Embryo quality
Embryo quality is the ability of an embryo to perform successfully in terms of conferring a high pregnancy rate and/or resulting in a healthy person. Embryo profiling is the estimation of embryo quality by qualification and/or quantification of various parameters. Estimations of embryo quality guides the choice in embryo selection in in vitro fertilization.
In general, embryo profiling for prediction of pregnancy rates focuses mainly on visual profiles and short-term
Prediction of pregnancy rates
Microscopy
Embryo quality is mainly evaluated by microscopy at certain time points using a morphological scoring system. This has shown to significantly improve
Number of cells and division rhythm: The optimal number of cells is 4 at day 2 and 8 at day 3 (A quality). In day 3 9-10 cells is B, >=10 is C (suboptimal) and <=4 is D (barely implant). A normal division rate is to double cell number each 24 hours. A higher rate implies chromosomal abnormalities and a lower rate entails possible embryo arrest (it is dying).
Fragmentation: happens due to cell apoptosis and can be quantified by the % of the embryo total volume eccupied by fragments. Fragments are cytoplasm fractions without nuclei.
Cells symmetry and size: it is normal that all blastomeres had same or similar size in embryos with 2, 4 or 8 cells, while for the rest of embryos, a certain variety in cells size is normal. When the number of cells is impaired, if all of them have the same size, it is considered asymmetrical. Those embryos with one big size blasomere is considered abnormal and is associated with high rate of polyploidy.
Multinucleation: multinucleated blastomeres on day 2 and day 3 is associated to a lower implantation rate. These embryos often are mosaics or with aneuploidy. It is more related to abnormalities on day 2 than on day 3.
Cytoplasm aspect: the presence of vesicles on day 3 is considered a sign of embryo genome activation and, therefore, of good prognosis. The presence of vacuoles is a sign of bad prognosis.[2]
Molecular analysis
Molecular analysis can be performed by taking one of the cells from an embryo. The analysis can vary in extent from a single target biomarker to entire genomes, transcriptomes, proteomes and metabolomes. The results may be used to score embryos by comparing the patterns with ones that have previously been found among embryos in successful versus unsuccessful pregnancies:[10]
Transcriptome profiling
In transcriptome evaluation, gene expression profiling studies of human embryos are limited due to legal and ethical issues.[10]
In addition, microRNA (miRNA) and cell-free DNA (cfDNA) can be sampled from the vicinity of embryos, functioning as transcriptome-level-markers of embryo quality.[11]
Proteome profiling
Proteome profiling of embryos can indirectly be evaluated by sampling of proteins found in the vicinity of embryos, thereby providing a non-invasive method of embryo profiling.[10] Examples of protein markers evaluated in such profiling include CXCL13 and granulocyte-macrophage colony-stimulating factor, where lower protein amounts are associated with higher implantation rates.[10] The presence of soluble HLA-G might be considered as another parameter if a choice has to be made between embryos of equal visible quality.[1]
Another level of opportunity can be achieved by having the evaluation of the embryo profile tailored to the maternal status in regard to, for example health or immune status, potentially further detailed by similar profiling of the maternal genome, transcriptome, proteome and metabolome. Two examples of proteins that may be included in maternal profiling are endometrium-derived stathmin and annexin A2, whose down- and up-regulation, respectively, are associated with higher rates of successful implantation.[10]
Genome profiling
A systematic review and meta-analysis of existing
A major drawback of genomic profiling for embryo quality is that the results generally rely on the assessment of a single cell, PGP has inherent limitations as the tested cell may not be representative of the embryo because of mosaicism.[12]
When used for women of advanced maternal age and for patients with repetitive IVF failure, PGP is mainly carried out as a screening for detection of chromosomal abnormalities such as
In addition to screening for specific abnormalities, techniques are in development that can avail for up to
Health prediction
The main method currently used to predict the health of a resultant person of an embryo is