center in New York responded to Dr. Wachter and Dr. Jha on Twitter. “There ARE data though that show that 1 shot alone did not elicit sufficient T-cell nor antibody response. This might also lead to mutations resistant to the vaccines. Dangerous!”

Other physicians took to Twitter to point out that changing the recommendations at this point could further erode public confidence in COVID-19 immunization. For example, Deirdre Habermehl, MD, wrote, “We’ve spent months telling the public the best route is to follow the science and now without data think a course correction based on a guesstimate is ok? Public confidence is low enough and the real issue is logistics at this point.”

Dr. Shen and Dr. Bottazzi have disclosed no relevant financial relationships.

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

A proposal to delay administration of the second dose of COVID-19 vaccines – suggested as a strategy to boost the number of people who get some degree of protection from a single immunization with the Pfizer/BioNTech or Moderna vaccines – is inciting a strong debate among clinicians and public health officials.

Proponents argue that getting some degree of protection to a greater number of Americans is worthwhile, particularly as case numbers and hospitalizations continue to rise and with the emergence of a more contagious variant.

Opponents raise concerns about diverting from the two-dose schedule evaluated in clinical trials, including a lack of data on long-term protection from a single dose. They also suggest a longer interval between dosing could increase resistance of SARS-CoV-2 virus.

It is time to consider delaying the second dose, Robert M. Wachter, MD, at the University of California San Francisco, and Ashish Jha, MD, MPH, at Brown University in Providence, R.I., wrote in an opinion piece in The Washington Post Jan. 3. 

The two experts state that supply constraints, distribution bottlenecks, and hundreds of thousands of new infections daily prompted them to change their stance on administering COVID-19 vaccines according to the two-dose clinical trial regimen. Furthermore, they cited a study in the New England Journal of Medicine that suggests 80%-90% efficacy for preventing SARS-CoV-2 infection following one dose of the Moderna vaccine. 

Not everyone agrees one dose is a good idea. “Clinical trials with specific schedules for vaccine dosing – that’s the whole basis of the scientific evidence,” Maria Elena Bottazzi, PhD, associate dean of the National School of Tropical Medicine at Baylor College of Medicine in Houston, said in an interview.

After one dose “the immune system is learning, but it’s not ideal. That’s why you need the second dose,” Dr. Bottazzi said. “I appreciate the urgency and the anxiety ... but the data support [that] clinical efficacy requires two doses.”

Another proposed strategy to extend the current supply of COVID-19 vaccines to more Americans involves splitting the current dosage of the Moderna vaccine in half. Officials in the United States and the United Kingdom are reportedly considering this approach. In the United States, the Food and Drug Administration would have to approve any dosing change.
 

Agreeing to disagree

Dr. Wachter shared a link to his opinion piece on Twitter, stating that “We both came to this view because of the slow rollout & the new variant. But it’s a tough call and reasonable people will disagree.”

As predicted, the tweet elicited a number of strong opinions.

“There are no correct answers but there’s data deficiency, plenty of fodder and need for healthy, intellectual debate. That wouldn’t be occurring if there was an ample supply of vaccines,” Eric Topol, MD, director of the Scripps Translational Science Institute and editor-in-chief of Medscape, tweeted on Jan. 3.

“If the problem were with the supply of the vaccine, one might make an argument for focusing on 1st dose. But the problem is in distribution of the vaccine & giving actual doses,” John Grohol, PsyD, tweeted.

“Right now we don’t have a supply issue, we have a distribution issue,” Angela Shen, ScD, MPH, a research scientist in the Vaccine Education Center at Children’s Hospital of Philadelphia, said in an interview. Emergency use authorization for the Johnson & Johnson and other COVID-19 vaccines in development could further boost available supplies, she added.

“The clinical trials studied two doses,” Dr. Shen said. “We don’t have data that one dose is going to have lasting protection.” 
 

Does new variant change equation?

Dr. Wachter and Dr. Jha, in their editorial, cited a quote from former boxing champion Mike Tyson: “Everybody has a plan until they’ve been punched in the mouth.” ‘Punches’ such as the new variant, the high number of cases and deaths in the United States, and other problems prompted them to advocate for the delayed dosing strategy.

“Appreciate the concern for the new variant – I think it’s worth noting that we’re punching ourselves in the mouth with the slow vaccine rollout, which is the first problem to solve,” Jake Quinton, MD, an internist at UCLA Health in Los Angeles, noted on Twitter.

 

Vaccine and public resistance raised

“I agree with the problem but not with the proposed solution, which is guesswork not based on data,” the Jan Grimm Lab at Memorial Sloan Kettering Cancer Center in New York responded to Dr. Wachter and Dr. Jha on Twitter. “There ARE data though that show that 1 shot alone did not elicit sufficient T-cell nor antibody response. This might also lead to mutations resistant to the vaccines. Dangerous!”

Other physicians took to Twitter to point out that changing the recommendations at this point could further erode public confidence in COVID-19 immunization. For example, Deirdre Habermehl, MD, wrote, “We’ve spent months telling the public the best route is to follow the science and now without data think a course correction based on a guesstimate is ok? Public confidence is low enough and the real issue is logistics at this point.”

Dr. Shen and Dr. Bottazzi have disclosed no relevant financial relationships.

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

A proposal to delay administration of the second dose of COVID-19 vaccines – suggested as a strategy to boost the number of people who get some degree of protection from a single immunization with the Pfizer/BioNTech or Moderna vaccines – is inciting a strong debate among clinicians and public health officials.

Proponents argue that getting some degree of protection to a greater number of Americans is worthwhile, particularly as case numbers and hospitalizations continue to rise and with the emergence of a more contagious variant.

Opponents raise concerns about diverting from the two-dose schedule evaluated in clinical trials, including a lack of data on long-term protection from a single dose. They also suggest a longer interval between dosing could increase resistance of SARS-CoV-2 virus.

