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Grand Rounds

How Does Letrozole Compare to Clomiphene Citrate for Women with Unexplained Infertility?

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BACKGROUND AND PURPOSE:

  • There is previous evidence for the use of letrozole for ovulation induction in women with PCOS (see ‘Related ObG Topic’ below)
  • Letrozole, an aromatase inhibitor, has other potential benefits as well, including lack of antiestrogenic effects on endometrium, shorter half-life and fewer side effects
  • Eskew et al. (Obstetrics & Gynecology, 2019) compared effectiveness of letrozole vs. clomiphene for ovarian stimulation in women with unexplained infertility

METHODS:

  • Systematic review and meta-analysis
    • RCTs comparing clomiphene citrate with letrozole
    • Participants
      • Unexplained infertility >1 year
      • Normal ovulation
      • At least 1 patent tube
      • ≥5 million sperm/mL after wash and before IUI
  • Primary outcome: Positive pregnancy test per patient
  • Secondary outcomes included
    • Positive pregnancy test per cycle | Clinical pregnancy | Live birth | Spontaneous miscarriage | Twins | Mean serum estradiol (E2) | Endometrial thickness | Number of dominant follicles

RESULTS:

  • 8 RCTs | 2,647 women
  • Primary outcome: Positive pregnancy test per patient
    • No significant differences were found comparing letrozole (24%) to clomiphene citrate (23%)
    • Pooled Relative risk (RR) 1.08 (95% CI, 0.85–1.36)
  • Significant heterogeneity was noted between studies (I2=60.8%, with >30% considered significant)
  • There were also no significant differences in secondary outcomes
    • Clinical pregnancy: Pooled RR 1.15 (95% CI 0.71–1.85)
    • Live birth: Pooled RR 0.94 (95% CI, 0.83–1.08)
    • Spontaneous miscarriage: Pooled RR 0.92 (95% CI, 0.61–1.38)
  • Twin gestation: Pooled RR 0.81 (95% CI, 0.39–1.68)
  • Mean serum E2 was significantly lower in the letrozole group

CONCLUSION:

  • Letrozole does not appear to confer any benefit when compared to clomiphene citrate for ovarian stimulation in women with unexplained infertility
  • The authors acknowledge an important limitation in this study was the high heterogeneity between studies

Learn More – Primary Sources:

Letrozole Compared With Clomiphene Citrate for Unexplained Infertility – A Systematic Review and Meta-analysis

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Related ObG Topics:

Infertility Evaluation: Who, When and How
PCOS: Targeting Treatments to Improve Reproductive Outcomes and Reduce CVD
Cochrane Review: Letrozole vs Clomiphene Citrate for the Treatment of infertility in Women with PCOS

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