L26/O-285 Killer-cell ig-like receptor (KIR) polymorphisms influence endometrial dysbiosis, chronic endometritis, and antibiotic response in infertile women

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Abstract Study question To determine the possible association between activating KIR genes, endometrial dysbiosis, chronic endometritis, and antibiotic treatment response in infertile women. Summary answer Absence of activating KIR genes, particularly KIR2DS1, is associated with higher prevalence of dysbiosis and chronic endometritis and poorer antibiotic response. What is known already Endometrial dysbiosis and chronic endometritis are increasingly recognised inflammatory conditions associated with infertility and poor reproductive outcomes. Both conditions involve alterations of the endometrial immune microenvironment. Uterine natural killer (uNK) cells represent the predominant immune population in the endometrium and are tightly regulated by killer-cell immunoglobulin-like receptors (KIRs), which modulate their functional activity, widely implicated in key processes in reproduction. However, the contribution of KIR-mediated uNK regulation to these inflammatory conditions remains poorly understood. Study design, size, duration This multicentric retrospective study included 308 Caucasian infertile women undergoing assisted reproduction between January 2021 and June 2024. KIR genotypes and specific activating KIR genes were analysed in relation to endometrial dysbiosis, chronic endometritis, other inflammatory conditions, and antibiotic treatment response. Participants/materials, setting, methods Women under 45 years attending IVF centres in Spain were included. All had undergone KIR genotyping and endometrial biopsy for dysbiosis (EMMA®) and/or chronic endometritis (ALICE®). Prevalence of endometrial conditions and number of antibiotic cycles required were compared according to KIR genotypes and presence of KIR2DS1 and KIR3DS1 genes using appropriate statistical tests. Main results and the role of chance Endometrial dysbiosis was diagnosed in 67.9% of tested patients and chronic endometritis in 28.4%. Women lacking the activating KIR2DS1 gene showed a significantly higher prevalence of endometrial dysbiosis (75.2% vs. 54.7%, p = 0.0017) and chronic endometritis (33.3% vs. 19.4%, p = 0.015) compared to those women carrying this gene. Similarly, absence of KIR3DS1 was associated with increased dysbiosis prevalence (75.7% vs. 56.0%, p = 0.0025). Among patients requiring antibiotic treatment, KIR2DS1-negative women needed significantly more treatment cycles to achieve a normal endometrial biopsy than carriers (1.7±0.7 vs. 1.2±0.4, p = 0.0026). KIR genotype (AA, AB, BB) was not associated with any condition. Limitations, reasons for caution Although these findings provide insights into the immunogenetic regulation of the endometrial immune microenvironment, they should be interpreted with caution due to the retrospective nature of the study, the heterogeneity of antibiotic regimens, and the lack of KIR expression or functional analyses. Wider implications of the findings These findings support a role for immunogenetic factors in these pathologies and contribute to a better understanding of the immune mechanisms involved in endometrial inflammatory conditions. Analysis of KIR genes may help refine patient stratification and represents a step towards more personalised diagnostic and therapeutic approaches in reproductive medicine. Trial registration number No

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