Preimplantation genetic testing (PGT) is a procedure used to identify genetic abnormalities 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 chromosome abnormality.
Yes. There are three types of PGT:
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 failed IVF cycles, a prior pregnancy or child with certain chromosome abnormalities, or based on maternal age. However, there is notable controversy about the benefits of PGT-A (see questions 14 and 15).
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. 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.
All three types of PGT are performed in a similar fashion. 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 at a later date.
In addition to the biopsied cells from the embryo(s), other DNA samples are often required for PGT. In order to perform PGT-A, blood samples from the patient and their partner must be collected in our office prior to the egg retrieval. Please see question 6 if you are using an anonymous donor.
For PGT-M and PGT-SR, the required samples vary. The laboratory performing PGT-M or PGT-SR 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 from other family members. In some cases, the male partner may also need to provide a sperm sample.
Possibly. For PGT-A, we have laboratory options that do not require additional samples from the sperm or egg donor. For PGT-M or PGT-SR, each case is unique and must be reviewed by a genetic counselor. In some cases, it may not be possible for the laboratory to develop reliable testing for embryos created using an anonymous donor.
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 centers experience, the survival rate of embryos that were biopsied and later thawed is 97%.
The decision to have PGT needs to be made well in advance of your IVF cycle. If PGT is part of your plan, our office will open a case with the laboratory. This allows them to check your insurance benefits and confirm payment options.Additionally, blood samples from the patient, their partner and/or donor, and sometimes other family members must be collected in advance (see question 5).
For PGT-M and PGT-SR, 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 patients embryo(s). The test development phase can take up to 8-12 weeks after all required DNA samples are received. This process must be fully completed before an IVF cycle (stimulation medications) will be started.
Yes. PGT-A screens for chromosome abnormalities that occur randomlyin a portion of any womans eggs or mans sperm. 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 laboratory we use most often (Natera) uses a single nucleotide polymorphism (SNP) microarray and DNA samples from the individuals who contributed the eggs and sperm to perform PGT-A. Nateras testing can detect three types of chromosome abnormalities.It is primarily designed to ensure an embryo has the correct number of chromosomes (euploidy). PGT-A screens embryos for whole missing chromosomes (monosomy), whole extra chromosomes (trisomy), or an entire extra set of 23 chromosomes (triploidy).Second, PGT-A at Natera screens for missing or extra pieces of chromosomes (deletions or duplications). These deletions and duplications must be large, accounting for 15% of the total length of that chromosome, to potentially be detected. Finally, PGT-A at Natera screens for uniparental disomy (UPD) of chromosomes 6, 7, 11, 14, and 15. UPD occurs when an embryo receives two copies of a chromosome from one biological parent, and no copies from the other. UPD of these five chromosomes can result in poor pregnancy outcomes or a child with serious health issues.
Chromosome abnormalities are common in embryos. Overall, the laboratory we use most often (Natera) reports that 51% of the day 5 embryo biopsies they test have normal chromosomes and 49% have abnormal chromosomes.The percentage of chromosomally normal embryos expected is most strongly influenced by the age of the person providing the egg (see question 12).
Chromosome abnormalities can happen in any embryo or pregnancy simply by chance. However, the chance for missing or extra chromosomes (aneuploidy) does increase with the age of the person providing the egg. For a woman who is less than 30 years old, the laboratory we use most often (Natera) finds that 31% of the day 5 embryos have abnormal PGT-A results. For women ages 30-34, the frequency of abnormal PGT-A results increases slightly to 36%. For women ages 35-39, 50% of day 5 embryos have abnormal PGT-A results. For women ages 40 or older, Natera reports that 68% of day 5 embryos have abnormal PGT-A results.
Please remember these are averages so you may have a greater or smaller percentage of normal embryos 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 a woman will have available to test also tends to decrease with age.
Mosaicism refers to a mixture of two or more types of cells within the same embryo. On day 5, an embryo is made up of approximately 120 cells.The lab will remove 5-10 of these cells for PGT. We expect all of the embryos cells to be identical so testing this small sample will give us accurate information about the whole embryo in most cases. 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.
Sometimes the 5-10 biopsied cells contain a mixture of chromosomally normal and abnormal cells.If mosaicism is reported by the laboratory, those embryos would only be considered for transfer if the patient has no chromosomally normal (euploid) embryos available. The decision to use a mosaic embryo for transfer is complicated and requires careful genetic counseling. Data about the potential of mosaic embryos to result in a healthy pregnancy and child are still being gathered. Multiple studies have found mosaic embryos have poorer outcomes compared to those with normal chromosome results.
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, a single chromosomally normal embryo is transferred reducing the chance of multiples (e.g. twins or triplets). PGT-A may also be helpful when a patient has excess embryos they plan to store for future use. Since embryos with aneuploidy are more likely to result in a failed IVF cycle or miscarriage, PGT-A provides additional information about the reproductive potential of those embryos. PGT-A also reduces the likelihood of the birth of a child with a detectable chromosome condition like Down syndrome. 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.
Yes. First, PGT-A adds significant additional cost that may not be covered by insurance (see question 21). Some patients may have to undergo more than one IVF cycle in order to get a chromosomally normal 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. A frozen embryo transfer will be scheduled after the PGT results are available. Third, the PGT process poses a small risk to the embryo(s) (see question 7). Finally, although uncommon, inaccurate PGT results may lead to the transfer of an embryo with a chromosome abnormality that was not detected or the non-transfer of an embryo with potential to result in a healthy pregnancy.
PGT-M or PGT-SR are options for 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 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 such as Down syndrome, Turner syndrome, Klinefelter syndrome, trisomy 13, trisomy 18, PGT-A does nottest embryos for any specific genetic diseases or syndromes.
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.
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 that has been 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.
No.PGT only screens for certain chromosome abnormalities (PGT-A or PGT-SR) or one 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.There is no genetic test that 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.
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 analyzingfetal DNA in a sample of a pregnant womans 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 may also screen for the sex chromosomes (X and Y), other trisomies, triploidy (having an extra copy of every chromosome), and certain microdeletions (missing sections of a chromosome that cause known syndromes such as 22q11.2 deletion syndrome). The benefits of NIPT are that it can be doneas early as 9 weeksof pregnancy,and since it is performed on a blood sample from the pregnant woman, 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.
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.
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 or PGT-SR for a Robertsonian translocation is $1,795 for up to eight embryos. The self-pay price for PGT-SR for a reciprocal translocation or inversion 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.
Once the laboratory receives the embryo biopsy samples and has received payment for the testing, results are expected in approximately 7-10 days.
Your physician or genetic counselor will call you with your PGT results. At that time, we will review how many embryos are appropriate for transfer.
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 or uniparental disomy (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 that are not caused by detectable chromosome abnormalities. Normal PGT-A results cannot guarantee a successful IVF cycle or prevent miscarriage.
Abnormal PGT-A results mean the laboratory detected a chromosome abnormality.Embryos with abnormal PGT-A results are not recommended for transfer because they are expected to result in a failed IVF cycle, miscarriage, or the birth of a child with serious health issues.
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 normal 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 would not be 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 that, at this time, PGT-SR does not distinguish between embryos with normal chromosomes and those with a balanced translocation or inversion.Since carriers of a balanced translocation or chromosome inversion are typically healthy, those embryos are reasonable to transfer. A routine chromosome study (karyotype) can be done through CVS, amniocentesis, or on a blood sample after delivery to determine if the child inherited the balanced translocation or inversion.
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 cycle.
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Preimplantation Genetic Testing - Fertility & Reproductive Medicine Center
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