Preconception and first-trimester metformin on pregnancy outcomes in women with polycystic ovary syndrome: a systematic review and meta-analysis.

Abstract

This study aimed to explore the effects of preconception and first-trimester metformin use on pregnancy outcomes in women with polycystic ovary syndrome. MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials were searched from database inception to August 1, 2024. Randomized controlled trials of metformin started before conception and continued at least until a positive pregnancy test compared with either placebo or no treatment in women with polycystic ovary syndrome were included. A systematic review and meta-analysis was conducted. Pooled odds ratios with 95% confidence intervals were calculated for the following key outcomes: miscarriage (primary) and clinical pregnancy and live birth (secondary). The studies were assessed for quality using the Cochrane risk-of-bias tool for randomized trials (RoB 2) and the Grading of Recommendations, Assessment, Development, and Evaluation approach. Indirect comparisons were performed for all key outcomes on the timing of metformin treatment using the Bucher technique. A total of 12 trustworthy studies (involving 1708 women) were included in the meta-analysis, all of which were graded low to moderate quality. Women who received preconception metformin that was continued throughout the first trimester of pregnancy showed higher clinical pregnancy rates (odds ratio, 1.57 [95% confidence interval, 1.11-2.23]), a possible reduction in miscarriage (odds ratio, 0.64 [95% confidence interval, 0.32-1.25]), and possible increase in live birth (odds ratio, 1.24 [95% confidence interval, 0.59-2.61]) than women who received either a placebo or no treatment. Women who stopped metformin once pregnant not only had an increase in clinical pregnancy rate (odds ratio, 1.35 [95% confidence interval, 1.01-1.80]) but also had an indication of an increase in miscarriage rate (odds ratio, 1.46 [95% confidence interval, 0.73-2.90]) compared with those who received a placebo or no treatment. Indirect comparisons between metformin continued through the first trimester of pregnancy and metformin stopped once pregnant consistently demonstrated a trend favoring the continuation of metformin: clinical pregnancy odds ratio of 1.16 (95% confidence interval, 0.74-1.83), miscarriage odds ratio of 0.44 (95% confidence interval, 0.17-1.16), and live birth odds ratio of 1.14 (95% confidence interval, 0.41-3.13). Continuing metformin treatment throughout the first trimester of pregnancy may reduce the risk of miscarriage and increase live birth rates in women with polycystic ovary syndrome. Continuation of metformin seems to have greater clinical benefit than discontinuation of metformin after a positive pregnancy test. There is a need for further high-quality research.