Spatial and temporal changes in follicle distribution in the human ovarian cortex

Abstract

Research question: How does follicle distribution evolve in the human ovarian cortex between the ages of 20 and 35 years?

Design: Fragments of ovarian cortex from women undergoing unilateral oophorectomy for fertility preservation were obtained for quantitative histological assessment, including recording the two-dimensional coordinates of the follicles. Data were analysed using spatial statistical methods.

Results: A total of 53 ovarian cortex tissue samples, containing 1-803 follicles each, were obtained from 14 women aged 20-35 years. Primordial and transitory follicles lay in a clustered manner in the human ovarian cortex, with an average cluster radius of around 270 µm (95% confidence interval 154-377 µm; n = 49). Follicle density declined with age (P = 0.006, n = 13), and the distance from the nearest neighbouring follicle increased (P = 0.004, n = 13). Cluster radius decreased with age (P = 0.02, n = 13), but the degree of clustering tended to increase (P = 0.11, n = 13). In the majority of the samples, follicles at different stages lay in different clusters (P < 0.05, n = 13).

Conclusions: This study shows that primordial and transitory follicles lie in different clusters in the human ovarian cortex. Spatio-temporal computer simulation suggests that interfollicular signals may hinder follicle loss and may therefore drive clustered follicle distribution. In clinical practice, the woman's age should be taken into account when assessing follicle density, as follicle distribution is increasingly clustered with advancing age.

Keywords: Fertility preservation; Follicle distribution; Follicle dynamics; Human ovarian cortex; Reproductive ageing.