Combined metformin and clomiphene citrate versus highly purified FSH for ovulation induction in clomiphene-resistant PCOS women: a randomised controlled trial

Abstract

Aim. To compare the effect of combined metformin–clomiphene citrate (CC) with highly purified urinary FSH (HP-uFSH) for ovulation induction in CC-resistant women with polycystic ovary syndrome (PCOS).Methods. One-hundred fifty-three anovulatory women with CC-resistant PCOS were selected in this randomised controlled trial. Patients received combined metformin–CC (n = 75, 205 cycles) or HP-uFSH (n = 78, 186 cycles) for three cycles. Outcome measures were; Ovulation rate, number of growing and mature follicles, serum E2, serum P, endometrial thickness, pregnancy and miscarriage rates.Results. The ovulation rate per cycle was significantly higher in the HP-uFSH group (83.8% vs. 62%, p = 0.01). The number of follicles ≥12 mm ≥14 mm and ≥18 mm on the hCG day was significantly greater in the HP-uFSH group (p = 0.01, p = 0.02 and p = 0.03, respectively). Pregnancy occurred in 23/205 cycles (11.2%) in combined metformin–CC group and 40/186 cycles (21.5%) in the HP-uFSH group; the difference was statistically significant (p = 0.02). Two patients in the HP-uFSH group suffered mild OHSS.Conclusions. Combined metformin–CC resulted in modest ovulation and pregnancy rates without side effects. It is logical to offer this first for CC-resistant PCOS women before resorting to more expensive alternatives especially in developing communities where economic aspects of therapy are important.