title: Letrozole versus clomiphene for infertility in the polycystic ovary syndrome.
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. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and others; ClinicalTrials.gov number, NCT00719186.).
authors.affiliation: The authors' affiliations are listed in the Appendix.
authors.forename: Richard S
authors.initials: RS
authors.lastname: Legro
authors.forename: Robert G
authors.initials: RG
authors.lastname: Brzyski
authors.forename: Michael P
authors.initials: MP
authors.lastname: Diamond
authors.forename: Christos
authors.initials: C
authors.lastname: Coutifaris
authors.forename: William D
authors.initials: WD
authors.lastname: Schlaff
authors.forename: Peter
authors.initials: P
authors.lastname: Casson
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Christman
authors.forename: Hao
authors.initials: H
authors.lastname: Huang
authors.forename: Qingshang
authors.initials: Q
authors.lastname: Yan
authors.forename: Ruben
authors.initials: R
authors.lastname: Alvero
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Haisenleder
authors.forename: Kurt T
authors.initials: KT
authors.lastname: Barnhart
authors.forename: G Wright
authors.initials: GW
authors.lastname: Bates
authors.forename: Rebecca
authors.initials: R
authors.lastname: Usadi
authors.forename: Scott
authors.initials: S
authors.lastname: Lucidi
authors.forename: Valerie
authors.initials: V
authors.lastname: Baker
authors.forename: J C
authors.initials: JC
authors.lastname: Trussell
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Krawetz
authors.forename: Peter
authors.initials: P
authors.lastname: Snyder
authors.forename: Dana
authors.initials: D
authors.lastname: Ohl
authors.forename: Nanette
authors.initials: N
authors.lastname: Santoro
authors.forename: Esther
authors.initials: E
authors.lastname: Eisenberg
authors.forename: Heping
authors.initials: H
authors.lastname: Zhang
mesh_terms: D000328:Adult; D002996:Clomiphene / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D005300:Fertility Agents, Female / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D007247:Infertility, Female / Q000188:drug therapy* / Q000209:etiology; D053208:Kaplan-Meier Estimate; D000077289:Letrozole; D050498:Live Birth; D008183:Luteal Phase; D008297:Male; D009570:Nitriles / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D010060:Ovulation / Q000187:drug effects; D011085:Polycystic Ovary Syndrome / Q000150:complications*; D011247:Pregnancy; D011788:Quality of Life; D014230:Triazoles / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D005300:Fertility Agents, Female; D009570:Nitriles; D014230:Triazoles; D002996:Clomiphene; D000077289:Letrozole