Metabolomics and its application for non-invasive embryo assessment in IVF

Abstract

Morphology and cleavage rate remain the mainstay of embryo assessment. However, a number of additional technologies for this application are under investigation. These include the measurement of glucose, lactate, pyruvate or amino acid levels in the embryo culture media, assessment of oxygen consumption by the embryo, genomic and proteomic profiling, and most recently, analytical examination of the embryonic metabolome. As the number of assisted reproduction cycles increases worldwide, improvements in the ability to quickly and non-invasively identify the best embryos for transfer remain a critical goal for reproductive medicine. Recent studies suggest that metabolomic profiling of embryo culture media using optical and non-optical spectroscopies may provide a useful adjunct to the current embryo assessment strategies and provide insight into the phenotype of embryos with increasing reproductive potential.

Receiver operating characteristic (ROC) analysis of day 5 morphology grading and metabolomic Viability Score on predicting implantation outcome

“…It is noteworthy that our initial studies on the application of metabolomic profiling to embryo assessment used both Raman and NIR-spectroscopies [21,22], both vibrational spectroscopies (see [16] for comparison) that can be performed on-site using small size instruments compatible with the environment of an IVF laboratory. In our more recent studies [23,24], and in the current study, we utilized NIR spectroscopy as this technology has a sensitivity and specificity comparable to Raman, and is less costly, therefore has more potential for clinical application.…”

“…As extensive data from animal models and human IVF [14][15][16] suggest that there are metabolic differences between cleavage stage embryos and blastocysts, a novel spectral model for day 5 embryos was developed as described in our previous publications [21,23,25]. Discrimination between FCA+ and FCA− embryos consisted of determining a parsimonious combination of spectral regions from the NIR metabolomic profiles that estimated pregnancy outcomes by inverse least-squares regression and genetic algorithm (GA) optimization.…”

“…Within this context, spent embryo culture media nutrient and metabolite content has been studied to determine an embryo's metabolic activity as a reflection of its viability. Pyruvate, lactate, glucose, and amino acids in the embryo culture medium have all been reported to correlate with embryo development and implantation potential (see [15,16] for review). Global assessment of the embryo culture media proteome [17] as well as specific proteins such as soluble human leukocyte antigen-G (sHLA-G) [18,19] have also been studied as predictors of embryo viability.…”

“…Metabolomics, is the systematic study of this dynamic inventory of metabolites, as small molecular biomarkers representing the functional phenotype in a biological system (see [16] for review). Using various forms of spectral and analytical approaches, metabolomics attempts to determine and quantify metabolites associated with physiologic and pathologic states (see [16] for review).…”

A highly sensitive electrochemiluminescence immunoassay for detecting human embryonic human chorionic gonadotropin in spent embryo culture media during IVF-ET cycle

“…Furthermore, these results together illustrated that the embryonic beta-hCG secretion was consistent with morphological grading in blastocyst stage, and the detection of beta-hCG in culture media by ECLIA may become one of the biomarkers of embryonic development as well. The metabolomic profile was different between embryos resulted in pregnancy and embryos that did not [1,11]. Sivakumar R reported that the concentration of beta-hCG on day2 embryos did not rely on embryo development when they were transferred at blastocyst stage [4].…”