Abstract: We included nine randomised controlled trials involving a total of 816 women with PCOS. When metformin was compared with placebo there was no clear evidence of a difference between the groups in live birth rates (OR 1.39, 95% CI 0.81 to 2.40, five RCTs, 551 women, I2 = 52%, low-quality evidence). Our findings suggest that for a woman with a 32 % chance of achieving a live birth using placebo, the corresponding chance using metformin treatment would be between 28% and 53%. When metformin was compared with placebo or no treatment, clinical pregnancy rates were higher in the metformin group (OR 1.52; 95% CI 1.07 to 2.15; eight RCTs, 775 women, I2 = 18%, moderate-quality evidence). This suggests that for a woman with a 31% chance of achieving a clinical pregnancy using placebo or no treatment, the corresponding chance using metformin treatment would be between 32% and 49%. The risk of ovarian hyperstimulation syndrome was lower in the metformin group (OR 0.29; 95% CI 0.18 to 0.49, eight RCTs, 798 women, I2 = 11%, moderate-quality evidence). This suggests that for a woman with a 27% risk of having OHSS without metformin the corresponding chance using metformin treatment would be between 6% and 15%. Side effects (mostly gastrointestinal) were more common in the metformin group (OR 4.49, 95% CI 1.88 to 10.72, for RCTs, 431 women, I2=57%, low quality evidence) The overall quality of the evidence was moderate for the outcomes of clinical pregnancy, OHSS and miscarriage, and low for other outcomes. The main limitations in the evidence were imprecision and inconsistency. This review found no conclusive evidence that metformin treatment before or during ART cycles improved live birth rates in women with PCOS. However, the use of this insulin-sensitising agent increased clinical pregnancy rates and decreased the risk of OHSS.

Plain-language summary: The review included nine randomised controlled trials involving a total of 816 women who were randomised to receive metformin (411) versus placebo or no treatment (405). The trials were conducted in the Czech Republic, Italy, Jordan, Norway, Turkey and the United Kingdom. The evidence is current to October 2014. When metformin was compared with placebo or no treatment, there was no conclusive evidence of a difference between the groups in live birth rates, but pregnancy rates were higher in the metformin group, and the risk of OHSS was lower. We estimated that for a woman with a 32 % chance of achieving a live birth using placebo, the corresponding chance using metformin would be between 28% and 53%. For a woman with a 31% chance of achieving a clinical pregnancy without metformin, the corresponding chance using metformin would be between 32% and 49%. For a woman with a 27% risk of ovarian hyperstimulation syndrome (OHSS) without metformin, the corresponding chance using metformin would be between 6% and 15%. Side effects (mostly gastrointestinal) were more common in the metformin group, though only four studies reported this outcome. The overall quality of the evidence was moderate for the outcomes of clinical pregnancy, OHSS and miscarriage, and low for other outcomes. The main limitations in the evidence were imprecision and inconsistency. We found no conclusive evidence that metformin treatment before or during ART cycles improved live birth rates in women with PCOS. However, the use of this insulin-sensitising agent increased clinical pregnancy rates and decreased the risk of OHSS.