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。作为一个主要的招募网站和协议的开发者，我们在之前的资金周期中为RMN的生产力做出了重大贡献。Legro博士从该周期的概念方案被优先考虑为第一项研究进行，他成为已完成的妊娠多囊卵巢综合征研究（PPCOS）的首席研究员，以及药理学附录。这些发现将对多囊卵巢综合征女性的治疗产生显著影响。该大学和系在生殖和临床研究方面具有优势，这加强了该地点的生殖生殖网络单位。此外，女性和男性不育症的外科和医学治疗的临床项目已经建立并相互联系。致力于生殖医学（辅助生殖技术、男科和生殖内分泌学）的实验室和美国国立卫生研究院支持的临床研究中心加强了临床和研究项目。RMN单位的拟议行政结构包括首席研究员Richard S. Legro，生殖内分泌学研究部主任，男性不育专业的联合研究员，泌尿科的J.C. Trussell，以及具有统计遗传学专业知识的生物统计学家，健康评估科学部的Gary Chase博士。在这个周期中，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实质性贡献，我们预计重新设计的RMN现在能够同时执行多个方案。我们提出了一个概念方案，该方案建立在PCOS的研究结果和经验的基础上，并提出了一项双盲随机双臂试验，将枸橼酸克罗米芬与来曲唑用于不育的PCOS妇女，以确定活产的主要结局方面的优势，并描述这两种药物的安全性。我们还将探讨次要的重要结局，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，有助于了解反应机制，并且实际上只有在NIH的支持下才能进行，因为孕妇和胎儿都参与其中。

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.