Women's Health

Women opt for sterilization for a variety of reasons, but the goal is the same: to avoid getting pregnant.

But a head-to-head study of two forms of female sterilization has found surprisingly high rates of failure with the procedures.

The study compared the effectiveness of hysteroscopic sterilization, a nonincisional procedure, and minimally invasive laparoscopic sterilization. Although both methods prevented pregnancy in the vast majority of women, each was associated with more than a 6% failure rate 5 years after the procedure.

That figure is “much higher than expected,” said Aileen Gariepy, MD, MPH, the director of complex family planning at Weill Cornell Medicine, New York, who led the study.

The American College of Obstetricians and Gynecologists reported that the chance of pregnancy after sterilization is less than 1%, Dr. Gariepy said. “Women and pregnancy-capable people considering sterilization should be informed that, after the procedure, they have at least a 6% – not 1% – chance of pregnancy in the next 5 years.”

The study was published in Fertility and Sterility.

For laparoscopic sterilization, surgeons close or sever the fallopian tubes to prevent eggs from reaching the uterus and becoming fertilized.

Hysteroscopic sterilization involves the implantation of small, flexible metal coils into each fallopian tube, a process that produces inflammation and scarring that in turn prevents pregnancy. This method, called Essure and formerly marketed by Bayer, received approval by the Food and Drug Administration in 2002. But the agency received thousands of reports of adverse events with Essure, prompting regulators in 2016 to add a boxed warning to the product label about the risk for adverse events, including perforation, migration of the coils, allergic reactions, and pain.

Bayer pulled Essure from the market in 2019, citing decreased sales of the product. Some women did not have the device removed, however, and questions remain about its effectiveness, according to the researchers.

In the new study, Dr. Gariepy and colleagues examined Medicaid claims for 5906 hysteroscopic and 23,965 laparoscopic sterilizations performed in California between 2008 and 2014. They excluded sterilizations that were performed immediately after delivery, which involve a different approach.

The average age of the women in the study was 33 years.

The study found that, 5 years after the sterilization procedure, 6% of women in either group had become pregnant.

Despite the surprising new data, Chailee Moss, MD, an assistant professor of gynecology and obstetrics at Johns Hopkins University Medical Center, Baltimore, said she did not think the study would significantly affect the way she counsels her patients.

The main reason, she said, is that the study relied on an analysis of medical claims, which “is likely inferior to careful review of individual patient records or prospective collection of clinical data.” Home pregnancy tests may easily be excluded from such data and that patients can undergo ultrasound and termination procedures that would likely not be included in the data the researchers analyzed.

Dr. Moss added that the study was limited to California and that the researchers could not determine pregnancy rates for women who moved out of the state and thus received pregnancy care elsewhere. Nor did the authors account for the use of assistive reproductive technology, which can facilitate pregnancy after sterilization despite the success of the original procedure.

Dr. Gariepy, however, said the study may in fact have undercounted pregnancies and that the failure rates might be even higher than 6%, noting that California is “one of the largest, most populous and most diverse states” in terms of race, ethnicity, and other factors, making the new findings highly generalizable.

“I agree that study results should be confirmed by new nationwide study to determine risk of pregnancy after different sterilization methods,” she said. “Nevertheless, this retrospective cohort study delivers a strong signal that doctors and patients need to know about.”

Dr. Gariepy is on the board of directors of the Society of Family Planning. Dr. Moss has received research funding from Merck.

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

Women opt for sterilization for a variety of reasons, but the goal is the same: to avoid getting pregnant.

But a head-to-head study of two forms of female sterilization has found surprisingly high rates of failure with the procedures.

The study compared the effectiveness of hysteroscopic sterilization, a nonincisional procedure, and minimally invasive laparoscopic sterilization. Although both methods prevented pregnancy in the vast majority of women, each was associated with more than a 6% failure rate 5 years after the procedure.

That figure is “much higher than expected,” said Aileen Gariepy, MD, MPH, the director of complex family planning at Weill Cornell Medicine, New York, who led the study.

The American College of Obstetricians and Gynecologists reported that the chance of pregnancy after sterilization is less than 1%, Dr. Gariepy said. “Women and pregnancy-capable people considering sterilization should be informed that, after the procedure, they have at least a 6% – not 1% – chance of pregnancy in the next 5 years.”

The study was published in Fertility and Sterility.

For laparoscopic sterilization, surgeons close or sever the fallopian tubes to prevent eggs from reaching the uterus and becoming fertilized.

Hysteroscopic sterilization involves the implantation of small, flexible metal coils into each fallopian tube, a process that produces inflammation and scarring that in turn prevents pregnancy. This method, called Essure and formerly marketed by Bayer, received approval by the Food and Drug Administration in 2002. But the agency received thousands of reports of adverse events with Essure, prompting regulators in 2016 to add a boxed warning to the product label about the risk for adverse events, including perforation, migration of the coils, allergic reactions, and pain.

Bayer pulled Essure from the market in 2019, citing decreased sales of the product. Some women did not have the device removed, however, and questions remain about its effectiveness, according to the researchers.

In the new study, Dr. Gariepy and colleagues examined Medicaid claims for 5906 hysteroscopic and 23,965 laparoscopic sterilizations performed in California between 2008 and 2014. They excluded sterilizations that were performed immediately after delivery, which involve a different approach.

The average age of the women in the study was 33 years.

The study found that, 5 years after the sterilization procedure, 6% of women in either group had become pregnant.

Despite the surprising new data, Chailee Moss, MD, an assistant professor of gynecology and obstetrics at Johns Hopkins University Medical Center, Baltimore, said she did not think the study would significantly affect the way she counsels her patients.

The main reason, she said, is that the study relied on an analysis of medical claims, which “is likely inferior to careful review of individual patient records or prospective collection of clinical data.” Home pregnancy tests may easily be excluded from such data and that patients can undergo ultrasound and termination procedures that would likely not be included in the data the researchers analyzed.

Dr. Moss added that the study was limited to California and that the researchers could not determine pregnancy rates for women who moved out of the state and thus received pregnancy care elsewhere. Nor did the authors account for the use of assistive reproductive technology, which can facilitate pregnancy after sterilization despite the success of the original procedure.

Dr. Gariepy, however, said the study may in fact have undercounted pregnancies and that the failure rates might be even higher than 6%, noting that California is “one of the largest, most populous and most diverse states” in terms of race, ethnicity, and other factors, making the new findings highly generalizable.

“I agree that study results should be confirmed by new nationwide study to determine risk of pregnancy after different sterilization methods,” she said. “Nevertheless, this retrospective cohort study delivers a strong signal that doctors and patients need to know about.”

Dr. Gariepy is on the board of directors of the Society of Family Planning. Dr. Moss has received research funding from Merck.

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

Women opt for sterilization for a variety of reasons, but the goal is the same: to avoid getting pregnant.

But a head-to-head study of two forms of female sterilization has found surprisingly high rates of failure with the procedures.

The study compared the effectiveness of hysteroscopic sterilization, a nonincisional procedure, and minimally invasive laparoscopic sterilization. Although both methods prevented pregnancy in the vast majority of women, each was associated with more than a 6% failure rate 5 years after the procedure.

That figure is “much higher than expected,” said Aileen Gariepy, MD, MPH, the director of complex family planning at Weill Cornell Medicine, New York, who led the study.

The American College of Obstetricians and Gynecologists reported that the chance of pregnancy after sterilization is less than 1%, Dr. Gariepy said. “Women and pregnancy-capable people considering sterilization should be informed that, after the procedure, they have at least a 6% – not 1% – chance of pregnancy in the next 5 years.”

The study was published in Fertility and Sterility.

For laparoscopic sterilization, surgeons close or sever the fallopian tubes to prevent eggs from reaching the uterus and becoming fertilized.

Hysteroscopic sterilization involves the implantation of small, flexible metal coils into each fallopian tube, a process that produces inflammation and scarring that in turn prevents pregnancy. This method, called Essure and formerly marketed by Bayer, received approval by the Food and Drug Administration in 2002. But the agency received thousands of reports of adverse events with Essure, prompting regulators in 2016 to add a boxed warning to the product label about the risk for adverse events, including perforation, migration of the coils, allergic reactions, and pain.

Bayer pulled Essure from the market in 2019, citing decreased sales of the product. Some women did not have the device removed, however, and questions remain about its effectiveness, according to the researchers.

In the new study, Dr. Gariepy and colleagues examined Medicaid claims for 5906 hysteroscopic and 23,965 laparoscopic sterilizations performed in California between 2008 and 2014. They excluded sterilizations that were performed immediately after delivery, which involve a different approach.

The average age of the women in the study was 33 years.

The study found that, 5 years after the sterilization procedure, 6% of women in either group had become pregnant.

Despite the surprising new data, Chailee Moss, MD, an assistant professor of gynecology and obstetrics at Johns Hopkins University Medical Center, Baltimore, said she did not think the study would significantly affect the way she counsels her patients.

The main reason, she said, is that the study relied on an analysis of medical claims, which “is likely inferior to careful review of individual patient records or prospective collection of clinical data.” Home pregnancy tests may easily be excluded from such data and that patients can undergo ultrasound and termination procedures that would likely not be included in the data the researchers analyzed.

Dr. Moss added that the study was limited to California and that the researchers could not determine pregnancy rates for women who moved out of the state and thus received pregnancy care elsewhere. Nor did the authors account for the use of assistive reproductive technology, which can facilitate pregnancy after sterilization despite the success of the original procedure.

Dr. Gariepy, however, said the study may in fact have undercounted pregnancies and that the failure rates might be even higher than 6%, noting that California is “one of the largest, most populous and most diverse states” in terms of race, ethnicity, and other factors, making the new findings highly generalizable.

“I agree that study results should be confirmed by new nationwide study to determine risk of pregnancy after different sterilization methods,” she said. “Nevertheless, this retrospective cohort study delivers a strong signal that doctors and patients need to know about.”

Dr. Gariepy is on the board of directors of the Society of Family Planning. Dr. Moss has received research funding from Merck.

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

A new blood test performed in the second trimester could help identify pregnancies at risk of early and very early spontaneous preterm birth (sPTB), based on a prospective cohort trial.

The cell-free RNA (cfRNA) profiling tool could guide patient and provider decision-making, while the underlying research illuminates biological pathways that may facilitate novel interventions, reported lead author Joan Camunas-Soler, PhD, of Mirvie, South San Francisco, and colleagues.

“Given the complex etiology of this heterogeneous syndrome, it would be advantageous to develop predictive tests that provide insight on the specific pathophysiology leading to preterm birth for each particular pregnancy,” Dr. Camunas-Soler and colleagues wrote in the American Journal of Obstetrics and Gynecology. “Such an approach could inform the development of preventive treatments and targeted therapeutics that are currently lacking/difficult to implement due to the heterogeneous etiology of sPTB.”

Currently, the best predictor of sPTB is previous sPTB, according to the investigators. Although a combination approach that incorporates cervical length and fetal fibronectin in cervicovaginal fluid is “of use,” they noted, “this is not standard of care in the U.S.A. nor recommended by the American College of Obstetricians and Gynecologists or the Society for Maternal-Fetal Medicine.” Existing molecular tests lack clinical data and may be inaccurate across diverse patient populations, they added.

The present study aimed to address these shortcomings by creating a second-trimester blood test for predicting sPTB. To identify relevant biomarkers, the investigators compared RNA profiles that were differentially expressed in three types of cases: term birth, early sPTB, and very early sPTB.

Among 242 women who contributed second-trimester blood samples for analysis, 194 went on to have a term birth. Of the remaining 48 women who gave birth spontaneously before 35 weeks’ gestation, 32 delivered between 25 and 35 weeks (early sPTB), while 16 delivered before 25 weeks’ gestation (very early sPTB). Slightly more than half of the patients were White, about one-third were Black, approximately 10% were Asian, and the remainder were of unknown race/ethnicity. Cases of preeclampsia were excluded.

The gene discovery and modeling process revealed 25 distinct genes that were significantly associated with early sPTB, offering a risk model with a sensitivity of 76% and a specificity of 72% (area under the curve, 0.80; 95% confidence interval, 0.72-0.87). Very early sPTB was associated with a set of 39 genes, giving a model with a sensitivity of 64% and a specificity of 80% (area under the curve = 0.76; 95% CI, 0.63-0.87).

Characterization of the two RNA profiles offered a glimpse into the underlying biological processes driving preterm birth. The genes predicting early sPTB are largely responsible for extracellular matrix degradation and remodeling, which could, “in terms of mechanism, reflect ongoing processes associated with cervical shortening, a feature often detected some weeks prior to sPTB,” the investigators wrote. In contrast, genes associated with very early sPTB are linked with insulinlike growth factor transport, which drives fetal growth and placentation. These findings could lead to development of pathway-specific interventions, Dr. Camunas-Soler and colleagues suggested.

According to coauthor Michal A. Elovitz, MD, the Hilarie L. Morgan and Mitchell L. Morgan President’s Distinguished Professor in Women’s Health at the University of Pennsylvania, Philadelphia, and chief medical advisor at Mirvie, the proprietary RNA platform moves beyond “unreliable and at times biased clinical factors such as race, BMI, and maternal age” to offer a “precision-based approach to pregnancy health.”

Excluding traditional risk factors also “promises more equitable care than the use of broad sociodemographic factors that often result in bias,” she added, noting that this may help address the higher rate of pregnancy complications among Black patients.

When asked about the potential for false-positive results, considering reported specificity rates of 72%-80%, Dr. Elovitz suggested that such concerns among pregnant women are an “unfortunate misconception.”

“It is not reflective of what women want regarding knowledge about the health of their pregnancy,” she said in a written comment. “Rather than be left in the dark, women want to be prepared for what is to come in their pregnancy journey.”

In support of this statement, Dr. Elovitz cited a recent study involving women with preeclampsia and other hypertensive disorders in pregnancy. A questionnaire showed that women appreciated pregnancy risk models when making decisions, and reported that they would have greater peace of mind if such tests were available.

*This story was updated on 4/26/2022. 

A new blood test performed in the second trimester could help identify pregnancies at risk of early and very early spontaneous preterm birth (sPTB), based on a prospective cohort trial.

The cell-free RNA (cfRNA) profiling tool could guide patient and provider decision-making, while the underlying research illuminates biological pathways that may facilitate novel interventions, reported lead author Joan Camunas-Soler, PhD, of Mirvie, South San Francisco, and colleagues.

“Given the complex etiology of this heterogeneous syndrome, it would be advantageous to develop predictive tests that provide insight on the specific pathophysiology leading to preterm birth for each particular pregnancy,” Dr. Camunas-Soler and colleagues wrote in the American Journal of Obstetrics and Gynecology. “Such an approach could inform the development of preventive treatments and targeted therapeutics that are currently lacking/difficult to implement due to the heterogeneous etiology of sPTB.”

Currently, the best predictor of sPTB is previous sPTB, according to the investigators. Although a combination approach that incorporates cervical length and fetal fibronectin in cervicovaginal fluid is “of use,” they noted, “this is not standard of care in the U.S.A. nor recommended by the American College of Obstetricians and Gynecologists or the Society for Maternal-Fetal Medicine.” Existing molecular tests lack clinical data and may be inaccurate across diverse patient populations, they added.

The present study aimed to address these shortcomings by creating a second-trimester blood test for predicting sPTB. To identify relevant biomarkers, the investigators compared RNA profiles that were differentially expressed in three types of cases: term birth, early sPTB, and very early sPTB.

Among 242 women who contributed second-trimester blood samples for analysis, 194 went on to have a term birth. Of the remaining 48 women who gave birth spontaneously before 35 weeks’ gestation, 32 delivered between 25 and 35 weeks (early sPTB), while 16 delivered before 25 weeks’ gestation (very early sPTB). Slightly more than half of the patients were White, about one-third were Black, approximately 10% were Asian, and the remainder were of unknown race/ethnicity. Cases of preeclampsia were excluded.

The gene discovery and modeling process revealed 25 distinct genes that were significantly associated with early sPTB, offering a risk model with a sensitivity of 76% and a specificity of 72% (area under the curve, 0.80; 95% confidence interval, 0.72-0.87). Very early sPTB was associated with a set of 39 genes, giving a model with a sensitivity of 64% and a specificity of 80% (area under the curve = 0.76; 95% CI, 0.63-0.87).

Characterization of the two RNA profiles offered a glimpse into the underlying biological processes driving preterm birth. The genes predicting early sPTB are largely responsible for extracellular matrix degradation and remodeling, which could, “in terms of mechanism, reflect ongoing processes associated with cervical shortening, a feature often detected some weeks prior to sPTB,” the investigators wrote. In contrast, genes associated with very early sPTB are linked with insulinlike growth factor transport, which drives fetal growth and placentation. These findings could lead to development of pathway-specific interventions, Dr. Camunas-Soler and colleagues suggested.

According to coauthor Michal A. Elovitz, MD, the Hilarie L. Morgan and Mitchell L. Morgan President’s Distinguished Professor in Women’s Health at the University of Pennsylvania, Philadelphia, and chief medical advisor at Mirvie, the proprietary RNA platform moves beyond “unreliable and at times biased clinical factors such as race, BMI, and maternal age” to offer a “precision-based approach to pregnancy health.”

Excluding traditional risk factors also “promises more equitable care than the use of broad sociodemographic factors that often result in bias,” she added, noting that this may help address the higher rate of pregnancy complications among Black patients.

When asked about the potential for false-positive results, considering reported specificity rates of 72%-80%, Dr. Elovitz suggested that such concerns among pregnant women are an “unfortunate misconception.”

“It is not reflective of what women want regarding knowledge about the health of their pregnancy,” she said in a written comment. “Rather than be left in the dark, women want to be prepared for what is to come in their pregnancy journey.”

In support of this statement, Dr. Elovitz cited a recent study involving women with preeclampsia and other hypertensive disorders in pregnancy. A questionnaire showed that women appreciated pregnancy risk models when making decisions, and reported that they would have greater peace of mind if such tests were available.

*This story was updated on 4/26/2022. 

A new blood test performed in the second trimester could help identify pregnancies at risk of early and very early spontaneous preterm birth (sPTB), based on a prospective cohort trial.

The cell-free RNA (cfRNA) profiling tool could guide patient and provider decision-making, while the underlying research illuminates biological pathways that may facilitate novel interventions, reported lead author Joan Camunas-Soler, PhD, of Mirvie, South San Francisco, and colleagues.

“Given the complex etiology of this heterogeneous syndrome, it would be advantageous to develop predictive tests that provide insight on the specific pathophysiology leading to preterm birth for each particular pregnancy,” Dr. Camunas-Soler and colleagues wrote in the American Journal of Obstetrics and Gynecology. “Such an approach could inform the development of preventive treatments and targeted therapeutics that are currently lacking/difficult to implement due to the heterogeneous etiology of sPTB.”

Currently, the best predictor of sPTB is previous sPTB, according to the investigators. Although a combination approach that incorporates cervical length and fetal fibronectin in cervicovaginal fluid is “of use,” they noted, “this is not standard of care in the U.S.A. nor recommended by the American College of Obstetricians and Gynecologists or the Society for Maternal-Fetal Medicine.” Existing molecular tests lack clinical data and may be inaccurate across diverse patient populations, they added.

The present study aimed to address these shortcomings by creating a second-trimester blood test for predicting sPTB. To identify relevant biomarkers, the investigators compared RNA profiles that were differentially expressed in three types of cases: term birth, early sPTB, and very early sPTB.

Among 242 women who contributed second-trimester blood samples for analysis, 194 went on to have a term birth. Of the remaining 48 women who gave birth spontaneously before 35 weeks’ gestation, 32 delivered between 25 and 35 weeks (early sPTB), while 16 delivered before 25 weeks’ gestation (very early sPTB). Slightly more than half of the patients were White, about one-third were Black, approximately 10% were Asian, and the remainder were of unknown race/ethnicity. Cases of preeclampsia were excluded.

The gene discovery and modeling process revealed 25 distinct genes that were significantly associated with early sPTB, offering a risk model with a sensitivity of 76% and a specificity of 72% (area under the curve, 0.80; 95% confidence interval, 0.72-0.87). Very early sPTB was associated with a set of 39 genes, giving a model with a sensitivity of 64% and a specificity of 80% (area under the curve = 0.76; 95% CI, 0.63-0.87).

Characterization of the two RNA profiles offered a glimpse into the underlying biological processes driving preterm birth. The genes predicting early sPTB are largely responsible for extracellular matrix degradation and remodeling, which could, “in terms of mechanism, reflect ongoing processes associated with cervical shortening, a feature often detected some weeks prior to sPTB,” the investigators wrote. In contrast, genes associated with very early sPTB are linked with insulinlike growth factor transport, which drives fetal growth and placentation. These findings could lead to development of pathway-specific interventions, Dr. Camunas-Soler and colleagues suggested.

