Letrozole compared with clomiphene citrate for unexplained infertility: A systematic review and meta-analysis

Ashley M. Eskew*, Bronwyn S. Bedrick, Angela Hardi, Carolyn R.T. Stoll, Graham A. Colditz, Methodius G. Tuuli, Emily S. Jungheim

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

12 Scopus citations


OBJECTIVE:To estimate the clinical effectiveness, as determined by positive pregnancy test, of letrozole compared with clomiphene citrate for ovarian stimulation in patients with unexplained infertility.DATA SOURCES:We conducted a systematic review and meta-analysis of data from electronic databases including Ovid-MEDLINE, EMBASE, Scopus, Cochrane Database of Systematic Reviews, Cochrane Register of Controlled Trials, Database of Abstracts of Reviews of Effects, and ClinicalTrials.gov.METHODS:We searched for concepts of unexplained infertility, letrozole, clomiphene citrate, and clinical outcomes including pregnancy and live birth. Studies were included if they were randomized controlled trials (RCTs) comparing clomiphene citrate with letrozole in patients with unexplained infertility. Eight RCTs including 2,647 patients with unexplained infertility were included. Primary outcome was positive pregnancy test per patient. Secondary outcomes included positive pregnancy test per cycle, clinical pregnancy, live birth, spontaneous miscarriage, twin gestation, mean serum estradiol (E2), endometrial thickness, and number of dominant follicles. The Cochrane Q test and Higgin's I2 were used to assess heterogeneity. Random effects models were used to obtain pooled relative risks (RR) and 95% CIs.TABULATION, INTEGRATION, AND RESULTS:In analysis per patient, there was no significant difference in positive pregnancy test between patients treated with letrozole compared with clomiphene citrate (24% vs 23%, pooled RR 1.08, 95% CI 0.85-1.36). Significant heterogeneity was noted between studies (I2=60.8%). There were no significant differences in 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), or twin gestation (pooled RR 0.81, 95% CI 0.39-1.68). Mean serum E2 was significantly lower in the letrozole group than in the clomiphene citrate group.CONCLUSION:Although limited by heterogeneity, studies of ovarian stimulation in women with unexplained infertility show no difference in clinical outcomes between letrozole and clomiphene citrate.

Original languageEnglish (US)
Pages (from-to)437-444
Number of pages8
JournalObstetrics and gynecology
Issue number3
StatePublished - Mar 1 2019
Externally publishedYes

ASJC Scopus subject areas

  • Obstetrics and Gynecology


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