Noninvasive metabolomic profiling of embryo culture media using proton nuclear magnetic resonance correlates with reproductive potential of embryos in women undergoing in vitro fertilization

Objective: To identify biomarkers associated with reproductive outcome using proton nuclear magnetic resonance (H-1 NMR) metabolomic profiling of embryo culture media. Design: Retrospective study. Setting: An academic assisted reproductive technology (ART) program; a university research center. Patient(s): Women undergoing ART treatment. Intervention(s): Spent-media samples from embryos that resulted in pregnancy and delivery (n = 17) and samples (n = 17) from embryos that failed to implant were individually collected on day 3, and evaluated using H-1 NMR spectroscopy. The spectra obtained were quantified by integrating six biomarker signals in the aliphatic region after baseline subtraction. Using a multivariate analysis, a model that calculates a viability index for each spectrum was developed. Sensitivity and specificity of-predicting pregnancy (described as implantation and delivery) were calculated. Main Outcome Measure(S): The H-1 NMR metabolomic profile of embryo culture media and embryo viability. Result(s): Glutamate concentrations determined by H-1 NMR were significantly higher in spent culture media of embryos that resulted in pregnancy and delivery compared to those that failed to implant. Similarly, viability indices calculated by H-1 NMR using the weighted coefficients of glutamate and alanine/lactate ratio quantities were higher for embryos that implanted and resulted in a delivery. Proton NMR spectroscopy predicted viability of individual embryos with a sensitivity of 88.2% and a specificity of 88.2%. Conclusion(s): Metabolomic profile of spent embryo culture media using H-1 NMR correlates with the reproductive potential of embryos. (Fertil Steril(R) 2008;90:2183-9. (C) 2008 by American Society for Reproductive Medicine.)