According to coauthor Michal A. Elovitz, MD, the Hilarie L. Morgan and Mitchell L. Morgan President’s Distinguished Professor in Women’s Health at the University of Pennsylvania, Philadelphia, and chief medical advisor at Mirvie, the proprietary RNA platform moves beyond “unreliable and at times biased clinical factors such as race, BMI, and maternal age” to offer a “precision-based approach to pregnancy health.”

Excluding traditional risk factors also “promises more equitable care than the use of broad sociodemographic factors that often result in bias,” she added, noting that this may help address the higher rate of pregnancy complications among Black patients.

When asked about the potential for false-positive results, considering reported specificity rates of 72%-80%, Dr. Elovitz suggested that such concerns among pregnant women are an “unfortunate misconception.”

“It is not reflective of what women want regarding knowledge about the health of their pregnancy,” she said in a written comment. “Rather than be left in the dark, women want to be prepared for what is to come in their pregnancy journey.”

In support of this statement, Dr. Elovitz cited a recent study involving women with preeclampsia and other hypertensive disorders in pregnancy. A questionnaire showed that women appreciated pregnancy risk models when making decisions, and reported that they would have greater peace of mind if such tests were available.

*This story was updated on 4/26/2022. 

Pregnant women who had a higher adherence to a Mediterranean-style diet had a lower risk of preeclampsia, according to the results of a new study.

“As an observational study, it obviously has limitations that need to be considered, but these results build on other evidence that Mediterranean diet reduces cardiovascular risk and extends those findings to pregnancy as preeclampsia is a cardiovascular outcome,” senior author Noel T. Mueller, PhD, associate professor at Johns Hopkins Bloomberg School of Public Health, Baltimore, said in an interview.

The study was published online April 20 in the Journal of the American Heart Association.

The authors noted that preeclampsia, characterized by a range of symptoms including hypertension, proteinuria, and end-organ dysfunction, is a disorder that occurs in up to 5%-10% of all pregnant women worldwide, and is more common in Black women. It is a major cause of maternal and fetal morbidity and raises the risk for long-term cardiovascular disease (CVD), including chronic hypertension, coronary artery disease, ischemic stroke, and heart failure.

Children born to mothers with preeclampsia are at an elevated risk of having higher blood pressure and other abnormal cardiometabolic parameters.

The authors noted that multiple studies have demonstrated the benefit of the Mediterranean diet – characterized primarily by high intake of vegetables, fruits, and unsaturated fats – in reducing cardiovascular risk in the nonpregnant population. The current study was conducted to investigate whether benefits could also be seen in pregnant women in the form of a reduced risk of preeclampsia.

For the study, which used data from the Boston Birth Cohort, maternal sociodemographic and dietary data were obtained from 8,507 women via interview and food frequency questionnaire within 24-72 hours of giving birth. A Mediterranean-style diet score was calculated from the food frequency questionnaire. Additional clinical information, including physician diagnoses of preexisting conditions and preeclampsia, were extracted from medical records.

Of the women in the sample, 848 developed preeclampsia, of whom 47% were Black, and 28% were Hispanic.

After multivariable adjustment, the greatest adherence to a Mediterranean-style diet was associated with lower odds of developing preeclampsia (adjusted odds ratio comparing tertile 3 to tertile 1, 0.78; 95% confidence interval [CI], 0.64-0.96).

A subgroup analysis of Black women demonstrated a similar benefit with an adjusted odds ratio comparing tertile 3 to tertile 1 of 0.74 (95% CI, 0.76-0.96).

“In this racially and ethnically diverse cohort, women who had greater adherence to a Mediterranean-style diet during pregnancy had a greater than 20% lower odds of developing preeclampsia, after [adjustment] for potential confounders. In addition, the evidence for the protective effect of a Mediterranean-style diet against the odds of developing preeclampsia remained present in a subgroup analysis of Black women,” the researchers concluded.

Asked whether this would be enough evidence to recommend a Mediterranean diet to pregnant women, Dr. Mueller said that the organizations that issue dietary guidelines would probably require replication of these results and also possibly a randomized trial in a diverse population group before advocating such a diet.

“That is something we would like to do but this will take time and money,” he added.

Lead study author Anum Minhas, MD, Johns Hopkins University, Baltimore, said that in the meantime she would be recommending a Mediterranean diet to her pregnant patients. 

“The Mediterranean diet is a very healthy way of eating. I can’t see any downside of following such a diet in pregnancy, especially for high-risk women – those with obesity, hypertension or gestational diabetes, and there are likely other potential benefits such as reduced weight gain and reduced gestational diabetes,” she said.  

Dr. Mueller said he appreciated this pragmatic approach. “Sometimes there can be hesitation on making recommendations from observational studies, but the alternative to recommending this diet is either no recommendations on diet or recommending an alternative diet,” he said. “The Mediterranean diet or the DASH diet, which is quite similar, have shown by far the most evidence of cardioprotection of any diets. They have been shown to reduce blood pressure and lipids and improve cardiovascular risk, and I think we can now assume that that likely extends to pregnancy. I feel comfortable for this diet to be recommended to pregnant women.”

But he added: “Having said that, there is still a need for a randomized trial in pregnancy. We think it works but until we have a randomized trial we won’t know for sure, and we won’t know how much of a benefit we can get.”

Commenting on the study, JoAnn Manson, MD, chief of the division of preventive medicine at Brigham and Women’s Hospital, Boston, pointed out that this type of observational study is important for hypothesis generation but cannot prove cause and effect relationships.

“The evidence is promising enough,” said Dr. Manson, who was not involved with this study. But she added that to move forward, a randomized trial in women at elevated risk of preeclampsia would be needed, beginning in early pregnancy, if not earlier.

“In the meantime,” she noted, “several large-scale cohorts could be leveraged to look at diet assessed before or during pregnancy to see if this dietary pattern is prospectively related to lower risk of preeclampsia.

“With additional supportive data, and in view of the diet’s safety and general cardiovascular benefits, it could become a major tool for preventing adverse pregnancy outcomes.”

The Boston Birth Cohort study was supported in part by grants from the March of Dimes, the National Institutes of Health, and the Health Resources and Services Administration of the U.S. Department of Health and Human Services. The authors have disclosed no relevant financial relationships.

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

Pregnant women who had a higher adherence to a Mediterranean-style diet had a lower risk of preeclampsia, according to the results of a new study.

“As an observational study, it obviously has limitations that need to be considered, but these results build on other evidence that Mediterranean diet reduces cardiovascular risk and extends those findings to pregnancy as preeclampsia is a cardiovascular outcome,” senior author Noel T. Mueller, PhD, associate professor at Johns Hopkins Bloomberg School of Public Health, Baltimore, said in an interview.

The study was published online April 20 in the Journal of the American Heart Association.

The authors noted that preeclampsia, characterized by a range of symptoms including hypertension, proteinuria, and end-organ dysfunction, is a disorder that occurs in up to 5%-10% of all pregnant women worldwide, and is more common in Black women. It is a major cause of maternal and fetal morbidity and raises the risk for long-term cardiovascular disease (CVD), including chronic hypertension, coronary artery disease, ischemic stroke, and heart failure.

Children born to mothers with preeclampsia are at an elevated risk of having higher blood pressure and other abnormal cardiometabolic parameters.

The authors noted that multiple studies have demonstrated the benefit of the Mediterranean diet – characterized primarily by high intake of vegetables, fruits, and unsaturated fats – in reducing cardiovascular risk in the nonpregnant population. The current study was conducted to investigate whether benefits could also be seen in pregnant women in the form of a reduced risk of preeclampsia.

For the study, which used data from the Boston Birth Cohort, maternal sociodemographic and dietary data were obtained from 8,507 women via interview and food frequency questionnaire within 24-72 hours of giving birth. A Mediterranean-style diet score was calculated from the food frequency questionnaire. Additional clinical information, including physician diagnoses of preexisting conditions and preeclampsia, were extracted from medical records.

Of the women in the sample, 848 developed preeclampsia, of whom 47% were Black, and 28% were Hispanic.

After multivariable adjustment, the greatest adherence to a Mediterranean-style diet was associated with lower odds of developing preeclampsia (adjusted odds ratio comparing tertile 3 to tertile 1, 0.78; 95% confidence interval [CI], 0.64-0.96).

A subgroup analysis of Black women demonstrated a similar benefit with an adjusted odds ratio comparing tertile 3 to tertile 1 of 0.74 (95% CI, 0.76-0.96).

“In this racially and ethnically diverse cohort, women who had greater adherence to a Mediterranean-style diet during pregnancy had a greater than 20% lower odds of developing preeclampsia, after [adjustment] for potential confounders. In addition, the evidence for the protective effect of a Mediterranean-style diet against the odds of developing preeclampsia remained present in a subgroup analysis of Black women,” the researchers concluded.

Asked whether this would be enough evidence to recommend a Mediterranean diet to pregnant women, Dr. Mueller said that the organizations that issue dietary guidelines would probably require replication of these results and also possibly a randomized trial in a diverse population group before advocating such a diet.

“That is something we would like to do but this will take time and money,” he added.

Lead study author Anum Minhas, MD, Johns Hopkins University, Baltimore, said that in the meantime she would be recommending a Mediterranean diet to her pregnant patients. 

“The Mediterranean diet is a very healthy way of eating. I can’t see any downside of following such a diet in pregnancy, especially for high-risk women – those with obesity, hypertension or gestational diabetes, and there are likely other potential benefits such as reduced weight gain and reduced gestational diabetes,” she said.  

Dr. Mueller said he appreciated this pragmatic approach. “Sometimes there can be hesitation on making recommendations from observational studies, but the alternative to recommending this diet is either no recommendations on diet or recommending an alternative diet,” he said. “The Mediterranean diet or the DASH diet, which is quite similar, have shown by far the most evidence of cardioprotection of any diets. They have been shown to reduce blood pressure and lipids and improve cardiovascular risk, and I think we can now assume that that likely extends to pregnancy. I feel comfortable for this diet to be recommended to pregnant women.”

But he added: “Having said that, there is still a need for a randomized trial in pregnancy. We think it works but until we have a randomized trial we won’t know for sure, and we won’t know how much of a benefit we can get.”

Commenting on the study, JoAnn Manson, MD, chief of the division of preventive medicine at Brigham and Women’s Hospital, Boston, pointed out that this type of observational study is important for hypothesis generation but cannot prove cause and effect relationships.

“The evidence is promising enough,” said Dr. Manson, who was not involved with this study. But she added that to move forward, a randomized trial in women at elevated risk of preeclampsia would be needed, beginning in early pregnancy, if not earlier.

“In the meantime,” she noted, “several large-scale cohorts could be leveraged to look at diet assessed before or during pregnancy to see if this dietary pattern is prospectively related to lower risk of preeclampsia.

“With additional supportive data, and in view of the diet’s safety and general cardiovascular benefits, it could become a major tool for preventing adverse pregnancy outcomes.”

The Boston Birth Cohort study was supported in part by grants from the March of Dimes, the National Institutes of Health, and the Health Resources and Services Administration of the U.S. Department of Health and Human Services. The authors have disclosed no relevant financial relationships.

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

Pregnant women who had a higher adherence to a Mediterranean-style diet had a lower risk of preeclampsia, according to the results of a new study.

“As an observational study, it obviously has limitations that need to be considered, but these results build on other evidence that Mediterranean diet reduces cardiovascular risk and extends those findings to pregnancy as preeclampsia is a cardiovascular outcome,” senior author Noel T. Mueller, PhD, associate professor at Johns Hopkins Bloomberg School of Public Health, Baltimore, said in an interview.

The study was published online April 20 in the Journal of the American Heart Association.

The authors noted that preeclampsia, characterized by a range of symptoms including hypertension, proteinuria, and end-organ dysfunction, is a disorder that occurs in up to 5%-10% of all pregnant women worldwide, and is more common in Black women. It is a major cause of maternal and fetal morbidity and raises the risk for long-term cardiovascular disease (CVD), including chronic hypertension, coronary artery disease, ischemic stroke, and heart failure.

Children born to mothers with preeclampsia are at an elevated risk of having higher blood pressure and other abnormal cardiometabolic parameters.

The authors noted that multiple studies have demonstrated the benefit of the Mediterranean diet – characterized primarily by high intake of vegetables, fruits, and unsaturated fats – in reducing cardiovascular risk in the nonpregnant population. The current study was conducted to investigate whether benefits could also be seen in pregnant women in the form of a reduced risk of preeclampsia.

For the study, which used data from the Boston Birth Cohort, maternal sociodemographic and dietary data were obtained from 8,507 women via interview and food frequency questionnaire within 24-72 hours of giving birth. A Mediterranean-style diet score was calculated from the food frequency questionnaire. Additional clinical information, including physician diagnoses of preexisting conditions and preeclampsia, were extracted from medical records.

Of the women in the sample, 848 developed preeclampsia, of whom 47% were Black, and 28% were Hispanic.

After multivariable adjustment, the greatest adherence to a Mediterranean-style diet was associated with lower odds of developing preeclampsia (adjusted odds ratio comparing tertile 3 to tertile 1, 0.78; 95% confidence interval [CI], 0.64-0.96).

A subgroup analysis of Black women demonstrated a similar benefit with an adjusted odds ratio comparing tertile 3 to tertile 1 of 0.74 (95% CI, 0.76-0.96).

“In this racially and ethnically diverse cohort, women who had greater adherence to a Mediterranean-style diet during pregnancy had a greater than 20% lower odds of developing preeclampsia, after [adjustment] for potential confounders. In addition, the evidence for the protective effect of a Mediterranean-style diet against the odds of developing preeclampsia remained present in a subgroup analysis of Black women,” the researchers concluded.

Asked whether this would be enough evidence to recommend a Mediterranean diet to pregnant women, Dr. Mueller said that the organizations that issue dietary guidelines would probably require replication of these results and also possibly a randomized trial in a diverse population group before advocating such a diet.

“That is something we would like to do but this will take time and money,” he added.

Lead study author Anum Minhas, MD, Johns Hopkins University, Baltimore, said that in the meantime she would be recommending a Mediterranean diet to her pregnant patients. 

“The Mediterranean diet is a very healthy way of eating. I can’t see any downside of following such a diet in pregnancy, especially for high-risk women – those with obesity, hypertension or gestational diabetes, and there are likely other potential benefits such as reduced weight gain and reduced gestational diabetes,” she said.  

Dr. Mueller said he appreciated this pragmatic approach. “Sometimes there can be hesitation on making recommendations from observational studies, but the alternative to recommending this diet is either no recommendations on diet or recommending an alternative diet,” he said. “The Mediterranean diet or the DASH diet, which is quite similar, have shown by far the most evidence of cardioprotection of any diets. They have been shown to reduce blood pressure and lipids and improve cardiovascular risk, and I think we can now assume that that likely extends to pregnancy. I feel comfortable for this diet to be recommended to pregnant women.”

But he added: “Having said that, there is still a need for a randomized trial in pregnancy. We think it works but until we have a randomized trial we won’t know for sure, and we won’t know how much of a benefit we can get.”

Commenting on the study, JoAnn Manson, MD, chief of the division of preventive medicine at Brigham and Women’s Hospital, Boston, pointed out that this type of observational study is important for hypothesis generation but cannot prove cause and effect relationships.

“The evidence is promising enough,” said Dr. Manson, who was not involved with this study. But she added that to move forward, a randomized trial in women at elevated risk of preeclampsia would be needed, beginning in early pregnancy, if not earlier.

“In the meantime,” she noted, “several large-scale cohorts could be leveraged to look at diet assessed before or during pregnancy to see if this dietary pattern is prospectively related to lower risk of preeclampsia.

“With additional supportive data, and in view of the diet’s safety and general cardiovascular benefits, it could become a major tool for preventing adverse pregnancy outcomes.”

The Boston Birth Cohort study was supported in part by grants from the March of Dimes, the National Institutes of Health, and the Health Resources and Services Administration of the U.S. Department of Health and Human Services. The authors have disclosed no relevant financial relationships.

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

Women diagnosed with early breast cancer facing surgery often have a choice of having all of their breast or only a part of the breast removed.

A new study shows that a patient’s satisfaction with their breasts at 10 years after surgery is similar for both groups of women.

However, superior psychosocial and sexual well-being at 10 years after surgery was reported by women who underwent breast-conserving surgery and adjuvant radiation therapy (RT), compared with those who underwent mastectomy and reconstruction.

“These findings may inform preference-sensitive decision-making for women with early-stage breast cancer,” write the authors, led by Benjamin D. Smith, MD, department of radiation oncology, University of Texas MD Anderson Cancer Center, Houston.

The study was published online in JAMA Surgery.

These findings have important implications for patient decision-making, given that more women eligible for breast-conserving surgery are opting for a mastectomy, say Sudheer Vemuru, MD, from the University of Colorado at Denver, Aurora, and colleagues, writing in an accompanying editorial.

“Overall, the preponderance of evidence suggests superior short-term and long-term patient-reported outcomes in patients with early-stage breast cancer undergoing breast conserving surgery compared with mastectomy,” they comment.
 

Study details

For their study, Dr. Smith and colleagues conducted a comparative effectiveness research study using data from the Texas Cancer Registry and identified women diagnosed with stage 0-II breast cancer and treated with breast-conserving surgery or mastectomy and reconstruction between 2006 and 2008.

A total of 647 patients were included in their analysis (40%; 356 had undergone breast-conserving surgery; 291 had undergone mastectomy and reconstruction), 551 (85.2%) confirmed treatment with breast-conserving surgery with RT (n = 315) or mastectomy and reconstruction without RT (n = 236).

The median age of the cohort was 53 years and the median time from diagnosis to survey was 10.3 years. Mastectomy and reconstruction were more common among women who were White, younger, node positive, had larger tumors, had bilateral breast cancer, received chemotherapy, and had higher income.

The primary outcome was patient satisfaction with their breasts, as measured with the BREAST-Q patient-reported outcome measure. Secondary outcomes included physical well-being, psychosocial well-being, and sexual well-being. The EuroQol Health-Related Quality of Life 5-Dimension, 3-Level gaged health utility, and local therapy decisional regret was measured via the Decisional Regret Scale.

Using breast-conserving surgery plus RT as the referent, the authors did not find any significant differences in breast satisfaction, physical well-being, health utility, or decisional regret among the study cohorts: breast satisfaction: effect size, 2.71 (P = .30); physical well-being: effect size, –1.80 (P = .36); health utility: effect size, –0.003 (P = .83); and decisional regret: effect size, 1.32 (P = .61).

However, psychosocial well-being (effect size, –8.61; P < .001) and sexual well-being (effect size, –10.68; P < .001) were significantly worse among women who had undergone mastectomy and reconstruction without RT.

They noted that interactions of race and ethnicity and age by treatment group were not significant for reported satisfaction with breast outcomes. But the findings “indicated that the burden of poor long-term QOL outcomes was greater among younger individuals, those with lower educational attainment and income, and certain racial and ethnic minority populations,” they write. “These findings suggest that opportunities exist to enhance equity in the long-term QOL of individuals with breast cancer.”

The editorialists note that previous studies have also found diminished quality of life following mastectomy compared with breast-conserving surgery. However, most of these prior studies included patients undergoing breast-conserving surgery without RT, patients undergoing mastectomy without reconstruction, and patients undergoing mastectomy with RT.

In contrast, this latest study “directly compared breast-conserving surgery with RT vs. mastectomy and reconstruction without RT to avoid those potential confounders,” they point out.

The study was supported by grants from the National Cancer Institute and other bodies. Several of the study authors disclosed relationships with industry and/or with nonprofit organizations. The full list can be found with the original article. Editorialist Clara Lee, MD, reported receiving grants from the Agency for Healthcare Research and Quality during the conduct of the study.

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

Women diagnosed with early breast cancer facing surgery often have a choice of having all of their breast or only a part of the breast removed.

A new study shows that a patient’s satisfaction with their breasts at 10 years after surgery is similar for both groups of women.

However, superior psychosocial and sexual well-being at 10 years after surgery was reported by women who underwent breast-conserving surgery and adjuvant radiation therapy (RT), compared with those who underwent mastectomy and reconstruction.

“These findings may inform preference-sensitive decision-making for women with early-stage breast cancer,” write the authors, led by Benjamin D. Smith, MD, department of radiation oncology, University of Texas MD Anderson Cancer Center, Houston.

The study was published online in JAMA Surgery.

