Women's Health

Getting a COVID-19 mRNA vaccine did not affect pregnancy rates for women trying to conceive with in vitro fertilization or ovarian response to treatment, findings of a new study indicate.

The study was led by Sarit Avraham, MD, with the IVF unit, department of obstetrics and gynecology, Shamir Medical Center in Tzrifi, Israel. The findings were published online in Fertility and Sterility in a preproof version.

“Women should be vaccinated for COVID-19 prior to attempting to conceive via IVF treatments, given the higher risk of severe illness in pregnant women,” the authors wrote.

Doubts arose from “the theoretical concept of the supposed similarity between the SARS-CoV-2 spike protein and the syncytin protein that is speculated to take part in the fertilization process and the formation of the placenta,” the authors wrote.

Some then assumed that the COVID vaccine might kick off an immune response that could affect implantation and pregnancy. But this study and others before it found otherwise.

Researchers included 200 vaccinated women trying to conceive with IVF treatments in the retrospective study, and compared them with 200 unvaccinated patients of similar age (average age in both groups, 36 years) who were not previously infected with COVID-19. All the women were undergoing IVF from January to April 2021 and all the vaccinated women completed two doses of the BNT162b2 (Pfizer/BioNTech) vaccine at least 2 weeks before ovarian stimulation.

Researchers compared the average number of oocytes retrieved and clinical pregnancy rates between the two groups.
 

No difference between groups

Two hundred patients underwent oocyte retrieval 14-68 days after receiving a COVID shot; there was no significant difference by vaccination status in the number retrieved per cycle (10.63 in the vaccinated group vs. 10.72 in the unvaccinated group; P = .93).

There was also no difference in the clinical pregnancy rates after fresh embryo transfers. The rate among 128 vaccinated patients was 32.8% versus 33.1% in the 133 unvaccinated patients (P = .96), with 42 and 44 clinical pregnancies, respectively.

A total of 113 patients (66 in the study group and 47 in the controls) underwent freeze-all cycles to preserve fertility and fertilization rates were similar between vaccinated and unvaccinated (55.43% vaccinated vs. 54.29% unvaccinated; P = .73). The average number of cryopreserved embryos was 3.59 (vaccinated) versus 3.28 (unvaccinated) (P = .80).

In a subanalysis of outcomes by age, researchers found vaccination status had no effect on number of oocytes or pregnancy rates in the 39-and-older group. That’s important because it shows the vaccine did not affect outcomes even in a population with reduced ovarian reserves, the authors wrote.

The authors noted one of the study’s limitations is that it didn’t include information about vaccination or past infection status of the male partners.
 

Question should be put to rest

Sarah Cross, MD, a maternal-fetal medicine specialist at the University of Minnesota, Minneapolis, said the study is the biggest she’s seen that concludes COVID vaccinations are safe and highly encouraged for women before trying to conceive, but other smaller studies have come to the same conclusion.

She pointed to research including a study from 2021 with similar findings that concluded: “Physicians and public health personnel can counsel women of reproductive age that neither previous illness with COVID-19 nor antibodies produced from vaccination to COVID-19 will cause sterility.”

She said she thinks the question of whether COVID shots are safe with IVF has been answered and the results of the latest study add proof to counter misinformation around the issue.

“The COVID-19 vaccine does not affect fertility,” she said. “I don’t know how many more [studies] we need.”

The harm is in not getting vaccinated, she said. Pregnancy significantly increases a woman’s chance of getting severe COVID, the need for hospitalization, mechanical ventilation, and risk of death.

“I personally have never had a hospitalized patient who’s been vaccinated,” Dr. Cross said. “The worst thing for the fetus is to have a critically ill mother.”

Dr. Cross, whose high-risk patients include those seeking counseling before IVF, added: “I would counsel all of them that they should absolutely get vaccinated prior to pregnancy, when they’re pregnant, whenever it is, as soon as they possibly can.”

The study authors and Dr. Cross report no relevant financial relationships.

Getting a COVID-19 mRNA vaccine did not affect pregnancy rates for women trying to conceive with in vitro fertilization or ovarian response to treatment, findings of a new study indicate.

The study was led by Sarit Avraham, MD, with the IVF unit, department of obstetrics and gynecology, Shamir Medical Center in Tzrifi, Israel. The findings were published online in Fertility and Sterility in a preproof version.

“Women should be vaccinated for COVID-19 prior to attempting to conceive via IVF treatments, given the higher risk of severe illness in pregnant women,” the authors wrote.

Doubts arose from “the theoretical concept of the supposed similarity between the SARS-CoV-2 spike protein and the syncytin protein that is speculated to take part in the fertilization process and the formation of the placenta,” the authors wrote.

Some then assumed that the COVID vaccine might kick off an immune response that could affect implantation and pregnancy. But this study and others before it found otherwise.

Researchers included 200 vaccinated women trying to conceive with IVF treatments in the retrospective study, and compared them with 200 unvaccinated patients of similar age (average age in both groups, 36 years) who were not previously infected with COVID-19. All the women were undergoing IVF from January to April 2021 and all the vaccinated women completed two doses of the BNT162b2 (Pfizer/BioNTech) vaccine at least 2 weeks before ovarian stimulation.

Researchers compared the average number of oocytes retrieved and clinical pregnancy rates between the two groups.
 

No difference between groups

Two hundred patients underwent oocyte retrieval 14-68 days after receiving a COVID shot; there was no significant difference by vaccination status in the number retrieved per cycle (10.63 in the vaccinated group vs. 10.72 in the unvaccinated group; P = .93).

There was also no difference in the clinical pregnancy rates after fresh embryo transfers. The rate among 128 vaccinated patients was 32.8% versus 33.1% in the 133 unvaccinated patients (P = .96), with 42 and 44 clinical pregnancies, respectively.

A total of 113 patients (66 in the study group and 47 in the controls) underwent freeze-all cycles to preserve fertility and fertilization rates were similar between vaccinated and unvaccinated (55.43% vaccinated vs. 54.29% unvaccinated; P = .73). The average number of cryopreserved embryos was 3.59 (vaccinated) versus 3.28 (unvaccinated) (P = .80).

In a subanalysis of outcomes by age, researchers found vaccination status had no effect on number of oocytes or pregnancy rates in the 39-and-older group. That’s important because it shows the vaccine did not affect outcomes even in a population with reduced ovarian reserves, the authors wrote.

The authors noted one of the study’s limitations is that it didn’t include information about vaccination or past infection status of the male partners.
 

Question should be put to rest

Sarah Cross, MD, a maternal-fetal medicine specialist at the University of Minnesota, Minneapolis, said the study is the biggest she’s seen that concludes COVID vaccinations are safe and highly encouraged for women before trying to conceive, but other smaller studies have come to the same conclusion.

She pointed to research including a study from 2021 with similar findings that concluded: “Physicians and public health personnel can counsel women of reproductive age that neither previous illness with COVID-19 nor antibodies produced from vaccination to COVID-19 will cause sterility.”

She said she thinks the question of whether COVID shots are safe with IVF has been answered and the results of the latest study add proof to counter misinformation around the issue.

“The COVID-19 vaccine does not affect fertility,” she said. “I don’t know how many more [studies] we need.”

The harm is in not getting vaccinated, she said. Pregnancy significantly increases a woman’s chance of getting severe COVID, the need for hospitalization, mechanical ventilation, and risk of death.

“I personally have never had a hospitalized patient who’s been vaccinated,” Dr. Cross said. “The worst thing for the fetus is to have a critically ill mother.”

Dr. Cross, whose high-risk patients include those seeking counseling before IVF, added: “I would counsel all of them that they should absolutely get vaccinated prior to pregnancy, when they’re pregnant, whenever it is, as soon as they possibly can.”

The study authors and Dr. Cross report no relevant financial relationships.

Getting a COVID-19 mRNA vaccine did not affect pregnancy rates for women trying to conceive with in vitro fertilization or ovarian response to treatment, findings of a new study indicate.

The study was led by Sarit Avraham, MD, with the IVF unit, department of obstetrics and gynecology, Shamir Medical Center in Tzrifi, Israel. The findings were published online in Fertility and Sterility in a preproof version.

“Women should be vaccinated for COVID-19 prior to attempting to conceive via IVF treatments, given the higher risk of severe illness in pregnant women,” the authors wrote.

Doubts arose from “the theoretical concept of the supposed similarity between the SARS-CoV-2 spike protein and the syncytin protein that is speculated to take part in the fertilization process and the formation of the placenta,” the authors wrote.

Some then assumed that the COVID vaccine might kick off an immune response that could affect implantation and pregnancy. But this study and others before it found otherwise.

Researchers included 200 vaccinated women trying to conceive with IVF treatments in the retrospective study, and compared them with 200 unvaccinated patients of similar age (average age in both groups, 36 years) who were not previously infected with COVID-19. All the women were undergoing IVF from January to April 2021 and all the vaccinated women completed two doses of the BNT162b2 (Pfizer/BioNTech) vaccine at least 2 weeks before ovarian stimulation.

Researchers compared the average number of oocytes retrieved and clinical pregnancy rates between the two groups.
 

No difference between groups

Two hundred patients underwent oocyte retrieval 14-68 days after receiving a COVID shot; there was no significant difference by vaccination status in the number retrieved per cycle (10.63 in the vaccinated group vs. 10.72 in the unvaccinated group; P = .93).

There was also no difference in the clinical pregnancy rates after fresh embryo transfers. The rate among 128 vaccinated patients was 32.8% versus 33.1% in the 133 unvaccinated patients (P = .96), with 42 and 44 clinical pregnancies, respectively.

A total of 113 patients (66 in the study group and 47 in the controls) underwent freeze-all cycles to preserve fertility and fertilization rates were similar between vaccinated and unvaccinated (55.43% vaccinated vs. 54.29% unvaccinated; P = .73). The average number of cryopreserved embryos was 3.59 (vaccinated) versus 3.28 (unvaccinated) (P = .80).

In a subanalysis of outcomes by age, researchers found vaccination status had no effect on number of oocytes or pregnancy rates in the 39-and-older group. That’s important because it shows the vaccine did not affect outcomes even in a population with reduced ovarian reserves, the authors wrote.

The authors noted one of the study’s limitations is that it didn’t include information about vaccination or past infection status of the male partners.
 

Question should be put to rest

Sarah Cross, MD, a maternal-fetal medicine specialist at the University of Minnesota, Minneapolis, said the study is the biggest she’s seen that concludes COVID vaccinations are safe and highly encouraged for women before trying to conceive, but other smaller studies have come to the same conclusion.

She pointed to research including a study from 2021 with similar findings that concluded: “Physicians and public health personnel can counsel women of reproductive age that neither previous illness with COVID-19 nor antibodies produced from vaccination to COVID-19 will cause sterility.”

She said she thinks the question of whether COVID shots are safe with IVF has been answered and the results of the latest study add proof to counter misinformation around the issue.

“The COVID-19 vaccine does not affect fertility,” she said. “I don’t know how many more [studies] we need.”

The harm is in not getting vaccinated, she said. Pregnancy significantly increases a woman’s chance of getting severe COVID, the need for hospitalization, mechanical ventilation, and risk of death.

“I personally have never had a hospitalized patient who’s been vaccinated,” Dr. Cross said. “The worst thing for the fetus is to have a critically ill mother.”

Dr. Cross, whose high-risk patients include those seeking counseling before IVF, added: “I would counsel all of them that they should absolutely get vaccinated prior to pregnancy, when they’re pregnant, whenever it is, as soon as they possibly can.”

The study authors and Dr. Cross report no relevant financial relationships.

March is Women’s History Month. Many women have served in all branches of government health care over centuries and are worthy of celebrating. These nurses, physicians, pharmacists, and other allied health professionals devoted their time and talents, compassion, and competence to deliver and improve the care of wounded service members, disabled veterans, and the underresourced in our communities. To honor the collective contribution of women to federal practice in the Indian Health Service, Public Health Service Core, US Department of Veterans Affairs (VA) and the US Department of Defense, this column examines one pioneer in women’s federal practice—Margaret D. Craighill, MD—who epitomizes the spirit of the selfless dedication that generations of women have given to public service. Craighill is an ideal choice to represent this noble cadre of women as her career spanned active military duty, public health, and the Veterans Health Administration.

Craighill was a graduate of several of the finest institutions of medical training in the United States. Born in Southport, North Carolina, in 1898, she earned her undergraduate degree Phi Beta Kappa and master’s degree from the University of Wisconsin.² She set her sights on becoming a physician at a period in American history when many prominent medical schools accepted few women. A marked exception—due to the fund raising and lobbying of influential women—was the prestigious Johns Hopkins University School of Medicine.³ She graduated in 1924 and held a postgraduate position at Yale Medical School. She then worked as a physiologist at a military arsenal, a pathologist, a general surgeon, and completed a residency in obstetrics and gynecology. This broad training gave her the diverse expertise she would need for her future work.⁴

Craighill came from a military family: Her father was a colonel in the engineering corps, and her grandfather rose to become chief engineer of the Army.⁵ Along with many of America’s best and brightest, Craighill left her successful medical career as dean of the Women’s Medical College of Pennsylvania to join the war effort. Author Alan G. Knight points out, more than in civilian medicine, gender stereotypes kept women from entering the military: Women were expected and accepted as nurses, not doctors.⁵ But in 1943 Congress passed and President Roosevelt signed the Sparkman-Johnson Bill, enabling women to enter the then all-male Army and Navy Medical Corps. Craighill took advantage of this opportunity and accepted an appointment to the Women’s Army Corps (WAC) as a major in 1943 at age 45 years, becoming the first woman physician to be commissioned an officer in the Army.

Major Craighill’s initial assignment was to the Office of the Surgeon General in the Preventive Medicine Division as the consultant for health and welfare of women. Here, she served as liaison to another innovation in women’s history in military medicine—the WAC. Journeying 56,000 miles to war zones in multiple countries, she assessed the health of 160,000 Army nurses and other staff whose focus was public health and infectious disease and hygiene. The history of women in medicine in and out of federal service is marked by overcoming innumerable biases and barriers. Craighill faced the prevailing presumption that women were unfit for military duty. In an early example of evidence-based medicine, she disproved this theory, showing that women were faring well doing hard jobs in tough environments.⁴

Their fortitude is more remarkable considering induction examinations for women during World War II were cursory and not tailored to address women’s health care needs. Based on her visits to WACs in theater and at home, Craighill observed recruits suffering from previously undiagnosed gynecologic and psychiatric conditions that adversely affected their health and function. She advocated for comprehensive standardized examinations that would detect many of these disorders.⁵

Craighill promoted other prejudices of her era. WAC command wanted to win public approval of women in the service and was concerned that lesbian relationships and “heterosexual promiscuity” would damage their public relations aims. They pressured Craighill to develop induction examinations that would screen lesbians and women with behavioral problems. She urged tolerance of homosexual behavior until it was proven.

Though clearly discriminatory and personally offensive to gay persons in federal service, we must recognize that only last year did the Pentagon move to overturn the prior administration’s prohibition against transgender persons serving in uniform.⁶ In this light Craighill, as the first female physician-leader in a 1940s military, adopted a relatively progressive stance.

Craighill rose to the rank of lieutenant colonel and received the Legion of Merit award for her exemplary wartime service. In 1945, she earned another first when she was appointed to be a consultant on the medical care of women veterans. For women veterans, gaining access to newly earned benefits and receiving appropriate care were serious problems that Craighill worked to solve. For many women veterans, those challenges remain, and Craighill’s legacy summons us to take up the charge to empower women in federal health professions to enhance the quality of care women veterans receive in all sectors of US medicine.

Critics and advocates agree that the VA still has a long way to go to achieve equity and excellence in our care for women veterans.^7,8 Craighill’s position stands as a landmark in this effort. During her VA tenure, Craighill entered a residency in the first class of the Menninger School of Psychiatry in Topeka, Kansas, and completed psychoanalytic training. Her wartime experiences had convinced her of the need to provide high-quality mental health care to women veterans. She put her new psychosomatic knowledge and skills to use, serving as the chief of a women’s health clinic at the VA Hospital in Topeka and published several important scholarly papers.^5,9Craighill went on to have a distinguished career in academic medicine, underscoring the long and valuable relationship of US medicine and the scholarly medical community. Once her psychiatric training was finished, she returned to private practice, ending her career as chief psychiatrist at Connecticut College for Women.

Craighill made a significant contribution to the role of women in federal practice. She was a visionary in her conviction that women, whether physicians, nurses, or other health care professionals, had the gifts and the grit to serve with distinction and valor and that their military service entitled them in war and peace to gender-sensitive health care. As the epigraph for this editorial shows, Craighill knew the path for women in federal practice or service while not easy is well worth treading. Her pioneering career can inspire all those women who today and in the future choose to follow in her footsteps.

March is Women’s History Month. Many women have served in all branches of government health care over centuries and are worthy of celebrating. These nurses, physicians, pharmacists, and other allied health professionals devoted their time and talents, compassion, and competence to deliver and improve the care of wounded service members, disabled veterans, and the underresourced in our communities. To honor the collective contribution of women to federal practice in the Indian Health Service, Public Health Service Core, US Department of Veterans Affairs (VA) and the US Department of Defense, this column examines one pioneer in women’s federal practice—Margaret D. Craighill, MD—who epitomizes the spirit of the selfless dedication that generations of women have given to public service. Craighill is an ideal choice to represent this noble cadre of women as her career spanned active military duty, public health, and the Veterans Health Administration.

Craighill was a graduate of several of the finest institutions of medical training in the United States. Born in Southport, North Carolina, in 1898, she earned her undergraduate degree Phi Beta Kappa and master’s degree from the University of Wisconsin.² She set her sights on becoming a physician at a period in American history when many prominent medical schools accepted few women. A marked exception—due to the fund raising and lobbying of influential women—was the prestigious Johns Hopkins University School of Medicine.³ She graduated in 1924 and held a postgraduate position at Yale Medical School. She then worked as a physiologist at a military arsenal, a pathologist, a general surgeon, and completed a residency in obstetrics and gynecology. This broad training gave her the diverse expertise she would need for her future work.⁴

Craighill came from a military family: Her father was a colonel in the engineering corps, and her grandfather rose to become chief engineer of the Army.⁵ Along with many of America’s best and brightest, Craighill left her successful medical career as dean of the Women’s Medical College of Pennsylvania to join the war effort. Author Alan G. Knight points out, more than in civilian medicine, gender stereotypes kept women from entering the military: Women were expected and accepted as nurses, not doctors.⁵ But in 1943 Congress passed and President Roosevelt signed the Sparkman-Johnson Bill, enabling women to enter the then all-male Army and Navy Medical Corps. Craighill took advantage of this opportunity and accepted an appointment to the Women’s Army Corps (WAC) as a major in 1943 at age 45 years, becoming the first woman physician to be commissioned an officer in the Army.

