CYP pharmacogenetic markers as predictors of IVF efficacy in anovulatory infertility

Background. Anovulatory infertility remains one of the leading causes of impaired fertility in women of reproductive age. The efficacy of in vitro fertilization (IVF) programs demonstrates interindividual variability, which necessitates the identification of reliable predictive markers to optimize personalized stimulation protocols. The role of pharmacogenetic variants of cytochrome P450 genes in predicting IVF outcomes in this condition remains insufficiently studied, which determines the relevance of this pilot study.
Objective. To evaluate the association of polymorphic variants of cytochrome P450 genes (CYP2A6, CYP2C9, CYP2C19, CYP2D6, CYP3A4, CYP3A5) with the achievement of clinical pregnancy in IVF programs in patients with anovulatory infertility.
Materials and methods. This prospective pilot cohort study included 96 patients divided into two groups: those who achieved pregnancy after their first IVF attempt (group 1, n = 48) and those with three or more failed cycles in their history (group 2, n = 48). Genotyping of 19 single‑nucleotide polymorphisms was performed using whole‑genome typing on Infinium Global Screening Array‑24 v3.0 biochips. Statistical analysis included the Pearson χ² test, Fisher's exact test, and the Monte Carlo permutation test (10,000 permutations).
Results. Statistically significant associations were identified between polymorphisms in CYP2A6 (rs8192733, rs56113850, rs57897628) and CYP2C19 (rs4244285) and IVF outcomes. For rs8192733, associations were found for the G/G genotype of CYP2A6 with an unsuccessful IVF cycle (OR = 0.105; 95 % CI 0.105–0.316; p < 0.001) and for the C/C and C/G genotypes with a successful procedure (OR = 4.795; 95 % CI 1.212–18.963; p = 0.031 and OR = 3.176; 95 % CI 1.202–8.395; p = 0.031, respectively). For the rs56113850 polymorphism in CYP2A6, the C/T genotype was associated with a favorable outcome (OR = 3.095; 95 % CI 1.284–7.458; p = 0.010), while the T/T genotype was associated with a negative outcome (OR = 0.286; 95 % CI 0.100–0.812; p = 0.015). The homozygous A/A genotype of the rs57897628 polymorphism in CYP2A6 was associated with a lower probability of pregnancy (OR = 0.256; 95 % CI 0.091–0.725; p = 0.005). For the CYP2C19 gene (rs4244285), the G/A genotype was associated with effective IVF (OR = 7.500; 95 % CI 2.016–27.901; p = 0.001).
Conclusion. According to the obtained results, CYP gene polymorphisms can serve as potential pharmacogenetic markers for predicting IVF effectiveness in patients with anovulatory infertility.

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