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

Мұқаба

Дәйексөз келтіру

Толық мәтін

Ашық рұқсат Ашық рұқсат
Рұқсат жабық Рұқсат берілді
Рұқсат жабық Рұқсат ақылы немесе тек жазылушылар үшін

Аннотация

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.

Негізгі сөздер

Толық мәтін

Рұқсат жабық

Авторлар туралы

Ekaterina Romanova

Siberian State Medical University

Хат алмасуға жауапты Автор.
Email: katyromanova24@mail.ru
ORCID iD: 0009-0006-1925-538X

Student

Ресей, 2, Moskovsky Trakt St., Tomsk, 634050

Kira Sidorenkova

Siberian State Medical University

Email: kirasidorenkova@mail.ru
ORCID iD: 0009-0007-6263-6716

PhD Student at the Department of Obstetrics and Gynecology

Ресей, 2, Moskovsky Trakt St., Tomsk, 634050

Ilya Petrov

Siberian State Medical University

Email: obgynsib@gmail.com
ORCID iD: 0000-0002-0697-3896

Dr. Med. Sci., Professor at the Department of Obstetrics and Gynecology

Ресей, 2, Moskovsky Trakt St., Tomsk, 634050

Lyudmila Spirina

Siberian State Medical University; Research Institute of Oncology of the Tomsk National Research Medical Center of the Russian Academy of Sciences

Email: spirinalvl@mail.ru
ORCID iD: 0000-0002-5269-736X

Dr. Med. Sci., Professor, Head of the Department of Biochemistry and Molecular Biology with a Course of Clinical Laboratory Diagnostics; Leading Researcher at the Laboratory of Tumor Biochemistry

Ресей, 2, Moskovsky Trakt St., Tomsk, 634050; 5, Kooperativny Lane, Tomsk, 634009

Yulia Samoylova

Siberian State Medical University; Novosibirsk National Research State University

Email: samoilova_y@inbox.ru
ORCID iD: 0000-0002-2667-4842

Dr. Med. Sci., Professor at the Department of Faculty Therapy with Clinical Pharmacology, Professor at the Department of Pediatrics with Endocrinology, Head of the Clinical Research Center; Director of the Institute of Medicine and Medical Technologies; Chief Specialist for Medical Prevention of the Department of Health of the Tomsk Region

Ресей, 2, Moskovsky Trakt St., Tomsk, 634050; 1, Pirogov St., Novosibirsk, 630090

Marina Stakheeva

Siberian State Medical University; Research Institute of Oncology of the Tomsk National Research Medical Center of the Russian Academy of Sciences

Email: stakheyevam@oncology.tomsk.ru
ORCID iD: 0000-0003-0601-2240

Dr. Med. Sci., Professor at the Department of Biochemistry and Molecular Biology with a Course of Clinical Laboratory Diagnostics; Leading Researcher at the Laboratory of Tumor Biochemistry

Ресей, 2, Moskovsky Trakt St., Tomsk, 634050; 5, Kooperativny Lane, Tomsk, 634009

Evgeny Merkulov

Siberian State Medical University

Email: evmerc@mail.ru
ORCID iD: 0000-0002-7082-9389

Laboratory Assistant at the Department of Biochemistry and Molecular Biology with a Course of Clinical Laboratory Diagnostics

Ресей, 2, Moskovsky Trakt St., Tomsk, 634050

Yulia Okkel

Siberian State Medical University

Email: okkel_uv@mail.ru
ORCID iD: 0000-0001-6386-1535

PhD, Teaching Assistant at the Department of Obstetrics and Gynecology

Ресей, 2, Moskovsky Trakt St., Tomsk, 634050

Marina Kubykina

Siberian State Medical University

Email: marina.kubykina@mail.ru
ORCID iD: 0009-0002-4598-1079

Obstetrician-Gynecologist, Reproductologist at the Assisted Reproductive Technology Centre

Ресей, 2, Moskovsky Trakt St., Tomsk, 634050

Yana Arkhipova

Siberian State Medical University

Email: yana_98@icloud.com
ORCID iD: 0009-0002-1062-7344

Obstetrician-Gynecologist, Reproductologist at the Assisted Reproductive Technology Centre

