Our overall goal is to improve the reproductive health of men and women, thereby fostering the birth of healthy and wanted children. The objective of this application is to become part of the Cooperative Multicenter Reproductive Medicine Network (CMRMN). We are committed to cooperative research and offer a large patient base (including an unusually high percentage of minorities) from which to enroll subjects into Network protocols. We propose to achieve this objective by documenting that Wayne State's spectrum of research expertise and resources is consistent with successful participation in the Network; by providing evidence of Wayne State's commitment and track record in cooperative clinical research; and by providing a 'concept' protocol as proof of our ability to conceive and design a cooperative project. It is our expectation that we would be an integral and contributing member of the CMRMN in research identified by other members, and as an innovator of new projects. In particular, we would contribute to genome-wide screening for genetic differences that could explain the pathogenesis of reproductive abnormalities. One of our long-range research goals is to identify congenital and acquired genetic causes of male infertility, so that highly specific counseling and/or therapy can be offered to affected couples considering assisted reproductive technologies as a solution to infertility. The specific objective of our concept protocol is to identify genes, through the innovative application of microarray technology, closely associated with male factor infertility. The central hypothesis for the proposed research is that gene transcripts (mRNA species) contained in the sperm of infertile males will differ qualitatively and quantitatively, compared to those of fertile men, thereby allowing candidates for 'infertility genes' to be identified. The rationale is that once candidate genes have been identified by cooperative genome-wide screening, hypothesis-driven research can be formulated to determine whether they relate casually to one or more genetic forms of male factor infertility. We will test our central hypothesis by pursuing two specific aims: 1) identify the extent to which the profile of gene transcripts varies in the sperm of fertile males; and 2) identify gene transcripts that are expressed differently in the sperm of infertile, compared to fertile, men. The CMRMN is vital to successful completion of the protocol; it will assure the power needed to interpret results accurately. The proposed translational research is innovative because it combines clinical and basic molecular genetic expertise in a cooperative effort that will employ new analytical (microarray) technology to cost- effectively obtain clues to the genetic causes of male factor infertility. The outcomes will be significant because they will provide the foundations for definitive analysis of genetic factors that negatively affect male fertility, thereby leading to highly accurate, inexpensive diagnostic tests for genetic causes of male factor infertility, and in some cases, allow the prescription of specific replacement therapy.

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 #
5U10HD039005-03
Application #
6536148
Study Section
Special Emphasis Panel (ZHD1-DRG-D (05))
Program Officer
Parrott, Estella C
Project Start
2000-06-30
Project End
2005-03-31
Budget Start
2002-04-01
Budget End
2003-03-31
Support Year
3
Fiscal Year
2002
Total Cost
$308,208
Indirect Cost
Name
Wayne State University
Department
Obstetrics & Gynecology
Type
Schools of Medicine
DUNS #
City
Detroit
State
MI
Country
United States
Zip Code
48202
Greenwood, Eleni A; Pasch, Lauri A; Cedars, Marcelle I et al. (2018) Insulin resistance is associated with depression risk in polycystic ovary syndrome. Fertil Steril 110:27-34
Evans-Hoeker, Emily A; Eisenberg, Esther; Diamond, Michael P et al. (2018) Major depression, antidepressant use, and male and female fertility. Fertil Steril 109:879-887
Hansen, Karl R; Eisenberg, Esther; Baker, Valerie et al. (2018) Midluteal Progesterone: A Marker of Treatment Outcomes in Couples With Unexplained Infertility. J Clin Endocrinol Metab 103:2743-2751
Kent, James; Dodson, William C; Kunselman, Allen et al. (2018) Gestational Weight Gain in Women With Polycystic Ovary Syndrome: A Controlled Study. J Clin Endocrinol Metab 103:4315-4323
Diamond, Michael P; Legro, Richard S; Coutifaris, Christos et al. (2017) Sexual function in infertile women with polycystic ovary syndrome and unexplained infertility. Am J Obstet Gynecol 217:191.e1-191.e19
Styer, Aaron K; Jin, Susan; Liu, Dan et al. (2017) Association of uterine fibroids and pregnancy outcomes after ovarian stimulation-intrauterine insemination for unexplained infertility. Fertil Steril 107:756-762.e3
Engmann, Lawrence; Jin, Susan; Sun, Fangbai et al. (2017) Racial and ethnic differences in the polycystic ovary syndrome metabolic phenotype. Am J Obstet Gynecol 216:493.e1-493.e13
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
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
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

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