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

• 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
• 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

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）：男性不育症是一个普遍和毁灭性的问题，患病率正在上升，其中大部分与肥胖有关。然而，非辅助生殖技术（ART）治疗仍然处于初级阶段，研究很少。卵胞浆内单精子注射体外受精（IVF/ICSI）虽然有效，但价格昂贵，情感创伤，并可能存在重大潜在风险。经验医学治疗（EMT）在男性少精症中提倡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（一种芳香化酶抑制剂）；两者都通过减少下丘脑-垂体轴上的雌激素负反馈而起作用。来曲唑可能通过阻断外周雄激素对雌二醇的芳构化，为肥胖男性提供额外的益处。尽管普遍使用，但缺乏关于EMT有效性的数据，特别是关于活产率的数据。我们假设，当与控制排卵诱导(COI)/宫内人工授精（lUl）联合使用时，EMT代表有效的治疗。我们的首要假设是，对于非阻塞性少弱精子症和不孕症的男性，8个月的EMT疗程和连续4次COH/IUIs将显著提高活产率