Ресей, 2, Moskovsky Trakt St., Tomsk, 634050

Әдебиет тізімі

  1. Ban M., Jiao J., Zhou J., Cui L., Wang H., Chen Z.J. Association of age at menarche and different causes of infertility: a retrospective study of 7634 women undergoing assisted reproductive technology. J. Ovarian Res. 2025; 18(1): 40. https://dx.doi.org/10.1186/s13048-025-01629-y
  2. Loukopoulos T., Zikopoulos A., Kolibianakis E., Vatopoulou A., Gkrozou F., Sotiriou S. et al. High-Risk outcomes in in vitro fertilization pregnancies for women of a very advanced maternal age: insights from a multi-hospital study in Greece. J. Clin. Med. 2025; 14(4): 1323. https://dx.doi.org/10.3390/jcm14041323
  3. Moreira T., Leal C., Barreiro M., Tomé A., Vale-Fernandes E. Predictors of pregnancy after artificial insemination in women with polycystic ovary syndrome. JBRA Assist. Reprod. 2025; 29(2): 201-10. https://dx.doi.org/10.5935/ 1518-0557.20240095
  4. Basso C.G., Rocha B.A., Hauer I.R., Cruz J.C., Filho F.F., Barbosa F. et al. Associations between urinary and follicular fluid concentrations of phthalate metabolites and reproductive outcomes in Brazilian women undergoing fertility treatment. Reprod. Toxicol. 2025; 133: 108868. https://dx.doi.org/10.1016/ j.reprotox.2025.108868
  5. Sarapik A., Velthut A., Haller-Kikkatalo K., Faure G.C., Béné M.C., de Carvalho Bittencourt M. et al. Follicular proinflammatory cytokines and chemokines as markers of IVF success. Clin. Dev. Immunol. 2012; 2012: 606459. https://dx.doi.org/10.1155/2012/606459
  6. Базиева Т.А., Ордиянц И.М., Джабраилова Б.А., Тунгузбиева Р.У. Современные представления о нарушениях состояния эндометрия при привычном невынашивании. Медицинский вестник Юга России. 2022; 13(4): 53-7. [Bazieva T.A., Ordiyants I.M., Dzhabrailova B.A., Tunguzbieva R.U. Modern ideas about the violation of endometrial receptivity in recurrent miscarriage. Medical Herald of the South of Russia. 2022; 13(4): 53-7 (in Russian)]. https://dx.doi.org/10.21886/2219-8075-2022-13-4-53-57
  7. Хонина Н.А., Андреева Е.А., Тихонова М.А., Баторов Е.В., Останин А.А., Пасман Н.М., Черных Е.Р. Интерлейкин-6 как возможный регулятор интрафолликулярных Foxp3+-регуляторных T-клеток у женщин в цикле экстракорпорального оплодотворения. Иммунология. 2019; 40(2): 30-7. [Khonina N.A., Andreeva E.A., Tikhonova M.A., Batorov E.V., Ostanin A.A., Pasman N.M., Chernykh E.R. Interleukin-6 as a possible regulator of intrafollicular FoxP3+ T-cells in women undergoing IVF treatmen. Immunologiya. 2019; 40(2): 30-7 (in Russian)]. https://dx.doi.org/10.24411/0206-4952-2019-12005
  8. Artini P.G., Scarfò G., Marzi I., Fusi J., Obino M.E., Franzoni F. et al. Oxidative stress-related signaling pathways predict oocytes' fertilization in vitro and embryo quality. Int. J. Mol. Sci. 2022; 23(21): 13442. https://dx.doi.org/10.3390/ijms232113442
  9. Rimon-Dahari N., Yerushalmi-Heinemann L., Alyagor L., Dekel N. Ovarian Folliculogenesis. Results Probl. Cell. Differ. 2016; 58: 167-90; https://dx.doi.org/10.1007/978-3-319-31973-5_7
  10. Волченок Д.А., Тихоновская О.А., Мустафина Л.Р., Логвинов С.В. Экспрессия факторов паракринной регуляции в яичниках крыс при коррекции экспериментальных функциональных кист яичников. Journal of Siberian Medical Sciences. 2019; 1: 67-77. [Volchenok D.A., Tikhonovskaya O.A., Mustafina L.R., Logvinov S.V. Expression of paracrine regulation factors in rat’s ovaries when correcting experimental functional ovarian cysts. Journal of Siberian Medical Sciences. 2019; 1: 67-77 (in Russian)]. https://dx.doi.org/10.31549/2542-1174-2019-1-67-77