Major Craighill’s initial assignment was to the Office of the Surgeon General in the Preventive Medicine Division as the consultant for health and welfare of women. Here, she served as liaison to another innovation in women’s history in military medicine—the WAC. Journeying 56,000 miles to war zones in multiple countries, she assessed the health of 160,000 Army nurses and other staff whose focus was public health and infectious disease and hygiene. The history of women in medicine in and out of federal service is marked by overcoming innumerable biases and barriers. Craighill faced the prevailing presumption that women were unfit for military duty. In an early example of evidence-based medicine, she disproved this theory, showing that women were faring well doing hard jobs in tough environments.⁴

Their fortitude is more remarkable considering induction examinations for women during World War II were cursory and not tailored to address women’s health care needs. Based on her visits to WACs in theater and at home, Craighill observed recruits suffering from previously undiagnosed gynecologic and psychiatric conditions that adversely affected their health and function. She advocated for comprehensive standardized examinations that would detect many of these disorders.⁵

Craighill promoted other prejudices of her era. WAC command wanted to win public approval of women in the service and was concerned that lesbian relationships and “heterosexual promiscuity” would damage their public relations aims. They pressured Craighill to develop induction examinations that would screen lesbians and women with behavioral problems. She urged tolerance of homosexual behavior until it was proven.

Though clearly discriminatory and personally offensive to gay persons in federal service, we must recognize that only last year did the Pentagon move to overturn the prior administration’s prohibition against transgender persons serving in uniform.⁶ In this light Craighill, as the first female physician-leader in a 1940s military, adopted a relatively progressive stance.

Craighill rose to the rank of lieutenant colonel and received the Legion of Merit award for her exemplary wartime service. In 1945, she earned another first when she was appointed to be a consultant on the medical care of women veterans. For women veterans, gaining access to newly earned benefits and receiving appropriate care were serious problems that Craighill worked to solve. For many women veterans, those challenges remain, and Craighill’s legacy summons us to take up the charge to empower women in federal health professions to enhance the quality of care women veterans receive in all sectors of US medicine.

Critics and advocates agree that the VA still has a long way to go to achieve equity and excellence in our care for women veterans.^7,8 Craighill’s position stands as a landmark in this effort. During her VA tenure, Craighill entered a residency in the first class of the Menninger School of Psychiatry in Topeka, Kansas, and completed psychoanalytic training. Her wartime experiences had convinced her of the need to provide high-quality mental health care to women veterans. She put her new psychosomatic knowledge and skills to use, serving as the chief of a women’s health clinic at the VA Hospital in Topeka and published several important scholarly papers.^5,9Craighill went on to have a distinguished career in academic medicine, underscoring the long and valuable relationship of US medicine and the scholarly medical community. Once her psychiatric training was finished, she returned to private practice, ending her career as chief psychiatrist at Connecticut College for Women.

Craighill made a significant contribution to the role of women in federal practice. She was a visionary in her conviction that women, whether physicians, nurses, or other health care professionals, had the gifts and the grit to serve with distinction and valor and that their military service entitled them in war and peace to gender-sensitive health care. As the epigraph for this editorial shows, Craighill knew the path for women in federal practice or service while not easy is well worth treading. Her pioneering career can inspire all those women who today and in the future choose to follow in her footsteps.

March is Women’s History Month. Many women have served in all branches of government health care over centuries and are worthy of celebrating. These nurses, physicians, pharmacists, and other allied health professionals devoted their time and talents, compassion, and competence to deliver and improve the care of wounded service members, disabled veterans, and the underresourced in our communities. To honor the collective contribution of women to federal practice in the Indian Health Service, Public Health Service Core, US Department of Veterans Affairs (VA) and the US Department of Defense, this column examines one pioneer in women’s federal practice—Margaret D. Craighill, MD—who epitomizes the spirit of the selfless dedication that generations of women have given to public service. Craighill is an ideal choice to represent this noble cadre of women as her career spanned active military duty, public health, and the Veterans Health Administration.

Craighill was a graduate of several of the finest institutions of medical training in the United States. Born in Southport, North Carolina, in 1898, she earned her undergraduate degree Phi Beta Kappa and master’s degree from the University of Wisconsin.² She set her sights on becoming a physician at a period in American history when many prominent medical schools accepted few women. A marked exception—due to the fund raising and lobbying of influential women—was the prestigious Johns Hopkins University School of Medicine.³ She graduated in 1924 and held a postgraduate position at Yale Medical School. She then worked as a physiologist at a military arsenal, a pathologist, a general surgeon, and completed a residency in obstetrics and gynecology. This broad training gave her the diverse expertise she would need for her future work.⁴

Craighill came from a military family: Her father was a colonel in the engineering corps, and her grandfather rose to become chief engineer of the Army.⁵ Along with many of America’s best and brightest, Craighill left her successful medical career as dean of the Women’s Medical College of Pennsylvania to join the war effort. Author Alan G. Knight points out, more than in civilian medicine, gender stereotypes kept women from entering the military: Women were expected and accepted as nurses, not doctors.⁵ But in 1943 Congress passed and President Roosevelt signed the Sparkman-Johnson Bill, enabling women to enter the then all-male Army and Navy Medical Corps. Craighill took advantage of this opportunity and accepted an appointment to the Women’s Army Corps (WAC) as a major in 1943 at age 45 years, becoming the first woman physician to be commissioned an officer in the Army.

Major Craighill’s initial assignment was to the Office of the Surgeon General in the Preventive Medicine Division as the consultant for health and welfare of women. Here, she served as liaison to another innovation in women’s history in military medicine—the WAC. Journeying 56,000 miles to war zones in multiple countries, she assessed the health of 160,000 Army nurses and other staff whose focus was public health and infectious disease and hygiene. The history of women in medicine in and out of federal service is marked by overcoming innumerable biases and barriers. Craighill faced the prevailing presumption that women were unfit for military duty. In an early example of evidence-based medicine, she disproved this theory, showing that women were faring well doing hard jobs in tough environments.⁴

Their fortitude is more remarkable considering induction examinations for women during World War II were cursory and not tailored to address women’s health care needs. Based on her visits to WACs in theater and at home, Craighill observed recruits suffering from previously undiagnosed gynecologic and psychiatric conditions that adversely affected their health and function. She advocated for comprehensive standardized examinations that would detect many of these disorders.⁵

Craighill promoted other prejudices of her era. WAC command wanted to win public approval of women in the service and was concerned that lesbian relationships and “heterosexual promiscuity” would damage their public relations aims. They pressured Craighill to develop induction examinations that would screen lesbians and women with behavioral problems. She urged tolerance of homosexual behavior until it was proven.

Though clearly discriminatory and personally offensive to gay persons in federal service, we must recognize that only last year did the Pentagon move to overturn the prior administration’s prohibition against transgender persons serving in uniform.⁶ In this light Craighill, as the first female physician-leader in a 1940s military, adopted a relatively progressive stance.

Craighill rose to the rank of lieutenant colonel and received the Legion of Merit award for her exemplary wartime service. In 1945, she earned another first when she was appointed to be a consultant on the medical care of women veterans. For women veterans, gaining access to newly earned benefits and receiving appropriate care were serious problems that Craighill worked to solve. For many women veterans, those challenges remain, and Craighill’s legacy summons us to take up the charge to empower women in federal health professions to enhance the quality of care women veterans receive in all sectors of US medicine.

Critics and advocates agree that the VA still has a long way to go to achieve equity and excellence in our care for women veterans.^7,8 Craighill’s position stands as a landmark in this effort. During her VA tenure, Craighill entered a residency in the first class of the Menninger School of Psychiatry in Topeka, Kansas, and completed psychoanalytic training. Her wartime experiences had convinced her of the need to provide high-quality mental health care to women veterans. She put her new psychosomatic knowledge and skills to use, serving as the chief of a women’s health clinic at the VA Hospital in Topeka and published several important scholarly papers.^5,9Craighill went on to have a distinguished career in academic medicine, underscoring the long and valuable relationship of US medicine and the scholarly medical community. Once her psychiatric training was finished, she returned to private practice, ending her career as chief psychiatrist at Connecticut College for Women.

Craighill made a significant contribution to the role of women in federal practice. She was a visionary in her conviction that women, whether physicians, nurses, or other health care professionals, had the gifts and the grit to serve with distinction and valor and that their military service entitled them in war and peace to gender-sensitive health care. As the epigraph for this editorial shows, Craighill knew the path for women in federal practice or service while not easy is well worth treading. Her pioneering career can inspire all those women who today and in the future choose to follow in her footsteps.

Long or irregular menstrual cycles in relatively young women are linked an increased risk of both prevalent and incident nonalcoholic fatty liver disease (NAFLD), according to a cross-sectional study that included data on more than 70,000 women.

“Our results indicate that menstrual irregularity, which is easier to diagnose and usually presented earlier than PCOS [polycystic ovary syndrome] highlights the possibility of identifying premenopausal women at risk of developing NAFLD,” reported a team of authors primarily from Sungkyunkwan University, Seoul, South Korea.

The study evaluated women aged younger than 40 years who were participating in the Kangbuk Samsung Health Study, which involves a comprehensive biennial health examination at health centers in South Korea. Of the 135,090 women enrolled over a 6-year period who had at least one follow-up examination, 72,092 were available for analysis after excluding for a sizable list of confounding factors such as liver disease and infections; exposure to steatogenic medications, such as corticosteroids; hysterectomy; and pregnancy.
 

NAFLD prevalence climbs with longer menses

Of these women, 36.378 (27.7%) had menstrual cycles of 26-30 days and were identified as the index group. The prevalence of NAFLD in this group was 5.8%. For those with a menstrual cycle of 31-39 days, the prevalence rate climbed to 7.2%. For those with a menstrual cycle of at least 40 days or too irregular to estimate, the prevalence was 9.7%. The prevalence was 7.1% for those with a menstrual cycle less than 21 days.

The results of this study were published in the Journal of Clinical Endocrinology & Metabolism.

In those without NAFLD at baseline who were then followed for a mean of 4.4 years, there were 4,524 incident cases of NAFLD. Incidence density was calculated per 103 patient-years. In the index group, the rate was 18.4. It climbed to 20.2 for those with a menstrual cycle of 31-39 days and then to 22.9 for those with a menstrual cycle of at least 40 days. For those with a cycle of fewer than 21 days, the rate was 26.8.

After adjusting for age, body mass index, insulin resistance, and other confounders, the hazard ratio for incident NAFLD for those with long or irregular menstrual cycles compared with the incident group corresponded with a 22% increased risk (HR, 1.22; 95% confidence interval, 1.14-1.31). When calculated in a time-dependent analysis, the risk of NAFLD was increased by almost 50% (HR, 1.49; 95% CI, 1.38-1.60).


 

Risk persists with PCOS exclusion

PCOS has previously been associated with increased risk of NAFLD, but the association between long or irregular menstrual cycles and NAFLD persisted after women with PCOS were excluded.

The mechanism that links menstrual irregularity with NAFLD is unclear, but the investigators said that estrogen exposure is implicated. In addition to a previously reported associated between low estradiol levels and antiestrogens such as tamoxifen with increased risk of NAFLD, they cited studies associating estrogen replacement therapy with a reduced risk of NAFLD. The role of estrogen in suppressing inflammation, oxidative stress, and insulin resistance are all activities that might link more regular menses with a reduced risk of NAFLD, the authors contended.

Women older than 40 years were excluded from this analysis to reduce the possibility of perimenopausal changes as a confounding factor.

Of study limitations acknowledged by the investigators, the presence of NAFLD was diagnosed on ultrasonography rather than histology. Information on sex hormone or prolactin levels was not captured in relation to NAFLD incidence, and the lack of exposure to estrogen replacement therapy and oral contraceptives was based on self-reports from the participants.

Still, the large study size and the consistency of results after adjustment for multiple risk factors argue that long and irregular menstrual cycles do identify women at risk for NAFLD. One implication is that irregular menses can be a marker for NAFLD risk.

“Our findings do not prove a causal relationship, but they show that long or irregular menstrual cycles were significantly associated with an increased risk of developing NAFLD,” said Seungho Ryu, MD, PhD, a professor at the Sungkyunkwan University. Senior author of this study, Dr. Ryu emphasized in an interview that the association “was not explained by obesity or any other risk factor for NAFLD.”
 

Lifestyle changes may lower risk

The message is that “young women with long or irregular menstrual cycles may benefit from lifestyle changes to reduce the risk of NAFLD,” Dr. Ryu stated.

The Study of Women’s Health Across the Nation, which was started in 1994, has not evaluated NAFLD, but it did show a relationship between longer menstrual cycles and more cardiometabolic risk factors, according to Nanette Santoro MD, professor and chair, department of obstetrics & gynecology, University of Colorado at Denver, Aurora.

This suggests that others are “thinking along the same lines,” but in discussing this study with this news organization, she characterized some of the design elements as well as some of the findings in this study as “peculiar.”

In addition to a “very, very narrow definition of regular cycles,” she questioned the consistent hazard ratio for NAFLD for those with long cycles relative to other types of irregular menses. Presuming that the group with longer cycles would have included at least some patients with undiagnosed PCOS, she was would have expected that the risk would have been highest in this group. While conceding that differences in body composition of Korean women is a potential explanation for this apparent discrepancy, “I would like to see confirmed in other samples of women with more detailed metabolic assessments to understand who is at risk,” she said.

Not least problematic for the strength of the conclusions, the hazard ratio for NAFLD among women with long or irregular menstrual cycles was “pretty low.” She described this as a level at which the risk “is very susceptible to confounding and unlikely to influence clinical practice.”

Anuja Dokras, MD, PHD, a professor of obstetrics and gynecology and director of the PCOS Center at the University of Pennsylvania, Philadelphia, also questioned whether undiagnosed PCOS might have skewed the data.

“There is increasing data on the association between PCOS and NAFLD. Irregular menses is a key criterion for PCOS, and PCOS is the commonest reason for anovulation,” she said. Dr. Dokras therefore considered it possible that patients with unrecognized PCOS were included in the study, weakening the claim that risk of NAFLD and long menstrual cycles remains significant after controlling for PCOS.

Dr. Ryu and coinvestigators, Dr. Santoro, and Dr. Dokras reported no potential conflicts of interest.

Long or irregular menstrual cycles in relatively young women are linked an increased risk of both prevalent and incident nonalcoholic fatty liver disease (NAFLD), according to a cross-sectional study that included data on more than 70,000 women.

“Our results indicate that menstrual irregularity, which is easier to diagnose and usually presented earlier than PCOS [polycystic ovary syndrome] highlights the possibility of identifying premenopausal women at risk of developing NAFLD,” reported a team of authors primarily from Sungkyunkwan University, Seoul, South Korea.

The study evaluated women aged younger than 40 years who were participating in the Kangbuk Samsung Health Study, which involves a comprehensive biennial health examination at health centers in South Korea. Of the 135,090 women enrolled over a 6-year period who had at least one follow-up examination, 72,092 were available for analysis after excluding for a sizable list of confounding factors such as liver disease and infections; exposure to steatogenic medications, such as corticosteroids; hysterectomy; and pregnancy.
 

NAFLD prevalence climbs with longer menses

Of these women, 36.378 (27.7%) had menstrual cycles of 26-30 days and were identified as the index group. The prevalence of NAFLD in this group was 5.8%. For those with a menstrual cycle of 31-39 days, the prevalence rate climbed to 7.2%. For those with a menstrual cycle of at least 40 days or too irregular to estimate, the prevalence was 9.7%. The prevalence was 7.1% for those with a menstrual cycle less than 21 days.

The results of this study were published in the Journal of Clinical Endocrinology & Metabolism.

In those without NAFLD at baseline who were then followed for a mean of 4.4 years, there were 4,524 incident cases of NAFLD. Incidence density was calculated per 103 patient-years. In the index group, the rate was 18.4. It climbed to 20.2 for those with a menstrual cycle of 31-39 days and then to 22.9 for those with a menstrual cycle of at least 40 days. For those with a cycle of fewer than 21 days, the rate was 26.8.

After adjusting for age, body mass index, insulin resistance, and other confounders, the hazard ratio for incident NAFLD for those with long or irregular menstrual cycles compared with the incident group corresponded with a 22% increased risk (HR, 1.22; 95% confidence interval, 1.14-1.31). When calculated in a time-dependent analysis, the risk of NAFLD was increased by almost 50% (HR, 1.49; 95% CI, 1.38-1.60).


 

Risk persists with PCOS exclusion

PCOS has previously been associated with increased risk of NAFLD, but the association between long or irregular menstrual cycles and NAFLD persisted after women with PCOS were excluded.

The mechanism that links menstrual irregularity with NAFLD is unclear, but the investigators said that estrogen exposure is implicated. In addition to a previously reported associated between low estradiol levels and antiestrogens such as tamoxifen with increased risk of NAFLD, they cited studies associating estrogen replacement therapy with a reduced risk of NAFLD. The role of estrogen in suppressing inflammation, oxidative stress, and insulin resistance are all activities that might link more regular menses with a reduced risk of NAFLD, the authors contended.

Women older than 40 years were excluded from this analysis to reduce the possibility of perimenopausal changes as a confounding factor.

Of study limitations acknowledged by the investigators, the presence of NAFLD was diagnosed on ultrasonography rather than histology. Information on sex hormone or prolactin levels was not captured in relation to NAFLD incidence, and the lack of exposure to estrogen replacement therapy and oral contraceptives was based on self-reports from the participants.

Still, the large study size and the consistency of results after adjustment for multiple risk factors argue that long and irregular menstrual cycles do identify women at risk for NAFLD. One implication is that irregular menses can be a marker for NAFLD risk.

“Our findings do not prove a causal relationship, but they show that long or irregular menstrual cycles were significantly associated with an increased risk of developing NAFLD,” said Seungho Ryu, MD, PhD, a professor at the Sungkyunkwan University. Senior author of this study, Dr. Ryu emphasized in an interview that the association “was not explained by obesity or any other risk factor for NAFLD.”
 

Lifestyle changes may lower risk

The message is that “young women with long or irregular menstrual cycles may benefit from lifestyle changes to reduce the risk of NAFLD,” Dr. Ryu stated.

The Study of Women’s Health Across the Nation, which was started in 1994, has not evaluated NAFLD, but it did show a relationship between longer menstrual cycles and more cardiometabolic risk factors, according to Nanette Santoro MD, professor and chair, department of obstetrics & gynecology, University of Colorado at Denver, Aurora.

This suggests that others are “thinking along the same lines,” but in discussing this study with this news organization, she characterized some of the design elements as well as some of the findings in this study as “peculiar.”

In addition to a “very, very narrow definition of regular cycles,” she questioned the consistent hazard ratio for NAFLD for those with long cycles relative to other types of irregular menses. Presuming that the group with longer cycles would have included at least some patients with undiagnosed PCOS, she was would have expected that the risk would have been highest in this group. While conceding that differences in body composition of Korean women is a potential explanation for this apparent discrepancy, “I would like to see confirmed in other samples of women with more detailed metabolic assessments to understand who is at risk,” she said.

