Preimplantation Genetic Testing
Preimplantation genetic testing (PGT) is a genetic test that is performed on biopsied cells from an embryo. In order to do PGT, in vitro fertilization (IVF) is required. IVF is when eggs are retrieved and fertilized by sperm, creating an embryo. A biopsy of about 5-10 cells is performed when the embryo is about 5 or 6 days old. The reason the biopsy occurs at this point of the embryo’s development for two reasons. The first reason is because the embryo has about 200 cells. The second reason is because those cells are starting to organize. Those cells organize into an outside layer and inside layer. I like to imagine a peach as an embryo, where the outside fuzzy layer is akin to the outside layer of the embryo which is called the trophectoderm. The trophectoderm cells will become the future placenta and supporting structures of the pregnancy. The seed in the peach is akin to the inner layer of the embryo which is called the inner cell mass which will eventually become the baby. The outside layer of the embryo is biopsied. Those 5-10 cells are sent to a genetic laboratory that will run the PGT analysis.
There are three main PGT tests available:
Preimplantation Genetic Testing for Aneuploidy (PGT-A)
Preimplantation Genetic Testing for Monogenic Conditions (PGT-M)
Preimplantation Genetic Testing for Structural Rearrangements (PGT-SR)
PGT-A
PGT-A is the most common PGT test performed. PGT-A assesses the embryo for aneuploidy. Aneuploidy means there are too many or too few chromosomes. PGT-A can be considered for anyone undergoing IVF because anyone can have an embryo or embryos with aneuploidy. However, as a woman or person with ovaries ages, the chance for aneuploidy increases, so this screen is particularly helpful if a someone is over 35 years of age. If an embryo has too many or too few chromosomes, then this can lead to implantation failure, miscarriage, or a child with health concerns such as intellectual disability and/or birth defects.
The goal of PGT-A is to help with embryo prioritization. Usually people have more than one embryo that is available to transfer, so PGT-A is a way to determine which should be transferred first. There are a few results that are possible with PGT-A: normal (also known as euploid-the science word to describe the typical number of chromosomes), abnormal (also known as aneuploid) and mosaic. Normal results mean that there is the expected number of chromosomes, and the embryo is believed to have the best chance to implant and continue on as a pregnancy. An abnormal result indicates there is not the typical number of chromosomes. If an abnormal embryo is transferred, the expectation is that implantation failure or miscarriage may occur.
Mosaic results are a bit more tricky-please check out this article, Preimplantation Genetic Testing for Aneuploidy Considerations: Embryo Mosaicism, to learn more about this result. A mosaic result indicates there is a mixture of results. It may be that some of the chromosomes are normal and some are abnormal. One explanation for why the results appear that way may be that some cells have normal chromosomes and some cells have abnormal chromosomes. The issues with the mosaic result, which is generally not the issue with abnormal or normal results, is that the chromosome makeup of the rest of the embryo cannot be inferred and it is difficult to know what to expect if the mosaic embryo is transferred. It may result as a miscarriage, implantation failure, ongoing pregnancy without the initial reported abnormality, or rarely an ongoing pregnancy with the initial reported abnormality.
PGT-SR
PGT-SR is the test option for individuals who have a structural rearrangement (also known as a balanced rearrangement or translocation) within their chromosomes. This means they have all the chromosomes they need, but those chromosomes are arranged in a way that when go on to have a pregnancy or embryo, they may give too many or too few chromosomes which can lead to aneuploidy in the embryo. An aneuploid embryo, if transferred, can lead to implantation failure, miscarriage, or a child with intellectual disability and/or birth defects.
PGT-SR assesses the chromosomes for the embryo, with particular focus on the potential chromosome imbalances that can result from the parent’s structural rearrangement. A person may learn they have a structural rearrangement after they have their chromosomes assessed through a karyotype. They may have a karyotype if they have a history of unexplained recurrent miscarriages, unexplained infertility, or a previous pregnancy that had a chromosomal abnormality.
PGT-M
PGT-M assesses the embryos for monogenic (also known as single gene conditions) conditions. A monogenic condition is caused by one gene that is nonfunctional. Cystic fibrosis is one example of a monogenic condition. If a couple are known carriers of a condition, then they could have PGT-M to detect which embryos may have the condition and which do not. They can then only transfer the embryos without the condition. If someone has a genetic condition such as Marfan Syndrome or BRCA1, then they can also consider this testing to select against embryos that inherited the genetic condition.
Usually genetic testing laboratories have a review process to identify if a family’s case is amenable to PGT-M.
Limitations
It is important to know that PGT testing has limitations. One limitation is this assessment is considered screening not diagnostic testing. This means that the screen can reduce the possibility of the condition(s), but it cannot eliminate the possibility. The lab performing the screen will have a accuracy rate.
Another limitation is the cells that are biopsied are ones that will become the future placenta and not the future baby. Therefore, the baby’s cells are never tested for directly. While it is most likely the baby’s genetics will match the genetics of the future placenta, this is not always the case.
Lastly, PGT requires a biopsy of an embryo and for the embryo to be cryopreserved while waiting for results, then thawed to be transferred. These steps are added pressures to the embryo and may impact the embryo’s ability to become a pregnancy. The risk is believed to be small, but still a risk nonetheless.
Please talk to your healthcare provider to determine what, if any, PGT test is appropriate for you.
Resources:
Viotti M, Victor AR, Barnes FL, Zouves CG, Besser AG, Grifo JA, Cheng EH, Lee MS, Horcajadas JA, Corti L, Fiorentino F, Spinella F, Minasi MG, Greco E, Munné S. Using outcome data from one thousand mosaic embryo transfers to formulate an embryo ranking system for clinical use. Fertil Steril. 2021 May;115(5):1212-1224. doi: 10.1016/j.fertnstert.2020.11.041. Epub 2021 Mar 6. PMID: 33685629.
* This blog constitutes general information about genetic testing and medical screening. This blog does not offer or provide medical advice or diagnosis, and nothing in this blog should be construed as medical advice or diagnosis. Do not rely on the information in this blog/article to make medical management decisions. Please consult with a medical professional before making those decisions. Do not delay in seeking professional medical advice if you think you have a medical concern. Do not disregard professional medical advice based on any information received in this blog.
