Validation of the power model of ovarian non-growing follicle depletion associated with aging

Abstract

The primary determinant of reproductive aging in women is the progressive decline in ovarian non-growing follicles (NGFs). This pool of NGFs, inclusive of the ovarian primordial, intermediate and primary follicles, constitutes the ovarian reserve. Ultimately the depletion of the NGF pool results in menopause. We have previously characterized the decline in NGFs associated with aging, determining that a power model taking the form y = axb + c, where a, b, and c are constants and y = NGF count at age x, best characterizes the decline in the log-transformed NGF count associated with increasing age. This investigation was aimed at validating the power model of ovarian NGF decay within the context of an independent data set. Prospective cross-sectional study, university setting. Normal ovaries were collected from 55 women (age 28-52 years) undergoing oophorectomy for benign indications. Using systematic random sampling rules and a validated fractionator/optical disector technique, ovarian NGF counts were determined. The goodness-of-fit of predicted NGF counts based on the power model {Log (NGF count) = (-0.00019)*(age in years)2.452 + 5.717} and those observed in the validation set was assessed with a chi-square goodness of fit test, where a p-value > 0.05 is considered a good fit for the model. The power model was an excellent fit to the observed data (p = 0.97). The average difference between observed and expected NGF count was 0.17 (95% CI -0.02,0.345). This difference would translate into a discrepancy of ∼506 NGFs at the predicted menopause threshold of ∼758 NGFs. This investigation, with an independent set of ovarian NGF counts, validates the power model of ovarian NGF depletion associated with aging. These findings confirm the utility of the power model as the best available characterization of the decline in ovarian NGFs from birth to menopause.