1. What is preimplantation genetic testing (PGT)?

Preimplantation genetic testing (PGT) is a procedure used to identify genetic differences in embryos created with in vitro fertilization (IVF).  PGT is performed before embryos are transferred to the uterus.  The goal of PGT is to significantly reduce the chances of transferring an embryo with a specific genetic condition or certain types of chromosome abnormalities.

2. Are there different types of PGT?

Yes. There are three types of PGT:

  1. Preimplantation genetic testing for aneuploidy (PGT-A): This type of PGT screens embryos for certain chromosome abnormalities. Human embryos typically have 23 pairs of chromosomes (46 total) in each cell.  One chromosome in each pair is contributed by the egg, and the other is contributed by the sperm.  It is common for embryos to have random chromosome abnormalities such as a missing or extra chromosome, which is called aneuploidy.  In the majority of cases, these chromosome abnormalities happen by chance and are not inherited from a parent or donor.  Embryos with aneuploidy are more likely to result in miscarriage or a failed transfer.  Some types of aneuploidy may result in the birth of a baby with a chromosome condition such as Down syndrome or Turner syndrome.
  2. Preimplantation genetic testing for monogenic disorders (PGT-M): This type of PGT is performed when a patient has an increased risk for a specific genetic condition to occur in their embryos.  PGT-M is appropriate when an individual is affected with a genetic condition that could be passed on to their children, for individuals who are carriers for an X-linked condition, or when an individual and their partner or donor are both carriers for the same autosomal recessive condition.
  3. Preimplantation genetic testing for structural rearrangements (PGT-SR): This type of PGT is performed when a patient or their partner has a rearrangement of their own chromosomes such as a translocation or inversion.  A person with a translocation or inversion is at increased risk to produce embryos with missing or extra pieces of chromosomes.  Embryos with missing or extra pieces of chromosomes are more likely to result in miscarriage, stillbirth, or a child with serious health issues.
3. Who should have PGT performed for their embryo(s)?

PGT-A can be performed for any IVF cycle, but the decision to have this testing is complex and should be made after careful discussion with your physician or genetic counselor.  PGT-A is most often considered for patients who have had recurrent pregnancy losses (miscarriages), multiple unsuccessful IVF cycles or transfers, a prior pregnancy or child with certain chromosome abnormalities, or based on the age of the individual providing the eggs.  There remains debate about the benefits of PGT-A (see questions 15 and 16).

By contrast, PGT-M and PGT-SR are only performed when the patient, their partner, and/or their donor have abnormal genetic test results that put the embryos at increased risk for a genetic disorder or specific chromosome abnormalities.  PGT-M is an option for patients with an increased risk for a single gene disorder in their embryos such as cystic fibrosis or sickle cell anemia.  PGT-SR is an option for patients who have a chromosome translocation or inversion.  PGT-M and PGT-SR allow patients the opportunity to reduce the risk of having an affected child prior to becoming pregnant.

4. How is PGT performed?

All three types of PGT are performed in a similar way.  The patient goes through their IVF cycle and egg retrieval as recommended by their physician.  Their embryo(s) are monitored in our laboratory until day 5 or 6 when they are referred to as blastocysts.  At that time, a small number of cells are biopsied (removed) from each embryo and shipped to an outside laboratory for PGT.  The cells are taken from a part of the blastocyst called the trophectoderm, which will eventually form the placenta.  These cells are expected to be representative of the rest of the embryo; however, this may not always be the case due to circumstances such as mosaicism (see question 13).  The embryo(s) must be frozen while PGT is performed.  An embryo with normal PGT results would be selected, thawed, and transferred to the uterus of the patient or their gestational carrier at a later date.

5. What types of samples are needed for PGT?

In addition to the biopsied cells from the embryo(s), other DNA samples may be required for PGT.  Some versions of PGT-A and PGT-SR may require DNA samples from the patient and their partner or donor which must be collected prior to the egg retrieval.  Please see question 6 if you are using a non-directed (anonymous) egg or sperm donor.

For PGT-M, the required samples vary.  The laboratory performing PGT-M will evaluate your unique case and determine what samples are needed to develop testing for your embryo(s).  This may include blood and/or saliva from the individuals contributing the eggs and sperm as well as DNA samples from other family members.  In some cases, a sperm sample may also need to be provided.