It is time to consider delaying the second dose, Robert M. Wachter, MD, at the University of California San Francisco, and Ashish Jha, MD, MPH, at Brown University in Providence, R.I., wrote in an opinion piece in The Washington Post Jan. 3. 

The two experts state that supply constraints, distribution bottlenecks, and hundreds of thousands of new infections daily prompted them to change their stance on administering COVID-19 vaccines according to the two-dose clinical trial regimen. Furthermore, they cited a study in the New England Journal of Medicine that suggests 80%-90% efficacy for preventing SARS-CoV-2 infection following one dose of the Moderna vaccine. 

Not everyone agrees one dose is a good idea. “Clinical trials with specific schedules for vaccine dosing – that’s the whole basis of the scientific evidence,” Maria Elena Bottazzi, PhD, associate dean of the National School of Tropical Medicine at Baylor College of Medicine in Houston, said in an interview.

After one dose “the immune system is learning, but it’s not ideal. That’s why you need the second dose,” Dr. Bottazzi said. “I appreciate the urgency and the anxiety ... but the data support [that] clinical efficacy requires two doses.”

Another proposed strategy to extend the current supply of COVID-19 vaccines to more Americans involves splitting the current dosage of the Moderna vaccine in half. Officials in the United States and the United Kingdom are reportedly considering this approach. In the United States, the Food and Drug Administration would have to approve any dosing change.
 

Agreeing to disagree

Dr. Wachter shared a link to his opinion piece on Twitter, stating that “We both came to this view because of the slow rollout & the new variant. But it’s a tough call and reasonable people will disagree.”

As predicted, the tweet elicited a number of strong opinions.

“There are no correct answers but there’s data deficiency, plenty of fodder and need for healthy, intellectual debate. That wouldn’t be occurring if there was an ample supply of vaccines,” Eric Topol, MD, director of the Scripps Translational Science Institute and editor-in-chief of Medscape, tweeted on Jan. 3.

“If the problem were with the supply of the vaccine, one might make an argument for focusing on 1st dose. But the problem is in distribution of the vaccine & giving actual doses,” John Grohol, PsyD, tweeted.

“Right now we don’t have a supply issue, we have a distribution issue,” Angela Shen, ScD, MPH, a research scientist in the Vaccine Education Center at Children’s Hospital of Philadelphia, said in an interview. Emergency use authorization for the Johnson & Johnson and other COVID-19 vaccines in development could further boost available supplies, she added.

“The clinical trials studied two doses,” Dr. Shen said. “We don’t have data that one dose is going to have lasting protection.” 
 

Does new variant change equation?

Dr. Wachter and Dr. Jha, in their editorial, cited a quote from former boxing champion Mike Tyson: “Everybody has a plan until they’ve been punched in the mouth.” ‘Punches’ such as the new variant, the high number of cases and deaths in the United States, and other problems prompted them to advocate for the delayed dosing strategy.

“Appreciate the concern for the new variant – I think it’s worth noting that we’re punching ourselves in the mouth with the slow vaccine rollout, which is the first problem to solve,” Jake Quinton, MD, an internist at UCLA Health in Los Angeles, noted on Twitter.

 

Vaccine and public resistance raised

“I agree with the problem but not with the proposed solution, which is guesswork not based on data,” the Jan Grimm Lab at Memorial Sloan Kettering Cancer Center in New York responded to Dr. Wachter and Dr. Jha on Twitter. “There ARE data though that show that 1 shot alone did not elicit sufficient T-cell nor antibody response. This might also lead to mutations resistant to the vaccines. Dangerous!”

Other physicians took to Twitter to point out that changing the recommendations at this point could further erode public confidence in COVID-19 immunization. For example, Deirdre Habermehl, MD, wrote, “We’ve spent months telling the public the best route is to follow the science and now without data think a course correction based on a guesstimate is ok? Public confidence is low enough and the real issue is logistics at this point.”

Dr. Shen and Dr. Bottazzi have disclosed no relevant financial relationships.

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

The United States started 2021 they way it ended 2020: Setting new records amidst the coronavirus pandemic.

Courtesy NIAID-RML

The country passed the 20 million mark for coronavirus cases on Friday, setting the mark sometime around noon, according to Johns Hopkins University’s COVID-19 tracker. The total is nearly twice as many as the next worst country – India, which has 10.28 million cases.

Along with the case count, more than 346,000 Americans have now died of COVID-19, the disease caused by the coronavirus. That is 77% more fatalities than Brazil, which ranks second globally with 194,949 deaths.

More than 125,370 coronavirus patients were hospitalized on Thursday, the fourth record-setting day in a row, according to the COVID Tracking Project.

Going by official tallies, it took 292 days for the United States to reach its first 10 million cases, and just 54 more days to double it, CNN reported.

Meanwhile, 12.41 million doses of COVID-19 vaccines have been distributed in the United States as of Wednesday, according to the Centers for Disease Control and Prevention. Yet only 2.8 million people have received the first of a two-shot regimen.

The slower-than-hoped-for rollout of the Pfizer and Moderna vaccines comes as a new variant of the coronavirus has emerged in a third state. Florida officials announced a confirmed case of the new variant – believed to have originated in the United Kingdom – in Martin County in southeast Florida.

The state health department said on Twitter that the patient is a man in his 20s with no history of travel. The department said it is working with the CDC to investigate.

The variant has also been confirmed in cases in Colorado and California. It is believed to be more contagious. The BBC reported that the new variant increases the reproduction, or “R number,” by 0.4 and 0.7. The UK’s most recent R number has been estimated at 1.1-1.3, meaning anyone who has the coronavirus could be assumed to spread it to up to 1.3 people.

The R number needs to be below 1.0 for the spread of the virus to fall.

