Mendelian randomization study reveals causal associations between plasma metabolites, immune cell phenotypes, and ovarian hyperstimulation syndrome

In this study, we employed Mendelian randomization (MR) analysis to explore the causal relationships between immune cell phenotypes, plasma metabolites, and ovarian hyperstimulation syndrome (OHSS). Through the analysis of 731 immune cell phenotypes and 1400 plasma metabolites, we identified 32 immune cell phenotypes that are causally related to OHSS, with 18 phenotypes identified as protective and 14 as risk factors. Notably, the TCRgd AC phenotype was the most significant risk factor associated with OHSS. Our findings also revealed that among the 10 plasma metabolites causally linked to OHSS, three acted as protective factors, while seven were identified as risk factors. The Alpha-ketoglutarate to alanine ratio stood out as the most significant protective metabolite. Further investigation established a causal link between the EM DN (CD4-CD8-) AC immune cell phenotype and the Alpha-ketoglutarate to alanine ratio. Reverse MR analysis indicated that OHSS influences the expression of HLA-DR on myeloid OC cells. Mediation analysis suggested a non-significant mediation effect of the Alpha-ketoglutarate to alanine ratio in the pathway from immune cells to OHSS, accounting for −8.68 % of the total effect. Collectively, our results underscore the role of specific immune cell phenotypes and plasma metabolites in the pathogenesis of OHSS, revealing potential targets for developing interventions aimed at reducing the risk of OHSS.