Human ovarian reserve from conception to the menopause

Area of Science:

• Reproductive biology
• Quantitative histology
• Biomathematics

Background:

• The human ovary has a finite number of non-growing follicles (NGFs) established before birth.
• NGF populations naturally decline with age, leading to menopause around 50-51 years.
• Understanding ovarian reserve dynamics is crucial for fertility counseling.

Purpose of the Study:

• To develop a mathematical model for age-related non-growing follicle (NGF) populations in the human ovary.
• To track NGF decline from conception through menopause.
• To provide a quantitative basis for understanding ovarian reserve.

Main Methods:

• Data from eight histological studies (n=325) spanning conception to 51 years were analyzed.
• Collected NGF population data were fitted to 20 peak function models.
• The best-fit model, an asymmetric double Gaussian cumulative (ADC) curve, was selected based on the highest r2 correlation coefficient.

Main Results:

• The study successfully modeled log-adjusted NGF populations using a five-parameter ADC curve (r2 = 0.81).
• For ages up to 25 years, the ADC model showed a high correlation (r2 = 0.95).
• Estimates indicate only 12% of pre-birth NGFs remain by age 30 and 3% by age 40.
• NGF recruitment rate increases from birth to age 14, then declines towards menopause.

Conclusions:

• This is the first model to describe human ovarian reserve from conception to menopause.
• The model explains 81% of NGF population variance due to age alone.
• Findings offer a scientific basis for fertility counseling in various patient populations, including cancer survivors.