Women who take progesterone in the year before becoming pregnant may reduce their risk for miscarriage by as much as 18%, according to a new study analyzing tens of thousands of pregnancies nationwide.

Progesterone is commonly prescribed to regulate menstrual cycles, prevent premature birth, and support fertility treatment. Previous research suggests taking the hormone, supports implantation and early placental development, after conception can reduce the risk for miscarriage in women with a history of early pregnancy loss or unexplained bleeding during pregnancy, although results have been mixed across studies.

“An 18% reduction in risk is clinically meaningful, though the benefit to an individual patient will vary based on their baseline risk and other factors,” said Kersten Bartelt, RN, research clinician at Epic Research and author of the new study. “The insights from this study can aid in shared decision-making between a clinician and their patients who have experienced a prior pregnancy loss.”

Progesterone therapy, while generally safe, can cause mild side effects such as breast tenderness, nausea, and bloating.

For the study, Bartelt and her colleagues used a two-team review method to conduct the analysis. One team developed the study design and identified eligible patients using electronic health data from Cosmos, a nationwide electronic health record network of more than 300 million patients across 1700 hospitals and 40,000 clinics. A separate, blinded team replicated and verified the analysis to ensure consistency and reduce bias.

Bartelt and her colleagues examined data from more than 84,000 pregnancies among women with a history of pregnancy losses at any stage. The study included women aged 15-49 years with a documented history of at least one prior miscarriage.

To reduce bias, the study excluded women who began progesterone after conception, when it might have been prescribed to treat emerging complications.

Women who used progesterone before conceiving had an 18% (hazard ratio, 0.82; 95% CI, 0.73-0.93) lower risk for miscarriage compared with women who did not take the hormone.

Rachel McConnell, MD, assistant professor of obstetrics and gynecology at the Vagelos College of Physicians and Surgeons at Columbia University in New York City, said the findings are encouraging and consistent with what she has observed in practice.

“From a clinical standpoint, an 18% reduction in miscarriage risk is beneficial,” McConnell, who was not involved with the study, said.

If replicated, Bartelt said the findings could inform updates to clinical guidelines.

Translating the findings into practice could pose challenges, especially in identifying and supporting at-risk women before pregnancy.

“Barriers could include timely identification of the need before conception, access, coverage, and understanding of the treatment plan,” Bartelt said.

McConnell and Bartelt reported having no financial conflicts of interest.

Lara Salahi is a health journalist based in Boston.