6. Can I do PGT if I am using sperm or eggs from a non-directed (anonymous) donor?

Possibly.  For PGT-A and PGT-SR, we have options that do not require additional DNA samples from the sperm or egg donor.  For PGT-M, each case is unique and must be reviewed by a genetic counselor. For individuals using a sperm donor, PGT-M may be possible but require the purchase of an additional vial of sperm. In some cases, it may not be possible for the laboratory to develop reliable testing for embryos created using a non-directed (anonymous) donor, especially if a DNA sample from that donor is not available. This is common with non-directed (anonymous) egg donors.

7. Are there risks to the embryo(s) from the PGT process?

Yes.  The biopsy process, which removes cells from each embryo for PGT, has a small chance of damaging the embryo.  Additionally, since the embryo(s) must be frozen while PGT is performed, they must also undergo a thawing procedure prior to transfer.  In our center’s experience, the survival rate of embryos that were biopsied and later thawed is approximately 97%.

8. When do I need to decide if I would like to do PGT?

The decision to have PGT needs to be made well in advance of your IVF cycle.  If PGT is part of your IVF plan, our office will open a case with the laboratory.  This allows them to check your insurance benefits and confirm payment options.  Additionally, DNA samples from the patient, their partner or donor, and sometimes other family members may need to be collected in advance of the IVF cycle (see question 5).

For PGT-M, there is a test development phase during which the laboratory confirms if they will be able to reliably detect the specific genetic condition in the patient’s embryo(s).  The test development phase can take up to 6-12 weeks after all required DNA samples are received.  This process must be fully completed before an IVF cycle (stimulation medications) will be started.

9. I do not have a family history of any chromosome conditions. Could PGT for aneuploidy (PGT-A) still be appropriate for me?

Yes. PGT-A screens for chromosome abnormalities that can occur randomly in any individual’s embryos. Chromosome abnormalities are common in embryos and are not usually inherited. Therefore, we do not expect patients to have a family history of any chromosome conditions. The main risk factor is the age of the person contributing the eggs (see question 12).

10. What types of chromosome abnormalities does PGT-A screen for?

PGT-A is primarily designed to ensure an embryo has the correct number of chromosomes, which is also called being euploid.  PGT-A screens embryos for whole missing chromosomes (monosomies) and whole extra chromosomes (trisomies). PGT-A also screens for missing or extra pieces of chromosomes (deletions or duplications, respectively).  Deletions and duplications must be large to potentially be detected. Some, but not all, versions of PGT-A may detect additional types of chromosome abnormalities such as mosaicism and uniparental disomy (UPD).  Our genetic counselor will review the types of results that can be detected at your appointment.

11. What are the chances my embryo(s) will have abnormal chromosomes if I do PGT-A?

Chromosome abnormalities are common in embryos.  Everyone has a chance to have embryos with chromosome abnormalities (aneuploidy). An individual’s risk for abnormal PGT-A results is most strongly influenced by the age of the person providing the eggs (see question 12).

12. Is the risk for chromosome abnormalities in my embryo(s) related
to age?

Yes. While chromosome abnormalities can happen in any embryo or pregnancy, the chance for missing or extra chromosomes (aneuploidy) does increase with the age of the person providing the egg(s).  The lab we use most often (Natera) reports the following chances for abnormal results based on the age of the person providing the egg(s): 33% for individuals under 30 years old, 38% for individuals who are 30-34 years old, 47% for individuals who are 35-37 years old, 60% for individuals who are 38-40 years old, 76% for individuals who are 41-42 years old, and 84% for individuals who are 43 years or older at the time of egg retrieval.

Please remember these are averages so you may have more or less embryos with abnormal PGT-A results than expected based on age.  In some IVF cycles, a patient may not have any embryos with normal PGT-A results to transfer.  It is also important to keep in mind that the number of embryos an individual will have available to test also tends to decrease with the age of the person providing the eggs.

