Comparison of IL-1β, IL-17 and IL-18 Levels in the Follicular Microenvironment in Tubal Factor and Unexplained Infertility Cases in IVF Cycles

Oya Korkmaz, Seda Karabulut, Pelin Macit
In: Journal of Advances in VetBio Science and Techniques · 2026 · pp. 76–84 · doi:10.31797/vetbio.1820373 · W7160447087
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Unexplained infertility cases showed higher follicular fluid IL-1β, IL-17, IL-18, and oxidant markers, with lower antioxidant capacity, impacting pregnancy outcomes.

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This study measured interleukin-1β, interleukin-17, and interleukin-18, along with total antioxidant capacity (TAC) and total oxidant capacity (TOC), in follicular fluid and serum from 70 IVF patients split into tubal factor infertility (n=35) versus unexplained infertility (n=35), and assessed associations with oocyte/embryo quality and clinical pregnancy outcomes. In the unexplained infertility group, follicular fluid showed significantly higher IL-1β, IL-17, and IL-18 and redox imbalance (lower TAC with higher TOC and OSI), while serum levels did not differ between groups; follicular fluid cytokines correlated positively with TOC/OSI and negatively with TAC. Logistic regression indicated follicular fluid IL-18 and OSI as independent factors reducing the likelihood of clinical pregnancy, and the authors interpret the findings as follicular inflammasome–Th17 activation with oxidative stress; a key limitation is the small, single-center sample restricted to two infertility categories without external validation. Relevance to endometriosis: the paper focuses on inflammatory cytokines and oxidative stress in follicular microenvironments relevant to pelvic inflammatory disease contexts but does not explicitly discuss endometriosis or adenomyosis.

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Abstract

This study compares follicular fluid (FF) and serum IL-1β, IL-17, and IL-18 levels, as well as total antioxidant (TAC) and total oxidant (TOC) capacities in cases of tubal factor and unexplained infertility, and to investigate the relationship of these parameters with oocyte and embryo quality and clinical pregnancy outcomes. Seventy patients undergoing IVF cycles were divided into two groups: tubal factor (n = 35) and unexplained infertility (n = 35). IL-1β, IL-17, and IL-18 levels in FF and serum samples were measured by ELISA; TAC and TOC were measured spectrophotometrically. Intergroup differences and correlations between biochemical markers and embryological variables were statistically analysed. In the unexplained infertility group, IL-1β, IL-17, IL-18 levels were significantly higher, TAC levels were lower, and TOC and OSI values were increased, particularly in follicular fluid (p < 0.05). No significant differences were found in serum levels. In FF, positive correlations were found between cytokine levels and TOC and OSI, and negative correlations with TAC. In logistic regression analysis, FF IL- 18 (OR = 0.78, p = 0.02) and OSI (OR = 0.82, p = 0.03) were independent factors reducing the likelihood of clinical pregnancy. Cases of unexplained infertility are characterised by follicular microenvironment inflammasome-Th17 activation and redox imbalance. This condition may adversely affect oocyte and embryo quality. Analysis of IL-1β, IL-17, IL-18, TAC, TOC, and OSI levels in FF and serum may guide diagnostic differentiation and targeted treatment strategies. The findings suggest that antioxidant and inflammasome-targeted approaches may be potential adjunctive treatment options in unexplained infertility.
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Abstract

