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? Design Fragments of ovarian cortex from women who underwent unilateral oophorectomy for fertility preservation were obtained for quantitative histological assessment, including recording of the two-dimensional coordinates of follicles. Data were analysed using spatial statistical methods. Results From 14 patients aged 20-35 years, 53 ovarian cortex tissue samples were obtained, containing 1-803 follicles. Primordial and transitory follicles lay in a clustered manner in the human ovarian cortex, with an average cluster radius of ∼ 270 μm (95% CI range 154 – 377 µm; n = 49). Follicle density declined with age (p = 0.006, n = 13) and the distance to the nearest neighbouring follicle increased (p = 0.004, n = 13). The 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 of different stages lay in different clusters (p Conclusions This study shows that primordial and transitory follicles lie in different clusters in the human ovarian cortex. Spatiotemporal computer simulation suggests that interfollicular signals may hinder follicle loss and therefore may drive clustered follicle distribution. In clinical practice, the patient's age should be taken into account when assessing follicle density, as follicle distribution is increasingly clustered with advancing age.