Metformin Use Before Assisted Reproductive Technology and Pregnancy Outcomes in Women With Polycystic Ovary Syndrome: A Nationwide Cohort Study

Metformin has been hypothesized to improve ovulation and pregnancy rates in women with polycystic ovary syndrome (PCOS) undergoing assisted reproductive technology (ART). This population-based cohort study assessed pregnancy outcomes associated with metformin use prior to ART in women with PCOS. We included 10,178 women with PCOS undergoing their first fresh embryo transfer cycle under the national health insurance program of South Korea between 2017 and 2021. Women who received metformin for ovulation induction within 12 weeks prior to ovarian stimulation were compared with those who did not receive metformin. ART outcomes included successful oocyte retrieval, embryo transfer, and clinical pregnancy, while pregnancy outcomes included spontaneous abortion, preterm birth, and live birth. Overlap-weighted risk ratios (RR) were calculated for each outcome. Among the study population, 2,149 (21.1%) had used metformin prior to ovarian stimulation, and 8,029 (78.9%) had not. Metformin use did not improve or worsen ART outcomes, with comparable rates of oocyte retrieval (RR: 1.01, 95% confidence interval 1.00-1.02) and clinical pregnancy (RR: 1.05, 1.00-1.11), as well as no increased rates of spontaneous abortion (RR: 1.01, 0.84-1.21), preterm birth (RR: 0.99, 0.84-1.18), or live birth (RR: 1.05, 0.99-1.12). Subgroup analyses suggested modest benefits, including higher clinical pregnancy or live birth rates, among women aged ≥ 35 years, those undergoing a GnRH antagonist protocol, and those with ≥ 30 days of metformin use. In conclusion, metformin pretreatment before ART was not associated with any clinically meaningful benefits or harms in pregnancy outcomes among women with PCOS.