This study compares follicular fluid (FF) and serum IL-1β, IL-17, and IL-18 levels, as well as total antioxidant (TAC) and total oxidant (TOC) capacities in cases of tubal factor and unexplained infertility, and to investigate the relationship of these parameters with oocyte and embryo quality and clinical pregnancy outcomes. Seventy patients undergoing IVF cycles were divided into two groups: tubal factor (n = 35) and unexplained infertility (n = 35). IL-1β, IL-17, and IL-18 levels in FF and serum samples were measured by ELISA; TAC and TOC were measured spectrophotometrically. Intergroup differences and correlations between biochemical markers and embryological variables were statistically analysed. In the unexplained infertility group, IL-1β, IL-17, IL-18 levels were significantly higher, TAC levels were lower, and TOC and OSI values were increased, particularly in follicular fluid (p < 0.05). No significant differences were found in serum levels. In FF, positive correlations were found between cytokine levels and TOC and OSI, and negative correlations with TAC. In logistic regression analysis, FF IL- 18 (OR = 0.78, p = 0.02) and OSI (OR = 0.82, p = 0.03) were independent factors reducing the likelihood of clinical pregnancy. Cases of unexplained infertility are characterised by follicular microenvironment inflammasome-Th17 activation and redox imbalance. This condition may adversely affect oocyte and embryo quality. Analysis of IL-1β, IL-17, IL-18, TAC, TOC, and OSI levels in FF and serum may guide diagnostic differentiation and targeted treatment strategies. The findings suggest that antioxidant and inflammasome-targeted approaches may be potential adjunctive treatment options in unexplained infertility.

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References

- Adamczak, R., Ukleja-Sokołowska, N., Lis, K., & Dubiel, M. (2021). Function of follicular cytokines: roles played during maturation, development and implantation of embryo. Medicina, 57(11), 1251. https://doi.org/10.3390/medicina57111251 - Albeitawi, S., Bani-Mousa, S. U., Jarrar, B., Aloqaily, I., Al-Shlool, N., Alsheyab, G., Kassab, A., Qawasmi, B., & Awaisheh, A. (2025). Associations between follicular fluid biomarkers and IVF/ICSI outcomes in normo-ovulatory women-a systematic review. Biomolecules, 15(3), 443. https://doi.org/10.3390/biom15030443 - Ameho, S., & Klutstein, M. (2025). The effect of chronic inflammation on female fertility. Reproduction, 169(4), e240197. https://doi.org/10.1530/REP-24-0197 - Ozatik, O., Aydin, Y., Hassa, H., Ulusoy, D., Ogut, S., & Sahin, F. (2013). Relationship between oxidative stress and clinical pregnancy in assisted reproductive technology treatment cycles. Journal of Assisted Reproduction and Genetics, 30(6), 765–772. https://doi.org/10.1007/s10815-013-0005-2 - Barroso-Villa, G., Valdespin-Fierro, C., Weiser-Smeke, A. E., Machargo-Gordillo, A. P., Flores-Pliego, A., Palma-Lara, I., & Oehninger, S. (2023). Follicular fluid biomarkers for prediction of human IVF outcome in women with poor ovarian response. Middle East Fertility Society Journal, 28(1), 2. https://doi.org/10.1186/s43043-023-00128-8 - Batóg, G., Dołoto, A., Bąk, E., Piątkowska-Chmiel, I., Krawiec, P., Pac-Kożuchowska, E., & Herbet, M. (2023). The interplay of oxidative stress and immune dysfunction in Hashimoto's thyroiditis and polycystic ovary syndrome: A comprehensive review. Frontiers in Immunology, 14, 1211231. https://doi.org/10.3389/fimmu.2023.1211231 - Begum, I. A. (2025). Oxidative stress: Oocyte quality and infertility. Reproductive Toxicology, 137, 109011. https://doi.org/10.1016/j.reprotox.2025.109011 - Berkel, C. (2024). Inducers and inhibitors of pyroptotic death of granulosa cells in models of premature ovarian insufficiency and polycystic ovary syndrome. Reproductive Sciences, 31(10), 2972–2992. https://doi.org/10.1007/s43032-024-01643-3 Details Primary Language English Subjects Biochemistry and Cell Biology (Other) Journal Section Research Article Authors Oya Korkmaz * 0000-0003-2923-5869 Türkiye Seda Karabulut 0000-0003-3302-5004 Türkiye Pelin Macit 0000-0002-5666-0687 Türkiye Publication Date May 6, 2026 Submission Date November 9, 2025 Acceptance Date March 15, 2026 Published in Issue Year 2026 Number: 2

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