Although genetic testing of a single or small number of cells is highly challenging, preimplantation genetic testing (PGT) has established itself as a viable alternative to invasive prenatal diagnosis.
What is PGT-M?
Pre-implantation genetic testing refers to a collection of genetic tests used to analyze embryos before transfer. Preimplantation genetic testing—monogenic diseases (PGT-M), targets single gene disorders, and preimplantation genetic testing—aneuploidy (PGT-A) is a broader test that screens for aneuploidy on all chromosomes, including 22 pairs of autosomes and the sex chromosomes X and Y.
Pre-implantation genetic testing-structural rearrangements (PGT-SR) are used to assess the risk for chromosome gains and losses linked to parental structural chromosomal abnormalities (such as translocations, inversions, deletions, and insertions). (1)
As a new development, the general methods now allow simultaneous analysis of PGT-M and PGT-A. The PGT domain is heading toward a sequencing-based, all-in-one solution for PGT-M, PGT-SR, and PGT-A as innovative algorithms are created and sequencing costs continue to decrease. (2)
How is the testing process?
Before starting a clinical cycle, expectant parents receive thorough genetic and reproductive counseling. There may also be psychological support available. Blood samples are taken for preclinical research after parents sign informed consent forms. This often entails blood samples and genetic data from pertinent first-degree relatives for PGT-M.
Ovarian stimulation and preclinical reproductive research are identical to those done on patients receiving conventional IVF. For a preclinical genetic study, both partners’ traditional karyotypes are necessary. Testing for carriers of common genetic variations for hemoglobinopathies, spinomuscular atrophy, and cystic fibrosis can be used to supplement this. These individual screening tests will probably be phased out in favor of extended carrier screening soon.
Monogenic disease preclinical genetic research depends on test design (targeted and genome-wide testing) and approach (direct testing involving detection of pathogenic variants versus indirect testing based on genetic markers). (4)
How does the PGT-M test result?
False positive and false negative results are conceivable with preimplantation genetic testing, regardless of the technique used. A “normal” or negative preimplantation genetic test result is not a guarantee that a newborn will not have genetic abnormalities, and patients and healthcare professionals should be aware of this. Indeed, there is a 1% risk of misdiagnosis.
All patients undergoing preimplantation genetic testing-aneuploidy should be provided with conventional diagnostic testing or screening for aneuploidy following the recommendations for all pregnant women.
If concurrent preimplantation genetic testing-aneuploidy is not conducted, it is especially crucial to offer diagnostic testing or screening for aneuploidy after preimplantation genetic testing-monogenic or preimplantation genetic testing-structural rearrangements. (3)
What does PGT-M detect?
Preimplantation genetic testing for monogenic disorders is used to test for a specific genetic pathogenic mutation responsible for a disease carried by one or both parents or even a lost child. With this technique combined with IVF, it is possible to test the embryos cultured in the laboratory and allow for the transfer of the embryos free of the tested mutation.
Additionally, preimplantation genetic testing for monogenic diseases can be used to identify human leukocyte antigen-compatible (HLA-matched) unaffected embryos with the aim of allowing ill family members to receive compatible bone marrow transplants or cord blood transfusions.
What do you expect in the PGT-M test?
PGT-M targets single-gene disorders. Only a few cells from the early embryo, often the blastocyst stage, are used in pre-implantation genetic testing for monogenic diseases, and while misdiagnosis is possible, it is uncommon with current methods. By using chorionic villus sampling (CVS) or amniocentesis, preimplantation genetic testing-confirmation of monogenic results should be provided. (6)
Is PGT-M covered by insurance?
It’s important to note that PGT-M can be a costly procedure, and the cost may vary depending on the country, clinic, and number of embryos being tested. Some clinics may offer financing options or payment plans to help make PGT-M more affordable for patients who need it.
Despite these exorbitant costs, there is very little insurance coverage in the USA for IVF using PGT. For people who meet specific requirements, every significant insurance carrier pays for genetic counseling and testing. Prospective parents may have few options for risk management in the context of reproductive decision-making, after being informed about their own genetic risks and, consequently, the genetic risks of their future babies.
In Turkey, PGT-M is legal and available in many IVF clinics. However, whether PGT-M is covered by insurance in Turkey depends on the relevant insurance policy and strict criteria. The Turkish healthcare system operates on a public-private partnership model, with universal healthcare coverage provided by the government-funded Social Security Institution (SSI).
It’s recommended that you contact your insurance provider to confirm whether PGT-M is covered and to what extent. If PGT-M is not covered by insurance, you may want to explore other financing options or consider seeking treatment at a clinic that offers more affordable PGT-M options.
Daar, J., Benward, J., Collins, L., Davis, J., Davis, O., Francis, L., … & Zweifel, J. (2018). Use of preimplantation genetic testing for monogenic defects (PGT-M) for adult-onset conditions: an Ethics Committee opinion. Fertility and sterility, 109(6), 989-992.