From the Guidelines
The grading of embryos has limited solid evidence supporting its ability to predict pregnancy outcomes, and its clinical utility remains controversial due to the lack of proof of efficacy in increasing live births. While embryo grading systems are widely used in IVF clinics to assess embryo quality based on morphological characteristics like cell number, fragmentation, and blastocyst development, their correlation with actual implantation and live birth rates is modest at best, as noted in a recent study published in Genetics in Medicine 1. Studies show that even embryos with poor morphological grades can result in healthy pregnancies, while those with excellent grades may fail to implant. More advanced techniques like preimplantation genetic testing (PGT) provide stronger evidence for embryo selection by detecting chromosomal abnormalities, though this approach has its own limitations, including the risks associated with IVF, such as preeclampsia, abnormal placentation, cesarean section, prematurity, low birth weight, and miscarriage, as highlighted in a statement by the American College of Medical Genetics and Genomics (ACMG) 1.
The subjective nature of traditional grading, variation between embryologists, and the inability to assess genetic composition through visual inspection alone contribute to the limited predictive value. Despite these limitations, embryo grading remains a standard practice because it's non-invasive, inexpensive, and provides some useful information when combined with other factors in embryo selection decisions. However, the American College of Obstetricians and Gynecologists (ACOG) states that routine use of PGT-A for IVF in infertile women is not proven, emphasizing the need for caution and further research in this area 1.
Some key points to consider include:
- The clinical utility of PGT-A to select euploid embryos remains controversial due to the lack of proof of efficacy in increasing live births 1.
- The implementation of PGT-P has been challenged by several groups of scientists and professional societies, including the American Society of Human Genetics, the European Society of Human Genetics, and the European Society of Human Reproduction and Embryology, all of which have called the utilization of PGT-P unethical and reject its use in clinical care 1.
- The use of PGT-P has not been proven to provide clinical utility—in short, the practice has moved too fast with too little evidence, as concluded by the ACMG 1.
From the Research
Embryo Grading Evidence
The grading of embryos has been studied extensively in various research papers. The evidence suggests that embryo grading systems are useful in predicting embryo implantation rates.
- A study published in Fertility and Sterility in 2010 found that day 3 parameters, such as cell number and embryo grade, are more predictive of successful implantation rates than pronuclear morphology (Z-scores) 2.
- Another study published in Panminerva Medica in 2022 reviewed various methods for gamete and embryo assessment, including morphology assessment, and found that identifying the embryo with the highest implantation potential can reduce the number of embryos transferred without compromising pregnancy chances 3.
- A review published in the International Journal of Molecular Sciences in 2020 discussed the use of preimplantation genetic testing (PGT) for selecting euploid embryos and improving clinical outcomes, highlighting the importance of embryo selection in IVF treatments 4.
- An earlier review published in Placenta in 2003 proposed a sequential scoring system for assessing embryo viability, using morphological scoring systems and other indicators such as rate of cleavage 5.
- A more recent review published in Molecular Human Reproduction in 2016 discussed the importance of morphological criteria in assessing human embryo development, even with the advent of time-lapse and 'OMICS' technologies, and proposed that key morphological features should be included in selection algorithms 6.
Key Findings
The studies suggest that:
- Embryo grading systems can predict implantation rates
- Morphological assessment is a critical tool for embryo selection
- Preimplantation genetic testing can improve clinical outcomes
- A combination of morphological and other indicators can be used to assess embryo viability
- Time-lapse and 'OMICS' technologies can aid in embryo selection, but morphological criteria remain important.