“There is a huge difference in how easily the variant virus spreads,” Professor Axel Gandy of London’s Imperial College told BBC News. “This is the most serious change in the virus since the epidemic began.”

A version of this article first appeared on WebMD.com.

The United States started 2021 they way it ended 2020: Setting new records amidst the coronavirus pandemic.

Courtesy NIAID-RML

The country passed the 20 million mark for coronavirus cases on Friday, setting the mark sometime around noon, according to Johns Hopkins University’s COVID-19 tracker. The total is nearly twice as many as the next worst country – India, which has 10.28 million cases.

Along with the case count, more than 346,000 Americans have now died of COVID-19, the disease caused by the coronavirus. That is 77% more fatalities than Brazil, which ranks second globally with 194,949 deaths.

More than 125,370 coronavirus patients were hospitalized on Thursday, the fourth record-setting day in a row, according to the COVID Tracking Project.

Going by official tallies, it took 292 days for the United States to reach its first 10 million cases, and just 54 more days to double it, CNN reported.

Meanwhile, 12.41 million doses of COVID-19 vaccines have been distributed in the United States as of Wednesday, according to the Centers for Disease Control and Prevention. Yet only 2.8 million people have received the first of a two-shot regimen.

The slower-than-hoped-for rollout of the Pfizer and Moderna vaccines comes as a new variant of the coronavirus has emerged in a third state. Florida officials announced a confirmed case of the new variant – believed to have originated in the United Kingdom – in Martin County in southeast Florida.

The state health department said on Twitter that the patient is a man in his 20s with no history of travel. The department said it is working with the CDC to investigate.

The variant has also been confirmed in cases in Colorado and California. It is believed to be more contagious. The BBC reported that the new variant increases the reproduction, or “R number,” by 0.4 and 0.7. The UK’s most recent R number has been estimated at 1.1-1.3, meaning anyone who has the coronavirus could be assumed to spread it to up to 1.3 people.

The R number needs to be below 1.0 for the spread of the virus to fall.

“There is a huge difference in how easily the variant virus spreads,” Professor Axel Gandy of London’s Imperial College told BBC News. “This is the most serious change in the virus since the epidemic began.”

A version of this article first appeared on WebMD.com.

The United States started 2021 they way it ended 2020: Setting new records amidst the coronavirus pandemic.

Courtesy NIAID-RML

The country passed the 20 million mark for coronavirus cases on Friday, setting the mark sometime around noon, according to Johns Hopkins University’s COVID-19 tracker. The total is nearly twice as many as the next worst country – India, which has 10.28 million cases.

Along with the case count, more than 346,000 Americans have now died of COVID-19, the disease caused by the coronavirus. That is 77% more fatalities than Brazil, which ranks second globally with 194,949 deaths.

More than 125,370 coronavirus patients were hospitalized on Thursday, the fourth record-setting day in a row, according to the COVID Tracking Project.

Going by official tallies, it took 292 days for the United States to reach its first 10 million cases, and just 54 more days to double it, CNN reported.

Meanwhile, 12.41 million doses of COVID-19 vaccines have been distributed in the United States as of Wednesday, according to the Centers for Disease Control and Prevention. Yet only 2.8 million people have received the first of a two-shot regimen.

The slower-than-hoped-for rollout of the Pfizer and Moderna vaccines comes as a new variant of the coronavirus has emerged in a third state. Florida officials announced a confirmed case of the new variant – believed to have originated in the United Kingdom – in Martin County in southeast Florida.

The state health department said on Twitter that the patient is a man in his 20s with no history of travel. The department said it is working with the CDC to investigate.

The variant has also been confirmed in cases in Colorado and California. It is believed to be more contagious. The BBC reported that the new variant increases the reproduction, or “R number,” by 0.4 and 0.7. The UK’s most recent R number has been estimated at 1.1-1.3, meaning anyone who has the coronavirus could be assumed to spread it to up to 1.3 people.

The R number needs to be below 1.0 for the spread of the virus to fall.

“There is a huge difference in how easily the variant virus spreads,” Professor Axel Gandy of London’s Imperial College told BBC News. “This is the most serious change in the virus since the epidemic began.”

A version of this article first appeared on WebMD.com.

The practice of medical students giving unconsented pelvic exams to women patients under anesthesia seems to be continuing, although recent new laws aim to change the situation.

“When I was doing ob.gyn. as a med student, the attending would have me do a pelvic right after the patient was under and before we started surgery,” said one participant in an online forum. “We didn’t exactly get permission but it was for teaching purposes.”

Yet others don’t see what the commotion is about. “There are a hundred things that are done during a surgery that don’t require your specific consent (some of them much more ‘humiliating’ than a pelvic exam). ... There’s not really much left to be shy about during a gyn/rectal/prostate surgery, let me put it that way,” one doctor wrote.

However, many physicians are adamantly opposed to the practice, and laws intended to stop or limit it are being enacted throughout the nation.
 

Renewed concerns have prompted new state laws

A few states have required consent for pelvic exams for many years, beginning with California in 2003. But up until 2019, providing pelvic exams without informed consent was illegal in only six states.

Continuing reports of unauthorized pelvic exams indicate that the practice has not disappeared. University of Michigan professor Maya M. Hammoud, MD, past president of the Association of Professors of Gynecology and Obstetrics, and many others attribute renewed interest in the issue to a 2018 article in the journal Bioethics by Phoebe Friesen, a medical ethicist at McGill University, Montreal, that laid out the ethical arguments against the practice.

Starting in 2019, an outpouring of new state bills have been introduced, and nine more states have passed laws. In addition, 14 other states considered similar bills but did not pass them, in some cases because teaching institutions argued that they were already dealing with the issue. This happened in Connecticut and Massachusetts, after representatives of Yale University, New Haven, Conn., met with legislators.

