Objective To investigate ubiquitination-related genes closely associated with recurrent implantation failure(RIF)based on bioinformatics and explore their interaction with immune infiltration.Methods GSE111974,GSE26787,and GSE223672 data sets were selected from the Gene Expression Omnibus(GEO),with GSE111974 serving as the training set for differential analysis.Differentially expressed ubiquitination-related genes(DEUGs)related to RIF were obtained by intersecting differentially expressed genes with ubiquitination genes,and then hub genes were screened using machine learning.The expression of hub genes in endometrial cell clusters was analyzed using GSE223672.The ss GSEA algorithm was used to determine the proportion of immune cells between samples and the correlation between immune cells and hub genes.Results KLHL13,UCHL1,TOP2A,and USP33 were identified as characteristic genes in RIF.Among these,TOP2A exhibited the highest expression in endometrial mesenchymal stem cells,whereas USP33 was predominantly expressed in mesenchymal stem cells and endothelial cells.In RIF,CD8+T cells,neutrophils,and Th l cells were suppressed,while helper T cells were significantly active.KLHL13 expression was positively correlated with APC co-stimulation,whereas USP33 expression was negatively correlated.Additionally,TOP2A and UCHL1 expression showed negative correlations with T helper cell infiltration.Conclusion KLHL13,UCHL1,TOP2A,and USP33 are diagnostic markers of RIF and affect RIF by regulating immune cell infiltration.