Letrozole versus Clomiphene for Infertility in the Polycystic Ovary Syndrome
- 10 July 2014
- journal article
- research article
- Published by Massachusetts Medical Society in The New England Journal of Medicine
- Vol. 371 (2), 119-129
- https://doi.org/10.1056/nejmoa1313517
Abstract
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. 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. 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. As compared with clomiphene, letrozole was associated with higher live-birth and ovulation rates among infertile women with the polycystic ovary syndrome. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and others; ClinicalTrials.gov number, NCT00719186.)Keywords
This publication has 22 references indexed in Scilit:
- The Pregnancy in Polycystic Ovary Syndrome II (PPCOS II) trial: Rationale and design of a double-blind randomized trial of clomiphene citrate and letrozole for the treatment of infertility in women with polycystic ovary syndromeContemporary Clinical Trials, 2012
- Endometrial Shedding Effect on Conception and Live Birth in Women With Polycystic Ovary SyndromeObstetrics & Gynecology, 2012
- Anastrozole single-dose protocol in women with oligo- or anovulatory infertility: results of a randomized phase II dose–response studyFertility and Sterility, 2011
- Anastrozole vs. clomiphene citrate in infertile women with ovulatory dysfunction: a phase II, randomized, dose-finding studyFertility and Sterility, 2011
- Differences between the non-steroidal aromatase inhibitors anastrozole and letrozole – of clinical importance?British Journal of Cancer, 2011
- Total Testosterone Assays in Women with Polycystic Ovary Syndrome: Precision and Correlation with HirsutismJournal of Clinical Endocrinology & Metabolism, 2010
- World Health Organization reference values for human semen characteristics*‡Human Reproduction Update, 2009
- Predictors of Pregnancy in Women with Polycystic Ovary SyndromeJournal of Clinical Endocrinology & Metabolism, 2009
- Comparison of clomiphene citrate, metformin, or the combination of both for first-line ovulation induction, achievement of pregnancy, and live birth in Asian women with polycystic ovary syndrome: a randomized controlled trialFertility and Sterility, 2009
- Effect of clomifene citrate plus metformin and clomifene citrate plus placebo on induction of ovulation in women with newly diagnosed polycystic ovary syndrome: randomised double blind clinical trialBMJ, 2006