Pharmacogenomics in reproductive medicine: from genetic code to outcome

Nataliia Vladykina opens practical pharmacogenomics in reproductive medicine with a talk on moving from the genetic code to the clinical result and, above all, on overcoming a hypo-response to stimulation.

The starting point is the POSEIDON 1–2 groups: patients with a suboptimal response in whom standard doses yield fewer oocytes than the reserve predicts. This is exactly where genetics is especially useful.

The central theme is FSH-receptor polymorphisms, above all the Asn680Ser variant and position 307. Different genotypes "read" the same FSH dose differently, determining receptor sensitivity.

It is important to clearly separate a mutation from a polymorphism: a mutation may switch function off entirely, whereas a polymorphism only shifts the response — and this distinction has direct clinical consequences.

As a marker of suboptimal response Vladykina uses the FOI (follicle-to-oocyte index): it helps objectify the "shortfall" of oocytes relative to the antral pool.

To interpret polymorphisms the speaker relies on the Delphi consensus (Alviggi, Conforti), which frames how to translate genetic findings into protocol decisions.

FSH β-chain polymorphisms and the variant LH are examined separately: it is these profiles that indicate when standard FSH is insufficient and recombinant LH must be added to the protocol.

The GenOx 2025 study is cited, showing synergy of the FSH and LH receptors: their joint genetic characterisation predicts the response more accurately than either marker alone.

Vladykina also accounts for ethnic differences: the sensitivity and frequencies of polymorphisms differ between European and Asian populations (Hu 2024, Huang 2025 data), which matters for transferring results.