A Randomized Trial of Letrozole vs Clomiphene in Infertile Women with PCOS

描述（由申请人提供）：这是宾夕法尼亚州立大学医学院RMN单元的竞争性更新。作为一个主要的招聘网站和协议的开发者，我们在上一个供资周期中为RMN的生产力做出了重大贡献。Legro博士从该周期开始的概念方案被优先考虑为第一项研究，他成为已完成的多囊卵巢综合征妊娠研究（PPCOS）的首席研究员，以及药物遗传学附录。这些发现将对PCOS女性的治疗产生显着影响。该大学和部门在生殖和临床研究方面具有优势，增强了该网站的RMN单位。此外，在男女不育症的外科和医学治疗的临床方案是完善的和相互关联的。致力于生殖医学（辅助生殖技术，男科和生殖内分泌学）的实验室和NIH支持的临床研究中心加强了临床和研究计划。拟议的风险管理网络股的行政结构包括一名首席调查员Richard S. Legro，医学博士生殖内分泌学研究部主任，男性不育症专业合作研究者，J.C. Trussell，来自泌尿科，以及具有统计遗传学专业知识的生物统计学家，加里蔡斯博士，来自健康评估科学系。在本周期中，我们计划完成PPCOS研究的辅助研究和子分析，并为所有新方案做出重大贡献，我们预计重新设计的RMN现在将能够同时执行多个方案。我们提出了一个概念协议，这是建立在PPCOS的发现和经验，并提出了一个双盲随机两组试验克罗米芬柠檬酸盐与来曲唑在不孕症妇女PCOS建立优势的主要结果活产，以及描绘两种药物的安全性。我们还将探讨次要的重要结果，如多胎妊娠，流产率，妊娠并发症和预测因素，包括候选反应基因等位基因。这些研究对于建立安全有效的无排卵性不孕症治疗方法至关重要，有助于理解反应机制，并且考虑到孕妇和胎儿的参与，实际上只有在NIH的支持下才可能进行。

DESCRIPTION (provided by applicant): This is a competing renewal of the Penn State College of Medicine RMN Unit. We have contributed significantly to the productivity of the RMN in the prior funding cycle as a major recruiting site and developer of protocols. Dr. Legro's concept protocol from that cycle was prioritized as the first study to be undertaken, and he became the Lead Investigator of the completed Pregnancy in Polycystic Ovary Syndrome Study (PPCOS), as well as a pharmacogenetic addendum. These findings will have a marked impact on the treatment of women with PCOS. The University and Department have strengths in reproductive and clinical research that enhance the RMN unit at this site. Additionally clinical programs in the surgical and medical treatment of female and male infertility are well established and interlinked. Laboratories dedicated to reproductive medicine (assisted reproductive technologies, andrology, and reproductive endocrinology) and an NIH-supported Clinical Research Center enhance the clinical and research programs. The proposed administrative structure for the RMN Unit includes a Principal Investigator, Richard S. Legro, M.D. Director of the Division of Reproductive Endocrinology Research, A Co-Investigator with expertise in Male Infertility, J.C. Trussell, from the Division of Urology, and a Biostatistician with expertise in statistical genetics, Gary Chase, Ph.D, from the Department of Health Evaluation Sciences. In this cycle we plan to complete ancillary studies and sub-analyses from the PPCOS study as well as materially contribute to all new protocols and we anticipate that the redesigned RMN will now be able to conduct multiple protocols concurrently. We propose a concept protocol, which builds on the findings and experience garnered in PPCOS, and propose a double blind randomized two armed trial of clomiphene citrate vs. letrozole in infertile women with PCOS to establish superiority in terms of the primary outcome of live birth as well as to delineate the safety profile of the two drugs. We will also explore secondary important outcomes such as multiple pregnancy, abortion rates, pregnancy complications, and predictive factors including candidate response gene alleles. These studies are essential to establishing safe and efficacious treatments for anovulatory infertility, contributing to understanding of response mechanisms, and realistically are only likely to be conducted with the support of NIH given the involvement of pregnant women and fetuses.