Document Type


Original Publication Date


Journal/Book/Conference Title

The New England Journal of Medicine



DOI of Original Publication



Originally Published at

Date of Submission

December 2014



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.

Full Text of Background...


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.

Full Text of Methods...


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

Full Text of Results...


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; number, NCT00719186.)


From The New England Journal of Medicine, Legro, R. S., Btyzski, R. G., Diamond, M. P. et al., Letrozole versus Clomiphene for Infertility in the Polycystic Ovary Syndrome, Vol. 371, Page 119, Copyright © 2014 Massachusetts Medical Society. Reprinted with permission.

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VCU Obstetrics and Gynecology Publications

nejmoa1313517_appendix.pdf (520 kB)
Supplementary Appendix

nejmoa1313517_protocol.pdf (3368 kB)

nejmoa1313517_disclosures.pdf (739 kB)
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