Table 1.
Studies addressing methods to evaluate mammalian embryos by non-invasive or invasive techniques.
| Authors | Technique | Nature | Species | Embryo stage | Compared to what traditional technique | On what parameters | Pros | Contras | Sample Size |
|---|---|---|---|---|---|---|---|---|---|
| Lindner & Wright, 1983 | Morphological assessment by stereomicroscopy | Noninvasive | Bovine | From morula to hatched blastocyst | Physiological parameters of devel-opment kinetics and pregnancy rates | Embryo stage and quality (excellent, good, fair and poor) on pregnan-cy rates | Embryo quality was a useful predictor of the pregnancy rate | Subjectivity of the embryo quality assessment; excellent and good qualities had no difference on pregnancy rate | 783 |
| Gardner & Schoolcraft, 1999 | Morphological assessment by stereomicroscopy | Noninvasive | Human | Blastocyst | Morphological aspects of the trophectoderm and inner cell mass | Blastocyst quality based on grades | Validated worldwide by embryologists and clinicians due its useful relation with pregnancy establishment | Does not cover all aspects of the aberrant morphology and it is limited to blastocyst stage | ND |
| Balaban et al., 2006 | Morphological assessment by stereomicroscopy | Noninvasive | Human | Blastocyst | Comparison between the Gardner and Dokras systems of evaluation | Clinical pregnancy, implantation rate and multiple pregnancies | Both systems were practical and accurate, good to predict blastocysts with high implantation potential and to limit the number of embryo transfer to avoid multiple pregnancies | Lack of a single and unified system and a standard to evaluate | 132 |
| Richardson et al., 2015 | Simplified method to evaluate blastocysts | Noninvasive | Human | Day 5 blastocyst | Traditional method to evaluate embryo morphology | New and simpli-fied method with less parameters to assess | Faster and easier than the traditional method (Gardner & Schoolcraft, 1999) with similar or better results than a more complex system | Method rarely used by clinicians | 80 |
| Shiku et al., 2001 | Scanning electrochemical microscopy (SECM) | Noninvasive | Bovine | From morula to blastocyst | NA | Results showed that morulae with higher oxygen consumption were faster to develop into blastocysts. The method could be just a complement or to change the way how the embryo is chosen | Noninvasive technique that could be reliable to the embryo viability assessment and development | Not well established and worldwide acceptation | 19 |
| Braga et al., 2015 | Mass spectrometry to charac-terize (“fin-gerprint”) the culture medium conditioned by the embryo | Noninvasive | Human | Day 3 of culture | Spectroscopy | To identify potential embryo lipid biomarkers that are predictors to preview blastocyst formation | Promising approach to identify embryos that should be cultured until Day 5 or cryopreserved | 50 | |
| Yang et al., 2012 | Chromosomal screening by array Comparative Genomic Hybridization (aCGH) | Invasive | Human | Day 5 | NA | Together with morphological evaluation presented the best results | Produced clinical pregnancy more frequently and a lower abortion rate when compared to embryos chosen without a CGH | Demands skills from the embryologist and complex equipment to perform the invasive technique | 814 |
| Kropp et al., 2014 | Micro RNA (miRNA) profile | Noninvasive | Bovine and Human | Day 5 or 6 | NA | Potential to develop noninvasive biomarkers to predict embryo quality | Embryo quality related with some miRNA expression | Needs more studies and development of robust and accurate biomarkers | 216 (bovine embryos) |
| Kakourou et al., 2013 | Transcriptomic analysis | Invasive | Human | Blastocyst | NA | Results highlighted the importance of the hormones and their receptors but lack a physiologic comprehension of their role on the early development | Future analyses could identify new biomarkers that predict embryo development potential | Still an experimental method that needs more studies | 03 |
| Farin et al., 1995 | Videotape assessment of embryo images | Noninvasive | Bovine | From morula to blastocyst | NA | Way to measure interembryologist agreement. Quality | Good to excellent agreement existed for classifying Day 7 embryos by stage and by extremes of quality grade (grades 1 and 4). It was proposed a simple grading criteia to maximize agreement among evaluators | There was poor agreement of evaluators by degree of abnormal morphology (Grades 2 and 3) | 40 |
| VerMilyea et al., 2014 | Timelapse | Noninvasive | Human | Day 1 to 3 | NA | Strong predic-tion of the clinical pregnancy when related to P2 (time between 1st and 2nd mitosis or 2 cellstage duration) and P3 (time between 2nd and 3rd mito-sis or 3 cell-stage duration) | Automatized predictive model | Not suitable to blastocyst evaluation | 375 |