These findings have important implications for patient decision-making, given that more women eligible for breast-conserving surgery are opting for a mastectomy, say Sudheer Vemuru, MD, from the University of Colorado at Denver, Aurora, and colleagues, writing in an accompanying editorial.

“Overall, the preponderance of evidence suggests superior short-term and long-term patient-reported outcomes in patients with early-stage breast cancer undergoing breast conserving surgery compared with mastectomy,” they comment.
 

Study details

For their study, Dr. Smith and colleagues conducted a comparative effectiveness research study using data from the Texas Cancer Registry and identified women diagnosed with stage 0-II breast cancer and treated with breast-conserving surgery or mastectomy and reconstruction between 2006 and 2008.

A total of 647 patients were included in their analysis (40%; 356 had undergone breast-conserving surgery; 291 had undergone mastectomy and reconstruction), 551 (85.2%) confirmed treatment with breast-conserving surgery with RT (n = 315) or mastectomy and reconstruction without RT (n = 236).

The median age of the cohort was 53 years and the median time from diagnosis to survey was 10.3 years. Mastectomy and reconstruction were more common among women who were White, younger, node positive, had larger tumors, had bilateral breast cancer, received chemotherapy, and had higher income.

The primary outcome was patient satisfaction with their breasts, as measured with the BREAST-Q patient-reported outcome measure. Secondary outcomes included physical well-being, psychosocial well-being, and sexual well-being. The EuroQol Health-Related Quality of Life 5-Dimension, 3-Level gaged health utility, and local therapy decisional regret was measured via the Decisional Regret Scale.

Using breast-conserving surgery plus RT as the referent, the authors did not find any significant differences in breast satisfaction, physical well-being, health utility, or decisional regret among the study cohorts: breast satisfaction: effect size, 2.71 (P = .30); physical well-being: effect size, –1.80 (P = .36); health utility: effect size, –0.003 (P = .83); and decisional regret: effect size, 1.32 (P = .61).

However, psychosocial well-being (effect size, –8.61; P < .001) and sexual well-being (effect size, –10.68; P < .001) were significantly worse among women who had undergone mastectomy and reconstruction without RT.

They noted that interactions of race and ethnicity and age by treatment group were not significant for reported satisfaction with breast outcomes. But the findings “indicated that the burden of poor long-term QOL outcomes was greater among younger individuals, those with lower educational attainment and income, and certain racial and ethnic minority populations,” they write. “These findings suggest that opportunities exist to enhance equity in the long-term QOL of individuals with breast cancer.”

The editorialists note that previous studies have also found diminished quality of life following mastectomy compared with breast-conserving surgery. However, most of these prior studies included patients undergoing breast-conserving surgery without RT, patients undergoing mastectomy without reconstruction, and patients undergoing mastectomy with RT.

In contrast, this latest study “directly compared breast-conserving surgery with RT vs. mastectomy and reconstruction without RT to avoid those potential confounders,” they point out.

The study was supported by grants from the National Cancer Institute and other bodies. Several of the study authors disclosed relationships with industry and/or with nonprofit organizations. The full list can be found with the original article. Editorialist Clara Lee, MD, reported receiving grants from the Agency for Healthcare Research and Quality during the conduct of the study.

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

Women diagnosed with early breast cancer facing surgery often have a choice of having all of their breast or only a part of the breast removed.

A new study shows that a patient’s satisfaction with their breasts at 10 years after surgery is similar for both groups of women.

However, superior psychosocial and sexual well-being at 10 years after surgery was reported by women who underwent breast-conserving surgery and adjuvant radiation therapy (RT), compared with those who underwent mastectomy and reconstruction.

“These findings may inform preference-sensitive decision-making for women with early-stage breast cancer,” write the authors, led by Benjamin D. Smith, MD, department of radiation oncology, University of Texas MD Anderson Cancer Center, Houston.

The study was published online in JAMA Surgery.

These findings have important implications for patient decision-making, given that more women eligible for breast-conserving surgery are opting for a mastectomy, say Sudheer Vemuru, MD, from the University of Colorado at Denver, Aurora, and colleagues, writing in an accompanying editorial.

“Overall, the preponderance of evidence suggests superior short-term and long-term patient-reported outcomes in patients with early-stage breast cancer undergoing breast conserving surgery compared with mastectomy,” they comment.
 

Study details

For their study, Dr. Smith and colleagues conducted a comparative effectiveness research study using data from the Texas Cancer Registry and identified women diagnosed with stage 0-II breast cancer and treated with breast-conserving surgery or mastectomy and reconstruction between 2006 and 2008.

A total of 647 patients were included in their analysis (40%; 356 had undergone breast-conserving surgery; 291 had undergone mastectomy and reconstruction), 551 (85.2%) confirmed treatment with breast-conserving surgery with RT (n = 315) or mastectomy and reconstruction without RT (n = 236).

The median age of the cohort was 53 years and the median time from diagnosis to survey was 10.3 years. Mastectomy and reconstruction were more common among women who were White, younger, node positive, had larger tumors, had bilateral breast cancer, received chemotherapy, and had higher income.

The primary outcome was patient satisfaction with their breasts, as measured with the BREAST-Q patient-reported outcome measure. Secondary outcomes included physical well-being, psychosocial well-being, and sexual well-being. The EuroQol Health-Related Quality of Life 5-Dimension, 3-Level gaged health utility, and local therapy decisional regret was measured via the Decisional Regret Scale.

Using breast-conserving surgery plus RT as the referent, the authors did not find any significant differences in breast satisfaction, physical well-being, health utility, or decisional regret among the study cohorts: breast satisfaction: effect size, 2.71 (P = .30); physical well-being: effect size, –1.80 (P = .36); health utility: effect size, –0.003 (P = .83); and decisional regret: effect size, 1.32 (P = .61).

However, psychosocial well-being (effect size, –8.61; P < .001) and sexual well-being (effect size, –10.68; P < .001) were significantly worse among women who had undergone mastectomy and reconstruction without RT.

They noted that interactions of race and ethnicity and age by treatment group were not significant for reported satisfaction with breast outcomes. But the findings “indicated that the burden of poor long-term QOL outcomes was greater among younger individuals, those with lower educational attainment and income, and certain racial and ethnic minority populations,” they write. “These findings suggest that opportunities exist to enhance equity in the long-term QOL of individuals with breast cancer.”

The editorialists note that previous studies have also found diminished quality of life following mastectomy compared with breast-conserving surgery. However, most of these prior studies included patients undergoing breast-conserving surgery without RT, patients undergoing mastectomy without reconstruction, and patients undergoing mastectomy with RT.

In contrast, this latest study “directly compared breast-conserving surgery with RT vs. mastectomy and reconstruction without RT to avoid those potential confounders,” they point out.

The study was supported by grants from the National Cancer Institute and other bodies. Several of the study authors disclosed relationships with industry and/or with nonprofit organizations. The full list can be found with the original article. Editorialist Clara Lee, MD, reported receiving grants from the Agency for Healthcare Research and Quality during the conduct of the study.

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

Poverty is known to be associated with poor health outcomes throughout life. Now, new research has shown that, from as early as the second trimester of pregnancy, fetuses are already feeling the effects of poverty.

“There is a well-recognized health inequality where quality and duration of life are lower among the most poor. This divide is present both within and between countries,” said Steve Turner, who led the study.

Given the association of poverty and low birth weight, the authors of the new multi-national study, published in the Journal of Epidemiology and Community Health, hypothesized that “individuals from highest household income compared to those with lowest household income will have increased fetal size in the second and third trimester and birth.”

For their study, researchers from the University of Aberdeen gathered details of ante-natal and birth size – second and third trimester fetal ultrasound measurements of estimated fetal weight, biparietal diameter, and femur length, as well as birth measurements of weight, occipitofrontal circumference, and crown heel length – from eight cohorts that included 21,714 individuals from nations including Scotland, England, Saudi Arabia, the U.S., Netherlands, Spain, Norway, Sweden, and France.

They then related these to household income, taking into account other factors, including mother’s age, height, number of other children, and smoking, analyzing the data using cross-sectional two-stage individual patient data analyses and a longitudinal one-stage individual patient data analysis.
 

Household income closely related to birth size

The authors found that higher household income was associated with larger fetal head size and weight but not length, from the second half of pregnancy, compared with lowest household income. They said that their results argue for “a relationship where household income is closely related to birth size.”

The results showed that, across the countries studied, babies were smaller at birth if they came from a lower income household, and this discrepancy in size was already apparent at 20 weeks gestation.

“This is the first time that size differences have been found at such an early stage of development,” the authors said, “and also the first time it has been compared across continents.”

Professor Turner pointed out that “what this study shows is that the inequality, as seen by reduced size in fetal life, is present long before birth, and this poverty gap widens between twenty weeks gestation and birth.”

He added: “Basically, regardless of whether you live in Saudi, the U.S., or Europe, and accounting for things that might affect fetal growth, if your parents are poor, you will be smaller before birth and at birth compared to if your parents were not poor.”
 

Increase engagement with pregnant mothers living in poverty

He emphasized how this was problematic, as small size before and after birth puts an individual at “increased risk for many serious illnesses in later life.”

The authors hope that this study will encourage health care providers to recognize the health risks associated with lower income for mothers and their unborn children and to provide more support and guidance to mitigate the risks.

They said, “interventions aimed at softening the impact of poverty on pregnant mothers could reduce incidence of small for gestational age and the associated burden of excessive morbidity and mortality throughout the life course.”

Professor Turner described how the mechanisms that drive this inequity may be explained by pregnant mothers from poor households having difficulty in accessing or engaging with antenatal care. 

“We would like to see health care providers around the world strive to increase engagement with pregnant mothers living in poverty,” he said. “This engagement will reward all of society by putting unborn children on a trajectory to longer and healthier lives.”

A version of this article first appeared on Medscape UK.

Poverty is known to be associated with poor health outcomes throughout life. Now, new research has shown that, from as early as the second trimester of pregnancy, fetuses are already feeling the effects of poverty.

“There is a well-recognized health inequality where quality and duration of life are lower among the most poor. This divide is present both within and between countries,” said Steve Turner, who led the study.

Given the association of poverty and low birth weight, the authors of the new multi-national study, published in the Journal of Epidemiology and Community Health, hypothesized that “individuals from highest household income compared to those with lowest household income will have increased fetal size in the second and third trimester and birth.”

For their study, researchers from the University of Aberdeen gathered details of ante-natal and birth size – second and third trimester fetal ultrasound measurements of estimated fetal weight, biparietal diameter, and femur length, as well as birth measurements of weight, occipitofrontal circumference, and crown heel length – from eight cohorts that included 21,714 individuals from nations including Scotland, England, Saudi Arabia, the U.S., Netherlands, Spain, Norway, Sweden, and France.

They then related these to household income, taking into account other factors, including mother’s age, height, number of other children, and smoking, analyzing the data using cross-sectional two-stage individual patient data analyses and a longitudinal one-stage individual patient data analysis.
 

Household income closely related to birth size

The authors found that higher household income was associated with larger fetal head size and weight but not length, from the second half of pregnancy, compared with lowest household income. They said that their results argue for “a relationship where household income is closely related to birth size.”

The results showed that, across the countries studied, babies were smaller at birth if they came from a lower income household, and this discrepancy in size was already apparent at 20 weeks gestation.

“This is the first time that size differences have been found at such an early stage of development,” the authors said, “and also the first time it has been compared across continents.”

Professor Turner pointed out that “what this study shows is that the inequality, as seen by reduced size in fetal life, is present long before birth, and this poverty gap widens between twenty weeks gestation and birth.”

He added: “Basically, regardless of whether you live in Saudi, the U.S., or Europe, and accounting for things that might affect fetal growth, if your parents are poor, you will be smaller before birth and at birth compared to if your parents were not poor.”
 

Increase engagement with pregnant mothers living in poverty

He emphasized how this was problematic, as small size before and after birth puts an individual at “increased risk for many serious illnesses in later life.”

The authors hope that this study will encourage health care providers to recognize the health risks associated with lower income for mothers and their unborn children and to provide more support and guidance to mitigate the risks.

They said, “interventions aimed at softening the impact of poverty on pregnant mothers could reduce incidence of small for gestational age and the associated burden of excessive morbidity and mortality throughout the life course.”

Professor Turner described how the mechanisms that drive this inequity may be explained by pregnant mothers from poor households having difficulty in accessing or engaging with antenatal care. 

“We would like to see health care providers around the world strive to increase engagement with pregnant mothers living in poverty,” he said. “This engagement will reward all of society by putting unborn children on a trajectory to longer and healthier lives.”

A version of this article first appeared on Medscape UK.

Poverty is known to be associated with poor health outcomes throughout life. Now, new research has shown that, from as early as the second trimester of pregnancy, fetuses are already feeling the effects of poverty.

“There is a well-recognized health inequality where quality and duration of life are lower among the most poor. This divide is present both within and between countries,” said Steve Turner, who led the study.

Given the association of poverty and low birth weight, the authors of the new multi-national study, published in the Journal of Epidemiology and Community Health, hypothesized that “individuals from highest household income compared to those with lowest household income will have increased fetal size in the second and third trimester and birth.”

For their study, researchers from the University of Aberdeen gathered details of ante-natal and birth size – second and third trimester fetal ultrasound measurements of estimated fetal weight, biparietal diameter, and femur length, as well as birth measurements of weight, occipitofrontal circumference, and crown heel length – from eight cohorts that included 21,714 individuals from nations including Scotland, England, Saudi Arabia, the U.S., Netherlands, Spain, Norway, Sweden, and France.

They then related these to household income, taking into account other factors, including mother’s age, height, number of other children, and smoking, analyzing the data using cross-sectional two-stage individual patient data analyses and a longitudinal one-stage individual patient data analysis.
 

Household income closely related to birth size

The authors found that higher household income was associated with larger fetal head size and weight but not length, from the second half of pregnancy, compared with lowest household income. They said that their results argue for “a relationship where household income is closely related to birth size.”

The results showed that, across the countries studied, babies were smaller at birth if they came from a lower income household, and this discrepancy in size was already apparent at 20 weeks gestation.

“This is the first time that size differences have been found at such an early stage of development,” the authors said, “and also the first time it has been compared across continents.”

Professor Turner pointed out that “what this study shows is that the inequality, as seen by reduced size in fetal life, is present long before birth, and this poverty gap widens between twenty weeks gestation and birth.”

He added: “Basically, regardless of whether you live in Saudi, the U.S., or Europe, and accounting for things that might affect fetal growth, if your parents are poor, you will be smaller before birth and at birth compared to if your parents were not poor.”
 

Increase engagement with pregnant mothers living in poverty

He emphasized how this was problematic, as small size before and after birth puts an individual at “increased risk for many serious illnesses in later life.”

The authors hope that this study will encourage health care providers to recognize the health risks associated with lower income for mothers and their unborn children and to provide more support and guidance to mitigate the risks.

They said, “interventions aimed at softening the impact of poverty on pregnant mothers could reduce incidence of small for gestational age and the associated burden of excessive morbidity and mortality throughout the life course.”

Professor Turner described how the mechanisms that drive this inequity may be explained by pregnant mothers from poor households having difficulty in accessing or engaging with antenatal care. 

“We would like to see health care providers around the world strive to increase engagement with pregnant mothers living in poverty,” he said. “This engagement will reward all of society by putting unborn children on a trajectory to longer and healthier lives.”

A version of this article first appeared on Medscape UK.

A cell phone rings in a red-brick bungalow in a village in India. A woman on the other end of the phone tells Ms. SK, a community health worker, that menstruation has started. Ms. SK guns her scooter through the dusty streets for 15 minutes in 30° C (86° F) heat.

A 32-year-old woman, waiting in the shade of a blue corrugated-iron roof, hands over a green polythene bag. Ms. SK whisks the package to the local health center and tucks it into a –20° C freezer. The following week, it will ride in dry ice to the National Institute for Research in Reproductive and Child Health Laboratory in Mumbai for human papillomavirus (HPV) testing.

The two women are participants in the world’s first community-based validation trial of cervical screening using menstrual pads.

This moment in rural India at first glance appears to have little relevance to wealthy countries such as the United States.

However, public health officials in both countries are trying to solve the same problem: how to prevent unnecessary deaths from cervical cancer by reaching women who have never or rarely been screened.

The United States has more in common with India than it may care to admit.

“In the U.S., we still have pockets of disparities that actually have incidence rates [of cervical cancer] comparable to many low- and middle-income countries,” said Vikrant Sahasrabuddhe, MBBS, DrPh, MPH, of the National Cancer Institute, where he heads the HPV and cervical cancer prevention clinical research program for the National Institutes of Health.

The incidence of cervical cancer in India is approximately 19 per 100,000 women. For the past 15 years incidence in the United States has stalled at approximately 7 per 100,000.

In India, there are no organized screening programs and most cervical cancer is regional or distant metastatic at diagnosis.

In the United States, 52% of new cases are advanced, and half of these are among women who have never or rarely been screened.

“There is a critical need for new strategies to reach this population,” Dr. Sahasrabuddhe said. “We absolutely have to do something out of the box creatively.”

Almost all cervical cancers are triggered by HPV, most commonly high-risk HPV-16 and HPV-18, although there are more than 200 types. HPV testing is taking over from cytology (Papanicolaou test) for secondary prevention of cervical cancer.

The trial of screening for HPV in menstrual pads that is ongoing in India was the brainchild of Atul Budukh, PhD, a government public health researcher and professor at the Centre for Cancer Epidemiology, Tata Memorial Centre, Mumbai.

Dr. Budukh’s eyes were opened to the scale of the problem when he participated in a cluster-randomized trial funded by the Bill and Melinda Gates Foundation. The study, published in 2009 in the New England Journal of Medicine, involved 131,746 rural women in the Osmanabad district of India.

A team of researchers from India and France compared outcomes for women over 8 years after cervical screening by HPV, cytology, or visual inspection with acetic acid. The control group was usual care, where women were advised how to seek screening at local hospitals. Women who screened positive were referred for colposcopy, biopsy, and treatment.

Over the 8-year follow-up, advanced cervical cancer was found in twice as many women left to their own devices, compared with women who had HPV testing during the study (82 vs. 39; hazard ratio for HPV, 0.47; 95% confidence interval, 0.32-0.69).

Similarly, cervical cancer deaths in the control group were nearly two times higher than among the women who were screened for HPV in the study (64 vs. 34; HR for HPV, 0.52; 95% CI, 0.33-0.83).

The study proved that rural Indian women were dying unnecessarily because they weren’t seeking cervical screening. And education wasn’t the problem.

“When we go and educate [a rural woman] about ... risk factors and the need to undergo screening, she understands it very well,” said Dr. Budukh. “She is ready to come but her priority is her bread and butter – she will lose her daily wages.”

Dr. Budukh and his team negotiated with local employers so that women could come to screening clinics, but they soon realized this wasn’t scalable.

One year after the NEJM publication, Dr. Budukh found what he was looking for.

A team of Hong Kong clinicians, headed by Sze Chuen Cesar Wong of the Hong Kong Cancer Institute, published a paper in 2010 in the Journal of Clinical Microbiology showing that menstrual pads provide reliable HPV results in women with and without cervical disease.

The Hong Kong team tested sanitary napkins for HPV from 235 of their patients with cervical intraepithelial neoplasia or condyloma acuminatum before and after treatment. Samples were compared with those from 323 women without cervical disease; for HPV in sanitary napkins the sensitivity was 82.8%, specificity was 93.1%, and positive and negative predictive values were 90% and 87.9%, respectively.

The authors pointed out that menstrual pad testing was the only truly noninvasive approach to HPV screening versus the other self-sampling methods such as tampons and cytobrushes. Also, these self-sampling tests require specialized liquid-based transport media. A menstrual pad needs only a plastic bag.

Dr. Budukh had his at-home solution for the hard-working rural women of India.

With funding from the Indian government, Dr. Budukh’s team put together a validation trial that ran from 2013 to 2016 in 18 rural villages in two separate districts: Ahmednagar and Pune.

Local health workers went house to house to recruit women and get family buy-in for this culturally delicate project. Participants were instructed to use their regular sanitary protection – most commonly a washable cloth – and told to call the health worker on the first day of menstruation. Health workers gave each woman a Ziploc bag for the pad and, for privacy, an outer polythene sac.

In Ahmednagar, all women who provided their pad also got screened with Hybrid Capture 2 (HC2; Qiagen) by a mobile screening unit. In Pune, only the positive cases underwent HC2. Screening was also extended to anyone who requested it, but these people were not included in the final analysis.

Genomic DNA was extracted from three 5 mm–sized punches in the pad using a commercial kit, QIAamp DNA Micro, and the quality and purity of the DNA checked by Implen NanoPhotometer.

