TNFΑ, IL-6, 25 (OH) VITAMIN D LEVELS IN FOLLICULAR FLUID AS PREDICTORS OF PREGNANCY IN POLYCYSTIC OVARY SYNDROME



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Abstract

Changes in cytokine levels and 25(OH) vitamin D in follicular fluid may be a prediction of the pregnancy. The purpose of this study is to identify associations between follicular fluid levels of TNFα, IL-6, IFNγ, IL-10, and 25(OH) vitamin D in PCOS and IVF outcomes. Materials and methods: 48 women were examined, including 24 women with PCOS (group 1 (study)) and 24 women without PCOS (women with tubal factor infertility) (group 2 (control). Women in both groups were comparable for age and BMI. TNFα, IL-6, IFNγ, IL-10, and 25(OH) vitamin D were analyzed in follicular fluid obtained after transvaginal follicle puncture in the IVF program. The Mann-Whitney U test was used. ROC curve analysis was used to assess discriminatory ability in predicting outcome. Differences were considered statistically significant at p < 0.05. Results: TNFα in group 1 was 5,9 times higher, IL-6 2.4 times higher compared to the control group (p < 0.001). IFNγ and IL-10 did not differ between groups (p > 0.05). 25(OH) vitamin D in group 1 was 2.1 times lower compared to group 2 (p < 0.0001). A moderate inverse relationship was found in patients of group 1 (r = – 0.455, p = 0.026) between the level of 25 (OH) vitamin D and TNFα and an inverse moderate relationship in group 1 (r = – 0.398, p < 0.05) between the level of 25 (OH) vitamin D and IL-6. The onset of pregnancy was predicted by the following values: TNFα – 12.9 pg/ml (AUC = 0.908; 95% CI: 0.818 – 0.999, p < 0.001). IL-6 – 10.4 pg/ml (AUC = 0.916; 95% CI: 0.829 – 1.000, p < 0.001), 25 (OH) vitamin D – 26.6 ng/ml (AUC = 0.986; 95% CI: 0.953 – 1.000, p < 0.001). Conclusions: To improve the outcomes of the IVF program in PCOS, it is necessary to determine TNFα, IL-6, 25 (OH) vitamin D in follicular fluid during oocyte retrieval, which can affect the positive prognosis for pregnancy.

About the authors

Olga Valikova

Pacific State Medical University, Vladivostok, Russia;
Regional Clinical Hospital № 2 Vladivostok

Email: renalex.99@mail.ru
ORCID iD: 0009-0003-5026-3773
SPIN-code: 2827-5828

junior research assistant interdisciplinary laboratory center Pacific State Medical University

Russian Federation

Victoria Vladimirovna Zdor

Pacific State Medical University, Vladivostok, Russia

Email: zdor.vv@tgmu.ru
ORCID iD: 0000-0003-1085-3632
SPIN-code: 5018-1630

MD, PhD,  prof, leading researcher Pacific State Medical University

Russian Federation

Elena Vladimirovna Markelova

Pacific State Medical University, Vladivostok, Russia

Email: markelova.ev@tgmu.ru
ORCID iD: 0000-0001-5846-851X
SPIN-code: 3661-5026

PhD,  prof, Vice – Rector for  Research Activities, Head of the Department of normal and pathological physiology Pacific State Medical University

Russian Federation

Andrey Victorovich Boroda

A.V. Zhirmunsky National Scientific Center of Marine Biology
Far East Branch of Russian Academy of Sciences. The laboratory of Cell technology

Author for correspondence.
Email: borodandy@gmail.com

PhD, Senior Researcher, Deputy Director for Scientific Activities.

Russian Federation

References

  1. Adamyan L.V., Andreeva E.N., Absatarova Y.S., Grigoryan O.R., Dedov I.I., Melnichenko G.A., Smetnik A.A., Suturina L.V., Filippov O.S., Sheremetyeva E.V., Uvarova E.V., Khashchenko S.P., Chernukha G.E., Yarmolinskaya M.I. [Russian national clinical recommendations «polycystic ovary syndrome». version of 2025 year] Bulletin of Reproductive Health. 2025;4(3):28-39.;Russian.doi:https://doi.org/10.14341/brh12773.
  2. Amato G, Conte M, Mazziotti G, Lalli E, Vitolo G, Tucker AT, Bellastella A, Carella C, Izzo A. Serum and follicular fluid cytokines in polycystic ovary syndrome during stimulated cycles. Obstet Gynecol. 2003 Jun;101(6):1177-82. doi: 10.1016/s0029-7844(03)00233-3. PMID: 12798522.
  3. Bøllehuus Hansen L, Rehfeld A, de Neergaard R, Nielsen JE, Iversen LH, Boisen IM, Mortensen LJ, Lanske B, Almstrup K, Carlsen E, Berg AH, Jørgensen N, Andersen AN, Juul A, Blomberg Jensen M. Selection of High-Quality Spermatozoa May Be Promoted by Activated Vitamin D in the Woman. J Clin Endocrinol Metab. 2017 Mar 1;102(3):950-961. doi: 10.1210/jc.2016-3008. PMID: 27977320.
  4. Fu Y, Wang YH, Wang L, Huang MR. Correlation between follicular fluid of 25-hydroxyvitamin D level and endocrine function, ovarian function and insulin resistance in women with polycystic ovary syndrome. J Physiol Pharmacol. 2025 Jun;76(3). doi: 10.26402/jpp.2025.3.07. Epub 2025 Jul 16. PMID: 40698789.
  5. Huang X, Yin Z, Xu J, Wu H, Wang Y. The Inflammatory State of Follicular Fluid Combined with Negative Emotion Indicators can Predict Pregnancy Outcomes in Patients with PCOS. Reprod Sci. 2024 Aug;31(8):2493-2507. doi: 10.1007/s43032-024-01538-3. Epub 2024 Apr 23. PMID: 38653858.
  6. Obeagu EI, Obeagu GU. From menses to ovulation: the immunomodulatory role of monocyte cytokines in menstrual cycle physiology and reproductive health - a narrative review. Ann Med Surg (Lond). 2025 Oct 7;87(12):8453-8459. doi: 10.1097/MS9.0000000000004021. PMID: 41377340; PMCID: PMC12688960.
  7. Ozyurt R, Karakus C. Follicular fluid 25-hydroxyvitamin D levels determine fertility outcome in patients with polycystic ovary syndrome. Taiwan J Obstet Gynecol. 2022 Jul;61(4):620-625. doi: 10.1016/j.tjog.2022.03.041. PMID: 35779910.
  8. Seaward Brain HP, Georgiou C, Mason HD, Rice S. The effect of vitamin D (1,25-(OH)2-D3) on human theca and granulosa cell function. Reproduction. 2025 Mar 25;169(4):e250002. doi: 10.1530/REP-25-0002. PMID: 40100123.
  9. Wang B, Hao M, Yang Q, Li J, Guo Y. Follicular fluid soluble receptor for advanced glycation endproducts (sRAGE): a potential protective role in polycystic ovary syndrome. J Assist Reprod Genet. 2016 Jul;33(7):959-65. doi: 10.1007/s10815-016-0704-6. Epub 2016 Mar 24. PMID: 27011370; PMCID: PMC4930779.

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