TY - JOUR
T1 - Letrozole versus clomiphene for infertility in the polycystic ovary syndrome
AU - Legro, Richard S.
AU - Brzyski, Robert G.
AU - Diamond, Michael P.
AU - Coutifaris, Christos
AU - Schlaff, William D.
AU - Casson, Peter
AU - Christman, Gregory M.
AU - Huang, Hao
AU - Yan, Qingshang
AU - Alvero, Ruben
AU - Haisenleder, Daniel J.
AU - Barnhart, Kurt T.
AU - Wright Bates, G.
AU - Usadi, Rebecca
AU - Lucidi, Scott
AU - Baker, Valerie
AU - Trussell, J. C.
AU - Krawetz, Stephen A.
AU - Snyder, Peter
AU - Ohl, Dana
AU - Santoro, Nanette
AU - Eisenberg, Esther
AU - Zhang, Heping
N1 - Funding Information:
Supported by grants from the NICHD (U10 HD27049, to Dr. Coutifaris; U10 HD38992, to Dr. Legro; U10HD055925, to Dr. Zhang; U10 HD39005, to Dr. Diamond; U10 HD38998, to Dr. Schlaff; U10 HD055936, to Dr. Christman; U10 HD055942, to Dr. Brzyski; and U10 HD055944, to Dr. Casson; and U54-HD29834, to the University of Virginia Center for Research in Reproduction Ligand Assay and Analysis Core of the Specialized Cooperative Centers Program in Reproduction and Infertility Research); and by the National Center for Research Resources and the National Center for Advancing Translational Sciences through an NIH grant (UL1 TR000127) to Pennsylvania State University.
Funding Information:
Dr. Legro reports receiving consulting fees from Ferring Pharmaceuticals, AstraZeneca, and Euroscreen. Dr. Diamond reports receiving consulting fees from EMD Serono and serving on the board of directors of and owning stock in Advanced Reproductive Care. Dr. Santoro reports receiving grant support from Bayer and holding stock options in MenoGeniX. No other potential conflict of interest relevant to this article was reported.
PY - 2014
Y1 - 2014
N2 - 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.
AB - 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.
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U2 - 10.1056/NEJMoa1313517
DO - 10.1056/NEJMoa1313517
M3 - Article
C2 - 25006718
AN - SCOPUS:84903901465
SN - 0028-4793
VL - 371
SP - 119
EP - 129
JO - New England Journal of Medicine
JF - New England Journal of Medicine
IS - 2
ER -