TY - JOUR
T1 - Letrozole, gonadotropin, or clomiphene for unexplained infertility
AU - Diamond, M. P.
AU - Legro, R. S.
AU - Coutifaris, C.
AU - Alvero, R.
AU - Robinson, R. D.
AU - Casson, P.
AU - Christman, G. M.
AU - Ager, J.
AU - Huang, H.
AU - Hansen, K. R.
AU - Baker, V.
AU - Usadi, R.
AU - Seungdamrong, A.
AU - Bates, G. W.
AU - Rosen, R. M.
AU - Haisenleder, D.
AU - Krawetz, S. A.
AU - Barnhart, K.
AU - Trussell, J. C.
AU - Ohl, D.
AU - Jin, Y.
AU - Santoro, N.
AU - Eisenberg, E.
AU - Zhang, H.
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 - 2015/9/24
Y1 - 2015/9/24
N2 - BACKGROUND: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.METHODS: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.RESULTS: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.CONCLUSIONS: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.)
AB - BACKGROUND: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.METHODS: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.RESULTS: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.CONCLUSIONS: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.)
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U2 - 10.1056/NEJMoa1313517
DO - 10.1056/NEJMoa1313517
M3 - Article
C2 - 25006718
AN - SCOPUS:84903901465
SN - 0028-4793
VL - 373
SP - 1230
EP - 1240
JO - New England Journal of Medicine
JF - New England Journal of Medicine
IS - 13
ER -