Not least problematic for the strength of the conclusions, the hazard ratio for NAFLD among women with long or irregular menstrual cycles was “pretty low.” She described this as a level at which the risk “is very susceptible to confounding and unlikely to influence clinical practice.”

Anuja Dokras, MD, PHD, a professor of obstetrics and gynecology and director of the PCOS Center at the University of Pennsylvania, Philadelphia, also questioned whether undiagnosed PCOS might have skewed the data.

“There is increasing data on the association between PCOS and NAFLD. Irregular menses is a key criterion for PCOS, and PCOS is the commonest reason for anovulation,” she said. Dr. Dokras therefore considered it possible that patients with unrecognized PCOS were included in the study, weakening the claim that risk of NAFLD and long menstrual cycles remains significant after controlling for PCOS.

Dr. Ryu and coinvestigators, Dr. Santoro, and Dr. Dokras reported no potential conflicts of interest.

Long or irregular menstrual cycles in relatively young women are linked an increased risk of both prevalent and incident nonalcoholic fatty liver disease (NAFLD), according to a cross-sectional study that included data on more than 70,000 women.

“Our results indicate that menstrual irregularity, which is easier to diagnose and usually presented earlier than PCOS [polycystic ovary syndrome] highlights the possibility of identifying premenopausal women at risk of developing NAFLD,” reported a team of authors primarily from Sungkyunkwan University, Seoul, South Korea.

The study evaluated women aged younger than 40 years who were participating in the Kangbuk Samsung Health Study, which involves a comprehensive biennial health examination at health centers in South Korea. Of the 135,090 women enrolled over a 6-year period who had at least one follow-up examination, 72,092 were available for analysis after excluding for a sizable list of confounding factors such as liver disease and infections; exposure to steatogenic medications, such as corticosteroids; hysterectomy; and pregnancy.
 

NAFLD prevalence climbs with longer menses

Of these women, 36.378 (27.7%) had menstrual cycles of 26-30 days and were identified as the index group. The prevalence of NAFLD in this group was 5.8%. For those with a menstrual cycle of 31-39 days, the prevalence rate climbed to 7.2%. For those with a menstrual cycle of at least 40 days or too irregular to estimate, the prevalence was 9.7%. The prevalence was 7.1% for those with a menstrual cycle less than 21 days.

The results of this study were published in the Journal of Clinical Endocrinology & Metabolism.

In those without NAFLD at baseline who were then followed for a mean of 4.4 years, there were 4,524 incident cases of NAFLD. Incidence density was calculated per 103 patient-years. In the index group, the rate was 18.4. It climbed to 20.2 for those with a menstrual cycle of 31-39 days and then to 22.9 for those with a menstrual cycle of at least 40 days. For those with a cycle of fewer than 21 days, the rate was 26.8.

After adjusting for age, body mass index, insulin resistance, and other confounders, the hazard ratio for incident NAFLD for those with long or irregular menstrual cycles compared with the incident group corresponded with a 22% increased risk (HR, 1.22; 95% confidence interval, 1.14-1.31). When calculated in a time-dependent analysis, the risk of NAFLD was increased by almost 50% (HR, 1.49; 95% CI, 1.38-1.60).


 

Risk persists with PCOS exclusion

PCOS has previously been associated with increased risk of NAFLD, but the association between long or irregular menstrual cycles and NAFLD persisted after women with PCOS were excluded.

The mechanism that links menstrual irregularity with NAFLD is unclear, but the investigators said that estrogen exposure is implicated. In addition to a previously reported associated between low estradiol levels and antiestrogens such as tamoxifen with increased risk of NAFLD, they cited studies associating estrogen replacement therapy with a reduced risk of NAFLD. The role of estrogen in suppressing inflammation, oxidative stress, and insulin resistance are all activities that might link more regular menses with a reduced risk of NAFLD, the authors contended.

Women older than 40 years were excluded from this analysis to reduce the possibility of perimenopausal changes as a confounding factor.

Of study limitations acknowledged by the investigators, the presence of NAFLD was diagnosed on ultrasonography rather than histology. Information on sex hormone or prolactin levels was not captured in relation to NAFLD incidence, and the lack of exposure to estrogen replacement therapy and oral contraceptives was based on self-reports from the participants.

Still, the large study size and the consistency of results after adjustment for multiple risk factors argue that long and irregular menstrual cycles do identify women at risk for NAFLD. One implication is that irregular menses can be a marker for NAFLD risk.

“Our findings do not prove a causal relationship, but they show that long or irregular menstrual cycles were significantly associated with an increased risk of developing NAFLD,” said Seungho Ryu, MD, PhD, a professor at the Sungkyunkwan University. Senior author of this study, Dr. Ryu emphasized in an interview that the association “was not explained by obesity or any other risk factor for NAFLD.”
 

Lifestyle changes may lower risk

The message is that “young women with long or irregular menstrual cycles may benefit from lifestyle changes to reduce the risk of NAFLD,” Dr. Ryu stated.

The Study of Women’s Health Across the Nation, which was started in 1994, has not evaluated NAFLD, but it did show a relationship between longer menstrual cycles and more cardiometabolic risk factors, according to Nanette Santoro MD, professor and chair, department of obstetrics & gynecology, University of Colorado at Denver, Aurora.

This suggests that others are “thinking along the same lines,” but in discussing this study with this news organization, she characterized some of the design elements as well as some of the findings in this study as “peculiar.”

In addition to a “very, very narrow definition of regular cycles,” she questioned the consistent hazard ratio for NAFLD for those with long cycles relative to other types of irregular menses. Presuming that the group with longer cycles would have included at least some patients with undiagnosed PCOS, she was would have expected that the risk would have been highest in this group. While conceding that differences in body composition of Korean women is a potential explanation for this apparent discrepancy, “I would like to see confirmed in other samples of women with more detailed metabolic assessments to understand who is at risk,” she said.

Not least problematic for the strength of the conclusions, the hazard ratio for NAFLD among women with long or irregular menstrual cycles was “pretty low.” She described this as a level at which the risk “is very susceptible to confounding and unlikely to influence clinical practice.”

Anuja Dokras, MD, PHD, a professor of obstetrics and gynecology and director of the PCOS Center at the University of Pennsylvania, Philadelphia, also questioned whether undiagnosed PCOS might have skewed the data.

“There is increasing data on the association between PCOS and NAFLD. Irregular menses is a key criterion for PCOS, and PCOS is the commonest reason for anovulation,” she said. Dr. Dokras therefore considered it possible that patients with unrecognized PCOS were included in the study, weakening the claim that risk of NAFLD and long menstrual cycles remains significant after controlling for PCOS.

Dr. Ryu and coinvestigators, Dr. Santoro, and Dr. Dokras reported no potential conflicts of interest.

Expulsion of intrauterine devices was significantly more likely when the devices were inserted within the first 3 days after delivery compared with later insertions, based on data from more than 300,000 women.

Intrauterine devices are effective contraception, and current guidelines support immediate postpartum IUD insertion as a safe, effective, and convenient option, Mary Anne Armstrong, MA, of Kaiser Permanente Northern California, Oakland, and colleagues wrote. Although IUD expulsion rates are low overall, data from previous studies suggest that timing of insertion may affect expulsion rates, and that breastfeeding may play a role.

In the Association of Perforation and Expulsion of Intrauterine Devices (APEX-IUD) cohort study published in JAMA Network Open, the researchers reviewed data from the electronic health records at four sites; the study population included women aged 50 years and younger who underwent IUD insertion between 2001 and 2018.

The women were grouped by postpartum status and timing of IUD placement: 0-3 days, 4 days to 6 weeks, 6-14 weeks, 14-52 weeks, and nonpostpartum (defined as more than 52 weeks or no evidence of delivery).

The researchers also compared expulsion rates in postpartum women who were and were not breastfeeding at the time of IUD insertion based on clinical records, diagnostic codes, or questionnaires at well-baby visits.

The total study population included 326,658 women with a mean age of 32.0 years; 42% were non-Hispanic White, 17.2% were Hispanic other, 13.0% were Hispanic White, 11.9% were Asian or Pacific Islander, 8.7% were non-Hispanic Black, and 0.2% were Hispanic Black. Approximately 80% of the IUDs were levonorgestrel releasing.

A total of 8,943 expulsions were reported, for an overall expulsion rate of 13.94 per 1,000 person-years.

The adjusted hazard ratios for IUD expulsion were 5.34, 1.22, 1.06, and 1.43 for women with insertion times, respectively, of 0-3 days, 4 days to 6 or fewer weeks, 6-14 weeks, and 14-52 weeks. Women with nonpostpartum IUD insertion served as the referent.

The 5-year cumulative incidence of IUD expulsion was highest with placement between 0 and 3 days post partum and lowest with placement at 6-14 weeks postpartum (10.73% and 3.18%, respectively).

“Within the group with IUD insertions 0-3 days postpartum, the highest expulsion rates were discovered within 12 weeks of insertion, with the highest incidence rate occurring at week 6 (844 per 1,000 person-years), a time women are commonly seen post delivery,” the researchers noted.

In a subcohort of 94,817 women with known breastfeeding status, the 5-year cumulative incidence of expulsion was 3.49% for breastfeeding women and 4.57% for nonbreastfeeding women, with an adjusted HR of 0.71 for breastfeeding versus not breastfeeding.

“While women who accept immediate postpartum IUD placement report high satisfaction rates, information on women’s preferences and satisfaction associated with different timing of postpartum placement would also be helpful to understand the benefit-risk profile,” the researchers wrote in their discussion of the findings. “The fact that most expulsions in the immediate postpartum group occurred early presents an opportunity to mitigate risk of unrecognized expulsion and unintended pregnancy via counseling on signs of expulsion and follow-up examination.”

The study findings were limited by several factors including the potential misclassification of exposures and the primary outcome of expulsion, especially since some postpartum women may be lactating whether or not they are breastfeeding, the researchers noted. Other limitations included the combination of complete and partial expulsions, and the dating of IUD expulsion based on when it came to medical attention, which was not necessarily when it occurred. More data are needed on the potential association between lactational amenorrhea and lower expulsion risk among postpartum women who are breastfeeding.

However, the results were strengthened by the large and diverse study population, the use of linked mother-infant records to identify exposures, and the use electronic health records to identify outcomes, and the data can inform patient counseling for postpartum IUDs, the researchers concluded.
 

Study reflects findings from Europe

“The FDA mandated this study in response to a European study, EURAS-IUD1, a European prospective observational study that enrolled 61,448 participants between 2006 and 2012,” Ms. Armstrong said in an interview. In the European study “women breastfeeding at the time of device insertion or with the device inserted at 36 weeks’ postpartum or less had higher risk of uterine perforation. The FDA wanted to know if the risks were similar in the United States population”

The APEX-IUD study was designed to reflect current United States clinical practice. “The aims of APEX-IUD are to evaluate risk of IUD-related uterine perforation and device expulsion among women who are breastfeeding or within 12 months postpartum at insertion. The perforation outcome is addressed in a separate paper,” Ms. Armstrong noted.

“We were not surprised by the findings; they aligned with previous findings and confirm the overall safety of intrauterine devices,” said Ms. Armstrong. “Data from this study provides IUD expulsion risk estimates that can be used to inform clinical practice and preinsertion counseling. IUD insertions 0-3 days postpartum might decrease the risk of unintended pregnancy and provide more convenience and efficiency for new mothers. This has proven to be especially important during the pandemic. The higher risk of expulsion at 0-3 days post partum must be balanced with the low IUD-related uterine perforation risk to provide a comprehensive picture that aids in clinical decision-making.

“Potential barriers to postpartum IUD placement include lack of provision of education on the range of contraceptive options available during prenatal care and failure or inability of hospital inpatient units to stock the intrauterine devices for use when needed,” said Ms. Armstrong.

Looking ahead, “future research could evaluate risk factors for partial versus complete expulsions, the association of preinsertion counseling with recognition of potential expulsions and corresponding IUD failure rates, and whether ultrasound verification of IUD position in the uterus after insertion is associated with expulsion risk,” she said.
 

Identifying risk factors informs patient counseling

“The current study examines breastfeeding at time of IUD insertion as a risk factor for expulsion,” Iris Krishna, MD, of Emory University, Atlanta, said in an interview. “There is biologic plausibility that breastfeeding may be a risk factor of IUD expulsion. Breastfeeding stimulates secretion of oxytocin, a hormone which plays a key role in the contraction of the uterus during labor and uterine involution postpartum. It also plays a key role in the contraction of milk ducts to allow for milk letdown. Because of its dual role some mothers may occasionally report uterine cramping with breastfeeding. Prior studies have suggested that breastfeeding may be associated with an increased risk of uterine perforation with postpartum IUD placement, but how breastfeeding may contribute to risk of IUD expulsion has not been studied extensively.”

The current data are consistent with previous studies suggesting the highest risk of IUD expulsion is with placement in the immediate postpartum period (0-3 days). “In a subcohort analysis by breastfeeding status, the risk of IUD expulsion was lower for women who were breastfeeding versus not breastfeeding;” however, “these findings may be due to amenorrhea that can also be seen with breastfeeding,” Dr. Krishna said. “Menstrual bleeding is an independent risk factor for IUD expulsion and not having menstrual bleeding while breastfeeding may lower risk of expulsion.

“Patients should be counseled on the benefits of immediate postpartum IUD placement, the risk of IUD expulsion, and alternative contraception options to be able to make an informed decision about the right contraception for them,” Dr. Krishna emphasized. “Clinicians can reassure patients that the uterine cramping they may feel while breastfeeding does not appear to increase the risk of IUD expulsion and that the amenorrhea that may result from breastfeeding also may lower the risk of IUD expulsion.”

The study was supported by Bayer through support to RTI Health Solutions, Kaiser Permanente Northern California, Kaiser Permanente Southern California, Kaiser Permanente Washington, and the Regenstrief Institute. Ms. Armstrong and several coauthors disclosed support from Bayer during the study. Dr. Krishna had no relevant disclosures.

Expulsion of intrauterine devices was significantly more likely when the devices were inserted within the first 3 days after delivery compared with later insertions, based on data from more than 300,000 women.

Intrauterine devices are effective contraception, and current guidelines support immediate postpartum IUD insertion as a safe, effective, and convenient option, Mary Anne Armstrong, MA, of Kaiser Permanente Northern California, Oakland, and colleagues wrote. Although IUD expulsion rates are low overall, data from previous studies suggest that timing of insertion may affect expulsion rates, and that breastfeeding may play a role.

In the Association of Perforation and Expulsion of Intrauterine Devices (APEX-IUD) cohort study published in JAMA Network Open, the researchers reviewed data from the electronic health records at four sites; the study population included women aged 50 years and younger who underwent IUD insertion between 2001 and 2018.

The women were grouped by postpartum status and timing of IUD placement: 0-3 days, 4 days to 6 weeks, 6-14 weeks, 14-52 weeks, and nonpostpartum (defined as more than 52 weeks or no evidence of delivery).

The researchers also compared expulsion rates in postpartum women who were and were not breastfeeding at the time of IUD insertion based on clinical records, diagnostic codes, or questionnaires at well-baby visits.

The total study population included 326,658 women with a mean age of 32.0 years; 42% were non-Hispanic White, 17.2% were Hispanic other, 13.0% were Hispanic White, 11.9% were Asian or Pacific Islander, 8.7% were non-Hispanic Black, and 0.2% were Hispanic Black. Approximately 80% of the IUDs were levonorgestrel releasing.

A total of 8,943 expulsions were reported, for an overall expulsion rate of 13.94 per 1,000 person-years.

The adjusted hazard ratios for IUD expulsion were 5.34, 1.22, 1.06, and 1.43 for women with insertion times, respectively, of 0-3 days, 4 days to 6 or fewer weeks, 6-14 weeks, and 14-52 weeks. Women with nonpostpartum IUD insertion served as the referent.

The 5-year cumulative incidence of IUD expulsion was highest with placement between 0 and 3 days post partum and lowest with placement at 6-14 weeks postpartum (10.73% and 3.18%, respectively).

“Within the group with IUD insertions 0-3 days postpartum, the highest expulsion rates were discovered within 12 weeks of insertion, with the highest incidence rate occurring at week 6 (844 per 1,000 person-years), a time women are commonly seen post delivery,” the researchers noted.

In a subcohort of 94,817 women with known breastfeeding status, the 5-year cumulative incidence of expulsion was 3.49% for breastfeeding women and 4.57% for nonbreastfeeding women, with an adjusted HR of 0.71 for breastfeeding versus not breastfeeding.

“While women who accept immediate postpartum IUD placement report high satisfaction rates, information on women’s preferences and satisfaction associated with different timing of postpartum placement would also be helpful to understand the benefit-risk profile,” the researchers wrote in their discussion of the findings. “The fact that most expulsions in the immediate postpartum group occurred early presents an opportunity to mitigate risk of unrecognized expulsion and unintended pregnancy via counseling on signs of expulsion and follow-up examination.”

The study findings were limited by several factors including the potential misclassification of exposures and the primary outcome of expulsion, especially since some postpartum women may be lactating whether or not they are breastfeeding, the researchers noted. Other limitations included the combination of complete and partial expulsions, and the dating of IUD expulsion based on when it came to medical attention, which was not necessarily when it occurred. More data are needed on the potential association between lactational amenorrhea and lower expulsion risk among postpartum women who are breastfeeding.

However, the results were strengthened by the large and diverse study population, the use of linked mother-infant records to identify exposures, and the use electronic health records to identify outcomes, and the data can inform patient counseling for postpartum IUDs, the researchers concluded.
 

Study reflects findings from Europe

“The FDA mandated this study in response to a European study, EURAS-IUD1, a European prospective observational study that enrolled 61,448 participants between 2006 and 2012,” Ms. Armstrong said in an interview. In the European study “women breastfeeding at the time of device insertion or with the device inserted at 36 weeks’ postpartum or less had higher risk of uterine perforation. The FDA wanted to know if the risks were similar in the United States population”

The APEX-IUD study was designed to reflect current United States clinical practice. “The aims of APEX-IUD are to evaluate risk of IUD-related uterine perforation and device expulsion among women who are breastfeeding or within 12 months postpartum at insertion. The perforation outcome is addressed in a separate paper,” Ms. Armstrong noted.

“We were not surprised by the findings; they aligned with previous findings and confirm the overall safety of intrauterine devices,” said Ms. Armstrong. “Data from this study provides IUD expulsion risk estimates that can be used to inform clinical practice and preinsertion counseling. IUD insertions 0-3 days postpartum might decrease the risk of unintended pregnancy and provide more convenience and efficiency for new mothers. This has proven to be especially important during the pandemic. The higher risk of expulsion at 0-3 days post partum must be balanced with the low IUD-related uterine perforation risk to provide a comprehensive picture that aids in clinical decision-making.

