Preimplantation Genetic Testing for Chromosomal Aneuploidy (PGT-A)
Day 5 Trophectoderm Biopsy
Preimplantation genetic testing for chromosomal aneuploidy (PGT-A), historically known as comprehensive chromosomal screening (CCS) or preimplantation genetic screening (PGS), is a technique to assess all 23 pairs of chromosomes in human embryos for abnormalities. It allows us to identify embryos that are more likely to be chromosomally normal to replace into the uterus. By doing so, the pregnancy rate can be improved and the miscarriage rate can be reduced. It also reduces the chance of chromosomal abnormalities in the fetus.
The most common reason for failure of an in vitro fertilization cycle is the transfer of chromosomally abnormal embryo(s), thus leading to failure of implantation or miscarriage if conception occurs. Embryos are biopsied on day 5 of embryo development, called the blastocyst stage. Usually, about 5-10 cells are taken from the trophectoderm portion of each blastocyst. The trophectoderm is the part that will form the placenta later.
The most common reason for failure of an in vitro fertilization cycle is the transfer of chromosomally abnormal embryo(s), thus leading to failure of implantation or miscarriage if conception occurs. Embryos are biopsied on day 5 of embryo development, called the blastocyst stage. Usually, about 5-10 cells are taken from the trophectoderm portion of each blastocyst. The trophectoderm is the part that will form the placenta later.
After the biopsy, the blastocysts are then frozen to allow time for the PGT-A. The biopsied cells are then sent by courier to the PGT laboratory for analysis. Blastocysts that are found to be chromosomally normal based on the PGT-A test results are subsequently transferred in a frozen embryo transfer cycle. Generally, the embryo survival rate after a freeze and a thaw is very good but there is no guarantee that they survive the process.
This technique may help individuals and couples with recurrent pregnancy loss, repeated IVF implantation failure, or when the female partner is at a higher risk of having eggs with chromosomal abnormalities (an example being a female partner of age greater than 35) by providing chromosomal information about the embryos to help with embryo selection prior to transferring them into the uterus.
It is very important for individuals or couples to understand the limitations of PGT-A before deciding to proceed.
- PGT-A assesses only chromosomes, not single gene disorders such as cystic fibrosis, hemophilia, thalassemia, Huntington’s disease, etc., or multifactorial diseases such as autism. Subtle chromosomal abnormalities can still be potentially missed by the technique.
- The PGT-A result on each embryo is not 100% accurate. The error rate, which is generally not higher than 5%, may be due to a technical aspect of the testing or a phenomenon called chromosomal mosaicism in human embryos. Previous studies have shown that an early human embryo may contain cells of different chromosomal content. This limits the ability of using the biopsied cells to determine the chromosomal content of the rest of the embryo with certainty. Hence, there is a small chance that PGT-A may be erroneous in determining that an embryo is normal when it is not, and vice versa. As a result, the current recommendation is that the standard prenatal genetic testing stays the same after PGT-A has been performed.
- There are occasions when PGT-A does not yield results and the chromosomal status of embryos remains undetermined.
- Due to the occurrence of chromosomal mosaicism in human embryos, the PGT-A result may indicate possible chromosome mosaicism. Embryos with such PGT-A results have a combination of chromosomally normal and abnormal cells. There is a concern that transferring these mosaic embryos is more likely to lead to failure to conceive, increased risk of miscarriages, abnormal placental function, and even abnormal live births due to the chromosomal mosaicism. Transfer of these embryos should only be considered when there is no alternative and only after further genetic counseling has been done to discuss the clinical implication of the specific type of mosaicism in each of these embryos.
- PGT-A does not guarantee pregnancy or normal live birth. Miscarriages and fetal chromosomal abnormalities can still occur after PGT-A although much less frequently.
Individuals or couples must, however, consider the potential benefits and limitations of the technology before deciding whether they would like to proceed with this.Individuals or couples who have more specific genetic concerns, such has a family history or personal medical history of genetic conditions should make arrangements for genetic counseling to assess the genetic risk of them having offspring with specific genetic diseases. Depending on the result of their assessment by medical geneticists, they may benefit from a technology called preimplantation genetic testing for single gene disorders (PGT-M) for their specific conditions. Likewise, individuals or couples who have known rearrangement of chromosomes called translocation or inversion should make arrangements to be seen in consultation regarding the option of preimplantation genetic testing for structural rearrangement (PGT-SR).
Please feel free to discuss the above with your physician.