Laws against the practice have been passed by 15 states, including California, Florida, Illinois, and New York. Some teaching institutions have recently been clamping down on the practice, while many teaching physicians insist that at this point, it has all but ended.
 

A practice that may still continue

For many years, ethicists, women’s rights groups, state legislators, and organized medicine have been trying to eliminate the practice of unauthorized pelvic exams by medical students. Several key medical groups have come out against it, including the American Medical Association, the Association of American Medical Colleges, and the American College of Obstetricians and Gynecologists.

“Fifteen years ago, studies found a substantial number of cases, but my sense is that most of that has stopped,” said Dr. Hammoud. 

Yet despite these changes, there are some disturbing signs that the practice persists.

“I don’t have data, but anecdotally I see it still going on,” said Peter Ubel, MD, a professor at Duke University, Durham, N.C., who was involved in one of those early studies. “Every so often when I’m making a speech, a medical student tells me about performing a pelvic exam without getting permission.

“Perhaps in some cases the attending [physician] did get permission and didn’t tell the medical student, but that would also be a problem,” Dr. Ubel said. “The medical student should be informed that permission was given. This helps them be sensitive to the need to get consent.”

In a 2019 survey of medical students, 92% said they performed a pelvic exam on an anesthetized female patient, and of those, 61% did so without explicit patient consent.

The survey – involving 101 medical students at seven U.S. medical schools – also found that 11% of the medical students said they were extremely uncomfortable with the practice. But nearly one-third of the medical students said that opting out might jeopardize their grades and future careers.

“I tried to opt out once from doing a pelvic exam when I hadn’t met the patient beforehand,” one of them wrote. “The resident told me no.”
 

Some physicians defend the practice

Why do many medical students and doctors think that getting consent for pelvic exams is not necessary?

Some argue that patients implicitly give consent when they walk through the doors of a teaching hospital. “Sorry, but you inherently agree to that when you’re seen in an academic teaching hospital,” wrote one participant in a Student Doctor Network forum. “You agree to have residents and medical students participate in your care, not just an attending. If you just want an attending, then you are free to go to a nonteaching hospital. That’s the deal.”

Others argued that since the anesthetized patient couldn’t feel what was going on, it shouldn’t matter. “Things like pelvic exams, rectal exams, or even heroic trauma surgery occur for training purposes when there is no memory, no sensation and no harm to be done [and] society gains a better practitioner of the art of medicine,” a physician in Columbus, Ohio, wrote on Quora, an online forum.

Some doctors argue that they don’t ask for specific consent when they touch a variety of other body parts, and pelvic exams should be no different. Pelvic exams are needed before surgery of the pelvic area, but they have also been given to women undergoing surgery in a different part of the body.

In 2019 a woman told Deseret News in Utah that she had been recovering from stomach surgery when a resident physician mentioned something she had noticed “when we looked at your cervix.” When she asked why the physician had examined her cervix to prepare for stomach surgery, “no one could give her a good answer.”
 

A ‘positive goal’ doesn’t make it okay

What is missing in many defenses of the practice is any recognition that genitals are the most intimate part of the body, and that a patient’s desire for privacy ought to come first. In a survey of women undergoing gynecologic surgery, 72% expected to be asked for consent before medical students undertook pelvic examinations under anesthesia.

Overruling patients’ concerns about their own privacy is unethical, said Eli Y. Adashi, MD, professor of medical science and former dean of medicine and biological sciences at Brown University, Providence, R.I.

Dr. Adashi said the principle of patient autonomy in medical ethics directs that patients must be involved in decision-making about their care – even when caretakers are pursuing a positive goal, such as helping to educate future doctors.

“Conducting pelvic exams on unconscious women without their specific consent is simply untenable and never has been tenable, and it ought to be discontinued if it hasn’t been already,” says Dr. Adashi, who wrote an opinion piece on the issue for JAMA.

Furthermore, it has been shown that ignoring the need to get consent for pelvic exams makes physicians less concerned about getting patient consent in general. A study led by Dr. Ubel found that medical students who had completed an ob.gyn. clerkship thought getting patients’ consent was significantly less important than those who had not completed that clerkship.
 

Why give pelvic exams to anesthetized women?

Despite the controversy, a number of medical educators continue to direct medical students to perform pelvic exams on anesthetized women. Why is that?

“Pelvic exams are not easy to do,” Dr. Hammoud said. “Learners need to keep working on them; they have to do a lot of them in order to do them well.”

To teach pelvic exams, most medical schools provide standardized patients – paid volunteers who submit to exams and critique the medical student’s work afterwards – but these encounters are limited because of their cost, says Guy Benrubi, MD, professor and emeritus chair of the department of obstetrics and gynecology at the University of Florida, Jacksonville.

He said teaching programs therefore need to supplement exams on standardized patients with exams on unpaid volunteers who provide consent. Programs prefer anesthetized patients, Dr. Benrubi said, because they are easier for novices to work on. “With patients under anesthesia, the muscles are relaxed and it’s easier for learners to detect organs. All the same, you need to get consent.”
 

Teaching institutions stiffen consent requirements

Faced with growing opposition to pelvic exams without consent, teaching institutions as well as gynecologic educators have recently been tightening their policies.

Dr. Hammoud said she has always informed patients orally about the possibility of medical students performing pelvic exams on them, but now some institutions, including her own, want a more involved process. The university recently began consent in writing for pelvic exams.

In addition, the university also now requires that medical students meet patients before performing pelvic exams and that teaching physicians explain the students’ involvement.

Dr. Hammoud said some institutions now require a separate consent form for pelvic exams, but the University of Michigan simply directs that the possibility of the patient getting a pelvic exam be part of the consent form.

