Letrozole versus Clomiphene for Infertility in the Polycystic Ovary Syndrome

• Published in: The New England journal of medicine Vol. 371; no. 2; pp. 119 - 129
• Main Authors: Legro, Richard S, Brzyski, Robert G, Diamond, Michael P, Coutifaris, Christos, Schlaff, William D, Casson, Peter, Christman, Gregory M, Huang, Hao, Yan, Qingshang, Alvero, Ruben, Haisenleder, Daniel J, Barnhart, Kurt T, Bates, G. Wright, Usadi, Rebecca, Lucidi, Scott, Baker, Valerie, Trussell, J.C, Krawetz, Stephen A, Snyder, Peter, Ohl, Dana, Santoro, Nanette, Eisenberg, Esther, Zhang, Heping
• Format: Journal Article
• Language: English
• Published: United States Massachusetts Medical Society 10-07-2014
• Subjects: Adult; Aromatase; Clomiphene; Clomiphene - adverse effects; Clomiphene - pharmacology; Clomiphene - therapeutic use; Congenital defects; Double-Blind Method; Fallopian tube; Fatigue; Female; Fertility Agents, Female - adverse effects; Fertility Agents, Female - pharmacology; Fertility Agents, Female - therapeutic use; Humans; Infertility; Infertility, Female - drug therapy; Infertility, Female - etiology; Kaplan-Meier Estimate; Letrozole; Live Birth; Luteal Phase; Male; Nitriles - adverse effects; Nitriles - pharmacology; Nitriles - therapeutic use; Ovaries; Ovulation; Ovulation - drug effects; Polycystic ovary syndrome; Polycystic Ovary Syndrome - complications; Pregnancy; Quality of Life; Reproductive health; Triazoles - adverse effects; Triazoles - pharmacology; Triazoles - therapeutic use; Uterus; Womens health
• ISSN: 0028-4793; 1533-4406
• DOI: 10.1056/NEJMoa1313517

This double-blind, multicenter, randomized trial showed that letrozole, as compared with clomiphene, was associated with higher live-birth and ovulation rates among infertile women with the polycystic ovary syndrome.
The polycystic ovary syndrome, which is diagnosed on the basis of hyperandrogenism, oligo-ovulation with associated oligomenorrhea, and polycystic ovaries on ultrasonography, affects 5 to 10% of reproductive-age women and is the most common cause of anovulatory infertility.
1
Although the syndrome is a complex reproductive–metabolic disorder, the hypothalamic–pituitary axis has been the target of first-line ovulation-induction therapy. Clomiphene citrate, a selective estrogen-receptor modulator that antagonizes the negative feedback of estrogen at the hypothalamus with a consequent increase in ovarian stimulation by endogenous gonadotropin, has been used for this indication for decades.
Clomiphene has drawbacks, including its overall poor efficacy (only a . . .