Assisted Reproductive Technology (ART) Predictors Study

The goals of this research proposal are to further our understanding of the reproductive
aging process in women and to improve our ability to clinically assess and model
reproductive aging. Reproductive aging is a continuous process that begins many years prior
to menopause. Women in their late 30s and early 40s usually maintain normal menstrual
function and ovulatory status, yet fertility in these women is considerably compromised
compared to younger women. The primary mechanism of reproductive aging is through the
process of ovarian primordial follicle (egg) depletion, a process that exhibits considerable
variation between women. As a result, the age at which an individual begins to experience
infertility and menstrual cycle changes secondary to follicle depletion also varies
significantly and is difficult to predict. The clinical assessment of the number of
primordial follicles remaining in the ovary has traditionally relied upon the measurement of
ovarian or pituitary hormones such as FSH, estradiol, and inhibin B. Unfortunately, these
measures are all indirect and poorly sensitive in the assessment of ovarian reserve. More
recently, serum levels of anti-Müllerian hormone (AMH) and the ovarian antral follicle count
have been utilized as clinical measures of ovarian reserve. Both have been correlated with
chronological age and have some predictive power in determining stimulation quantity (the
number of oocytes obtained at the time of egg-recovery) in in-vitro fertilization (IVF)
treatment cycles. Reproductive aging in women; however, is more than just the depletion of
oocytes from a woman's ovaries, but also involves a decline in oocyte quality. The
predictive value of these clinical markers of ovarian reserve with regards to oocyte quality
is unknown. Additionally, new tools developed to assess biological aging in other organ
systems such as white blood cell telomere length and the measurement of advanced glycation
end products (AGEs) through skin autofluorescence have not been evaluated with respect to
the reproductive aging process. This proposal seeks to develop better models of normal
female reproductive aging by identifying novel markers of ovarian reserve and determining
their relationship with both oocyte quantity and quality obtained during IVF treatment
cycles.