Noninvasive metabolomic profiling of human embryo culture media using Raman spectroscopy predicts embryonic reproductive potential: a prospective blinded pilot study

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

“…Our findings extend previously published data [21][22][23][24] by demonstrating that metabolomic models alone or in combination with morphology allow an improved prediction of embryo viability compared to morphology. Therefore, our study introduces metabolomic profiling as a rapid, and non-invasive technology that can provide an objective assessment aiding in the decision of which embryo(s) to transfer in the IVF laboratory.…”

“…More importantly, using the algorithm developed with the training set, Viability Scores obtained for the "Validation set" achieved a high accuracy in 61 samples collected in 3 centers using different types of culture media. Our findings, combined with previous reports [21,22], suggest that an algorithm developed using spectroscopybased metabolomic profiling can aid in the accurate prediction of viability across a multitude of culture media types and culture volumes.…”

“…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.…”

Prediction of embryo implantation potential by mass spectrometry fingerprinting of the culture medium

“…In this study, we applied direct fingerprinting by ESI-Q-ToF-MS. MS fingerprinting analysis has been applied to a variety of biological models and even for bovine embryo culture medium quality control (Sawaya et al 2004, Marques et al 2006, de Souza et al 2007a, 2007b, Souza et al 2008, Ferreira et al 2009, Saraiva et al 2009). Although diverse analytical techniques that are primarily based on spectroscopy technologies, such as near-infrared, RAMAN, and proton NMR, have been used as noninvasive tools to predict embryo viability (Seli et al 2007, Nagy et al 2008, Scott et al 2008, Ahlstrom et al 2011, Hardarson et al 2012, to our knowledge, this is the first report that uses MS fingerprinting to predict human embryo implantation potential. Whereas spectroscopic techniques are based on the measurement of physical events resulting from the interaction of organic molecules with electromagnetic radiation, MS characterizes the molecular composition of a sample (Ferreira et al 2010).…”

“…These approaches include the measurement of glucose, lactate, pyruvate, or amino acid levels in the embryo culture media, as well as the assessment of oxygen consumption by the embryo, and genomic and proteomic profiling (Gardner et al 2001, Houghton et al 2002, Brison et al 2004, Lopes et al 2005, Dominguez et al 2008, Katz-Jaffe et al 2009). Most recently, analytical examination of the embryonic metabolome (Seli et al 2007, Bromer & Seli 2008, Scott et al 2008, Katz-Jaffe et al 2009, Aydiner et al 2010, Ferreira et al 2010, Ahlstrom et al 2011, Cortezzi et al 2011, Hardarson et al 2012 has also been evaluated, particularly applying spectroscopy methods. The metabolome refers to the complete stock of small compounds, such as metabolic intermediates and signaling molecules that are found within a biological sample.…”