The team followed the same protocol for PCR HPV assay as the team from Hong Kong.

The results were published in the European Journal of Cancer Prevention in 2018.

The concordance rate for a positive result between the menstrual pad sample and conventional HPV sampling was 98.8% for Ahmednagar and 95.2% for samples from Pune. The sensitivity for the first study was 83% and the specificity 99% – similar to that for the women in Hong Kong. The second study had lower sensitivity and specificity (67% and 88%), partly because of poor storage as a result of frequent power cuts.

The total cost per woman was $30.78.

“I was very excited when we saw the results,” Dr. Budukh recalled. “That day I couldn’t sleep ... such a wonderful result! I was excited to start the next phase immediately.”

Dr. Budukh has applied to the Indian government for funding for a larger trial involving 3,000 women. If successful, he hopes such evidence would be sufficient to convince the Indian government to make menstrual pad screening standard procedure for the 390 million women who live in India’s countryside.

Testing never-screened women for cervical cancer using menstrual pads appears to be relatively reliable, convenient, private, noninvasive, and incredibly cheap.

So who else has tried it?

The first published account of HPV in menstrual blood was a 2003 study by Tommy Tong and colleagues at the Princess Margaret Hospital in Hong Kong. The authors heralded, with lamentable optimism, “a new paradigm in cervical cancer screening.”

In the following 20 years, just six more studies appeared: two from Dr. Budukh’s field trial in India and four from hospital-based pilot studies in Hong Kong (in 2010 and 2018), South Korea (in 2016), and mainland China (in 2021). All these studies, although small, were published in top-flight journals and demonstrate high concordance between conventional high-risk HPV testing and menstrual-blood tests.

This news organization tried to find a U.S. thought-leader who had heard of the approach.

Elizabeth Fontham, MPH, DrPh, is the founding dean of the school of public health at Louisiana State University Health Center in New Orleans, and president of the American Cancer Society. Dr. Fontham said in an email that she had “no plans to evaluate the impact related to menstrual pads, but perhaps others have looked into that.”

Joy Melnikow, MD, MPH, was first author on the evidence synthesis driving the current cervical cancer screening recommendations from the U.S. Preventive Services Task Force. When asked about menstrual pad testing for HPV, she said she had “not heard of it before.”

The USPSTF guidelines don’t mention sanitary pads but acknowledge that “self-collection may be one strategy for increasing screening rates among populations where they are currently low.”

The USPSTF methodology excludes data from countries that don’t match the United States on the Human Development Index “or [are] not applicable to U.S. clinical settings or populations.” (Presumably, data from Hong Kong and South Korea would qualify; Indian data would not.)

Dr. Sahasrabuddhe of the NCI hadn’t heard of menstrual pad testing either, but he has a different explanation for lack of interest in this approach – or, indeed, any form of self-sampling for cervical cancer screening – in the United States.

“We have not seen movement happen in this space for years. ... If there is one intervention that we can simplify, that still has not been made widely available, it is self-sampling ... [but] we don’t have [Food and Drug Administration] approval for it,” Dr. Sahasrabuddhe said.

“Our system, at least in the U.S., is based on industry manufacturers seeking an approval for a particular way of collection and then clinicians and clinical-guideline bodies signing on. ... For a lot of reasons industry has shied away over the past several years, so far, at least, on seeking approval for self-sampling-based approaches,” he commented.

Dr. Sahasrabuddhe aims to change that. He heads a new NCI-led initiative called “The Last Mile,” a nationwide clinical trial supported by federal agencies, industry partners, and professional societies. The goal is to validate self-sampled HPV testing as non-inferior to specimens collected by providers. The team is currently finalizing the methodology of the study, so Dr. Sahasrabuddhe could not share the self-sampling methods that will be on trial, nor the industry partners who have signed up.

The following tests are approved in the United States for physician-collected HPV screening: Hybrid Capture 2, used in the Indian studies (Qiagen); cobas HPV (Roche); Aptima (Hologic); Cervista (Hologic); and Onclarity (Becton Dickinson).

Dr. Sahasrabuddhe said that, while a sanitary pad in a Ziploc bag is unlikely to make the grade for The Last Mile study, he doesn’t totally dismiss their potential and said the NCI is always open to new ideas.

“We are not supporting anybody specifically for menstrual pad-based collection device development,” Dr. Sahasrabuddhe said, “But if they fulfill other criteria for a small business–based grant application, they absolutely are welcome to apply for NCI funding for this.”

Said Dr. Melnikow: “Pre-COVID, the head of [the World Health Organization] said that we could eliminate cervical cancer from the globe and that we have the tools to do that now. And he’s right.”

Dr. Budukh, Dr. Melnikow, and Dr. Sahasrabuddhe disclosed no relevant financial relationships.

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

A cell phone rings in a red-brick bungalow in a village in India. A woman on the other end of the phone tells Ms. SK, a community health worker, that menstruation has started. Ms. SK guns her scooter through the dusty streets for 15 minutes in 30° C (86° F) heat.

A 32-year-old woman, waiting in the shade of a blue corrugated-iron roof, hands over a green polythene bag. Ms. SK whisks the package to the local health center and tucks it into a –20° C freezer. The following week, it will ride in dry ice to the National Institute for Research in Reproductive and Child Health Laboratory in Mumbai for human papillomavirus (HPV) testing.

The two women are participants in the world’s first community-based validation trial of cervical screening using menstrual pads.

This moment in rural India at first glance appears to have little relevance to wealthy countries such as the United States.

However, public health officials in both countries are trying to solve the same problem: how to prevent unnecessary deaths from cervical cancer by reaching women who have never or rarely been screened.

The United States has more in common with India than it may care to admit.

“In the U.S., we still have pockets of disparities that actually have incidence rates [of cervical cancer] comparable to many low- and middle-income countries,” said Vikrant Sahasrabuddhe, MBBS, DrPh, MPH, of the National Cancer Institute, where he heads the HPV and cervical cancer prevention clinical research program for the National Institutes of Health.

The incidence of cervical cancer in India is approximately 19 per 100,000 women. For the past 15 years incidence in the United States has stalled at approximately 7 per 100,000.

In India, there are no organized screening programs and most cervical cancer is regional or distant metastatic at diagnosis.

In the United States, 52% of new cases are advanced, and half of these are among women who have never or rarely been screened.

“There is a critical need for new strategies to reach this population,” Dr. Sahasrabuddhe said. “We absolutely have to do something out of the box creatively.”

Almost all cervical cancers are triggered by HPV, most commonly high-risk HPV-16 and HPV-18, although there are more than 200 types. HPV testing is taking over from cytology (Papanicolaou test) for secondary prevention of cervical cancer.

The trial of screening for HPV in menstrual pads that is ongoing in India was the brainchild of Atul Budukh, PhD, a government public health researcher and professor at the Centre for Cancer Epidemiology, Tata Memorial Centre, Mumbai.

Dr. Budukh’s eyes were opened to the scale of the problem when he participated in a cluster-randomized trial funded by the Bill and Melinda Gates Foundation. The study, published in 2009 in the New England Journal of Medicine, involved 131,746 rural women in the Osmanabad district of India.

A team of researchers from India and France compared outcomes for women over 8 years after cervical screening by HPV, cytology, or visual inspection with acetic acid. The control group was usual care, where women were advised how to seek screening at local hospitals. Women who screened positive were referred for colposcopy, biopsy, and treatment.

Over the 8-year follow-up, advanced cervical cancer was found in twice as many women left to their own devices, compared with women who had HPV testing during the study (82 vs. 39; hazard ratio for HPV, 0.47; 95% confidence interval, 0.32-0.69).

Similarly, cervical cancer deaths in the control group were nearly two times higher than among the women who were screened for HPV in the study (64 vs. 34; HR for HPV, 0.52; 95% CI, 0.33-0.83).

The study proved that rural Indian women were dying unnecessarily because they weren’t seeking cervical screening. And education wasn’t the problem.

“When we go and educate [a rural woman] about ... risk factors and the need to undergo screening, she understands it very well,” said Dr. Budukh. “She is ready to come but her priority is her bread and butter – she will lose her daily wages.”

Dr. Budukh and his team negotiated with local employers so that women could come to screening clinics, but they soon realized this wasn’t scalable.

One year after the NEJM publication, Dr. Budukh found what he was looking for.

A team of Hong Kong clinicians, headed by Sze Chuen Cesar Wong of the Hong Kong Cancer Institute, published a paper in 2010 in the Journal of Clinical Microbiology showing that menstrual pads provide reliable HPV results in women with and without cervical disease.

The Hong Kong team tested sanitary napkins for HPV from 235 of their patients with cervical intraepithelial neoplasia or condyloma acuminatum before and after treatment. Samples were compared with those from 323 women without cervical disease; for HPV in sanitary napkins the sensitivity was 82.8%, specificity was 93.1%, and positive and negative predictive values were 90% and 87.9%, respectively.

The authors pointed out that menstrual pad testing was the only truly noninvasive approach to HPV screening versus the other self-sampling methods such as tampons and cytobrushes. Also, these self-sampling tests require specialized liquid-based transport media. A menstrual pad needs only a plastic bag.

Dr. Budukh had his at-home solution for the hard-working rural women of India.

With funding from the Indian government, Dr. Budukh’s team put together a validation trial that ran from 2013 to 2016 in 18 rural villages in two separate districts: Ahmednagar and Pune.

Local health workers went house to house to recruit women and get family buy-in for this culturally delicate project. Participants were instructed to use their regular sanitary protection – most commonly a washable cloth – and told to call the health worker on the first day of menstruation. Health workers gave each woman a Ziploc bag for the pad and, for privacy, an outer polythene sac.

In Ahmednagar, all women who provided their pad also got screened with Hybrid Capture 2 (HC2; Qiagen) by a mobile screening unit. In Pune, only the positive cases underwent HC2. Screening was also extended to anyone who requested it, but these people were not included in the final analysis.

Genomic DNA was extracted from three 5 mm–sized punches in the pad using a commercial kit, QIAamp DNA Micro, and the quality and purity of the DNA checked by Implen NanoPhotometer.

The team followed the same protocol for PCR HPV assay as the team from Hong Kong.

The results were published in the European Journal of Cancer Prevention in 2018.

The concordance rate for a positive result between the menstrual pad sample and conventional HPV sampling was 98.8% for Ahmednagar and 95.2% for samples from Pune. The sensitivity for the first study was 83% and the specificity 99% – similar to that for the women in Hong Kong. The second study had lower sensitivity and specificity (67% and 88%), partly because of poor storage as a result of frequent power cuts.

The total cost per woman was $30.78.

“I was very excited when we saw the results,” Dr. Budukh recalled. “That day I couldn’t sleep ... such a wonderful result! I was excited to start the next phase immediately.”

Dr. Budukh has applied to the Indian government for funding for a larger trial involving 3,000 women. If successful, he hopes such evidence would be sufficient to convince the Indian government to make menstrual pad screening standard procedure for the 390 million women who live in India’s countryside.

Testing never-screened women for cervical cancer using menstrual pads appears to be relatively reliable, convenient, private, noninvasive, and incredibly cheap.

So who else has tried it?

The first published account of HPV in menstrual blood was a 2003 study by Tommy Tong and colleagues at the Princess Margaret Hospital in Hong Kong. The authors heralded, with lamentable optimism, “a new paradigm in cervical cancer screening.”

In the following 20 years, just six more studies appeared: two from Dr. Budukh’s field trial in India and four from hospital-based pilot studies in Hong Kong (in 2010 and 2018), South Korea (in 2016), and mainland China (in 2021). All these studies, although small, were published in top-flight journals and demonstrate high concordance between conventional high-risk HPV testing and menstrual-blood tests.

This news organization tried to find a U.S. thought-leader who had heard of the approach.

Elizabeth Fontham, MPH, DrPh, is the founding dean of the school of public health at Louisiana State University Health Center in New Orleans, and president of the American Cancer Society. Dr. Fontham said in an email that she had “no plans to evaluate the impact related to menstrual pads, but perhaps others have looked into that.”

Joy Melnikow, MD, MPH, was first author on the evidence synthesis driving the current cervical cancer screening recommendations from the U.S. Preventive Services Task Force. When asked about menstrual pad testing for HPV, she said she had “not heard of it before.”

The USPSTF guidelines don’t mention sanitary pads but acknowledge that “self-collection may be one strategy for increasing screening rates among populations where they are currently low.”

The USPSTF methodology excludes data from countries that don’t match the United States on the Human Development Index “or [are] not applicable to U.S. clinical settings or populations.” (Presumably, data from Hong Kong and South Korea would qualify; Indian data would not.)

Dr. Sahasrabuddhe of the NCI hadn’t heard of menstrual pad testing either, but he has a different explanation for lack of interest in this approach – or, indeed, any form of self-sampling for cervical cancer screening – in the United States.

“We have not seen movement happen in this space for years. ... If there is one intervention that we can simplify, that still has not been made widely available, it is self-sampling ... [but] we don’t have [Food and Drug Administration] approval for it,” Dr. Sahasrabuddhe said.

“Our system, at least in the U.S., is based on industry manufacturers seeking an approval for a particular way of collection and then clinicians and clinical-guideline bodies signing on. ... For a lot of reasons industry has shied away over the past several years, so far, at least, on seeking approval for self-sampling-based approaches,” he commented.

Dr. Sahasrabuddhe aims to change that. He heads a new NCI-led initiative called “The Last Mile,” a nationwide clinical trial supported by federal agencies, industry partners, and professional societies. The goal is to validate self-sampled HPV testing as non-inferior to specimens collected by providers. The team is currently finalizing the methodology of the study, so Dr. Sahasrabuddhe could not share the self-sampling methods that will be on trial, nor the industry partners who have signed up.

The following tests are approved in the United States for physician-collected HPV screening: Hybrid Capture 2, used in the Indian studies (Qiagen); cobas HPV (Roche); Aptima (Hologic); Cervista (Hologic); and Onclarity (Becton Dickinson).

Dr. Sahasrabuddhe said that, while a sanitary pad in a Ziploc bag is unlikely to make the grade for The Last Mile study, he doesn’t totally dismiss their potential and said the NCI is always open to new ideas.

“We are not supporting anybody specifically for menstrual pad-based collection device development,” Dr. Sahasrabuddhe said, “But if they fulfill other criteria for a small business–based grant application, they absolutely are welcome to apply for NCI funding for this.”

Said Dr. Melnikow: “Pre-COVID, the head of [the World Health Organization] said that we could eliminate cervical cancer from the globe and that we have the tools to do that now. And he’s right.”

Dr. Budukh, Dr. Melnikow, and Dr. Sahasrabuddhe disclosed no relevant financial relationships.

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

A cell phone rings in a red-brick bungalow in a village in India. A woman on the other end of the phone tells Ms. SK, a community health worker, that menstruation has started. Ms. SK guns her scooter through the dusty streets for 15 minutes in 30° C (86° F) heat.

A 32-year-old woman, waiting in the shade of a blue corrugated-iron roof, hands over a green polythene bag. Ms. SK whisks the package to the local health center and tucks it into a –20° C freezer. The following week, it will ride in dry ice to the National Institute for Research in Reproductive and Child Health Laboratory in Mumbai for human papillomavirus (HPV) testing.

The two women are participants in the world’s first community-based validation trial of cervical screening using menstrual pads.

This moment in rural India at first glance appears to have little relevance to wealthy countries such as the United States.

However, public health officials in both countries are trying to solve the same problem: how to prevent unnecessary deaths from cervical cancer by reaching women who have never or rarely been screened.

The United States has more in common with India than it may care to admit.

“In the U.S., we still have pockets of disparities that actually have incidence rates [of cervical cancer] comparable to many low- and middle-income countries,” said Vikrant Sahasrabuddhe, MBBS, DrPh, MPH, of the National Cancer Institute, where he heads the HPV and cervical cancer prevention clinical research program for the National Institutes of Health.

The incidence of cervical cancer in India is approximately 19 per 100,000 women. For the past 15 years incidence in the United States has stalled at approximately 7 per 100,000.

In India, there are no organized screening programs and most cervical cancer is regional or distant metastatic at diagnosis.

In the United States, 52% of new cases are advanced, and half of these are among women who have never or rarely been screened.

“There is a critical need for new strategies to reach this population,” Dr. Sahasrabuddhe said. “We absolutely have to do something out of the box creatively.”

Almost all cervical cancers are triggered by HPV, most commonly high-risk HPV-16 and HPV-18, although there are more than 200 types. HPV testing is taking over from cytology (Papanicolaou test) for secondary prevention of cervical cancer.

The trial of screening for HPV in menstrual pads that is ongoing in India was the brainchild of Atul Budukh, PhD, a government public health researcher and professor at the Centre for Cancer Epidemiology, Tata Memorial Centre, Mumbai.

Dr. Budukh’s eyes were opened to the scale of the problem when he participated in a cluster-randomized trial funded by the Bill and Melinda Gates Foundation. The study, published in 2009 in the New England Journal of Medicine, involved 131,746 rural women in the Osmanabad district of India.

A team of researchers from India and France compared outcomes for women over 8 years after cervical screening by HPV, cytology, or visual inspection with acetic acid. The control group was usual care, where women were advised how to seek screening at local hospitals. Women who screened positive were referred for colposcopy, biopsy, and treatment.

Over the 8-year follow-up, advanced cervical cancer was found in twice as many women left to their own devices, compared with women who had HPV testing during the study (82 vs. 39; hazard ratio for HPV, 0.47; 95% confidence interval, 0.32-0.69).

Similarly, cervical cancer deaths in the control group were nearly two times higher than among the women who were screened for HPV in the study (64 vs. 34; HR for HPV, 0.52; 95% CI, 0.33-0.83).

The study proved that rural Indian women were dying unnecessarily because they weren’t seeking cervical screening. And education wasn’t the problem.

“When we go and educate [a rural woman] about ... risk factors and the need to undergo screening, she understands it very well,” said Dr. Budukh. “She is ready to come but her priority is her bread and butter – she will lose her daily wages.”

Dr. Budukh and his team negotiated with local employers so that women could come to screening clinics, but they soon realized this wasn’t scalable.

One year after the NEJM publication, Dr. Budukh found what he was looking for.

A team of Hong Kong clinicians, headed by Sze Chuen Cesar Wong of the Hong Kong Cancer Institute, published a paper in 2010 in the Journal of Clinical Microbiology showing that menstrual pads provide reliable HPV results in women with and without cervical disease.

The Hong Kong team tested sanitary napkins for HPV from 235 of their patients with cervical intraepithelial neoplasia or condyloma acuminatum before and after treatment. Samples were compared with those from 323 women without cervical disease; for HPV in sanitary napkins the sensitivity was 82.8%, specificity was 93.1%, and positive and negative predictive values were 90% and 87.9%, respectively.

The authors pointed out that menstrual pad testing was the only truly noninvasive approach to HPV screening versus the other self-sampling methods such as tampons and cytobrushes. Also, these self-sampling tests require specialized liquid-based transport media. A menstrual pad needs only a plastic bag.

Dr. Budukh had his at-home solution for the hard-working rural women of India.

With funding from the Indian government, Dr. Budukh’s team put together a validation trial that ran from 2013 to 2016 in 18 rural villages in two separate districts: Ahmednagar and Pune.

Local health workers went house to house to recruit women and get family buy-in for this culturally delicate project. Participants were instructed to use their regular sanitary protection – most commonly a washable cloth – and told to call the health worker on the first day of menstruation. Health workers gave each woman a Ziploc bag for the pad and, for privacy, an outer polythene sac.

In Ahmednagar, all women who provided their pad also got screened with Hybrid Capture 2 (HC2; Qiagen) by a mobile screening unit. In Pune, only the positive cases underwent HC2. Screening was also extended to anyone who requested it, but these people were not included in the final analysis.

Genomic DNA was extracted from three 5 mm–sized punches in the pad using a commercial kit, QIAamp DNA Micro, and the quality and purity of the DNA checked by Implen NanoPhotometer.

The team followed the same protocol for PCR HPV assay as the team from Hong Kong.

The results were published in the European Journal of Cancer Prevention in 2018.

The concordance rate for a positive result between the menstrual pad sample and conventional HPV sampling was 98.8% for Ahmednagar and 95.2% for samples from Pune. The sensitivity for the first study was 83% and the specificity 99% – similar to that for the women in Hong Kong. The second study had lower sensitivity and specificity (67% and 88%), partly because of poor storage as a result of frequent power cuts.

The total cost per woman was $30.78.

“I was very excited when we saw the results,” Dr. Budukh recalled. “That day I couldn’t sleep ... such a wonderful result! I was excited to start the next phase immediately.”

