ABSTRACT Background Anti‐β2GPI/HLA‐DR autoantibodies may be involved in recurrent implantation failure (RIF) and recurrent pregnancy loss (RPL). We examined their association with the endometrial microbiome and chronic endometritis (CE). Methods In this cross‐sectional study, 141 women (54 RIF, 87 RPL) were enrolled. Serum anti‐β2GPI/HLA‐DR positivity was defined using 99th/95th percentile cut‐offs. Endometrial microbiome was assessed by 16S rRNA sequencing, focusing on reproductive‐failure–related species ( Gardnerella, Prevotella, Atopobium, Dialister, Anaerococcus, Ureaplasma, Mycoplasma ). Microbiome and CE were compared by antibody status in RIF and RPL. Results In RIF, antibody‐positive women more frequently had Lactobacillus iners (99‰ and 95‰ cut‐offs: 71.4% vs. 23.4%, p = 0.03; and 70.0% vs. 20.5%, p = 0.026) and reproductive‐failure–related bacterial species (99‰: 100% vs. 51.1%, p = 0.016; 95‰: 90.0% vs. 52.3%, p = 0.032). In multivariable analysis with 95‰ cut‐off, Lactobacillus iners (OR 13.1, p = 0.003) and reproductive‐failure–related species (OR 9.64, p = 0.029) were independently associated with antibody positivity. In RPL, Anaerococcus was more frequent in antibody‐positive women. CE frequency did not differ by antibody status in RIF or RPL. Conclusion Anti‐β2GPI/HLA‐DR antibody positivity was associated with endometrial dysbiosis and may serve as a biomarker of abnormal intrauterine environment in reproductive failure.
Ono et al. (2026) studied this question.