Continuing Metformin in Early Pregnancy May reduce miscarriage risk and Benefit Women with PCOS: Study

A new study published in the American Journal of Obstetrics and Gynaecology revealed that for women with polycystic ovary syndrome (PCOS), continuing metformin during the first trimester significantly reduced miscarriage risk and improved clinical pregnancy and live birth rates.

PCOS has been linked to poor pregnancy outcomes, such as an increased risk of miscarriage and gestational diabetes. And the common medication being researched to help pregnant women with PCOS is metformin. Thus, to investigate the impact of preconception and first-trimester metformin usage on pregnancy outcomes in women with PCOS, this research was carried out.

From database creation until August 1st, 2024, searches were conducted throughout Embase, MEDLINE, and the Cochrane Central Register of Controlled Trials. In women with PCOS, metformin was compared to either a placebo or no therapy in randomized controlled studies that began preconception and lasted at least until a positive pregnancy test.

For the primary outcome of miscarriage and the secondary outcome of clinical pregnancy and live birth, the pooled odds ratio (OR) with 95% CI was computed. The Cochrane risk-of-bias tool for randomised trials (RoB-2) and the Grading of Recommendations, Assessment, Development, and Evaluation technique were used to evaluate the quality of the studies. Using Bucher's approach, indirect comparisons were conducted for all significant outcomes regarding the time of metformin administration.

The meta-analysis comprised 12 reliable studies with 1,708 women, all of which were rated as low to moderate quality. When compared to either placebo or no treatment, women who received preconception metformin and continued it throughout the first trimester had higher clinical pregnancy rates (OR 1.57, 95% CI 1.11-2.23), a potential decrease in miscarriage (OR 0.64, 95% CI 0.32-1.25), and a potential increase in live birth (OR 1.24, 95% CI 0.59-2.61).

The women who discontinued using metformin after becoming pregnant experienced a higher clinical pregnancy rate (OR 1.35, 95% CI 1.01-1.80) and a possible increase in miscarriage rate (OR 1.46, 95% CI 0.73-2.90), when compared to placebo or no therapy.

There was a consistent trend in favor of continuing metformin through the first trimester as opposed to stopping it once pregnant, as evidenced by the following indirect comparisons: clinical pregnancy OR 1.16 (95% CI 0.74-1.83), miscarriage OR 0.44 (95% CI 0.17-1.16), and live birth OR 1.14 (95% CI 0.41-3.13).

Overall, women with PCOS may have higher live birth rates and a lower chance of miscarriage if they continue taking metformin during the first trimester. It seems that continuing metformin after a positive pregnancy test has more clinical benefits than discontinuing it. 

Reference:

Cheshire, J., Garg, A., Smith, P., Devall, A. J., Coomarasamy, A., & Dhillon-Smith, R. K. (2025). Preconception and first trimester metformin on pregnancy outcomes in women with polycystic ovary syndrome: a systematic review and meta-analysis. American Journal of Obstetrics and Gynecology. https://doi.org/10.1016/j.ajog.2025.05.038