Distinct Systemic Inflammatory Signatures in Women with Endometriosis and Infertility Without Endometriosis: Implications for Assisted Reproduction

Luana Ghilea (Seleș), Laura Maghiar, Viorela-Romina Murvai, Goman Marius, Alin Bodog, Carmen Anca Huniadi
In: Medicina · 2026 · vol. 62(9) , pp. 1641 · doi:10.3390/medicina62091641 · W7204454491
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This study found that women with endometriosis and infertile women without the condition exhibit distinct systemic inflammatory profiles, characterized by a higher IL-6/TNF-α ratio in endometriosis, compared to healthy controls.

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Abstract

Background and Objectives: Endometriosis is a chronic inflammatory disease associated with impaired fertility, but the extent to which its systemic inflammatory profile differs from that observed in infertile women without endometriosis remains incompletely understood. This study aimed to characterize and compare the systemic inflammatory profiles of women with endometriosis, infertile women without endometriosis, and healthy controls by evaluating serum interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and high-sensitivity C-reactive protein (hs-CRP). In addition, the study explored the IL-6/TNF-α ratio as an indicator of inflammatory balance and evaluated its relationship with ovarian reserve. Materials and Methods: This observational comparative study included 87 women divided into three groups: healthy controls (n = 29), women with endometriosis (n = 29), and infertile women without endometriosis (n = 29). Serum IL-6, TNF-α, and hs-CRP concentrations were determined specifically for the present study, whereas the corresponding clinical and embryological data were retrieved from medical records. Group comparisons were performed using the Kruskal–Wallis test followed by Dunn’s post hoc test with Holm correction. The IL-6/TNF-α ratio was calculated as an exploratory indicator of inflammatory balance. Associations between inflammatory biomarkers and anti-Müllerian hormone (AMH) concentrations were assessed using Spearman’s correlation analysis. Results: Significant differences in serum inflammatory biomarkers were observed among the three groups. IL-6 concentrations were significantly increased in both women with endometriosis and infertile women without endometriosis compared with healthy controls, whereas TNF-α concentrations were significantly elevated only in infertile women without endometriosis compared with both healthy controls and women with endometriosis (adjusted p < 0.001 for both comparisons). Differences in hs-CRP were more modest but remained significant overall. Women with endometriosis exhibited a significantly higher IL-6/TNF-α ratio than infertile women without endometriosis, suggesting distinct inflammatory patterns between these conditions. No significant correlations were identified between circulating inflammatory biomarkers and AMH concentrations. Conclusions: Women with endometriosis and infertile women without endometriosis exhibit distinct systemic inflammatory profiles rather than simply different levels of inflammation. The IL-6/TNF-α ratio may provide additional information regarding the balance of inflammatory pathways beyond the isolated evaluation of individual cytokines. Larger prospective studies integrating systemic and local inflammatory biomarkers with assisted reproductive outcomes are warranted to validate these findings and further explore their clinical relevance.

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