Impact of fertility status on epigenetic indicators of future health risk

One way to identify women at increased risk for CVD and MetS is through examining differences in DNA methylation. DNA methylation is one mechanism through which gene expression responds to changes in the environment, hormone status, or other physiologic processes. These changes may occur prior to the onset of symptomatic disease and can identify women at increased risk for adverse outcomes.

This study will evaluate three DNA methylation-based predictors of long-term health, CVD, and MetS in women with infertility and women without infertility who are undergoing in vitro fertilization. We will also evaluate associations with low ovarian reserve, which is predictive of time to menopause and may also associate with increased risk. First, we will assess an indicator of cellular age acceleration that is predictive of health-span and all-cause mortality.

Then, we will leverage combinations of CpG sites to predict a CVD methylation risk score and a separate MetS methylation risk score. We hypothesize that infertility and low ovarian reserve will be associated with increased age acceleration, which would serve as a general marker of future disease and mortality. We hypothesize that the CVD methylation risk score will be associated with infertility and low ovarian reserve due to putative links between infertility and later development of CVD.

Finally, we hypothesize that infertility and low ovarian reserve will be associated with increased MetS methylation risk scores as obesity and other MetS risk factors play a role in infertility.