We found a direct relationship between embryo metabolism and reproductive sucess [SRBT Clinical Science Award – ASRM]
Overture presented at the 76th American Society for Reproductive Medicine (ASRM) the research A novel non-invasive metabolomics approach to screen embryos for aneuploidy, which proposes a new form of non-invasive embryo selection of the embryo and predicts the success of its implantation, thanks to its metabolomic study. The research, led by José A. Horcajadas and me, has been awarded for its great contribution to reproductive medicine.
Since the beginning of assisted reproduction, embryo selection has been key to improve success rates. Knowing which embryo has the greatest chance of implantation is paramount to achieve successful treatment. Preimplantation Genetic Diagnosis of Aneuploidy (PGD-A) selects embryos without chromosomal abnormalities. Aneuploid embryo production increases with maternal age, from 30% in young women to 80% in more than 40. However, PGT-A is an invasive technique that requires a biopsy of the embryo.
In this study, we propose to take a further step. Our idea was not only to identify the embryos with chromosomal problems but also to identify the 30% of euploid embryos that do not implant for other reasons.
Metabolomics as an alternative to PGD
Metabolomics is the science that studies the chemical footprint left by the cellular processes. Previous studies had suggested that the metabolism of an embryo offered valuable information about their health and viability. In this research we have found large differences in the concentration of metabolites in the culture media of chromosomally healthy embryos and those that had some disease chromosome, which opens the door to a non-invasive diagnosis of the embryo without biopsy and, therefore, to the improvement of the success rates in reproduction.
The culture medium in which the embryo develops, after In Vitro Fertilization (IVF), is a huge source of information. Cellular processes leave a mark that we have been able to decipher. Thanks to this study we know that metabolomics will not only tell us which embryo is euploid or aneuploid, but could indicate its viability in pregnancy, so we could improve pregnancy rates through a predictive model.
Concordance of 97.5% versus embryo biopsy
To carry out this research, a metabolomic study was conducted on a total of 80 embryo culture samples collected between day 3 and day 5 of development.
A key step in the work was to apply various statistical and automatic learning techniques, to identify the most important metabolites to be used as biomarkers. A total of sixty were identified as the most significant to built the diagnostic algorithm.
The results were consistent with the results of classical PGT – with a 97.5% accurate prediction, with only one misclassified embryo.
Metabolites, the new chromosomal markers of the embryo
Among the conclusions of this work, we highlight the differences in metabolite concentration in the culture media of euploid embryos and those who had chromosome problems, which confirms that we can infer the metabolic state of the embryo by analyzing compounds in culture media.
Now we are planning a new randomized clinical study and non-selection study to validate the technique, in order to offer it to fertility centers. The non-invasive analysis of the embryo and the prediction of its implantation could form part of the standard reproductive treatment and improve reproductive medicine.
Other benefits of this procedure are that it does not require arriving at day 6 development of the embryo, nor is it necessary to transport a refrigerated sample of it, as in the case of non-invasive PGD. Another advantage of this diagnosis is that we will be able to detect those euploid embryos that do not implant, for different reasons, before the transfer, reducing 30% the failures of implantation that occur for this reason.