Michael P Diamond1, Richard S Legro2, Christos Coutifaris3, Ruben Alvero4, Randal D Robinson5, Peter Casson6, Gregory M Christman7, Joel Ager8, Hao Huang9, Karl R Hansen10, Valerie Baker11, Rebecca Usadi12, Aimee Seungdamrong13, G Wright Bates14, R Mitchell Rosen15, Daniel Haisonleder16, Stephen A Krawetz8, Kurt Barnhart3, J C Trussell17, Yufeng Jin9, Nanette Santoro4, Esther Eisenberg18, Heping Zhang9. 1. Department of Obstetrics and Gynecology, Georgia Regents University, Augusta, Georgia; Department of Obstetrics and Gynecology, Wayne State University, Detroit, Michigan. Electronic address: Michael.Diamond@gru.edu. 2. Department of Obstetrics and Gynecology, Pennsylvania State University, Hershey, Pennsylvania. 3. Department of Obstetrics and Gynecology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania. 4. Department of Obstetrics and Gynecology, University of Colorado, Denver, Colorado. 5. Department of Obstetrics and Gynecology, University of Texas Health Science Center at San Antonio, San Antonio, Texas. 6. Department of Obstetrics and Gynecology, University of Vermont, Burlington, Vermont. 7. Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, Michigan. 8. Department of Obstetrics and Gynecology, Wayne State University, Detroit, Michigan. 9. Department of Biostatistics, Yale University School of Public Health, New Haven, Connecticut. 10. Department of Obstetrics and Gynecology, University of Oklahoma College of Medicine, Oklahoma City, Oklahoma. 11. Stanford University Medical Center, Stanford, California. 12. Carolinas Medical Center, Charlotte, North Carolina. 13. New Jersey Medical School - University of Medicine and Dentistry of New Jersey, Rutgers, New Jersey. 14. University of Alabama Birmingham, Birmingham, Alabama. 15. Department of Reproductive Endocrinology and Infertility, University of California, San Francisco, California. 16. Ligand Core Laboratory University of Virginia Center for Research in Reproduction, Charlottesville, Virginia. 17. Upstate University Hospital, Syracuse, New York. 18. Fertility and Infertility Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Rockville, Maryland.
Abstract
OBJECTIVE: To identify baseline characteristics of women with unexplained infertility to determine whether treatment with an aromatase inhibitor will result in a lower rate of multiple gestations than current standard ovulation induction medications. DESIGN: Randomized, prospective clinical trial. SETTING: Multicenter university-based clinical practices. PATIENT(S): A total of 900 couples with unexplained infertility. INTERVENTION(S): Collection of baseline demographics, blood samples, and ultrasonographic assessments. MAIN OUTCOME MEASURE(S): Demographic, laboratory, imaging, and survey characteristics. RESULT(S): Demographic characteristics of women receivingclomiphene citrate (CC), letrozole, or gonadotropins for ovarian stimulation were very consistent. Their mean age was 32.2 ± 4.4 years and infertility duration was 34.7 ± 25.7 months, with 59% primary infertility. More than one-third of the women were current or past smokers. The mean body mass index (BMI) was 27 and mean antimüllerian hormone level was 2.6; only 11 women (1.3%) had antral follicle counts of <5. Similar observations were identified for hormonal profiles, ultrasound characterization of the ovaries, semen parameters, and quality of life assessments in both male and female partners. CONCLUSION(S): The cause of infertility in the couples recruited to this treatment trial is elusive, as the women were regularly ovulating and had evidence of good ovarian reserve both by basal FSH, antimüllerian hormone levels, and antral follicle counts; the male partners had normal semen parameters. The three treatment groups have common baseline characteristics, thereby providing comparable patient populations for testing the hypothesis that use of letrozole for ovarian stimulation can reduce the rates of multiples from that observed with gonadotropin and CC treatment. CLINICAL TRIAL REGISTRATION NUMBER: NCT 01044862.