“Potential barriers to postpartum IUD placement include lack of provision of education on the range of contraceptive options available during prenatal care and failure or inability of hospital inpatient units to stock the intrauterine devices for use when needed,” said Ms. Armstrong.

Looking ahead, “future research could evaluate risk factors for partial versus complete expulsions, the association of preinsertion counseling with recognition of potential expulsions and corresponding IUD failure rates, and whether ultrasound verification of IUD position in the uterus after insertion is associated with expulsion risk,” she said.
 

Identifying risk factors informs patient counseling

“The current study examines breastfeeding at time of IUD insertion as a risk factor for expulsion,” Iris Krishna, MD, of Emory University, Atlanta, said in an interview. “There is biologic plausibility that breastfeeding may be a risk factor of IUD expulsion. Breastfeeding stimulates secretion of oxytocin, a hormone which plays a key role in the contraction of the uterus during labor and uterine involution postpartum. It also plays a key role in the contraction of milk ducts to allow for milk letdown. Because of its dual role some mothers may occasionally report uterine cramping with breastfeeding. Prior studies have suggested that breastfeeding may be associated with an increased risk of uterine perforation with postpartum IUD placement, but how breastfeeding may contribute to risk of IUD expulsion has not been studied extensively.”

The current data are consistent with previous studies suggesting the highest risk of IUD expulsion is with placement in the immediate postpartum period (0-3 days). “In a subcohort analysis by breastfeeding status, the risk of IUD expulsion was lower for women who were breastfeeding versus not breastfeeding;” however, “these findings may be due to amenorrhea that can also be seen with breastfeeding,” Dr. Krishna said. “Menstrual bleeding is an independent risk factor for IUD expulsion and not having menstrual bleeding while breastfeeding may lower risk of expulsion.

“Patients should be counseled on the benefits of immediate postpartum IUD placement, the risk of IUD expulsion, and alternative contraception options to be able to make an informed decision about the right contraception for them,” Dr. Krishna emphasized. “Clinicians can reassure patients that the uterine cramping they may feel while breastfeeding does not appear to increase the risk of IUD expulsion and that the amenorrhea that may result from breastfeeding also may lower the risk of IUD expulsion.”

The study was supported by Bayer through support to RTI Health Solutions, Kaiser Permanente Northern California, Kaiser Permanente Southern California, Kaiser Permanente Washington, and the Regenstrief Institute. Ms. Armstrong and several coauthors disclosed support from Bayer during the study. Dr. Krishna had no relevant disclosures.

Expulsion of intrauterine devices was significantly more likely when the devices were inserted within the first 3 days after delivery compared with later insertions, based on data from more than 300,000 women.

Intrauterine devices are effective contraception, and current guidelines support immediate postpartum IUD insertion as a safe, effective, and convenient option, Mary Anne Armstrong, MA, of Kaiser Permanente Northern California, Oakland, and colleagues wrote. Although IUD expulsion rates are low overall, data from previous studies suggest that timing of insertion may affect expulsion rates, and that breastfeeding may play a role.

In the Association of Perforation and Expulsion of Intrauterine Devices (APEX-IUD) cohort study published in JAMA Network Open, the researchers reviewed data from the electronic health records at four sites; the study population included women aged 50 years and younger who underwent IUD insertion between 2001 and 2018.

The women were grouped by postpartum status and timing of IUD placement: 0-3 days, 4 days to 6 weeks, 6-14 weeks, 14-52 weeks, and nonpostpartum (defined as more than 52 weeks or no evidence of delivery).

The researchers also compared expulsion rates in postpartum women who were and were not breastfeeding at the time of IUD insertion based on clinical records, diagnostic codes, or questionnaires at well-baby visits.

The total study population included 326,658 women with a mean age of 32.0 years; 42% were non-Hispanic White, 17.2% were Hispanic other, 13.0% were Hispanic White, 11.9% were Asian or Pacific Islander, 8.7% were non-Hispanic Black, and 0.2% were Hispanic Black. Approximately 80% of the IUDs were levonorgestrel releasing.

A total of 8,943 expulsions were reported, for an overall expulsion rate of 13.94 per 1,000 person-years.

The adjusted hazard ratios for IUD expulsion were 5.34, 1.22, 1.06, and 1.43 for women with insertion times, respectively, of 0-3 days, 4 days to 6 or fewer weeks, 6-14 weeks, and 14-52 weeks. Women with nonpostpartum IUD insertion served as the referent.

The 5-year cumulative incidence of IUD expulsion was highest with placement between 0 and 3 days post partum and lowest with placement at 6-14 weeks postpartum (10.73% and 3.18%, respectively).

“Within the group with IUD insertions 0-3 days postpartum, the highest expulsion rates were discovered within 12 weeks of insertion, with the highest incidence rate occurring at week 6 (844 per 1,000 person-years), a time women are commonly seen post delivery,” the researchers noted.

In a subcohort of 94,817 women with known breastfeeding status, the 5-year cumulative incidence of expulsion was 3.49% for breastfeeding women and 4.57% for nonbreastfeeding women, with an adjusted HR of 0.71 for breastfeeding versus not breastfeeding.

“While women who accept immediate postpartum IUD placement report high satisfaction rates, information on women’s preferences and satisfaction associated with different timing of postpartum placement would also be helpful to understand the benefit-risk profile,” the researchers wrote in their discussion of the findings. “The fact that most expulsions in the immediate postpartum group occurred early presents an opportunity to mitigate risk of unrecognized expulsion and unintended pregnancy via counseling on signs of expulsion and follow-up examination.”

The study findings were limited by several factors including the potential misclassification of exposures and the primary outcome of expulsion, especially since some postpartum women may be lactating whether or not they are breastfeeding, the researchers noted. Other limitations included the combination of complete and partial expulsions, and the dating of IUD expulsion based on when it came to medical attention, which was not necessarily when it occurred. More data are needed on the potential association between lactational amenorrhea and lower expulsion risk among postpartum women who are breastfeeding.

However, the results were strengthened by the large and diverse study population, the use of linked mother-infant records to identify exposures, and the use electronic health records to identify outcomes, and the data can inform patient counseling for postpartum IUDs, the researchers concluded.
 

Study reflects findings from Europe

“The FDA mandated this study in response to a European study, EURAS-IUD1, a European prospective observational study that enrolled 61,448 participants between 2006 and 2012,” Ms. Armstrong said in an interview. In the European study “women breastfeeding at the time of device insertion or with the device inserted at 36 weeks’ postpartum or less had higher risk of uterine perforation. The FDA wanted to know if the risks were similar in the United States population”

The APEX-IUD study was designed to reflect current United States clinical practice. “The aims of APEX-IUD are to evaluate risk of IUD-related uterine perforation and device expulsion among women who are breastfeeding or within 12 months postpartum at insertion. The perforation outcome is addressed in a separate paper,” Ms. Armstrong noted.

“We were not surprised by the findings; they aligned with previous findings and confirm the overall safety of intrauterine devices,” said Ms. Armstrong. “Data from this study provides IUD expulsion risk estimates that can be used to inform clinical practice and preinsertion counseling. IUD insertions 0-3 days postpartum might decrease the risk of unintended pregnancy and provide more convenience and efficiency for new mothers. This has proven to be especially important during the pandemic. The higher risk of expulsion at 0-3 days post partum must be balanced with the low IUD-related uterine perforation risk to provide a comprehensive picture that aids in clinical decision-making.

“Potential barriers to postpartum IUD placement include lack of provision of education on the range of contraceptive options available during prenatal care and failure or inability of hospital inpatient units to stock the intrauterine devices for use when needed,” said Ms. Armstrong.

Looking ahead, “future research could evaluate risk factors for partial versus complete expulsions, the association of preinsertion counseling with recognition of potential expulsions and corresponding IUD failure rates, and whether ultrasound verification of IUD position in the uterus after insertion is associated with expulsion risk,” she said.
 

Identifying risk factors informs patient counseling

“The current study examines breastfeeding at time of IUD insertion as a risk factor for expulsion,” Iris Krishna, MD, of Emory University, Atlanta, said in an interview. “There is biologic plausibility that breastfeeding may be a risk factor of IUD expulsion. Breastfeeding stimulates secretion of oxytocin, a hormone which plays a key role in the contraction of the uterus during labor and uterine involution postpartum. It also plays a key role in the contraction of milk ducts to allow for milk letdown. Because of its dual role some mothers may occasionally report uterine cramping with breastfeeding. Prior studies have suggested that breastfeeding may be associated with an increased risk of uterine perforation with postpartum IUD placement, but how breastfeeding may contribute to risk of IUD expulsion has not been studied extensively.”

The current data are consistent with previous studies suggesting the highest risk of IUD expulsion is with placement in the immediate postpartum period (0-3 days). “In a subcohort analysis by breastfeeding status, the risk of IUD expulsion was lower for women who were breastfeeding versus not breastfeeding;” however, “these findings may be due to amenorrhea that can also be seen with breastfeeding,” Dr. Krishna said. “Menstrual bleeding is an independent risk factor for IUD expulsion and not having menstrual bleeding while breastfeeding may lower risk of expulsion.

“Patients should be counseled on the benefits of immediate postpartum IUD placement, the risk of IUD expulsion, and alternative contraception options to be able to make an informed decision about the right contraception for them,” Dr. Krishna emphasized. “Clinicians can reassure patients that the uterine cramping they may feel while breastfeeding does not appear to increase the risk of IUD expulsion and that the amenorrhea that may result from breastfeeding also may lower the risk of IUD expulsion.”

The study was supported by Bayer through support to RTI Health Solutions, Kaiser Permanente Northern California, Kaiser Permanente Southern California, Kaiser Permanente Washington, and the Regenstrief Institute. Ms. Armstrong and several coauthors disclosed support from Bayer during the study. Dr. Krishna had no relevant disclosures.

This study was published on Medrxiv.org as a preprint and has not yet been peer reviewed.

Key takeaways

• in analyses of more than 100,000 women that used Mendelian randomization (MR) as a tool to reduce residual confounding.
• The MR analyses showed no significant association between ANM and breast cancer, endometrial cancer, ovarian cancer, coronary heart disease, ischemic stroke, and Alzheimer’s disease.
• The clear lack of a causal effect of ANM on the outcomes of coronary heart disease and ischemic stroke in the MR analyses despite a strong inverse association seen in the observational data of this study (without MR) suggests residual confounding plays a substantial role in driving the observed outcomes.

Why this matters

• The authors said that, to their knowledge, this is the first study that has shown a causal association between older ANM and higher risk of postmenopausal lung cancer.
• This finding was directionally opposite to the significant protective effect of increased ANM documented in an observational analysis of roughly the same data as well as prior reports that did not use MR. This “notable inconsistency” suggests very substantial residual confounding without MR that could be driven by factors such as smoking, diet, and exercise.
• If these results are replicated in additional datasets, it would highlight a need for randomized, controlled trials of antiestrogen therapies in postmenopausal women for the prevention or treatment of lung cancer.

Study design

• The study included data from 106,853 postmenopausal women enrolled in the Women’s Health Initiative (WHI) and 95,464 women who were 37-73 years old included in the UK Biobank (UKB). Analyses for each outcome also included data from smaller numbers of women obtained from several additional datasets.
• The MR analysis used up to 55 single-nucleotide polymorphisms previously discovered through a genome-wide association study of about 70,000 women of European ancestry and independent of all datasets analyzed in the current study. The authors included all single-nucleotide polymorphisms with a consistent direction of effect on ANM.
• The MR analysis for lung cancer included 113,371 women from the two primary datasets and an additional 3012 women from six additional datasets.
• The MR analysis for bone fracture involved 113,239 women from the WHI and UKB only. The MR analysis for osteoporosis involved 137,080 women from the WHI, UKB, and one additional external dataset.

Key results

• Results from a meta-analysis of the MR results using data from the WHI, UKB, and the additional datasets showed ANM was causally associated with an increased risk of lung cancer by an odds ratio of 1.35 for each 5-year increase in ANM. In contrast, the adjusted observational analysis of data just from the WHI and UKB showed a significant 11% relative risk reduction in the incidence of lung cancer for each 5-year increase in ANM.
• The MR results also showed causally protective effects for fracture, with a 24% relative risk reduction, and for osteoporosis, with a 19% relative risk reduction for each 5-year increase in ANM.
• The MR analyses showed no significant association between AMN and outcome for breast cancer, endometrial cancer, ovarian cancer, coronary heart disease, ischemic stroke, and Alzheimer’s disease.

Limitations

The main limitation of the MR study was the potential for inadequate power for assessing some outcomes despite the large overall size of the study cohort. Lack of adequate power may be responsible for some of the nonsignificant associations seen in the study, such as for breast and endometrial cancers, where substantial prior evidence has implicated increased risk through the effects of prolonged exposure to endogenous or exogenous estrogens.

The healthy cohort effect in the UKB is a known weakness of this dataset that may have limited the number of cases and generalizability of findings.

Osteoporosis and Alzheimer’s disease were self-reported.

The study only included participants of European ancestry because most subjects in most of the cohorts examined were White women and the applied MR instruments were found by genome-wide association studies run predominantly in White women. The authors said the causal effects of ANM need study in more diverse populations.
 

Disclosures

• The study received no commercial funding.
• None of the authors had disclosures.

This is a summary of a preprint research study, “Genetic evidence for causal relationships between age at natural menopause and the risk of aging-associated adverse health outcomes,” written by authors primarily based at Stanford University School of Medicine i

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

This study was published on Medrxiv.org as a preprint and has not yet been peer reviewed.

Key takeaways

• in analyses of more than 100,000 women that used Mendelian randomization (MR) as a tool to reduce residual confounding.
• The MR analyses showed no significant association between ANM and breast cancer, endometrial cancer, ovarian cancer, coronary heart disease, ischemic stroke, and Alzheimer’s disease.
• The clear lack of a causal effect of ANM on the outcomes of coronary heart disease and ischemic stroke in the MR analyses despite a strong inverse association seen in the observational data of this study (without MR) suggests residual confounding plays a substantial role in driving the observed outcomes.

Why this matters

• The authors said that, to their knowledge, this is the first study that has shown a causal association between older ANM and higher risk of postmenopausal lung cancer.
• This finding was directionally opposite to the significant protective effect of increased ANM documented in an observational analysis of roughly the same data as well as prior reports that did not use MR. This “notable inconsistency” suggests very substantial residual confounding without MR that could be driven by factors such as smoking, diet, and exercise.
• If these results are replicated in additional datasets, it would highlight a need for randomized, controlled trials of antiestrogen therapies in postmenopausal women for the prevention or treatment of lung cancer.

Study design

• The study included data from 106,853 postmenopausal women enrolled in the Women’s Health Initiative (WHI) and 95,464 women who were 37-73 years old included in the UK Biobank (UKB). Analyses for each outcome also included data from smaller numbers of women obtained from several additional datasets.
• The MR analysis used up to 55 single-nucleotide polymorphisms previously discovered through a genome-wide association study of about 70,000 women of European ancestry and independent of all datasets analyzed in the current study. The authors included all single-nucleotide polymorphisms with a consistent direction of effect on ANM.
• The MR analysis for lung cancer included 113,371 women from the two primary datasets and an additional 3012 women from six additional datasets.
• The MR analysis for bone fracture involved 113,239 women from the WHI and UKB only. The MR analysis for osteoporosis involved 137,080 women from the WHI, UKB, and one additional external dataset.

Key results

• Results from a meta-analysis of the MR results using data from the WHI, UKB, and the additional datasets showed ANM was causally associated with an increased risk of lung cancer by an odds ratio of 1.35 for each 5-year increase in ANM. In contrast, the adjusted observational analysis of data just from the WHI and UKB showed a significant 11% relative risk reduction in the incidence of lung cancer for each 5-year increase in ANM.
• The MR results also showed causally protective effects for fracture, with a 24% relative risk reduction, and for osteoporosis, with a 19% relative risk reduction for each 5-year increase in ANM.
• The MR analyses showed no significant association between AMN and outcome for breast cancer, endometrial cancer, ovarian cancer, coronary heart disease, ischemic stroke, and Alzheimer’s disease.

Limitations

The main limitation of the MR study was the potential for inadequate power for assessing some outcomes despite the large overall size of the study cohort. Lack of adequate power may be responsible for some of the nonsignificant associations seen in the study, such as for breast and endometrial cancers, where substantial prior evidence has implicated increased risk through the effects of prolonged exposure to endogenous or exogenous estrogens.

The healthy cohort effect in the UKB is a known weakness of this dataset that may have limited the number of cases and generalizability of findings.

Osteoporosis and Alzheimer’s disease were self-reported.

The study only included participants of European ancestry because most subjects in most of the cohorts examined were White women and the applied MR instruments were found by genome-wide association studies run predominantly in White women. The authors said the causal effects of ANM need study in more diverse populations.
 

Disclosures

• The study received no commercial funding.
• None of the authors had disclosures.

This is a summary of a preprint research study, “Genetic evidence for causal relationships between age at natural menopause and the risk of aging-associated adverse health outcomes,” written by authors primarily based at Stanford University School of Medicine i

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

This study was published on Medrxiv.org as a preprint and has not yet been peer reviewed.

Key takeaways

• in analyses of more than 100,000 women that used Mendelian randomization (MR) as a tool to reduce residual confounding.
• The MR analyses showed no significant association between ANM and breast cancer, endometrial cancer, ovarian cancer, coronary heart disease, ischemic stroke, and Alzheimer’s disease.
• The clear lack of a causal effect of ANM on the outcomes of coronary heart disease and ischemic stroke in the MR analyses despite a strong inverse association seen in the observational data of this study (without MR) suggests residual confounding plays a substantial role in driving the observed outcomes.

Why this matters

• The authors said that, to their knowledge, this is the first study that has shown a causal association between older ANM and higher risk of postmenopausal lung cancer.
• This finding was directionally opposite to the significant protective effect of increased ANM documented in an observational analysis of roughly the same data as well as prior reports that did not use MR. This “notable inconsistency” suggests very substantial residual confounding without MR that could be driven by factors such as smoking, diet, and exercise.
• If these results are replicated in additional datasets, it would highlight a need for randomized, controlled trials of antiestrogen therapies in postmenopausal women for the prevention or treatment of lung cancer.

Study design

• The study included data from 106,853 postmenopausal women enrolled in the Women’s Health Initiative (WHI) and 95,464 women who were 37-73 years old included in the UK Biobank (UKB). Analyses for each outcome also included data from smaller numbers of women obtained from several additional datasets.
• The MR analysis used up to 55 single-nucleotide polymorphisms previously discovered through a genome-wide association study of about 70,000 women of European ancestry and independent of all datasets analyzed in the current study. The authors included all single-nucleotide polymorphisms with a consistent direction of effect on ANM.
• The MR analysis for lung cancer included 113,371 women from the two primary datasets and an additional 3012 women from six additional datasets.
• The MR analysis for bone fracture involved 113,239 women from the WHI and UKB only. The MR analysis for osteoporosis involved 137,080 women from the WHI, UKB, and one additional external dataset.