13. What is mosaicism?

Mosaicism refers to a mixture of two or more types of cells within the same embryo.  Most often it refers to an embryo with some cells that are chromosomally normal (euploid) and some cells that are chromosomally abnormal (aneuploid). On day 5, an embryo is made up of approximately 120 cells.  Our embryologists will remove 5-10 of these cells for PGT.  In most cases, we expect all of the embryo’s cells to be identical so testing this small sample will give us accurate information about the whole embryo.  However, if the embryo has mosaicism, the 5-10 cells which are biopsied may not accurately represent all of the cells of the embryo.  For instance, the biopsied cells may be chromosomally normal, but other untested cells within the embryo are abnormal.  Conversely, the 5-10 biopsied cells may be chromosomally abnormal, but other cells within the embryo are normal.  This can result in false positive or false negative PGT results. If the 5-10 biopsied cells contain a mixture of chromosomally normal and abnormal cells, a mosaic result may be reported by the PGT laboratory. The detection and reporting of mosaic results varies by laboratory, and our genetic counselor will review the specifics with you.

14. What are my options for embryos with mosaic PGT-A results?

Our clinic will transfer embryos with mosaic PGT-A results if a patient wishes to do so.  We require the use of any chromosomally normal (euploid) embryos first.  Additionally, we require a genetic counseling appointment to review your embryo’s results as well as our current understanding of the risks and benefits of transfer.  The decision to transfer an embryo with mosaic results is complex, and our understanding of these embryos is changing rapidly. While some studies have found a higher risk for miscarriage and a lower live birth rate with the transfer of mosaic embryos compared to euploid embryos, there have been many successful live births published.  Data about long-term outcomes for children born after the transfer of embryos with mosaic results is still lacking. Before proceeding with the transfer of an embryo with a mosaic PGT-A result, the patient and their partner (if applicable) will be required to sign a waiver acknowledging they have been counseled about the risks and benefits.

If a patient does not wish to transfer an embryo with mosaic PGT-A results, they may choose to continue to cryopreserve the embryo for potential use in the future, discard the embryo, or donate the embryo for research.

15. What are the benefits of PGT-A?

There are several potential benefits of PGT-A.  For patients with several good quality embryos, PGT-A is an additional tool that may assist in the selection of the best embryo for transfer.  For patients whose embryos have PGT-A, we recommend the transfer of a single chromosomally normal embryo which reduces the chance of multiples (e.g. twins or triplets) and increased risk of complications associated with those types of pregnancy.  PGT-A may also be helpful when a patient has excess embryos they plan to store for future attempts at pregnancy.  Since embryos with aneuploidy are more likely to result in a failed transfer or miscarriage, PGT-A results provides additional information about the reproductive potential of those stored embryos and a more complete picture of what a patient has available for the future.  Normal PGT-A results also reduce the likelihood of the birth of a child with certain detectable chromosome condition like Down syndrome, trisomy 13, or trisomy 18.  Study outcomes have been mixed when considering whether PGT-A helps to reduce a patient’s miscarriage risk and increase their likelihood of a live birth and may depend on the characteristics of the individual patient (such as their age). If you are interested in learning more about PGT-A, we recommend you discuss this test with your physician and our genetic counselor.  We can review your individual circumstances to help you determine if PGT-A is right for you.

16. Are there any downsides or risks to PGT-A?

Yes, and we believe these are important to acknowledge.  First, PGT-A adds significant additional cost that may not be covered by insurance (see question 22).  Some patients may have to undergo more than one IVF cycle in order to get a chromosomally normal or mosaic embryo for transfer, further increasing their costs.  Second, the embryo(s) must be frozen while PGT is performed so patients are unable to do a fresh transfer. Instead, a frozen embryo transfer will be scheduled after the PGT results are available.  Third, the PGT process involves a biopsy which poses a small risk of harm to the embryo(s) (see question 7).  Fourth, there is a small (1%-2%) chance the lab may get inconclusive results for an embryo meaning they are unable to determine whether the embryo is chromosomally normal or abnormal. Finally, although uncommon, inaccurate PGT results (i.e. false positives and false negatives) may lead to the transfer of an embryo with a chromosome abnormality that was not detected or the decision not to use an embryo with the potential to result in a healthy pregnancy.