Dr. Budukh has applied to the Indian government for funding for a larger trial involving 3,000 women. If successful, he hopes such evidence would be sufficient to convince the Indian government to make menstrual pad screening standard procedure for the 390 million women who live in India’s countryside.

Testing never-screened women for cervical cancer using menstrual pads appears to be relatively reliable, convenient, private, noninvasive, and incredibly cheap.

So who else has tried it?

The first published account of HPV in menstrual blood was a 2003 study by Tommy Tong and colleagues at the Princess Margaret Hospital in Hong Kong. The authors heralded, with lamentable optimism, “a new paradigm in cervical cancer screening.”

In the following 20 years, just six more studies appeared: two from Dr. Budukh’s field trial in India and four from hospital-based pilot studies in Hong Kong (in 2010 and 2018), South Korea (in 2016), and mainland China (in 2021). All these studies, although small, were published in top-flight journals and demonstrate high concordance between conventional high-risk HPV testing and menstrual-blood tests.

This news organization tried to find a U.S. thought-leader who had heard of the approach.

Elizabeth Fontham, MPH, DrPh, is the founding dean of the school of public health at Louisiana State University Health Center in New Orleans, and president of the American Cancer Society. Dr. Fontham said in an email that she had “no plans to evaluate the impact related to menstrual pads, but perhaps others have looked into that.”

Joy Melnikow, MD, MPH, was first author on the evidence synthesis driving the current cervical cancer screening recommendations from the U.S. Preventive Services Task Force. When asked about menstrual pad testing for HPV, she said she had “not heard of it before.”

The USPSTF guidelines don’t mention sanitary pads but acknowledge that “self-collection may be one strategy for increasing screening rates among populations where they are currently low.”

The USPSTF methodology excludes data from countries that don’t match the United States on the Human Development Index “or [are] not applicable to U.S. clinical settings or populations.” (Presumably, data from Hong Kong and South Korea would qualify; Indian data would not.)

Dr. Sahasrabuddhe of the NCI hadn’t heard of menstrual pad testing either, but he has a different explanation for lack of interest in this approach – or, indeed, any form of self-sampling for cervical cancer screening – in the United States.

“We have not seen movement happen in this space for years. ... If there is one intervention that we can simplify, that still has not been made widely available, it is self-sampling ... [but] we don’t have [Food and Drug Administration] approval for it,” Dr. Sahasrabuddhe said.

“Our system, at least in the U.S., is based on industry manufacturers seeking an approval for a particular way of collection and then clinicians and clinical-guideline bodies signing on. ... For a lot of reasons industry has shied away over the past several years, so far, at least, on seeking approval for self-sampling-based approaches,” he commented.

Dr. Sahasrabuddhe aims to change that. He heads a new NCI-led initiative called “The Last Mile,” a nationwide clinical trial supported by federal agencies, industry partners, and professional societies. The goal is to validate self-sampled HPV testing as non-inferior to specimens collected by providers. The team is currently finalizing the methodology of the study, so Dr. Sahasrabuddhe could not share the self-sampling methods that will be on trial, nor the industry partners who have signed up.

The following tests are approved in the United States for physician-collected HPV screening: Hybrid Capture 2, used in the Indian studies (Qiagen); cobas HPV (Roche); Aptima (Hologic); Cervista (Hologic); and Onclarity (Becton Dickinson).

Dr. Sahasrabuddhe said that, while a sanitary pad in a Ziploc bag is unlikely to make the grade for The Last Mile study, he doesn’t totally dismiss their potential and said the NCI is always open to new ideas.

“We are not supporting anybody specifically for menstrual pad-based collection device development,” Dr. Sahasrabuddhe said, “But if they fulfill other criteria for a small business–based grant application, they absolutely are welcome to apply for NCI funding for this.”

Said Dr. Melnikow: “Pre-COVID, the head of [the World Health Organization] said that we could eliminate cervical cancer from the globe and that we have the tools to do that now. And he’s right.”

Dr. Budukh, Dr. Melnikow, and Dr. Sahasrabuddhe disclosed no relevant financial relationships.

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

In the presentation of secondary amenorrhea, pregnancy is the No. 1 differential diagnosis. Once this has been excluded, an algorithm is initiated to determine the etiology, including an assessment of the hypothalamic-pituitary-ovarian axis. While the early onset of ovarian failure can be physically and psychologically disrupting, the effect on fertility is an especially devastating event. Previously identified by terms including premature ovarian failure and premature menopause, “primary ovarian insufficiency” (POI) is now the preferred designation. This month’s article will address the diagnosis, evaluation, and management of POI.

The definition of POI is the development of primary hypogonadism before the age of 40 years. Spontaneous POI occurs in approximately 1 in 250 women by age 35 years and 1 in 100 by age 40 years. After excluding pregnancy, the clinician should determine signs and symptoms that can lead to expedited and cost-efficient testing.

Consequences

POI is an important risk factor for bone loss and osteoporosis, especially in young women who develop ovarian dysfunction before they achieve peak adult bone mass. At the time of diagnosis of POI, a bone density test (dual-energy x-ray absorptiometry) should be obtained. Women with POI may also develop depression and anxiety as well as experience an increased risk for cardiovascular morbidity and mortality, possibly related to endothelial dysfunction.

Young women with spontaneous POI are at increased risk of developing autoimmune adrenal insufficiency (AAI), a potentially fatal disorder. Consequently, to diagnose AAI, serum adrenal cortical and 21-hydroxylase antibodies should be measured in all women who have a karyotype of 46,XX and experience spontaneous POI. Women with AAI have a 50% risk of developing adrenal insufficiency. Despite initial normal adrenal function, women with positive adrenal cortical antibodies should be followed annually.
 

Causes (see table for a more complete list)

Iatrogenic

Known causes of POI include chemotherapy/radiation often in the setting of cancer treatment. The three most commonly used drugs, cyclophosphamide, cisplatin, and doxorubicin, cause POI by inducing death and/or accelerated activation of primordial follicles and increased atresia of growing follicles. The most damaging agents are alkylating drugs. A cyclophosphamide equivalent dose calculator has been established for ovarian failure risk stratification from chemotherapy based on the cumulative dose of alkylating agents received.

One study estimated the radiosensitivity of the oocyte to be less than 2 Gy. Based upon this estimate, the authors calculated the dose of radiotherapy that would result in immediate and permanent ovarian failure in 97.5% of patients as follows:

• 20.3 Gy at birth
• 18.4 Gy at age 10 years
• 16.5 Gy at age 20 years
• 14.3 Gy at age 30 years

Genetic

Approximately 10% of cases are familial. A family history of POI raises concern for a fragile X premutation. Fragile X syndrome is an X-linked form of intellectual disability that is one of the most common causes of mental retardation worldwide. There is a strong relationship between age at menopause, including POI, and premutations for fragile X syndrome. The American College of Obstetricians and Gynecologists recommends that women with POI or an elevated follicle-stimulating hormone (FSH) level before age 40 years without known cause be screened for FMR1 premutations. Approximately 6% of cases of POI are associated with premutations in the FMR1 gene.

Turner syndrome is one of the most common causes of POI and results from the lack of a second X chromosome. The most common chromosomal defect in humans, TS occurs in up to 1.5% of conceptions, 10% of spontaneous abortions, and 1 of 2,500 live births.

Serum antiadrenal and/or anti–21-hydroxylase antibodies and antithyroid antiperoxidase antibodies, can aid in the diagnosis of adrenal gland, ovary, and thyroid autoimmune causes, which is found in 4% of women with spontaneous POI. Testing for the presence of 21-hydroxylase autoantibodies or adrenal autoantibodies is sufficient to make the diagnosis of autoimmune oophoritis in women with proven spontaneous POI.

The etiology of POI remains unknown in approximately 75%-90% of cases. However, studies using whole exome or whole genome sequencing have identified genetic variants in approximately 30%-35% of these patients.
 

Risk factors

Factors that are thought to play a role in determining the age of menopause, include genetics (e.g., FMR1 premutation and mosaic Turner syndrome), ethnicity (earlier among Hispanic women and later in Japanese American women when compared with White women), and smoking (reduced by approximately 2 years ).

Regarding ovarian aging, the holy grail of the reproductive life span is to predict menopause. While the definitive age eludes us, anti-Müllerian hormone levels appear to show promise. An ultrasensitive anti-Müllerian hormone assay (< 0.01 ng/mL) predicted a 79% probability of menopause within 12 months for women aged 51 and above; the probability was 51% for women below age 48.
 

Diagnosis

The three P’s of secondary amenorrhea are physiological, pharmacological, or pathological and can guide the clinician to a targeted evaluation. Physiological causes are pregnancy, the first 6 months of continuous breastfeeding (from elevated prolactin), and natural menopause. Pharmacological etiologies, excluding hormonal treatment that suppresses ovulation (combined oral contraceptives, gonadotropin-releasing hormone agonist/antagonist, or danazol), include agents that inhibit dopamine thereby increasing serum prolactin, such as metoclopramide; phenothiazine antipsychotics, such as haloperidol; and tardive dystonia dopamine-depleting medications, such as reserpine. Pathological causes include pituitary adenomas, thyroid disease, functional hypothalamic amenorrhea from changes in weight, exercise regimen, and stress.

Management

About 50%-75% of women with 46,XX spontaneous POI experience intermittent ovarian function and 5%-10% of women remain able to conceive. Anecdotally, a 32-year-old woman presented to me with primary infertility, secondary amenorrhea, and suspected POI based on vasomotor symptoms and elevated FSH levels. Pelvic ultrasound showed a hemorrhagic cyst, suspicious for a corpus luteum. Two weeks thereafter she reported a positive home urine human chorionic gonadotropin test and ultimately delivered twins. Her diagnosis of POI with amenorrhea remained postpartum.

Unless there is an absolute contraindication, estrogen therapy should be prescribed to women with POI to reduce the risk of osteoporosis, cardiovascular disease, and urogenital atrophy as well as to maintain sexual health and quality of life. For those with an intact uterus, women should receive progesterone because of the risk of endometrial hyperplasia from unopposed estrogen. Rather than oral estrogen, the use of transdermal or vaginal delivery of estrogen is a more physiological approach and provides lower risks of venous thromboembolism and gallbladder disease. Of note, standard postmenopausal hormone therapy, which has a much lower dose of estrogen than combined estrogen-progestin contraceptives, does not provide effective contraception. Per ACOG, systemic hormone treatment should be prescribed until age 50-51 years to all women with POI.

For fertility, women with spontaneous POI can be offered oocyte or embryo donation. The uterus does not age reproductively, unlike oocytes, therefore women can achieve reasonable pregnancy success rates through egg donation despite experiencing menopause.
 

Future potential options

Female germline stem cells have been isolated from neonatal mice and transplanted into sterile adult mice, who then were able to produce offspring. In a second study, oogonial stem cells were isolated from neonatal and adult mouse ovaries; pups were subsequently born from the oocytes. Further experiments are needed before the implications for humans can be determined.

Emotionally traumatic for most women, POI disrupts life plans, hopes, and dreams of raising a family. The approach to the patient with POI involves the above evidence-based testing along with empathy from the health care provider.

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

In the presentation of secondary amenorrhea, pregnancy is the No. 1 differential diagnosis. Once this has been excluded, an algorithm is initiated to determine the etiology, including an assessment of the hypothalamic-pituitary-ovarian axis. While the early onset of ovarian failure can be physically and psychologically disrupting, the effect on fertility is an especially devastating event. Previously identified by terms including premature ovarian failure and premature menopause, “primary ovarian insufficiency” (POI) is now the preferred designation. This month’s article will address the diagnosis, evaluation, and management of POI.

The definition of POI is the development of primary hypogonadism before the age of 40 years. Spontaneous POI occurs in approximately 1 in 250 women by age 35 years and 1 in 100 by age 40 years. After excluding pregnancy, the clinician should determine signs and symptoms that can lead to expedited and cost-efficient testing.

Consequences

POI is an important risk factor for bone loss and osteoporosis, especially in young women who develop ovarian dysfunction before they achieve peak adult bone mass. At the time of diagnosis of POI, a bone density test (dual-energy x-ray absorptiometry) should be obtained. Women with POI may also develop depression and anxiety as well as experience an increased risk for cardiovascular morbidity and mortality, possibly related to endothelial dysfunction.

Young women with spontaneous POI are at increased risk of developing autoimmune adrenal insufficiency (AAI), a potentially fatal disorder. Consequently, to diagnose AAI, serum adrenal cortical and 21-hydroxylase antibodies should be measured in all women who have a karyotype of 46,XX and experience spontaneous POI. Women with AAI have a 50% risk of developing adrenal insufficiency. Despite initial normal adrenal function, women with positive adrenal cortical antibodies should be followed annually.
 

Causes (see table for a more complete list)

Iatrogenic

Known causes of POI include chemotherapy/radiation often in the setting of cancer treatment. The three most commonly used drugs, cyclophosphamide, cisplatin, and doxorubicin, cause POI by inducing death and/or accelerated activation of primordial follicles and increased atresia of growing follicles. The most damaging agents are alkylating drugs. A cyclophosphamide equivalent dose calculator has been established for ovarian failure risk stratification from chemotherapy based on the cumulative dose of alkylating agents received.

One study estimated the radiosensitivity of the oocyte to be less than 2 Gy. Based upon this estimate, the authors calculated the dose of radiotherapy that would result in immediate and permanent ovarian failure in 97.5% of patients as follows:

• 20.3 Gy at birth
• 18.4 Gy at age 10 years
• 16.5 Gy at age 20 years
• 14.3 Gy at age 30 years

Genetic

Approximately 10% of cases are familial. A family history of POI raises concern for a fragile X premutation. Fragile X syndrome is an X-linked form of intellectual disability that is one of the most common causes of mental retardation worldwide. There is a strong relationship between age at menopause, including POI, and premutations for fragile X syndrome. The American College of Obstetricians and Gynecologists recommends that women with POI or an elevated follicle-stimulating hormone (FSH) level before age 40 years without known cause be screened for FMR1 premutations. Approximately 6% of cases of POI are associated with premutations in the FMR1 gene.

Turner syndrome is one of the most common causes of POI and results from the lack of a second X chromosome. The most common chromosomal defect in humans, TS occurs in up to 1.5% of conceptions, 10% of spontaneous abortions, and 1 of 2,500 live births.

Serum antiadrenal and/or anti–21-hydroxylase antibodies and antithyroid antiperoxidase antibodies, can aid in the diagnosis of adrenal gland, ovary, and thyroid autoimmune causes, which is found in 4% of women with spontaneous POI. Testing for the presence of 21-hydroxylase autoantibodies or adrenal autoantibodies is sufficient to make the diagnosis of autoimmune oophoritis in women with proven spontaneous POI.

The etiology of POI remains unknown in approximately 75%-90% of cases. However, studies using whole exome or whole genome sequencing have identified genetic variants in approximately 30%-35% of these patients.
 

Risk factors

Factors that are thought to play a role in determining the age of menopause, include genetics (e.g., FMR1 premutation and mosaic Turner syndrome), ethnicity (earlier among Hispanic women and later in Japanese American women when compared with White women), and smoking (reduced by approximately 2 years ).

Regarding ovarian aging, the holy grail of the reproductive life span is to predict menopause. While the definitive age eludes us, anti-Müllerian hormone levels appear to show promise. An ultrasensitive anti-Müllerian hormone assay (< 0.01 ng/mL) predicted a 79% probability of menopause within 12 months for women aged 51 and above; the probability was 51% for women below age 48.
 

Diagnosis

The three P’s of secondary amenorrhea are physiological, pharmacological, or pathological and can guide the clinician to a targeted evaluation. Physiological causes are pregnancy, the first 6 months of continuous breastfeeding (from elevated prolactin), and natural menopause. Pharmacological etiologies, excluding hormonal treatment that suppresses ovulation (combined oral contraceptives, gonadotropin-releasing hormone agonist/antagonist, or danazol), include agents that inhibit dopamine thereby increasing serum prolactin, such as metoclopramide; phenothiazine antipsychotics, such as haloperidol; and tardive dystonia dopamine-depleting medications, such as reserpine. Pathological causes include pituitary adenomas, thyroid disease, functional hypothalamic amenorrhea from changes in weight, exercise regimen, and stress.

Management

About 50%-75% of women with 46,XX spontaneous POI experience intermittent ovarian function and 5%-10% of women remain able to conceive. Anecdotally, a 32-year-old woman presented to me with primary infertility, secondary amenorrhea, and suspected POI based on vasomotor symptoms and elevated FSH levels. Pelvic ultrasound showed a hemorrhagic cyst, suspicious for a corpus luteum. Two weeks thereafter she reported a positive home urine human chorionic gonadotropin test and ultimately delivered twins. Her diagnosis of POI with amenorrhea remained postpartum.

Unless there is an absolute contraindication, estrogen therapy should be prescribed to women with POI to reduce the risk of osteoporosis, cardiovascular disease, and urogenital atrophy as well as to maintain sexual health and quality of life. For those with an intact uterus, women should receive progesterone because of the risk of endometrial hyperplasia from unopposed estrogen. Rather than oral estrogen, the use of transdermal or vaginal delivery of estrogen is a more physiological approach and provides lower risks of venous thromboembolism and gallbladder disease. Of note, standard postmenopausal hormone therapy, which has a much lower dose of estrogen than combined estrogen-progestin contraceptives, does not provide effective contraception. Per ACOG, systemic hormone treatment should be prescribed until age 50-51 years to all women with POI.

For fertility, women with spontaneous POI can be offered oocyte or embryo donation. The uterus does not age reproductively, unlike oocytes, therefore women can achieve reasonable pregnancy success rates through egg donation despite experiencing menopause.
 

Future potential options

Female germline stem cells have been isolated from neonatal mice and transplanted into sterile adult mice, who then were able to produce offspring. In a second study, oogonial stem cells were isolated from neonatal and adult mouse ovaries; pups were subsequently born from the oocytes. Further experiments are needed before the implications for humans can be determined.

Emotionally traumatic for most women, POI disrupts life plans, hopes, and dreams of raising a family. The approach to the patient with POI involves the above evidence-based testing along with empathy from the health care provider.

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

In the presentation of secondary amenorrhea, pregnancy is the No. 1 differential diagnosis. Once this has been excluded, an algorithm is initiated to determine the etiology, including an assessment of the hypothalamic-pituitary-ovarian axis. While the early onset of ovarian failure can be physically and psychologically disrupting, the effect on fertility is an especially devastating event. Previously identified by terms including premature ovarian failure and premature menopause, “primary ovarian insufficiency” (POI) is now the preferred designation. This month’s article will address the diagnosis, evaluation, and management of POI.

The definition of POI is the development of primary hypogonadism before the age of 40 years. Spontaneous POI occurs in approximately 1 in 250 women by age 35 years and 1 in 100 by age 40 years. After excluding pregnancy, the clinician should determine signs and symptoms that can lead to expedited and cost-efficient testing.

Consequences

POI is an important risk factor for bone loss and osteoporosis, especially in young women who develop ovarian dysfunction before they achieve peak adult bone mass. At the time of diagnosis of POI, a bone density test (dual-energy x-ray absorptiometry) should be obtained. Women with POI may also develop depression and anxiety as well as experience an increased risk for cardiovascular morbidity and mortality, possibly related to endothelial dysfunction.

Young women with spontaneous POI are at increased risk of developing autoimmune adrenal insufficiency (AAI), a potentially fatal disorder. Consequently, to diagnose AAI, serum adrenal cortical and 21-hydroxylase antibodies should be measured in all women who have a karyotype of 46,XX and experience spontaneous POI. Women with AAI have a 50% risk of developing adrenal insufficiency. Despite initial normal adrenal function, women with positive adrenal cortical antibodies should be followed annually.
 

Causes (see table for a more complete list)

Iatrogenic

Known causes of POI include chemotherapy/radiation often in the setting of cancer treatment. The three most commonly used drugs, cyclophosphamide, cisplatin, and doxorubicin, cause POI by inducing death and/or accelerated activation of primordial follicles and increased atresia of growing follicles. The most damaging agents are alkylating drugs. A cyclophosphamide equivalent dose calculator has been established for ovarian failure risk stratification from chemotherapy based on the cumulative dose of alkylating agents received.

