The University of Colorado is uniquely positioned to be an active and valuable unit in the Cooperative Reproductive Medicine Network (RMN) of the NICHD. This proposal takes advantage of our extensive experience in clinical protocol development and a highly successful record as effective contributors to many large multicenter trials including the existing RMN since 2000. The geographic and population diversity represented by our location as one of the very few academic reproductive medicine centers in the Rocky Mountain region is an additional important asset that we bring to the RMN. Our concept proposal is entitled """"""""Male Obesity Hypothesis for Infertility: Treatment Options"""""""". Male obesity reduces fertility regardless of the body mass of the female partner. Observational studies have clearly demonstrated that obese men exhibit a compromise in reproductive hormones and semen parameters. A gap in knowledge exists as no clinical trials have been conducted to address treatments for obesity-related male Infertility. Use of aromatase inhibitors in men leads to improvement of compromised sperm parameters and reproductive hormones but pregnancy data is sparse. The central hypothesis of this proposal is that an abnormal endocrine milieu found in obese infertile men negatively impacts reproductive function and can be reversed with aromatase inhibitors. We seek to conduct a multi-center, randomized, double-blind, placebo-controlled trial of an aromatase inhibitor, letrozole, in infertile obese men. Guide by available observational data, this hypothesis will be tested by pursuing three specific aims: 1) To compare the efficacy of an aromatase inhibitor, letrozole, to placebo for the treatment of subfertility in obese men, using live birth as the primary outcome and clinical pregnancy as the secondary outcome;2) To determine which prospective parameters characterize response to letrozole;and 3) To determine if dietary lipid intake (assessed by red blood cell membrane fatty acid composition) is associated with success of fertility treatment in obese men. The mechanistic approach aimed at correcting the underlying hormonal imbalance represents a novel therapeutic strategy and we shall attempt to further correlate attributes of the treated males with metabolic outcomes of their offspring.
The proposed research is relevant to public health because obesity is increasingly one of the most significant sources of morbidity in the United States. Discoveries made in this study may yield insights that will benefit other areas of obesity research, particularly those having to do with diet and hormonal interactions. This project will advance the goal of ameliorating the impact of obesity on human health.
|Greenwood, Eleni A; Pasch, Lauri A; Cedars, Marcelle I et al. (2018) Insulin resistance is associated with depression risk in polycystic ovary syndrome. Fertil Steril 110:27-34|
|Evans-Hoeker, Emily A; Eisenberg, Esther; Diamond, Michael P et al. (2018) Major depression, antidepressant use, and male and female fertility. Fertil Steril 109:879-887|
|Hansen, Karl R; Eisenberg, Esther; Baker, Valerie et al. (2018) Midluteal Progesterone: A Marker of Treatment Outcomes in Couples With Unexplained Infertility. J Clin Endocrinol Metab 103:2743-2751|
|Kent, James; Dodson, William C; Kunselman, Allen et al. (2018) Gestational Weight Gain in Women With Polycystic Ovary Syndrome: A Controlled Study. J Clin Endocrinol Metab 103:4315-4323|
|Diamond, Michael P; Legro, Richard S; Coutifaris, Christos et al. (2017) Sexual function in infertile women with polycystic ovary syndrome and unexplained infertility. Am J Obstet Gynecol 217:191.e1-191.e19|
|Engmann, Lawrence; Jin, Susan; Sun, Fangbai et al. (2017) Racial and ethnic differences in the polycystic ovary syndrome metabolic phenotype. Am J Obstet Gynecol 216:493.e1-493.e13|
|Legro, Richard S; Dodson, William C; Kunselman, Allen R et al. (2016) Benefit of Delayed Fertility Therapy With Preconception Weight Loss Over Immediate Therapy in Obese Women With PCOS. J Clin Endocrinol Metab 101:2658-66|
|Mumford, Sunni L; Legro, Richard S; Diamond, Michael P et al. (2016) Baseline AMH Level Associated With Ovulation Following Ovulation Induction in Women With Polycystic Ovary Syndrome. J Clin Endocrinol Metab 101:3288-96|
|Pal, Lubna; Zhang, Heping; Williams, Joanne et al. (2016) Vitamin D Status Relates to Reproductive Outcome in Women With Polycystic Ovary Syndrome: Secondary Analysis of a Multicenter Randomized Controlled Trial. J Clin Endocrinol Metab 101:3027-35|
|Hansen, Karl R; He, Amy Linnea W; Styer, Aaron K et al. (2016) Predictors of pregnancy and live-birth in couples with unexplained infertility after ovarian stimulation-intrauterine insemination. Fertil Steril 105:1575-1583.e2|
Showing the most recent 10 out of 43 publications