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 receiveletrozole 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.).
RCT Entities:
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: Richard S Legro; Allen R Kunselman; Robert G Brzyski; Peter R Casson; Michael P Diamond; William D Schlaff; Gregory M Christman; Christos Coutifaris; Hugh S Taylor; Esther Eisenberg; Nanette Santoro; Heping Zhang Journal: Contemp Clin Trials Date: 2012-01-13 Impact factor: 2.226
Authors: Marie L Misso; Jennifer L A Wong; Helena J Teede; Roger Hart; Luk Rombauts; Angela M Melder; Robert J Norman; Michael F Costello Journal: Hum Reprod Update Date: 2012-03-19 Impact factor: 15.610
Authors: Laure Morin-Papunen; Anni S Rantala; Leila Unkila-Kallio; Aila Tiitinen; Maritta Hippeläinen; Antti Perheentupa; Helena Tinkanen; Risto Bloigu; Katri Puukka; Aimo Ruokonen; Juha S Tapanainen Journal: J Clin Endocrinol Metab Date: 2012-03-14 Impact factor: 5.958
Authors: Michael P Diamond; Michael Kruger; Nanette Santoro; Heping Zhang; Peter Casson; William Schlaff; Christos Coutifaris; Robert Brzyski; Gregory Christman; Bruce R Carr; Peter G McGovern; Nicholas A Cataldo; Michael P Steinkampf; Gabriella G Gosman; John E Nestler; Sandra Carson; Evan E Myers; Esther Eisenberg; Richard S Legro Journal: Obstet Gynecol Date: 2012-05 Impact factor: 7.661
Authors: Richard S Legro; William D Schlaff; Michael P Diamond; Christos Coutifaris; Peter R Casson; Robert G Brzyski; Gregory M Christman; J C Trussell; Stephen A Krawetz; Peter J Snyder; Dana Ohl; Sandra A Carson; Michael P Steinkampf; Bruce R Carr; Peter G McGovern; Nicholas A Cataldo; Gabriella G Gosman; John E Nestler; Evan R Myers; Nanette Santoro; Esther Eisenberg; Meizhuo Zhang; Heping Zhang Journal: J Clin Endocrinol Metab Date: 2010-09-08 Impact factor: 5.958
Authors: Trevor G Cooper; Elizabeth Noonan; Sigrid von Eckardstein; Jacques Auger; H W Gordon Baker; Hermann M Behre; Trine B Haugen; Thinus Kruger; Christina Wang; Michael T Mbizvo; Kirsten M Vogelsong Journal: Hum Reprod Update Date: 2009-11-24 Impact factor: 15.610
Authors: Michael P Diamond; Richard S Legro; Christos Coutifaris; Ruben Alvero; Randal D Robinson; Peter A Casson; Gregory M Christman; Hao Huang; Karl R Hansen; Valerie Baker; Rebecca Usadi; Aimee Seungdamrong; G Wright Bates; R Mitchell Rosen; William Schlaff; Daniel Haisenleder; Stephen A Krawetz; Kurt Barnhart; J C Trussell; Nanette Santoro; Esther Eisenberg; Heping Zhang Journal: Am J Obstet Gynecol Date: 2017-04-26 Impact factor: 8.661
Authors: Hao Huang; Hongying Kuang; Fangbai Sun; Michael P Diamond; Richard S Legro; Christos Coutifaris; Ruben Alvero; Randal D Robinson; Peter R Casson; Gregory M Christman; Karl R Hansen; Nanette Santoro; Esther Eisenberg; Heping Zhang Journal: Fertil Steril Date: 2019-03-27 Impact factor: 7.329
Authors: Mindy S Christianson; Richard S Legro; Susan Jin; Esther Eisenberg; Michael P Diamond; Karl R Hansen; Wendy Vitek; Aaron K Styer; Peter Casson; Christos Coutifaris; Gregory M Christman; Ruben Alvero; Elizabeth E Puscheck; Alicia Y Christy; Fangbai Sun; Heping Zhang; Alex J Polotsky; Nanette Santoro Journal: J Assist Reprod Genet Date: 2018-09-07 Impact factor: 3.412
Authors: Rebecca S Usadi; Michael P Diamond; Richard S Legro; William D Schlaff; Karl R Hansen; Peter Casson; Gregory Christman; G Wright Bates; Valerie Baker; Aimee Seungdamrong; Mitchell P Rosen; Scott Lucidi; Tracey Thomas; Hao Huang; Nanette Santoro; Esther Eisenberg; Heping Zhang; Ruben Alvero Journal: Contemp Clin Trials Date: 2015-09-18 Impact factor: 2.226