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）：男性不育症是一个常见且具有破坏性的问题，并且患病率正在增加，其中很大一部分与肥胖有关。然而，非辅助生殖技术（ART）治疗仍然处于初级阶段，研究也很少。胞浆内单精子注射 (IVF/ICSI) 体外受精虽然有效，但价格昂贵、会造成精神创伤，并且可能带来重大的潜在风险。提倡对少精子症男性进行经验性药物治疗（EMT），使用克罗米芬柠檬酸盐（CC；一种选择性雌激素受体调节剂）或来曲唑（一种芳香酶抑制剂）；两者都通过减少雌激素对下丘脑-垂体轴的负反馈起作用。来曲唑可能通过阻止外周雄激素芳香化为雌二醇而为肥胖男性带来额外的好处。尽管使用广泛，但关于 EMT 功效的数据却很少，特别是在活产率方面。我们假设，当与控制排卵诱导 (COI)/宫腔内人工授精 (IUl) 结合使用时，EMT 代表了有效的治疗方法。我们的总体假设是，对于患有非梗阻性少精症和不孕症的男性来说，为期八个月的 EMT 疗程和连续四次 COH/IUI 将显着改善活产率费率。我们提出一项为期 8 个月的三臂（克罗米芬、来曲唑、安慰剂）随机研究设计，以确定 EMT 是否能显着改善非梗阻性男性不育症夫妇的活产妊娠结局。我们还将确定来曲唑在独立于风险的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/IUI 的组合可能代表一种具有成本效益且有效的治疗特发性少精子症的方法，特别是当它与肥胖有关时。如果我们证明来曲唑是肥胖男性最有效的疗法，这将为未来的治疗干预措施提供进一步信息。如果来曲唑的作用与代谢综合征状态无关，那么与肥胖相关的男性因素的病因就明确了。这种疗法的潜在好处是巨大的：1）降低医疗费用； 2）改善妊娠结局； 3) 改善先前不孕夫妇的生活质量。