CYP1 polymorphisms and endometrial thickness on the day of ovulation trigger administration

Background. Endometrial thickness on the day of ovulation trigger administration is a marker demonstrating endometrial readiness for embryo transfer in IVF programs. The proliferative response of the endometrium to stimulation is due to the action of estrogens, the effect of which is determined by the rate of biotransformation, dependent on the activity of cytochrome P450 (CYP). Genetic polymorphism of these enzymes can lead to variability in endometrial response to stimulation.

Objective. To determine the association of polymorphic variants of the CYP1A1, CYP1A2, and CYP1B1 genes with endometrial response in IVF programs in women with anovulatory infertility.

Materials and methods. The prospective pilot study included 96 patients (mean age 30.5±2.5 years) with anovulatory infertility who received standardized treatment according to a short gonadotropin-releasing hormone antagonist protocol. 13 single nucleotide polymorphisms were genotyped in genes CYP1A1, CYP1A2, CYP1B1 on the Illumina iScan platform. Statistical processing was carried out in the Statistica 12.5 program (StatSoft ).

Results. For rs762551 of the gene, endometrial thickness increased from C/C genotype to A/A (p < 0.001; Cohen's d > 0.6). The C/C homozygous genotype rs2470890 was associated with significantly smaller endometrial thickness compared to the C/T (p=0.007) and T/T (p < 0.001) genotypes. Carriers of the C/C genotypes rs10012, A/A rs1056827 and A/A rs2617266 of the CYP1B1 gene had a greater endometrial thickness than carriers of other genotypes (p < 0.05).

Conclusion. The found associations of the rs2470890, rs762551 CYP1A2 gene and rs10012, rs1056827, rs2617266 CYP1B1 gene polymorphisms with endometrial thickness on the day of ovulation trigger administration indicate that genetically determined features of estrogen metabolism may directly affect the proliferative response of the endometrium under stimulation, indicating the potential relevance of these markers for personalizing endometrial preparation protocols in IVF cycles.

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