In this competing renewal, the Penn State RMN site brings significant strengths including 1) the PI providing leadership as Lead Investigator on the PPCOS II protocol, 2) serving as the top recruiter for two of the main RMN protocols in the last funding cycle, 3) supplying top quality data to the Data Coordinating Center, 4) providing key leadership on multiple committees, 5) authoring multiple high impact manuscripts, 6) facilitating collaborative ancillary studies in and out of the RMN, and 7) mentoring the next generation of clinical investigators. We propose to maintain our lead female and male investigators, as well as our experienced Nurse Study Coordinator/Research Assistant and add investigators with pediatric and adult endocrinology expertise as well as biostatistical expertise to assist us in bot designing new trials and writing up the results from our previous RMN studies. Additionally, we will partner with the University of Rochester in years 3-5, which will serve as a subsite for the studies we design for the RMN as well as provide investigator support and intellectual input for our concept protocol. Our site will continue to recruit in the surrounding rural areas around Penn State Hershey combined with a more urban/suburban population in Rochester. Our concept protocol builds on substantial preliminary data from a currently funded R01 trial based at Penn State (OWL PCOS) which allows for realistic projections of sample size, dropout rate and adverse event rates. Our RCT will test the hypothesis that a four month preconception weight loss arm in overweight/obese women with PCOS will improve live birth compared to a control intervention of continuous OCP in a total of 306 subjects. All women will then undergo four cycles of ovulation induction with an oral agent with timed intercourse. Additionally we will study women who conceive during pregnancy, and enroll infants in our Pregnancy Registry for 5 years. Participating male partners will be studied systematically throughout the trial. Our trial uniquely extends from preconception to infancy, utilizes a proven weight loss intervention, incorporates a unique multidisciplinary team of kinesiologist, nutritionist, and behavioral psychologist, and builds on the infrastructure of previous RMN studies.

Public Health Relevance

In this competing renewal of our RMN site, we will continue our excellent track record of performance in infertility trials. We propose as a concept protocol, two arm clinical trial of a preconception intervention of weight loss vs. continuous OCP in overweight/obese women with PCOS designed to improve live birth rates. This study addresses an important public health issue on how to best treat infertility in overweight/obese women.

Agency
National Institute of Health (NIH)
Type
Cooperative Clinical Research--Cooperative Agreements (U10)
Project #
5U10HD038992-12
Application #
8740517
Study Section
Special Emphasis Panel (ZHD1)
Program Officer
De Paolo, Louis V
Project Start
Project End
Budget Start
Budget End
Support Year
12
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Pennsylvania State University
Department
Obstetrics & Gynecology
Type
Schools of Medicine
DUNS #
City
Hershey
State
PA
Country
United States
Zip Code
17033
Mumford, Sunni L; Legro, Richard S; Diamond, Michael P et al. (2016) Baseline AMH Level Associated With Ovulation Following Ovulation Induction in Women With Polycystic Ovary Syndrome. J Clin Endocrinol Metab 101:3288-96
Hansen, Karl R; He, Amy Linnea W; Styer, Aaron K et al. (2016) Predictors of pregnancy and live-birth in couples with unexplained infertility after ovarian stimulation-intrauterine insemination. Fertil Steril 105:1575-1583.e2
Pal, Lubna; Zhang, Heping; Williams, Joanne et al. (2016) Vitamin D Status Relates to Reproductive Outcome in Women With Polycystic Ovary Syndrome: Secondary Analysis of a Multicenter Randomized Controlled Trial. J Clin Endocrinol Metab 101:3027-35
Legro, Richard S; Dodson, William C; Kunselman, Allen R et al. (2016) Benefit of Delayed Fertility Therapy With Preconception Weight Loss Over Immediate Therapy in Obese Women With PCOS. J Clin Endocrinol Metab 101:2658-66
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
McAllister, Jan M; Legro, Richard S; Modi, Bhavi P et al. (2015) Functional genomics of PCOS: from GWAS to molecular mechanisms. Trends Endocrinol Metab 26:118-24
Legro, Richard S (2015) Pregnancy in polycystic ovary syndrome I: lessons from a pragmatic explanatory with repository clinical trial. Semin Reprod Med 33:213-9
Kuang, Hongying; Jin, Susan; Thomas, Tracey et al. (2015) Predictors of participant retention in infertility treatment trials. Fertil Steril 104:1236-43.e1-2
Diamond, Michael P; Legro, Richard S; Coutifaris, Christos et al. (2015) Letrozole, Gonadotropin, or Clomiphene for Unexplained Infertility. N Engl J Med 373:1230-40
Hayes, M Geoffrey; Urbanek, Margrit; Ehrmann, David A et al. (2015) Genome-wide association of polycystic ovary syndrome implicates alterations in gonadotropin secretion in European ancestry populations. Nat Commun 6:7502

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