Qualification system for embryos – what does it look like?
IVF specialists often talk about embryo quality and how important it is to the entire process. What, exactly, makes an embryo “good” or “bad”? How do embryologists decide which embryos are the best ones to transfer? Can embryo quality be influenced by the patient?
In 3on1 #IVFANSWERS we asked three IVF experts one question. To tell us everything there is to know about embryos and how they judge their quality.
Our experts are:
- Dr Minerva Ferrer, Crea Assisted Reproduction Medical Center, Spain
- Dr Renata Huttelova, IVF Cube, Czech Republic
- Dr Harry Karpouzis, Pelargos IVF, Greece
Answer from Dr Ferrer
Embryos can develop for up to five or six days before they are implanted into the mother’s uterus. Their development is evaluated according to consensus criteria established by experts. The criteria are based on morphology parameters: cell number, cell size and their symmetry at specific points of their development. More recently, time-lapse technology has also allowed embryologists to observe morphokinetic parameters which are associated with normal embryo development. Unlike prior methods, this tool allows us to observe embryo development as it happens, instead of just monitoring the embryo at predetermined points in time.
Overall, embryo classification systems use morphological parameters to determine the development potential of each embryo, as well as employing morphokinetic data as added value to evaluate embryo viability.
In our clinic, we use the grading system established by the Spanish Society for Reproductive Biology. The scoring scheme classified embryos into four different categories, from the highest (A) to the lowest (D). It is worth noting that an embryo’s classification may change over the course of its development – for instance, a grade A embryo on day three may not result in a grade A blastocyst on day 5.
Answer from Dr Huttelova
Embryo quality could be evaluated by morphological parameters, as well as the timing of the cell division. Morphological parameters include the number of cells, as well as stage specificity, fragmentation, and others. This grading system is normally used until the embryo reaches the third day of its development.
On day four, the cells within the embryo undergo compaction, which we can also use to determine the embryo’s overall quality. On day five, when the embryo reaches the blastocyst stage, we use a different grading system based on the blastocyst expansion rate, and its hatching status. We measure the inner cell mass and the quality of the trophectoderm. The expansion of the blastocyst can be measured by examining the cavity of the embryo, which could be small, full or expanded; or, if we see the blastocyst expand past – hatch out of – the zona pellucida, which indicates that it reached or is reaching the final stage of its development. The same grading system is used for the trophectoderm, which later on becomes the placenta; we evaluate how many cells it consists of and how compacted the cells are. Evaluating embryos by the timing of the cell division requires a special time-lapse incubator. Using this approach we are able to record the entirety of the embryo’s development, which gives us data that is then fed into software which can help determine the embryos with the best potential for implantation.
Answer from Dr Karpouzis
The embryo quality grading system rates embryos by their morphology. The embryologists examine the embryos either on day three or day five of development in order to evaluate specific aspects of their growth. It’s important to understand that even a “perfect embryo” is not 100% guaranteed to be genetically perfect. Even in morphologically perfect embryos there is a significant amount of chromosomally abnormal embryos – this mainly depends on the age of the woman and the quality of the sperm.
On the other hand, if the embryo is not perfect morphologically, it does not mean the embryo will not implant successfully; in fact, we have seen a lot of pregnancies as a result of a morphologically imperfect embryo.
The aspects evaluated by the embryologists are different for embryos on day three than for those on day five of their development. There are also different grading system used in the laboratories. The most common one grades a blastocyst with a number and two letters, for example 4AB.
So when a patient undergoes an IVF treatment, whether through egg donation or using her own eggs, and sees a doctor’s note stating a day three embryo is grade three, or that a blastocyst is rated 4AA, what does that actually mean?
Let’s look at day three embryos first. What happens on day three is that the embryo’s cells are dividing, but the overall size of the embryo is not increasing. A normal embryo on day three has between six and ten cells, with the ideal number usually being eight cells. The quality of the embryo, however, does not only depend on the number of cells; there are also other qualities that need to be considered, such as fragmentation. Sometimes, as the embryo develops, the cytoplasm inside of it breaks down into smaller fragments. An ideal embryo on day three does not have any fragments; a grade two embryo may have a small number of fragments, while a grade three may have a large amount. Cell size is another important factor – the cells should be synchronous, that is, they should have been divided in the same way and be of the same size. So – an ideal day three embryo should have eight cells, all of the same size, with no fragmentation. However, it doesn’t mean that an embryo which deviates from these parameters will not reach the blastocyst stage or not implant correctly.
Day five embryos – embryos which reach the blastocyst stage – keep dividing while also increasing in size. It also starts developing a cavity inside; in an ideal situation, this cavity is surrounded by cells and has a mass inside. This mass is called the inner-cell mass, while the outside is called the trophectoderm. We grade the embryos with a number, which signifies how much the embryo has expanded. For instance, a grade 1 blastocyst has a cavity which takes up less than half of the overall size of the embryo, a grade 2 has a cavity which is larger than half, a grade 3 takes up almost the entire embryo, and a grade 4 is an expanded blastocyst with a very thin layer of cells surrounding it.
After we determine the size of the embryo, we observe the hatching process of the embryo, or rather, how far along in the process the embryo is. Hatching means exactly what you think it means – the embryo breaks the surrounding cell lining and starts expanding outwards. We assign letters, such as AA, AB, or AC to each embryo. The first letter grades the inner cell mass and the second grades the quality and the morphology of the blastocyst. This grading system allows embryologists to evaluate which embryos have more potential of resulting in a successful pregnancy.
Historically, however, grading systems such as this one have had a significant degree of subjectivity – that is, the grade given to each embryo depends on the embryologist. This is where technology comes into play. These days, many embryologic laboratories use a device known as an embryoscope, which allows us to monitor the cell division within the embryo and use sophisticated algorithms to reduce the amount of subjectivity in the grading process.
However, keep in mind that a morphologically correct embryo does not necessarily mean it’s also genetically correct.