N-Acetyl cysteine and clomiphene citrate for induction of ovulation in polycystic ovary syndrome: a cross-over trial

Acta Obstet Gynecol Scand. 2007;86(2):218-22. doi: 10.1080/00016340601090337.


Objective: To compare clomiphene citrate plus N-acetyl cysteine versus clomiphene citrate for inducing ovulation in patients with polycystic ovary syndrome.

Design: Prospective cross-over trial.

Setting: University teaching hospital and a private practice setting.

Patients: Five hundred and seventy-three patients were treated with clomiphene citrate for one menstrual cycle among which 470 patients were treated with clomiphene citrate plus N-acetyl cysteine for another cycle. All women suffered from polycystic ovary syndrome.

Interventions: Patients had clomiphene citrate 50-mg tablets twice daily alone or with N-acetyl cysteine 1,200 mg/day orally for 5 days starting on day 3 of the menstrual cycle.

Outcome measures: Primary outcomes were number of mature follicles, serum E2, serum progesterone, and endometrial thickness. Secondary outcome was the occurrence of pregnancy.

Results: Ovulation rate improved significantly after the addition of N-acetyl cysteine (17.9% versus 52.1%). Although the number of mature follicles was more in the N-acetyl cysteine group (2.1+/-0.88 versus 3.2+/-0.93), the difference was not statistically significant. The mean E2 levels (pg/ml) at the time of human chorionic gonadotropine injection, serum progesterone levels (ng/ml) on days 21-23 of the cycle, and the endometrial thickness were significantly improved in the N-acetyl cysteine group. The overall pregnancy rate was 11.5% in the N-acetyl cysteine group. Insulin resistance occurred in 260 patients (55.4%). There was no significant difference between the insulin resistance group (n = 260) and non-insulin resistance group (n = 210) as regards ovulation rate, number of follicles, serum E2 (pg/ml), serum progesterone (ng/ml), endometrial thickness (mm), or pregnancy rate.

Conclusion: N-Acetyl cysteine is proved effective in inducing or augmenting ovulation in polycystic ovary patients.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Acetylcysteine / administration & dosage*
  • Adult
  • Chorionic Gonadotropin / administration & dosage*
  • Clomiphene / administration & dosage*
  • Cross-Over Studies
  • Drug Therapy, Combination
  • Endometrium / drug effects*
  • Estrogens / blood
  • Female
  • Fertility Agents, Female / administration & dosage*
  • Follicle Stimulating Hormone / blood
  • Humans
  • Infertility, Female / drug therapy*
  • Infertility, Female / etiology
  • Luteinizing Hormone / blood
  • Ovary / diagnostic imaging
  • Ovulation Induction / methods*
  • Polycystic Ovary Syndrome / blood
  • Polycystic Ovary Syndrome / drug therapy*
  • Pregnancy
  • Progesterone / blood
  • Prospective Studies
  • Testosterone / blood
  • Ultrasonography


  • Chorionic Gonadotropin
  • Estrogens
  • Fertility Agents, Female
  • Clomiphene
  • Testosterone
  • Progesterone
  • Luteinizing Hormone
  • Follicle Stimulating Hormone
  • Acetylcysteine