Cytokine levels and lipid peroxidation status in the blood, follicular fluid, and saliva of infertile women and their relationship with the effectiveness of in vitro fertilization
Romanova E.A., Sidorenkova K.A., Petrov I.A., Spirina L.V., Samoilova Yu.G., Stakheeva M.N., Merkulov E.D., Okkel Yu.V., Kubykina M.I., Arkhipova Ya.I.
Infertility affects approximately 17% of couples worldwide, representing approximately one-sixth of the adult population, underscoring the significance of this issue. The causes of infertility are diverse and affect human reproductive function. However, the role of immune disorders in the development of acute and chronic infectious and inflammatory diseases of the reproductive system in women has not yet been thoroughly investigated.
Objective: To determine the levels of TNF-α, interleukin-8, interleukin-10, VEGF, MCP-1, malondialdehyde, and the activity of catalase and superoxide dismutase (SOD) in the blood serum, follicular fluid, and saliva of infertile women undergoing in vitro fertilization (IVF), and to assess their impact on treatment effectiveness.
Materials and methods: This study included 32 women diagnosed with infertility who were undergoing IVF treatment. The participants were comparable in age (35.4 (4.4) years]). The study materials included blood serum, non-blood-contaminated follicular fluid samples, and saliva.
Cytokine levels (TNF-α, interleukin-8, interleukin-10, VEGF, and MCP-1) in the biological fluids were measured using enzyme immunoassays. Lipid peroxidation was assessed by measuring malondialdehyde levels and catalase and superoxide dismutase (SOD) activities.
Results: The cytokine levels in the follicular fluid were higher than those in the blood serum and saliva, regardless of IVF effectiveness. In women who successfully completed the IVF program (group 1), interleukin-8 levels increased 1.27-fold, MCP-1 levels increased 1.42-fold, and SOD activity decreased 2.54-fold in the follicular fluid. No significant differences were observed in the serum and saliva parameters.
Conclusion: The study found that follicular fluid contained the highest concentrations of cytokines, whereas TNF-α levels were nearly undetectable. In patients with favorable IVF outcomes, interleukin-8 and MCP-1 levels in the follicular fluid were higher than those in patients with negative IVF results. Distinct features of the cytokine profile were identified that may serve as potential predictors of ART program outcomes in patients diagnosed with infertility.
Authors' contributions: Spirina L.V., Romanova E.A., Samoilova Yu.G., Stakheeva M.N., Okkel Yu.V. – conception and design of the study; Sidorenkova K.A., Romanova E.A. – data collection and processing; Romanova E.A., Merkulov E.D. – statistical analysis; Spirina L.V., Romanova E.A., Kubykina M.I. – drafting of the manuscript; Spirina L.V., Petrov I.A., Samoilova Yu.G., Stakheeva M.N., Arkhipova Ya.I. – editing of the manuscript. All authors approved the final version of the article before submission, agreed to be accountable for all aspects of the study, implying appropriate investigation and resolution of questions related to the accuracy or integrity of any part of the study.
Conflicts of interest: The authors have no conflicts of interest to declare.
Funding: The study was conducted with financial support from the Siberian State Medical University.
Ethical Approval: The study was reviewed and approved by the Research Ethics Committee of the Siberian State Medical University (Ref. No: №8 of 18.01.2023).
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.
For citation: Romanova E.A., Sidorenkova K.A., Petrov I.A., Spirina L.V., Samoilova Yu.G., Stakheeva M.N., Merkulov E.D., Okkel Yu.V., Kubykina M.I., Arkhipova Ya.I. Cytokine levels and lipid peroxidation status in
the blood, follicular fluid, and saliva of infertile women and their relationship with
the effectiveness of in vitro fertilization.
Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2025; (8): 124-132 (in Russian)
https://dx.doi.org/10.18565/aig.2025.94
Keywords
cytokines
lipid peroxidation
ART effectiveness
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Received 07.04.2025
Accepted 10.07.2025
About the Authors
Ekaterina A. Romanova, student, Siberian State Medical University, Ministry of Health of Russia, 634050, Russia, Tomsk, Moscowski Trakt str., 2, katyromanova24@mail.ru, https://orcid.org/0009-0006-1925-538XKira A. Sidorenkova, PhD student at the Department of Obstetrics and Gynecology, Siberian State Medical University, Ministry of Health of Russia, 634050, Russia, Tomsk, Moscowski Trakt str., 2, +7(952)884-37-49, kirasidorenkova@mail.ru, https://orcid.org/ 0009-0007-6263-6716
Ilya A. Petrov, Dr. Med. Sci., Professor at the Department of Obstetrics and Gynecology, Siberian State Medical University, Ministry of Health of Russia, 634050, Russia, Tomsk, Moscowski Trakt str., 2, +7(952)899-83-66, obgynsib@gmail.com, https://orcid.org/0000-0002-0697-3896
Liudmila V. Spirina, Dr. Med. Sci., Professor, Head of the Department of Biochemistry and Molecular Biology with a course of clinical laboratory diagnostics, Siberian State Medical University, Ministry of Health of Russia, 634050, Russia, Tomsk, Moscowski Trakt str., 2; Leading Researcher at the Laboratory of Tumor Biochemistry, Research Institute of Oncology of Tomsk Scientific Research Center, 634009, Russia, Tomsk, Cooperative lane, 5, spirinalvl@mail.ru, https://orcid,org/0000-0002-5269-736X
Iuliia G. Samoilova, Dr. Med. Sci., Professor, Professor at the Department of Faculty Therapy with Clinical Pharmacology, Professor at the Department of Pediatrics with Endocrinology, Head of the Clinical Research Center, Siberian State Medical University, Ministry of Health of Russia, 634050, Russia, Tomsk, Moscowski Trakt str., 2; Chief Specialist for Medical Prevention of the Department of Health of the Tomsk Region, 634050, Russia, Tomsk, Moscowski Trakt str., 4; Director of the Institute of Medicine and Medical Technologies, Novosibirsk National Research State University, 630090, Russia, Novosibirsk, Pirogova str., 1, +7(913)826-74-24, samoilova_y@inbox.ru,
https://orcid.org/0000-0002-2667-4842
Marina N. Stakheeva, Dr. Med. Sci., Professor at the Department of Biochemistry and Molecular Biology with a course of clinical laboratory diagnostics, Siberian State Medical University, Ministry of Health of Russia, 634050, Russia, Tomsk, Moscowski Trakt str., 2; Leading Researcher at the Laboratory of Tumor Biochemistry, Research Institute of Oncology of Tomsk Scientific Research Center, 634009, Russia, Tomsk, Cooperative lane, 5, stakheyevam@oncology.tomsk.ru, https://orcid,org/0000-0003-0601-2240
Evgeny D. Merkulov, Laboratory Assistant, Siberian State Medical University, Ministry of Health of Russia, 634050, Russia, Tomsk, Moscowski Trakt str., 2,
evmerc@mail.ru, https://orcid,org/0000-0002-7082-9389
Iuliia V. Okkel, PhD, Teaching Assistant at the Department of Obstetrics and Gynecology, Siberian State Medical University, Ministry of Health of Russia, 634050, Russia, Tomsk, Moscowski Trakt str., 2, okkel_uv@mail.ru, https://orcid.org/0000-0001-6386-1535
Marina I. Kubykina, Obstetrician-Gynecologist, Reproductologist at the Center of ART, Siberian State Medical University, Ministry of Health of Russia, 634050, Russia, Tomsk, Moscowski Trakt str., 2, +7(983)235-54-21, marina.kubykina@mail.ru, https://orcid.org/0009-0002-4598-1079
Yana I. Arkhipova, Obstetrician-Gynecologist, Reproductologist at the Center of ART, Siberian State Medical University, Ministry of Health of Russia, 634050, Russia, Tomsk, Moscowski Trakt str., 2, +7(952)885-98-31, yana_98@icloud.com, https://orcid.org/0009-0002-1062-7344
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