Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Metabolomics Integration in Assisted Reproductive Technologies for Enhanced Embryo Selection Beyond Morphokinetic Analysis

Version 1 : Received: 31 July 2023 / Approved: 31 July 2023 / Online: 1 August 2023 (14:34:26 CEST)

A peer-reviewed article of this Preprint also exists.

Pinto, S.; Guerra-Carvalho, B.; Crisóstomo, L.; Rocha, A.; Barros, A.; Alves, M.G.; Oliveira, P.F. Metabolomics Integration in Assisted Reproductive Technologies for Enhanced Embryo Selection Beyond Morphokinetic Analysis. International Journal of Molecular Sciences 2023, 25, 491, doi:10.3390/ijms25010491. Pinto, S.; Guerra-Carvalho, B.; Crisóstomo, L.; Rocha, A.; Barros, A.; Alves, M.G.; Oliveira, P.F. Metabolomics Integration in Assisted Reproductive Technologies for Enhanced Embryo Selection Beyond Morphokinetic Analysis. International Journal of Molecular Sciences 2023, 25, 491, doi:10.3390/ijms25010491.

Abstract

Embryo quality evaluation during in vitro development is vital for the success of assisted reproductive technologies (ART). However, the subjective morphological assessment by embryologists may result in inconsistencies that affect the selection of the best embryo for transfer. To provide a more comprehensive evaluation of embryo quality, we performed the integration of embryo metabolomics with standardized morphokinetic classification. The culture medium of 55 embryos (from 21 couples undergoing ICSI) was collected at two timepoints (day 3 and 5). Samples were split into Good (n=29), Lagging (n=19) and Bad (n=10) according to embryo morphokinetic evaluation. Embryo metabolic performance was assessed by 1H-NMR, monitoring the variation of specific metabolites (pyruvate, lactate, alanine, glutamine, acetate, formate). Adjusted metabolite differentials were observed during the first three days of culture and found to be discriminative of embryo quality at the end of day 5. Pyruvate, alanine, glutamine, and acetate were major contributors to this discrimination. Good and Lagging embryos were found to export and accumulate pyruvate and glutamine in the 3 first days of culture, while Bad embryos consumed them. This suggests that Bad embryos have a less active metabolism than Good and Lagging embryos and these two metabolites as putative biomarkers for embryo quality. This study provides a more comprehensive evaluation of embryo quality and can lead to improvements in ART by enabling the selection of the best embryos. By combining morphological assessment and metabolomics, the selection of high-quality embryos with the potential to result in successful pregnancies may become more accurate and consistent.

Keywords

Embryo quality evaluation; Morphokinetic assessment; Embryo metabolomics; Pyruvate; Glutamine

Subject

Medicine and Pharmacology, Reproductive Medicine

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