Metabolomic markers of biological fluid in women with reproductive failure: a systematic review of current literatures

Understanding metabolic changes in reproductive failure, including early miscarriage (EM), recurrent miscarriage (RM), and repeated implantation failure (RIF), may be beneficial to understand the pathophysiology, thus improving pregnancy outcomes. Nine metabolomic profiling studies in women with reproductive failures (4 for EM, 3 for RM, and 2 for RIF) were included for systematic review. In total 78, 75, and 25 significant metabolites were identified and 40, 40, and 34 metabolic pathways were enriched in EM, RM, and RIF, respectively. Among them, 7 and 11 metabolites, and 28 and 28 pathways were shared between EM and RM and between RM and RIF, respectively. Notably, histidine metabolism has the highest impact in EM; phenylalanine, tyrosine, and tryptophan biosynthesis. Ubiquinone and other terpenoid-quinone biosynthesis metabolism have the highest impact factor in RM; alanine, aspartate, and glutamate metabolism have the highest impact factor in RIF. This study not only summarized the common and distinct metabolites and metabolic pathways in different reproductive failures but also summarized limitations of the study designs and methodologies. Hence, further investigations and validations of these metabolites are still urgently needed to understand the underlying metabolic mechanism for the development and treatment of reproductive failures. Nine metabolomic studies related to reproductive failure were included in this review. Though alterations in metabolites were identified, study designs and methodologies remained controversial. Hence, further studies and validation are necessary.