This requirement, called “explicit consent,” was endorsed by APGO. It differs from having a separate consent form for pelvic exams, which would highlight the possibility of a pelvic exam, as many women’s rights activists are calling for.

Why not have a separate form? Dr. Hammoud is concerned that it would unnecessarily alarm patients. “When you point out a certain issue, you’re in effect saying to the patient that this is not normal,” she said, noting that, when asked for consent to do the exams, most women agree to it.
 

New wave of state laws prompted by renewed concerns

Dr. Hammoud thinks the laws are unnecessary. “These laws are excessive for the vast majority of physicians who practice ethically. The profession should come up with its own standards rather than having a plethora of laws.”

Several of the more recent laws have a broader scope than the original laws. The original laws simply state that medical students or physicians must get informed consent, but they did not stipulate how informed consent should be obtained. (The laws also typically prohibit pelvic exams when surgery will be in a different area of the body.)

The new laws often follow this format, but some go well beyond it. Some also apply to rectal exams (Maine and Maryland), to men as well as women (Utah and Maryland) requires separate consent (Utah), and require consent for all pelvic exams (Florida). 
 

The struggle over Florida’s law

The original Florida bill was drafted in 2019 by state Sen. Lauren Book, a Democrat who is a victims’ rights advocate working with women who have undergone sexual trauma. In written comments for this article, she says not getting consent for pelvic exams is still going on.

“This disturbing practice is commonplace at medical schools and teaching hospitals across the country – including several Florida universities, based on accounts from current and former medical students and faculty,” Sen. Book stated. “At best, these exams have been wrongful learning experiences for medical students or at worst, the equivalent of a sexual assault.”

Dr. Ubel took exception to linking the teaching activities to sexual assault. “I understand why many women would be horrified by this practice, but it’s not as bad as it seems,” he said. “There is nothing sexual or prurient about these exams, and they are motivated purely by a desire to teach people to be better doctors. That said, patients have the right to say, ‘I don’t want it done to me.’ ” 

In early 2020, Dr. Benrubi was part of a coalition of medical groups that was trying to influence Sen. Book’s bill as it went through the legislature. Sen. Book’s original bill was relatively mild, “but then, late in the process, it was changed into a more sweeping bill with some unclear language,” he said.

The final version was passed and signed into law by Gov. Ron DeSantis, a conservative Republican, in June.

Dr. Benrubi said that a large number of state legislators, including Sen. Book, have been agreeable to fixing the bill. This was supposed to happen in a special session in the fall, but that never materialized, and so the fix will have to wait until the regular session in early 2021.

“The law should not apply to patients undergoing routine pelvic exams,” Dr. Benrubi said. “It should only apply to women patients under anesthesia.”

But while organized medicine wants to walk back the law, Dr. Book wants to expand it. “This upcoming session, I look forward to working with physicians to continue to hone this new law, and to work toward inclusion for males. Everyone has a right to consent.”

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

The practice of medical students giving unconsented pelvic exams to women patients under anesthesia seems to be continuing, although recent new laws aim to change the situation.

“When I was doing ob.gyn. as a med student, the attending would have me do a pelvic right after the patient was under and before we started surgery,” said one participant in an online forum. “We didn’t exactly get permission but it was for teaching purposes.”

Yet others don’t see what the commotion is about. “There are a hundred things that are done during a surgery that don’t require your specific consent (some of them much more ‘humiliating’ than a pelvic exam). ... There’s not really much left to be shy about during a gyn/rectal/prostate surgery, let me put it that way,” one doctor wrote.

However, many physicians are adamantly opposed to the practice, and laws intended to stop or limit it are being enacted throughout the nation.
 

Renewed concerns have prompted new state laws

A few states have required consent for pelvic exams for many years, beginning with California in 2003. But up until 2019, providing pelvic exams without informed consent was illegal in only six states.

Continuing reports of unauthorized pelvic exams indicate that the practice has not disappeared. University of Michigan professor Maya M. Hammoud, MD, past president of the Association of Professors of Gynecology and Obstetrics, and many others attribute renewed interest in the issue to a 2018 article in the journal Bioethics by Phoebe Friesen, a medical ethicist at McGill University, Montreal, that laid out the ethical arguments against the practice.

Starting in 2019, an outpouring of new state bills have been introduced, and nine more states have passed laws. In addition, 14 other states considered similar bills but did not pass them, in some cases because teaching institutions argued that they were already dealing with the issue. This happened in Connecticut and Massachusetts, after representatives of Yale University, New Haven, Conn., met with legislators.

Laws against the practice have been passed by 15 states, including California, Florida, Illinois, and New York. Some teaching institutions have recently been clamping down on the practice, while many teaching physicians insist that at this point, it has all but ended.
 

A practice that may still continue

For many years, ethicists, women’s rights groups, state legislators, and organized medicine have been trying to eliminate the practice of unauthorized pelvic exams by medical students. Several key medical groups have come out against it, including the American Medical Association, the Association of American Medical Colleges, and the American College of Obstetricians and Gynecologists.

“Fifteen years ago, studies found a substantial number of cases, but my sense is that most of that has stopped,” said Dr. Hammoud. 

Yet despite these changes, there are some disturbing signs that the practice persists.

“I don’t have data, but anecdotally I see it still going on,” said Peter Ubel, MD, a professor at Duke University, Durham, N.C., who was involved in one of those early studies. “Every so often when I’m making a speech, a medical student tells me about performing a pelvic exam without getting permission.

“Perhaps in some cases the attending [physician] did get permission and didn’t tell the medical student, but that would also be a problem,” Dr. Ubel said. “The medical student should be informed that permission was given. This helps them be sensitive to the need to get consent.”

In a 2019 survey of medical students, 92% said they performed a pelvic exam on an anesthetized female patient, and of those, 61% did so without explicit patient consent.

