How Are Embryos Mosaic?
Mosaicism is a fairly new term in the world of IVF, but it refers to an embryo that consists of cells with both normal and abnormal chromosomes. In other words, some of the embryo’s cells have the right amount of DNA, while other cells do not.
As a reminder
Embryos all begin as one cell: a fertilized egg, or zygote. During fertilization, the sperm deposits its DNA into the egg, creating an embryo with two sets of DNA (one from the sperm and one from the egg). Unlike other cells in the body, sperm and (mature) egg cells only consist of one set of DNA. Chromosomes are long strands of DNA, and a sperm and egg should each consist of 23 chromosomes. Thus, a fertilized egg should consist of 23 pairs (or 46 total) chromosomes.
That one cell then undergoes a process known as mitosis, or cell division. During this process, the cell’s DNA is replicated so that the new cell gets a copy of the DNA and a copy also remains with the original cell. The result is two cells with identical DNA.
When things go wrong
Sometimes, an egg and/or sperm with the wrong amount of DNA create an embryo. As a result, the embryo receives the wrong number of chromosomes. When the embryo undergoes cell division, it also replicates the wrong number of chromosomes, which continues throughout cell division. As a result, the embryo’s cells consist of the wrong amount of DNA and the embryo is considered aneuploid. Aneuploid embryos have low success rates and are the leading cause of early miscarriages. Thus, PGT-A is often implemented to screen an embryo’s cells and determine how many have the right number of chromosomes.
You would think that DNA replication would cause all of the cells to have the same DNA, but mosaic embryos actually disprove this. Mosaicism is believed to stem from something called nondisjunction during mitosis, during which a new cell is given a different amount of DNA than the original cell. The result is two cells with different amounts of DNA.
Nondisjunction isn’t always a bad thing. For example, an embryo that originally had the wrong amount of DNA may be able to “self-correct” the error. In this case, some of the original cells would have the wrong amount of DNA, but the newer cells would have the right amount of DNA. The percentage of normal and abnormal cells depends on how early this “self-correction” occurred.
But nondisjunction can also be disadvantageous. For example, an embryo that originally had the right amount of DNA may have an error occur during cell division that causes the new cell to receive the wrong amount of DNA. In this case, the original cells would have the right amount of DNA, but the new cells would not. Again, the severity depends on how early nondisjunction occurred.
Levels of mosaicism
Mosaic embryos typically fall on a scale depending on the percentage of cells that are normal. Though these thresholds can vary between genetic testing companies, we often see embryos with 20-50% abnormal cells referred to as low mosaic embryos, and embryos with 50-80% abnormal cells referred to as high level mosaic embryos.
Low level mosaic embryos have resulted in healthy live births. Surprisingly, mosaicism is often not detected in newborns who were once mosaic embryos. However, high level mosaic embryos have lower success rates.
What to do if I have a mosaic embryo
It’s recommended that you speak with a certified genetic counselor if you have questions about your mosaic embryo. Depending on the severity and abnormality, an embryo may be suitable for transfer. This discussion will help you determine if your mosaic embryo should be transferred or not.
