Effect of Metformin (MTF) Intervention During Pregnancy in Women With Polycystic Ovarian Syndrome (PCOS): A Systematic Review

Metformin (MTF) is a commonly prescribed medication for women with polycystic ovarian syndrome (PCOS), but its impact on pregnancy outcomes in women with PCOS remains controversial. This systematic review aims to evaluate the effects of MTF intervention on pregnancy outcomes in women with PCOS and the impact of MTF on offspring. A comprehensive search is conducted in PubMed, Google Scholar, and ScienceDirect databases from 2019 up to May 16, 2023. Only review articles and meta-analyses are included, focusing on women with PCOS who received MTF during pregnancy or as part of infertility treatment. The primary outcomes of interest are clinical pregnancy rate (CPR), miscarriage rate, preterm birth rate, and live birth rate. Secondary outcomes are the safety profile of MTF. Data extraction and quality assessment are performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and the assessment using the multiple systematic reviews (AMSTAR) 2 tool, respectively. The initial search produced 1877 studies. Thirteen studies were included in the review. While the use of MTF during pregnancy in women with PCOS may have some benefits in reducing certain pregnancy complications such as pregnancy-induced hypertension (PIH), gestational diabetes mellitus (GDM), preeclampsia, preterm delivery, reducing the risk of ovarian hyperstimulation syndrome (OHSS) in women with PCOS undergoing in vitro fertilization (IVF); however, there is no significant difference in clinical pregnancy and live birth rates overall, but subgroup analysis suggests potential benefits for women with a higher body mass index (BMI). MTF is associated with a larger fetal head circumference and potential long-term effects on offspring's BMI and obesity. Further research is needed to better understand the optimal dosing of MTF, long-term effects, and effects in specific subgroups. The heterogeneity of the included studies limited the ability to analyze the data effectively, leading to challenges in drawing definitive conclusions.