Role of sRAGE in clinical heterogeneity and inflammation in endometriosis patients undergoing IVF; case-control study

Background Endometriosis is a multifactorial, chronic inflammatory disorder that affects a substantial proportion of women during their reproductive years and is frequently associated with pelvic pain and infertility. Accumulating evidence suggests that advanced glycation end products (AGEs), generated through dietary exposure and oxidative stress, may contribute to disease progression by activating the receptor for AGEs (RAGE), thereby promoting inflammatory and fibrotic signaling pathways. Rather than serving as an initiating factor, the AGE–RAGE axis is increasingly recognized as an amplifier of persistent inflammation and lesion persistence in endometriosis. The soluble isoform of RAGE (sRAGE) acts as a circulating decoy receptor that sequesters AGEs and attenuates downstream pro-inflammatory cascades. Although dysregulated sRAGE concentrations have been documented in various metabolic and reproductive conditions, its specific role in endometriosis—particularly within the follicular microenvironment and in relation to inflammatory status—remains incompletely characterized.

In this prospective case–control study, 71 women of reproductive age undergoing controlled ovarian stimulation and oocyte retrieval for in vitro fertilization (IVF) were enrolled. The case group included 40 women with confirmed endometriosis, while 31 women without endometriosis served as controls. Detailed clinical histories were obtained for both groups. Serum and follicular fluid samples were collected, and sRAGE concentrations were quantified using enzyme-linked immunosorbent assay (ELISA).

No significant differences were observed between groups regarding age or body mass index. Both serum and follicular fluid sRAGE concentrations were significantly elevated in women with endometriosis compared with controls (both P < 0.001). Evaluation of clinical heterogeneity demonstrated significantly lower follicular fluid sRAGE levels among endometriosis women with concomitant allergic conditionsnull (P = 0.012). Within the endometriosis cohort, sRAGE concentrations did not vary significantly according to pain severity, including dysmenorrhea, pelvic pain, or dyspareunia. Likewise, no significant associations were identified with thyroid disorders, gastrointestinal disease, adenomyosis, migraine, asthma, diabetes, or multiple sclerosis. Furthermore, sRAGE levels were not correlated with the number of retrieved oocytes or embryos in either group.

Women with endometriosis exhibited significantly elevated serum and follicular fluid sRAGE levels, suggesting altered AGE–RAGE axis activity. However, the absence of association with ovarian response indicates that sRAGE may reflect inflammatory status rather than reproductive outcomes. Similar content being viewed by others Abbreviations - sRAG: - soluble Receptor for Advanced Glycation End Product - AGE: - Advanced Glycation End Product - FF: - fulicular fluid - PCOS: - Polysystic Ovary Syndrom

We thank all participants who were involved in the present study. We also would like to extend our appreciation to university of Shahid Beheshti endocrinology department laboratory, for their sincere contributions in all laboratory procedures. Surgical teams in several hospitals are highly appreciated for their assistance in biopsy collection. Funding This project was a postdoc project of Dr. Neda Emami and supported by Department of Gynaecology and Obstetrics, Tehran University of Medical Sciences, Tehran, Iran. Author information Authors and Affiliations Corresponding author Ethics declarations Ethics approval and consent to participate The study was approved by the ethics committee of Tehran university of Medical Science (IR. TUMS.MEDICINE. REC.1403.269) and written informed consent were taken from all participants. Consent for publication N/A. Helsinki statement This study was conducted in accordance with the ethical principles outlined in the Declaration of Helsinki (as revised in 2013). The research protocol was reviewed and approved by the Institutional Ethics Committee of Tehran university of Medical Science (Approval No: IR. TUMS.MEDICINE. REC.1403.269). All participants were fully informed about the study objectives and procedures, and written informed consent was obtained prior to enrollment. Participation was voluntary, and confidentiality of personal and clinical data was strictly maintained throughout the study. 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-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, 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 you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. 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-nc-nd/4.0/. About this article Cite this article Emami, N., Moini, A. Role of sRAGE in clinical heterogeneity and inflammation in endometriosis patients undergoing IVF; case-control study. BMC Endocr Disord (2026). https://doi.org/10.1186/s12902-026-02416-6 Received: Accepted: Published: DOI: https://doi.org/10.1186/s12902-026-02416-6