In the current era women often delay attempts to conceive to their thirties and forties, ages associated with higher rates of infertility due to reproductive aging. Despite variability in the age of onset of infertility, no validated markers exist to monitor an individual woman's fertility. The objective of this project is to examine the ability of markers of ovarian aging to predict infertility due to reproductive aging, with the long term goal to develop a model that projects individual loss of reproductive potential. We hypothesize that markers of ovarian aging are associated with natural fecundability (probability of conception per menstrual cycle), predictive of infertility, and associated with the probability of live birth. The proposed study will enroll 750 women from the community, who desire to conceive, and obtain baseline measures of ovarian aging: early follicular phase serum follicle stimulating hormone (FSH) and anti-m|llerian hormone (AMH). Participants will be actively followed throughout their attempts to conceive over the following twelve months. During that time, women will conduct standardized pregnancy testing and complete a daily and monthly diary for collection of detailed exposure data. Pregnancy follow-up will include ultrasound assessment for viability and a pregnancy outcome report. These methods will allow us to address our primary research aims: 1) Establish the marker of ovarian aging that best predicts infertility. To address this aim we will determine a) measures of association between FSH (in urine and serum) and AMH and lack of conception at 6 and 12 months and b) test characteristics (e.g. sensitivity &specificity) of each marker;2) Develop a predictive model for age-related infertility, incorporating demographics, reproductive history, and markers of ovarian aging;and 3) Generate preliminary estimates of the association between markers of ovarian aging and miscarriage. Our study is innovative in its use of a population of unproven reproductive potential with previous access to contraception and at risk for reproductive aging. Results from this research, combined with research by others, will allow women to predict their current and future reproductive potential, ultimately allowing them more reproductive control.

Public Health Relevance

In the current era women often delay attempts to conceive to their thirties and forties, ages associated with higher rates of infertility due to reproductive aging. A simple, validated measure of reproductive potential would be of major benefit to women, who are considering initiating or delaying childbearing. Given that unproven home urinary kits are already being marketed, a prospective study to determine their ability to predict infertility in the general population is imperative.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
1R01HD067683-01A1
Application #
8116183
Study Section
Integrative and Clinical Endocrinology and Reproduction Study Section (ICER)
Program Officer
Eisenberg, Esther
Project Start
2011-04-15
Project End
2016-03-31
Budget Start
2011-04-15
Budget End
2012-03-31
Support Year
1
Fiscal Year
2011
Total Cost
$553,623
Indirect Cost
Name
University of North Carolina Chapel Hill
Department
Obstetrics & Gynecology
Type
Schools of Medicine
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
Jukic, Anne Marie Z; Wilcox, Allen J; McConnaughey, D Robert et al. (2018) 25-Hydroxyvitamin D and Long Menstrual Cycles in a Prospective Cohort Study. Epidemiology 29:388-396
Lyttle Schumacher, Brianna M; Jukic, Anne Marie Z; Steiner, Anne Z (2018) Antimüllerian hormone as a risk factor for miscarriage in naturally conceived pregnancies. Fertil Steril 109:1065-1071.e1
Jukic, Anne Marie Z; Baird, Donna D; Wilcox, Allen J et al. (2018) 25-Hydroxyvitamin D (25(OH)D) and biomarkers of ovarian reserve. Menopause 25:811-816
Crawford, Natalie M; Fenton, Suzanne E; Strynar, Mark et al. (2017) Effects of perfluorinated chemicals on thyroid function, markers of ovarian reserve, and natural fertility. Reprod Toxicol 69:53-59
Steiner, Anne Z; Pritchard, David; Stanczyk, Frank Z et al. (2017) Association Between Biomarkers of Ovarian Reserve and Infertility Among Older Women of Reproductive Age. JAMA 318:1367-1376
Crawford, Natalie M; Pritchard, David A; Herring, Amy H et al. (2017) Prospective evaluation of luteal phase length and natural fertility. Fertil Steril 107:749-755
Crawford, Natalie M; Pritchard, David A; Herring, Amy H et al. (2016) Prospective evaluation of the impact of intermenstrual bleeding on natural fertility. Fertil Steril 105:1294-1300
Casilla-Lennon, Marianne M; Meltzer-Brody, Samantha; Steiner, Anne Z (2016) The effect of antidepressants on fertility. Am J Obstet Gynecol 215:314.e1-5
Steiner, Anne Z; Jukic, Anne Marie Z (2016) Impact of female age and nulligravidity on fecundity in an older reproductive age cohort. Fertil Steril 105:1584-1588.e1
Steiner, Anne Z; Pritchard, David A; Young, Steven L et al. (2014) Peri-implantation intercourse lowers fecundability. Fertil Steril 102:178-82

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