Letrozole versus clomiphene for infertility in the polycystic ovary syndrome

Richard S. Legro, Robert G. Brzyski, Michael P. Diamond, Christos Coutifaris, William D. Schlaff, Peter Casson, Gregory M. Christman, Hao Huang, Qingshang Yan, Ruben Alvero, Daniel J. Haisenleder, Kurt T. Barnhart, G. Wright Bates, Rebecca Usadi, Scott Lucidi, Valerie Baker, J. C. Trussell, Stephen A. Krawetz, Peter Snyder, Dana OhlNanette Santoro, Esther Eisenberg, Heping Zhang

Research output: Contribution to journalArticle

Abstract

BACKGROUND: Clomiphene is the current first-line infertility treatment in women with the polycystic ovary syndrome, but aromatase inhibitors, including letrozole, might result in better pregnancy outcomes. METHODS: In this double-blind, multicenter trial, we randomly assigned 750 women, in a 1:1 ratio, to receive letrozole or clomiphene for up to five treatment cycles, with visits to determine ovulation and pregnancy, followed by tracking of pregnancies. The polycystic ovary syndrome was defined according to modified Rotterdam criteria (anovulation with either hyperandrogenism or polycystic ovaries). Participants were 18 to 40 years of age, had at least one patent fallopian tube and a normal uterine cavity, and had a male partner with a sperm concentration of at least 14 million per milliliter; the women and their partners agreed to have regular intercourse with the intent of conception during the study. The primary outcome was live birth during the treatment period. RESULTS: Women who received letrozole had more cumulative live births than those who received clomiphene (103 of 374 [27.5%] vs. 72 of 376 [19.1%], P=0.007; rate ratio for live birth, 1.44; 95% confidence interval, 1.10 to 1.87) without significant differences in overall congenital anomalies, though there were four major congenital anomalies in the letrozole group versus one in the clomiphene group (P=0.65). The cumulative ovulation rate was higher with letrozole than with clomiphene (834 of 1352 treatment cycles [61.7%] vs. 688 of 1425 treatment cycles [48.3%], P<0.001). There were no significant between-group differences in pregnancy loss (49 of 154 pregnancies in the letrozole group [31.8%] and 30 of 103 pregnancies in the clomiphene group [29.1%]) or twin pregnancy (3.4% and 7.4%, respectively). Clomiphene was associated with a higher incidence of hot flushes, and letrozole was associated with higher incidences of fatigue and dizziness. Rates of other adverse events were similar in the two treatment groups. CONCLUSIONS: As compared with clomiphene, letrozole was associated with higher live-birth and ovulation rates among infertile women with the polycystic ovary syndrome.

Original languageEnglish (US)
Pages (from-to)119-129
Number of pages11
JournalNew England Journal of Medicine
Volume371
Issue number2
DOIs
StatePublished - 2014

ASJC Scopus subject areas

  • Medicine(all)

Fingerprint Dive into the research topics of 'Letrozole versus clomiphene for infertility in the polycystic ovary syndrome'. Together they form a unique fingerprint.

  • Cite this

    Legro, R. S., Brzyski, R. G., Diamond, M. P., Coutifaris, C., Schlaff, W. D., Casson, P., Christman, G. M., Huang, H., Yan, Q., Alvero, R., Haisenleder, D. J., Barnhart, K. T., Wright Bates, G., Usadi, R., Lucidi, S., Baker, V., Trussell, J. C., Krawetz, S. A., Snyder, P., ... Zhang, H. (2014). Letrozole versus clomiphene for infertility in the polycystic ovary syndrome. New England Journal of Medicine, 371(2), 119-129. https://doi.org/10.1056/NEJMoa1313517