One study estimated the radiosensitivity of the oocyte to be less than 2 Gy. Based upon this estimate, the authors calculated the dose of radiotherapy that would result in immediate and permanent ovarian failure in 97.5% of patients as follows:

• 20.3 Gy at birth
• 18.4 Gy at age 10 years
• 16.5 Gy at age 20 years
• 14.3 Gy at age 30 years

Genetic

Approximately 10% of cases are familial. A family history of POI raises concern for a fragile X premutation. Fragile X syndrome is an X-linked form of intellectual disability that is one of the most common causes of mental retardation worldwide. There is a strong relationship between age at menopause, including POI, and premutations for fragile X syndrome. The American College of Obstetricians and Gynecologists recommends that women with POI or an elevated follicle-stimulating hormone (FSH) level before age 40 years without known cause be screened for FMR1 premutations. Approximately 6% of cases of POI are associated with premutations in the FMR1 gene.

Turner syndrome is one of the most common causes of POI and results from the lack of a second X chromosome. The most common chromosomal defect in humans, TS occurs in up to 1.5% of conceptions, 10% of spontaneous abortions, and 1 of 2,500 live births.

Serum antiadrenal and/or anti–21-hydroxylase antibodies and antithyroid antiperoxidase antibodies, can aid in the diagnosis of adrenal gland, ovary, and thyroid autoimmune causes, which is found in 4% of women with spontaneous POI. Testing for the presence of 21-hydroxylase autoantibodies or adrenal autoantibodies is sufficient to make the diagnosis of autoimmune oophoritis in women with proven spontaneous POI.

The etiology of POI remains unknown in approximately 75%-90% of cases. However, studies using whole exome or whole genome sequencing have identified genetic variants in approximately 30%-35% of these patients.
 

Risk factors

Factors that are thought to play a role in determining the age of menopause, include genetics (e.g., FMR1 premutation and mosaic Turner syndrome), ethnicity (earlier among Hispanic women and later in Japanese American women when compared with White women), and smoking (reduced by approximately 2 years ).

Regarding ovarian aging, the holy grail of the reproductive life span is to predict menopause. While the definitive age eludes us, anti-Müllerian hormone levels appear to show promise. An ultrasensitive anti-Müllerian hormone assay (< 0.01 ng/mL) predicted a 79% probability of menopause within 12 months for women aged 51 and above; the probability was 51% for women below age 48.
 

Diagnosis

The three P’s of secondary amenorrhea are physiological, pharmacological, or pathological and can guide the clinician to a targeted evaluation. Physiological causes are pregnancy, the first 6 months of continuous breastfeeding (from elevated prolactin), and natural menopause. Pharmacological etiologies, excluding hormonal treatment that suppresses ovulation (combined oral contraceptives, gonadotropin-releasing hormone agonist/antagonist, or danazol), include agents that inhibit dopamine thereby increasing serum prolactin, such as metoclopramide; phenothiazine antipsychotics, such as haloperidol; and tardive dystonia dopamine-depleting medications, such as reserpine. Pathological causes include pituitary adenomas, thyroid disease, functional hypothalamic amenorrhea from changes in weight, exercise regimen, and stress.

Management

About 50%-75% of women with 46,XX spontaneous POI experience intermittent ovarian function and 5%-10% of women remain able to conceive. Anecdotally, a 32-year-old woman presented to me with primary infertility, secondary amenorrhea, and suspected POI based on vasomotor symptoms and elevated FSH levels. Pelvic ultrasound showed a hemorrhagic cyst, suspicious for a corpus luteum. Two weeks thereafter she reported a positive home urine human chorionic gonadotropin test and ultimately delivered twins. Her diagnosis of POI with amenorrhea remained postpartum.

Unless there is an absolute contraindication, estrogen therapy should be prescribed to women with POI to reduce the risk of osteoporosis, cardiovascular disease, and urogenital atrophy as well as to maintain sexual health and quality of life. For those with an intact uterus, women should receive progesterone because of the risk of endometrial hyperplasia from unopposed estrogen. Rather than oral estrogen, the use of transdermal or vaginal delivery of estrogen is a more physiological approach and provides lower risks of venous thromboembolism and gallbladder disease. Of note, standard postmenopausal hormone therapy, which has a much lower dose of estrogen than combined estrogen-progestin contraceptives, does not provide effective contraception. Per ACOG, systemic hormone treatment should be prescribed until age 50-51 years to all women with POI.

For fertility, women with spontaneous POI can be offered oocyte or embryo donation. The uterus does not age reproductively, unlike oocytes, therefore women can achieve reasonable pregnancy success rates through egg donation despite experiencing menopause.
 

Future potential options

Female germline stem cells have been isolated from neonatal mice and transplanted into sterile adult mice, who then were able to produce offspring. In a second study, oogonial stem cells were isolated from neonatal and adult mouse ovaries; pups were subsequently born from the oocytes. Further experiments are needed before the implications for humans can be determined.

Emotionally traumatic for most women, POI disrupts life plans, hopes, and dreams of raising a family. The approach to the patient with POI involves the above evidence-based testing along with empathy from the health care provider.

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

All along, Julia Maeda knew she wanted to have her baby naturally. For her, that meant in a hospital, vaginally, without an epidural for pain relief.

This was her first pregnancy. And although she is a nurse, she was working with cancer patients at the time, not with laboring mothers or babies. “I really didn’t know what I was getting into,” said Ms. Maeda, now 32. “I didn’t do much preparation.”

Her home state of Mississippi has the highest cesarean section rate in the United States – nearly 4 in 10 women who give birth there deliver their babies via C-section. Almost 2 weeks past her due date in 2019, Ms. Maeda became one of them after her doctor came to her bedside while she was in labor.

“‘You’re not in distress, and your baby is not in distress – but we don’t want you to get that way, so we need to think about a C-section,’” she recalled her doctor saying. “I was totally defeated. I just gave in.”

C-sections are sometimes necessary and even lifesaving, but public health experts have long contended that too many performed in the U.S. aren’t. They argue it is major surgery accompanied by significant risk and a high price tag.

Overall, 31.8% of all births in the U.S. were C-sections in 2020, just a slight tick up from 31.7% the year before, according to the latest data from the Centers for Disease Control and Prevention. But that’s close to the peak in 2009, when it was 32.9%. And the rates are far higher in many states, especially across the South.

These high C-section rates have persisted – and in some states, such as Alabama and Kentucky, even grown slightly – despite continual calls to reduce them. And although the pandemic presented new challenges for pregnant women, research suggests that the U.S. C-section rate was unaffected by COVID. Instead, obstetricians and other health experts say the high rate is an intractable problem.

Some states, such as California and New Jersey, have reduced their rates through a variety of strategies, including sharing C-section data with doctors and hospitals. But change has proved difficult elsewhere, especially in the South and in Texas, where women are generally less healthy heading into their pregnancies and maternal and infant health problems are among the highest in the United States.

“We have to restructure how we think about C-sections,” said Veronica Gillispie-Bell, MD, an ob.gyn. who is medical director of the Louisiana Perinatal Quality Collaborative, Kenner, La., a group of 43 birthing hospitals focused on lowering Louisiana’s C-section rate. “It’s a lifesaving technique, but it’s also not without risks.”

She said C-sections, like any operation, create scar tissue, including in the uterus, which may complicate future pregnancies or abdominal surgeries. C-sections also typically lead to an extended hospital stay and recovery period and increase the chance of infection. Babies face risks, too. In rare cases, they can be nicked or cut during an incision. 

Although C-sections are sometimes necessary, public health leaders say these surgeries have been overused in many places. Black women, particularly, are more likely to give birth by C-section than any other racial group in the country. Often, hospitals and even regions have wide, unexplained variations in rates.

“If you were delivering in Miami-Dade County, you had a 75% greater chance of having a cesarean than in northern Florida,” said William Sappenfield, MD, an ob.gyn. and epidemiologist at the University of South Florida, Tampa, who has studied the state’s high C-section rate.

Some physicians say their rates are driven by mothers who request the procedure, not by doctors. But Rebekah Gee, MD, an ob.gyn. at Louisiana State University Healthcare Network, New Orleans, and former secretary of the Louisiana Department of Health, said she saw C-section rates go dramatically up at 4 and 5 p.m. – around the time when doctors tend to want to go home.

She led several initiatives to improve birth outcomes in Louisiana, including leveling Medicaid payment rates to hospitals for vaginal deliveries and C-sections. In most places, C-sections are significantly more expensive than vaginal deliveries, making high C-section rates not only a concern for expectant mothers but also for taxpayers.

Medicaid pays for 60% of all births in Louisiana, according to KFF, and about half of all births in most Southern states, compared with 42% nationally. That’s one reason some states – including Louisiana, Tennessee, and Minnesota – have tried to tackle high C-section rates by changing how much Medicaid pays for them. But payment reform alone isn’t enough, Dr. Gee said.

“There was a guy in central Louisiana who was doing more C-sections and early elective deliveries than anyone in the U.S.,” she said. “When you have a culture like that, it’s hard to shift from it.”

Linda Schwimmer, president and CEO of the New Jersey Health Care Quality Institute, said many hospitals and doctors don’t even know their C-section rates. Sharing this data with doctors and hospitals – and making it public – made some providers uncomfortable, she said, but it ultimately worked. New Jersey’s C-section rate among first-time, low-risk mothers dropped from 33.1% in 2013 to 26.7% 6 years later once the state began sharing these data, among other initiatives.

The New Jersey Health Care Quality Institute and other groups like it around the country focus on reducing a subset of C-sections called “nulliparous, term, singleton, vertex” C-sections, or surgeries on first-time, full-term moms giving birth to a single infant who is positioned head-down in the uterus.

NTSV C-sections are important to track because women who have a C-section during their first pregnancy face a 90% chance of having another in subsequent pregnancies. Across the U.S., the rate for these C-sections was 25.9% in 2020 and 25.6% in 2019.

Elliott Main, MD, a maternal-fetal specialist at Stanford (Calif.) University and the medical director of the California Maternal Quality Care Collaborative, coauthored a paper, published in JAMA last year, that outlines interventions the collaborative took that lowered California’s NTSV C-Section rate from 26.0% in 2014 to 22.8% in 2019. Nationally, the rate was unchanged during that period.  

Allowing women to labor for longer stretches of time before resorting to surgery is important, he said.

The cervix must be 10 cm dilated before a woman gives birth. The threshold for “active labor” used to be when the cervix was dilated at least 4 cm. In more recent years, though, the onset of active labor has been changed to 5-6 cm.

“People show up at the hospital too early,” said Toni Hill, president of the Mississippi Midwives Alliance. “If you show up to the hospital at 2-3 centimeters, you can be at 2-3 centimeters for weeks. I don’t even consider that labor.”

Too often, she said, women at an early stage of labor end up being induced and deliver via C-section.

“It’s almost like, at this point, C-sections are being handed out like lollipops,” said LA’Patricia Washington, a doula based in Jackson, Miss. Doulas are trained, nonmedical workers who help parents before, during, and after delivery.

Ms. Washington works with a nonprofit group, the Jackson Safer Childbirth Experience, that pays for doulas to help expectant mothers in the region. Some state Medicaid programs, such as New Jersey’s, reimburse for services by doulas because research shows they can reduce C-section rates. California has been trying to roll out the same benefit for its Medicaid members.

In 2020, when Julia Maeda became pregnant again, she paid out-of-pocket for a doula to attend the birth. The experience of having her son via C-section the previous year had been “emotionally and psychologically traumatic,” Ms. Maeda said.

She told her ob.gyn. that she wanted a VBAC, short for “vaginal birth after cesarean.” But, she said, “he just shook his head and said, ‘That’s not a good idea.’”

She had VBAC anyway. Ms. Maeda credits her doula with making it happen. 

“Maybe just her presence relayed to the nursing staff that this was something I was serious about,” Ms. Maeda said. “They want you to have your baby during business hours. And biology doesn’t work that way.”
 

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

All along, Julia Maeda knew she wanted to have her baby naturally. For her, that meant in a hospital, vaginally, without an epidural for pain relief.

This was her first pregnancy. And although she is a nurse, she was working with cancer patients at the time, not with laboring mothers or babies. “I really didn’t know what I was getting into,” said Ms. Maeda, now 32. “I didn’t do much preparation.”

Her home state of Mississippi has the highest cesarean section rate in the United States – nearly 4 in 10 women who give birth there deliver their babies via C-section. Almost 2 weeks past her due date in 2019, Ms. Maeda became one of them after her doctor came to her bedside while she was in labor.

“‘You’re not in distress, and your baby is not in distress – but we don’t want you to get that way, so we need to think about a C-section,’” she recalled her doctor saying. “I was totally defeated. I just gave in.”

C-sections are sometimes necessary and even lifesaving, but public health experts have long contended that too many performed in the U.S. aren’t. They argue it is major surgery accompanied by significant risk and a high price tag.

Overall, 31.8% of all births in the U.S. were C-sections in 2020, just a slight tick up from 31.7% the year before, according to the latest data from the Centers for Disease Control and Prevention. But that’s close to the peak in 2009, when it was 32.9%. And the rates are far higher in many states, especially across the South.

These high C-section rates have persisted – and in some states, such as Alabama and Kentucky, even grown slightly – despite continual calls to reduce them. And although the pandemic presented new challenges for pregnant women, research suggests that the U.S. C-section rate was unaffected by COVID. Instead, obstetricians and other health experts say the high rate is an intractable problem.

Some states, such as California and New Jersey, have reduced their rates through a variety of strategies, including sharing C-section data with doctors and hospitals. But change has proved difficult elsewhere, especially in the South and in Texas, where women are generally less healthy heading into their pregnancies and maternal and infant health problems are among the highest in the United States.

“We have to restructure how we think about C-sections,” said Veronica Gillispie-Bell, MD, an ob.gyn. who is medical director of the Louisiana Perinatal Quality Collaborative, Kenner, La., a group of 43 birthing hospitals focused on lowering Louisiana’s C-section rate. “It’s a lifesaving technique, but it’s also not without risks.”

She said C-sections, like any operation, create scar tissue, including in the uterus, which may complicate future pregnancies or abdominal surgeries. C-sections also typically lead to an extended hospital stay and recovery period and increase the chance of infection. Babies face risks, too. In rare cases, they can be nicked or cut during an incision. 

Although C-sections are sometimes necessary, public health leaders say these surgeries have been overused in many places. Black women, particularly, are more likely to give birth by C-section than any other racial group in the country. Often, hospitals and even regions have wide, unexplained variations in rates.

“If you were delivering in Miami-Dade County, you had a 75% greater chance of having a cesarean than in northern Florida,” said William Sappenfield, MD, an ob.gyn. and epidemiologist at the University of South Florida, Tampa, who has studied the state’s high C-section rate.

Some physicians say their rates are driven by mothers who request the procedure, not by doctors. But Rebekah Gee, MD, an ob.gyn. at Louisiana State University Healthcare Network, New Orleans, and former secretary of the Louisiana Department of Health, said she saw C-section rates go dramatically up at 4 and 5 p.m. – around the time when doctors tend to want to go home.

She led several initiatives to improve birth outcomes in Louisiana, including leveling Medicaid payment rates to hospitals for vaginal deliveries and C-sections. In most places, C-sections are significantly more expensive than vaginal deliveries, making high C-section rates not only a concern for expectant mothers but also for taxpayers.

Medicaid pays for 60% of all births in Louisiana, according to KFF, and about half of all births in most Southern states, compared with 42% nationally. That’s one reason some states – including Louisiana, Tennessee, and Minnesota – have tried to tackle high C-section rates by changing how much Medicaid pays for them. But payment reform alone isn’t enough, Dr. Gee said.

“There was a guy in central Louisiana who was doing more C-sections and early elective deliveries than anyone in the U.S.,” she said. “When you have a culture like that, it’s hard to shift from it.”

Linda Schwimmer, president and CEO of the New Jersey Health Care Quality Institute, said many hospitals and doctors don’t even know their C-section rates. Sharing this data with doctors and hospitals – and making it public – made some providers uncomfortable, she said, but it ultimately worked. New Jersey’s C-section rate among first-time, low-risk mothers dropped from 33.1% in 2013 to 26.7% 6 years later once the state began sharing these data, among other initiatives.

The New Jersey Health Care Quality Institute and other groups like it around the country focus on reducing a subset of C-sections called “nulliparous, term, singleton, vertex” C-sections, or surgeries on first-time, full-term moms giving birth to a single infant who is positioned head-down in the uterus.

NTSV C-sections are important to track because women who have a C-section during their first pregnancy face a 90% chance of having another in subsequent pregnancies. Across the U.S., the rate for these C-sections was 25.9% in 2020 and 25.6% in 2019.

Elliott Main, MD, a maternal-fetal specialist at Stanford (Calif.) University and the medical director of the California Maternal Quality Care Collaborative, coauthored a paper, published in JAMA last year, that outlines interventions the collaborative took that lowered California’s NTSV C-Section rate from 26.0% in 2014 to 22.8% in 2019. Nationally, the rate was unchanged during that period.  

Allowing women to labor for longer stretches of time before resorting to surgery is important, he said.

The cervix must be 10 cm dilated before a woman gives birth. The threshold for “active labor” used to be when the cervix was dilated at least 4 cm. In more recent years, though, the onset of active labor has been changed to 5-6 cm.

“People show up at the hospital too early,” said Toni Hill, president of the Mississippi Midwives Alliance. “If you show up to the hospital at 2-3 centimeters, you can be at 2-3 centimeters for weeks. I don’t even consider that labor.”

Too often, she said, women at an early stage of labor end up being induced and deliver via C-section.

“It’s almost like, at this point, C-sections are being handed out like lollipops,” said LA’Patricia Washington, a doula based in Jackson, Miss. Doulas are trained, nonmedical workers who help parents before, during, and after delivery.

Ms. Washington works with a nonprofit group, the Jackson Safer Childbirth Experience, that pays for doulas to help expectant mothers in the region. Some state Medicaid programs, such as New Jersey’s, reimburse for services by doulas because research shows they can reduce C-section rates. California has been trying to roll out the same benefit for its Medicaid members.

In 2020, when Julia Maeda became pregnant again, she paid out-of-pocket for a doula to attend the birth. The experience of having her son via C-section the previous year had been “emotionally and psychologically traumatic,” Ms. Maeda said.

She told her ob.gyn. that she wanted a VBAC, short for “vaginal birth after cesarean.” But, she said, “he just shook his head and said, ‘That’s not a good idea.’”

She had VBAC anyway. Ms. Maeda credits her doula with making it happen. 

“Maybe just her presence relayed to the nursing staff that this was something I was serious about,” Ms. Maeda said. “They want you to have your baby during business hours. And biology doesn’t work that way.”
 

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

All along, Julia Maeda knew she wanted to have her baby naturally. For her, that meant in a hospital, vaginally, without an epidural for pain relief.

This was her first pregnancy. And although she is a nurse, she was working with cancer patients at the time, not with laboring mothers or babies. “I really didn’t know what I was getting into,” said Ms. Maeda, now 32. “I didn’t do much preparation.”

Her home state of Mississippi has the highest cesarean section rate in the United States – nearly 4 in 10 women who give birth there deliver their babies via C-section. Almost 2 weeks past her due date in 2019, Ms. Maeda became one of them after her doctor came to her bedside while she was in labor.

“‘You’re not in distress, and your baby is not in distress – but we don’t want you to get that way, so we need to think about a C-section,’” she recalled her doctor saying. “I was totally defeated. I just gave in.”

C-sections are sometimes necessary and even lifesaving, but public health experts have long contended that too many performed in the U.S. aren’t. They argue it is major surgery accompanied by significant risk and a high price tag.

Overall, 31.8% of all births in the U.S. were C-sections in 2020, just a slight tick up from 31.7% the year before, according to the latest data from the Centers for Disease Control and Prevention. But that’s close to the peak in 2009, when it was 32.9%. And the rates are far higher in many states, especially across the South.

These high C-section rates have persisted – and in some states, such as Alabama and Kentucky, even grown slightly – despite continual calls to reduce them. And although the pandemic presented new challenges for pregnant women, research suggests that the U.S. C-section rate was unaffected by COVID. Instead, obstetricians and other health experts say the high rate is an intractable problem.

Some states, such as California and New Jersey, have reduced their rates through a variety of strategies, including sharing C-section data with doctors and hospitals. But change has proved difficult elsewhere, especially in the South and in Texas, where women are generally less healthy heading into their pregnancies and maternal and infant health problems are among the highest in the United States.

“We have to restructure how we think about C-sections,” said Veronica Gillispie-Bell, MD, an ob.gyn. who is medical director of the Louisiana Perinatal Quality Collaborative, Kenner, La., a group of 43 birthing hospitals focused on lowering Louisiana’s C-section rate. “It’s a lifesaving technique, but it’s also not without risks.”

