What does PGT test for?

Couples struggling with infertility may benefit from preimplantation genetic testing (PGT), which can increase the chances of having a successful pregnancy. Infertility clinics will perform PGT testing before implanting an embryo into the uterus for IVF. This article outlines what PGT is, discusses who could benefit from it, and explains the different types of PGT.

What is PGT? 

Preimplantation genetic testing (PGT) is an option for couples undergoing in vitro fertilization (IVF). This testing screens the embryos for potential genetic and chromosomal abnormalities before implanting them into the uterus. PGT plays a crucial role in selecting the embryos with the highest chance of success during fertility treatments, like IVF, for implantation. Only the unaffected embryos are transferred to the uterus for implantation to increase the success of implantation.

Is PGT for Me? Who Can It Help? 

There are many factors to consider when deciding to have PGT. Reasons to consider PGT include:

• Previous pregnancy with aneuploidy (chromosome abnormality)
• Two or more miscarriages
• Couples at risk of having a child affected with an inherited genetic disorder
• Previously failed embryo implantation
• Women who are diagnosed with unexplained infertility
• Women over the age of 35
• Numerous unsuccessful fertility treatments

It is best to consult with a fertility specialist to make the best-informed decision. A fertility specialist will go over your health history, individual fertility journey and will be able to answer any questions.

Understanding the Different Types of PGT 

There are three different types of PGT. Preimplantation genetic testing-monogenic (PGT-M) testing targets a single gene disorder. Preimplantation genetic-testing aneuploid (PGT-A) is a broader test that screens for one or more extra or missing chromosomes, known as aneuploidy. Fertility clinics may recommend preimplantation genetic testing-structural rearrangements (PGT-SR) for concerns of translocations. Translocations are when two chromosomes break off and switch places.

Fertility specialists recommend conducting PGT during the blastocyst phase of an embryo, which is an early developmental stage of an embryo. Embryologists can also complete this testing at the embryo's later stages if needed. When performing PGT, embryologists will biopsy about 5-10 cells from the trophectoderm layer or the outer layer of an embryo that turns into the placenta. These cells do not require a biopsy of the inner cell mass, which turns into the developing fetus.

PGT-A (Aneuploidy Screening)

The PGT-A screens embryos for whole chromosome abnormalities. An embryo should have 46 chromosomes, of which half come from the egg and the other half from the sperm. PGT-A screens for any missing or extra chromosomes that may lead to failure of the embryo to implant, a miscarriage, or cause significant health issues for the child after birth. This screening counts the 46 chromosomes in an embryo to determine if there are any extra or missing chromosomes, a condition clinically referred to as aneuploidy. PGT-A screening can reduce the risk of having a child with genetic or chromosome abnormality, like Down syndrome, by identifying abnormal embryos so that transfer to a uterus can be avoided It can also help identify embryos with the greatest chance to implant during IVF, resulting in pregnancy.

Because PGT-A can identify embryos with high probability of implantation some fertility specialists recommended transferring only one embryo to avoid complications that may arise in pregnant patients with multiple fetuses.

Screening all 46 chromosomes means that the embryo sex is also available. This can benefit situations where a genetic disease is inherited based on embryo sex. Chromosomal abnormality in a developing fetus can lead to an increased risk of stillbirth, shortened lifespan, or cause significant medical problems after the child is born and is the leading cause of pregnancy loss. Screening the embryos for chromosomal abnormalities can avoid some of these situations and decreases the risk of miscarriage.

Additional testing of PGT-A adds extra cost to IVF. Insurance may not help cover the cost of PGT-A testing with the fertility treatment. Genetic screening tests also require embryologists to remove 5-10 cells from the trophectoderm, which are the cells that become the placenta. Testing is usually performed during the blastocyst stage of an embryo to decrease the risk of damage. The inner cells of the embryo that develop into the fetus are not disturbed. The risk of damage to the embryo is very low when performed in labs that routinely perform PGT screening.

Testing can deliver a false negative or false positive result. Healthy embryos can remain unused or for an embryo transfer with chromosomal abnormalities to occur due to test results. The test uses cells from the placenta and not the fetus, so it is not considered a diagnostic test. However, early genetic screenings also test cells from the placenta. Testing on the DNA of the fetus is not available until 15 weeks of pregnancy through an amniocentesis.

PGT-M (Monogenetic/single gene disorders)

PGT-M tests for a specific genetic mutation associated with a known diagnosis or known predisposition within the family. PGT-M does not test for all single gene disorders at once and will not detect genetic alterations present for the first time in one family member due to a variant. This type of testing uses cytogenetic or molecular techniques for single-gene disorders, like Huntington's disease, cystic fibrosis, or Fragile X syndrome. This includes single-gene disorders that are autosomal dominant and recessive or X-linked. PGT-M testing can also test for hereditary cancer syndromes like breast and ovarian cancer and Lynch syndrome. Furthermore, PGT-M can assist in detecting embryos that are compatible with human leukocyte antigens. These embryos can then be gestated so that ill family members can receive bone marrow transplants or cord blood transfusions compatible with their immune systems.

PGT-M tests a few cells from the early embryo, usually in the blastocyst stage. Misdiagnosis is possible but rare. To confirm the results of PGT-M, fertility specialists may recommend chorionic villus sampling (CVS) or amniocentesis.

PGT-SR (Structural Rearrangements)

Embryos at risk for chromosome rearrangement, when pieces of chromosomes are missing, duplicated, or rearranged, may consider having PGT-SR testing. It is important to consider genetic counseling and preimplantation genetic screening with the discovery of structural rearrangement in either parent. An individual with a chromosomal rearrangement is at an increased risk of experiencing recurrent pregnancy loss or having a child with a chromosomal rearrangement. If someone has experienced two or more pregnancy losses, fertility specialists may recommend a karyotype screening to check for any possible chromosomal rearrangement before beginning IVF. Testing for PGT-SR can lower the chances of experiencing another pregnancy loss or giving birth to a baby with a chromosomal abnormality.

It's important to note that PGT-SR testing has certain limitations. For instance, this type of testing cannot distinguish between an embryo with a typical karyotype and one with a balanced form of familial chromosome rearrangement. Individuals who carry balanced chromosome rearrangement involving imprinted genes are susceptible to irregularities related to uniparental disomy. This occurs when the embryo receives both copies of a chromosome from one parent instead of inheriting one from each parent. Uniparental disomy cannot be excluded from all preimplantation genetic testing analysis methods. A fertility specialist may recommend CVS or amniocentesis to confirm PGT-SR results.

Helping With Your Fertility Journey

Preimplantation genetic testing can help increase the chances of successful implantation for IVF patients. There are various reasons it may be considered. If you have been struggling with infertility, discuss your situation with one of our fertility specialists at Advanced Fertility Care to determine if PGT is right for you.

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