The Causal Relationship Between Immune Cells and Infertility: A Mendelian Randomisation Study

ABSTRACT Objective Infertility has emerged as a significant global public health concern, with a multitude of complex underlying causes. Epidemiological evidence indicates that immunological factors are significant contributors to the aetiology of infertility. However, previous studies on the relationship between immune inflammation and infertility have yielded inconclusive results. Methods Mendelian randomisation (MR) is an emerging statistical method that employs exposure‐related genetic variation as an instrumental variable (IV) to infer causal relationships between immune cells and infertility by modelling the principle of random assignment in Mendelian genetics. In this study, MR was employed to assess the causal relationship between 731 immune cell signatures and infertility. The data utilized in this study were obtained from publicly available genome‐wide association studies (GWAS) and validated IVs, which were employed to fulfil the essential assumptions of MR analysis. Results The Mendelian randomisation analysis revealed a total of 27 statistically significant immune cell phenotypes out of 731. The risk factor with the largest odds ratio (OR) was CD28 − CD25 ++ CD8 + %T cell [OR, 1.21; 95% confidence interval (CI), 1.04–1.42], while the protective factor with the largest OR was activated and resting Treg AC (OR, 0.89; 95% CI, 0.82–0.97). Conclusion The present study has demonstrated a correlation between certain characteristics of immune cells and female infertility. These results provide clues for further research into the immune mechanisms of infertility and may inform the development of novel therapeutic strategies.