  11. Hidalgo A.I., Ulloa-Leal C., Gajardo G., López G., Carretta D., Burgos R.A. et al. Ovulation induced by intrauterine seminal plasma increases total protein, PGE2, IL-8, and IL-1β in uterine fluid of llamas (Lama glama). Animals. 2023; 13(4): 554. https://dx.doi.org/10.3390/ani13040554
  12. Gonzalez M.B., Lane M., Knight E.J., Robker R.L. Inflammatory markers in human follicular fluid correlate with lipid levels and body mass index. J. Reprod. Immunol. 2018; 130: 25-9. https://dx.doi.org/10.1016/j.jri.2018.08.005
  13. Лихачева В.В., Зорина Р.М., Баженова Л.Г., Маркдорф А.Г., Архипова С.В., Филимонов С.Н. Содержание и прогностическое значение некоторых цитокинов в сыворотке крови и фолликулярной жидкости у женщин с синдромом поликистозных яичников, участвующих в программе ЭКО. Медицина в Кузбассе. 2017; 16(4): 34-8. [Likhacheva V.V., Zorina R.M., Bazhenova L.G., Markdorf A.G., Arkhipova S.V., Filimonov S.N. Content and prognostic value of some cytokines in blood serum and follicular fluid in women with polycystic ovary syndrome participating in the IVF program. Medicine in Kuzbass. 2017; 16(4): 34-8 (in Russian)].
  14. Mahdian S., Zarrabi M., Moini A., Shahhoseini M., Movahedi M. In silico evidence for prednisone and progesterone efficacy in recurrent implantation failure treatment. J. Mol. Model. 2022; 28(4): 105. https://dx.doi.org/10.1007/s00894-022-05093-z
  15. Awonuga A.O., Camp O.G., Abu-Soud H.M. A review of nitric oxide and oxidative stress in typical ovulatory women and in the pathogenesis of ovulatory dysfunction in PCOS. Reprod. Biol. Endocrinol. 2023; 21(1): 111. https://dx.doi.org/10.1186/s12958-023-01159-6
  16. Dai M., Hong L., Yin T., Liu S. Disturbed follicular microenvironment in polycystic ovary syndrome: relationship to oocyte quality and infertility. Endocrinology. 2024; 165(4): bqae023. https://dx.doi.org/10.1210/endocr/bqae023
  17. Приказ Минздрава России от 31.07.2020 № 803н «О порядке использования вспомогательных репродуктивных технологий, противопоказаниях и ограничениях к их применению» (зарегистрировано в Минюсте России 19.10.2020 № 60457). Доступно по: https://www.consultant.ru/document/cons_doc_LAW_365474/ [Order of the Ministry of Health of the Russian Federation No. 803n dated July 31, 2020 "On the procedure for using assisted reproductive technologies, contraindications, and restrictions on their use" (registered with the Ministry of Justice of the Russian Federation on October 19, 2020, No. 60457). Available at: https://www.consultant.ru/document/cons_doc_LAW_365474/ (in Russian)].
  18. Приказ Минздрава России от 30.08.2012 № 107н (ред. от 01.02.2018) «О порядке использования вспомогательных репродуктивных технологий, противопоказаниях и ограничениях к их применению» (зарегистрировано в Минюсте России 12.02.2013 № 27010). Доступно по: https://www.consultant.ru/document/cons_doc_LAW_142595/ [Order of the Ministry of Health of the Russian Federation No. 107n dated August 30, 2012 (as amended on February 1, 2018) "On the procedure for using assisted reproductive technologies, contraindications, and restrictions on their use" (registered with the Ministry of Justice of the Russian Federation on February 12, 2013, No. 27010). Available at: https://www.consultant.ru/document/cons_doc_LAW_142595/(in Russian)].