She said C-sections, like any operation, create scar tissue, including in the uterus, which may complicate future pregnancies or abdominal surgeries. C-sections also typically lead to an extended hospital stay and recovery period and increase the chance of infection. Babies face risks, too. In rare cases, they can be nicked or cut during an incision. 

Although C-sections are sometimes necessary, public health leaders say these surgeries have been overused in many places. Black women, particularly, are more likely to give birth by C-section than any other racial group in the country. Often, hospitals and even regions have wide, unexplained variations in rates.

“If you were delivering in Miami-Dade County, you had a 75% greater chance of having a cesarean than in northern Florida,” said William Sappenfield, MD, an ob.gyn. and epidemiologist at the University of South Florida, Tampa, who has studied the state’s high C-section rate.

Some physicians say their rates are driven by mothers who request the procedure, not by doctors. But Rebekah Gee, MD, an ob.gyn. at Louisiana State University Healthcare Network, New Orleans, and former secretary of the Louisiana Department of Health, said she saw C-section rates go dramatically up at 4 and 5 p.m. – around the time when doctors tend to want to go home.

She led several initiatives to improve birth outcomes in Louisiana, including leveling Medicaid payment rates to hospitals for vaginal deliveries and C-sections. In most places, C-sections are significantly more expensive than vaginal deliveries, making high C-section rates not only a concern for expectant mothers but also for taxpayers.

Medicaid pays for 60% of all births in Louisiana, according to KFF, and about half of all births in most Southern states, compared with 42% nationally. That’s one reason some states – including Louisiana, Tennessee, and Minnesota – have tried to tackle high C-section rates by changing how much Medicaid pays for them. But payment reform alone isn’t enough, Dr. Gee said.

“There was a guy in central Louisiana who was doing more C-sections and early elective deliveries than anyone in the U.S.,” she said. “When you have a culture like that, it’s hard to shift from it.”

Linda Schwimmer, president and CEO of the New Jersey Health Care Quality Institute, said many hospitals and doctors don’t even know their C-section rates. Sharing this data with doctors and hospitals – and making it public – made some providers uncomfortable, she said, but it ultimately worked. New Jersey’s C-section rate among first-time, low-risk mothers dropped from 33.1% in 2013 to 26.7% 6 years later once the state began sharing these data, among other initiatives.

The New Jersey Health Care Quality Institute and other groups like it around the country focus on reducing a subset of C-sections called “nulliparous, term, singleton, vertex” C-sections, or surgeries on first-time, full-term moms giving birth to a single infant who is positioned head-down in the uterus.

NTSV C-sections are important to track because women who have a C-section during their first pregnancy face a 90% chance of having another in subsequent pregnancies. Across the U.S., the rate for these C-sections was 25.9% in 2020 and 25.6% in 2019.

Elliott Main, MD, a maternal-fetal specialist at Stanford (Calif.) University and the medical director of the California Maternal Quality Care Collaborative, coauthored a paper, published in JAMA last year, that outlines interventions the collaborative took that lowered California’s NTSV C-Section rate from 26.0% in 2014 to 22.8% in 2019. Nationally, the rate was unchanged during that period.  

Allowing women to labor for longer stretches of time before resorting to surgery is important, he said.

The cervix must be 10 cm dilated before a woman gives birth. The threshold for “active labor” used to be when the cervix was dilated at least 4 cm. In more recent years, though, the onset of active labor has been changed to 5-6 cm.

“People show up at the hospital too early,” said Toni Hill, president of the Mississippi Midwives Alliance. “If you show up to the hospital at 2-3 centimeters, you can be at 2-3 centimeters for weeks. I don’t even consider that labor.”

Too often, she said, women at an early stage of labor end up being induced and deliver via C-section.

“It’s almost like, at this point, C-sections are being handed out like lollipops,” said LA’Patricia Washington, a doula based in Jackson, Miss. Doulas are trained, nonmedical workers who help parents before, during, and after delivery.

Ms. Washington works with a nonprofit group, the Jackson Safer Childbirth Experience, that pays for doulas to help expectant mothers in the region. Some state Medicaid programs, such as New Jersey’s, reimburse for services by doulas because research shows they can reduce C-section rates. California has been trying to roll out the same benefit for its Medicaid members.

In 2020, when Julia Maeda became pregnant again, she paid out-of-pocket for a doula to attend the birth. The experience of having her son via C-section the previous year had been “emotionally and psychologically traumatic,” Ms. Maeda said.

She told her ob.gyn. that she wanted a VBAC, short for “vaginal birth after cesarean.” But, she said, “he just shook his head and said, ‘That’s not a good idea.’”

She had VBAC anyway. Ms. Maeda credits her doula with making it happen. 

“Maybe just her presence relayed to the nursing staff that this was something I was serious about,” Ms. Maeda said. “They want you to have your baby during business hours. And biology doesn’t work that way.”
 

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

Kelsey Kennedy is a Family Nurse Practitioner (FNP) and has been working as a nurse practitioner in the Women's Health Institute at the Cleveland Clinic in General Gynecology for the past three years. She has her undergraduate degree from Saint Louis University and completed her graduate studies at Walsh University. She works with patients providing annual/wellness care, contraceptive counseling, abnormal bleeding evaluation and addresses many other non-OB gynecologic issues. The best part about her job is connecting with women and empowering the women she serves to be in control of their reproductive health and wellness.

As a nurse practitioner focused on benign gynecological treatment, what is your role as it relates to uterine fibroids, which are benign non-cancerous tumors?

Ms. Kennedy: As Nurse Practitioner (NP) working in GYN, I see both common and complex gynecologic, sexual, reproductive, menopausal issues. We really do it all. The NP collaborates with the entire medical health care team, including physicians, medical assistants, nursing, and administrators.

In the outpatient office practice with the Cleveland Clinic, I provide mostly benign or general GYN care, which means I see a lot of annual wellness exams, infection checks, birth control consults, and abnormal bleeding. I see patients that may have complaints of heavy periods, pelvic pain, pressure, but they might not have a formal diagnosis or know exactly why they have such heavy periods. Sometimes I see patients that have never even heard of fibroids. It’s my job to take a thorough history, perform a physical exam, and order any additional testing indicated to get the workup started to figure out exactly what's going on.

Abnormal uterine bleeding is defined as a change in the frequency, duration, or amount of menstrual bleeding. It's a common GYN complaint that affects anywhere from 10% to 30% of reproductive age women. In fact, abnormal bleeding is the reason for 1/3 of all outpatient GYN visits and a common cause of abnormal uterine bleeding is fibroids.

So just to review, fibroids are those benign, meaning non-cancerous, tumors made of smooth muscle tissue. Fibroids affect up to 40% of women of reproductive age. And by age 50, up to 70% of women have at least one fibroid. Fibroids are very common. It is important to know that only about 25% of fibroids are clinically significant or problematic enough to require intervention. With that being said, we know that fibroids can be asymptomatic, but often, they can cause pain and bleeding.

Some situations that occur that might make me suspect fibroids include a history of periods that are regular, once monthly, but progressively becoming heavier and heavier over time; periods that last longer than seven days; menstrual bleeding so heavy patients soak through overnight pads or their clothes during the day or overnight; menstrual bleeding with large clots; pelvic pain; pressure; urinary frequency, which could be related to fibroids pressing on the bladder; or constipation, which we know has many causes but can sometimes be related to fibroids pressing on the rectum. That’s it.

What impact does Long-Acting Reversible Contraception, or LARC, have on the uterus?

Ms. Kennedy: Generally speaking, Long-Acting Reversible Contraception, or LARC, is a broad category of birth control methods that provide contraception for an extended period of time-- anywhere from 3 to 10 years, depending on the type you choose. The best part about LARC options is they do not require user action. It's 99% effective in preventing unwanted pregnancy. I like to call it set-it-and-forget-it birth control.

The LARC options we have included are all the IUDs, which consists of the Paragard or copper IUD, and the three different hormonal IUDs-- the Mirena, Kyleena, and the Skyla. That also includes the Nexplanon arm implant. Out of all these LARC options, the Mirena IUD is the only one that’s FDA approved to treat heavy menstrual bleeding which can include heavy menstrual bleeding related to fibroids. The Mirena is FDA approved right now for seven years of use, which is a nice long time to get a lot of good benefit.

The Mirena IUD, specifically, is a T-shaped device that's placed in the uterus. It releases a steady local, meaning the hormone is released pretty much just in the uterus, amount of levonorgestrel, which is a second-generation synthetic progesterone. Basically, it's a hormone. The Mirena releases 20 micrograms of levonorgestrel into the uterus every day. What this hormone does is cause a dramatic reduction of blood flow by changing the endometrium, or the lining of the uterus.

The Mirena IUD was found to reduce blood loss by 86% after three months of use and by up to 97% after 12 months of use. This big reduction in bleeding subsequently leads to an increase in iron and hemoglobin levels in women with heavy bleeding and fibroids.

Hysterectomy has long been the definitive solution for abnormal bleeding that doesn't respond to our usual treatments. But since the Mirena was developed in the 1990s, more and more evidence has come to light that the Mirena can be a safe and effective medical alternative to hysterectomy. Many women benefit from and seek other management options for bleeding and heavy bleeding relating to fibroids other than hysterectomy because they might desire future childbearing, or they just might want to retain their uterus.

In addition, we also know that fibroids typically regress in menopause. Using the Mirena IUD is a great solution to control heavy bleeding that a woman can use until they're in menopause and no longer having periods. The Mirena IUD is much less invasive than a hysterectomy and has lower risk for complications.

What steps do you take to identify encounters that might impose challenges as it relates to the uterine structure?

Ms. Kennedy: One thing that may impose a challenge in using the Mirena IUD to manage heavy bleeding related to fibroids is the specific size and location of the fibroids. Submucosal fibroids, also called intracavitary fibroids, grow into the uterus. These submucosal fibroids grow just below the inner lining of the uterus. They often cause more bleeding and problems than other types of fibroids because they crowd the uterine space. If the submucosal fibroid is too big or filling up too much of the uterine cavity, there may not be enough room for us to place a Mirena IUD.

The rates of IUD expulsion are increased in patients with fibroids that distort the uterine cavity. That's one thing we definitely want to consider. I typically refer these patients to one of my GYN surgeon colleagues to determine if the submucosal fibroid should be removed hysteroscopically in the OR. Sometimes after removing these submucosal fibroids via hysteroscopy in the OR, the surgeons will place the Mirena IUD at the end of the case.

I think you touched on this a little bit, but are there methods, in addition to IUDs, that would assist in managing heavy menstrual bleeding associated with uterine fibroids?

Ms. Kennedy: Yes. We have several current methods to manage heavy menstrual bleeding associated with uterine fibroids. One method is simply expectant management or watchful waiting. This means that the amount of bleeding or pain a woman is having related to fibroids is neither severe nor debilitating for her, but we continue to monitor them closely. We usually review what criteria the patient should look out for that may indicate she needs to follow up on, for us to take a closer look at her fibroids. Typically, that would be worsening bleeding or worsening pain.

Some oral medication options are hormonal methods which can include combined oral birth control pills, oral progesterone pills, and sometimes we use injections such as Depo-Provera, which is typically used for birth control. Oral contraceptives can reduce bleeding associated with fibroids by about 40% to 50%.

We also have non-hormonal medications like tranexamic acid, or Lysteda, which is an antifibrinolytic agent that women take only during their monthly periods for up to five days. Women who have a history of clots cannot take this drug. However, for women who can safely use this medication, on average, Lysteda has been shown to reduce the amount of blood loss during monthly periods by about 40%. There are other medication options, including GnRH antagonists that I don't prescribe as often.

The Mirena IUD, as we've discussed, is also such a great option to reduce heavy menstrual bleeding in women which can reduce menstrual bleeding by 86% to 97%. That’s a big jump. For patients that might need procedural interventions or surgical approaches, that may be most appropriate if they are having bulk symptoms associated with their fibroids like pelvic pain, pelvic pressure, urinary, or frequency. These kinds of symptoms are caused by the sheer size of the fibroids or from the fibroids pressing on surrounding structures. Bulk symptoms often do not improve much with medications or the IUDs. Those options address bleeding associated with fibroids much better.

How likely are women to stay on these medications that have contraceptive benefits based on the impact it may have in relation to uterine fibroids?

Ms. Kennedy: In one study that examined the effectiveness of the Mirena IUD versus other medications, including oral progesterone therapy to manage heavy bleeding, 76% of women using the Mirena IUD wished to continue the treatment compared to 22% of women that wished to continue the oral progestin therapy.

In another prospective observational clinical study, 82.5% of women had improvement of heavy menstrual bleeding with the Mirena. They continued to use the Mirena after 12 months. The Mirena IUD is effective in controlling heavy menstrual bleeding related to fibroids in about 77% of cases. The most common side effect is menstrual spotting for a few months after insertion. But overall, we do see a pretty high user satisfaction rate.

Kelsey Kennedy is a Family Nurse Practitioner (FNP) and has been working as a nurse practitioner in the Women's Health Institute at the Cleveland Clinic in General Gynecology for the past three years. She has her undergraduate degree from Saint Louis University and completed her graduate studies at Walsh University. She works with patients providing annual/wellness care, contraceptive counseling, abnormal bleeding evaluation and addresses many other non-OB gynecologic issues. The best part about her job is connecting with women and empowering the women she serves to be in control of their reproductive health and wellness.

As a nurse practitioner focused on benign gynecological treatment, what is your role as it relates to uterine fibroids, which are benign non-cancerous tumors?

Ms. Kennedy: As Nurse Practitioner (NP) working in GYN, I see both common and complex gynecologic, sexual, reproductive, menopausal issues. We really do it all. The NP collaborates with the entire medical health care team, including physicians, medical assistants, nursing, and administrators.

In the outpatient office practice with the Cleveland Clinic, I provide mostly benign or general GYN care, which means I see a lot of annual wellness exams, infection checks, birth control consults, and abnormal bleeding. I see patients that may have complaints of heavy periods, pelvic pain, pressure, but they might not have a formal diagnosis or know exactly why they have such heavy periods. Sometimes I see patients that have never even heard of fibroids. It’s my job to take a thorough history, perform a physical exam, and order any additional testing indicated to get the workup started to figure out exactly what's going on.

Abnormal uterine bleeding is defined as a change in the frequency, duration, or amount of menstrual bleeding. It's a common GYN complaint that affects anywhere from 10% to 30% of reproductive age women. In fact, abnormal bleeding is the reason for 1/3 of all outpatient GYN visits and a common cause of abnormal uterine bleeding is fibroids.

So just to review, fibroids are those benign, meaning non-cancerous, tumors made of smooth muscle tissue. Fibroids affect up to 40% of women of reproductive age. And by age 50, up to 70% of women have at least one fibroid. Fibroids are very common. It is important to know that only about 25% of fibroids are clinically significant or problematic enough to require intervention. With that being said, we know that fibroids can be asymptomatic, but often, they can cause pain and bleeding.

Some situations that occur that might make me suspect fibroids include a history of periods that are regular, once monthly, but progressively becoming heavier and heavier over time; periods that last longer than seven days; menstrual bleeding so heavy patients soak through overnight pads or their clothes during the day or overnight; menstrual bleeding with large clots; pelvic pain; pressure; urinary frequency, which could be related to fibroids pressing on the bladder; or constipation, which we know has many causes but can sometimes be related to fibroids pressing on the rectum. That’s it.

What impact does Long-Acting Reversible Contraception, or LARC, have on the uterus?

Ms. Kennedy: Generally speaking, Long-Acting Reversible Contraception, or LARC, is a broad category of birth control methods that provide contraception for an extended period of time-- anywhere from 3 to 10 years, depending on the type you choose. The best part about LARC options is they do not require user action. It's 99% effective in preventing unwanted pregnancy. I like to call it set-it-and-forget-it birth control.

The LARC options we have included are all the IUDs, which consists of the Paragard or copper IUD, and the three different hormonal IUDs-- the Mirena, Kyleena, and the Skyla. That also includes the Nexplanon arm implant. Out of all these LARC options, the Mirena IUD is the only one that’s FDA approved to treat heavy menstrual bleeding which can include heavy menstrual bleeding related to fibroids. The Mirena is FDA approved right now for seven years of use, which is a nice long time to get a lot of good benefit.

The Mirena IUD, specifically, is a T-shaped device that's placed in the uterus. It releases a steady local, meaning the hormone is released pretty much just in the uterus, amount of levonorgestrel, which is a second-generation synthetic progesterone. Basically, it's a hormone. The Mirena releases 20 micrograms of levonorgestrel into the uterus every day. What this hormone does is cause a dramatic reduction of blood flow by changing the endometrium, or the lining of the uterus.

The Mirena IUD was found to reduce blood loss by 86% after three months of use and by up to 97% after 12 months of use. This big reduction in bleeding subsequently leads to an increase in iron and hemoglobin levels in women with heavy bleeding and fibroids.

Hysterectomy has long been the definitive solution for abnormal bleeding that doesn't respond to our usual treatments. But since the Mirena was developed in the 1990s, more and more evidence has come to light that the Mirena can be a safe and effective medical alternative to hysterectomy. Many women benefit from and seek other management options for bleeding and heavy bleeding relating to fibroids other than hysterectomy because they might desire future childbearing, or they just might want to retain their uterus.

In addition, we also know that fibroids typically regress in menopause. Using the Mirena IUD is a great solution to control heavy bleeding that a woman can use until they're in menopause and no longer having periods. The Mirena IUD is much less invasive than a hysterectomy and has lower risk for complications.

What steps do you take to identify encounters that might impose challenges as it relates to the uterine structure?

Ms. Kennedy: One thing that may impose a challenge in using the Mirena IUD to manage heavy bleeding related to fibroids is the specific size and location of the fibroids. Submucosal fibroids, also called intracavitary fibroids, grow into the uterus. These submucosal fibroids grow just below the inner lining of the uterus. They often cause more bleeding and problems than other types of fibroids because they crowd the uterine space. If the submucosal fibroid is too big or filling up too much of the uterine cavity, there may not be enough room for us to place a Mirena IUD.

The rates of IUD expulsion are increased in patients with fibroids that distort the uterine cavity. That's one thing we definitely want to consider. I typically refer these patients to one of my GYN surgeon colleagues to determine if the submucosal fibroid should be removed hysteroscopically in the OR. Sometimes after removing these submucosal fibroids via hysteroscopy in the OR, the surgeons will place the Mirena IUD at the end of the case.

I think you touched on this a little bit, but are there methods, in addition to IUDs, that would assist in managing heavy menstrual bleeding associated with uterine fibroids?

Ms. Kennedy: Yes. We have several current methods to manage heavy menstrual bleeding associated with uterine fibroids. One method is simply expectant management or watchful waiting. This means that the amount of bleeding or pain a woman is having related to fibroids is neither severe nor debilitating for her, but we continue to monitor them closely. We usually review what criteria the patient should look out for that may indicate she needs to follow up on, for us to take a closer look at her fibroids. Typically, that would be worsening bleeding or worsening pain.

Some oral medication options are hormonal methods which can include combined oral birth control pills, oral progesterone pills, and sometimes we use injections such as Depo-Provera, which is typically used for birth control. Oral contraceptives can reduce bleeding associated with fibroids by about 40% to 50%.

We also have non-hormonal medications like tranexamic acid, or Lysteda, which is an antifibrinolytic agent that women take only during their monthly periods for up to five days. Women who have a history of clots cannot take this drug. However, for women who can safely use this medication, on average, Lysteda has been shown to reduce the amount of blood loss during monthly periods by about 40%. There are other medication options, including GnRH antagonists that I don't prescribe as often.

The Mirena IUD, as we've discussed, is also such a great option to reduce heavy menstrual bleeding in women which can reduce menstrual bleeding by 86% to 97%. That’s a big jump. For patients that might need procedural interventions or surgical approaches, that may be most appropriate if they are having bulk symptoms associated with their fibroids like pelvic pain, pelvic pressure, urinary, or frequency. These kinds of symptoms are caused by the sheer size of the fibroids or from the fibroids pressing on surrounding structures. Bulk symptoms often do not improve much with medications or the IUDs. Those options address bleeding associated with fibroids much better.

How likely are women to stay on these medications that have contraceptive benefits based on the impact it may have in relation to uterine fibroids?

Ms. Kennedy: In one study that examined the effectiveness of the Mirena IUD versus other medications, including oral progesterone therapy to manage heavy bleeding, 76% of women using the Mirena IUD wished to continue the treatment compared to 22% of women that wished to continue the oral progestin therapy.

In another prospective observational clinical study, 82.5% of women had improvement of heavy menstrual bleeding with the Mirena. They continued to use the Mirena after 12 months. The Mirena IUD is effective in controlling heavy menstrual bleeding related to fibroids in about 77% of cases. The most common side effect is menstrual spotting for a few months after insertion. But overall, we do see a pretty high user satisfaction rate.

