The world of assisted reproductive technology has opened new doors for couples seeking to build their families. Preimplantation Genetic Testing (PGT) has emerged as a revolutionary tool that can help increase the chances of a successful pregnancy and a healthy child. Three common types of PGT, PGT-A (Preimplantation Genetic Testing for Aneuploidy), PGT-SR (Preimplantation for Structural Rearrangements), and PGT-M (Preimplantation Genetic Testing for Monogenic Disorders), serve distinct purposes in the world of reproductive genetics. In this blog post, we'll explore the key differences between PGT-A and PGT-M, shedding light on their unique applications and benefits.

PGT-A: Uncovering Chromosomal Abnormalities

PGT-A, or Preimplantation Genetic Testing for Aneuploidy, is a genetic testing technique designed to identify chromosomal abnormalities in embryos. Chromosomal abnormalities, such as having an extra chromosome or missing chromosome, can lead to implantation failure, miscarriage, or the birth of a child with developmental disabilities.

How PGT-A Works:

1. IVF and Embryo Development: After the female has undergone controlled ovarian hyperstimulation and her eggs have been retrieved, fertilization occurs, and the resulting embryos are cultured in the embryology lab until they reach the blastocyst stage (typically 5 days after the egg retrieval).

2. Embryo Biopsy: The viable embryos are then biopsied. The biopsy involves taking a small sample of cells from the outer edge of the embryo called the trophectoderm. Removing cells from this area of the embryo does not affect the development of the fetus as the cells from the trophectoderm are predetermined to develop into the placenta. The biopsied embryos are then frozen and the cell samples from each embryo are analyzed at a PGT lab.

3. Genetic Analysis: The extracted cells are analyzed to determine whether the embryos have a normal number of chromosomes (euploid) or if they exhibit abnormalities (aneuploid).

4. Selection: Based on the results, only euploid embryos are selected for transfer, increasing the chances of a successful pregnancy and decreasing the chance of miscarriage.

PGT-M: Detecting Single Gene Mutations

PGT-M, or Preimplantation Genetic Testing for Monogenic Disorders, is a technique used to detect single gene mutations responsible for monogenic disorders. Monogenic disorders are caused by mutations in a single gene and can lead to conditions such as cystic fibrosis, sickle cell anemia, and Huntington's disease.

How PGT-M Works:

1. Family History, Recessive Carrier Genetic Screening & Genetic Counseling: There are many inherited genetic traits that can be passed down from generation to generation. This is why it is important to have a thorough family history. Additionally, couples who both are found to be carriers of the same genetic trait are at risk of having a child affected by that disorder. The couple will then undergo genetic counseling to better understand the disorder, the severity of the disorder, and discuss options for PGT-M.

2. PGT-M Test Development: Information about your monogenic disorder will be sent to the PGT lab for review to ensure that an accurate test can be created for embryo screening. The ability for PGT-M to be offered for a specific gene mutation is influenced by many factors, most cases are able to be screened for with great accuracy, but not all. To build your unique PGT-M test, DNA samples from the sperm and egg source (and potentially from one or more other family members) are used to identify the unique DNA mutation that is associated with the monogenic disorder you are carriers for. Once identified, the PGT lab will review which genetic testing methods will be needed in order to give the most accurate results identifying embryos that are affected by the gene mutation. It can take 4 – 8 weeks for unique PGT-M case to be reviewed and the test to be finalized.

3. IVF, Embryo development, and Embryo Biopsy: The process of controlled ovarian hyperstimulation, egg retrieval, and embryo biopsy is the same as PGT-A. Embryos are cultured and biopsied at the blastocyst stage.

4. Genetic Analysis: Typically, PGT-A is performed in conjunction with PGT-M. The extracted cells are analyzed first to determine whether the embryos have a normal number of chromosomes (euploid) or if they exhibit abnormalities (aneuploid). All euploid embryos are then analyzed to determine whether the embryos carry or are affected by the mutation responsible for the monogenic disorder.

5. Selection: Only embryos that are chromosomally normal and are either carriers or unaffected by the single gene mutation are chosen for transfer, reducing the risk of having a child with the disorder.

Understand the Key Differences

• Targeted Genetic Analysis: The primary difference between PGT-A and PGT-M is the type of genetic analysis. PGT-A focuses on chromosomal abnormalities, while PGT-M targets specific inherited monogenic disorders.

• Application: PGT-A is routinely used in IVF cycle to rule out embryos with major chromosomal defects, while PGT-M is only used in cases where there is a known genetic disorder based on family history or recessive carrier screening.

Preimplantation Genetic Testing, whether PGT-A or PGT-M, plays a crucial role in modern reproductive medicine, enabling people to make informed decisions about their family's genetic health. Understanding the distinctions between PGT-A and PGT-M is essential for those considering these techniques. Both PGT-A and PGT-M have the potential to increase the likelihood of a successful pregnancy, but their applications are specific to different genetic concerns. Before you prepare for your IVF cycle, be sure to discuss these testing options with your reproductive endocrinologist so that you can be empowered in knowing what testing options are right for you.