Differential metabolic profiling of non pure trisomy 21 human preimplantation embryos

We aim to investigate the metabolomic signature of trisomy 21 human embryos, suggesting that differential metabolomic markers found in spent media could be used for chromosomal embryo selection.

Immaculada Sanchez Ribas, M.D., Marisa Riqueros, B.Sc., Pablo Vime, Ph.D., Leonor Puchades-Carrasco, Ph.D., Thomas Jönsson, Ph.D., Antonio Pineda-Lucena, Ph.D., Agustín Ballesteros, M.D., Francisco Dominguez, Ph.D., Carlos Simon, M.D.

Volume 98, Issue 5, Pages 1157-1164.e2, November 2012


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.

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).

IVF clinic/preimplantation genetic diagnosis (PGD) unit facilities.

One hundred seventy-one spent media samples obtained from human IVF embryos from patients included in our PGD program.

Metabolomic profiling of embryo spent media, using liquid chromatography/gas chromatography coupled to MS and NMR.

Main Outcome:
Comparative identification of the metabolites present in the spent media from normal versus trisomy/monosomy 21 day 3 embryos.

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.

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 prior to embryo transfer.

  • This article highlights the importance of continued research in the area of non-invasive testing of embryos. There are a couple of things that I have questions about. When the authors tested for so many different metabolites, isn’t it just by chance that one or two will come up significantly different. Also culture media was evaluated from PN to Day 3, but no mention of what was done with the media spent from Day 3 to Day 5, why not evaluate that as well? Other than that I do applaud the authors for this study and hope to see many others pursue investigations regarding non-invasive testing of embryos.

    • Francisco Dominguez

      Many thanks for the positive comments on the paper. It has been a tough work due to the limitation of the sample.

      Regarding the first question, when we measure hundreds of metabolites we are exposed to chance variation, in fact when we applied the statistical analyses to our data only 4 of these 92 identified metabolites were found statistically differentially expressed. The probability that each of these metabolites could be altered by chance is about 5%, but we are pretty confident with our results because we have seen a good separation of euploid and aneuploidy embryos using PCA analysis with these markers (data not shown in the paper).

      Regarding the second question, we also collect spent media samples from day 3 to day 5, with similar results, but the reason to focus on day3 was that in the future we planned to develop new non invasive techniques to diagnose aneuploidy and as sooner as we can detect this changes in metabolites, the better.

      Again, thanks for the comments.

      Francisco Dominguez

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