Male infertility is a common and devastating problem, and the prevalence is increasing, much of which is related to obesity. However, non-Assisted Reproductive Technology (ART) treatment remains rudimentary and poorly studied. In Vitro Fertilization with intracytoplasmic sperm injection (IVF/ICSI), while effective, is expensive, emotionally traumatizing, and may carry significant potential risks. Empiric medical treatment (EMT) treatment with either clomiphene citrate (CC;a selective estrogen receptor modulator) or letrozole (an aromatase inhibitor) in men with oligospermia has been advocated;both act by decreasing estrogen negative feedback on the hypothalamic-pituitary axis. Letrozole may offer additional benefit to obese men by blocking peripheral androgen aromatization to estradiol. Despite prevalent use, a paucity of data exists as to efficacy of EMT, particularly in regards to live birth rates. We hypothesize that when used in conjunction with controlled ovulation induction (COI)/intrauterine insemination (lUl), EMT represents effective therapy. Our overarching hypothesis is that an eight-month course of EMT and four consecutive COH/IUIs in men with non-obstructive oligo-asthenospermia and infertility will significantly improve live birth rates. We propose an 8 month three-arm (clomiphene, letrozole, placebo) randomized study design to determine if EMT significantly improves live birth pregnancy outcomes in couples with non-obstructive male infertility We also will determine if letrozole works better in obese men independent of risk factors for metabolic syndrome. If our overall hypothesis is true then the combination of EMT and COH/IUIs may represent a cost effective and efficacious treatment for idiopathic oligospermia, especially as it pertains to obesity. If we show letrozole is the most effective therapy in obese men, this will further inform future therapeutic interventions. If the letrozole effect is independent of metabolic syndrome status, the etiology of obesity-related male factor is clarified. The potential benefits of this therapy are enormous: 1) reduced healthcare cost;2) improved pregnancy outcomes;and 3) improved quality of life for previously infertile couples.

Public Health Relevance

Effective non IVF treatment of the increasing problem of idiopathic oligospermia will reduce health care costs, allow for couples with limited means to have a family, and reduce the adverse pregnancy out comes associated with IVF/ICSI. Unequivocal demonstration of efficacy of clomiphene, and particularly letrozole offers new insights into the cause of this devastating and increasingly prevalent problem.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Cooperative Clinical Research--Cooperative Agreements (U10)
Project #
2U10HD055944-06
Application #
8588703
Study Section
Special Emphasis Panel (ZHD1-DSR-L (55))
Program Officer
De Paolo, Louis V
Project Start
2007-08-24
Project End
2015-06-30
Budget Start
2013-09-24
Budget End
2014-06-30
Support Year
6
Fiscal Year
2013
Total Cost
$15,250
Indirect Cost
$48,995
Name
University of Vermont & St Agric College
Department
Obstetrics & Gynecology
Type
Schools of Medicine
DUNS #
066811191
City
Burlington
State
VT
Country
United States
Zip Code
05405
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