Kelsey Kennedy is a Family Nurse Practitioner (FNP) and has been working as a nurse practitioner in the Women's Health Institute at the Cleveland Clinic in General Gynecology for the past three years. She has her undergraduate degree from Saint Louis University and completed her graduate studies at Walsh University. She works with patients providing annual/wellness care, contraceptive counseling, abnormal bleeding evaluation and addresses many other non-OB gynecologic issues. The best part about her job is connecting with women and empowering the women she serves to be in control of their reproductive health and wellness.

As a nurse practitioner focused on benign gynecological treatment, what is your role as it relates to uterine fibroids, which are benign non-cancerous tumors?

Ms. Kennedy: As Nurse Practitioner (NP) working in GYN, I see both common and complex gynecologic, sexual, reproductive, menopausal issues. We really do it all. The NP collaborates with the entire medical health care team, including physicians, medical assistants, nursing, and administrators.

In the outpatient office practice with the Cleveland Clinic, I provide mostly benign or general GYN care, which means I see a lot of annual wellness exams, infection checks, birth control consults, and abnormal bleeding. I see patients that may have complaints of heavy periods, pelvic pain, pressure, but they might not have a formal diagnosis or know exactly why they have such heavy periods. Sometimes I see patients that have never even heard of fibroids. It’s my job to take a thorough history, perform a physical exam, and order any additional testing indicated to get the workup started to figure out exactly what's going on.

Abnormal uterine bleeding is defined as a change in the frequency, duration, or amount of menstrual bleeding. It's a common GYN complaint that affects anywhere from 10% to 30% of reproductive age women. In fact, abnormal bleeding is the reason for 1/3 of all outpatient GYN visits and a common cause of abnormal uterine bleeding is fibroids.

So just to review, fibroids are those benign, meaning non-cancerous, tumors made of smooth muscle tissue. Fibroids affect up to 40% of women of reproductive age. And by age 50, up to 70% of women have at least one fibroid. Fibroids are very common. It is important to know that only about 25% of fibroids are clinically significant or problematic enough to require intervention. With that being said, we know that fibroids can be asymptomatic, but often, they can cause pain and bleeding.

Some situations that occur that might make me suspect fibroids include a history of periods that are regular, once monthly, but progressively becoming heavier and heavier over time; periods that last longer than seven days; menstrual bleeding so heavy patients soak through overnight pads or their clothes during the day or overnight; menstrual bleeding with large clots; pelvic pain; pressure; urinary frequency, which could be related to fibroids pressing on the bladder; or constipation, which we know has many causes but can sometimes be related to fibroids pressing on the rectum. That’s it.

What impact does Long-Acting Reversible Contraception, or LARC, have on the uterus?

Ms. Kennedy: Generally speaking, Long-Acting Reversible Contraception, or LARC, is a broad category of birth control methods that provide contraception for an extended period of time-- anywhere from 3 to 10 years, depending on the type you choose. The best part about LARC options is they do not require user action. It's 99% effective in preventing unwanted pregnancy. I like to call it set-it-and-forget-it birth control.

The LARC options we have included are all the IUDs, which consists of the Paragard or copper IUD, and the three different hormonal IUDs-- the Mirena, Kyleena, and the Skyla. That also includes the Nexplanon arm implant. Out of all these LARC options, the Mirena IUD is the only one that’s FDA approved to treat heavy menstrual bleeding which can include heavy menstrual bleeding related to fibroids. The Mirena is FDA approved right now for seven years of use, which is a nice long time to get a lot of good benefit.

The Mirena IUD, specifically, is a T-shaped device that's placed in the uterus. It releases a steady local, meaning the hormone is released pretty much just in the uterus, amount of levonorgestrel, which is a second-generation synthetic progesterone. Basically, it's a hormone. The Mirena releases 20 micrograms of levonorgestrel into the uterus every day. What this hormone does is cause a dramatic reduction of blood flow by changing the endometrium, or the lining of the uterus.

The Mirena IUD was found to reduce blood loss by 86% after three months of use and by up to 97% after 12 months of use. This big reduction in bleeding subsequently leads to an increase in iron and hemoglobin levels in women with heavy bleeding and fibroids.

Hysterectomy has long been the definitive solution for abnormal bleeding that doesn't respond to our usual treatments. But since the Mirena was developed in the 1990s, more and more evidence has come to light that the Mirena can be a safe and effective medical alternative to hysterectomy. Many women benefit from and seek other management options for bleeding and heavy bleeding relating to fibroids other than hysterectomy because they might desire future childbearing, or they just might want to retain their uterus.

In addition, we also know that fibroids typically regress in menopause. Using the Mirena IUD is a great solution to control heavy bleeding that a woman can use until they're in menopause and no longer having periods. The Mirena IUD is much less invasive than a hysterectomy and has lower risk for complications.

What steps do you take to identify encounters that might impose challenges as it relates to the uterine structure?

Ms. Kennedy: One thing that may impose a challenge in using the Mirena IUD to manage heavy bleeding related to fibroids is the specific size and location of the fibroids. Submucosal fibroids, also called intracavitary fibroids, grow into the uterus. These submucosal fibroids grow just below the inner lining of the uterus. They often cause more bleeding and problems than other types of fibroids because they crowd the uterine space. If the submucosal fibroid is too big or filling up too much of the uterine cavity, there may not be enough room for us to place a Mirena IUD.

The rates of IUD expulsion are increased in patients with fibroids that distort the uterine cavity. That's one thing we definitely want to consider. I typically refer these patients to one of my GYN surgeon colleagues to determine if the submucosal fibroid should be removed hysteroscopically in the OR. Sometimes after removing these submucosal fibroids via hysteroscopy in the OR, the surgeons will place the Mirena IUD at the end of the case.

I think you touched on this a little bit, but are there methods, in addition to IUDs, that would assist in managing heavy menstrual bleeding associated with uterine fibroids?

Ms. Kennedy: Yes. We have several current methods to manage heavy menstrual bleeding associated with uterine fibroids. One method is simply expectant management or watchful waiting. This means that the amount of bleeding or pain a woman is having related to fibroids is neither severe nor debilitating for her, but we continue to monitor them closely. We usually review what criteria the patient should look out for that may indicate she needs to follow up on, for us to take a closer look at her fibroids. Typically, that would be worsening bleeding or worsening pain.

Some oral medication options are hormonal methods which can include combined oral birth control pills, oral progesterone pills, and sometimes we use injections such as Depo-Provera, which is typically used for birth control. Oral contraceptives can reduce bleeding associated with fibroids by about 40% to 50%.

We also have non-hormonal medications like tranexamic acid, or Lysteda, which is an antifibrinolytic agent that women take only during their monthly periods for up to five days. Women who have a history of clots cannot take this drug. However, for women who can safely use this medication, on average, Lysteda has been shown to reduce the amount of blood loss during monthly periods by about 40%. There are other medication options, including GnRH antagonists that I don't prescribe as often.

The Mirena IUD, as we've discussed, is also such a great option to reduce heavy menstrual bleeding in women which can reduce menstrual bleeding by 86% to 97%. That’s a big jump. For patients that might need procedural interventions or surgical approaches, that may be most appropriate if they are having bulk symptoms associated with their fibroids like pelvic pain, pelvic pressure, urinary, or frequency. These kinds of symptoms are caused by the sheer size of the fibroids or from the fibroids pressing on surrounding structures. Bulk symptoms often do not improve much with medications or the IUDs. Those options address bleeding associated with fibroids much better.

How likely are women to stay on these medications that have contraceptive benefits based on the impact it may have in relation to uterine fibroids?

Ms. Kennedy: In one study that examined the effectiveness of the Mirena IUD versus other medications, including oral progesterone therapy to manage heavy bleeding, 76% of women using the Mirena IUD wished to continue the treatment compared to 22% of women that wished to continue the oral progestin therapy.

In another prospective observational clinical study, 82.5% of women had improvement of heavy menstrual bleeding with the Mirena. They continued to use the Mirena after 12 months. The Mirena IUD is effective in controlling heavy menstrual bleeding related to fibroids in about 77% of cases. The most common side effect is menstrual spotting for a few months after insertion. But overall, we do see a pretty high user satisfaction rate.

Heart rate variability (HRV), as assessed during a deep breathing test, may lead to improved diagnosis of post-traumatic stress disorder, according to a study published in Frontiers in Psychiatry.

It is estimated that between 8% and 15% of clinically recognized pregnancies and up to 30% of all pregnancies result in miscarriage – a loss that can be devastating for everyone. There are limited data on the strength of the association between perinatal loss and subsequent common mental health disorders, such as anxiety, depression, and PTSD. The prevalence of PTSD among this group is still unknown, and one of the factors that contribute to the absence of data is that diagnostic evaluation is subjective.

To address this issue, researchers from Anhembi Morumbi University (UAM) in São José dos Campos, Brazil, along with teams in the United States and United Arab Emirates (UAE), investigated biomarkers for the severity of PTSD. The hope is that the research will enable psychiatrists to assess women who experience pregnancy loss more objectively. Study author Ovidiu Constantin Baltatu, MD, PhD, a professor at Brazil’s UAM and the UAE’s Khalifa University, spoke to this news organization about the study.

Under the guidance of Dr. Baltatu, psychologist Cláudia de Faria Cardoso carried out the research as part of her studies in biomedical engineering at UAM. Fifty-three women were recruited; the average age of the cohort was 33 years. All participants had a history of at least one perinatal loss. Pregnancy loss intervals ranged from less than 40 days to more than 6 months.

Participants completed a clinical interview and a questionnaire; PTSD symptoms were assessed on the basis of criteria in the DSM-5. The instrument used for the assessment was the Brazilian version of the Post-traumatic Stress Disorder Checklist (PCL-5). In addition, to evaluate general autonomic dysfunction, patients completed the Composite Autonomic Symptom Score 31 (COMPASS-31) questionnaire.

HRV was assessed during a deep breathing test using an HRV scanner system with wireless electrocardiography that enabled real-time data analysis and visualization. The investigators examined the following HRV measures: standard deviation (SD) of normal R-R wave intervals (SDNN), square root of the mean of the sum of the squares of differences between adjacent normal R wave intervals, and the number of all R-R intervals in which the change in consecutive normal sinus intervals exceeds 50 ms divided by the total number of R-R intervals measured.

Of the 53 participants, 25 had been diagnosed with pregnancy loss–induced PTSD. The results indicated a significant association between PCL-5 scores and HRV indices. The SDNN index effectively distinguished between patients with PTSD and those without.

To Dr. Baltatu, HRV indices reflect dysfunction of the autonomic nervous system (ANS), one of the major neural pathways activated by stress.

Although the deep breathing test has been around for a long time, it’s not widely used in current clinical practice, he said. According to him, maximum and minimum heart rates during breathing at six cycles per minute can typically be used to calculate the inspiratory-to-expiratory ratio, thus providing an indication of ANS function. “Our group introduced the study of HRV during deep breathing test, which is a step forward,” he said.

The methodology used by the team was well received by the participants. “With the deep breathing test, the women were able to look at a screen and see real-time graphics displaying the stress that they were experiencing after having suffered trauma. This visualization of objective measures was perceived as an improved care,” said Dr. Baltatu.

In general, HRV provides a more objective means of diagnosing PTSD. “Normally, PTSD is assessed through a questionnaire and an interview with psychologists,” said Dr. Baltatu. The subjectivity of the assessment is one of the main factors associated with the underdiagnosis of this condition, he explained.

It is important to remember that other factors, such as a lack of awareness about the problem, also hinder the diagnosis of PTSD in this population, Dr. Baltatu added. Women who have had a miscarriage often don’t think that their symptoms may result from PTSD. This fact highlights why it is so important that hospitals have a clinical psychologist on staff. In addition, Dr. Baltatu pointed out that a woman who experiences a pregnancy loss usually has negative memories of the hospital and is therefore reluctant to reach out for professional help. “In our study, all psychological care and assessments took place outside of a hospital setting, which the participants seemed to appreciate,” he emphasized.

Dr. Baltatu and his team are conducting follow-up research. The preliminary results indicate that the biomarkers identified in the study are promising in the assessment of patients’ clinical progress. This finding may reflect the fact that the HRV indices have proven useful not only in diagnosing but also in monitoring women in treatment, because they are able to identify which patients are responding better to treatment.

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

Heart rate variability (HRV), as assessed during a deep breathing test, may lead to improved diagnosis of post-traumatic stress disorder, according to a study published in Frontiers in Psychiatry.

It is estimated that between 8% and 15% of clinically recognized pregnancies and up to 30% of all pregnancies result in miscarriage – a loss that can be devastating for everyone. There are limited data on the strength of the association between perinatal loss and subsequent common mental health disorders, such as anxiety, depression, and PTSD. The prevalence of PTSD among this group is still unknown, and one of the factors that contribute to the absence of data is that diagnostic evaluation is subjective.

To address this issue, researchers from Anhembi Morumbi University (UAM) in São José dos Campos, Brazil, along with teams in the United States and United Arab Emirates (UAE), investigated biomarkers for the severity of PTSD. The hope is that the research will enable psychiatrists to assess women who experience pregnancy loss more objectively. Study author Ovidiu Constantin Baltatu, MD, PhD, a professor at Brazil’s UAM and the UAE’s Khalifa University, spoke to this news organization about the study.

Under the guidance of Dr. Baltatu, psychologist Cláudia de Faria Cardoso carried out the research as part of her studies in biomedical engineering at UAM. Fifty-three women were recruited; the average age of the cohort was 33 years. All participants had a history of at least one perinatal loss. Pregnancy loss intervals ranged from less than 40 days to more than 6 months.

Participants completed a clinical interview and a questionnaire; PTSD symptoms were assessed on the basis of criteria in the DSM-5. The instrument used for the assessment was the Brazilian version of the Post-traumatic Stress Disorder Checklist (PCL-5). In addition, to evaluate general autonomic dysfunction, patients completed the Composite Autonomic Symptom Score 31 (COMPASS-31) questionnaire.

HRV was assessed during a deep breathing test using an HRV scanner system with wireless electrocardiography that enabled real-time data analysis and visualization. The investigators examined the following HRV measures: standard deviation (SD) of normal R-R wave intervals (SDNN), square root of the mean of the sum of the squares of differences between adjacent normal R wave intervals, and the number of all R-R intervals in which the change in consecutive normal sinus intervals exceeds 50 ms divided by the total number of R-R intervals measured.

Of the 53 participants, 25 had been diagnosed with pregnancy loss–induced PTSD. The results indicated a significant association between PCL-5 scores and HRV indices. The SDNN index effectively distinguished between patients with PTSD and those without.

To Dr. Baltatu, HRV indices reflect dysfunction of the autonomic nervous system (ANS), one of the major neural pathways activated by stress.

Although the deep breathing test has been around for a long time, it’s not widely used in current clinical practice, he said. According to him, maximum and minimum heart rates during breathing at six cycles per minute can typically be used to calculate the inspiratory-to-expiratory ratio, thus providing an indication of ANS function. “Our group introduced the study of HRV during deep breathing test, which is a step forward,” he said.

The methodology used by the team was well received by the participants. “With the deep breathing test, the women were able to look at a screen and see real-time graphics displaying the stress that they were experiencing after having suffered trauma. This visualization of objective measures was perceived as an improved care,” said Dr. Baltatu.

In general, HRV provides a more objective means of diagnosing PTSD. “Normally, PTSD is assessed through a questionnaire and an interview with psychologists,” said Dr. Baltatu. The subjectivity of the assessment is one of the main factors associated with the underdiagnosis of this condition, he explained.

It is important to remember that other factors, such as a lack of awareness about the problem, also hinder the diagnosis of PTSD in this population, Dr. Baltatu added. Women who have had a miscarriage often don’t think that their symptoms may result from PTSD. This fact highlights why it is so important that hospitals have a clinical psychologist on staff. In addition, Dr. Baltatu pointed out that a woman who experiences a pregnancy loss usually has negative memories of the hospital and is therefore reluctant to reach out for professional help. “In our study, all psychological care and assessments took place outside of a hospital setting, which the participants seemed to appreciate,” he emphasized.

Dr. Baltatu and his team are conducting follow-up research. The preliminary results indicate that the biomarkers identified in the study are promising in the assessment of patients’ clinical progress. This finding may reflect the fact that the HRV indices have proven useful not only in diagnosing but also in monitoring women in treatment, because they are able to identify which patients are responding better to treatment.

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

Heart rate variability (HRV), as assessed during a deep breathing test, may lead to improved diagnosis of post-traumatic stress disorder, according to a study published in Frontiers in Psychiatry.

It is estimated that between 8% and 15% of clinically recognized pregnancies and up to 30% of all pregnancies result in miscarriage – a loss that can be devastating for everyone. There are limited data on the strength of the association between perinatal loss and subsequent common mental health disorders, such as anxiety, depression, and PTSD. The prevalence of PTSD among this group is still unknown, and one of the factors that contribute to the absence of data is that diagnostic evaluation is subjective.

To address this issue, researchers from Anhembi Morumbi University (UAM) in São José dos Campos, Brazil, along with teams in the United States and United Arab Emirates (UAE), investigated biomarkers for the severity of PTSD. The hope is that the research will enable psychiatrists to assess women who experience pregnancy loss more objectively. Study author Ovidiu Constantin Baltatu, MD, PhD, a professor at Brazil’s UAM and the UAE’s Khalifa University, spoke to this news organization about the study.

Under the guidance of Dr. Baltatu, psychologist Cláudia de Faria Cardoso carried out the research as part of her studies in biomedical engineering at UAM. Fifty-three women were recruited; the average age of the cohort was 33 years. All participants had a history of at least one perinatal loss. Pregnancy loss intervals ranged from less than 40 days to more than 6 months.

Participants completed a clinical interview and a questionnaire; PTSD symptoms were assessed on the basis of criteria in the DSM-5. The instrument used for the assessment was the Brazilian version of the Post-traumatic Stress Disorder Checklist (PCL-5). In addition, to evaluate general autonomic dysfunction, patients completed the Composite Autonomic Symptom Score 31 (COMPASS-31) questionnaire.

HRV was assessed during a deep breathing test using an HRV scanner system with wireless electrocardiography that enabled real-time data analysis and visualization. The investigators examined the following HRV measures: standard deviation (SD) of normal R-R wave intervals (SDNN), square root of the mean of the sum of the squares of differences between adjacent normal R wave intervals, and the number of all R-R intervals in which the change in consecutive normal sinus intervals exceeds 50 ms divided by the total number of R-R intervals measured.

Of the 53 participants, 25 had been diagnosed with pregnancy loss–induced PTSD. The results indicated a significant association between PCL-5 scores and HRV indices. The SDNN index effectively distinguished between patients with PTSD and those without.

To Dr. Baltatu, HRV indices reflect dysfunction of the autonomic nervous system (ANS), one of the major neural pathways activated by stress.

Although the deep breathing test has been around for a long time, it’s not widely used in current clinical practice, he said. According to him, maximum and minimum heart rates during breathing at six cycles per minute can typically be used to calculate the inspiratory-to-expiratory ratio, thus providing an indication of ANS function. “Our group introduced the study of HRV during deep breathing test, which is a step forward,” he said.

The methodology used by the team was well received by the participants. “With the deep breathing test, the women were able to look at a screen and see real-time graphics displaying the stress that they were experiencing after having suffered trauma. This visualization of objective measures was perceived as an improved care,” said Dr. Baltatu.

In general, HRV provides a more objective means of diagnosing PTSD. “Normally, PTSD is assessed through a questionnaire and an interview with psychologists,” said Dr. Baltatu. The subjectivity of the assessment is one of the main factors associated with the underdiagnosis of this condition, he explained.

It is important to remember that other factors, such as a lack of awareness about the problem, also hinder the diagnosis of PTSD in this population, Dr. Baltatu added. Women who have had a miscarriage often don’t think that their symptoms may result from PTSD. This fact highlights why it is so important that hospitals have a clinical psychologist on staff. In addition, Dr. Baltatu pointed out that a woman who experiences a pregnancy loss usually has negative memories of the hospital and is therefore reluctant to reach out for professional help. “In our study, all psychological care and assessments took place outside of a hospital setting, which the participants seemed to appreciate,” he emphasized.

Dr. Baltatu and his team are conducting follow-up research. The preliminary results indicate that the biomarkers identified in the study are promising in the assessment of patients’ clinical progress. This finding may reflect the fact that the HRV indices have proven useful not only in diagnosing but also in monitoring women in treatment, because they are able to identify which patients are responding better to treatment.

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