Metformin Timing and Pregnancy Outcomes in PCOS

TOPLINE:

For women with polycystic ovary syndrome (PCOS), continuing preconception metformin throughout the first trimester rather than stopping it at the positive pregnancy test might reduce the risk for miscarriage and improve pregnancy outcomes.

METHODOLOGY:

• Researchers conducted a meta-analysis by searching the literature across MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials databases to determine how the timing of metformin treatment specifically affects pregnancy outcomes in women with PCOS.
• They included 12 randomised controlled trials including 1708 women with PCOS and compared preconception metformin, continued until at least pregnancy confirmation, with placebo or no treatment.
• The primary outcome was the miscarriage rate; secondary outcomes were the clinical pregnancy rate and live birth rate.
• Indirect comparisons between continuing metformin throughout the first trimester and stopping it at pregnancy confirmation were performed using the Bucher technique to evaluate key pregnancy outcomes.

TAKEAWAY:

• Women who continued preconception metformin throughout the first trimester had a lower risk for miscarriage (odds ratio [OR], 0.64; 95% CI, 0.32-1.25) and higher clinical pregnancy rates (OR, 1.57; 95% CI, 1.11-2.23) and live birth rates (OR, 1.24; 95% CI, 0.59-2.61) than those who received either placebo or no treatment.
• Women who stopped metformin at pregnancy confirmation showed a higher risk for miscarriage (OR, 1.46; 95% CI, 0.73-2.90) and higher clinical pregnancy rates (OR, 1.35; 95% CI, 1.01-1.80) than those who received either placebo or no treatment.
• Women who continued metformin throughout the first trimester experienced a lower risk for miscarriage (OR, 0.44; 95% CI, 0.17-1.16) and higher clinical pregnancy rates (OR, 1.16; 95% CI, 0.74-1.83) and live birth rates (OR, 1.14; 95% CI, 0.41-3.13) than those who stopped metformin at the positive pregnancy test.

IN PRACTICE:

“The [study] findings suggest that discontinuing metformin upon pregnancy confirmation may cause a delayed ‘rebound’ effect, potentially increasing insulin resistance and adversely affecting pregnancy outcomes later in the first trimester,” the authors wrote.

SOURCE:

This study was led by James Cheshire, PhD, Birmingham Women’s and Children’s NHS Foundation Trust, Birmingham, England. It was published online on June 03, 2025, in the American Journal of Obstetrics and Gynecology.

LIMITATIONS:

The major limitation of this study was the heterogeneous nature of the population and the overall low quality of evidence. Findings may not be applicable to all PCOS phenotypes as the study did not account for differences in phenotypes and degrees of hyperandrogenism and insulin resistance in women with PCOS. Many studies did not stratify pregnancy outcome data on the basis of BMI, preventing meaningful subgroup analyses and potentially affecting the findings.

DISCLOSURES:

This study did not receive any external funding. The authors declared having no competing interests.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.