Efficacy and safety of metformin in pregnant women with polycystic ovary syndrome: a systematic review with meta-analysis of randomized and non-randomized controlled trials

Objective To evaluate the efficacy and safety of using metformin in pregnant women with polycystic ovarian syndrome (PCOS) and to explore the most effective and safe protocol by using a meta-analysis method. Methods Medline, EMBASE, Cochrane Library, and other databases were searched for randomized controlled trials and prospective cohort studies enrolling pregnant women with PCOS on receiving metformin or placebo or nothing. Subgroup analyses were undertaken. Results A total of 17 studies involving 2899 patients were included. Compared with control group, the use of metformin significantly reduced the incidence of preterm delivery (cumulative rate 3.86% vs 9.19%, relative risk (RR), 0.42 [95% confidence interval (CI), 0.25-0.71,]; p = .001), early miscarriage (cumulative rate 6.58% vs 18.35%, RR, 0.40 [95% CI, 0.20-0.78]; p = .007), gestational diabetes (cumulative rate 12.86% vs 22.91%, RR, 0.48 [95% CI, 0.26-0.89]; p = .02), and pre-eclampsia (cumulative rate 4.95% vs 7.72%, RR, 0.61 [95% CI, 0.40-0.93]; p = .02), the need for insulin treatment throughout pregnancy (cumulative rate 2.14% vs 5.12%, RR, 0.43 [95% CI, 0.22-0.85]; p = .01), and weight gain of pregnant women (mean difference, -2.45, [95% CI, -3.04 to -1.85]; p < .00001). Conclusions The use of metformin in pregnant women with PCOS can significantly reduce maternal complications. No significant difference was observed in serious maternal adverse events. The efficacy and safety of metformin are worthy of recognition.