Follicle Depletion Is a Threshold

01The evidence

• Studies of follicle loss have described episodes in which a treatment or event damages the majority of remaining follicles, which is the behaviour of a threshold system rather than a gradual decline.Human Reproduction

02The tension

Ovarian ageing is modelled as a decay curve, and fertility is projected from a marker by assuming the curve continues. Patients are counselled with a trajectory that implies a predictable decline, which does not match the abrupt changes that clinicians observe.

03The theory

A follicle pool is depleted by recruitment and by atresia. Recruitment is regulated, and atresia removes a fraction. As the pool shrinks, the fraction removed per cycle rises, so the decline accelerates rather than remaining linear.

That produces a curve that is flat for a long time and then steep, which looks like a threshold. The markers inherit the shape, so a single measurement cannot distinguish a woman on the flat part from one near the cliff.

The prediction is that longitudinal markers should show a change point rather than a constant slope, and that the age at the change point should be more predictive of menopause than the level at any single visit.

The clinical consequence is that a single measurement should be interpreted as a position, not a trajectory, and that repeated measurement is needed to locate the change point.

04What this is not

05Predictions

• P1Longitudinal markers should show a change point rather than a constant slope.
• P2The change-point age should predict menopause better than any single level.
• P3Single-measurement projections should err in both directions depending on position.

06What would refute it

Markers declining linearly across the transition would restore the curve.

07What it would change

It would change counselling and the design of fertility-preservation decisions.