{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:38:58Z","timestamp":1787027938286,"version":"build-2736575974"},"reference-count":41,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2025,7,12]],"date-time":"2025-07-12T00:00:00Z","timestamp":1752278400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Background: Recurrent implantation failure (RIF) poses a major challenge in assisted reproductive technologies, with thin endometrium (\u22647 mm) being a frequently observed yet poorly understood condition. Emerging evidence implicates nuclear factor-kappa B (NF-\u03baB), 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. Objective: We aim to evaluate the expression levels of endometrial NF-\u03baB in patients with RIF and thin endometrium and to determine its potential as a predictive biomarker for live birth outcomes following IVF treatment. Methods: In this prospective case\u2013control study, 158 women were categorized into three groups: Group 1 (RIF with thin endometrium, \u22647 mm, n = 52), Group 2 (RIF with normal endometrium, &gt;7 mm, n = 38), and fertile controls (n = 68). NF-\u03baB 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-\u03baB. Results: NF-\u03baB expression was significantly elevated in Group 1 compared to Group 2 and controls (p = 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-\u03baB is an independent predictor of live birth (p = 0.045). Histological findings revealed increased NF-\u03baB staining in luminal and glandular epithelial cells in the thin endometrium group. Conclusions: Increased endometrial NF-\u03baB expression is associated with thin endometrium and reduced live birth rates in RIF patients. NF-\u03baB 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-\u03baB may represent a promising strategy to improve implantation outcomes.<\/jats:p>","DOI":"10.3390\/diagnostics15141762","type":"journal-article","created":{"date-parts":[[2025,7,14]],"date-time":"2025-07-14T07:54:23Z","timestamp":1752479663000},"page":"1762","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["NF-\u03baB as an Inflammatory Biomarker in Thin Endometrium: Predictive Value for Live Birth in Recurrent Implantation Failure"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7128-7550","authenticated-orcid":false,"given":"Zercan","family":"Kal\u0131","sequence":"first","affiliation":[{"name":"Private G\u00f6zde Hospital, 44100 Malatya, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4907-5890","authenticated-orcid":false,"given":"Pervin","family":"Karl\u0131","sequence":"additional","affiliation":[{"name":"Private Clinic, 55020 Samsun, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatma","family":"Tan\u0131l\u0131r","sequence":"additional","affiliation":[{"name":"Private Clinic, 21100 Diyarbak\u0131r, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P\u0131nar","family":"K\u0131r\u0131c\u0131","sequence":"additional","affiliation":[{"name":"Gynecology and Obstetric Department, Turgut \u00d6zal University, 44210 Malatya, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serhat","family":"Ege","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Dicle University, 21070 Diyarbak\u0131r, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Ma, Y., Gao, X., and Li, Y. (2023). Recurrent implantation failure: A comprehensive summary from etiology to treatment. Front. Endocrinol., 13.","DOI":"10.3389\/fendo.2022.1061766"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"ESHRE Working Group on Recurrent Implantation Failure (2023). ESHRE good practice recommendations on recurrent implantation failure. Hum. Reprod. Open., 2023, hoad023.","DOI":"10.1093\/hropen\/hoad023"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Macklon, N. (2025). Resolving recurrent implantation failure. Reprod. Biomed. Online, 50.","DOI":"10.1016\/j.rbmo.2025.104827"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1007\/s10815-025-03436-2","article-title":"Comparative efficacy of intrauterine infusion treatments for recurrent implantation failure: A network meta-analysis of randomized controlled trials","volume":"42","author":"Jiang","year":"2025","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Liu, K.E., Hartman, M., Mahutte, N., and Luo, Z.C. (2025). Association of endometrial thickness with live birth rates among women undergoing fresh and frozen embryo transfer. Front. Cell Dev. Biol., 13.","DOI":"10.3389\/fcell.2025.1530953"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"hoad028","DOI":"10.1093\/hropen\/hoad028","article-title":"The thicker the endometrium, the better the neonatal outcomes?","volume":"2023","author":"Wu","year":"2023","journal-title":"Hum. Reprod. Open."},{"key":"ref_7","first-page":"12152","article-title":"Ultrasound-assessed endometrial receptivity measures for the prediction of pregnancy outcomes in IVF-ET: A meta-analysis","volume":"25","author":"Wang","year":"2023","journal-title":"Exp. Ther. