N-acetyl-cysteine is a novel adjuvant to clomiphene citrate in clomiphene citrate-resistant patients with polycystic ovary syndrome

Fertil Steril. 2005 Feb;83(2):367-70. doi: 10.1016/j.fertnstert.2004.07.960.


Objective: To evaluate the effect of N-acetyl-cysteine (NAC), a mucolytic drug with insulin sensitizing properties, as an adjuvant therapy in subjects with polycystic ovary syndrome (PCOS) resistant to clomiphene citrate (CC).

Design: Placebo-controlled, double-blind randomized trial.

Setting: University-based hospital and private infertility practice.

Patient(s): One hundred fifty women diagnosed with CC-resistant PCOS, aged 18-39 years undergoing therapy for infertility were included.

Intervention(s): The patients were assigned randomly to receive either NAC 1.2 g/d (group I) or placebo (group II) with CC 100 mg/d for 5 days starting at day 3 of the cycle.

Main outcome measure(s): Ovulation rate and pregnancy rate (PR).

Result(s): Combination of CC and NAC significantly increased both ovulation rate and PR in women with CC-resistant PCOS (49.3% vs. 1.3% and 21.3% vs. 0%, respectively). No cases of ovarian hyperstimulation syndrome (OHSS) were reported in the NAC group; two cases of miscarriage (12.5%) were reported.

Conclusion(s): The NAC as an adjuvant to CC was more effective than placebo for CC-resistant patients with PCOS. It is safe and well tolerated.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Acetylcysteine / administration & dosage*
  • Adolescent
  • Adult
  • Clomiphene / administration & dosage*
  • Drug Resistance
  • Drug Therapy, Combination
  • Female
  • Fertility Agents, Female / administration & dosage*
  • Humans
  • Polycystic Ovary Syndrome / drug therapy*
  • Pregnancy
  • Pregnancy Outcome*


  • Fertility Agents, Female
  • Clomiphene
  • Acetylcysteine