# Anti-β2GPI/HLA-DR Antibody, Chronic Endometritis, and Uterine Endometrial Microbiome in Women with Recurrent Pregnancy Loss: A Prospective Cohort Study

## TL;DR

This study explores new risk factors for recurrent pregnancy loss and finds that targeted treatments based on these factors can significantly improve live birth rates.

## Contribution

The study introduces a combined assessment of anti-β2GPI/HLA-DR antibody, chronic endometritis, and endometrial microbiome for RPL diagnosis and treatment.

## Key findings

- Anti-β2GPI/HLA-DR antibody was found in 18.4% of women with RPL.
- Combining new tests reduced unexplained RPL cases from 65.5% to 16.1%.
- Treated women with NLDM-2 had a 92.3% live birth rate.

## Abstract

Anti-β2GPI/HLA-DR antibody, chronic endometritis (CE), and endometrial dysbiosis are likely to be associated with the etiologies of recurrent pregnancy loss (RPL). This prospective cohort study aimed to investigate these new risk factors together with conventional causes for RPL, and to evaluate pregnancy outcomes in women individually treated. A total of 87 women with RPL underwent conventional assessment together with anti-β2GPI/HLA-DR antibody measurements, CD138 immunohistochemistry for CE, and 16S rRNA sequence analysis for endometrial microbiome. Women with anti-β2GPI/HLA-DR antibody, CE, and endometrial dysbiosis received low-dose aspirin and heparin, antibiotics, and probiotics, respectively. Pregnancy outcomes of the participants were assessed. Anti-β2GPI/HLA-DR antibody, CE, non-Lactobacillus-dominant microbiome (NLDM)-1 (Lactobacillus + Bifidobacterium < 80%), and NLDM-2 (Lactobacillus without iners + Bifidobacterium < 80%) were detected in 16 (18.4%), 22 (25.3%), 27 (31.0%), and 46 (52.8%) women, respectively. Based on conventional assessment, 65.5% of women with RPL were classified as unexplained etiology; however, the percentage reduced to 16.1% when these new tests were assessed together. All 9 pregnancies with anti-β2GPI/HLA-DR antibody, 13 (92.9%) of 14 pregnancies with CE, and 24 (92.3%) of 26 pregnancies with NLDM-2 resulted in live birth. Assessment of these new tests may be clinically useful for reducing the proportion of unexplained RPL, and for providing high live birth rates if women receive relevant treatments.