Use of letrozole and clomiphene citrate combined with gonadotropins in clomiphene-resistant infertile women with polycystic ovary syndrome: a prospective study

Drug Des Devel Ther. 2015 Nov 11:9:6001-8. doi: 10.2147/DDDT.S83259. eCollection 2015.

Abstract

Background: Gonadotropin has been used to stimulate ovulation in clomiphene-resistant infertile women with polycystic ovary syndrome (PCOS), but it is associated with overstimulated cycles with the development of many follicles. The aim of the study was to evaluate the effectiveness and efficacy of letrozole and clomiphene citrate (CC) combined with human menopausal gonadotropin (HMG) in CC-resistant infertile women with PCOS.

Methods: Ninety-four women received the letrozole + HMG, 90 women received CC + HMG, and 71 women received HMG only. All women received one treatment regimen in one treatment cycle. All patients were given HMG 75 IU on alternate days daily starting on day 3 or day 7 until the day of administration of human chorionic gonadotropin.

Results: The rate of monofollicular development was 80.2% in the letrozole + HMG group, 65.3% in the CC + HMG group, and 54.7% in the HMG-only group (P<0.05 for letrozole + HMG vs the other two groups). The number of developing follicles (≥14 mm follicles) and the cycle cancellation rate due to ovarian hyperresponse were the lowest in the letrozole + HMG group, but the difference was not significant. The ovulation and pregnancy rate were similar among the three protocols. The HMG dose needed and the mean duration of treatment were significantly lower in the letrozole + HMG and CC + HMG groups compared with the HMG-only group.

Conclusion: Letrozole in combination with HMG is an effective protocol for reducing the risks of hyperstimulation for ovarian induction in CC-resistant women with PCOS. This combination may be more appropriate in patients who are particularly sensitive to gonadotropin.

Keywords: clomiphene citrate; combination therapy; human menopausal gonadotropin; letrozole; polycystic ovary syndrome.

Publication types

  • Comparative Study
  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Clomiphene / administration & dosage*
  • Clomiphene / pharmacology
  • Dose-Response Relationship, Drug
  • Drug Therapy, Combination
  • Female
  • Fertility Agents, Female / administration & dosage
  • Fertility Agents, Female / pharmacology
  • Humans
  • Infertility, Female / drug therapy*
  • Infertility, Female / etiology
  • Letrozole
  • Menotropins / administration & dosage*
  • Menotropins / pharmacology
  • Nitriles / administration & dosage*
  • Nitriles / pharmacology
  • Ovarian Hyperstimulation Syndrome / prevention & control
  • Ovulation Induction / methods
  • Polycystic Ovary Syndrome / complications
  • Polycystic Ovary Syndrome / drug therapy*
  • Pregnancy
  • Pregnancy Rate
  • Prospective Studies
  • Treatment Outcome
  • Triazoles / administration & dosage*
  • Triazoles / pharmacology
  • Young Adult

Substances

  • Fertility Agents, Female
  • Nitriles
  • Triazoles
  • Clomiphene
  • Menotropins
  • Letrozole