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Problem: Soluble immune checkpoint molecules constitute the emerging novel mediators in immune regulation. Their role in the pathogenesis of endometriosis has not been fully addressed. In this study, we aimed to investigate the relationship between the clinical manifestation of endometriosis-associated infertility and the level of four soluble immune checkpoints: sCTLA4, sHLA-G, sPD-1, and sPD-L1. Method of study: The soluble immune checkpoint concentrations in serum and peritoneal fluid from 88 patients who underwent laparoscopy were evaluated by the enzyme-linked immunosorbent assay (ELISA). Clinical and hematological parameters were documented and analyzed. Results: Endometriosis cases were evident to have significantly higher levels of serum sPD-L1 and all four molecules in peritoneal fluid compared to non-endometriosis control. Contrary, no significant differences were found in the concentration of serum sCTLA-4, sHLA-G and, sPD-1 between endometriosis and control group. There were significant positive correlations between serum and peritoneal fluid concentrations of sCTLA-4, sPD-L1, and sHLA-G. Serum sPD-L1 could discriminate endometriosis-related infertility to other pathological control. At a cutoff of 14,61 pg/ mL, serum sPD-L1 had a sensitivity of 77% and specificity of 83%. Moreover, sPD-L1 level showed positive correlations with pelvic adhesion score and myeloid cell count. Conclusion: The elevated level of sPD-L1 in serum and immune checkpoint molecules in the peritoneal fluid could represent the hallmark of immune regulation in endometriosis. Serum sPD-L1 could serve as a potential noninvasive endometriosis biomarker. Also, the immune compartment related to the local immune checkpoint molecules may be implicated in biological mechanisms underlying endometriosisrelated infertility.

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Objective To evaluate IL-1β, IL-6, IL-8, and IL-12p70 levels in serum and peritoneal fluid in women related to infertility and pelvic pain. Methods Eighty-seven women were diagnosed with endometriosis or cases related to infertility. IL-1β, IL-6, IL-8, and IL-12p70 levels in serum and peritoneal fluid were determined by ELISA. Pain assessment was evaluated by the Visual Analog Scale (VAS) score. Results Serum IL-6 and IL-12p70 levels increased in women with endometriosis compared to the control group. Serum and peritoneal IL-8 and IL-12p70 levels correlated with VAS scores in infertile women. A positive correlation was also found between peritoneal IL-1β and IL-6 with VAS score. A significant difference in peritoneal IL-1β levels was associated with menstrual pelvic pain, while peritoneal IL-8 levels were related to dyspareunia, menstrual, and post-menstrual pelvic pain in infertile women. Conclusion An association of IL-8 and IL-12p70 levels were related to pain in endometriosis, as well as a relationship between cytokine expression and VAS score. Further studies should be addressed to investigate the precise mechanism of cytokine-related pain in endometriosis.