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"7254","DOI":"10.3390\/jcm13237254","article-title":"Does endometrial thickness or compaction impact the success of frozen embryo transfer cycles?","volume":"13","author":"Sharqawi","year":"2024","journal-title":"J. Clin. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.rbmo.2016.05.002","article-title":"Endometrial thickness as a predictor of pregnancy outcomes in 10 787 fresh IVF-ICSI cycles","volume":"33","author":"Yuan","year":"2016","journal-title":"Reprod. Biomed. Online"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.fertnstert.2023.02.035","article-title":"Effect of the endometrial thickness on the live birth rate: Insights from 959 single euploid frozen embryo transfers without a cutoff for thickness","volume":"120","author":"Ata","year":"2023","journal-title":"Fertil. Steril."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Lu, Y., Cherouveim, P., Jiang, V., Dimitriadis, I., James, K.E., Bormann, C., and Souter, I. (2024). Comparison of endometrial thickness in the same patients undergoing ovulation induction with clomiphene citrate or gonadotropins: A retrospective self-controlled study. Front. Endocrinol., 15.","DOI":"10.3389\/fendo.2024.1414481"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Qi, M., Jin, Y., Si, L., Fu, H., Shi, X., Liu, Y., Wang, Y., and Guo, R. (2025). Evaluation of the effects of estrogens on endometrial cancer cells of different grades. J. Biochem. Toxicol., 39.","DOI":"10.1002\/jbt.70129"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Evans, J., and Salamonsen, L.A. (2021). The menstrual endometrium: From physiology to future treatments. Front. Reprod. Health, 3.","DOI":"10.3389\/frph.2021.794352"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"13167","DOI":"10.3892\/mmr.2024.13167","article-title":"Angiogenesis signaling in endometriosis: Molecules, diagnosis and potential therapeutic targets","volume":"29","author":"Bo","year":"2024","journal-title":"Mol. Med. Rep."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2956","DOI":"10.1038\/s41467-017-02375-6","article-title":"Hypoxia and hypoxia-inducible factor-1\u03b1 are required for normal endometrial repair during menstruation","volume":"9","author":"Maybin","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1111\/aji.12161","article-title":"Increased nuclear expression of NF-\u03baB p65 subunit in the eutopic endometrium and ovarian endometriomas of women with advanced-stage endometriosis","volume":"70","author":"Kim","year":"2013","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_17","first-page":"314","article-title":"Pathophysiology and immune dysfunction in endometriosis","volume":"42","author":"Ahn","year":"2021","journal-title":"Endocr. Rev."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1111\/aji.12483","article-title":"Uterine immune profiling may help women with repeated unexplained embryo implantation failure after IVF","volume":"75","author":"Petitbarat","year":"2016","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1509","DOI":"10.1038\/nm.2498","article-title":"Deregulation of the serum- and glucocorticoid-inducible kinase SGK1 in the endometrium causes reproductive failure","volume":"17","author":"Salker","year":"2011","journal-title":"Nat. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"RAF-22-0115","DOI":"10.1530\/RAF-22-0115","article-title":"A systematic review of transcriptomic studies of the human endometrium reveals inconsistently reported differentially expressed genes","volume":"4","author":"Walker","year":"2023","journal-title":"Reprod. Fertil."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3897\/pharmacia.72.e143465","article-title":"The role of the transcription factor NF-\u03baB in the pathogenesis of inflammation and carcinogenesis. Modulation capabilities","volume":"72","author":"Kobakova","year":"2025","journal-title":"Pharmacia"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.canlet.2016.11.027","article-title":"NF-\u03baB-regulated exosomal miR-155 promotes the inflammation associated with arsenite carcinogenesis","volume":"388","author":"Chen","year":"2017","journal-title":"Cancer Lett."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1016\/j.fertnstert.2012.06.021","article-title":"Nuclear factor\u2013kappaB: A main regulator of inflammation and cell survival in endometriosis pathophysiology","volume":"98","author":"Devoto","year":"2012","journal-title":"Fertil. Steril."