The survey – involving 101 medical students at seven U.S. medical schools – also found that 11% of the medical students said they were extremely uncomfortable with the practice. But nearly one-third of the medical students said that opting out might jeopardize their grades and future careers.

“I tried to opt out once from doing a pelvic exam when I hadn’t met the patient beforehand,” one of them wrote. “The resident told me no.”
 

Some physicians defend the practice

Why do many medical students and doctors think that getting consent for pelvic exams is not necessary?

Some argue that patients implicitly give consent when they walk through the doors of a teaching hospital. “Sorry, but you inherently agree to that when you’re seen in an academic teaching hospital,” wrote one participant in a Student Doctor Network forum. “You agree to have residents and medical students participate in your care, not just an attending. If you just want an attending, then you are free to go to a nonteaching hospital. That’s the deal.”

Others argued that since the anesthetized patient couldn’t feel what was going on, it shouldn’t matter. “Things like pelvic exams, rectal exams, or even heroic trauma surgery occur for training purposes when there is no memory, no sensation and no harm to be done [and] society gains a better practitioner of the art of medicine,” a physician in Columbus, Ohio, wrote on Quora, an online forum.

Some doctors argue that they don’t ask for specific consent when they touch a variety of other body parts, and pelvic exams should be no different. Pelvic exams are needed before surgery of the pelvic area, but they have also been given to women undergoing surgery in a different part of the body.

In 2019 a woman told Deseret News in Utah that she had been recovering from stomach surgery when a resident physician mentioned something she had noticed “when we looked at your cervix.” When she asked why the physician had examined her cervix to prepare for stomach surgery, “no one could give her a good answer.”
 

A ‘positive goal’ doesn’t make it okay

What is missing in many defenses of the practice is any recognition that genitals are the most intimate part of the body, and that a patient’s desire for privacy ought to come first. In a survey of women undergoing gynecologic surgery, 72% expected to be asked for consent before medical students undertook pelvic examinations under anesthesia.

Overruling patients’ concerns about their own privacy is unethical, said Eli Y. Adashi, MD, professor of medical science and former dean of medicine and biological sciences at Brown University, Providence, R.I.

Dr. Adashi said the principle of patient autonomy in medical ethics directs that patients must be involved in decision-making about their care – even when caretakers are pursuing a positive goal, such as helping to educate future doctors.

“Conducting pelvic exams on unconscious women without their specific consent is simply untenable and never has been tenable, and it ought to be discontinued if it hasn’t been already,” says Dr. Adashi, who wrote an opinion piece on the issue for JAMA.

Furthermore, it has been shown that ignoring the need to get consent for pelvic exams makes physicians less concerned about getting patient consent in general. A study led by Dr. Ubel found that medical students who had completed an ob.gyn. clerkship thought getting patients’ consent was significantly less important than those who had not completed that clerkship.
 

Why give pelvic exams to anesthetized women?

Despite the controversy, a number of medical educators continue to direct medical students to perform pelvic exams on anesthetized women. Why is that?

“Pelvic exams are not easy to do,” Dr. Hammoud said. “Learners need to keep working on them; they have to do a lot of them in order to do them well.”

To teach pelvic exams, most medical schools provide standardized patients – paid volunteers who submit to exams and critique the medical student’s work afterwards – but these encounters are limited because of their cost, says Guy Benrubi, MD, professor and emeritus chair of the department of obstetrics and gynecology at the University of Florida, Jacksonville.

He said teaching programs therefore need to supplement exams on standardized patients with exams on unpaid volunteers who provide consent. Programs prefer anesthetized patients, Dr. Benrubi said, because they are easier for novices to work on. “With patients under anesthesia, the muscles are relaxed and it’s easier for learners to detect organs. All the same, you need to get consent.”
 

Teaching institutions stiffen consent requirements

Faced with growing opposition to pelvic exams without consent, teaching institutions as well as gynecologic educators have recently been tightening their policies.

Dr. Hammoud said she has always informed patients orally about the possibility of medical students performing pelvic exams on them, but now some institutions, including her own, want a more involved process. The university recently began consent in writing for pelvic exams.

In addition, the university also now requires that medical students meet patients before performing pelvic exams and that teaching physicians explain the students’ involvement.

Dr. Hammoud said some institutions now require a separate consent form for pelvic exams, but the University of Michigan simply directs that the possibility of the patient getting a pelvic exam be part of the consent form.

This requirement, called “explicit consent,” was endorsed by APGO. It differs from having a separate consent form for pelvic exams, which would highlight the possibility of a pelvic exam, as many women’s rights activists are calling for.

Why not have a separate form? Dr. Hammoud is concerned that it would unnecessarily alarm patients. “When you point out a certain issue, you’re in effect saying to the patient that this is not normal,” she said, noting that, when asked for consent to do the exams, most women agree to it.
 

New wave of state laws prompted by renewed concerns

Dr. Hammoud thinks the laws are unnecessary. “These laws are excessive for the vast majority of physicians who practice ethically. The profession should come up with its own standards rather than having a plethora of laws.”

Several of the more recent laws have a broader scope than the original laws. The original laws simply state that medical students or physicians must get informed consent, but they did not stipulate how informed consent should be obtained. (The laws also typically prohibit pelvic exams when surgery will be in a different area of the body.)

The new laws often follow this format, but some go well beyond it. Some also apply to rectal exams (Maine and Maryland), to men as well as women (Utah and Maryland) requires separate consent (Utah), and require consent for all pelvic exams (Florida). 
 

The struggle over Florida’s law

The original Florida bill was drafted in 2019 by state Sen. Lauren Book, a Democrat who is a victims’ rights advocate working with women who have undergone sexual trauma. In written comments for this article, she says not getting consent for pelvic exams is still going on.

