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医学院RMN单元的竞争性续签。在前一个供资周期中，我们作为主要的招聘网站和礼仪的制定者，对RMN的生产力作出了重大贡献。莱格罗博士那个周期的概念方案被优先考虑为第一个进行的研究，他成为多囊卵巢综合征完全妊娠研究(PPCOS)的首席研究员，以及一个药物遗传学附录。这些发现将对多囊卵巢综合征妇女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，这加强了该网站的RMN单位。此外，女性和男性不孕症的外科和内科治疗方面的临床方案已经确立并相互关联。致力于生殖医学(辅助生殖技术、男科学和生殖内分泌学)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。RMN股的拟议行政结构包括生殖内分泌学研究部主任理查德·S·莱格罗医学博士、泌尿科男性不育症专家J.C.特鲁塞尔和健康评价科学部一名具有统计遗传学专业知识的生物统计学家加里·蔡斯博士。在这个周期中，我们计划完成PPCOS研究的辅助研究和分分析，并对所有新的议定书作出实质性贡献，我们预计重新设计的RMN现在将能够同时执行多个议定书。我们在PPCOS的研究结果和经验的基础上提出了一个概念性的方案，并建议在患有PCOS的不孕妇女中进行克罗米芬和来曲唑的双盲随机双武装试验，以确立活产的主要结果的优势，并描述这两种药物的安全性。我们还将探讨次要结果，如多胎妊娠、流产率、妊娠并发症，以及包括候选反应基因等位基因在内的预测因素。这些研究对于建立安全有效的治疗无排卵性不孕症是必不可少的，有助于了解反应机制，而且实际上只有在NIH的支持下才可能进行，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.