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ORIGINAL RESEARCH
CYP1A2 pharmacogenetic markers as clinical pregnancy predictors in the in vitro fertilization programs for anovulatory infertility
1 National Research Mordovia State University, Saransk, Russia
2 Petrovsky Russian Scientific Center for Surgery, Moscow, Russia
3 Mordovian Republican Central Clinical Hospital, Saransk, Russia
4 Ivanovo State Medical University, Ivanovo, Russia
5 Russian Medical Academy of Continuous Professional Education, Moscow, Russia
Correspondence should be addressed: Anna V. Lapshtaeva
Bolshevistskaya, 68, Saransk, 430005, Russia; ur.liam@aveathspal_va
Author contribution: Sychev DA, Lapshtaeva AV — study concept and design, study management, manuscript writing and approval; Sychev IV, Marmuleva VS — statistical analysis, database work; Puzakova DV — technical editing; Lapshtaeva AV, Adamchik AI, Puzakova DV — search for literature, manuscript writing; Lapshtaeva AV, Adamchik AI — clinical and biological material collection.
Compliance with ethical standards: the study was approved by the ethics committee of the National Research Ogarev Mordovia State University (protocol no. 116 dated 12 May 2023). All the subject submitted the informed consent to take part in the study.
Anovulatory infertility remains a significant medical and social issue requiring the development of new approaches to personalized patient management in assisted reproductive technology programs. Pharmacogenetic testing of hormone metabolism gene polymorphisms can contribute to optimization of ovarian stimulation protocols and higher in vitro fertilization (IVF) efficacy. The study aimed to assess a possible association of polymorphic variants of CYP isoenzyme genes (CYP1A1, CYP1A2, CYP17А1, CYP19A1) with the IVF program clinical efficacy in patients with anovulatory infertility. A total of 18 polymorphisms of the CYP1A1, CYP1A2, CYP17A1, and CYP19A1 genes were analyzed by genotyping on the Illumina iScan platform. The CYP1A2 Т/Т rs2470890 and А/А rs762551 genotype carrier state is associated with the increased likelihood of getting pregnant (OR = 3.824; 95% CI: 1.150–12.713, p = 0.023 and OR = 4.030; 95% CI: 1.372–11.839, p = 0.009, respectively). As for other studied polymoprhisms, including rs1048943, rs1800031, rs4646903, rs2606345 (gene CYP1А1), rs2069514 (gene CYP1А2), rs743572, rs104894136 (gene CYP17А1), rs10046, rs936306, rs700518, rs749292, rs1062033, rs2470152, rs28757157, rs6493497, rs7176005 (CYP19А1), no significant differences in the abundance of genotypes between comparison groups were revealed (p > 0.05). The pilot study data obtained suggest the potential role of the CYP1A2 gene rs2470890 and rs762551 variants in modulation of the individual response to treatment and the IVF program efficacy in patients with anovulatory infertility.
Keywords: pharmacogenetics, anovulatory infertility, in vitro fertilization, cytochrome P450, CYP1A2, rs2470890, rs762551