This application is written in response to RFA-HD-13-016 to participate as a Clinical Site in an ongoing multicenter cooperative program designed to conduct clinical studies investigating problems in reproductive medicine. The application directly addresses the mission of the Reproductive Sciences Branch to ensure the birth of healthy, wanted babies through studies on human fertility and Infertility. The long term objectives of the proposed project are to improve live birth rates in infertile women with polycystic ovary syndrome (PCOS), and to explore the role of chronic Inflammation In the pathophysiology of PCOS-related infertility and in the response to fertility therapy in such individuals. First line therapy with clomiphene citrate fails to result in successful pregnancy in up to one-half of PCOS patients. However, the addition of dexamethasone (DEX) to CC shows promise as a safe, effective, inexpensive intervention in this population. We thus propose the following specific alms:
Specific Aim 1. To compare the live birth rate in women with PCOS treated with CC plus placebo to that in PCOS women treated with CC plus DEX;
Specific Aim 2. To compare serum hormone levels and markers of inflammation in women with PCOS treated with CC and placebo to those in PCOS women treated with CC plus DEX;
Specific Aim 3. To explore possible relationships between serum hormone levels and markers of inflammation or treatment-related changes in these parameters and ovulation and live born delivery rates. We will address these specific alms by conducting a double-blind, randomized trial of ovulation induction with CC plus DEX compared to CC plus placebo. Based on considerations described in the proposal we hypothesize that: 1) The live birth rate in women with PCOS treated with CC plus DEX will be 10% higher than the rate in women treated with CC plus placebo;2) Serum levels of dehydroepiandrosterone sulfate (DHEAS) and markers of inflammation will be reduced significantly in subjects treated with CC plus DEX compared to women treated with CC plus placebo;3) Lower levels of markers of inflammation in women treated with DEX will be associated with a higher likelihood of live born delivery.

Public Health Relevance

This proposal addresses an unmet need of infertile women. Up to one-half of women with PCOS either do not ovulate or do not conceive from first line therapy with clomiphene citrate (CC). Orally acting alternatives to CC have been ineffective at increasing live born delivery rates. The alternatives of ovulation induction with gonadotropins or in vitro fertilization place significant financial burdens and health risks on patients with PCOS due to their risk of ovarian hyperstimulation syndrome and multiple pregnancies.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Cooperative Clinical Research--Cooperative Agreements (U10)
Project #
5U10HD055942-07
Application #
8740523
Study Section
Special Emphasis Panel (ZHD1-DSR-L (55))
Program Officer
De Paolo, Louis V
Project Start
2007-09-07
Project End
2016-06-30
Budget Start
2014-07-01
Budget End
2015-06-30
Support Year
7
Fiscal Year
2014
Total Cost
$14,531
Indirect Cost
$4,811
Name
University of Texas Health Science Center
Department
Obstetrics & Gynecology
Type
Schools of Medicine
DUNS #
800772162
City
San Antonio
State
TX
Country
United States
Zip Code
78229
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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; 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
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Trussell, J C; Christman, Gregory M; Ohl, Dana A et al. (2011) Recruitment challenges of a multicenter randomized controlled varicocelectomy trial. Fertil Steril 96:1299-305
Schlaff, William D; Zhang, Heping; Diamond, Michael P et al. (2011) Increasing burden of institutional review in multicenter clinical trials of infertility: the Reproductive Medicine Network experience with the Pregnancy in Polycystic Ovary Syndrome (PPCOS) I and II studies. Fertil Steril 96:15-8
Zhang, Heping; Legro, Richard S; Zhang, Jeffrey et al. (2010) Decision trees for identifying predictors of treatment effectiveness in clinical trials and its application to ovulation in a study of women with polycystic ovary syndrome. Hum Reprod 25:2612-21

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