Before talking about what mosaic embryos are, it is helpful to describe how PGT-A works. PGT-A, or preimplantation genetic testing for aneuploidy, is a test used to determine the number of chromosomes in an embryo.
So, what is a chromosome?
DNA is a very long molecule, and to squeeze it inside our cells, it needs to be packed up tightly into structures called chromosomes. In humans, there are two copies of 23 chromosomes, to make 46 in total.
Embryos with these 46 chromosomes are normal or euploid, while the ones with the wrong number of chromosomes are abnormal or aneuploid. Aneuploid embryos have a very high chance of miscarrying or not implanting, so transferring these embryos is typically avoided.
PGT-A is performed by taking a small 5-10 cell biopsy sample of the embryo and then DNA sequencing it to determine the number of chromosomes in the cells. If all the biopsy cells have 46 chromosomes, then the corresponding embryo (from which the biopsy came) is considered euploid. If not, it is considered aneuploid.
Sometimes, the biopsy has a mix of euploid and aneuploid cells. It is called a mosaic. You can see how mosaic embryos contain a mix of euploid (blue) and aneuploid (red) cells below:
Source: Remembryo.com
What are the different types of mosaic embryos?
There are different ways to classify mosaic embryos, and some may be more suitable for transfer compared to others.
Mosaic embryos can be grouped based on the different amounts of aneuploid cells that the embryo contains. Generally, low-level mosaics have 20-40% aneuploid cells, while high-level mosaics have 40-80% aneuploid cells.
In some cases, a lab can classify these levels with different thresholds or can have different categories. For example, one lab might consider a low-level mosaic as having 20-30% cells, and a moderate-level as having 40-60% aneuploid cells. It just depends on the lab and how they do things.
Besides low- and high-level categorization, mosaics are also classified based on the type of abnormality they have.
There are “whole chromosome” and “segmental” mosaics.
In some cases, a whole chromosome is either missing or duplicated. So instead of having the normal number of chromosomes (46), maybe there’s 45 or 47. When whole chromosomes are involved, this is called a whole chromosome mosaic. Alternatively, segmental abnormalities are when only a piece of a chromosome is affected rather than the whole chromosome. Mosaics that have this kind of abnormality are called segmental mosaics.
How are mosaics prioritized for transfer?
Generally, low-level mosaics perform better than high-level mosaics and segmental mosaics perform better than whole chromosome mosaics. This is based on a 2021 study that transferred 1,000 mosaic embryos and ranked them based on their live birth rates. Another 2021 study found that mosaics with <50% aneuploid cells had equivalent live birth rates to euploids!
While this is encouraging, research on mosaics is constantly evolving, so it is best to consult with your doctor about which mosaic to transfer.
Another important point to consider is the specific chromosome that’s affected. Each mosaic will have aneuploid cells with a particular chromosome that’s affected. Certain affected chromosomes might be more concerning than others.
One example of this is chromosome 21 because individuals with three copies of chromosome 21 have Down syndrome. So transfering a mosaic with this abnormality may have increased risks of having a child with Down syndrome.
It is important to discuss mosaic embryo results with a genetic counselor to understand the risks.
Do mosaic embryos result in mosaic babies?
While mosaic embryos can result in mosaic babies, it is quite rare. In most cases, mosaic embryo transfers lead to the birth of healthy babies, and the risk of a newborn having the same abnormality as the mosaic embryo is very low.
Mosaic embryos can correct their mosaicism by removing their aneuploid cells in a process called “self-correction.”
Research is ongoing, but it looks like mosaic embryos can self-correct in one of two ways. Either the aneuploid cells die off, or they end up in the trophectoderm (the part of the embryo that does not become the fetus, but becomes the placenta, which can tolerate abnormal cells).
In conclusion, mosaic embryos provide a good alternative to euploid embryo transfers after PGT-A, with high success rates depending on the mosaic type.
by Sean Lauber
Embryoman (Sean Lauber) is a former embryologist and creator of Remembryo.com, where he provides weekly reviews of the latest IVF research. You can follow him on Facebook, Instagram and TikTok.
