Differential metabolic profiling of non-pure trisomy 21 human preimplantation embryos

Objective: To investigate the metabolomic signature of trisomy 21 preimplantation human embryos by a noninvasive approach using mass spectrometry-(MS-) and nuclear magnetic resonance spectroscopy-(NMR-) based metabolic profiling platforms. Design: A total of 171 spent media samples were collected from day 3 embryos and comparatively analyzed by MS analysis (chromosomally normal embryos, n = 15; trisomy 21 embryos, n = 15) and a matched control media group (without embryo, n = 14) and by NMR spectroscopy (normal embryos, n = 39; trisomy 21 embryos, n = 35; monosomy 21 embryos, n = 24) and a matched control media group (without embryo, n = 29). Setting: IVF clinic/preimplantation genetic diagnosis (PGD) unit facilities. Patient(s): One hundred seventy-one spent media samples obtained from human IVF embryos from patients included in our PGD program. Intervention(s): Metabolomic profiling of embryo spent media using liquid chromatography/gas chromatography coupled with MS and NMR. Main Outcome Measure(s): Comparative identification of the metabolites present in the spent media from normal versus trisomy/monosomy 21 day 3 embryos. Result(s): Two metabolites, caproate and androsterone sulphate, and two unknown compounds were differentially expressed between normal and trisomy 21 day 3 embryos. Furthermore, the NMR results indicate that there could be a correlation between the differences found between trisomy 21/monosomy 21 and the normal embryos in a spectral region compatible with isoleucine. Conclusion(s): This study suggests that the use of differential metabolomic markers found in spent media from preimplantation embryos could be a feasible method for the detection of aneuploidies before ET. (Fertil Steril (R) 2012;98:1157-64. (C) 2012 by American Society for Reproductive Medicine.)