Clinical response to controlled ovarian stimulation in IVF programs in women with anovulatory infertility: a pilot study

Lapshtaeva A.V., Sychev I.V., Puzakova D.V., Kostina Y.A., Adamchik A.I., Chilova R.A., Sychev D.A.

1) N.P. Ogarev National Research Mordovian State University, Saransk, Russia; 2) B.V. Petrovsky Russian Scientific Center of Surgery, Moscow, Russia; 3) Mordovian Republican Central Clinical Hospital, Saransk, Russia; 4) I.M. Sechenov First Moscow State Medical University, Moscow, Russia; 5) Russian Medical Academy of Continuous Professional Education, Moscow, Russia

Background: Dysfunction of the hypothalamic-pituitary-ovarian axis, leading to anovulation, is one of the most common causes of female reproductive dysfunction. When conservative hormonal therapy is ineffective, in vitro fertilization (IVF) programs with controlled ovarian stimulation (COS) are necessary. To improve the clinical efficacy of IVF programs, the search for additional markers that can predict the pharmacological response to COS is essential.
Objective: Evaluation of the relationship between polymorphic variants of the cytochrome P450 (CYP) genes: CYP1A1, CYP1A2, CYP17A1, and CYP19A1, and the main parameters of clinical response to COS in women with anovulation.
Materials and methods: This prospective cohort study included 60 patients with anovulatory infertility and normal ovarian reserve (mean age 29.4 ± 3.7 years) undergoing IVF with superovulation stimulation using a short protocol and gonadotropin-releasing hormone antagonists. Genotyping of 18 single nucleotide polymorphisms in the CYP1A1, CYP1A2, CYP17A1, and CYP19A1 genes was performed using the Illumina iScan platform.
Results: Carriage of the T/C rs1048943 genotype of the CYP1A1 gene was associated with a significant reduction in the number of oocytes retrieved. Variants rs10046 (A/A genotype), rs700518 (C/C), and rs1062033 (G/G) of the CYP19A1 gene demonstrated a significant association with the risk of developing a «poor» response (OR = 6.96; 6.96; 6.33, respectively; p < 0.05).
Conclusion: The obtained data from the pilot study demonstrate an association between CYP family genes and individual responses to COS in patients with anovulatory infertility, highlighting the importance of continued research and the development of personalized stimulation protocols. 

For citations: Lapshtaeva A.V., Sychev I.V., Puzakova D.V., Kostina Y.A., Adamchik A.I., Chilova R.A., Sychev D.A. Clinical response to controlled ovarian stimulation in IVF programs in women with anovulatory infertility: a pilot study. Pharmateca. 2026;33(4):161-171. (In Russ.). DOI: https://dx.doi.org/10.18565/pharmateca.2026.4.161-171

Authors’ contribution: D.A. Sychev, A.V. Lapshtaeva, R.A. Chilova – study concept and design, study supervision, writing and approval of the manuscript. I.V. Sychev – statistical analysis, working with a database. D.V. Puzakova – technical editing. A.V. Lapshtaeva, Y.A. Kostina,
A.I. Adamchik, D.V. Puzakova – literature search, manuscript writing. A.V. Lapshtaeva, A.I. Adamchik – collection of clinical and biological material.
Conflicts of interest: The authors confirm that they have no conflicts of interest to declare.
Funding: The study was conducted without any sponsorship.
Ethical Approval: Исследование одобрено локальным этическим комитетом ФГБОУ ВО «МГУ им. Н.П. Огарева», протокол №116 от 12.05.2023), исследование выполнено в соответствии с Хельсинской декларацией ВМА.
Patient Consent for Publication: All patients provided informed consent for the publication of their data.
Authors’ Data Sharing Statement: The data supporting the findings of this study are available upon request from the corresponding author after approval from the principal investigator.

Keywords

About the Authors

Anna V. Lapshtaeva, Cand. Sci. (Med.), Associate Professor, Associate Professor at the Department of Immunology, Microbiology, and Virology with a Course in Clinical Immunology and Allergology, N.P. Ogarev National Research Mordovian State University, Saransk, Russia; av_lapshtaeva@mail.ru, ORCID: https://orcid.org/0000-0003-4828-2476, Scopus Author ID: 57200385359, eLibrary SPIN: 9138-6257 (corresponding author)
I.V. Sychev, Researcher at the World-Class Genomic Research Center «Center for Predictive Genetics, Pharmacoge Department of Clinical Pharmacology and Personalized Therapy», B.V. Petrovsky Russian Scientific Center of Surgery, Moscow, Russia; sychev_iv@bk.ru, ORCID:
https://orcid.org/0000-0002-6454-2349, Scopus Author ID: 58597330600, eLibrary SPIN: 5162-3779
D.V. Puzakova, 5th-year student, General Medicine specialty, Medical Institute, N.P. Ogarev National Research Mordovian State University, Saransk, Russia; dashapuzakova.puzakova@yandex.ru, ORCID: https://orcid.org/0009-0003-3442-1225, eLibrary SPIN: 8812-1945
Y.A. Kostina, N.P. Ogarev National Research Mordovian State University, Saransk, Russia
A.I. Adamchik, Head of the Department of Assisted Reproductive Technologies, Mordovian Republican Central Clinical Hospital, Saransk, Russia; bikbaeva87@inbox.ru, ORCID: https://orcid.org/0009-0009-1856-2750
R.A. Chilova, Dr. Sci. (Med.), Associate Professor, Head of the Department of Obstetrics and Gynecology No. 1, Sechenov First Moscow State Medical University, Moscow, Russia; chilova_r_a@staff.sechenov.ru, ORCID: https://orcid.org/0000-0001-6331-310, Scopus Author ID: 26027727100, eLibrary SPIN: 4137-4848
D.A. Sychev, Dr. Sci. (Med.), Professor, Academician of the Russian Academy of Sciences, Scientific Director of the World-Class Genomic Research Center «Center for Predictive Genetics, Pharmacoge Department of Clinical Pharmacology and Personalized Therapy», B.V. Petrovsky Russian Scientific Center of Surgery; Head of the Department of Clinical Pharmacology and Therapy named after academician B.E. Votchal, Russian Medical Academy of Continuous Professional Education, Moscow, Russia; d.a.sychev.rmapo@rambler.ru, ORCID: https://orcid.org/0000-0002-4496-3680, Scopus Author ID: 7801389135, eLIBRARY: 4525-7556

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