“This disturbing practice is commonplace at medical schools and teaching hospitals across the country – including several Florida universities, based on accounts from current and former medical students and faculty,” Sen. Book stated. “At best, these exams have been wrongful learning experiences for medical students or at worst, the equivalent of a sexual assault.”

Dr. Ubel took exception to linking the teaching activities to sexual assault. “I understand why many women would be horrified by this practice, but it’s not as bad as it seems,” he said. “There is nothing sexual or prurient about these exams, and they are motivated purely by a desire to teach people to be better doctors. That said, patients have the right to say, ‘I don’t want it done to me.’ ” 

In early 2020, Dr. Benrubi was part of a coalition of medical groups that was trying to influence Sen. Book’s bill as it went through the legislature. Sen. Book’s original bill was relatively mild, “but then, late in the process, it was changed into a more sweeping bill with some unclear language,” he said.

The final version was passed and signed into law by Gov. Ron DeSantis, a conservative Republican, in June.

Dr. Benrubi said that a large number of state legislators, including Sen. Book, have been agreeable to fixing the bill. This was supposed to happen in a special session in the fall, but that never materialized, and so the fix will have to wait until the regular session in early 2021.

“The law should not apply to patients undergoing routine pelvic exams,” Dr. Benrubi said. “It should only apply to women patients under anesthesia.”

But while organized medicine wants to walk back the law, Dr. Book wants to expand it. “This upcoming session, I look forward to working with physicians to continue to hone this new law, and to work toward inclusion for males. Everyone has a right to consent.”

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

The practice of medical students giving unconsented pelvic exams to women patients under anesthesia seems to be continuing, although recent new laws aim to change the situation.

“When I was doing ob.gyn. as a med student, the attending would have me do a pelvic right after the patient was under and before we started surgery,” said one participant in an online forum. “We didn’t exactly get permission but it was for teaching purposes.”

Yet others don’t see what the commotion is about. “There are a hundred things that are done during a surgery that don’t require your specific consent (some of them much more ‘humiliating’ than a pelvic exam). ... There’s not really much left to be shy about during a gyn/rectal/prostate surgery, let me put it that way,” one doctor wrote.

However, many physicians are adamantly opposed to the practice, and laws intended to stop or limit it are being enacted throughout the nation.
 

Renewed concerns have prompted new state laws

A few states have required consent for pelvic exams for many years, beginning with California in 2003. But up until 2019, providing pelvic exams without informed consent was illegal in only six states.

Continuing reports of unauthorized pelvic exams indicate that the practice has not disappeared. University of Michigan professor Maya M. Hammoud, MD, past president of the Association of Professors of Gynecology and Obstetrics, and many others attribute renewed interest in the issue to a 2018 article in the journal Bioethics by Phoebe Friesen, a medical ethicist at McGill University, Montreal, that laid out the ethical arguments against the practice.

Starting in 2019, an outpouring of new state bills have been introduced, and nine more states have passed laws. In addition, 14 other states considered similar bills but did not pass them, in some cases because teaching institutions argued that they were already dealing with the issue. This happened in Connecticut and Massachusetts, after representatives of Yale University, New Haven, Conn., met with legislators.

Laws against the practice have been passed by 15 states, including California, Florida, Illinois, and New York. Some teaching institutions have recently been clamping down on the practice, while many teaching physicians insist that at this point, it has all but ended.
 

A practice that may still continue

For many years, ethicists, women’s rights groups, state legislators, and organized medicine have been trying to eliminate the practice of unauthorized pelvic exams by medical students. Several key medical groups have come out against it, including the American Medical Association, the Association of American Medical Colleges, and the American College of Obstetricians and Gynecologists.

“Fifteen years ago, studies found a substantial number of cases, but my sense is that most of that has stopped,” said Dr. Hammoud. 

Yet despite these changes, there are some disturbing signs that the practice persists.

“I don’t have data, but anecdotally I see it still going on,” said Peter Ubel, MD, a professor at Duke University, Durham, N.C., who was involved in one of those early studies. “Every so often when I’m making a speech, a medical student tells me about performing a pelvic exam without getting permission.

“Perhaps in some cases the attending [physician] did get permission and didn’t tell the medical student, but that would also be a problem,” Dr. Ubel said. “The medical student should be informed that permission was given. This helps them be sensitive to the need to get consent.”

In a 2019 survey of medical students, 92% said they performed a pelvic exam on an anesthetized female patient, and of those, 61% did so without explicit patient consent.

The survey – involving 101 medical students at seven U.S. medical schools – also found that 11% of the medical students said they were extremely uncomfortable with the practice. But nearly one-third of the medical students said that opting out might jeopardize their grades and future careers.

“I tried to opt out once from doing a pelvic exam when I hadn’t met the patient beforehand,” one of them wrote. “The resident told me no.”
 

Some physicians defend the practice

Why do many medical students and doctors think that getting consent for pelvic exams is not necessary?

Some argue that patients implicitly give consent when they walk through the doors of a teaching hospital. “Sorry, but you inherently agree to that when you’re seen in an academic teaching hospital,” wrote one participant in a Student Doctor Network forum. “You agree to have residents and medical students participate in your care, not just an attending. If you just want an attending, then you are free to go to a nonteaching hospital. That’s the deal.”

Others argued that since the anesthetized patient couldn’t feel what was going on, it shouldn’t matter. “Things like pelvic exams, rectal exams, or even heroic trauma surgery occur for training purposes when there is no memory, no sensation and no harm to be done [and] society gains a better practitioner of the art of medicine,” a physician in Columbus, Ohio, wrote on Quora, an online forum.

Some doctors argue that they don’t ask for specific consent when they touch a variety of other body parts, and pelvic exams should be no different. Pelvic exams are needed before surgery of the pelvic area, but they have also been given to women undergoing surgery in a different part of the body.

