The effect of metformin on ovarian stimulation and in vitro fertilization in insulin-resistant women with polycystic ovary syndrome: an open-label randomized cross-over trial

Metformin effectively restores insulin sensitivity in insulin-resistant women with polycystic ovary syndrome (PCOS). We examined whether metformin, given prior to and during ovarian stimulation for in vitro fertilization (IVF), altered follicle stimulating hormone (FSH) requirement and increased the number of collected oocytes in these women. Seventeen insulin-resistant women with PCOS were recruited to our IVF unit to receive two consecutive cycles of ovarian stimulation with or without metformin co-treatment, the order of treatments being randomized using a table of random numbers. Metformin treatment (1500 mg/day) started 3 weeks before downregulation with buserelin acetate and was continued throughout ovarian stimulation with human recombinant FSH. Nine women completed both cycles, the results of eight women being excluded because of pregnancy after the first cycle (n = 4) or because the protocol of the study was not followed (n = 4). Mean total FSH dose was 2301 IU (range 1500-6563 IU) in metformin cycles and 2174 IU (range 1200-3900 IU) in parallel control cycles, while the mean number of collected oocytes was 8.6 (range 2-28) and 4.6 (range 1-16), respectively. Bayesian analysis showed probabilities of 0.05 that metformin reduces FSH requirement by at least 10%, and of 0.61 that at least 10% more oocytes are collected after metformin co-treatment. Co-administration of metformin is therefore likely to increase the number of oocytes collected after ovarian stimulation in insulin-resistant women with PCOS but is unlikely to reduce the requirement for FSH.