Metformin treatment before and during IVF or ICSI in women with polycystic ovary syndrome

Background The use of insulin-sensitising agents, such as metformin, in women with polycystic ovary syndrome (PCOS) who are undergoing ovulation induction or in vitro fertilisation (IVF) cycles has been widely studied. Suppression of insulin levels with metformin might reduce the hyperinsulinaemia and hyperandrogenism suppression of the ovarian response. As a consequence, metformin could improve both pregnancy and live birth rates. Objectives To determine the effectiveness of metformin as a co-treatment during IVF or intra-cytoplasmic sperm injection (ICSI) in achieving pregnancy or live birth in women with PCOS. Search strategy The Menstrual Disorders and Subfertility Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), MEDLINE, EMBASE, LILACS, the meta Register of Controlled Trials, and reference lists of articles were searched (to week 4, September 2008). Selection criteria Types of studies: randomised controlled trials (RCTs) comparing metformin treatment with placebo or no treatment in women with PCOS who underwent IVF or ICSI treatment. Types of participants: women of reproductive age with anovulation due to PCOS with or without co-existing infertility factors. Types of interventions: metformin administered before and during IVF or ICSI treatment. Types of outcome measures: live birth rate, clinical pregnancy rate, miscarriage rate, incidence of ovarian hyperstimulation syndrome (OHSS), incidence of patient-reported side effects, serum estradiol level on the day of trigger, serum androgen level, and fasting insulin and glucose levels. Data collection analysis Two review authors independently extracted the data according to the protocol. The methods of randomisation and allocation concealment, and characteristics of the studied groups were evaluated. Main results This review found no evidence that metformin treatment before or during assisted reproductive technique (ART) cycles improved live birth or clinical pregnancy rates. The pooled odds ratio (OR) for live birth rate (3 RCTs) was 0.77 (95% CI 0.27 to 2.18) and for clinical pregnancy rate (5 RCTS) was 0.71 (95% CI 0.39 to 1.28). The risk of OHSS in women with PCOS and undergoing IVF or ICSI cycles was reduced with metformin (pooled OR 0.27, 95% CI 0.16 to 0.47). Authors' conclusions This review found no evidence that metformin treatment before or during ART cycles improves live birth or pregnancy rates. The risk of OHSS in women with PCOS and undergoing IVF or ICSI cycles was reduced with metformin. Further large RCTs are necessary to definitively answer if the use of metformin in PCOS women undergoing ART improves live birth and pregnancy rates.