Endometrial HOXA-10, HOXA-11, ß-1 integrin, ECM-1, FAK, and CD44 immunohistochemical expressions in endometriosis-related recurrent IVF failure: a retrospective case-control study

Background Endometriosis is a common cause of infertility and is frequently associated with recurrent implantation failure in assisted reproductive technologies. Impaired endometrial receptivity, mediated by altered transcription factors, adhesion molecules, and extracellular matrix components, has been proposed as a contributing mechanism. This study aimed to evaluate compartment-specific immunohistochemical expression patterns of HOXA-10, HOXA-11, CD44, β1 integrin, ECM-1, and focal adhesion kinase (FAK) in women with endometriosis-related implantation failure.

This retrospective case–control study was conducted at the IVF Unit of Gazi University Faculty of Medicine. The study group consisted of 34 infertile women with surgically confirmed endometriosis and recurrent IVF failure, subdivided into pre-receptive and receptive phases based on histological dating, while fertile women without infertility or endometriosis served as controls. Endometrial biopsies were obtained during the implantation window. Immunohistochemical expression was evaluated using semi-quantitative compartment-specific scoring, with ImageJ-based analysis used as supportive. Appropriate non-parametric statistical analyses were applied, and p < 0.05 was considered statistically significant.

No statistically significant intergroup differences were observed for stromal HOXA-10 or HOXA-11 expression between control, pre-receptive, and receptive groups. Glandular CD44 positivity was significantly increased in the receptive group compared with controls, while no significant difference was detected between pre-receptive and receptive phases after multiple comparison correction. β1 integrin expression did not demonstrate consistent phase-specific differences. In contrast, strong glandular ECM-1 expression was significantly reduced in both pre-receptive and receptive groups compared with controls, whereas stromal ECM-1 expression remained unchanged. Stromal FAK expression was significantly increased in both pre-receptive and receptive groups relative to controls, with no significant difference between these phases.

Endometriosis-related implantation failure is associated with distinct, compartment-specific alterations in endometrial receptivity markers that appear largely independent of physiological implantation timing. Reduced glandular ECM-1 expression and persistent stromal FAK accumulation suggest disease-specific epithelial–stromal dysregulation rather than delayed or shifted receptivity. Altered glandular CD44 expression in the receptive phase likely reflects endometriosis-associated epithelial adhesion changes rather than a phase-specific marker of functional receptivity. These findings highlight the importance of compartment-focused evaluation of endometrial receptivity in endometriosis-related infertility. Trial registration This study was retrospectively conducted and was not registered in a clinical trial registry. Similar content being viewed by others Data availability The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Uterine focal adhesions are retained at implantation after rat ovarian hyperstimulation. Reproduction. 2016;152(6):753–63. Acknowledgments dumyyyyy Third-party materials / permissions All figures and images are original to the authors; no third-party material was used and no permissions were required. Gels and blots This study did not include gels or blots; therefore, uncropped images are not applicable. Funding Not applicable. Author information Authors and Affiliations Contributions E.Ş.T. and M.E. designed and conducted the study and drafted the manuscript. Ö.E. and E.A.K. evaluated and interpreted the pathology preparations. S.S. performed the image analysis. A.E. evaluated patients with IVF failure. All authors read and approved the final manuscript. Corresponding author Ethics declarations Ethics approval and consent to participate This study was approved by the Ethics Committee of Gazi University (Date: 23 July 2020, Approval No: E-78167) and conducted in accordance with the principles of the Declaration of Helsinki. 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 Toruk, E.Ş., Kaplan, E.A., Sarıbaş, G.S. et al. Endometrial HOXA-10, HOXA-11, ß-1 integrin, ECM-1, FAK, and CD44 immunohistochemical expressions in endometriosis-related recurrent IVF failure: a retrospective case-control study. J Ovarian Res (2026). https://doi.org/10.1186/s13048-026-02072-3 Received: Accepted: Published: DOI: https://doi.org/10.1186/s13048-026-02072-3