Key results

• Results from a meta-analysis of the MR results using data from the WHI, UKB, and the additional datasets showed ANM was causally associated with an increased risk of lung cancer by an odds ratio of 1.35 for each 5-year increase in ANM. In contrast, the adjusted observational analysis of data just from the WHI and UKB showed a significant 11% relative risk reduction in the incidence of lung cancer for each 5-year increase in ANM.
• The MR results also showed causally protective effects for fracture, with a 24% relative risk reduction, and for osteoporosis, with a 19% relative risk reduction for each 5-year increase in ANM.
• The MR analyses showed no significant association between AMN and outcome for breast cancer, endometrial cancer, ovarian cancer, coronary heart disease, ischemic stroke, and Alzheimer’s disease.

Limitations

The main limitation of the MR study was the potential for inadequate power for assessing some outcomes despite the large overall size of the study cohort. Lack of adequate power may be responsible for some of the nonsignificant associations seen in the study, such as for breast and endometrial cancers, where substantial prior evidence has implicated increased risk through the effects of prolonged exposure to endogenous or exogenous estrogens.

The healthy cohort effect in the UKB is a known weakness of this dataset that may have limited the number of cases and generalizability of findings.

Osteoporosis and Alzheimer’s disease were self-reported.

The study only included participants of European ancestry because most subjects in most of the cohorts examined were White women and the applied MR instruments were found by genome-wide association studies run predominantly in White women. The authors said the causal effects of ANM need study in more diverse populations.
 

Disclosures

• The study received no commercial funding.
• None of the authors had disclosures.

This is a summary of a preprint research study, “Genetic evidence for causal relationships between age at natural menopause and the risk of aging-associated adverse health outcomes,” written by authors primarily based at Stanford University School of Medicine i

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

Kia Slade was 7 months pregnant, unvaccinated, and fighting for breath, her oxygen levels plummeting, when her son came into the world last May.

A severe case of COVID-19 pneumonia had left Ms. Slade delirious. When the intensive care team tried to place an oxygen mask on her face, she snatched it away, she recalled. Her baby’s heart rate began to drop.

Ms. Slade’s doctor performed an emergency cesarean section at her bedside in the intensive care unit, delivering baby Tristan 10 weeks early. He weighed just 2 pounds, 14 ounces, about half the size of small full-term baby.

But Ms. Slade wouldn’t meet him until July. She was on a ventilator in a medically-induced coma for 8 weeks, and she developed a serious infection and blood clot while unconscious. It was only after a perilous 2½ months in the hospital, during which her heart stopped twice, that Ms. Slade was vaccinated against COVID-19.

“I wish I had gotten the vaccine earlier,” said Ms. Slade, 42, who remains too sick to return to work as a special education teacher in Baltimore. Doctors “kept pushing me to get vaccinated, but there just wasn’t enough information out there for me to do it.”

A year ago, there was little to no vaccine safety data for pregnant people like Ms. Slade, because they had been excluded from clinical trials run by Pfizer, Moderna, and other vaccine makers.

Lacking data, health experts were unsure and divided about how to advise expectant parents. Although U.S. health officials permitted pregnant people to be vaccinated, the World Health Organization in January 2021 actually discouraged them from doing so; it later reversed that recommendation.

The uncertainty led many women to delay vaccination, and only about two-thirds of the pregnant people who have been tracked by the Centers for Disease Control and Prevention were fully vaccinated as of Feb. 5, 2022, leaving many expectant moms at a high risk of infection and life-threatening complications.

More than 29,000 pregnant people have been hospitalized with COVID-19 and 274 have died, according to the CDC.

“There were surely women who were hospitalized because there wasn’t information available to them,” said Paul A. Offit, MD, director of the Vaccine Education Center at the Children’s Hospital of Philadelphia.

Vaccine developers say that pregnant people – who have special health needs and risks – were excluded from clinical trials to protect them from potential side effects of novel technologies, including the Pfizer and Moderna mRNA vaccines and formulations made with cold viruses, such as the Johnson & Johnson vaccine.

But a KHN analysis also shows that pregnant people were left behind because including them in vaccine studies would have complicated and potentially delayed the delivery of COVID-19 vaccines to the broader population.

A growing number of women’s health researchers and advocates say that excluding pregnant people – and the months-long delay in recommending that they be immunized – helped fuel widespread vaccine hesitancy in this vulnerable group.

“Women and their unborn fetuses are dying of COVID infection,” said Jane Van Dis, MD, an ob.gyn. at the University of Rochester (N.Y.) Medical Center who has treated many patients like Ms. Slade. “Our failure as a society to vaccinate women in pregnancy will be remembered by the children and families who lost their mothers to this disease.”
 

New technology, uncertain risks

At the time COVID-19 vaccines were being developed, scientists had very little experience using mRNA vaccines in pregnant women, said Jacqueline Miller, MD, a senior vice president involved in vaccine research at Moderna.

“When you study anything in pregnant women, you have two patients, the mom and the unborn child,” Dr. Miller said. “Until we had more safety data on the platform, it wasn’t something we wanted to undertake.”

But Dr. Offit noted that vaccines have a strong record of safety in pregnancy and he sees no reason to have excluded pregnant people. None of the vaccines currently in use – including the chickenpox and rubella vaccines, which contain live viruses – have been shown to harm fetuses, he said. Doctors routinely recommend that pregnant people receive pertussis and flu vaccinations.

Dr. Offit, the coinventor of a rotavirus vaccine, said that some concerns about vaccines stem from commercial, not medical, interests. Drug makers don’t want to risk that their product will be blamed for any problems occurring in pregnant people, even if coincidental, he said.

“These companies don’t want bad news,” Dr. Offit said.

In the United States, health officials typically would have told expectant mothers not to take a vaccine that was untested during pregnancy, said Dr. Offit, a member of a committee that advises the Food and Drug Administration on vaccines.

Due to the urgency of the pandemic, health agencies instead permitted pregnant people to make up their own minds about vaccines without recommending them.

Women’s medical associations were also hampered by the lack of data. Neither the American College of Obstetricians and Gynecologists nor the Society for Maternal-Fetal Medicine actively encouraged pregnant people to be vaccinated until July 30, 2021, after the first real-world vaccine studies had been published. The CDC followed suit in August of 2021.

“If we had had this data in the beginning, we would have been able to vaccinate more women,” said Kelli Burroughs, MD, the department chair of obstetrics and gynecology at Memorial Hermann Sugar Land Hospital near Houston.

Yet anti-vaccine groups wasted no time in scaring pregnant people, flooding social media with misinformation about impaired fertility and harm to the fetus.

In the first few months after the COVID-19 vaccines were approved, some doctors were ambivalent about recommending them, and some still advise pregnant patients against vaccination.

An estimated 67% of pregnant people today are fully vaccinated, compared with about 89% of people 65 and older, another high-risk group, and 65% of Americans overall. Vaccination rates are lower among minorities, with 65% of expectant Hispanic mothers and 53% of pregnant African Americans fully vaccinated, according to the CDC.

Vaccination is especially important during pregnancy, because of increased risks of hospitalization, ICU admission, and mechanical ventilation, Dr. Burroughs said. A study released in February from the National Institutes of Health found that pregnant people with a moderate to severe COVID-19 infection also were more likely to have a C-section, deliver preterm, or develop a postpartum hemorrhage.

Black moms such as Ms. Slade were already at higher risk of maternal and infant mortality before the pandemic, because of higher underlying risks, unequal access to health care, and other factors. COVID-19 has magnified those risks, said Dr. Burroughs, who has persuaded reluctant patients by revealing that she had a healthy pregnancy and child after being vaccinated.

Ms. Slade said she has never opposed vaccines and had no hesitation about receiving other vaccines while pregnant. But she said she “just wasn’t comfortable” with COVID-19 shots.

“If there had been data out there saying the COVID shot was safe, and that nothing would happen to my baby and there was no risk of birth defects, I would have taken it,” said Ms. Slade, who has had type 2 diabetes for 12 years.
 

Working at warp speed

Government scientists at the NIH were concerned about the risk of COVID-19 to pregnant people from the very beginning and knew that expectant moms needed vaccines as much or more than anyone else, said Larry Corey, MD, a leader of the COVID-19 Prevention Network, which coordinated COVID-19 vaccine trials for the federal government.

But including pregnant volunteers in the larger vaccine trials could have led to interruptions and delays, Dr. Corey said. Researchers would have had to enroll thousands of pregnant volunteers to achieve statistically robust results that weren’t due to chance, he said.

Pregnancy can bring on a wide range of complications: gestational diabetes, hypertension, anemia, bleeding, blood clots, or problems with the placenta, for example. Up to 20% of people who know they’re pregnant miscarry. Because researchers would have been obliged to investigate any medical problem to make sure it wasn’t caused by one of the COVID-19 vaccines, including pregnant people might have meant having to hit pause on those trials, Dr. Corey said.

With death tolls from the pandemic mounting, “we had a mission to do this as quickly and as thoroughly as possible,” Dr. Corey said. Making COVID-19 vaccines available within a year “saved hundreds of thousands of lives.”

The first data on COVID-19 vaccine safety in pregnancy was published in April of 2021 when the CDC released an analysis of nearly 36,000 vaccinated pregnant people who had enrolled in a registry called V-safe, which allows users to log the dates of their vaccinations and any subsequent symptoms.

Later research showed that COVID-19 vaccines weren’t associated with increased risk of miscarriage or premature delivery.

Brenna Hughes, MD, a maternal-fetal medicine specialist and member of the American College of Obstetricians and Gynecologists’ COVID-19 expert group, agrees that adding pregnant people to large-scale COVID-19 vaccine and drug trials may have been impractical. But researchers could have launched parallel trials of pregnant women, once early studies showed the vaccines were safe in humans, she said.

“Would it have been hard? Everything with COVID is hard,” Dr. Hughes said. “But it would have been feasible.”

The FDA requires that researchers perform additional animal studies – called developmental and reproductive toxicity studies – before testing vaccines in pregnant people. Although these studies are essential, they take 5-6 months, and weren’t completed until late 2020, around the time the first COVID-19 vaccines were authorized for adults, said Emily Erbelding, MD, director of microbiology and infectious diseases at the National Institute of Allergy and Infectious Diseases, part of the NIH.

Pregnancy studies “were an afterthought,” said Irina Burd, MD, director of Johns Hopkins’ Integrated Research Center for Fetal Medicine and a professor of gynecology and obstetrics. “They should have been done sooner.”

The NIH is conducting a study of pregnant and postpartum people who decided on their own to be vaccinated, Dr. Erbelding said. The study is due to be completed by July 2023.

Janssen and Moderna are also conducting studies in pregnant people, both due to be completed in 2024.

Pfizer scientists encountered problems when they initiated a clinical trial, which would have randomly assigned pregnant people to receive either a vaccine or placebo. Once vaccines were widely available, many patients weren’t willing to take a chance on being unvaccinated until after delivery.

Pfizer has stopped recruiting patients and has not said whether it will publicly report any data from the trial.

Dr. Hughes said vaccine developers need to include pregnant people from the very beginning.

“There is this notion of protecting pregnant people from research,” Dr. Hughes said. “But we should be protecting patients through research, not from research.”
 

Recovering physically and emotionally

Ms. Slade still regrets being deprived of time with her children while she fought the disease.

Being on a ventilator kept her from spending those early weeks with her newborn, or from seeing her 9-year-old daughter, Zoe.

Even when Ms. Slade was finally able to see her son, she wasn’t able to tell him she loved him or sing a lullaby, or even talk at all, because of a breathing tube in her throat.

Today, Ms. Slade is a strong advocate of COVID-19 vaccinations, urging her friends and family to get their shots to avoid suffering the way she has.

Ms. Slade had to relearn to walk after being bedridden for weeks. Her many weeks on a ventilator may have contributed to her stomach paralysis, which often causes intense pain, nausea, and even vomiting when she eats or drinks. Ms. Slade weighs 50 pounds less today than before she became pregnant and has resorted to going to the emergency department when the pain is unbearable. “Most days, I’m just miserable,” she said.

Her family suffered as well. Like many babies born prematurely, Tristan, now nearly 9 months old and crawling, receives physical therapy to strengthen his muscles. At 15 pounds, Tristan is largely healthy, although his doctor said he has symptoms of asthma.

Ms. Slade said she would like to attend family counseling with Zoe, who rarely complains and tends to keep her feelings to herself. Ms. Slade said she knows her illness must have been terrifying for her little girl.

“The other day she was talking to me,” Ms. Slade said, “and she said, ‘You know, I almost had to bury you.’ ”
 

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.

Kia Slade was 7 months pregnant, unvaccinated, and fighting for breath, her oxygen levels plummeting, when her son came into the world last May.

A severe case of COVID-19 pneumonia had left Ms. Slade delirious. When the intensive care team tried to place an oxygen mask on her face, she snatched it away, she recalled. Her baby’s heart rate began to drop.

Ms. Slade’s doctor performed an emergency cesarean section at her bedside in the intensive care unit, delivering baby Tristan 10 weeks early. He weighed just 2 pounds, 14 ounces, about half the size of small full-term baby.

But Ms. Slade wouldn’t meet him until July. She was on a ventilator in a medically-induced coma for 8 weeks, and she developed a serious infection and blood clot while unconscious. It was only after a perilous 2½ months in the hospital, during which her heart stopped twice, that Ms. Slade was vaccinated against COVID-19.

“I wish I had gotten the vaccine earlier,” said Ms. Slade, 42, who remains too sick to return to work as a special education teacher in Baltimore. Doctors “kept pushing me to get vaccinated, but there just wasn’t enough information out there for me to do it.”

A year ago, there was little to no vaccine safety data for pregnant people like Ms. Slade, because they had been excluded from clinical trials run by Pfizer, Moderna, and other vaccine makers.

Lacking data, health experts were unsure and divided about how to advise expectant parents. Although U.S. health officials permitted pregnant people to be vaccinated, the World Health Organization in January 2021 actually discouraged them from doing so; it later reversed that recommendation.

The uncertainty led many women to delay vaccination, and only about two-thirds of the pregnant people who have been tracked by the Centers for Disease Control and Prevention were fully vaccinated as of Feb. 5, 2022, leaving many expectant moms at a high risk of infection and life-threatening complications.

More than 29,000 pregnant people have been hospitalized with COVID-19 and 274 have died, according to the CDC.

“There were surely women who were hospitalized because there wasn’t information available to them,” said Paul A. Offit, MD, director of the Vaccine Education Center at the Children’s Hospital of Philadelphia.

Vaccine developers say that pregnant people – who have special health needs and risks – were excluded from clinical trials to protect them from potential side effects of novel technologies, including the Pfizer and Moderna mRNA vaccines and formulations made with cold viruses, such as the Johnson & Johnson vaccine.

But a KHN analysis also shows that pregnant people were left behind because including them in vaccine studies would have complicated and potentially delayed the delivery of COVID-19 vaccines to the broader population.

A growing number of women’s health researchers and advocates say that excluding pregnant people – and the months-long delay in recommending that they be immunized – helped fuel widespread vaccine hesitancy in this vulnerable group.

“Women and their unborn fetuses are dying of COVID infection,” said Jane Van Dis, MD, an ob.gyn. at the University of Rochester (N.Y.) Medical Center who has treated many patients like Ms. Slade. “Our failure as a society to vaccinate women in pregnancy will be remembered by the children and families who lost their mothers to this disease.”
 

New technology, uncertain risks

At the time COVID-19 vaccines were being developed, scientists had very little experience using mRNA vaccines in pregnant women, said Jacqueline Miller, MD, a senior vice president involved in vaccine research at Moderna.

“When you study anything in pregnant women, you have two patients, the mom and the unborn child,” Dr. Miller said. “Until we had more safety data on the platform, it wasn’t something we wanted to undertake.”

But Dr. Offit noted that vaccines have a strong record of safety in pregnancy and he sees no reason to have excluded pregnant people. None of the vaccines currently in use – including the chickenpox and rubella vaccines, which contain live viruses – have been shown to harm fetuses, he said. Doctors routinely recommend that pregnant people receive pertussis and flu vaccinations.

Dr. Offit, the coinventor of a rotavirus vaccine, said that some concerns about vaccines stem from commercial, not medical, interests. Drug makers don’t want to risk that their product will be blamed for any problems occurring in pregnant people, even if coincidental, he said.

“These companies don’t want bad news,” Dr. Offit said.

In the United States, health officials typically would have told expectant mothers not to take a vaccine that was untested during pregnancy, said Dr. Offit, a member of a committee that advises the Food and Drug Administration on vaccines.

Due to the urgency of the pandemic, health agencies instead permitted pregnant people to make up their own minds about vaccines without recommending them.

Women’s medical associations were also hampered by the lack of data. Neither the American College of Obstetricians and Gynecologists nor the Society for Maternal-Fetal Medicine actively encouraged pregnant people to be vaccinated until July 30, 2021, after the first real-world vaccine studies had been published. The CDC followed suit in August of 2021.

“If we had had this data in the beginning, we would have been able to vaccinate more women,” said Kelli Burroughs, MD, the department chair of obstetrics and gynecology at Memorial Hermann Sugar Land Hospital near Houston.

Yet anti-vaccine groups wasted no time in scaring pregnant people, flooding social media with misinformation about impaired fertility and harm to the fetus.

In the first few months after the COVID-19 vaccines were approved, some doctors were ambivalent about recommending them, and some still advise pregnant patients against vaccination.

An estimated 67% of pregnant people today are fully vaccinated, compared with about 89% of people 65 and older, another high-risk group, and 65% of Americans overall. Vaccination rates are lower among minorities, with 65% of expectant Hispanic mothers and 53% of pregnant African Americans fully vaccinated, according to the CDC.

Vaccination is especially important during pregnancy, because of increased risks of hospitalization, ICU admission, and mechanical ventilation, Dr. Burroughs said. A study released in February from the National Institutes of Health found that pregnant people with a moderate to severe COVID-19 infection also were more likely to have a C-section, deliver preterm, or develop a postpartum hemorrhage.

Black moms such as Ms. Slade were already at higher risk of maternal and infant mortality before the pandemic, because of higher underlying risks, unequal access to health care, and other factors. COVID-19 has magnified those risks, said Dr. Burroughs, who has persuaded reluctant patients by revealing that she had a healthy pregnancy and child after being vaccinated.

Ms. Slade said she has never opposed vaccines and had no hesitation about receiving other vaccines while pregnant. But she said she “just wasn’t comfortable” with COVID-19 shots.

“If there had been data out there saying the COVID shot was safe, and that nothing would happen to my baby and there was no risk of birth defects, I would have taken it,” said Ms. Slade, who has had type 2 diabetes for 12 years.
 