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Wang, Y., Tang, Z., and Teng, X. (2024). New advances in the treatment of thin endometrium. Front. Endocrinol., 15.","DOI":"10.3389\/fendo.2024.1269382"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1038\/s41392-024-01757-9","article-title":"NF-\u03baB in biology and targeted therapy: New insights and translational implications","volume":"9","author":"Guo","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Dong, X., Zhou, M., Li, X., Huang, H., and Sun, Y. (2023). Gene profiling reveals the role of inflammation, abnormal uterine muscle contraction and vascularity in recurrent implantation failure. Front. Genet., 14.","DOI":"10.3389\/fgene.2023.1108805"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Rezaei, M., and Moghoofei, M. (2024). The role of viral infection in implantation failure: Direct and indirect effects. Reprod. Biol. Endocrinol., 22.","DOI":"10.1186\/s12958-024-01303-w"},{"key":"ref_28","unstructured":"Zhang, Q., Yang, D., Han, X., Wang, Y., Sun, Z., Wang, J., Zhao, X., Li, Y., Liu, X., and Xu, H. (2021). Role of NF-\u03baB signaling pathway in endometriosis: New insights and future therapeutic strategies. Front. Immunol., 12."},{"key":"ref_29","first-page":"1299","article-title":"Disturbed endometrial NF-\u03baB expression in women with recurrent implantation failure","volume":"33","author":"Ersahin","year":"2016","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.fertnstert.2006.05.077","article-title":"Aberrant expression of DNA methyltransferases DNMT1, DNMT3A, and DNMT3B in women with endometriosis","volume":"87","author":"Wu","year":"2007","journal-title":"Fertil. Steril."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1189\/jlb.0708395","article-title":"Embryonic implantation: Cytokines, adhesion molecules, and immune cells in establishing an implantation environment","volume":"85","author":"Macklon","year":"2009","journal-title":"J. Leukoc. Biol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1111\/j.1600-0897.2011.01039.x","article-title":"Peri-conceptual cytokines\u2014Setting the trajectory for embryo implantation, pregnancy and beyond","volume":"66","author":"Robertson","year":"2011","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1093\/humrep\/dez019","article-title":"Estrogen receptor \u03b2 upregulates CCL2 via NF-\u03baB signaling in endometriotic stromal cells and recruits macrophages to promote the pathogenesis of endometriosis","volume":"34","author":"Gou","year":"2019","journal-title":"Hum. Reprod."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Zdrojkowski, \u0141., Jasi\u0144ski, T., Ferreira-Dias, G., Pawli\u0144ski, B., and Domino, M. (2023). The Role of NF-\u03baB in Endometrial Diseases in Humans and Animals: A Review. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24032901"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/s43043-025-00219-8","article-title":"An overview of endometriosis and molecular target-based therapeutic approach","volume":"30","author":"Paul","year":"2025","journal-title":"Middle East. Fertil. Soc. J."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1111\/j.1600-0897.2009.00792.x","article-title":"Inflammation and implantation","volume":"63","author":"Dekel","year":"2010","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.ejogrb.2015.03.032","article-title":"Hysteroscopic polypectomy decreases NF-\u03baB1 expression in the mid-secretory endometrium of women with endometrial polyp","volume":"189","author":"Bozkurt","year":"2015","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol."},{"key":"ref_38","unstructured":"Centers for Disease Control and Prevention (CDC) (2025, July 04). 2022 Assisted Reproductive Technology Fertility Clinic Success Rates Report, Available online: https:\/\/www.cdc.gov\/art\/success-rates\/index.html."},{"key":"ref_39","unstructured":"Society for Assisted Reproductive Technology (SART) (2024). 2023 National Summary Report, SART. Available online: https:\/\/www.sartcorsonline.com\/rptcsr_publicmultyear.aspx."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Fan, J., Zhang, M., Wu, H., Ye, Z., and Wang, L. (2025). Estrogen Promotes Endometrial Cancer Development by Modulating ZNF626, SLK, and RFWD3 Gene Expression and Inducing Immune Inflammatory Changes. Biomedicines, 13.","DOI":"10.3390\/biomedicines13020498"},{"key":"ref_41","first-page":"485","article-title":"Myo-inositol: From induction of ovulation to menopausal disorder management","volume":"67","author":"Gullo","year":"2015","journal-title":"Minerva Ginecol."}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/15\/14\/1762\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T08:18:21Z","timestamp":1774340301000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/15\/14\/1762"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,12]]},"references-count":41,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2025,7]]}},"alternative-id":["diagnostics15141762"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics15141762","relation":{},"ISSN":["2075-4418"],"issn-type":[{"value":"2075-4418","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,12]]}}}