So you’ve decided to do pre-implantation genetic testing for aneuploidy (PGT-A) on your embryos, and now that you’ve gotten the results back you find out some of your embryos are mosaics. You’ve heard of aneuploid and euploid embryos before, but what is a mosaic embryo? Can mosaics be transferred?
Let’s take a step back for a second.
What is a mosaic embryo?
A euploid embryo is normal, and all of the cells in the embryo have the right number of chromosomes (46). An aneuploid embryo is abnormal, and all of its cells have a different number of chromosomes.
A mosaic is an embryo that has a mix of euploid and aneuploid cells. Mosaic embryos are pretty common and occur in about 1 in 5 embryos biopsied.
Credit: Remembryo
Different types of mosaic embryos
There are different types of mosaic embryos, and they can be categorized in two major ways.
One common way to categorize them is by the percentage of aneuploid cells present. Most labs consider a low-level mosaic as having 20-40% aneuploid cells, while a high-level mosaic has 40-80% aneuploid cells. Not all labs adhere to this rule, and some may have different ranges.
The other way they're categorized is by their type of chromosomal abnormality. Some mosaics have aneuploid cells with whole chromosomes affected, while others have only a segment of a chromosome affected.
Since they're a mix of normal and abnormal cells, mosaics are kind of in-between euploids and aneuploids in their potential for creating a pregnancy.
Can you transfer a mosaic embryo?
One large study compared live birth rates after transferring euploids and 1,000 mosaics. Mosaic embryos ranged from a 13.2% to 43.9% live birth rate, while euploids had a 52.3% live birth rate.
Generally, the best-performing mosaics were low-level and had only one chromosome affected. Segmental mosaics did well, also. High-level mosaics with more than 3 chromosomes affected had the lowest live birth rates. Based on this study and many others, guidelines have been put together to help patients and doctors in making informed decisions.
A group of PGT-A experts called the Preimplantation Genetic Diagnosis International Society (PGDIS), put together guidelines and have established a ranking order for mosaic transfers. There are other groups that have also created guidelines.
According to the PGDIS, low-level mosaic embryos are given priority over high-level mosaics, and whole chromosome mosaics are given priority over segmental mosaics. Some recent studies have found that segmental mosaics have reasonable success rates, and these guidelines are constantly evolving as new research comes out.
Mosaic embryos and birth defects
You may be wondering, "What about birth defects?" There’s only been a handful of cases where mosaic embryos have resulted in the birth of a baby with the same affected chromosome, despite transferring mosaics with every type of chromosomal abnormality.
Because of how rare it is to transfer a mosaic and have a baby with an affected chromosome, the new PGDIS guidelines don’t consider the chromosome that’s affected in the mosaic when prioritizing mosaic transfers. However, these guidelines are always changing, and it’s best to discuss transferring “high-risk” mosaics, such as a mosaic with trisomy 21, with your doctor and a genetic counselor.
So if mosaic embryos have aneuploid cells, how do they result in healthy babies without any abnormalities? It turns out that mosaic embryos have the ability to “self-correct” and remove aneuploid cells. Pretty cool, right?
Mosaic embryo self-correction
Research is ongoing, but there are a couple of methods for mosaic embryo self-correction: The first method is that the mosaic embryo’s euploid cells outgrow the aneuploid cells. This could be because the aneuploid cells grow very slowly, or they die, leading to a situation where the euploid cells dominate.
Another method for self-correction is for aneuploid cells to become selectively enriched in the trophectoderm. In a blastocyst, the two major types of cells are the inner cell mass, which becomes the fetus, and the trophectoderm, which becomes the placenta. The placenta can actually tolerate aneuploid cells, and in fact, mosaicism in the placenta is pretty common in natural pregnancies!
Image showing the different parts of a blastocyst. Credit: Remembryo.
Regardless of how the mosaic self-corrects itself, the end result is a euploid embryo that develops normally and has no detectable chromosomal abnormalities. Still, transferring mosaic embryos can be a bit nerve-racking, because of the concern that the embryo will not implant, or that it will develop into a baby with a genetic disorder.
Prenatal testing in pregnancies involving mosaic embryos
To help you feel more confident, the PGDIS recommends prenatal testing for all transfers involving mosaic embryos. Non-invasive prenatal testing typically just tests the placental tissue, while amniocentesis tests the baby’s tissue and will give a more definite answer. However, there are risks in performing amniocentesis and this should be discussed with your doctor.
The bottom line is this: Transferring mosaic embryos doesn’t need to be scary. Just think of all of the women out there who haven’t done PGT-A and are transferring mosaic embryos without even knowing it. Mosaic embryos can have variable success rates, but they do work, and there's always hope.
For more information on mosaic embryos, visit my Complete Guide To Mosaic Embryos.
Sean Lauber aka "Embryoman" is a former embryologist and creator of Remembryo.com, where he provides weekly summaries of the latest IVF research. You can also follow him on Facebook, Instagram and TikTok.