  19. Алегина Е.В., Тетруашвили Н.К., Агаджанова А.А., Трофимов Д.Ю., Донников А.Е. Полиморфизм гена интерлейкина-8 у женщин с привычными потерями беременности. Акушерство и гинекология. 2015; 9: 33-7. [Alegina E.V., Tetruashvili N.K., Agadzhanova A.A., Trofimov D.Yu., Donnikov A.E. Interleukin-8 gene polymorphism in women with recurrent miscarriages. Obstetrics and Gynecology. 2015; (9): 33-7 (in Russian)].
  20. Соснин Д.Ю., Галькович К.Р. Содержание моноцитарного хемотаксического фактора в нормальной сперме и в образцах эякулята с пониженной фертильностью. Пермский медицинский журнал. 2019; 36(3): 28-37. [Sosnin D.Yu., Galkovich K.R. Monocyte chemotactic factor content in normal sperm and in samples of ejaculate with diminished fertility. Perm Medical Journal. 2019; 36(3): 28-37 (in Russian)]. https://dx.doi.org/10.17816/pmj36328-37
  21. Турдыбекова Я.Г. Фолликулогенез и фолликулярный запас яичника в норме и патологии: аспекты (этапы) клинико-морфологического изучения (литературный обзор). Вестник Казахского Национального медицинского университета. 2019; 1: 41-5. [Turdybekova Y.G. Folliculogenesis and follicular reserve of the ovary in health and disease: aspects of clinical and morphological study (review). Bulletin of the Kazakh National Medical University. 2019; (1): 41-5 (in Russian)].
  22. Граф А.В., Байжуманов А.А., Маслова М.В., Крушинская Я.В., Маклакова А.С., Соколова Н.А., Каменский А.А. Активность антиоксидантной системы при беременности в норме и при гипоксии. Вестник Московского университета. Серия 16. Биология. 2021; 76(3): 126-33. [Graf A.V., Baizhumanov A.A., Maslova M.V., Krushinskaya Y.V., Maklakova A.S., Sokolova N.A., Kamensky A.A. The antioxidant system activity during normal pregnancy and pregnancy following by hypoxic stress. Vestnik Moskovskogo universiteta. Seriya 16. Biologiya. 2021; 76(3): 126-33 (in Russian)].
  23. Пушкина Т.А., Токаев Э.С., Попова Т.С., Бородина Е.Н. Супероксиддисмутаза в составе антиоксидантной терапии: состояние вопроса и перспективы (обзор литературы). Журнал им. Н.В. Склифосовского «Неотложная медицинская помощь». 2016; 4: 42-7. [Pushkina T.A., Tokayev E.S., Popova T.S., Borodina E.N. Superoxide dismutase as a component of antioxidant therapy: current state of the issue and prospects (a literature review). Sklifosovsky journal of emergency medical care. 2016; (4): 42-7 (in Russian)].
  24. Меняйло М.Е., Малащенко В.В., Шмаров В.А., Газатова Н.Д., Мелащенко О.Б., Гончаров А.Г., Селедцова Г.В., Селедцов В.И. Интерлейкин-8 способен поддерживать провоспалительную активность моноцитов (макрофагов) человека. Гены и клетки. 2018; 13(1): 65-9. [Meniailo M.E., Malashchenko V.V., Shmarov V.A., Gazatova N.D., Melashchenko O.B., Goncharov A.G., Seledsova G.V., Seledsov V.I. Interleukin-8 is able to promote pro-inflammatory activity of human monocytes (macrophages). Genes and Cells. 2018; 13(1): 65-9 (in Russian)]. https://dx.doi.org/10.23868/201805007
  25. Bulavenko O.V., Kelman V.V. Effect of stress on ovulatory function. Reports of Vinnytsia National Medical University. 2023; 27(3): 523-7. https://dx.doi.org/10.31393/reports-vnmedical-2023-27(3)-28
  26. Hoffmann J.A., Gründler K., Richter D.U. Stubert J. Prediction of spontaneous preterm birth using CCL2 and CXCL10 in maternal serum of symptomatic high-risk pregnant women: a prospective cohort study. BMC Pregnancy Childbirth. 2023; 23(1): 697. https://dx.doi.org/10.1186/s12884-023-06016-3

Қосымша файлдар

Қосымша файлдар
Әрекет
1. JATS XML
Жүктеу
2. Figure. ROC curve for the model determining the probability of pregnancy outcome

Жүктеу (59KB)
Метадеректер

© Bionika Media, 2025