L26/P-316 Role of soluble receptor for advanced glycation end product in Clinical Heterogeneity and Inflammation in Endometriosis Patients Undergoing IVF

Abstract Study question Does serum and follicular fluid sRAGE associate with clinical heterogeneity and inflammatory markers in women with endometriosis undergoing IVF Summary answer Serum and follicular fluid sRAGE levels reflect clinical variability and inflammation in endometriosis, suggesting its potential as a biomarker for clinical heterogeneity and inflammation What is known already Endometriosis is a chronic inflammatory and estrogen-dependent disease associated with oxidative stress and reduced reproductive potential. Advanced glycation end products (AGEs) contribute to inflammation through activation of the RAGE signaling pathway. The soluble form of RAGE (sRAGE) acts as a decoy receptor with anti-inflammatory properties. Altered levels of sRAGE have been reported in several metabolic and reproductive disorders, but its role in endometriosis, particularly in relation to follicular environment, remains insufficiently understood Study design, size, duration This prospective case-control study was conducted on 71 reproductive-aged women undergoing controlled ovarian stimulation (COS) and oocyte retrieval for IVF in Tehran, Iran, from September 2024 to September 2025. Forty women diagnosed with endometriosis comprised the case group, while 31 women with male factor infertility served as controls. The study was approved by the Ethics Committee of Tehran University of Medical Sciences. Participants/materials, setting, methods 71reproductive-aged women undergoing IVF were enrolled. Both groups received standardized GnRH antagonist protocols. Gonadotropins were administered from day 3–5, and follicular growth monitored via ultrasound. Follicular fluid was collected from the first aspirated follicle, and blood samples obtained before anesthesia. Samples were centrifuged, stored at − 80 °C, and sRAGE levels measured using ELISA kits. Main results and the role of chance Baseline demographic characteristics were comparable between the endometriosis and control groups, with no significant differences in age or body mass index, reducing potential confounding. Serum and follicular fluid sRAGE concentrations were significantly higher in women with endometriosis compared with controls (both P < 0.001), demonstrating a strong association between endometriosis and altered sRAGE levels. Within the endometriosis group, sRAGE concentrations showed no significant differences across pain severity categories, including dysmenorrhea, pelvic pain, and dyspareunia, indicating that sRAGE levels are not directly associated with pain-related symptoms. Assessment of clinical heterogeneity revealed that follicular fluid sRAGE levels were significantly lower in women with allergic conditions (P = 0.012), while serum sRAGE showed a similar but non-significant trend. No significant associations were observed between sRAGE levels and other comorbidities, including thyroid disorders, gastrointestinal disease, adenomyosis, migraines, asthma, diabetes, or multiple sclerosis. Statistical analyses were performed using appropriate parametric and non-parametric tests, supporting that the observed significant findings are unlikely due to chance. However, results related to less prevalent comorbidities should be interpreted cautiously because of limited sample sizes. Limitations, reasons for caution • Observational design: Much of the evidence is cross-sectional or case–control, which shows associations but not causation. • Biological complexity: Endometriosis involves multiple pathways (hormonal, immune, angiogenic), so sRAGE is only one piece of a larger puzzle. • Heterogeneity of patients: Disease severity, lesion location, and comorbidities vary widely, making it difficult to standardize findings Wider implications of the findings • New therapeutic targets: Enhancing sRAGE activity or mimicking its decoy function may open novel treatment pathways. • Interdisciplinary studies: Linking gynecology, immunology, and nutrition science could accelerate understanding of endometriosis. • Clinical trials needed: Randomized studies on AGE-restricted diets and sRAGE modulation are essential to move from theory to practice. Trial registration number No