Preimplantation Genetic Testing in Donor Egg IVF

1. What is Preimplantation Genetic Testing?
2. What are the steps of PGT?
3. What exactly does PGT-A test for?
4. How is the embryo biopsy done? Is there any risk?
5. What are the types of results that the embryos receive after PGT-A?
6. What is PGT-A not able to test for – what are the limitations?
7. How accurate is PGT-A?
8. Does PGT-A replace the need to test the pregnancy for chromosomal disorders - what type of testing should I, or my gestational carrier, do in the pregnancy?
9. How much does PGT-A cost?
10. How should I decide whether to do PGT-A?

1. What is Preimplantation Genetic Testing?

PGT is optional genetic testing of embryos that can be done as part of the IVF process. Embryos can be tested to determine how many chromosomes they have or can be examined for a specific genetic (inherited) disease if there is a particular concern about an inherited condition in the sperm or egg provider or their family. There are three types of PGT:

• PGT-A (aneuploidy)

This is the most used type of PGT. Embryos are tested to determine how many chromosomes they have, in order to exclude from transfer embryos that cannot lead to a healthy pregnancy. The information in this blog post is primarily focused on PGT-A.

• PGT-M (monogenic)

In this case embryos are tested for a specific genetic disease that the embryos are known to be at risk for based on genetic testing in the sperm or egg provider. In donor egg IVF cycles, PGT-M is generally only performed only if a sperm provider is known to himself have a heritable, dominant condition that he could pass to his children, such as an inherited cancer syndrome or polycystic kidney disease. While PGT-M can theoretically be used for cases in which the sperm and egg provider both carry variants in the same recessive gene that were discovered on carrier screening, in donor egg IVF such “carrier/carrier” matches are usually avoided in the first place, making PGT-M unnecessary.

• PGT-SR (structural rearrangements)

This is the least commonly done type of PGT, which is only for families in which the sperm or egg provider is known to have a change in their own chromosomes (found on a test called a karyotype) that could be passed on to their offspring. It is used most often in couples who have had infertility or miscarriages, and is rarely needed in donor egg IVF.

2. What are the steps of PGT?

How PGT fits into the IVF process is generally the same at all clinics:

1. The egg donor undergoes stimulation to produce a number of eggs, which are extracted (retrieved);
2. Sperm and donor eggs are combined in the laboratory to create embryos;
3. Embryos are grown in the laboratory for 5-6 days, at which point the healthy embryos will have become blastocysts (~150 cell embryos);
4. Embryos undergoing PGT are biopsied – the embryologist uses a laser to carefully remove a handful of cells from each developing embryo;
5. Embryos are frozen while the biopsied cells are shipped to a specialized genetic PGT laboratory or tested on site;
6. PGT results are available in 1-2 weeks and communicated to the intended parent(s);
7. Embryos are selected for transfer based on their PGT results and quality (grading);
8. A frozen embryo transfer IVF cycle is started for the person who will carry the pregnancy (surrogate or intended mother).

3. What exactly does PGT-A test for?

PGT-A determines how many chromosomes there are in each embryo’s biopsied cells. Chromosomes are packages of genes, or DNA, within the cells. Humans normally have 46 chromosomes in each cell; 23 come from the sperm cell and 23 from the egg cell. The first 22 pairs of chromosomes are identified by number, 1 through 22, while the last pair reflects the sex of the embryo. Embryos with the normal number of chromosomes (46) are considered “euploid”, and those with an abnormal number of chromosomes are considered “aneuploid.” Aneuploidy is common in embryos; 15-30% of embryos created using young, healthy donor eggs are found to have extra or missing copies of chromosomes. If transferred, these embryos can fail to implant, cause miscarriage, or can lead to the birth of a child with health problems. The goal of PGT-A, therefore, is to exclude aneuploid embryos from transfer. PGT-A also identifies the chromosomal sex of the embryo (XX or XY).

4. How is the embryo biopsy done? Is there any risk?

The embryologists who perform embryo biopsies are generally very skilled and have usually performed many thousands of biopsies. Cells are removed from the area of the embryo that is developing into the placenta of the pregnancy, not the baby. There is a small risk of an embryo not surviving the biopsy procedure. This risk is generally very low (1-2% or less), but the clinic performing the biopsy should be able to share their own data regarding this risk. At the current time there are no conclusive long-term risks to the embryo, pregnancy, or the baby that results, related to the biopsy. Since the embryo(s) being tested must typically be frozen and later thawed for the transfer, there is a small risk of an embryo not surviving the thaw process. Again, this specific chance should be provided by the individual clinic, but it is generally < 5%.

