Molecular genetic predictors of the development of an unexpected poor response to ovarian stimulation in the in vitro fertilization program

• Irina S. Belova
• Svetlana G. Perminova
• Guzel V. Savostina

Abstract

The aim of the study was to evaluate the role of genetic polymorphisms in the pathogenesis of an unexpected poor response to ovarian stimulation (OS) in patients with normal parameters of the ovarian reserve (POSEI-DON 1 and 2).

Material and methods. The study analyzed the parameters of 161 OS cycles in patients with unpredictable poor response to OS (POSEIDON 1 and 2) and patients in the comparison group. All women who participated in the study underwent blood serum analysis for gene polymorphisms potentially involved in the development of unpredictable poor response.

Results. According to the autosomal recessive model of inheritance, the T allele of the rs4149056 T>C polymorphism of the SLCO1B1 gene is associated with an unpredictable poor response to OS in women of older reproductive age [p=0.002, OR 2.62 (1.34–5.12)]. There is a statistically significant difference in the occurrence of the genotype G/G polymorphism FSHR 2039 A>G gene in patients of POSEDON 1 and 2 and the control groups, which is associated with the receiving of fewer follicles on the day of introduction of the ovulation trigger as well as with a smaller number of oocyte-cumulus complexes and mature oocytes. Also the frequency of occurrence of the genotype G/G polymorphism rs4986938 of the ESR2 gene in patients with normal ovarian reserve parameters and an unexpected poor response to OS (POSEIDON 1 and 2) was significantly higher compared to the control group (53.1 and 48 versus 37.5%). Evaluation of gene polymorphisms in blood serum is a statistically significant prognostic marker of poor response to OS, including for women in the age group up to 35 years with normal AMH and CAF levels.

Conclusion. The use of a pharmacogenetic approach based on the study of the individual patient genotype is a relevant strategy for selecting a personalized protocol for ovarian stimulation and overcoming the unpredictable poor response to OS in a cohort of patients with normal parameters of ovarian reserve (POSEI-DON 1 and 2).

Keywords: unexpected poor response; ovarian stimulation; POSEIDON criteria; in vitro fertilization; single nucleotide polymorphism

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