A systematic review and meta-analysis of randomized controlled trials on metformin co-administration during gonadotrophin ovulation induction or IVF in women with polycystic ovary syndrome

Abstract
BACKGROUND: A systematic review of randomized controlled trials (RCTs) comparing whether metformin co-administration with gonadotrophins for ovulation induction (OI) with timed intercourse or IVF improves outcome in women with polycystic ovary syndrome (PCOS). METHODS: The quality of reporting of meta-analyses (QUOROM) guidelines were followed. A systematic computerized literature search of three bibliographic databases was performed. RESULTS: Eight RCTs were included in the overall review. Meta-analysis demonstrated that the co-administration of metformin to gonadotrophin OI does not significantly improve ovulation [odds ratio (OR) = 3.27; 95% confidence interval (95% CI) = 0.31–34.72] or pregnancy (OR = 3.46; 95% CI = 0.98–12.2) rates. Metformin co-administration to IVF treatment does not improve pregnancy (OR = 1.29; 95% CI = 0.84–1.98) or live birth (OR = 2.02, 95% CI = 0.98–4.14) rates but reduces the risk of ovarian hyperstimulation syndrome (OHSS) (OR = 0.21; 95% CI = 0.11–0.41, P < 0.00001). CONCLUSIONS: Current data on the use of metformin in the gonadotrophin OI or IVF treatment settings are inconclusive because of the review’s failure to exclude an important clinical treatment effect. Further RCTs are necessary to definitively clarify whether metformin co-administration during gonadotrophin OI or IVF will improve the efficacy of these treatments in PCOS women.