Reproductive healthLecture

Pharmacogenomics in Reproductive Medicine: From Genetic Code to Outcome

Lecture by Nataliia Vladykina, Medical Director of LITA clinic, reproductive medicine specialist and geneticist (Kyiv), on pharmacogenomics in ovarian stimulation. Why patients with a normal AMH and antral follicle count give a sub-optimal response and how to predict it: FSH receptor polymorphisms (Asn680Ser, position 307), the FOI index, the POSEIDON 1-2 classification, the Alviggi/Conforti Delphi consensus, FSH+LH receptor synergy from GenOx 2025, ethnic differences, Belen Lledó's AI prediction model and the rationale for urinary FSH in Ser-Ser carriers.

Nataliia Vladykina

Audio: UASubtitles: EN · UA · RU23 min

Nataliia Vladykina

Medical Director of the LITA reproductive clinic in Kyiv. Specialist in reproductive medicine, obstetrician-gynecologist and medical geneticist.

Ukraine

Why do standard FSH doses produce different results within the same demographic group? The answer lies in the genetics of the follicular apparatus. This lecture explores FSH receptor pharmacogenomics as a practical tool for individualizing ART stimulation — moving from an «average dose for everyone» to a targeted protocol based on the patient's genetic profile.

FSH receptor polymorphisms

FSH receptor polymorphisms determine the sensitivity of the follicular apparatus to exogenous FSH. Different genotypes call for different approaches to the starting dose and drug selection — from classical recombinant FSH to urinary FSH with stronger LH activity. The methodological distinction between mutations (complete loss of function) and polymorphisms (fine-tuning of the receptor) shapes how these markers are read in practice.

POSEIDON 1-2 and the FOI index

POSEIDON 1-2 defines «predicted poor responders» — younger patients with adequate ovarian reserve but a paradoxically weak response. The FOI index quantifies the gap between follicle count and oocytes retrieved. Combined with the genetic receptor profile, this shifts practice from an «average dose for everyone» to a targeted protocol — drug selection, starting dose, and adjunctive LH.

Ethnic specificity and LH supplementation

Current consensus statements confirm the role of LH supplementation for specific patient populations. A separate important aspect is the ethnic specificity of genetic markers: the same polymorphisms have different clinical significance across populations. This drives the need for local polymorphism maps. AI prediction models based on a panel of polymorphisms reach practical accuracy sufficient for routine clinical use.

For specific genotypes, urinary FSH often outperforms recombinant FSH in clinical outcomes — this has reshaped the routine approach. For intermediate genotypes — combined protocols with adjunctive LH. For wild type — standard doses remain effective. Receptor genotyping becomes a necessary part of the pre-cycle workup, not a «last resort when everything has already failed».

Topics covered

FSH receptor polymorphisms as the basis for individualizing stimulation
POSEIDON 1-2 and the FOI index in clinical practice
The role of LH supplementation in stimulation per current consensus
Ethnic specificity of genetic markers
AI models for predicting ovarian response
Urinary vs recombinant FSH for specific genotypes
Clinical algorithm for protocol selection based on genetic profile

Nataliia Vladykina

Medical Director of the LITA reproductive clinic in Kyiv. Specialist in reproductive medicine, obstetrician-gynecologist and medical geneticist.

Author of the lecture "Pharmacogenomics in Reproductive Medicine: From Genetic Code to Outcome"

Nataliia Vladykina

FSH receptor polymorphisms

POSEIDON 1-2 and the FOI index

Ethnic specificity and LH supplementation

Clinical takeaway

Topics covered

Nataliia Vladykina