17. What if I have a family history of a specific genetic condition? Can PGT detect that condition in my embryo(s)?

PGT-M or PGT-SR are options for many patients with a personal or family history of a specific genetic condition or chromosome rearrangement who wish to greatly reduce the chance of having a child affected by that condition.  If you are interested in PGT-M or PGT-SR, the first step is for our genetic counselor and the laboratory to review your abnormal genetic test results.  The laboratory will determine if they can develop a test for your embryos that can reliably identify which ones are affected.  Unfortunately, PGT-M or PGT-SR may not be able to be performed successfully in all cases due to technical limitations.

With the exception of a few chromosome conditions (e.g. Down syndrome, Turner syndrome, Klinefelter syndrome, trisomy 13, and trisomy 18), PGT-A does not test embryos for any specific genetic diseases or syndromes.

18. What information is required to perform PGT for a monogenic condition (PGT-M) or PGT for a structural rearrangement (PGT-SR)?

In order to perform PGT-M or PGT-SR, you must be able to provide documentation of the specific genetic abnormality.  For PGT-M, a copy of the abnormal genetic test results must be submitted to the laboratory.  These results must contain the specific gene and the specific variant(s) for which the patient wants to test their embryo(s).  For PGT-SR, a copy of the abnormal chromosome study (karyotype) documenting the specific translocation or inversion must be submitted.

19. How accurate are the results of PGT? Do I still need to have prenatal diagnosis (chorionic villus sampling or amniocentesis) if I have PGT?

The results of PGT are highly accurate; however, it is still considered a screening test.  This means false positives and false negatives can occur.  If you transfer an embryo tested by PGT, it is recommended you consider confirming the normal results through diagnostic prenatal testing such as chorionic villus sampling (CVS) or amniocentesis.  Non-invasive prenatal testing (NIPT) can also be used as a first-line screen for a limited number of chromosome abnormalities during pregnancy.  However, NIPT (like PGT) is also a screening test with the potential for false positives or false negatives.  Your physician or a genetic counselor can review these options with you in more detail as there are risks and limitations for each test that should be considered carefully.

20. Do normal PGT results eliminate the risk for my embryo(s) to have a genetic condition?

No.  PGT only screens for certain chromosome abnormalities (PGT-A or PGT-SR) or a specific genetic condition (PGT-M).  Every pregnancy has a risk of approximately 3%-5% to result in a child with a genetic condition or birth defect.  No genetic test can eliminate this risk or identify all diseases or birth defects. There is always a risk for a child to have a medical issue, regardless of the screening performed.

21. What other options are there for genetic testing if PGT is not right for me?

PGT is always optional.  If PGT is not right for you, there are several genetic testing options that can be performed during a pregnancy.  First, non-invasive prenatal testing (NIPT) screens for certain chromosome abnormalities by analyzing placental DNA in a sample of a pregnant individual’s blood.  It is also sometimes referred to as cell-free fetal DNA testing.  NIPT always screens for Down syndrome (trisomy 21), trisomy 18, and trisomy 13.  Some versions of NIPT also screen for the sex chromosomes (X and Y), other trisomies, triploidy (having an extra copy of every chromosome), and certain microdeletions (small missing pieces of a chromosome that cause known syndromes such as 22q11.2 deletion syndrome).  The benefits of NIPT are that it can be done as early as 9 weeks of pregnancy. Since it is performed on a blood sample from the pregnant individual, there is no risk to the pregnancy.  However, NIPT is still a screening test meaning false positives and false negatives can occur.  NIPT does not typically screen for single-gene conditions and may not be right for those with a translocation or inversion, but this is an evolving area.

Chorionic villus sampling (CVS) and amniocentesis are two additional options for prenatal genetic testing.  CVS can be performed in the first trimester between 10-13 weeks gestation, while amniocentesis can be performed in the second trimester between 15-24 weeks gestation.  CVS and amniocentesis can be used to test for chromosome abnormalities and/or a specific single-gene condition.  Both provide highly accurate genetic results.  While CVS and amniocentesis offer advantages over NIPT, both of these tests are invasive so they do pose a risk for miscarriage or other complications.  If you are interested in prenatal genetic testing, we recommend you review the benefits and limitations of these options with a physician or genetic counselor.

