Reproductive healthLecture

Pharmacogenomics of LH and FSH receptors

Carlo Alviggi

Audio: UA · RUSubtitles: UA · RU34 min

Carlo Alviggi

Professor, MD, PhD

Full Professor of Reproductive Medicine at the University of Naples Federico II and a founding member of the POSEIDON group. His research focuses on the role of LH in folliculogenesis and ovarian stimulation, endometriosis, oncofertility and reproductive endocrinology. Author of more than 100 indexed publications.

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Carlo Alviggi's lecture answers the question of why patients receiving identical gonadotropin doses show such different ovarian responses, and how the pharmacogenomics of FSH and LH receptors helps to explain and predict this variability. The focus shifts from standard protocols toward the molecular profile of the individual patient.

The analysis is built on the pharmacogenomics of FSH and the functionally linked FSH-LH system. The effect of an exogenous gonadotropin is determined not only by the administered dose but also by how a patient's genome encodes the receptors and the hormones themselves. It is at the level of ligand-receptor interaction that the differences later seen by the clinician as a good or a weak response first arise.

Particular attention is given to the classic lock-and-key model of hormone-receptor binding. Alviggi highlights its limitations: the real interaction is more complex than simple geometric complementarity, and current data point to the role of receptor conformational states and the modulating influence of LH. Recognising these limits reshapes how we interpret why the same drug behaves differently across patients.

An important section addresses the clearance and metabolism of gonadotropins, where individual variability is especially pronounced. Elimination rate and bioavailability differ between patients, so a fixed dose does not guarantee the same serum concentration or the same follicular stimulation. This pharmacokinetic layer complements the pharmacogenomic one and accounts for part of the unpredictability of cycles.

The central practical idea of the lecture is that polymorphisms of receptor and hormone genes serve as predictors of dose and response. Carrying certain FSH or LH receptor variants is associated with altered sensitivity, which may call for adjusting the starting dose or adding LH activity. This approach relies on the biology of the specific patient rather than on averaged protocol templates.

The material fits naturally into the philosophy of the POSEIDON group, which the speaker co-founded: the emphasis is on the prognosis of the outcome and on personalisation, not merely on the number of oocytes retrieved. Pharmacogenomics becomes a tool that turns the notion of the poor responder from a descriptive label into an explainable and potentially manageable phenomenon.

The practical takeaway for the clinic is that stimulation is moving steadily toward individualisation: assessing a patient's molecular background, treating the simplified lock-and-key model with caution, and accounting for pharmacokinetics allow a more reasoned choice of drug, dose, and the appropriateness of LH support. For the reproductive specialist this is the basis for more predictable and better-grounded protocols.

Carlo Alviggi

Author of the lecture "Pharmacogenomics of LH and FSH receptors"

Carlo Alviggi

Topics covered

Carlo Alviggi