The Utility of Empiric Medical Treatment of Infertile Oligo-asthenospermic Men

经验性药物治疗对不育少弱精子症男性的效用

基本信息

批准号：
8588703
负责人：
ELIZABETH A MCGEE
金额：
$ 1.53万
依托单位：
UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-08-24 至 2015-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8588703
关键词：
Advocate Alabama American Androgens Aromatase Inhibitors Birth Rate Child Child health care Climate Clinic Clinical Clinical Trials Network Clomiphene Clomiphene Citrate Collaborations Colorado Couples Cultural Diversity Data Data Coordinating Center Development Ensure Environment Estradiol Estrogens Ethics Etiology Exhibits Family Feedback Fertilization in Vitro Funding Future Goals Health Care Costs Human Development Infertility Institutes Intracytoplasmic Sperm Injections Joints Letrozole Live Birth Male Infertility Manuscripts Measures Medical Medicine Mentors Mentorship Metabolic syndrome Michigan Mission National Institute of Child Health and Human Development Nature Neonatal New York City Obesity Oligonucleotides Oligospermia Ovarian Stimulations Ovulation Induction Paper Pennsylvania Performance Peripheral Placebos Pregnancy Pregnancy Outcome Prevalence Production Productivity Protocols documentation Publishing Quality of life Randomized Randomized Controlled Trials Recording of previous events Recovery Registries Reproductive Medicine Reproductive Technology Research Research Design Research Personnel Resources Risk Risk Factors Sampling Scientist Selective Estrogen Receptor Modulators Sister Site Societies Specimen Structure Texas Therapeutic Intervention Translations Universities Vermont Work abstracting arm asthenospermia clinical care clinical research site college cost effective design effective therapy evidence base hypothalamic pituitary axis improved innovation insight interest intrauterine insemination male member men next generation patient population programs public health relevance racial/ethnic difference repository socioeconomics success

项目摘要

DESCRIPTION (provided by applicant): 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.

描述（由申请人提供）：男性不孕症是一个常见且破坏性的问题，并且患病率正在增加，其中很多与肥胖有关。但是，非辅助生殖技术（ART）处理仍然是基本的，研究不足。胞质内精子注射（IVF/ICSI）的体外受精虽然有效，但昂贵，在情感上创伤，并可能带来明显的潜在风险。已经提倡对寡素的男性中的柠檬酸克罗米芬（CC；选择性雌激素受体调节剂）或letrozole（一种选择性的雌激素受体调节剂）或letrozole的经验医学治疗（EMT）治疗。两者都通过减少下丘脑 - 垂体轴的雌激素负反馈来起作用。 letrozole可以通过将周围雄激素芳香化与雌二醇阻塞，从而为肥胖男性带来额外的好处。尽管使用了普遍的使用，但对于EMT的疗效仍然存在数据，尤其是关于活出生率。我们假设，当与受控排卵诱导（COI）/宫内授精（LUL）结合使用时，EMT代表有效的治疗。我们的总体假设是，在非刺激性寡素 - 植物学和不孕症的男性中，EMT和四个连续的COH/IUI的八个月和四个课程将显着改善活产费率。我们提出了一个8个月的三臂（克罗米芬，letrozole，安慰剂）随机研究设计设计，以确定EMT是否显着改善了非刺激性男性不育的夫妻的活产怀孕结局，我们还将确定letrozole在肥胖男性中是否效果更好代谢综合征的因素。如果我们的总体假设是正确的，那么EMT和COH/IUIS的组合可能代表了对特发性寡头植物的经济有效和有效的治疗方法，尤其是与肥胖有关。如果我们表明letrozole是肥胖男性中最有效的疗法，这将进一步为将来的治疗干预措施提供信息。如果letrozole效应与代谢综合征状态无关，则阐明与肥胖相关的男性因素的病因。这种疗法的潜在好处是巨大的：1）降低医疗保健成本； 2）改善妊娠结局； 3）改善以前不育夫妇的生活质量。