The overall goal of this collaborative Georgia Health Sciences University/Wayne State University renewal submission is to improve the reproductive health of men and women, thereby fostering the birth of healthy, desired children. To achieve this goal the applicants propose to continue to contribute a broad spectrum of research expertise and resources to the Reproductive Medicine Network (RMN). These include a commitment to and track record in cooperative clinical research - e.g., three protocols approved by the RMN Steering and Advisory Committees over the past five years, as well as a superior record of subject enrollment. The two institutions collectively offer an especially large patient base (including an extraordinarily high percentage of minorities) from which to enroll subjects into new and ongoing Network protocols. The concept protocol for the proposed period of support stems from recent secondary analysis of data from the RMN's Pregnancy in Polycystic Ovary Syndrome study, in which the applicants identified a novel outcome: the standard clinical practice of inducing a progestin-withdrawal bleed prior to administration of fertility medications dramatically decreased conception and live birth rates, compared to anovulatory women not treated with progestins. In view of this clear-cut observation, an innovative study has been designed to capitalize on it. The central hypothesis is that progestin administration to induce a withdrawal bleed will have a detrimental effect on live birth outcome in WHO Category II women with a prior anovulatory cycle. To test this hypothesis, we will pursue three specific aims: 1) Determine the rate of live births among such women receiving clomiphene citrate (CC), with or without preceding progestin withdrawal;2) Concomitantly determine the time to pregnancy in such women;and 3) Determine the influence of progestin withdrawal on the luteal phase hormonal milieu and the endometrium. The expected outcome is that renewal of our membership in the Network would allow continued contribution to the group's cooperative projects, as well as innovation of new research projects for consideration by the group. Coupled with our enlarged joint rural and urban population, documentation of being a major recruiter of racially diverse patients in RMN trials, stellar history of protocol compliance, strong history of oral and written dissemination of RMN results, and personalized attention to mentorship and training of junior clinical investigators, these are expected to have significant positive impact o the Network's capacity to attain its goal of identifying and/or improving diagnostic and therapeutic solutions to problems in reproductive medicine.

Public Health Relevance

Renewal of membership in the RMN will allow us to continue to make substantive contributions to understanding and treating problems in reproductive medicine, such as our concept protocol. If our concept study confirms our retrospective analysis, it would produce a paradigm shift in clinical care for WHO Category II women, significantly increasing pregnancy outcomes, and leading to rewriting of Ob/Gyn and REI practice guidelines. Additionally, serum and endometrial specimens will be placed in a biorepository for future biomarker, genomic, and proteomic studies, which will be made available along with the data collected in this study, for future evaluation by both the RMN and the entire reproductive science community.

National Institute of Health (NIH)
Cooperative Clinical Research--Cooperative Agreements (U10)
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Special Emphasis Panel (ZHD1)
Program Officer
De Paolo, Louis V
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Georgia Regents University
Obstetrics & Gynecology
Schools of Medicine
United States
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Brower, Meredith A; Jones, Michelle R; Rotter, Jerome I et al. (2015) Further investigation in europeans of susceptibility variants for polycystic ovary syndrome discovered in genome-wide association studies of Chinese individuals. J Clin Endocrinol Metab 100:E182-6
Legro, Richard S; Brzyski, Robert G; Diamond, Michael P et al. (2014) The Pregnancy in Polycystic Ovary Syndrome II study: baseline characteristics and effects of obesity from a multicenter randomized clinical trial. Fertil Steril 101:258-269.e8
Legro, Richard S; Brzyski, Robert G; Diamond, Michael P et al. (2014) Letrozole versus clomiphene for infertility in the polycystic ovary syndrome. N Engl J Med 371:119-29
Legro, Richard S; Chen, Gang; Kunselman, Allen R et al. (2014) Smoking in infertile women with polycystic ovary syndrome: baseline validation of self-report and effects on phenotype. Hum Reprod 29:2680-6
Jodar, Meritxell; Selvaraju, Sellappan; Sendler, Edward et al. (2013) The presence, role and clinical use of spermatozoal RNAs. Hum Reprod Update 19:604-24
Huang, Hao; Hansen, Karl R; Factor-Litvak, Pamela et al. (2012) Predictors of pregnancy and live birth after insemination in couples with unexplained or male-factor infertility. Fertil Steril 97:959-67
Legro, Richard S; Kunselman, Allen R; Brzyski, Robert G et al. (2012) The Pregnancy in Polycystic Ovary Syndrome II (PPCOS II) trial: rationale and design of a double-blind randomized trial of clomiphene citrate and letrozole for the treatment of infertility in women with polycystic ovary syndrome. Contemp Clin Trials 33:470-81
Diamond, Michael P; Kruger, Michael; Santoro, Nanette et al. (2012) Endometrial shedding effect on conception and live birth in women with polycystic ovary syndrome. Obstet Gynecol 119:902-8
Jones, Michelle R; Chua, Angela K; Mengesha, Emebet A et al. (2012) Metabolic and cardiovascular genes in polycystic ovary syndrome: a candidate-wide association study (CWAS). Steroids 77:317-22
Aubuchon, Mira; Kunselman, Allen R; Schlaff, William D et al. (2011) Metformin and/or clomiphene do not adversely affect liver or renal function in women with polycystic ovary syndrome. J Clin Endocrinol Metab 96:E1645-9

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