Reproductive healthLecture

Genetics of the ovarian response

Why do two patients with the same age, AMH and antral count respond differently to the same stimulation? A look at the genetic markers — FSHR, LHCGR, ESR polymorphisms — that increasingly drive personalised protocol design.

Belén Lledó

Audio: EN · UA · RUSubtitles: EN · RU · UA34 min

Belén Lledó

PhD

Scientific Director of Instituto Bernabeu Biotech, the genetics arm of the Instituto Bernabeu group, and coordinator of its R&D&I. A molecular biologist with a PhD and specialization in human genetics, she focuses on preimplantation genetic testing (PGT), reproductive genetics and the application of AI in genetic screening. Lecturer on the Master's in Reproductive Medicine at the University of Alicante.

LinkedIn →

Belén Lledó's lecture opens with an observation familiar to every reproductive specialist: two patients with identical clinical characteristics, on the same protocol, may show completely different ovarian responses. Increasingly, the explanation for this variability is sought not in the clinic but in the genetics of gonadotropin receptors.

The usual response predictors — AMH, basal FSH, antral follicle count — assess the ovary's "capacity" but not its sensitivity to the drugs. FSH- and LH-receptor polymorphisms change how a follicle reacts to a standard dose: one genotype needs less hormone, another needs more. This is the limitation of a purely clinical approach that the speaker addresses.

This concerns primarily receptor-gene polymorphisms — for example the well-studied FSHR variant at position 680 (Ser/Asn), as well as LH-receptor variants. The same protocol "meets" receptors of differing sensitivity in different patients, which explains the cases of "unexpected" hypo- or hyper-response not predicted by age or AMH.

The practical core is LH dosing guided by the LH-receptor genotype. A pharmacogenetic profile allows, for example, 37.5 IU for a favourable genotype and 75 IU for an unfavourable one, instead of a single one-size dose. This moves dose selection from intuition to a measurable biomarker.

The key figure comes from Instituto Bernabeu data: genotype-based dose individualisation raises the live-birth rate from 29% to 50%. The near-doubling is achieved not through more aggressive stimulation but through a closer match of dose to the biology of the individual patient.

Hence the practical question of when to genotype: before the first stimulation, to start correctly, or after an unexpectedly poor response. The lecture outlines the method's promise and limits — it does not replace clinical assessment but adds a layer earlier predictors missed.

The speaker also outlines the practical frame: genotyping is a one-off test whose result does not change over time and can be reused across all of a patient's future cycles. The limits are test cost and availability, and the fact that a panel covers only part of the known variants. The method is therefore positioned as a complement to clinical assessment, not a replacement.

For the clinician the conclusion is simple: "one dose for all" gives way to personalisation. The genetics of ovarian response is not abstract science but a tool that, in specific centres, is already changing measurable ART outcomes.

Topics covered

FSHR polymorphisms
LHCGR polymorphisms
ESR polymorphisms
Genotype-guided ovarian stimulation
Predictive value vs age and AMH

Belén Lledó

Author of the lecture "Genetics of the ovarian response"