Effects of metformin in women with polycystic ovary syndrome treated with gonadotrophins for in vitro fertilisation and intracytoplasmic sperm injection cycles: a systematic review and meta-analysis of randomised controlled trials

Background Metformin is widely used for treating women with polycystic ovary syndrome (PCOS), and many patients with PCOS who are infertile receive gonadotrophins while being treated with metformin. Objectives To assess the effects of metformin administration in infertile patients with PCOS who receive gonadotrophins for in vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI) cycles. Search strategy We searched international scientific databases, websites for the registration of trials, and bibliographies of retrieved articles, books, and review articles up to August 2012. Selection criteria Randomised controlled trials (RCTs). Data collection and analysis Authors independently reviewed and extracted the data. Main results Ten RCTs (with a total of 845 women with PCOS) were included in the final analysis. Metformin administration in IVF/ICSI cycles had no effect on the rates of pregnancy (OR 1.20, 95% CI 0.901.61) and live birth (OR 1.69, 95% CI 0.853.34). No effect of metformin dose, metformin pretreatment duration, and stopping time of metformin administration was observed on these reproductive end points. Metformin administration reduced the risk of ovarian hyperstimulation syndrome (OHSS; OR 0.27, 95% CI 0.160.46) and of miscarriage (OR 0.50, 95% CI 0.300.83), while increased that of implantation (OR 1.42, 95% CI 1.242.75). Author's conclusions In infertile patients with PCOS treated with gonadotrophins for IVF/ICSI cycles, metformin exerts no clinical effect on rates of pregnancy or live birth, but it reduces the risk of OHSS, and improves the rates of miscarriage and implantation. Further RCTs are needed to assess the reproductive effect of metformin in young well-selected patients with PCOS and specific phenotypes and features.