Metabolism of human embryos following cryopreservation: Implications for the safety and selection of embryos for transfer in clinical IVF

1H NMR based metabolic profiling of day 2 spent embryo media correlates with implantation potential

“…These results and those of previous studies demonstrate that spent embryo culture media from viable and non-viable embryos differs in its metabolite composition thus making its assessment a potential non-invasive method for the selection of embryos. Of the metabolites measured in this study, previous studies have measured alanine, glutamate, glycine, lactate, and tryptophan in relation to blastocyst formation and implantation [Brison et al 2004;Houghton et al 2002;Seli et al 2008;Stokes et al 2007]. However, to the best of our knowledge, levels of the metabolites 2-methylglutarate, 3-aminoisobutyrate, 3-hydroxyisovalerate, acetate, acetoacetate, citrate, and formate have not previously been analyzed in relation to pregnancy success.…”

“…Therefore a change in the formate to glycine ratio may be indicative of an alteration in this pathway. In addition to this, a decrease in glycine in the media of day 2 embryos has been shown to be significantly associated with clinical pregnancy [Brison et al 2004] and development of the embryo to the blastocyst stage [Houghton et al 2002;Stokes et al 2007]. The citrate to alanine ratio was decreased in the media of the positive pregnancy group.…”

“…Recent studies lend further evidence to this hypothesis as increased amino acid turnover has been positively correlated with DNA damage [Sturmey et al 2009] and cryopreserved human embryos that had the capacity to develop to the blastocyst stage upon subsequent thawing had a lower rate of amino acid turnover than those which arrested [Stokes et al 2007]. These studies demonstrated underlying metabolic differences between embryos of differing quality and thus provide the basis for the development of metabolic markers of viability for use in assisted reproductive technology.…”

Potential of inner cell mass outgrowth and amino acid turnover as markers of quality in the in vitro fertilization laboratory

“…Recently, many investigators have further described the use of noninvasive testing of culture media for prediction of human embryo quality (11,13,15,28). We have demonstrated that similar profiling for murine embryos is possible, with significant metabolic activity of alanine, aspartate, glutamine, leucine, and ornithine using LC-MS/MS technology.…”

Endometrial stem cells and human reproductive failure

“…Preliminary studies reported that decidualizing cell can respond selectively to presence of an abnormal embryo inhibiting the secretion of certain cytokines and growth factors, including IL-1β and HB-EGF, which seem to be important regulators of endometrial stromal cells motility (38). It has been hypothesized that compromised embryos produce high levels of ATP and reactive oxygen species and these products seem to provide decidualizing endometrial stromal cells with information on embryo quality (40,41). This concept has been confirmed by studies on primary endometrial stromal cell cultures from RM patients in which there is a lack of MSC, excessive inflammation, high influx of immune system cells and cellular stress.…”