Letrozole, Gonadotropin, or Clomiphene for Unexplained Infertility
- 24 September 2015
- journal article
- research article
- Published by Massachusetts Medical Society in The New England Journal of Medicine
- Vol. 373 (13), 1230-1240
- https://doi.org/10.1056/nejmoa1414827
Abstract
The standard therapy for women with unexplained infertility is gonadotropin or clomiphene citrate. Ovarian stimulation with letrozole has been proposed to reduce multiple gestations while maintaining live birth rates. We enrolled couples with unexplained infertility in a multicenter, randomized trial. Ovulatory women 18 to 40 years of age with at least one patent fallopian tube were randomly assigned to ovarian stimulation (up to four cycles) with gonadotropin (301 women), clomiphene (300), or letrozole (299). The primary outcome was the rate of multiple gestations among women with clinical pregnancies. After treatment with gonadotropin, clomiphene, or letrozole, clinical pregnancies occurred in 35.5%, 28.3%, and 22.4% of cycles, and live birth in 32.2%, 23.3%, and 18.7%, respectively; pregnancy rates with letrozole were significantly lower than the rates with standard therapy (gonadotropin or clomiphene) (P=0.003) or gonadotropin alone (P<0.001) but not with clomiphene alone (P=0.10). Among ongoing pregnancies with fetal heart activity, the multiple gestation rate with letrozole (9 of 67 pregnancies, 13%) did not differ significantly from the rate with gonadotropin or clomiphene (42 of 192, 22%; P=0.15) or clomiphene alone (8 of 85, 9%; P=0.44) but was lower than the rate with gonadotropin alone (34 of 107, 32%; P=0.006). All multiple gestations in the clomiphene and letrozole groups were twins, whereas gonadotropin treatment resulted in 24 twin and 10 triplet gestations. There were no significant differences among groups in the frequencies of congenital anomalies or major fetal and neonatal complications. In women with unexplained infertility, ovarian stimulation with letrozole resulted in a significantly lower frequency of multiple gestation but also a lower frequency of live birth, as compared with gonadotropin but not as compared with clomiphene. (Funded by the National Institutes of Health and others; ClinicalTrials.gov number, NCT01044862.)Keywords
This publication has 25 references indexed in Scilit:
- Extended letrozole regimen versus clomiphene citrate for superovulation in patients with unexplained infertility undergoing intrauterine insemination: A randomized controlled trialReproductive Biology and Endocrinology, 2011
- Estimation of the Contribution of Non–Assisted Reproductive Technology Ovulation Stimulation Fertility Treatments to US Singleton and Multiple BirthsAmerican Journal of Epidemiology, 2009
- Randomized controlled trial comparing superovulation with letrozole versus recombinant follicle-stimulating hormone combined with intrauterine insemination for couples with unexplained infertility who had failed clomiphene citrate stimulation and intrauterine inseminationFertility and Sterility, 2008
- Relationship between follicle number and (multiple) live birth rate after controlled ovarian hyperstimulation and intrauterine inseminationAmerican Journal of Obstetrics and Gynecology, 2007
- A comparison of letrozole to gonadotropins for ovulation induction, in subjects who failed to conceive with clomiphene citrateFertility and Sterility, 2007
- Congenital malformations among 911 newborns conceived after infertility treatment with letrozole or clomiphene citrateFertility and Sterility, 2006
- Letrozole vs. clomiphene citrate in patients with ovulatory infertilityFertility and Sterility, 2006
- A randomized trial of superovulation with two different doses of letrozoleFertility and Sterility, 2006
- A randomized trial of letrozole versus clomiphene citrate in women undergoing superovulationFertility and Sterility, 2004
- Efficacy of Superovulation and Intrauterine Insemination in the Treatment of InfertilityThe New England Journal of Medicine, 1999