5. What are the types of results that the embryos receive after PGT-A?

Each PGT laboratory is a bit different in how they categorize embryos after PGT-A, so it is important to talk to your IVF clinic or the laboratory itself to understand their results. In general, embryos can be classified as normal (euploid) or abnormal (aneuploid), and there is also a chance of having an inconclusive result that could indicate a need to rebiopsy an embryo to get clear results. Some laboratories also may classify certain embryos as “mosaic” (neither clearly normal nor abnormal chromosomes) which can necessitate further counseling to understand. Laboratories also differ in terms of whether they look for or report smaller chromosome changes called “segmental” aneuploidy, and what this means when it is found. Your physician or genetic counselor will be able to counsel you on your embryo’s results and help you make your embryo transfer plan using the information learned from PGT-A.

6. What is PGT-A not able to test for – what are the limitations?

PGT-A is generally only checking the total number of chromosomes in the embryo – it is not an overall genetic health screen that is looking for all inherited diseases or birth defects. It is not able to test for some rare chromosome abnormalities such as certain cases of “polyploidy” (when every chromosome is duplicated), or for extra or missing small pieces of chromosomes. If you or your egg donor have a personal or family history of a condition that is possibly genetic, or if your carrier screening results were abnormal, you should talk to your IVF health care team to make sure you understand your genetic risks and whether other types of PGT are indicated for you. In the rare case that PGT-M or PGT-SR is needed, you should receive more detailed information about those types of tests.

7. How accurate is PGT-A?

The accuracy of is usually quoted to be greater than 95% but less than 100%. The vast majority of embryos that test normal on PGT-A and implant will go on to make babies that have a normal number of chromosomes. In very rare cases PGT-A gives “false-negative” results and the baby has an extra or missing chromosome despite the PGT-A results having been normal. This can happen due to technical limitations of the testing or due to biological differences within the cells of the embryo (in rare cases the cells from the placenta test normal even though the cells that go on to make the baby may have an abnormal number of chromosomes; this is called “mosaicism”). There is also a small chance of a “false-positive,” in which case an embryo that could have resulted in a healthy baby is mistakenly called abnormal on PGT-A. You clinic or PGT-A laboratory can provide specifics about these risks for their test.

8. Does PGT-A replace the need to test the pregnancy for chromosomal disorders - what type of testing should I, or my gestational carrier, do in the pregnancy?

This is a personal decision and there is no “one size fits all” approach. There are many different tests available to obtain information about the baby’s chromosomes during pregnancy and you should discuss the options with your doctor and/or genetic counselor to determine what follow-up testing is right for you. Tests that can be done in pregnancy include both “diagnostic” tests (such as chorionic villus sampling and amniocentesis), which are highly accurate but are invasive and carry some risk of causing pregnancy complications such as miscarriage; and “screening” tests (such as the nuchal translucency ultrasound and the non-invasive prenatal screening (NIPS) blood test), which are non-invasive but require further clarification/testing in the event of an abnormal result. If you do PGT-A on your embryos, your prenatal provider should be made aware of this so they can provide you (and your surrogate, if indicated) with the appropriate follow-up options during the pregnancy.

9. How much does PGT-A cost?

Each clinic provides customized pricing for PGT-A. The cost generally includes the cost to biopsy the embryos; to ship the biopsies to an outside genetic laboratory; and to perform the PGT testing itself. Some clinics change a flat fee for testing up to a certain number of embryos, while others charge per embryo. There can be pros and cons to both models. As embryos typically need to be frozen in order to be tested, PGT costs may also include fees related to freezing and thawing embryos; however, some or all of these may have been incurred even without PGT-A.

10. How should I decide whether to do PGT-A?

Whether or not PGT-A is right for you will depend on several factors. It is important to understand the risks, possible benefits, and limitations of both the testing process and the information that is learned from the PGT-A results in order to make a decision. There are many factors to consider including medical, financial and even moral considerations. Some doctors routinely recommend PGT-A for IVF cycles using donor eggs in order to have as much information as possible about the embryos. Others note that the risk of aneuploidy is relatively low in egg donor cycles and believe the possible risks and costs may not be justifiable. It is also worth considering whether knowing the sex of the embryos is of interest to you, both for the first embryo transfer as well as for any future transfers. It is important to talk with your fertility care team who can help you reach the decision that is right for you.

Emily Mounts, MS, CGC

Emily Mounts is board-certified genetic counselor who has worked in reproductive genetics for 25 years. Most recently she directed the fertility genetic testing and counseling program at ORM Fertility in Portland, where she oversaw preimplantation genetic testing, genetic carrier screening, and the gamete donor genetic screening programs for 10 years. She has co-authored multiple publications on fertility genetics and frequently presents at national conferences. She is a former Chair of the American Society for Reproductive Medicine Genetic Counseling Professional Group. Emily completed her Bachelor’s degree at the University of Michigan and her Master’s degree in genetic counseling at the Medical College of Virginia.

Emily currently serves as an independent consultant helping clinics, agencies, labs, and ancillary businesses develop and streamline fertility genetics services, and can be reached through LinkedIn: https://www.linkedin.com/in/emilymounts/ or at emily@focusgeneticconsulting.com.

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