The IVF process can be a time filled with difficult decisions, and trying to work with your doctor to figure out the “right” next steps is often stressful. One of the biggest choices you will be faced with is whether or not to genetically test your embryos using preimplantation genetic testing (PGT). In addition to embryo grading, PGT can help improve your chances of selecting a healthy embryo for transfer, and ultimately, live birth. In this article, we’ll go through exactly what PGT is, and why you might want to consider it during IVF.
Embryo Grading vs. Preimplantation Genetic Testing
At this point, you could be wondering, “Why would I want to genetically test an embryo that has already been graded under a microscope?” While embryo grading can inform you about the quality of an embryo based on its size, shape, and structure; grading is not able to detect genetic changes that could negatively impact the embryo's health.
Preimplantation genetic testing goes a step further. It can inform you and your doctors if an embryo has extra or missing chromosomes (PGT-A for Aneuploidy), single gene conditions (PGT-M for Monogenic Conditions), or chromosome rearrangements (PGT-SR for Structural Rearrangements). We know that all of the information can be confusing, so we’ll break it down for you. Now let’s take a closer look at what these tests do, who they’re for, and the potential benefits!
What is PGT-A?
PGT-A, or Preimplantation Genetic Testing for Aneuploidy, screens an embryo for chromosomal abnormalities, the most common cause of miscarriage, regardless of conception method. Aneuploidy is the scientific term for extra or missing chromosomes or pieces of chromosomes. An aneuploid embryo contains too much or too little genetic material and will be less likely to lead to a birth. These chromosomal errors are common and can occur during the development of the sperm, the egg, or during fertilization.
“To perform PGT-A, we remove about 5 cells from an embryo that has about 200 cells and send them to genetic testing (at a laboratory like Natera) to see how many chromosomes the embryo has,” explains Dr. Allison K. Rodgers of Fertility Centers of Illinois. “The results can be either normal, which can lead to a healthy pregnancy, or abnormal (too many or too few chromosomes), which would either lead to no pregnancy, a miscarriage, or an abnormal pregnancy.”
Dr. Rodgers explains that PGT-A is often recommended for patients over the age of 35, those who have failed prior transfers of untested embryos, and those who have had a miscarriage or recurrent pregnancy loss. PGT-A is also advised for people with prior abnormal pregnancies or known genetic conditions in one or both parents, as well as those who would like the option of sex selection or embryo banking.
At any age, PGT-A can reduce the time to pregnancy during IVF, improve pregnancy rates, and can reduce the risk of miscarriage. Some forms of PGT-A can detect a chromosomal condition called mosaicism. Speak with your doctor or a genetic counselor if you’d like to learn more about PGT-A test options.
Mosaicism
Mosaicism occurs when an embryo has two different cell types instead of one. The chromosomal changes in mosaic embryos develop after fertilization, during cell division and early embryo growth. Whether an embryo’s mosaicism will cause health conditions or will lead to a miscarriage, depends on the type of aneuploidy in the mosaic cells and the proportion of cells affected.
Mosaicism is a heavily researched topic. In some cases, transferred mosaic embryos will result in a healthy birth. However, most mosaic embryos fail to implant or result in a miscarriage. In some situations, doctors will still transfer certain mosaic embryos with the hope that they will either self-correct over time or fail to implant if the mosaicism is too severe.
What is PGT-M?
PGT-M, or Preimplantation Genetic Testing for Single Gene/Monogenic Conditions, is a genetic test for IVF embryos that tests for single gene conditions. PGT-M is for patients who know that they are at a higher risk of having a child with a specific genetic condition, such as Huntington’s disease or cystic fibrosis. This risk is often discovered through carrier screening, a genetic test that finds gene changes that do not necessarily impact your health but could impact the health of your children. People who are affected by a genetic condition, who had a previously affected pregnancy, or who have family members that are affected, can use PGT-M to avoid passing on the condition.
“Our genes are like the letters of a huge book. When someone has a mutation for a gene, they are a carrier or they have an illness, and one of these letters in that huge book is incorrect. PGT-M is a tool to find that very precise area,” explains Dr. Jennifer Hirshfeld-Cytron of Fertility Centers of Illinois.
To perform PGT-M, your genetic laboratory takes a sample of you and your reproductive partner’s DNA (from a blood draw, cheek swab, or sperm collection), and uses it to develop a custom test that looks at the specific place in your genes where that letter is wrong. Your custom test is then performed on biopsy samples to determine which embryos have the condition and which don’t.
PGT-M can help prevent passing on single gene conditions, like cystic fibrosis, Tay Sachs, hereditary cancer syndromes, sickle cell anemia, and Huntington’s disease.
“The majority of illnesses like diabetes, heart disease, or autism are NOT the result of one gene, and therefore cannot be tested for by PGT-M, but for those that are, PGT-M can prevent transmission,” says Dr. Hirshfeld-Cytron.
What is PGT-SR?
The third form of PGT, PGT-SR, or Preimplantation Genetic Testing for Structural Rearrangements, benefits people with chromosomal structural rearrangement. Structural rearrangements occur when a piece of a person’s chromosome is present, but in a different place than usual. Typically, that person’s health is not affected by the rearrangement, but they are at higher risk for recurrent pregnancy loss. PGT-SR helps identify embryos that are not impacted by a structural rearrangement, and thus are most likely to result in a live birth.
Timeline and Next Steps
It can take a few weeks to receive your PGT results. For this reason, it is standard practice to freeze biopsied embryos for transfer at a later date. You’ll likely have the option to transfer your frozen embryos with your next cycle or any future cycle.
After the embryo’s cells are sent to a genetic testing lab like Natera, you and your team of doctors will discuss the results. By looking at all the available information, including genetic risks, you will know which embryo(s) will give you the best chances for a healthy baby. That’s pretty amazing knowledge to have.
Natera offers Spectrum Preimplantation Genetics™, a PGT that can be run in multiple formats to address unique patient needs, including simultaneous PGT-A and PGT-M on a single embryo biopsy. To learn more about Spectrum™ and the information it can provide, visit www.natera.com/spectrum.
Brighid Flynn is a freelance writer based in Philadelphia where she lives with her husband and puppy. She is just beginning her journey toward motherhood.
