The metabolomic profile of endometrial receptivity in recurrent miscarriage.

BACKGROUND: Endometrial receptivity has been the focus of continuous research for over eight decades; however, current clinical practice lacks an accurate test of endometrial receptivity to allow the prediction of successful pregnancy. We aimed to characterize the endometrial metabolomic profiles of women who suffered recurrent miscarriage using discovery metabolomics and to set the foundation for the development of an endometrial receptivity test. METHODS: This was a prospective multicenter cohort study led by the Tommy's National Centre for Miscarriage Research in Birmingham. Endometrial biopsies were obtained during the window of implantation from 24 women aged 18-35 years, who were not pregnant and regularly menstruating, diagnosed with unexplained recurrent miscarriage. The metabolite composition and relative concentrations of samples were analyzed applying ultra-high performance liquid chromatography-mass spectrometry to investigate water-soluble and lipid metabolites. RESULTS: Various metabolic perturbations are associated with observation of increased numbers of miscarriages. They relate to fatty acid metabolism including increased lipolysis and decreased medium chain fatty acid beta-oxidation, poorer mitochondrial health, and redox-active co-factors which are present at higher oxidative levels. Other metabolic perturbations are associated with observation of live birth following miscarriages. They relate to perturbed cholesterol-cholesterol sulphate metabolism, fatty acid metabolism including increased diacylglyceride lipolysis and decreased medium chain fatty acid beta-oxidation, and improved mitochondrial health. CONCLUSIONS: The present endometrial metabolomics discovery studies have implicated a small number of metabolic pathways and biological functions which are biologically important in miscarriage mechanisms.