Working at warp speed

Government scientists at the NIH were concerned about the risk of COVID-19 to pregnant people from the very beginning and knew that expectant moms needed vaccines as much or more than anyone else, said Larry Corey, MD, a leader of the COVID-19 Prevention Network, which coordinated COVID-19 vaccine trials for the federal government.

But including pregnant volunteers in the larger vaccine trials could have led to interruptions and delays, Dr. Corey said. Researchers would have had to enroll thousands of pregnant volunteers to achieve statistically robust results that weren’t due to chance, he said.

Pregnancy can bring on a wide range of complications: gestational diabetes, hypertension, anemia, bleeding, blood clots, or problems with the placenta, for example. Up to 20% of people who know they’re pregnant miscarry. Because researchers would have been obliged to investigate any medical problem to make sure it wasn’t caused by one of the COVID-19 vaccines, including pregnant people might have meant having to hit pause on those trials, Dr. Corey said.

With death tolls from the pandemic mounting, “we had a mission to do this as quickly and as thoroughly as possible,” Dr. Corey said. Making COVID-19 vaccines available within a year “saved hundreds of thousands of lives.”

The first data on COVID-19 vaccine safety in pregnancy was published in April of 2021 when the CDC released an analysis of nearly 36,000 vaccinated pregnant people who had enrolled in a registry called V-safe, which allows users to log the dates of their vaccinations and any subsequent symptoms.

Later research showed that COVID-19 vaccines weren’t associated with increased risk of miscarriage or premature delivery.

Brenna Hughes, MD, a maternal-fetal medicine specialist and member of the American College of Obstetricians and Gynecologists’ COVID-19 expert group, agrees that adding pregnant people to large-scale COVID-19 vaccine and drug trials may have been impractical. But researchers could have launched parallel trials of pregnant women, once early studies showed the vaccines were safe in humans, she said.

“Would it have been hard? Everything with COVID is hard,” Dr. Hughes said. “But it would have been feasible.”

The FDA requires that researchers perform additional animal studies – called developmental and reproductive toxicity studies – before testing vaccines in pregnant people. Although these studies are essential, they take 5-6 months, and weren’t completed until late 2020, around the time the first COVID-19 vaccines were authorized for adults, said Emily Erbelding, MD, director of microbiology and infectious diseases at the National Institute of Allergy and Infectious Diseases, part of the NIH.

Pregnancy studies “were an afterthought,” said Irina Burd, MD, director of Johns Hopkins’ Integrated Research Center for Fetal Medicine and a professor of gynecology and obstetrics. “They should have been done sooner.”

The NIH is conducting a study of pregnant and postpartum people who decided on their own to be vaccinated, Dr. Erbelding said. The study is due to be completed by July 2023.

Janssen and Moderna are also conducting studies in pregnant people, both due to be completed in 2024.

Pfizer scientists encountered problems when they initiated a clinical trial, which would have randomly assigned pregnant people to receive either a vaccine or placebo. Once vaccines were widely available, many patients weren’t willing to take a chance on being unvaccinated until after delivery.

Pfizer has stopped recruiting patients and has not said whether it will publicly report any data from the trial.

Dr. Hughes said vaccine developers need to include pregnant people from the very beginning.

“There is this notion of protecting pregnant people from research,” Dr. Hughes said. “But we should be protecting patients through research, not from research.”
 

Recovering physically and emotionally

Ms. Slade still regrets being deprived of time with her children while she fought the disease.

Being on a ventilator kept her from spending those early weeks with her newborn, or from seeing her 9-year-old daughter, Zoe.

Even when Ms. Slade was finally able to see her son, she wasn’t able to tell him she loved him or sing a lullaby, or even talk at all, because of a breathing tube in her throat.

Today, Ms. Slade is a strong advocate of COVID-19 vaccinations, urging her friends and family to get their shots to avoid suffering the way she has.

Ms. Slade had to relearn to walk after being bedridden for weeks. Her many weeks on a ventilator may have contributed to her stomach paralysis, which often causes intense pain, nausea, and even vomiting when she eats or drinks. Ms. Slade weighs 50 pounds less today than before she became pregnant and has resorted to going to the emergency department when the pain is unbearable. “Most days, I’m just miserable,” she said.

Her family suffered as well. Like many babies born prematurely, Tristan, now nearly 9 months old and crawling, receives physical therapy to strengthen his muscles. At 15 pounds, Tristan is largely healthy, although his doctor said he has symptoms of asthma.

Ms. Slade said she would like to attend family counseling with Zoe, who rarely complains and tends to keep her feelings to herself. Ms. Slade said she knows her illness must have been terrifying for her little girl.

“The other day she was talking to me,” Ms. Slade said, “and she said, ‘You know, I almost had to bury you.’ ”
 

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.

Kia Slade was 7 months pregnant, unvaccinated, and fighting for breath, her oxygen levels plummeting, when her son came into the world last May.

A severe case of COVID-19 pneumonia had left Ms. Slade delirious. When the intensive care team tried to place an oxygen mask on her face, she snatched it away, she recalled. Her baby’s heart rate began to drop.

Ms. Slade’s doctor performed an emergency cesarean section at her bedside in the intensive care unit, delivering baby Tristan 10 weeks early. He weighed just 2 pounds, 14 ounces, about half the size of small full-term baby.

But Ms. Slade wouldn’t meet him until July. She was on a ventilator in a medically-induced coma for 8 weeks, and she developed a serious infection and blood clot while unconscious. It was only after a perilous 2½ months in the hospital, during which her heart stopped twice, that Ms. Slade was vaccinated against COVID-19.

“I wish I had gotten the vaccine earlier,” said Ms. Slade, 42, who remains too sick to return to work as a special education teacher in Baltimore. Doctors “kept pushing me to get vaccinated, but there just wasn’t enough information out there for me to do it.”

A year ago, there was little to no vaccine safety data for pregnant people like Ms. Slade, because they had been excluded from clinical trials run by Pfizer, Moderna, and other vaccine makers.

Lacking data, health experts were unsure and divided about how to advise expectant parents. Although U.S. health officials permitted pregnant people to be vaccinated, the World Health Organization in January 2021 actually discouraged them from doing so; it later reversed that recommendation.

The uncertainty led many women to delay vaccination, and only about two-thirds of the pregnant people who have been tracked by the Centers for Disease Control and Prevention were fully vaccinated as of Feb. 5, 2022, leaving many expectant moms at a high risk of infection and life-threatening complications.

More than 29,000 pregnant people have been hospitalized with COVID-19 and 274 have died, according to the CDC.

“There were surely women who were hospitalized because there wasn’t information available to them,” said Paul A. Offit, MD, director of the Vaccine Education Center at the Children’s Hospital of Philadelphia.

Vaccine developers say that pregnant people – who have special health needs and risks – were excluded from clinical trials to protect them from potential side effects of novel technologies, including the Pfizer and Moderna mRNA vaccines and formulations made with cold viruses, such as the Johnson & Johnson vaccine.

But a KHN analysis also shows that pregnant people were left behind because including them in vaccine studies would have complicated and potentially delayed the delivery of COVID-19 vaccines to the broader population.

A growing number of women’s health researchers and advocates say that excluding pregnant people – and the months-long delay in recommending that they be immunized – helped fuel widespread vaccine hesitancy in this vulnerable group.

“Women and their unborn fetuses are dying of COVID infection,” said Jane Van Dis, MD, an ob.gyn. at the University of Rochester (N.Y.) Medical Center who has treated many patients like Ms. Slade. “Our failure as a society to vaccinate women in pregnancy will be remembered by the children and families who lost their mothers to this disease.”
 

New technology, uncertain risks

At the time COVID-19 vaccines were being developed, scientists had very little experience using mRNA vaccines in pregnant women, said Jacqueline Miller, MD, a senior vice president involved in vaccine research at Moderna.

“When you study anything in pregnant women, you have two patients, the mom and the unborn child,” Dr. Miller said. “Until we had more safety data on the platform, it wasn’t something we wanted to undertake.”

But Dr. Offit noted that vaccines have a strong record of safety in pregnancy and he sees no reason to have excluded pregnant people. None of the vaccines currently in use – including the chickenpox and rubella vaccines, which contain live viruses – have been shown to harm fetuses, he said. Doctors routinely recommend that pregnant people receive pertussis and flu vaccinations.

Dr. Offit, the coinventor of a rotavirus vaccine, said that some concerns about vaccines stem from commercial, not medical, interests. Drug makers don’t want to risk that their product will be blamed for any problems occurring in pregnant people, even if coincidental, he said.

“These companies don’t want bad news,” Dr. Offit said.

In the United States, health officials typically would have told expectant mothers not to take a vaccine that was untested during pregnancy, said Dr. Offit, a member of a committee that advises the Food and Drug Administration on vaccines.

Due to the urgency of the pandemic, health agencies instead permitted pregnant people to make up their own minds about vaccines without recommending them.

Women’s medical associations were also hampered by the lack of data. Neither the American College of Obstetricians and Gynecologists nor the Society for Maternal-Fetal Medicine actively encouraged pregnant people to be vaccinated until July 30, 2021, after the first real-world vaccine studies had been published. The CDC followed suit in August of 2021.

“If we had had this data in the beginning, we would have been able to vaccinate more women,” said Kelli Burroughs, MD, the department chair of obstetrics and gynecology at Memorial Hermann Sugar Land Hospital near Houston.

Yet anti-vaccine groups wasted no time in scaring pregnant people, flooding social media with misinformation about impaired fertility and harm to the fetus.

In the first few months after the COVID-19 vaccines were approved, some doctors were ambivalent about recommending them, and some still advise pregnant patients against vaccination.

An estimated 67% of pregnant people today are fully vaccinated, compared with about 89% of people 65 and older, another high-risk group, and 65% of Americans overall. Vaccination rates are lower among minorities, with 65% of expectant Hispanic mothers and 53% of pregnant African Americans fully vaccinated, according to the CDC.

Vaccination is especially important during pregnancy, because of increased risks of hospitalization, ICU admission, and mechanical ventilation, Dr. Burroughs said. A study released in February from the National Institutes of Health found that pregnant people with a moderate to severe COVID-19 infection also were more likely to have a C-section, deliver preterm, or develop a postpartum hemorrhage.

Black moms such as Ms. Slade were already at higher risk of maternal and infant mortality before the pandemic, because of higher underlying risks, unequal access to health care, and other factors. COVID-19 has magnified those risks, said Dr. Burroughs, who has persuaded reluctant patients by revealing that she had a healthy pregnancy and child after being vaccinated.

Ms. Slade said she has never opposed vaccines and had no hesitation about receiving other vaccines while pregnant. But she said she “just wasn’t comfortable” with COVID-19 shots.

“If there had been data out there saying the COVID shot was safe, and that nothing would happen to my baby and there was no risk of birth defects, I would have taken it,” said Ms. Slade, who has had type 2 diabetes for 12 years.
 

Working at warp speed

Government scientists at the NIH were concerned about the risk of COVID-19 to pregnant people from the very beginning and knew that expectant moms needed vaccines as much or more than anyone else, said Larry Corey, MD, a leader of the COVID-19 Prevention Network, which coordinated COVID-19 vaccine trials for the federal government.

But including pregnant volunteers in the larger vaccine trials could have led to interruptions and delays, Dr. Corey said. Researchers would have had to enroll thousands of pregnant volunteers to achieve statistically robust results that weren’t due to chance, he said.

Pregnancy can bring on a wide range of complications: gestational diabetes, hypertension, anemia, bleeding, blood clots, or problems with the placenta, for example. Up to 20% of people who know they’re pregnant miscarry. Because researchers would have been obliged to investigate any medical problem to make sure it wasn’t caused by one of the COVID-19 vaccines, including pregnant people might have meant having to hit pause on those trials, Dr. Corey said.

With death tolls from the pandemic mounting, “we had a mission to do this as quickly and as thoroughly as possible,” Dr. Corey said. Making COVID-19 vaccines available within a year “saved hundreds of thousands of lives.”

The first data on COVID-19 vaccine safety in pregnancy was published in April of 2021 when the CDC released an analysis of nearly 36,000 vaccinated pregnant people who had enrolled in a registry called V-safe, which allows users to log the dates of their vaccinations and any subsequent symptoms.

Later research showed that COVID-19 vaccines weren’t associated with increased risk of miscarriage or premature delivery.

Brenna Hughes, MD, a maternal-fetal medicine specialist and member of the American College of Obstetricians and Gynecologists’ COVID-19 expert group, agrees that adding pregnant people to large-scale COVID-19 vaccine and drug trials may have been impractical. But researchers could have launched parallel trials of pregnant women, once early studies showed the vaccines were safe in humans, she said.

“Would it have been hard? Everything with COVID is hard,” Dr. Hughes said. “But it would have been feasible.”

The FDA requires that researchers perform additional animal studies – called developmental and reproductive toxicity studies – before testing vaccines in pregnant people. Although these studies are essential, they take 5-6 months, and weren’t completed until late 2020, around the time the first COVID-19 vaccines were authorized for adults, said Emily Erbelding, MD, director of microbiology and infectious diseases at the National Institute of Allergy and Infectious Diseases, part of the NIH.

Pregnancy studies “were an afterthought,” said Irina Burd, MD, director of Johns Hopkins’ Integrated Research Center for Fetal Medicine and a professor of gynecology and obstetrics. “They should have been done sooner.”

The NIH is conducting a study of pregnant and postpartum people who decided on their own to be vaccinated, Dr. Erbelding said. The study is due to be completed by July 2023.

Janssen and Moderna are also conducting studies in pregnant people, both due to be completed in 2024.

Pfizer scientists encountered problems when they initiated a clinical trial, which would have randomly assigned pregnant people to receive either a vaccine or placebo. Once vaccines were widely available, many patients weren’t willing to take a chance on being unvaccinated until after delivery.

Pfizer has stopped recruiting patients and has not said whether it will publicly report any data from the trial.

Dr. Hughes said vaccine developers need to include pregnant people from the very beginning.

“There is this notion of protecting pregnant people from research,” Dr. Hughes said. “But we should be protecting patients through research, not from research.”
 

Recovering physically and emotionally

Ms. Slade still regrets being deprived of time with her children while she fought the disease.

Being on a ventilator kept her from spending those early weeks with her newborn, or from seeing her 9-year-old daughter, Zoe.

Even when Ms. Slade was finally able to see her son, she wasn’t able to tell him she loved him or sing a lullaby, or even talk at all, because of a breathing tube in her throat.

Today, Ms. Slade is a strong advocate of COVID-19 vaccinations, urging her friends and family to get their shots to avoid suffering the way she has.

Ms. Slade had to relearn to walk after being bedridden for weeks. Her many weeks on a ventilator may have contributed to her stomach paralysis, which often causes intense pain, nausea, and even vomiting when she eats or drinks. Ms. Slade weighs 50 pounds less today than before she became pregnant and has resorted to going to the emergency department when the pain is unbearable. “Most days, I’m just miserable,” she said.

Her family suffered as well. Like many babies born prematurely, Tristan, now nearly 9 months old and crawling, receives physical therapy to strengthen his muscles. At 15 pounds, Tristan is largely healthy, although his doctor said he has symptoms of asthma.

Ms. Slade said she would like to attend family counseling with Zoe, who rarely complains and tends to keep her feelings to herself. Ms. Slade said she knows her illness must have been terrifying for her little girl.

“The other day she was talking to me,” Ms. Slade said, “and she said, ‘You know, I almost had to bury you.’ ”
 

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.

Use of neuraxial analgesia for vaginal delivery is associated with a 14% decreased risk for severe maternal morbidity, in part from a reduction in postpartum hemorrhage, new research shows.

The findings indicate that increasing the use of epidural or combined spinal-epidural analgesia may improve maternal health outcomes, especially for Hispanic, Black, and uninsured women who are less likely than White women to receive these interventions, according to the researchers, who published their findings online in JAMA Network Open.

About 80% of non-Hispanic White women receive neuraxial analgesia during labor in the United States, compared with 70% of non-Hispanic Black women and 65% of Hispanic women, according to birth certificate data. Among women without health insurance, half receive epidurals.  

Programs that inform pregnant women about epidural use, expand Medicaid, and provide in-house obstetric anesthesia teams “may improve patient participation in clinical decision making and access to care,” study author Guohua Li, MD, DrPH, of Columbia University, New York, said in a statement about the research.

Earlier data from France showed that neuraxial analgesia is associated with reduced risk for severe postpartum hemorrhage. To examine the association between labor neuraxial analgesia and severe maternal morbidity in the United States, Dr. Li and colleagues analyzed more than 575,000 vaginal deliveries in New York hospitals between 2010 and 2017; about half (47.4%) of the women received epidurals during labor.

The researchers focused on severe maternal morbidity, including 16 complications, such as heart failure and sepsis, and five procedures, including hysterectomy and ventilation.

They also considered patient characteristics and comorbidities and hospital-related factors to identify patients who were at higher risk for injury or death.

Severe maternal morbidity occurred in 1.3% of the women. Of the 7,712 women with severe morbidity, more than one in three (35.6%) experienced postpartum hemorrhage.

The overall incidence of severe maternal morbidity was 1.3% among women who received an epidural injection and 1.4% among those who did not. In a weighted analysis, the adjusted odds ratio of severe maternal morbidity associated with epidurals was 0.86 (95% confidence interval, 0.82-0.90).

The study is limited by its observational design and does not prove causation, the authors acknowledged.

“Labor neuraxial analgesia may facilitate early evaluation and management of the third stage of labor to avoid escalation of postpartum hemorrhaging into grave complications and death,” study author Jean Guglielminotti, MD, PhD, an anesthesiologist at Columbia University, said in a statement.
 

Concerning trends

The Department of Health & Human Services has labeled severe maternal morbidity a public health priority. Recent data from the Centers for Disease Control and Prevention show an increase in maternal mortality rates and worsening disparities by race and ethnicity.

According to the CDC, 861 women died of maternal causes in 2020, up from 754 in 2019. The rate of maternal mortality increased from 20.1 to 23.8 deaths per 100,000 live births.

For Black women, however, the maternal mortality rate was far higher: 55.3 deaths per 100,000 live births – nearly triple the figure of 19.1 per 100,000 for White women. Between 2019 and 2020, the mortality rate increased significantly for Black and Hispanic women, but not White mothers.

Researchers affiliated with University of Toronto and the Hospital for Sick Children agreed in an accompanying editorial that more access to neuraxial labor analgesia for vaginal delivery might improve maternal health outcomes and “may be a strategy well worth pursuing in public health policy.”

The intervention is relatively safe and can “alleviate discomfort and distress,” they wrote.

Neuraxial anesthesia in surgical procedures has been shown to decrease the risk for complications like deep vein thrombosis, pulmonary embolus, transfusion requirements, and kidney failure, said editorialists Evelina Pankiv, MD; Alan Yang, MSc; and Kazuyoshi Aoyama, MD, PhD.

