Investigation of the effect of TNF-α levels on infertility duration and infertility characteristics in endometriosis patients presenting with infertility complaints

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Serum TNF-α levels were higher in infertile women with endometriosis compared to controls, but were not associated with infertility duration or ovarian reserve.

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This prospective comparative study enrolled 70 infertile women aged 20–37 years, including 35 with clinically and/or radiologically diagnosed endometriosis and 35 age-matched controls with unexplained infertility and no evidence of endometriosis, measuring serum TNF-α by ELISA and ovarian reserve using third-day AMH from records. Serum TNF-α levels were higher in the endometriosis group than controls, and after adjustment for age, BMI, smoking, and previous surgery, endometriosis status remained associated with higher log-transformed TNF-α, while the unadjusted association with AMH attenuated and was not statistically significant. Within the endometriosis group, TNF-α showed no association with infertility duration or AMH or with selected clinical characteristics. Limitations included modest sample size, clinical/radiologic case definition, potential selection bias, and lack of external validation for exploratory ROC findings. This paper is centrally about endometriosis — it tests whether serum TNF-α relates to infertility duration, ovarian reserve (AMH), and characteristics in infertile women with endometriosis.

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Abstract

BACKGROUND: Endometriosis is a chronic inflammatory disorder frequently associated with infertility. Tumor necrosis factor-alpha (TNF-α) is involved in inflammatory pathways; however, the clinical relevance of serum TNF-α in relation to infertility duration and ovarian reserve remains uncertain. METHODS: This prospective comparative study included 70 infertile women aged 20-37 years: 35 women with clinically and/or radiologically diagnosed endometriosis and 35 age-matched infertile controls with unexplained infertility and no clinical or imaging evidence of endometriosis. Serum TNF-α was measured using enzyme-linked immunosorbent assay. Hormonal parameters, including anti-Müllerian hormone (AMH), were obtained from third-day menstrual-cycle samples retrieved from clinical records. Associations between TNF-α, infertility duration, AMH, and clinical characteristics were evaluated. Exploratory adjusted analyses were performed for log-transformed TNF-α and AMH. RESULTS: Serum TNF-α levels were higher in the endometriosis group than in controls (median [IQR], 235.49 [124.33-390.31] vs. 64.58 [58.91-76.52] ng/L; p < 0.001). AMH levels were lower in the endometriosis group in unadjusted analysis (2.05 [1.67-3.41] vs. 3.30 [2.26-3.66] ng/mL; p = 0.029). After adjustment for age, BMI, smoking status, and previous surgical history, endometriosis group status remained associated with log-transformed TNF-α (β = 1.386, 95% CI 1.114 to 1.657; p < 0.001), whereas the association with AMH was attenuated (β=-0.824, 95% CI -1.817 to 0.169; p = 0.102). TNF-α was not associated with infertility duration or AMH within the endometriosis group. CONCLUSIONS: Serum TNF-α was elevated in infertile women with clinically and/or radiologically diagnosed endometriosis but was not associated with infertility duration, AMH, or selected clinical characteristics. The high discriminatory performance observed in ROC analysis should be interpreted as exploratory because of the modest sample size, clinical/radiologic case definition, potential selection bias, and lack of external validation. Serum TNF-α may reflect systemic inflammatory activity rather than infertility severity or ovarian reserve impairment.
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Abstract

Background Endometriosis is a chronic inflammatory disorder frequently associated with infertility. Tumor necrosis factor-alpha (TNF-α) is involved in inflammatory pathways; however, the clinical relevance of serum TNF-α in relation to infertility duration and ovarian reserve remains uncertain.

Methods

This prospective comparative study included 70 infertile women aged 20–37 years: 35 women with clinically and/or radiologically diagnosed endometriosis and 35 age-matched infertile controls with unexplained infertility and no clinical or imaging evidence of endometriosis. Serum TNF-α was measured using enzyme-linked immunosorbent assay. Hormonal parameters, including anti-Müllerian hormone (AMH), were obtained from third-day menstrual-cycle samples retrieved from clinical records. Associations between TNF-α, infertility duration, AMH, and clinical characteristics were evaluated. Exploratory adjusted analyses were performed for log-transformed TNF-α and AMH.

Results

Serum TNF-α levels were higher in the endometriosis group than in controls (median [IQR], 235.49 [124.33-390.31] vs. 64.58 [58.91–76.52] ng/L; p < 0.001). AMH levels were lower in the endometriosis group in unadjusted analysis (2.05 [1.67–3.41] vs. 3.30 [2.26–3.66] ng/mL; p = 0.029). After adjustment for age, BMI, smoking status, and previous surgical history, endometriosis group status remained associated with log-transformed TNF-α (β = 1.386, 95% CI 1.114 to 1.657; p < 0.001), whereas the association with AMH was attenuated (β=-0.824, 95% CI -1.817 to 0.169; p = 0.102). TNF-α was not associated with infertility duration or AMH within the endometriosis group.

Conclusions

Serum TNF-α was elevated in infertile women with clinically and/or radiologically diagnosed endometriosis but was not associated with infertility duration, AMH, or selected clinical characteristics. The high discriminatory performance observed in ROC analysis should be interpreted as exploratory because of the modest sample size, clinical/radiologic case definition, potential selection bias, and lack of external validation. Serum TNF-α may reflect systemic inflammatory activity rather than infertility severity or ovarian reserve impairment. Similar content being viewed by others Abbreviations - TNF-α: - Tumor necrosis factor-alpha - AMH: - Anti-Müllerian hormone - FSH: - Follicle-stimulating hormone - LH: - Luteinizing hormone - E2: - Estradiol - BMI: - Body mass index - HSG: - Hysterosalpingography - DIE: - Deep infiltrating endometriosis - ELISA: - Enzyme-linked immunosorbent assay - ROC: - Receiver operating characteristic - AUC: - Area under the curve - CI: - Confidence interval

Acknowledgements

Acknowledgements: This study was derived from a thesis registered in the National Thesis Center of the Council of Higher Education (YÖK) of Türkiye (Thesis No: 974200; Reference No: 10519228). The authors acknowledge the institutional support provided during the preparation of this work. Funding The authors received no specific funding for this work. Author information Authors and Affiliations Corresponding author Ethics declarations Ethics approval and consent to participate This study was conducted in accordance with the principles of the Declaration of Helsinki. Ethical approval was obtained from the Ankara City Hospital 2nd Clinical Research Ethics Committee (approval no. E2-22-2275; August 17, 2022). Written informed consent was obtained from all participants prior to enrollment. Consent for publication Not applicable. Competing interests The authors declare no competing interests. Additional information Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Rights and permissions Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. About this article Cite this article Özuyar Şimşek, G., Uzunlar, Ö., Özen, S. et al. Investigation of the effect of TNF-α levels on infertility duration and infertility characteristics in endometriosis patients presenting with infertility complaints. BMC Women's Health (2026). https://doi.org/10.1186/s12905-026-04586-w Received: Accepted: Published: DOI: https://doi.org/10.1186/s12905-026-04586-w

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