A Cochrane review [Abstract] 1 included 13 studies with a total of 1132 subjects. Metformin treatment before or during assisted reproductive technique cycles (long protocol with GnRH-agonist ; in vitro fertilisation, IVF or intra-cytoplasmic sperm injection, ICSI) compared to placebo or no treatment did not clearly improve live birth rate (OR 1.30, 95% CI 0.94 to 1.79; 6 trials; n=651, I² 47%, low-quality evidence). This suggests that for a woman with a 28 % chance of achieving a live birth using placebo, the corresponding chance using metformin treatment would be between 27% and 51%. The risk of ovarian hyperstimulation syndrome was reduced with metformin (RR 0.46, 95% CI 0.29 to 0.72; 11 trials; n=1091; I² 38%). This suggests that for a woman with a 20% risk of having OHSS without metformin the corresponding chance using metformin treatment would be between 6% and 14%.
Another Cochrane review [Abstract] 2 included 5 studies with a total of 264 subjects comparing gonadotrophins plus metformin versus gonadotrophins. The gonadotrophin used was recombinant FSH in 4 studies and highly purified FSH in one study. Metformin plus FSH was associated with a higher cumulative live birth rate when compared with FSH (odds ratio (OR) 2.31, 95% CI 1.23 to 4.34; 2 RCTs, n=180). This suggests that if the chance of live birth after FSH is assumed to be 27%, then the chance after addition of metformin would be between 32% and 60%. Metformin use was associated with a higher ongoing pregnancy rate and a higher clinical pregnancy rate. Results showed no evidence of a difference in multiple pregnancy rates between metformin plus FSH and FSH (OR 0.55, 95% CI 0.15 to 1.95; 4 RCTs, n=232) and no evidence of a difference in rates of miscarriage or OHSS.
Comment: The quality of evidence is downgraded by several issues in study quality and by imprecise results (few patients and wide confidence intervals).
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