{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T17:41:18Z","timestamp":1793727678767,"version":"4.6.1"},"reference-count":86,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T00:00:00Z","timestamp":1774828800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The recurrent implantation failure (RIF) remains a major clinical challenge in assisted reproduction. While endometrial immune dysregulation is implicated, its specific role and interaction with clinical factors are poorly defined. The lack of integrated, multimodal predictive models that combine clinical history with immune profiling limits personalized management.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This study conducted a retrospective cohort study of 110 RIF patients, collecting comprehensive clinical and immune parameters. Traditional statistics and machine learning were employed to identify key predictors and build predictive models. Model interpretability was assessed using SHAP analysis, and causal pathways were explored\n                      <jats:italic>via<\/jats:italic>\n                      mediation analysis and restricted cubic splines.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Previous implantation failure number was the strongest negative predictor (aOR = 0.74, 95% CI 0.60\u20130.91,\n                      <jats:italic>P<\/jats:italic>\n                      = 0.004). Endometrial CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cell proportion exhibited a positive, threshold\u2212dependent effect: above 2.0%, each 1% increase raised the odds of success by 25% (aOR = 1.25, 95% CI 1.03\u20131.52,\n                      <jats:italic>P<\/jats:italic>\n                      = 0.025). Embryo quality was an independent positive predictor (aOR = 1.62, 95% CI 1.04\u20132.53,\n                      <jats:italic>P<\/jats:italic>\n                      = 0.033). Machine\u2212learning modeling (XGBoost) achieved an AUC of 0.762 (95% CI 0.734\u20130.790). Mediation analysis revealed that 22.8% of the total effect of immune dysregulation on outcome was mediated through CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells. Furthermore, the protective effect of CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells was significantly enhanced in patients with severe immune disorder (interaction\n                      <jats:italic>P<\/jats:italic>\n                      = 0.034).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      This integrated clinical-immune signature underscores the pivotal, threshold-dependent role of endometrial CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells and the cumulative burden of previous failures in RIF. The internally validated machine-learning model offers a prognostic tool, and the elucidated CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cell-mediated pathway suggests a target for immunomodulation, advancing the precision management of RIF.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1788922","type":"journal-article","created":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T04:12:17Z","timestamp":1774843937000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Endometrial immune dysregulation shapes CD8+ T cell mediated reproductive outcomes in recurrent implantation failure: an integrated mechanistic and predictive analysis"],"prefix":"10.3389","volume":"17","author":[{"given":"Shan","family":"Jiang","sequence":"first","affiliation":[{"name":"Reproductive Center, Boai Hospital of Zhongshan","place":["Zhongshan, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yeqing","family":"Fu","sequence":"additional","affiliation":[{"name":"Reproductive Center, Boai Hospital of Zhongshan","place":["Zhongshan, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiufeng","family":"Lin","sequence":"additional","affiliation":[{"name":"Reproductive Center, Boai Hospital of Zhongshan","place":["Zhongshan, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingni","family":"Li","sequence":"additional","affiliation":[{"name":"Reproductive Center, Boai Hospital of Zhongshan","place":["Zhongshan, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhibin","family":"Huang","sequence":"additional","affiliation":[{"name":"Reproductive Center, Boai Hospital of Zhongshan","place":["Zhongshan, Guangdong, China"]},{"name":"The First School of Clinical Medicine, Guangdong Medical University","place":["Zhanjiang, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cong","family":"Zhou","sequence":"additional","affiliation":[{"name":"The First School of Clinical Medicine, Guangdong Medical University","place":["Zhanjiang, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yecheng","family":"Zou","sequence":"additional","affiliation":[{"name":"Reproductive Center, Boai Hospital of Zhongshan","place":["Zhongshan, Guangdong, China"]},{"name":"The First School of Clinical Medicine, Guangdong Medical University","place":["Zhanjiang, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yutong","family":"Li","sequence":"additional","affiliation":[{"name":"The First School of Clinical Medicine, Guangdong Medical University","place":["Zhanjiang, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"e2500918","DOI":"10.1002\/adhm.202500918","article-title":"Integration of bioengineered tools in assisted reproductive technologies","volume":"14","author":"Ak","year":"2025","journal-title":"Adv Healthc Mater"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/deaf036","article-title":"Cumulative live birth rates of 31\u2013478 untested embryos from 11\u2013463 women challenge traditional recurrent implantation failure definitions","volume":"40","author":"Dhaenens","year":"2025","journal-title":"Hum Reprod"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2023.11.036","article-title":"If recurrent implantation failure is rare, what could be the cause of repeated unsuccessful assisted reproductive technologies","volume":"121","author":"de Ziegler","year":"2024","journal-title":"Fertil Steril"},{"key":"B4","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1016\/j.fertnstert.2023.02.014","article-title":"Recurrent implantation failure: reality or a statistical mirage?: Consensus statement from the July 1, 2022 Lugano Workshop on recurrent implantation failure","volume":"120","author":"Pirtea","year":"2023","journal-title":"Fertil Steril"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/deae040","article-title":"Does recurrent implantation failure exist? 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