Benefits potentially could stem from improving blood flow, mitigating hypercoagulation, or reducing surgical stress response. But there are rare risks to consider as well, including hemorrhage, infection, and neurologic injury, they added.

Guglielminotti disclosed grants from the National Institute on Minority Health and Health Disparities. Dr. Aoyama reported receiving grants from the Perioperative Services Facilitator Grant Program and Hospital for Sick Children. The other authors disclosed no relevant financial relationships.

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

Use of neuraxial analgesia for vaginal delivery is associated with a 14% decreased risk for severe maternal morbidity, in part from a reduction in postpartum hemorrhage, new research shows.

The findings indicate that increasing the use of epidural or combined spinal-epidural analgesia may improve maternal health outcomes, especially for Hispanic, Black, and uninsured women who are less likely than White women to receive these interventions, according to the researchers, who published their findings online in JAMA Network Open.

About 80% of non-Hispanic White women receive neuraxial analgesia during labor in the United States, compared with 70% of non-Hispanic Black women and 65% of Hispanic women, according to birth certificate data. Among women without health insurance, half receive epidurals.  

Programs that inform pregnant women about epidural use, expand Medicaid, and provide in-house obstetric anesthesia teams “may improve patient participation in clinical decision making and access to care,” study author Guohua Li, MD, DrPH, of Columbia University, New York, said in a statement about the research.

Earlier data from France showed that neuraxial analgesia is associated with reduced risk for severe postpartum hemorrhage. To examine the association between labor neuraxial analgesia and severe maternal morbidity in the United States, Dr. Li and colleagues analyzed more than 575,000 vaginal deliveries in New York hospitals between 2010 and 2017; about half (47.4%) of the women received epidurals during labor.

The researchers focused on severe maternal morbidity, including 16 complications, such as heart failure and sepsis, and five procedures, including hysterectomy and ventilation.

They also considered patient characteristics and comorbidities and hospital-related factors to identify patients who were at higher risk for injury or death.

Severe maternal morbidity occurred in 1.3% of the women. Of the 7,712 women with severe morbidity, more than one in three (35.6%) experienced postpartum hemorrhage.

The overall incidence of severe maternal morbidity was 1.3% among women who received an epidural injection and 1.4% among those who did not. In a weighted analysis, the adjusted odds ratio of severe maternal morbidity associated with epidurals was 0.86 (95% confidence interval, 0.82-0.90).

The study is limited by its observational design and does not prove causation, the authors acknowledged.

“Labor neuraxial analgesia may facilitate early evaluation and management of the third stage of labor to avoid escalation of postpartum hemorrhaging into grave complications and death,” study author Jean Guglielminotti, MD, PhD, an anesthesiologist at Columbia University, said in a statement.
 

Concerning trends

The Department of Health & Human Services has labeled severe maternal morbidity a public health priority. Recent data from the Centers for Disease Control and Prevention show an increase in maternal mortality rates and worsening disparities by race and ethnicity.

According to the CDC, 861 women died of maternal causes in 2020, up from 754 in 2019. The rate of maternal mortality increased from 20.1 to 23.8 deaths per 100,000 live births.

For Black women, however, the maternal mortality rate was far higher: 55.3 deaths per 100,000 live births – nearly triple the figure of 19.1 per 100,000 for White women. Between 2019 and 2020, the mortality rate increased significantly for Black and Hispanic women, but not White mothers.

Researchers affiliated with University of Toronto and the Hospital for Sick Children agreed in an accompanying editorial that more access to neuraxial labor analgesia for vaginal delivery might improve maternal health outcomes and “may be a strategy well worth pursuing in public health policy.”

The intervention is relatively safe and can “alleviate discomfort and distress,” they wrote.

Neuraxial anesthesia in surgical procedures has been shown to decrease the risk for complications like deep vein thrombosis, pulmonary embolus, transfusion requirements, and kidney failure, said editorialists Evelina Pankiv, MD; Alan Yang, MSc; and Kazuyoshi Aoyama, MD, PhD.

Benefits potentially could stem from improving blood flow, mitigating hypercoagulation, or reducing surgical stress response. But there are rare risks to consider as well, including hemorrhage, infection, and neurologic injury, they added.

Guglielminotti disclosed grants from the National Institute on Minority Health and Health Disparities. Dr. Aoyama reported receiving grants from the Perioperative Services Facilitator Grant Program and Hospital for Sick Children. The other authors disclosed no relevant financial relationships.

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

Use of neuraxial analgesia for vaginal delivery is associated with a 14% decreased risk for severe maternal morbidity, in part from a reduction in postpartum hemorrhage, new research shows.

The findings indicate that increasing the use of epidural or combined spinal-epidural analgesia may improve maternal health outcomes, especially for Hispanic, Black, and uninsured women who are less likely than White women to receive these interventions, according to the researchers, who published their findings online in JAMA Network Open.

About 80% of non-Hispanic White women receive neuraxial analgesia during labor in the United States, compared with 70% of non-Hispanic Black women and 65% of Hispanic women, according to birth certificate data. Among women without health insurance, half receive epidurals.  

Programs that inform pregnant women about epidural use, expand Medicaid, and provide in-house obstetric anesthesia teams “may improve patient participation in clinical decision making and access to care,” study author Guohua Li, MD, DrPH, of Columbia University, New York, said in a statement about the research.

Earlier data from France showed that neuraxial analgesia is associated with reduced risk for severe postpartum hemorrhage. To examine the association between labor neuraxial analgesia and severe maternal morbidity in the United States, Dr. Li and colleagues analyzed more than 575,000 vaginal deliveries in New York hospitals between 2010 and 2017; about half (47.4%) of the women received epidurals during labor.

The researchers focused on severe maternal morbidity, including 16 complications, such as heart failure and sepsis, and five procedures, including hysterectomy and ventilation.

They also considered patient characteristics and comorbidities and hospital-related factors to identify patients who were at higher risk for injury or death.

Severe maternal morbidity occurred in 1.3% of the women. Of the 7,712 women with severe morbidity, more than one in three (35.6%) experienced postpartum hemorrhage.

The overall incidence of severe maternal morbidity was 1.3% among women who received an epidural injection and 1.4% among those who did not. In a weighted analysis, the adjusted odds ratio of severe maternal morbidity associated with epidurals was 0.86 (95% confidence interval, 0.82-0.90).

The study is limited by its observational design and does not prove causation, the authors acknowledged.

“Labor neuraxial analgesia may facilitate early evaluation and management of the third stage of labor to avoid escalation of postpartum hemorrhaging into grave complications and death,” study author Jean Guglielminotti, MD, PhD, an anesthesiologist at Columbia University, said in a statement.
 

Concerning trends

The Department of Health & Human Services has labeled severe maternal morbidity a public health priority. Recent data from the Centers for Disease Control and Prevention show an increase in maternal mortality rates and worsening disparities by race and ethnicity.

According to the CDC, 861 women died of maternal causes in 2020, up from 754 in 2019. The rate of maternal mortality increased from 20.1 to 23.8 deaths per 100,000 live births.

For Black women, however, the maternal mortality rate was far higher: 55.3 deaths per 100,000 live births – nearly triple the figure of 19.1 per 100,000 for White women. Between 2019 and 2020, the mortality rate increased significantly for Black and Hispanic women, but not White mothers.

Researchers affiliated with University of Toronto and the Hospital for Sick Children agreed in an accompanying editorial that more access to neuraxial labor analgesia for vaginal delivery might improve maternal health outcomes and “may be a strategy well worth pursuing in public health policy.”

The intervention is relatively safe and can “alleviate discomfort and distress,” they wrote.

Neuraxial anesthesia in surgical procedures has been shown to decrease the risk for complications like deep vein thrombosis, pulmonary embolus, transfusion requirements, and kidney failure, said editorialists Evelina Pankiv, MD; Alan Yang, MSc; and Kazuyoshi Aoyama, MD, PhD.

Benefits potentially could stem from improving blood flow, mitigating hypercoagulation, or reducing surgical stress response. But there are rare risks to consider as well, including hemorrhage, infection, and neurologic injury, they added.

Guglielminotti disclosed grants from the National Institute on Minority Health and Health Disparities. Dr. Aoyama reported receiving grants from the Perioperative Services Facilitator Grant Program and Hospital for Sick Children. The other authors disclosed no relevant financial relationships.

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

“Just relax, stop thinking about it and, more than likely, it will happen.” If ever there was a controversial subject in medicine, especially in reproduction, the relationship between stress and infertility would be high on the list. Who among us has not overheard or even personally shared with an infertility patient that they should try and reduce their stress to improve fertility? The theory is certainly not new. Hippocrates, back in the 5th century B.C., was one of the first to associate a woman’s psychological state with her reproductive potential. His contention was that a physical sign of psychological stress in women (which scholars later dubbed “hysteria”) could result in sterility. In medieval times, a German abbess and mystic named Hildegard of Bingen posited women suffering from melancholy – a condition that we today might call depression – were infertile as a result.

The deeper meaning behind the flippant advice to relax is implicit blame; that is, a woman interprets the link of stress and infertility as a declaration that she is sabotaging reproduction. Not only is this assumption flawed, but it does further damage to a woman’s emotional fragility. To provide the presumption of stress affecting reproduction, a recent survey of over 5,000 infertility patients found, remarkably, 98% considered emotional stress as either a cause or a contributor to infertility, and 31% believed stress was a cause of miscarriage, although racial differences existed (J Assist Reprod Genet. 2021 Apr;38[4]:877-87). This relationship was mostly seen in women who used complementary and alternative medicine, Black women, and those who frequented Internet search engines. Whereas women who had a professional degree, had more infertility insurance coverage, and were nonreligious were less likely to attribute stress to infertility. Intriguingly, the more engaged the physicians, the less patients linked stress with infertility, while the contrary also applied.

The power of stress can be exemplified by the pathophysiology of amenorrhea. Functional hypothalamic amenorrhea is the most common cause of the female athlete triad of secondary amenorrhea in women of childbearing age. It is a reversible disorder caused by stress related to weight loss, excessive exercise and/or traumatic mental experiences (Endocrines. 2021;2:203-11). Stress of infertility has also been demonstrated to be equivalent to a diagnosis of cancer and other major medical morbidities (J Psychosom Obstet Gynaecol. 1993;14[Suppl]:45-52).

A definitive link between stress and infertility is evasive because of the lack of controlled, prospective longitudinal studies and the challenge of reducing variables in the analysis. The question remains which developed initially – the stress or the infertility? Infertility treatment is a physical, emotional, and financial investment. Stress and the duration of infertility are correlative. The additive factor is that poor insurance coverage for costly fertility treatment can not only heighten stress but, concurrently, subject the patient to the risk of exploitation driven by desperation whereby they accept unproven “add-ons” offered with assisted reproductive technologies (ART).

Both acute and chronic stress affect the number of oocytes retrieved and fertilized with ART as well as live birth delivery and birth weights (Fertil Steril. 2001;76:675-87). Men are also affected by stress, which is manifested by decreased libido and impaired semen, further compromised as the duration of infertility continues. The gut-derived hormone ghrelin appears to play a role with stress and reproduction (Endocr Rev. 2017;38:432-67).

As the relationship between stress and infertility is far from proven, there are conflicting study results. Two meta-analyses failed to show any association between stress and the outcomes of ART cycles (Hum Reprod. 2011;26:2763-76; BMJ. 2011;342:d223). In contrast, a recent study suggested stress during infertility treatment was contributed by the variables of low spousal support, financial constraints, and social coercion in the early years of marriage (J Hum Reprod Sci. 2018;11:172-9). Emotional distress was found to be three times greater in women whose families had unrealistic expectations from treatments.

Fortunately, psychotherapy during the ART cycle has demonstrated a benefit in outcomes. Domar revealed psychological support and cognitive behavior therapy resulted in higher pregnancy rates than in the control group (Fertil Steril. 2000;73:805-12). Another recent study appears to support stress reduction improving reproductive potential (Dialogues Clin Neurosci. 2018;20[1]:41-7).

Given the evidence provided in this article, it behooves infertility clinics to address baseline (chronic) stress and acute stress (because of infertility) prior to initiating treatment (see Figure). While the definitive answer addressing the impact of stress on reproduction remains unknown, we may share with our patients a definition in which they may find enlightenment, “Stress is trying to control an event in which one is incapable.”

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

“Just relax, stop thinking about it and, more than likely, it will happen.” If ever there was a controversial subject in medicine, especially in reproduction, the relationship between stress and infertility would be high on the list. Who among us has not overheard or even personally shared with an infertility patient that they should try and reduce their stress to improve fertility? The theory is certainly not new. Hippocrates, back in the 5th century B.C., was one of the first to associate a woman’s psychological state with her reproductive potential. His contention was that a physical sign of psychological stress in women (which scholars later dubbed “hysteria”) could result in sterility. In medieval times, a German abbess and mystic named Hildegard of Bingen posited women suffering from melancholy – a condition that we today might call depression – were infertile as a result.

The deeper meaning behind the flippant advice to relax is implicit blame; that is, a woman interprets the link of stress and infertility as a declaration that she is sabotaging reproduction. Not only is this assumption flawed, but it does further damage to a woman’s emotional fragility. To provide the presumption of stress affecting reproduction, a recent survey of over 5,000 infertility patients found, remarkably, 98% considered emotional stress as either a cause or a contributor to infertility, and 31% believed stress was a cause of miscarriage, although racial differences existed (J Assist Reprod Genet. 2021 Apr;38[4]:877-87). This relationship was mostly seen in women who used complementary and alternative medicine, Black women, and those who frequented Internet search engines. Whereas women who had a professional degree, had more infertility insurance coverage, and were nonreligious were less likely to attribute stress to infertility. Intriguingly, the more engaged the physicians, the less patients linked stress with infertility, while the contrary also applied.

The power of stress can be exemplified by the pathophysiology of amenorrhea. Functional hypothalamic amenorrhea is the most common cause of the female athlete triad of secondary amenorrhea in women of childbearing age. It is a reversible disorder caused by stress related to weight loss, excessive exercise and/or traumatic mental experiences (Endocrines. 2021;2:203-11). Stress of infertility has also been demonstrated to be equivalent to a diagnosis of cancer and other major medical morbidities (J Psychosom Obstet Gynaecol. 1993;14[Suppl]:45-52).

A definitive link between stress and infertility is evasive because of the lack of controlled, prospective longitudinal studies and the challenge of reducing variables in the analysis. The question remains which developed initially – the stress or the infertility? Infertility treatment is a physical, emotional, and financial investment. Stress and the duration of infertility are correlative. The additive factor is that poor insurance coverage for costly fertility treatment can not only heighten stress but, concurrently, subject the patient to the risk of exploitation driven by desperation whereby they accept unproven “add-ons” offered with assisted reproductive technologies (ART).

Both acute and chronic stress affect the number of oocytes retrieved and fertilized with ART as well as live birth delivery and birth weights (Fertil Steril. 2001;76:675-87). Men are also affected by stress, which is manifested by decreased libido and impaired semen, further compromised as the duration of infertility continues. The gut-derived hormone ghrelin appears to play a role with stress and reproduction (Endocr Rev. 2017;38:432-67).

As the relationship between stress and infertility is far from proven, there are conflicting study results. Two meta-analyses failed to show any association between stress and the outcomes of ART cycles (Hum Reprod. 2011;26:2763-76; BMJ. 2011;342:d223). In contrast, a recent study suggested stress during infertility treatment was contributed by the variables of low spousal support, financial constraints, and social coercion in the early years of marriage (J Hum Reprod Sci. 2018;11:172-9). Emotional distress was found to be three times greater in women whose families had unrealistic expectations from treatments.

Fortunately, psychotherapy during the ART cycle has demonstrated a benefit in outcomes. Domar revealed psychological support and cognitive behavior therapy resulted in higher pregnancy rates than in the control group (Fertil Steril. 2000;73:805-12). Another recent study appears to support stress reduction improving reproductive potential (Dialogues Clin Neurosci. 2018;20[1]:41-7).

Given the evidence provided in this article, it behooves infertility clinics to address baseline (chronic) stress and acute stress (because of infertility) prior to initiating treatment (see Figure). While the definitive answer addressing the impact of stress on reproduction remains unknown, we may share with our patients a definition in which they may find enlightenment, “Stress is trying to control an event in which one is incapable.”

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

“Just relax, stop thinking about it and, more than likely, it will happen.” If ever there was a controversial subject in medicine, especially in reproduction, the relationship between stress and infertility would be high on the list. Who among us has not overheard or even personally shared with an infertility patient that they should try and reduce their stress to improve fertility? The theory is certainly not new. Hippocrates, back in the 5th century B.C., was one of the first to associate a woman’s psychological state with her reproductive potential. His contention was that a physical sign of psychological stress in women (which scholars later dubbed “hysteria”) could result in sterility. In medieval times, a German abbess and mystic named Hildegard of Bingen posited women suffering from melancholy – a condition that we today might call depression – were infertile as a result.

The deeper meaning behind the flippant advice to relax is implicit blame; that is, a woman interprets the link of stress and infertility as a declaration that she is sabotaging reproduction. Not only is this assumption flawed, but it does further damage to a woman’s emotional fragility. To provide the presumption of stress affecting reproduction, a recent survey of over 5,000 infertility patients found, remarkably, 98% considered emotional stress as either a cause or a contributor to infertility, and 31% believed stress was a cause of miscarriage, although racial differences existed (J Assist Reprod Genet. 2021 Apr;38[4]:877-87). This relationship was mostly seen in women who used complementary and alternative medicine, Black women, and those who frequented Internet search engines. Whereas women who had a professional degree, had more infertility insurance coverage, and were nonreligious were less likely to attribute stress to infertility. Intriguingly, the more engaged the physicians, the less patients linked stress with infertility, while the contrary also applied.

The power of stress can be exemplified by the pathophysiology of amenorrhea. Functional hypothalamic amenorrhea is the most common cause of the female athlete triad of secondary amenorrhea in women of childbearing age. It is a reversible disorder caused by stress related to weight loss, excessive exercise and/or traumatic mental experiences (Endocrines. 2021;2:203-11). Stress of infertility has also been demonstrated to be equivalent to a diagnosis of cancer and other major medical morbidities (J Psychosom Obstet Gynaecol. 1993;14[Suppl]:45-52).

A definitive link between stress and infertility is evasive because of the lack of controlled, prospective longitudinal studies and the challenge of reducing variables in the analysis. The question remains which developed initially – the stress or the infertility? Infertility treatment is a physical, emotional, and financial investment. Stress and the duration of infertility are correlative. The additive factor is that poor insurance coverage for costly fertility treatment can not only heighten stress but, concurrently, subject the patient to the risk of exploitation driven by desperation whereby they accept unproven “add-ons” offered with assisted reproductive technologies (ART).

