Modern understanding of folliculogenesis regulation

Folliculogenesis unfolds over roughly 175 days, and understanding its molecular machinery directly shapes the quality of ovarian stimulation. Galyna Strelko's lecture walks from the dormant primordial follicle to the mature oocyte, pointing out exactly where the clinician can intervene.

Follicle growth has two phases — FSH-independent and FSH-dependent — with an intermediate stage when the first FSH receptors appear. Dormancy of primordial follicles is maintained by the PTEN/PI3K pathway: PTEN phosphatase acts as a brake so the oocyte pool is not exhausted too quickly. AMH is an additional limiter of mass recruitment. Activation is driven by BMP-family growth factors (BMP-4, BMP-7), while the key oocyte–granulosa dialogue runs through BMP-15 and GDF9 — the oocyte governs its microenvironment, drives granulosa proliferation and restrains premature luteinisation. The practical takeaway: an incompetent oocyte cannot be "fixed" with vitamins, but preparation can begin well in advance.

A separate block covers central regulation. KNDy neurons (kisspeptin, neurokinin B, dynorphin) generate GnRH pulses: high frequency favours LH, low frequency FSH. Chronic stress, through cortisol, blunts sensitivity to neurokinin B, and energy deficit (below 20–30 kcal/kg) lowers LH pulsatility — which explains anovulation with weight loss and stress and grounds patient counselling.

Stimulation practice rests on the two-cell, two-gonadotropin theory. The lecture introduces the FSH threshold (the rise above baseline, roughly 50%, individually shaped by receptor polymorphisms) and the FSH window — how long FSH must act. Once a follicle reaches 14 mm it becomes LH-dependent and the FSH dose can be reduced. Gonadotropin isoforms are discussed: acidic forms are the "marathon runner" of the early cycle, alkaline forms the "sprinter" of ovulation; urinary and recombinant preparations differ in profile, and adding LH in the second phase mimics the needed shift.