One hundred-fifty overweight or obese infertile women (mean age, 29 years; range, 18-39 years) with polycystic ovary syndrome (PCOS) who had failed to ovulate after treatment with clomiphene citrate were randomly assigned to receive, in double-blind fashion, 600 mg of N-acetylcysteine (NAC) twice a day or placebo along with clomiphene citrate (100 mg/day) for five days starting at day three of the cycle. Compared with placebo, NAC significantly increased both the ovulation rate (49.3% vs. 1.3%; p < 0.0001) and the pregnancy rate (21.3% vs. 0%; p = 0.00006). No cases of ovarian hyperstimulation syndrome were reported in the NAC group. Two miscarriages occurred.

Comment: Clomiphene citrate is frequently used to induce ovulation in women with PCOS. Approximately 70% of women treated with this drug experience a return of menstruation and ovulation and 30% become pregnant within three months of treatment. The results of the present study suggest that the combination of NAC and clomiphene citrate is beneficial for some women with PCOS who have failed to respond to clomiphene citrate alone. While the mechanism of action of NAC is not known, it may work by improving the insulin resistance that is frequently associated with PCOS.

Rizk AY, et al. N-acetyl-cysteine is a novel adjuvant to clomiphene citrate in clomiphene citrate-resistant patients with polycystic ovary syndrome. Fertil Steril. 2005;83:367-370.