Preimplantation genetic testing (PGT) of embryos is an additional step in the IVF process. The goal of PGT is to test embryos for a specific genetic condition or a chromosomal abnormality in order to increase the chance of implantation, reduce the chance of miscarriage, and improve the odds of a healthy live birth.
The most common type of PGT is PGT-A, or PGT for spontaneous aneuploidy screening. Aneuploidy is defined as an abnormal amount of chromosomes. PGT-A is often recommended when a female patient is over the age of 35. The odds of a chromosomal abnormality in an embryo increases as the age of the egg increases.
Additionally, if you or your partner have any of the following medical conditions your provider may recommend PGT:
- Two or more miscarriages have occurred
- Two or more IVF cycles have not yielded a pregnancy
- Family history of genetic disease
- One or both partners are a carrier of genetic disease
- One or both partners are diagnosed with genetic disease
- The female partner is of advanced maternal age (>35)
- The male partner is of advanced paternal age (>40)
In each cell of the body, 23 pairs of chromosomes are present. When these chromosomes are incorrectly arranged or when an extra chromosome is present, missing or partially altered, a chromosomal abnormality known as aneuploidy is present.
Process of PGT
How is PGT performed?
All types of PGT involve a similar sequence of events. The patient undergoing IVF has their egg retrieval as scheduled. The eggs are inseminated with sperm and the resulting embryos are monitored in the lab until they develop to an expanded blastocyst (typically days 5 – 7 after egg retrieval). At this stage, a small number of cells are removed (biopsied) by an embryologist. This consists of a small catheter removing a few cells from the trophectoderm that will later develop into the placenta. The catheter does not impact the inner cell mass (future baby). The embryo is then immediately frozen and stored at the clinic while the biopsied cells are shipped to a PGT lab. Patients are notified of the PGT results typically about 3 weeks after the egg retrieval procedure.
Frequently Asked Questions about PGT
When do I need to decide if I want PGT?
We ask that patients decide if they will be doing PGT before starting an IVF cycle.
If I already have frozen embryos without PGT, can I still do PGT?
Embryos can be thawed and biopsied so, yes, you can do PGT after freezing them. At Kindbody, the odds that an embryo survives being frozen is 95-98%, so there is a small chance that it would not survive the thaw process. The embryo would need to be thawed twice in this case – the first time to be biopsied, then frozen again to await results, and thawed a second time just before it is transferred to the uterus. So there would be a small additional risk of loss after the second thaw.
If your intent is to move forward with PGT, we strongly recommend that you do this prior to the first cryopreservation if able.
Is PGT recommended if I am using a donor egg or sperm?
PGT is always an option. The age of the egg or sperm donor is often considered in this decision but there are unique circumstances to every case so we recommend you discuss this with your provider. In some situations, the use of PGT may further increase success even when using donor eggs or sperm. For donor eggs that are previously frozen, as compared to fresh, there may be a small additional risk of an additional freeze and thaw as mentioned in the question above.
What are the risks of PGT?
With every procedure there are always risks and benefits. First, to complete the PGT procedure, the embryo must develop into a blastocyst and be expanded enough to be safely biopsied. This typically happens 5 – 7 days after fertilization in the IVF lab. If the embryo is too small or less developed, we cannot complete PGT on that embryo.
PGT requires a biopsy. Most data suggests that the blastocyst biopsy is safe but it does require this procedure to obtain genetic results.
There is a risk of contaminating cells from sperm or cumulus cells, which nourish the egg as it matures in the body and are stripped from the egg after it is retrieved. This is why most labs strongly recommend or require ICSI (intracytoplasmic sperm injection) of a single sperm into the egg to reduce this risk.
Finally, PGT is not perfect and cannot test the entire genome. PGT is 96-99% accurate using the best technologies. There is a small chance that what we say is normal may be abnormal, and what we say is abnormal may be normal. Sex of embryos has a small error rate, so, if you are completing PGT for sex selection, keep this in mind.
Completing PGT means this will be a “freeze all cycle” in order to await results expected in a few weeks. This means you cannot do a fresh embryo transfer unless it is of an untested embryo or one tested in a previous cycle.
The risk of cost should also be considered as there is additional cost for the PGT procedure.
Finally, it is important to remember that embryos that aren’t healthy tend not to implant when transferred, and if they do implant, they tend to miscarry. There is currently no test or screening process that will completely eliminate the chance of miscarriage.
What does the biopsy entail? Does this hurt my embryo or future child?
Once a blastocyst forms, typically between days 5 – 7 after fertilization, the distinction between cells that will become a fetus (baby) and the placenta become more obvious under a microscope. The biopsy consists of a catheter removing a small number of cells from the trophectoderm that will later develop into the placenta. The catheter does not impact the inner cell mass (future baby). Most published data suggests the blastocyst biopsy does not hurt the embryo or impair outcomes in subsequent transfers.
I do not have a family history of chromosomal conditions. Which type of PGT test is best for me?
PGT-A is a screening tool recommended for all patients undergoing IVF, especially as age of the egg increases, as it screens for chromosome abnormalities that occur randomly when a sperm and egg joins and the cells begin to divide.
