N-Acetyl Cysteine Plus Clomiphene Citrate Versus Metformin and Clomiphene Citrate in Treatment of Clomiphene-Resistant Polycystic Ovary Syndrome: A Randomized Controlled Trial

Objective: To compare the effects of combined N-acetyl cysteine (NAC) and clomiphene citrate (CC) and of combined metformin and CC on ovulation induction in anovulatory CC-resistant women with polycystic ovary syndrome (PCOS). Methods: One hundred ninety-two women were randomized to receive either the NAC-CC drug combination (group A, n = 95) or the combined metformin-CC therapy (group B, n = 97) for three treatment cycles. The primary outcome measure was ovulation; secondary outcomes were number of follicles, serum estrogen and progesterone levels, posttreatment endometrial thickness, pregnancy, and miscarriage. Results: Over a 3-month follow-up period, women in group B had significantly higher ovulation and pregnancy rates compared with women in group A (69.1% vs. 20.0%, p = 0.002, and 22.7% vs. 5.3%, p = 0.020, respectively). The level of serum estrogen, the endometrial thickness on the day of human chorionic gonadotropin (hCG) administration, and the serum progesterone level on cycle days 21-23 were all significantly higher for women in group B than for those in group A. Additionally, a lower miscarriage rate was observed among women in group B than among those in group A. Conclusions: The efficacy of metformin-CC combination therapy is higher than that of NAC-CC for inducing ovulation and achieving pregnancy among CC-resistant PCOS patients.