Francisco Domínguez, Phd | Carlos Simón, MD, PhDOther Researchers:
Nowadays the unique method used to select the most viable embryo with the greatest potential in IVF implantation is based solely on morphological parameters. When properly combined with all currently known morphological criteria, the system reaches an acceptable reliability for clinical application.
However, a morphologically normal embryo does not mean that it has no chromosomal abnormalities, in fact, it is estimated that 70% of morphologically normal embryos have aneuploidies (Gutierrez-Mateo et al, 2004).
Preimplantation genetic diagnosis has been developed thanks to the advances that have occurred in assisted reproduction and the development of molecular biology techniques and cytogenetic tests because they are highly efficient and necessary to allow rapid detection of genetic abnormalities in cells that are obtained by embryo biopsy.
Today, we are investigating trough different techniques, such as determinations of the levels of glucose, lactate, pyruvate and amino acid determinations and evaluation of proteomic profiles (Katz-Jaffe et al. 2005, Dominguez et al F, 2008). Very recently we have begun to assess the metabolome (Scott R. et al., 2008) using infrared spectrometry technologies. However, obtaining metabolic profiles in embryo culture media using liquid chromatography and mass spectrometry (LC / MS) technology is not yet fully explored and may become a suitable method to analyze the culture media where embryos develop to select non invasive markers to differentiate good embryos with a high implantation capability from those with bad prognosis or aneuploid embryos.
These technologies are very new and virtually unexplored in the field of assisted reproduction, which opens great possibilities in the search for non-invasive markers in culture medium, which could be applied not only to the study of embryos from couples with high risk, but also extend to all those couples who undergo IVF and egg donation and has been detected in an abnormally high incidence of chromosomal abnormalities.
So our goal in this research is to develop new noninvasive diagnostic systems using both proteomics and metabolomics approaches for selecting embryos with more capacity of implantation and also for the detection of chromosomal abnormalities in embryos coming from IVF, analyzing the conditioned media in which are growing these embryos.
(A) Representative 1D-CPMG spectra of a matched control media sample (without embryo) measured at 298 K. (a) Full spectrum (d ¼ 0.50–8.50ppm), (b) magnification of aromatic region (d ¼ 8.50–5.00 ppm), and (c) aliphatic region (d ¼ 0.50–4.25 ppm). Peak assignments: 1, valine; 2, isoleucine; 3, leucine; 4, threonine; 5, lactate; 6, alanine; 7, lysine; 8, arginine; 9, proline; 10, methionine; 11, glutamic acid; 12, valine; 13, pyruvate; 14, methionine; 15, cystine; 16, lysine; 17, arginine; 18, EDTA; 19, glucose; 20, lactate; 21, threonine; 22, glucose; 23, tyrosine; 24, histidine; 25, phenylalanine; 26, tryptophan. (B) Comparison of the compatible isoleucine region between the NMR spectra of normal (red), T21 (blue), and M21 (green) embryos. Differences in NMR signal intensity were observed in the encircled region between groups of samples.
Dominguez F, Castello D, Remohí J, Simón C, Cobo A.
Effect of vitrification on human oocytes: a metabolic profiling study. Fertil Steril. 2013 Feb;99(2):565-72
Sánchez-Ribas I, Riqueros M, Vime P, Puchades-Carrasco L, Jönsson T, Pineda-Lucena A, Ballesteros A, Domínguez F, Simón.
Differential metabolic profiling of non-pure trisomy 21 human preimplantation embryos. 2012 Nov;98(5):1157-64.
Dominguez F, Gadea B, Mercader A, Esteban FJ, Pellicer A, Simón C.
Embryologic outcome and secretome profile of implanted blastocysts obtained after coculture in human endometrial epithelial cells versus the sequential system. Fertil Steril. 2010 Feb;93(3):774-782
Domínguez F, Gadea B, Esteban FJ, Horcajadas JA, Pellicer A, Simón C.
Comparative protein-profile analysis of implanted versus non-implanted human blastocysts. Hum Reprod. 2008 Sep;23(9):1993-2000.