RCT Entities:
OBJECTIVE: To identify baseline characteristics of women with unexplained infertility to determine whether treatment with an aromatase inhibitor will result in a lower rate of multiple gestations than current standard ovulation induction medications. DESIGN: Randomized, prospective clinical trial. SETTING: Multicenter university-based clinical practices. PATIENT(S): A total of 900 couples with unexplained infertility. INTERVENTION(S): Collection of baseline demographics, blood samples, and ultrasonographic assessments. MAIN OUTCOME MEASURE(S): Demographic, laboratory, imaging, and survey characteristics. RESULT(S): Demographic characteristics of women receiving clomiphene citrate (CC), letrozole, or gonadotropins for ovarian stimulation were very consistent. Their mean age was 32.2 ± 4.4 years and infertility duration was 34.7 ± 25.7 months, with 59% primary infertility. More than one-third of the women were current or past smokers. The mean body mass index (BMI) was 27 and mean antimüllerian hormone level was 2.6; only 11 women (1.3%) had antral follicle counts of <5. Similar observations were identified for hormonal profiles, ultrasound characterization of the ovaries, semen parameters, and quality of life assessments in both male and female partners. CONCLUSION(S): The cause of infertility in the couples recruited to this treatment trial is elusive, as the women were regularly ovulating and had evidence of good ovarian reserve both by basal FSH, antimüllerian hormone levels, and antral follicle counts; the male partners had normal semen parameters. The three treatment groups have common baseline characteristics, thereby providing comparable patient populations for testing the hypothesis that use of letrozole for ovarian stimulation can reduce the rates of multiples from that observed with gonadotropin and CC treatment. CLINICAL TRIAL REGISTRATION NUMBER: NCT 01044862.
Authors: Richard S Legro; Robert G Brzyski; Michael P Diamond; Christos Coutifaris; William D Schlaff; Ruben Alvero; Peter Casson; Gregory M Christman; Hao Huang; Qingshang Yan; Daniel J Haisenleder; Kurt T Barnhart; G Wright Bates; Rebecca Usadi; Richard Lucidi; Valerie Baker; J C Trussell; Stephen A Krawetz; Peter Snyder; Dana Ohl; Nanette Santoro; Esther Eisenberg; Heping Zhang Journal: Fertil Steril Date: 2013-10-21 Impact factor: 7.329
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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: R Matthew Coward; Christy Stetter; Allen Kunselman; J C Trussell; Mark C Lindgren; Ruben R Alvero; Peter Casson; Gregory M Christman; Christos Coutifaris; Michael P Diamond; Karl R Hansen; Stephen A Krawetz; Richard S Legro; Randal D Robinson; James F Smith; Anne Z Steiner; Robert A Wild; Heping Zhang; Nanette Santoro Journal: J Urol Date: 2019-07-08 Impact factor: 7.450
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: Nanette Santoro; Esther Eisenberg; J C Trussell; LaTasha B Craig; Clarisa Gracia; Hao Huang; Ruben Alvero; Peter Casson; Gregory Christman; Christos Coutifaris; Michael Diamond; Susan Jin; Richard S Legro; Randal D Robinson; William D Schlaff; Heping Zhang Journal: Hum Reprod Date: 2016-07-07 Impact factor: 6.918
Authors: Michael P Diamond; Richard S Legro; Christos Coutifaris; Ruben Alvero; Randal D Robinson; Peter Casson; Gregory M Christman; Joel Ager; Hao Huang; Karl R Hansen; Valerie Baker; Rebecca Usadi; Aimee Seungdamrong; G Wright Bates; R Mitchell Rosen; Daniel Haisenleder; Stephen A Krawetz; Kurt Barnhart; J C Trussell; Dana Ohl; Yufeng Jin; Nanette Santoro; Esther Eisenberg; Heping Zhang Journal: N Engl J Med Date: 2015-09-24 Impact factor: 91.245
Authors: Richard S Legro; Michael P Diamond; Christos Coutifaris; William D Schlaff; Ruben Alvero; Peter Casson; Gregory M Christman; R Mitchell Rosen; Marcelle I Cedars; Karl R Hansen; Randal Robinson; Valerie Baker; Rebecca Usadi; William C Dodson; Stephanie J Estes; Allen Kunselman; Christina Stetter; Kurt T Barnhart; R Matthew Coward; J C Trussell; Stephen A Krawetz; Nanette Santoro; Hao Huang; Heping Zhang; Esther Eisenberg Journal: Fertil Steril Date: 2020-05 Impact factor: 7.329
Authors: Karl R Hansen; Esther Eisenberg; Valerie Baker; Micah J Hill; Sixia Chen; Sara Talken; Michael P Diamond; Richard S Legro; Christos Coutifaris; Ruben Alvero; Randal D Robinson; Peter Casson; Gregory M Christman; Nanette Santoro; Heping Zhang; Robert A Wild Journal: J Clin Endocrinol Metab Date: 2018-07-01 Impact factor: 5.958
Authors: Erica T Wang; Michael P Diamond; Ruben Alvero; Peter Casson; Gregory M Christman; Christos Coutifaris; Karl R Hansen; Fangbai Sun; Richard S Legro; Randal D Robinson; Rebecca S Usadi; Margareta D Pisarska; Nanette F Santoro; Heping Zhang Journal: Fertil Steril Date: 2020-03 Impact factor: 7.329