Preimplantation genetic testing (PGT) is a screening test that analyzes the genetic material within a sample of cells from an embryo. This testing determines if the cells have any genetic abnormalities, which can interfere with implantation and ongoing pregnancy rates. PGT is >95% accurate.
There are 3 types of PGT:
1. PGT-A (aneuploidy): This determines if the cells in a biopsy sample have the correct number of chromosomes (normal cells have 46 chromosomes). The chromosomes consist of tightly wound DNA strands, which contain the genetic material for that cell. If a cell does not have the correct number of chromosomes, it is considered abnormal (aneuploid). Examples of aneuploidy include monosomies (missing a chromosome, such as Turner Syndrome or X0) and trisomies (have an extra chromosome, such as Down Syndrome or Trisomy 21).
2. PGT-M (monogenic): This determines if an embryo is affected by or a carrier of a monogenic disease. A monogenic disease is caused by a mutation of a single gene, meaning that one gene that is "mutated" causes the disease. Examples of monogenic diseases include cystic fibrosis, Huntington's disease, and Fragile X syndrome. PGT-M is not routinely performed and is only indicated if either parent (or donor) is affected by or a carrier of a specific monogenic disease. Both parents (or donor(s)) can complete carrier screening prior to an IVF cycle to determine if they are affected by or carriers of a panel of monogenic diseases. If this is the case, the genetic testing company can determine if the embryos are affected by or carriers of the same specific monogenic disease. PGT-A can be performed at the same time as PGT-M to determine if an embryo also has the correct number of chromosomes.
PGT-SR (structural rearrangement): This determines if an embryo is affected by a chromosomal misarrangement, such as a translocation or inversion. This is not routinely performed and is only indicated if either (or both) parents (or donor(s)) are affected by a structural rearrangement. A structural rearrangement occurs when part of a chromosome is not in the proper position (see image). In the case of an inversion, one part of a chromosome "turns around," so the new chromosome has a portion of it that is not in the correct orientation. A translocation occurs when a portion of a chromosome "switches places” with a portion of a different chromosome. For example, part of the first chromosome switches places with part of the second chromosome, resulting in 2 chromosomes with mismatched pieces attached to them. Some translocations, known as balanced translocations, are harmless and can cause no phenotypic (physical) changes. Other translocations, known as unbalanced translocations, can cause serious health problems in offspring. PGT-A can also be performed with PGT-SR to determine if an embryo has the correct number of chromosomes.
PGT is performed through an embryo biopsy procedure. In order for an embryo to be biopsied, it must be at a certain stage of development (usually the expanded blastocyst stage or higher) and of a certain quality. At this point, the embryo should consist of over 100 cells. During the biopsy procedure, 5-10 cells are removed from the embryo using a laser. Less than 5% of embryos do not survive the biopsy procedure, and those that do not survive are often of poorer quality. Any number of embryos can be biopsied.
The embryos are frozen in the IVF lab and remain stored there in liquid nitrogen. The biopsy samples, though, are kept frozen and are sent to a genetic testing company. The genetic testing company will amplify (make a lot of copies of) the DNA in the 5-10 cells and then will place those samples into a machine that analyzes their DNA. The machine will generate a report indicating how many of each chromosome are present (and if the embryo is affected by a monogenic disease or structural rearrangement, if those are being tested) in each sample. This report is then emailed to the IVF clinic. The entire process can take anywhere from 1-3 weeks to complete.
PGT results are based on the percentage of cells in a biopsy sample that have the correct number of chromosomes. Keep in mind that each company may have their own reference ranges, and some clinics may not report mosaic embryos. These are some typical reference ranges for PGT results:
1. If 80-100% of the cells in the sample are normal, the embryo is considered normal (euploid). Euploid embryos are recommended for transfer because they have a higher implantation rate and lower miscarriage rate then untested and abnormal embryos.
2. If 20-80% of the cells in the sample are normal, the embryo is considered mosaic. Mosaic embryos are new in the IVF field and are a highly-debated topic. Some clinics will transfer mosaic embryos, though most will require a consultation with a genetic counselor prior to transferring them. This is because mosaic embryos have shown to have lower implantation rates, higher miscarriage rates, and higher rates of preterm birth and birth defects. However, there are many healthy babies born from mosaic embryos. There is also a spectrum for mosaic embryos. If 20-40% of the cells are normal, the embryo is called a high mosaic. If 40-60% of the cells are normal the embryo is called a moderate mosaic. If 60-80% of the cells are normal, the embryo is called a low mosaic. Low mosaic embryos have the highest success rate of all mosaic embryos, but most clinics, including Pelex, still require a genetic consult prior to transferring them. Talk to your doctor for more information about mosaic embryos.
3. If 0-20% of the cells in the sample are normal, the embryo is considered abnormal (aneuploid). Aneuploid embryos have very small chances of implanting, and high incidences of miscarriage, preterm birth, and birth defects. For this reason, most clinics will not transfer abnormal embryos. It is also possible for embryos to have multiple abnormalities. If an embryo has more than 3 abnormalities, it is considered a complex abnormal embryo. If an embryo's chromosomes are very, very abnormal, the embryo is considered a chaotic abnormal embryo. At Pelex, you have the option to discard your abnormal embryos or donate them to research.
4. Non-informative (no read): the final possible result for PGT-A is non-informative (also called a no read). This occurs when there is not enough DNA in the biopsy sample for the machine to generate a result. These embryos will need to be thawed, biopsied, and frozen again. The new biopsy sample will then be sent to the genetic testing company, and the process will repeat.
Anyone can benefit from PGT, though it is most beneficial for women over 35 years of age. This is because a woman's egg number and quality begin to decline after 35 years of age, making the likelihood of having abnormal embryos higher, as well.
Studies have shown that PGT can actually lessen miscarriage rates up to 50% (again, this is mostly predominant in patients over 35). Further, though, it is possible for patients to have abnormal embryos even if they are under 36 years of age. Therefore, PGT can be useful for anyone going through IVF, though it is most beneficial for women over 35.
It's worth noting, though, that PGT is not perfect. It is a screening test that is only ~95% accurate. Additionally, embryos can still either fail to implant or miscarry even if they are deemed euploid. Finally, PGT is a very costly procedure that most insurance companies do not cover. Thus, it's important to weigh the pros and cons of PGT prior to your IVF cycle.
What Are Monogenic Disorders? - Classification & Most Common Types (invitra.com)
How PGT-A Reduces the Chance of Miscarriage | CooperSurgical Fertility Companies
Difference Between Inversion and Translocation | Definition, Types, Process, Effect, Similarities and Differences (pediaa.com)