Even if you have no personal history of chromosomal abnormalities and no family history of genetic conditions, everyone is still at risk for abnormal embryos. Conditions such as Down’s Syndrome, Turner syndrome, or other chromosomal imbalances can occur with egg or sperm from any age individual. We do know that as we age, the likelihood of chromosomally abnormal embryos increases. This is particularly true as the age of the egg increases.
Do I need to do anything to prepare for PGT?
Most importantly, discuss PGT with your provider in your consult. Once you have decided to pursue PGT, notify your team. Depending on the type of PGT the team may need to get approval from the PGT lab directly before proceeding. You must complete the associated PGT modules and consent forms prior to the start of your IVF cycle.
If we are doing PGT to test for a specific disease (PGT-M), then we need to take time to understand your DNA mutation or your partner’s DNA mutation. This often means blood or saliva samples are needed from the egg and sperm source or the carrier of the mutation in order to create DNA “probes” to test and compare to the embryo DNA. In some cases it is important to understand the heritage of the mutations so additional samples may be requested from your parents, siblings, or living children. If this cannot be done there are some situations where additional information can be gathered from embryos that have stopped developing in the lab as well. Extra information that is requested is done so to improve the accuracy of the results.
PGT-SR stands for structural rearrangement where a piece of DNA may be broken off or broken off and flipped on itself. In the process of DNA separation, in order to send only half of the amount to an egg or sperm, there tends to be more errors than predicted in cases of PGT-SR which is why it is very useful to reduce this risk. PGT-SR can detect larger deletions and duplications but may not be able to detect small ones. Most of these cases are unique and may require a consultation with a genetic counselor prior to preceding.
How accurate are my results?
PGT is 96-99% accurate using the best technologies. It is considered a screening test and does not have the capacity to screen for every possible scenario, so will not be 100% accurate in identifying all potential chromosomal or genetic anomalies. Make sure you discuss your results with your provider. We also recommend that you follow your provider’s recommendations on non-invasive prenatal testing once you are pregnant as well as amniocentesis recommendations in pregnancy to improve accuracy of and confirm results (in order to directly test fetal skin cells in fluid).
How long does it take to get my results?
Typically results are available about 3 – 4 weeks after the egg retrieval.
How will I receive my results?
Your Kindbody care PGT team will call you with your results and will share them in your patient portal. They will ask you if you want to know sex of the embryo when the report is shared. They will review your embryos and next steps. You do not need to call us to check in on the progress.
What is the cost of PGT?
The cost of PGT can range depending on many factors. Our pricing information is here. If you are a Kindbody member, your PGT may be included in your benefit.
If you are completing PGT-M there are potential added fees for running additional tests and creating a probe. If your case requires additional familial samples there also may be additional cost.
You will be responsible for fees from both the processes that occur in the lab to biopsy and freeze the embryo as well as lab fees for the genetics tests and shipping of samples.
Who should receive PGT?
We recommend that all patients undergoing IVF consider PGT. It is an optional test and it can potentially improve success of getting pregnant and staying pregnant. Please discuss PGT and types of PGT with your provider.
What is mosaicism?
Mosaicism is a result of PGT-A detecting a mix of abnormal (unbalanced) DNA in cells and normal (balanced) DNA in other cells. It is possible this result may be real or an artifact of the processing of the DNA or the testing. Some labs refer to low or high levels of mosaicism. All mosaic results must be discussed with your provider. There are circumstances where we consider transfer of mosaic embryos and some may still result in healthy pregnancies.
Does Kindbody transfer aneuploid (abnormal number of chromosomes) embryos?
At this time, we consider all cases on an individual basis. When embryos are mosaic or missing a partial amount of DNA they may be considered for transfer after extensive counseling with a genetic counselor and your provider. We also recommend that amniocentesis be performed to do further testing in the pregnancy.
What happens to my abnormal embryos?
The abnormal embryos are not discarded unless you direct us to do so after consultation with a provider and an additional consent. They are kept frozen primarily because we don’t know which are normal and abnormal until after PGT results are available. In the future these embryos can be discarded or donated to research. In many clinics, abnormal embryos would never be transferred, but as we continue to explore and understand the strength of PGT, in the future some abnormal embryos may be allowed to be transferred or considered for rebiopsy or additional testing.
How does the doctor know which embryo to transfer first?
If you did PGT, we start by looking at the embryos that are euploid (or suggest a normal balance of DNA). Of these embryos, we first look at when they were frozen. Those frozen on day 5 are a tiny bit stronger than those frozen on day 6, which are a tiny bit stronger than embryos frozen on day 7. Next, we look at the embryo grade and choose the highest grade.
Why did my embryo come back as “Undetermined”, “No result” or “Quality or quantity of DNA insufficient” when I did PGT?
Imagine this embryo is like a tiny piece of cells, smaller than a grain of sugar. We take a tiny pinch of that cell, so the amount of DNA that is examined is so incredibly small, it has to be sent to a lab where the lab amplifies the DNA on a machine. Any of the steps along the way could result in an embryo that we don’t get results for, however, you could go ahead and transfer the embryo depending on your own personal story and circumstances, or you could ask for the embryo to be retested. Consultation with a provider and a genetic counselor may be recommended or required.
