NF-κB as an Inflammatory Biomarker in Thin Endometrium: Predictive Value for Live Birth in Recurrent Implantation Failure

<b>Background:</b> Recurrent implantation failure (RIF) poses a major challenge in assisted reproductive technologies, with thin endometrium (≤7 mm) being a frequently observed yet poorly understood condition. Emerging evidence implicates nuclear factor-kappa B (NF-κB), a key transcription factor in inflammatory signaling, in impaired endometrial receptivity. However, its clinical relevance and prognostic value for live birth outcomes still need to be fully elucidated. <b>Objective:</b> We aim to evaluate the expression levels of endometrial NF-κB in patients with RIF and thin endometrium and to determine its potential as a predictive biomarker for live birth outcomes following IVF treatment. <b>Methods:</b> In this prospective case-control study, 158 women were categorized into three groups: Group 1 (RIF with thin endometrium, ≤7 mm, <i>n</i> = 52), Group 2 (RIF with normal endometrium, >7 mm, <i>n</i> = 38), and fertile controls (<i>n</i> = 68). NF-κB levels were assessed using ELISA and immunohistochemical histoscore. Pregnancy outcomes were compared across groups. ROC analysis and multivariable logistic regression were performed to assess the predictive value of NF-κB. <b>Results:</b> NF-κB expression was significantly elevated in Group 1 compared to Group 2 and controls (<i>p</i> = 0.0017). ROC analysis identified a cut-off value of 7.8 ng/mg for live birth prediction (AUC = 0.72, sensitivity 74%, specificity 75%). Multivariable analysis confirmed NF-κB is an independent predictor of live birth (<i>p</i> = 0.045). Histological findings revealed increased NF-κB staining in luminal and glandular epithelial cells in the thin endometrium group. <b>Conclusions:</b> Increased endometrial NF-κB expression is associated with thin endometrium and reduced live birth rates in RIF patients. NF-κB may serve not only as a biomarker of pathological inflammation but also as a prognostic tool for treatment stratification in IVF. Based on findings in the literature, the therapeutic targeting of NF-κB may represent a promising strategy to improve implantation outcomes.