Endometrial metabolomic profiling reveals disruption of fatty-acid metabolism in unexplained recurrent pregnancy loss.

RESEARCH QUESTION: Are specific plasma or endometrial metabolomic profiles associated with recurrent implantation failure (RIF), unexplained recurrent pregnancy loss (U-RPL), or both?

DESIGN

Prospective observational study of the plasma and endometrium from 80 women undergoing assisted reproductive technology. The women were classified into three groups: U-RPL (n = 19), RIF (n = 41) and controls (fertile women with male factor infertility, n = 20). A blood sample and an endometrial biopsy were collected during the window of implantation, 5-9 days after ovulation. Targeted and quantitative metabolomics analyses were conducted using high-performance liquid chromatography coupled with tandem mass spectrometry, using the Biocrates® MxP Quant 500 kit. A total of 630 metabolites were assessed using machine learning (ML) to identify specific metabolic profiles, and multivariate and univariate statistical approaches applied.

RESULTS

Of the 630 metabolites analysed, 494 were accurately quantified in plasma and 228 in endometrial samples. A distinct metabolomic signature was identified in the endometrium of patients who had experienced U-RPL, characterized by 16 highly relevant metabolites. This signature includes an overall decrease in medium chain acylcarnitines, along with a significant increase in diglycerides and triglycerides, as well as in certain phospholipids (glycerophosphates) and several ceramides.

CONCLUSION

A disruption of fatty acid metabolism was observed in the endometrium during the implantation window in U-RPL, paving the way for the identification of novel biomarkers of endometrial receptivity.