| Milewski et al., 2015 | Timelapse | Noninvasive | Human | Day 5 | NA | Based on time of cell divisions (2 and 5 blastomeres) and inter-val between 2nd and 3rd divisions, it was proposed a multivariate predictive model | Evaluation of morphokinetics parameters could provide data encompassing a long time frame of embryo development. This is the main advantage of the method, i.e. the opportunity to observe the embryo almost continuously | The method considers only morphokinetic parameters - such as the relative and absolute times of cell division – on the impact of the embryo capacity to reach the blastocyst stage | 162 |
| Wong et al., 2010 | Image analysis algorithm | Noninvasive | Human | Day 2 | NA | First algorithm attempt to ebryo development automatized analysis. Could predict the blastocyst stage of develop-ment | Automatized analysis of parameters | Unable to discriminate parameters to predict the development up to blastocyst and its quality | 242 |
| Santos Filho et al., 2012 | Support Vector Machine | Noninvasive | Human | Blastocyst | NA | Potential method to automatized embryo classification discriminating quality parameters of inner cell mass and trophectoderm | Method based only on the blastocyst image (numerical data mined from it with more discrimina-tory parameters than visual morphology assessment by human beings) | Semiautomatic meth-od was obtained and a fully automatized meth-od should be achieved | 73 |
| van Loender-sloot et al., 2014 | Logistic regression | Noninvasive | Human | Day 3 | Embryonic morphology | Early cleavage, blastomere number on days 2 and 3, morphologic pointing and presence of a morula no Day 3 of culture | Method capable to distinguish embryos with high implantation potential from those with moderated or low potential | 6021 | |
| Chen et al., 2016 | Data mining to produce a computer assisted scoring system based on multivariable logistic regression and multivariate adaptative re-gression spline | Noninvasive | Human | Day 1,2 and 3 | Embryonic morphology | Point grading system | Improvement on the generalization of the current predictive models | Promising approach although still experimental | 871 |
| Matos et al., 2014a | Artificial neural network | Noninvasive | Mouse | Blastocyst | Embryonic morphology | To avoid the subjectivity of the assessment done by a human examiner | Classification systems fully based on software | Needs an embryologist to manually to obtain numerical parameters from the embryo image | 98 |
| Matsuura et al., 2010 | Blastocyst quality score | Noninvasive | Human | Blastocyst | NA | New pointing system | Numerical classifi-cation system based on the Gardner & Schoolcraft (1999) criteria | There is a requirement for a huge number of embryos to produce statistical significance | 220 |
| Tejera et al., 2012 | Oxygen consumption measurement | Noninvasive | Human | Day 3 | NA | Oxygen consump-tion rate was associated with potential implantation and embryo quality | Technique used as a complementary pa-rameter to determine the embryo to be chosen | Not useful to predict implantation rates. The causes of this lack of predictability is the clinical relevance of other variables that are related to embryo quality | 84 |
| Thompson et al., 2016 | Multi-spectral imaging to evaluate the endogenous auto fluores-cence | Noninvasive | Human and Bovine | Early embryo stages | Diversity of techniques | The authors are trying to correlate the observed pattern of auto fluorescence with metabolic profile of the embryo. The aim is to predict the embryo quality during development of early embryos | High resolution imag-ing (single embryo), real time and noninvasive method that could be associated with others (e.g., tra-ditional morphological evaluation) besides computer based techniques. It is a current promise to determine the intracellular met-abolic activity | Experimental technique under evaluation | ND |
| López-Damián et al., 2008 | Transmission electron microscopy | Lethal | Bovine | Blastocyst | NA | Demonstrated the sub-cellular varia-tion of the embryos classified as fair grade by optical light microscopy and by stereomi-croscopy | Validated the ac-curacy of the IETS proposed system of embryo classification | Unable to evaluate an embryo intended to be transferred to the uterus, just to validate the accuracy of a technique on subcellular aspects | 30 |
Legend: Nature - invasiveness of the technique employed; Embryo stage – range of stages where the embryo was suitable or was used in the study; Compared to what traditional technique – when it was the case - that a new proposed technique had its efficacy compared to a traditional and well established one; On what parameters – when there was such comparison, did it occur, if not the case, in what primary parameters the authors evaluated the embryos; Sample size – the quantity of embryos used on the study; NA – not available; ND – not determined.