Does metformin affect the ovarian response to gonadotropins for in vitro fertilization treatment in patients with polycystic ovary syndrome and reduced ovarian reserve? A randomized controlled trial

Objective: To evaluate the effects of metformin on the ovarian response to gonadotropins given for in vitro fertilization (IVF) programs in patients with polycystic ovary syndrome (PCOS) and reduced ovarian reserve. Design: Prospective, parallel, randomized, double-blind, placebo-controlled clinical trial. Setting: Academic departments of obstetrics and gynecology, and a private IVF center. Patient(s): Primary infertile patients with PCOS older than 35 years and/or with a basal follicle-stimulating hormone (FSH) level higher than 10 IU/L who were scheduled for IVF cycles. Intervention(s): Gonadotropin-releasing hormone agonist flare-up protocol and high starting doses of recombinant FSH plus metformin or placebo tablets. Main Outcome Measure(s): Primary end point: cancellation rate for low ovarian response. Secondary end-points: other clinical, biochemical, and reproductive data. Result(s): Enrollment was stopped after 88 participants had been randomized and analyzed due to an unacceptable increased risk of poor ovarian response in the metformin arm. Statistically significant differences between the metformin and placebo groups were observed in the dose of gonadotropins used, peak estradiol levels, and the number of dominant follicles, retrieved oocytes, and metaphase II oocytes. Conclusion(s): In patients with PCOS and reduced ovarian reserve, metformin worsened the response to gonadotropins, and its administration should be stopped before the start of controlled ovarian hyperstimulation for IVF programs.