22. What is the cost of PGT? Is it covered by my insurance?

The cost of PGT depends on many factors including the type of PGT being performed, the number of embryos being tested, and which laboratory is performing the test.  Our office and the performing laboratory can assist you in determining your insurance coverage and expected out-of-pocket costs for PGT.

As an example, the laboratory we use most often (Natera) offers self-pay pricing for those without insurance coverage.  The self-pay price for PGT-A is $250 per embryo. The self-pay price for most cases of PGT-SR is $3,675 for up to eight embryos.  The self-pay price for PGT-M for one genetic condition is $6,000 for up to sixteen embryos.  There is also a $375 fee for shipping the embryo biopsy samples to Natera, which must almost always be paid out-of-pocket.

23. How long do PGT results take to return?

Once the laboratory receives the embryo biopsy samples and has received payment for the testing, results are expected in approximately 7-10 business days.

24. How will I receive my PGT results?

Our genetic counselor will call you with your PGT results. At that time, we will review how many embryos are appropriate for transfer.  After this discussion, a copy of your PGT report can also be shared with you through the patient portal (MyChart).

25. What do my PGT-A results mean?

An embryo with normal PGT-A results is predicted to have the correct number of chromosomes and no evidence of large chromosome deletions or duplications (see question 10).  PGT-A cannot detect all chromosome abnormalities such as small extra or missing pieces of chromosomes (microdeletions and microduplications).  PGT-A cannot detect any single-gene disorders.  Normal PGT-A results cannot rule out the possibility a child may be born with a birth defect, autism, developmental delay/intellectual disability, or serious health issues not caused by detectable chromosome abnormalities.  Normal PGT-A results cannot guarantee a successful transfer or prevent miscarriage.

Abnormal PGT-A results may refer to an embryo with either aneuploid or mosaic results.  Aneuploid means the embryo is predicted to have a chromosome abnormality present in all of the tested cells.  Most embryos with aneuploid PGT-A results are not recommended for transfer because they have a very low likelihood of resulting in a successful pregnancy.  Embryos with mosaic results are complex, but may be considered for transfer at our clinic (see questions 13 and 14).

26. What do my PGT-M or PGT-SR results mean?

An embryo with normal PGT-M results is predicted to be free of the genetic condition for which it was tested.  For autosomal recessive conditions, PGT-M will also identify whether the unaffected embryo is a carrier or not.  Since carriers of autosomal recessive conditions are not expected to have symptoms, those embryos may be transferred if the patient wishes.  Abnormal PGT-M results mean the embryo is expected to be affected with the condition for which it was tested.  Therefore, those embryos are typically not recommended for transfer.

An embryo with normal PGT-SR results is predicted to have the correct amount of each chromosome with no detectable missing or extra pieces.  The laboratory will look closely at the chromosomes involved in the translocation or inversion.  It is important to know PGT-SR does not distinguish between embryos with normal chromosomes and those with a balanced translocation or inversion like the parent.  Since carriers of a balanced translocation or chromosome inversion are typically healthy, those embryos are reasonable to transfer. A child born after normal PGT-SR testing should be offered the option to have chromosome testing prior to starting their own family to understand their reproductive risks and options.

27. Do normal PGT results guarantee a successful outcome?

No, but this is a very common misconception. Embryos with normal PGT results (of any type) can still fail to implant or result in a miscarriage. While many studies find the risk of miscarriage is lower in embryos with normal PGT-A results compared to untested embryos, especially when the individual providing the eggs is 35 years or older, pregnancy losses can still occur. Normal PGT-A results mean the potential for the embryo to result in a successful pregnancy is high, but normal chromosomes are just one of many factors that contribute to the successful birth of a baby.

28. Do I need genetic counseling?

We strongly encourage all patients who are interested in PGT to have an appointment with our genetic counselor.  This consultation will ensure you fully understand the risks, benefits, and limitations of this testing.  The genetic counselor will also determine if there are any additional concerns based on your personal and family history that should be addressed prior to your IVF

Have more questions?

Contact our Washington University Fertility Genetic Counselor at 314-286-2411