In 2019 a woman told Deseret News in Utah that she had been recovering from stomach surgery when a resident physician mentioned something she had noticed “when we looked at your cervix.” When she asked why the physician had examined her cervix to prepare for stomach surgery, “no one could give her a good answer.”
 

A ‘positive goal’ doesn’t make it okay

What is missing in many defenses of the practice is any recognition that genitals are the most intimate part of the body, and that a patient’s desire for privacy ought to come first. In a survey of women undergoing gynecologic surgery, 72% expected to be asked for consent before medical students undertook pelvic examinations under anesthesia.

Overruling patients’ concerns about their own privacy is unethical, said Eli Y. Adashi, MD, professor of medical science and former dean of medicine and biological sciences at Brown University, Providence, R.I.

Dr. Adashi said the principle of patient autonomy in medical ethics directs that patients must be involved in decision-making about their care – even when caretakers are pursuing a positive goal, such as helping to educate future doctors.

“Conducting pelvic exams on unconscious women without their specific consent is simply untenable and never has been tenable, and it ought to be discontinued if it hasn’t been already,” says Dr. Adashi, who wrote an opinion piece on the issue for JAMA.

Furthermore, it has been shown that ignoring the need to get consent for pelvic exams makes physicians less concerned about getting patient consent in general. A study led by Dr. Ubel found that medical students who had completed an ob.gyn. clerkship thought getting patients’ consent was significantly less important than those who had not completed that clerkship.
 

Why give pelvic exams to anesthetized women?

Despite the controversy, a number of medical educators continue to direct medical students to perform pelvic exams on anesthetized women. Why is that?

“Pelvic exams are not easy to do,” Dr. Hammoud said. “Learners need to keep working on them; they have to do a lot of them in order to do them well.”

To teach pelvic exams, most medical schools provide standardized patients – paid volunteers who submit to exams and critique the medical student’s work afterwards – but these encounters are limited because of their cost, says Guy Benrubi, MD, professor and emeritus chair of the department of obstetrics and gynecology at the University of Florida, Jacksonville.

He said teaching programs therefore need to supplement exams on standardized patients with exams on unpaid volunteers who provide consent. Programs prefer anesthetized patients, Dr. Benrubi said, because they are easier for novices to work on. “With patients under anesthesia, the muscles are relaxed and it’s easier for learners to detect organs. All the same, you need to get consent.”
 

Teaching institutions stiffen consent requirements

Faced with growing opposition to pelvic exams without consent, teaching institutions as well as gynecologic educators have recently been tightening their policies.

Dr. Hammoud said she has always informed patients orally about the possibility of medical students performing pelvic exams on them, but now some institutions, including her own, want a more involved process. The university recently began consent in writing for pelvic exams.

In addition, the university also now requires that medical students meet patients before performing pelvic exams and that teaching physicians explain the students’ involvement.

Dr. Hammoud said some institutions now require a separate consent form for pelvic exams, but the University of Michigan simply directs that the possibility of the patient getting a pelvic exam be part of the consent form.

This requirement, called “explicit consent,” was endorsed by APGO. It differs from having a separate consent form for pelvic exams, which would highlight the possibility of a pelvic exam, as many women’s rights activists are calling for.

Why not have a separate form? Dr. Hammoud is concerned that it would unnecessarily alarm patients. “When you point out a certain issue, you’re in effect saying to the patient that this is not normal,” she said, noting that, when asked for consent to do the exams, most women agree to it.
 

New wave of state laws prompted by renewed concerns

Dr. Hammoud thinks the laws are unnecessary. “These laws are excessive for the vast majority of physicians who practice ethically. The profession should come up with its own standards rather than having a plethora of laws.”

Several of the more recent laws have a broader scope than the original laws. The original laws simply state that medical students or physicians must get informed consent, but they did not stipulate how informed consent should be obtained. (The laws also typically prohibit pelvic exams when surgery will be in a different area of the body.)

The new laws often follow this format, but some go well beyond it. Some also apply to rectal exams (Maine and Maryland), to men as well as women (Utah and Maryland) requires separate consent (Utah), and require consent for all pelvic exams (Florida). 
 

The struggle over Florida’s law

The original Florida bill was drafted in 2019 by state Sen. Lauren Book, a Democrat who is a victims’ rights advocate working with women who have undergone sexual trauma. In written comments for this article, she says not getting consent for pelvic exams is still going on.

“This disturbing practice is commonplace at medical schools and teaching hospitals across the country – including several Florida universities, based on accounts from current and former medical students and faculty,” Sen. Book stated. “At best, these exams have been wrongful learning experiences for medical students or at worst, the equivalent of a sexual assault.”

Dr. Ubel took exception to linking the teaching activities to sexual assault. “I understand why many women would be horrified by this practice, but it’s not as bad as it seems,” he said. “There is nothing sexual or prurient about these exams, and they are motivated purely by a desire to teach people to be better doctors. That said, patients have the right to say, ‘I don’t want it done to me.’ ” 

In early 2020, Dr. Benrubi was part of a coalition of medical groups that was trying to influence Sen. Book’s bill as it went through the legislature. Sen. Book’s original bill was relatively mild, “but then, late in the process, it was changed into a more sweeping bill with some unclear language,” he said.

The final version was passed and signed into law by Gov. Ron DeSantis, a conservative Republican, in June.

Dr. Benrubi said that a large number of state legislators, including Sen. Book, have been agreeable to fixing the bill. This was supposed to happen in a special session in the fall, but that never materialized, and so the fix will have to wait until the regular session in early 2021.

“The law should not apply to patients undergoing routine pelvic exams,” Dr. Benrubi said. “It should only apply to women patients under anesthesia.”

But while organized medicine wants to walk back the law, Dr. Book wants to expand it. “This upcoming session, I look forward to working with physicians to continue to hone this new law, and to work toward inclusion for males. Everyone has a right to consent.”

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