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Researchers say progesterone supplementation was helpful to some pregnant women with a history of miscarriage. Getty Images
  • Researchers in the United Kingdom say progesterone treatments given to pregnant women with a history of miscarriage can make a difference.
  • Studies in previous years had concluded there was no measurable decrease in the rate of miscarriage in pregnant women given progesterone treatments.
  • Experts are mixed on whether progesterone supplementation should be standard care for pregnant women with a history of miscarriage.

Progesterone is a vital hormone in the creation of humans.

It’s crucial in a woman’s menstrual cycle and helps maintain the uterine wall during pregnancy.

A woman with low progesterone is more prone to have abnormal uterine bleeding if she’s not pregnant and more likely to miscarry if she is pregnant.

But supplementing women prone to miscarriage has historically been lacking.

Now a new round of research has some in the medical community arguing that publicly funded health systems should make it standard protocol.

The United Kingdom’s National Health Service (NHS) is exploring whether progesterone supplements should become standard care for women with a history of miscarriage who experience bleeding in the early parts of their latest pregnancy.

Experts there cite a growing body of research that suggests it’s both cost-effective and can increase the chance of a successful pregnancy.

One study published last week from researchers at the University of Birmingham and Tommy’s National Centre for Miscarriage Research suggests that England’s health system could bring more babies into the world with progesterone treatments.

That increase would rise to as much as 15 percent for women who have already had three or more miscarriages.

And, those researchers said, the country could do it all for an average of £204 — about $225 in U.S. dollars — per pregnancy.

While those financial results don’t transfer to industrialized countries without nationalized healthcare, the research could affect how providers weigh progesterone therapy in at-risk pregnancies.

Adam Devall, PhD, BMedSC, a study author and a senior clinical trial fellow at Birmingham and manager of its miscarriage research center, says that because up to a quarter of pregnancies end in miscarriage, their research could be beneficial to women at risk for having their pregnancies end early.

“The role of first trimester progesterone supplementation in the treatment of pregnancies at high risk of miscarriage is a long standing research question that has been debated in the medical literature for over 60 years,” Devall said in a statement.

“Thus far, policy makers have been unable to make evidence-based recommendations on the use of progesterone supplementation to improve outcomes,” he said.

The U.K. research team based their findings on two major clinical trials they led with government funding, dubbed PROMISE and PRISM.

PROMISE involved 836 women who had recurrent miscarriages at 45 hospitals in the United Kingdom and the Netherlands.

That study found that treating some of those women with progesterone equated to a 3 percent higher live birth rate, but it came with “substantial statistical uncertainty,” meaning the results could have been chalked up to chance.

The PRISM study involved nearly 4,200 women across 48 hospitals who had bleeding early in their pregnancies. That study also saw a difference of about 3 percent, and this difference was also not considered statistically significant.

However, the PRISM study was big enough to allow researchers to take a closer look at certain subgroups of women.

They found that progesterone treatments created a 5 percent increase in the number of babies born to women who had previously had one or more miscarriages.

Further, the researchers found that progesterone given to women who had three or more miscarriages created a 15 percent increase in live births compared with women given a placebo.

The PRISM study had another effect, according to an unpublished survey Birmingham conducted with 130 healthcare practitioners in the United Kingdom.

Before the results from the PRISM study were published last May in the New England Journal of Medicine, researchers said only 13 percent of practitioners offered treatments to women at risk for miscarriage.

Since then, 75 percent now offer the treatment.

The increase didn’t materialize when a NHS-funded trial in the United Kingdom using PROMISE data, published in the same journal 4 years before these studies, concluded “progesterone therapy in the first trimester of pregnancy did not result in a significantly higher rate of live births among women with a history of unexplained recurrent miscarriages.”

In essence, experts are mixed, with the consensus being that the latest research should be tossed on top of the already accumulating pile of information about hormone replacement therapy.

Dr. G. Thomas Ruiz, the OB-GYN lead at MemorialCare Orange Coast Medical Center in California, says many obstetricians have used progesterone based on anecdotal evidence from women who have had recurrent miscarriages.

However, he says, recent analysis of the PRISM and PROMISE studies may give credence to prescribing progesterone to women with a history of miscarriage during their first trimester.

“These studies may tip the balance toward treating with progesterone given the safety and relative low cost of the medication. The new studies do not disprove the older data, but suggest treatment may be of benefit,” Ruiz told Healthline. “So, given we have not done much for this patient population in the past, this is something safe to try.”

Others question whether progesterone treatments have an actionable effect.

Dr. Mitchell S. Kramer, chair of the OB-GYN department at Huntington Hospital in New York, says the latest Birmingham study doesn’t show a significantly higher rate of live births among women with recurrent miscarriages who were treated with progesterone, so using it for that reason is “of questionable benefit.”

“The results of this study should encourage doctors to counsel their patients about the questionable benefit of this therapy, although no significant downside has been identified,” Kramer told Healthline.

To others, the study points toward more specific places where future studies could focus when attempting to help pregnant women.

Dr. Kecia Gaither, director of perinatal services at NYC Health + Hospitals/Lincoln in New York, echoes the conclusions of the recent paper by pointing out that using progesterone for miscarriage has a strong scientific rationale.

She describes the functionality or “dysfunctionality” of the endometrium — the mucous membrane lining the uterus she describes as “a dynamic mixture of cells” — when exposed to low concentrations of progesterone.

In particular, Gaither notes, the study cites research that endometrial biopsies of women treated with progesterone showed the presence of cyclin E, which affects how cells replicate.

That, she tells Healthline, opens the door for more research that evaluates how cyclin E affects women who have had several miscarriages, along with those with bleeding in early pregnancy.

“The long and short of it — great study,” Gaither said, “which hopefully will take researchers and clinicians one step closer to treating patients with recurrent pregnancy loss successfully.”