Both acute and chronic stress affect the number of oocytes retrieved and fertilized with ART as well as live birth delivery and birth weights (Fertil Steril. 2001;76:675-87). Men are also affected by stress, which is manifested by decreased libido and impaired semen, further compromised as the duration of infertility continues. The gut-derived hormone ghrelin appears to play a role with stress and reproduction (Endocr Rev. 2017;38:432-67).

As the relationship between stress and infertility is far from proven, there are conflicting study results. Two meta-analyses failed to show any association between stress and the outcomes of ART cycles (Hum Reprod. 2011;26:2763-76; BMJ. 2011;342:d223). In contrast, a recent study suggested stress during infertility treatment was contributed by the variables of low spousal support, financial constraints, and social coercion in the early years of marriage (J Hum Reprod Sci. 2018;11:172-9). Emotional distress was found to be three times greater in women whose families had unrealistic expectations from treatments.

Fortunately, psychotherapy during the ART cycle has demonstrated a benefit in outcomes. Domar revealed psychological support and cognitive behavior therapy resulted in higher pregnancy rates than in the control group (Fertil Steril. 2000;73:805-12). Another recent study appears to support stress reduction improving reproductive potential (Dialogues Clin Neurosci. 2018;20[1]:41-7).

Given the evidence provided in this article, it behooves infertility clinics to address baseline (chronic) stress and acute stress (because of infertility) prior to initiating treatment (see Figure). While the definitive answer addressing the impact of stress on reproduction remains unknown, we may share with our patients a definition in which they may find enlightenment, “Stress is trying to control an event in which one is incapable.”

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

Less than half of women in the United States enter pregnancy in favorable cardiovascular health, new research suggests.

In 2019, among women aged 20 to 44 years with live births in the United States, only 40.2% were in favorable cardiovascular health prior to pregnancy, defined as normal weight, no diabetes, and no hypertension.

Although all regions and states showed a decline in prepregnancy favorable cardiometabolic health, there were significant differences among geographic regions in the country, the authors report. “These data reveal critical deficiencies and geographic disparities in prepregnancy cardiometabolic health,” they conclude.

“One of the things that we know in the U.S. is that the maternal mortality rate has been increasing, and there are significant differences at the state level in both adverse maternal outcomes, such as maternal mortality, as well as adverse pregnancy outcomes,” corresponding author Sadiya S. Khan, MD, MS, FACC, Northwestern University Feinberg School of Medicine, Chicago, told this news organization.

“These outcomes are often related to health factors that predate pregnancy,” Dr. Khan explained, “and the processes that begin at the very, very beginning of conception are informed by health factors prior to pregnancy, in particular cardiometabolic factors like body mass index or obesity, high blood pressure, and diabetes.”

The results were published online on Feb. 14 in a special “Go Red for Women” spotlight issue of Circulation.
 

Cardiometabolic health factors

Using maternal birth records from live births in the Centers for Disease Control and Prevention Natality Database between 2016 and 2019, the authors analyzed data on 14,174,625 women with live births aged 20 to 44 years. The majority (81.4%) were 20 to 34 years of age, 22.7% were Hispanic or Latina, and 52.7% were non-Hispanic White.

Favorable cardiometabolic health was defined as a BMI of 18 to 24.9 kg/m2, absence of diabetes, and absence of hypertension.

Although all regions and states experienced a decline in favorable cardiometabolic health during the study period of 2016 to 2019, with a drop overall of 3.2% – from 43.5 to 40.2 per 100 live births – it was especially true of the South and Midwest regions.

In 2019, favorable prepregnancy cardiometabolic health was lowest in the South (38.1%) and Midwest (38.8%) and highest in the West (42.2%) and Northeast (43.6%).

State by state, the lowest prevalence of favorable cardiometabolic health was found in Mississippi, at 31.2%, and highest in Utah, at 47.2%.

They also found a correlation between favorable cardiometabolic health and state-level percentages of high-school education or less and enrollment in Medicaid in 2019.

Similar to what has been seen with cardiovascular disease, “we observe that the states with the lowest prevalence of favorable cardiometabolic health were in the Southeast United States,” said Dr. Khan, “and similar geographic variation was observed with some more patterns in education and Medicaid coverage for birth, and these were used as proxies for socioeconomic status in those areas.”

Although Dr. Khan notes that the relationships cannot be determined to be causal from this analysis, she said that “it does suggest that upstream social determinants of health are important determinants of cardiometabolic health.”
 

Socioeconomic intervention

Dr. Khan noted that policies at the federal and state level can identify ways to “ensure that individuals who are thinking about pregnancy have access to health care and have access to resources, too, from a broad range of health determinants, including housing stability, food security, as well as access to health care be optimized prior to pregnancy.”

The authors note that this analysis may actually overestimate the prevalence of favorable cardiometabolic health, and data on cholesterol, diet, a distinction between type 1 and type 2 diabetes, and physical activity were not available.

Only individuals with live births were included, which could result in the elimination of a potentially high-risk group; however, late pregnancy losses represent less than 0.3% of all pregnancies, they say.

The authors conclude that “future research is needed to equitably improve health prior to pregnancy and quantify the potential benefits in cardiovascular disease outcomes for birthing individuals and their offspring.”

This work was supported by grants from the National Heart, Lung, and Blood Institute and American Heart Association Transformational Project Award awarded to Sadiya S. Khan.

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

Less than half of women in the United States enter pregnancy in favorable cardiovascular health, new research suggests.

In 2019, among women aged 20 to 44 years with live births in the United States, only 40.2% were in favorable cardiovascular health prior to pregnancy, defined as normal weight, no diabetes, and no hypertension.

Although all regions and states showed a decline in prepregnancy favorable cardiometabolic health, there were significant differences among geographic regions in the country, the authors report. “These data reveal critical deficiencies and geographic disparities in prepregnancy cardiometabolic health,” they conclude.

“One of the things that we know in the U.S. is that the maternal mortality rate has been increasing, and there are significant differences at the state level in both adverse maternal outcomes, such as maternal mortality, as well as adverse pregnancy outcomes,” corresponding author Sadiya S. Khan, MD, MS, FACC, Northwestern University Feinberg School of Medicine, Chicago, told this news organization.

“These outcomes are often related to health factors that predate pregnancy,” Dr. Khan explained, “and the processes that begin at the very, very beginning of conception are informed by health factors prior to pregnancy, in particular cardiometabolic factors like body mass index or obesity, high blood pressure, and diabetes.”

The results were published online on Feb. 14 in a special “Go Red for Women” spotlight issue of Circulation.
 

Cardiometabolic health factors

Using maternal birth records from live births in the Centers for Disease Control and Prevention Natality Database between 2016 and 2019, the authors analyzed data on 14,174,625 women with live births aged 20 to 44 years. The majority (81.4%) were 20 to 34 years of age, 22.7% were Hispanic or Latina, and 52.7% were non-Hispanic White.

Favorable cardiometabolic health was defined as a BMI of 18 to 24.9 kg/m2, absence of diabetes, and absence of hypertension.

Although all regions and states experienced a decline in favorable cardiometabolic health during the study period of 2016 to 2019, with a drop overall of 3.2% – from 43.5 to 40.2 per 100 live births – it was especially true of the South and Midwest regions.

In 2019, favorable prepregnancy cardiometabolic health was lowest in the South (38.1%) and Midwest (38.8%) and highest in the West (42.2%) and Northeast (43.6%).

State by state, the lowest prevalence of favorable cardiometabolic health was found in Mississippi, at 31.2%, and highest in Utah, at 47.2%.

They also found a correlation between favorable cardiometabolic health and state-level percentages of high-school education or less and enrollment in Medicaid in 2019.

Similar to what has been seen with cardiovascular disease, “we observe that the states with the lowest prevalence of favorable cardiometabolic health were in the Southeast United States,” said Dr. Khan, “and similar geographic variation was observed with some more patterns in education and Medicaid coverage for birth, and these were used as proxies for socioeconomic status in those areas.”

Although Dr. Khan notes that the relationships cannot be determined to be causal from this analysis, she said that “it does suggest that upstream social determinants of health are important determinants of cardiometabolic health.”
 

Socioeconomic intervention

Dr. Khan noted that policies at the federal and state level can identify ways to “ensure that individuals who are thinking about pregnancy have access to health care and have access to resources, too, from a broad range of health determinants, including housing stability, food security, as well as access to health care be optimized prior to pregnancy.”

The authors note that this analysis may actually overestimate the prevalence of favorable cardiometabolic health, and data on cholesterol, diet, a distinction between type 1 and type 2 diabetes, and physical activity were not available.

Only individuals with live births were included, which could result in the elimination of a potentially high-risk group; however, late pregnancy losses represent less than 0.3% of all pregnancies, they say.

The authors conclude that “future research is needed to equitably improve health prior to pregnancy and quantify the potential benefits in cardiovascular disease outcomes for birthing individuals and their offspring.”

This work was supported by grants from the National Heart, Lung, and Blood Institute and American Heart Association Transformational Project Award awarded to Sadiya S. Khan.

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

Less than half of women in the United States enter pregnancy in favorable cardiovascular health, new research suggests.

In 2019, among women aged 20 to 44 years with live births in the United States, only 40.2% were in favorable cardiovascular health prior to pregnancy, defined as normal weight, no diabetes, and no hypertension.

Although all regions and states showed a decline in prepregnancy favorable cardiometabolic health, there were significant differences among geographic regions in the country, the authors report. “These data reveal critical deficiencies and geographic disparities in prepregnancy cardiometabolic health,” they conclude.

“One of the things that we know in the U.S. is that the maternal mortality rate has been increasing, and there are significant differences at the state level in both adverse maternal outcomes, such as maternal mortality, as well as adverse pregnancy outcomes,” corresponding author Sadiya S. Khan, MD, MS, FACC, Northwestern University Feinberg School of Medicine, Chicago, told this news organization.

“These outcomes are often related to health factors that predate pregnancy,” Dr. Khan explained, “and the processes that begin at the very, very beginning of conception are informed by health factors prior to pregnancy, in particular cardiometabolic factors like body mass index or obesity, high blood pressure, and diabetes.”

The results were published online on Feb. 14 in a special “Go Red for Women” spotlight issue of Circulation.
 

Cardiometabolic health factors

Using maternal birth records from live births in the Centers for Disease Control and Prevention Natality Database between 2016 and 2019, the authors analyzed data on 14,174,625 women with live births aged 20 to 44 years. The majority (81.4%) were 20 to 34 years of age, 22.7% were Hispanic or Latina, and 52.7% were non-Hispanic White.

Favorable cardiometabolic health was defined as a BMI of 18 to 24.9 kg/m2, absence of diabetes, and absence of hypertension.

Although all regions and states experienced a decline in favorable cardiometabolic health during the study period of 2016 to 2019, with a drop overall of 3.2% – from 43.5 to 40.2 per 100 live births – it was especially true of the South and Midwest regions.

In 2019, favorable prepregnancy cardiometabolic health was lowest in the South (38.1%) and Midwest (38.8%) and highest in the West (42.2%) and Northeast (43.6%).

State by state, the lowest prevalence of favorable cardiometabolic health was found in Mississippi, at 31.2%, and highest in Utah, at 47.2%.

They also found a correlation between favorable cardiometabolic health and state-level percentages of high-school education or less and enrollment in Medicaid in 2019.

Similar to what has been seen with cardiovascular disease, “we observe that the states with the lowest prevalence of favorable cardiometabolic health were in the Southeast United States,” said Dr. Khan, “and similar geographic variation was observed with some more patterns in education and Medicaid coverage for birth, and these were used as proxies for socioeconomic status in those areas.”

Although Dr. Khan notes that the relationships cannot be determined to be causal from this analysis, she said that “it does suggest that upstream social determinants of health are important determinants of cardiometabolic health.”
 

Socioeconomic intervention

Dr. Khan noted that policies at the federal and state level can identify ways to “ensure that individuals who are thinking about pregnancy have access to health care and have access to resources, too, from a broad range of health determinants, including housing stability, food security, as well as access to health care be optimized prior to pregnancy.”

The authors note that this analysis may actually overestimate the prevalence of favorable cardiometabolic health, and data on cholesterol, diet, a distinction between type 1 and type 2 diabetes, and physical activity were not available.

Only individuals with live births were included, which could result in the elimination of a potentially high-risk group; however, late pregnancy losses represent less than 0.3% of all pregnancies, they say.

The authors conclude that “future research is needed to equitably improve health prior to pregnancy and quantify the potential benefits in cardiovascular disease outcomes for birthing individuals and their offspring.”

This work was supported by grants from the National Heart, Lung, and Blood Institute and American Heart Association Transformational Project Award awarded to Sadiya S. Khan.

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

More than half of abortions in the United States are now done with pills rather than surgery, according to a report from the Guttmacher Institute, a research group that supports abortion rights.

A survey of abortion providers showed that 54% of all U.S. abortions were done with medication in 2020, marking the first time the proportion of medication abortions topped 50%, Guttmacher said.

In 2017, the last time such a survey was done, 39% of abortions were performed by medication, Guttmacher said. The organization said 24% of abortions were done with medication in 2011 and 6% in 2001, the year after the FDA approved the pills.

The 54% estimate is based on early findings, Guttmacher said in a news release. It said that “final estimates will be released in late 2022 and the proportion for medication abortion use is not expected to fall below 50%.”

Rachel Jones, PhD, a Guttmacher researcher, said the higher use of abortion pills may be linked to increases in telemedicine because of the COVID-19 pandemic and the FDA’s decision last year to allow the mailing of abortion pills to patients, the Associated Press reported. Those changes mean women can now consult with a doctor online, receive the pills by mail, and complete the abortion at home.

Abortion pills are recommended for the first 10 weeks of pregnancy, though research shows they can be safe in some cases after 10 weeks, Guttmacher said. Patients take the pill mifepristone, which blocks a hormone needed for pregnancy to continue, and a few days later take the pill misoprostol, which causes cramping that empties the womb.

“The introduction and availability of medication abortion has proven to be a game changer in expanding abortion care in the United States, and it will likely be an even more important option for people to obtain an abortion as many states continue to pass legislation to bar or restrict abortion access,” Guttmacher said in the news release.

Arizona, Arkansas, and Texas have banned the mailing of abortion pills. Similar bans were approved in Montana, Oklahoma, and South Dakota but were blocked in the courts, Guttmacher said.

Sixteen state legislatures have proposed bans or restrictions on medication-induced abortion this year, while 32 states require this type of abortion to be prescribed by doctors.

In Texas, orders for abortion pills increased sharply after the state legislature approved a highly restrictive abortion law, Politico reported, citing a study in The Journal of the American Medical Association.

Orders went up 1,180% in the first week after the Texas law took effect in September, researchers said. Orders dipped somewhat in later weeks but remained 175% higher than before the Texas law took effect.

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

More than half of abortions in the United States are now done with pills rather than surgery, according to a report from the Guttmacher Institute, a research group that supports abortion rights.

A survey of abortion providers showed that 54% of all U.S. abortions were done with medication in 2020, marking the first time the proportion of medication abortions topped 50%, Guttmacher said.

In 2017, the last time such a survey was done, 39% of abortions were performed by medication, Guttmacher said. The organization said 24% of abortions were done with medication in 2011 and 6% in 2001, the year after the FDA approved the pills.

The 54% estimate is based on early findings, Guttmacher said in a news release. It said that “final estimates will be released in late 2022 and the proportion for medication abortion use is not expected to fall below 50%.”

Rachel Jones, PhD, a Guttmacher researcher, said the higher use of abortion pills may be linked to increases in telemedicine because of the COVID-19 pandemic and the FDA’s decision last year to allow the mailing of abortion pills to patients, the Associated Press reported. Those changes mean women can now consult with a doctor online, receive the pills by mail, and complete the abortion at home.

Abortion pills are recommended for the first 10 weeks of pregnancy, though research shows they can be safe in some cases after 10 weeks, Guttmacher said. Patients take the pill mifepristone, which blocks a hormone needed for pregnancy to continue, and a few days later take the pill misoprostol, which causes cramping that empties the womb.

“The introduction and availability of medication abortion has proven to be a game changer in expanding abortion care in the United States, and it will likely be an even more important option for people to obtain an abortion as many states continue to pass legislation to bar or restrict abortion access,” Guttmacher said in the news release.

Arizona, Arkansas, and Texas have banned the mailing of abortion pills. Similar bans were approved in Montana, Oklahoma, and South Dakota but were blocked in the courts, Guttmacher said.

Sixteen state legislatures have proposed bans or restrictions on medication-induced abortion this year, while 32 states require this type of abortion to be prescribed by doctors.

In Texas, orders for abortion pills increased sharply after the state legislature approved a highly restrictive abortion law, Politico reported, citing a study in The Journal of the American Medical Association.

Orders went up 1,180% in the first week after the Texas law took effect in September, researchers said. Orders dipped somewhat in later weeks but remained 175% higher than before the Texas law took effect.

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

More than half of abortions in the United States are now done with pills rather than surgery, according to a report from the Guttmacher Institute, a research group that supports abortion rights.

A survey of abortion providers showed that 54% of all U.S. abortions were done with medication in 2020, marking the first time the proportion of medication abortions topped 50%, Guttmacher said.

In 2017, the last time such a survey was done, 39% of abortions were performed by medication, Guttmacher said. The organization said 24% of abortions were done with medication in 2011 and 6% in 2001, the year after the FDA approved the pills.

The 54% estimate is based on early findings, Guttmacher said in a news release. It said that “final estimates will be released in late 2022 and the proportion for medication abortion use is not expected to fall below 50%.”

Rachel Jones, PhD, a Guttmacher researcher, said the higher use of abortion pills may be linked to increases in telemedicine because of the COVID-19 pandemic and the FDA’s decision last year to allow the mailing of abortion pills to patients, the Associated Press reported. Those changes mean women can now consult with a doctor online, receive the pills by mail, and complete the abortion at home.

Abortion pills are recommended for the first 10 weeks of pregnancy, though research shows they can be safe in some cases after 10 weeks, Guttmacher said. Patients take the pill mifepristone, which blocks a hormone needed for pregnancy to continue, and a few days later take the pill misoprostol, which causes cramping that empties the womb.

“The introduction and availability of medication abortion has proven to be a game changer in expanding abortion care in the United States, and it will likely be an even more important option for people to obtain an abortion as many states continue to pass legislation to bar or restrict abortion access,” Guttmacher said in the news release.

Arizona, Arkansas, and Texas have banned the mailing of abortion pills. Similar bans were approved in Montana, Oklahoma, and South Dakota but were blocked in the courts, Guttmacher said.

Sixteen state legislatures have proposed bans or restrictions on medication-induced abortion this year, while 32 states require this type of abortion to be prescribed by doctors.

In Texas, orders for abortion pills increased sharply after the state legislature approved a highly restrictive abortion law, Politico reported, citing a study in The Journal of the American Medical Association.

Orders went up 1,180% in the first week after the Texas law took effect in September, researchers said. Orders dipped somewhat in later weeks but remained 175% higher than before the Texas law took effect.

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