What was shown
A reframing of folliculogenesis built around the 2023 work of Antonio La Marca and the long-established two-cell two-gonadotrophin model. LH receptor structure and signalling, theca androgen synthesis under LH control, granulosa-cell aromatase under FSH control — and how the LH-FSH symphony shapes follicular competence at each stage.
Key findings
Follicles are gonadotrophin-dependent throughout development, not only at the antral stage. LH activity is required not just at the ovulatory peak but through late follicular maturation to support steroidogenesis and oocyte competence. LH and FSH act in complementary directions — the same receptor family, distinct cellular targets — and cannot be substituted for one another at full dose.
What this means in practice
Re-evaluate FSH-only protocols in patients with low or impaired LH activity, including older patients, LHCGR polymorphism carriers and hypogonadotrophic profiles. Build the protocol decision on a receptor-cell-hormone mental model rather than total gonadotrophin dose.
Caveats
Two-cell two-gonadotrophin is a model — real cycles add genotype, BMI, age and concurrent endocrine state on top. LH activity and HCG are not interchangeable in every clinical situation; their pharmacokinetics differ.
The speaker separately examines LH pulsatility: it is the frequency and amplitude of pulses, not just the mean level, that determine how the pituitary governs the follicle; a constant, non-pulsatile signal, by contrast, suppresses the response.
The practical consequence of the "receptor-cell-hormone" model is to understand at which level the fault arises: ligand deficiency (low LH), a receptor defect (LHCGR polymorphism) or an impaired cellular response. On this depends whether adding LH or changing the trigger will help, or whether it is a dead end for the patient's own oocytes.
The upshot: LH is not an "ovulation hormone" but a participant in the whole of folliculogenesis; a protocol that ignores its role in late maturation risks a formally normal oocyte yield with reduced competence.
The LH receptor belongs to the G-protein-coupled receptor family: ligand binding activates adenylate cyclase and the cAMP/protein kinase A cascade, while at high concentrations the phospholipase C pathway is also engaged. The density and functionality of these receptors on theca and luteinized granulosa cells determine the follicle's sensitivity to the gonadotropin.
The two-cell, two-gonadotropin model describes a division of labor: under LH, theca cells synthesize androgens from cholesterol, which diffuse into the granulosa, where FSH-dependent aromatase converts them into estradiol. Without a basal level of LH the substrate for aromatase is missing, and the rise in estradiol stalls.
The 2023 reappraisal shifted the emphasis: late stages of folliculogenesis proved more LH-dependent than previously thought, and the individual window of LH sensitivity should be considered when choosing a protocol. The pulsatile pattern of LH secretion provides the fine-tuning of steroidogenesis and final oocyte maturation.
Are antral follicles really gonadotrophin-dependent only at one stage — or all the way through? A walk through the LH receptor, the two-cell two-gonadotrophin model and what the 2023 reframing of folliculogenesis means for choosing a stimulation protocol.
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