Preimplantation genetic tests: what are they and why are they performed?

Preimplantation genetic testing (PGT) includes screening tests for aneuploidy (PGT-A), monogenic diseases (PGT-M), and structural chromosome abnormalities (PGT-SR) to select a healthy embryo during IVF and increase the chances of pregnancy success.

Preimplantation genetic testing (PGT) is an important tool in reproductive medicine that helps improve the effectiveness of IVF with PGT programs and significantly increase the chances of a healthy pregnancy. Let’s examine the main steps and the different types of tests.

Stages of PGT

1. Egg retrieval and fertilization with the partner's sperm.
2. Culture of embryos until the blastocyst stage.
3. Embryo biopsy: on the 5th or 6th day of development (sometimes on the 7th day), the embryologist removes 5 to 8 cells from the trophoblast layer (future placenta).
4. Genetic testing: the collected cells (biopsy) are examined for chromosomal abnormalities, monogenic diseases, or even the Rh factor to exclude any Rh incompatibility risk.
5. Embryo selection: after analysis of results, a euploid (chromosomally healthy) embryo is selected for transfer.

Types of preimplantation tests

PGT-A — aneuploidy screening test

PGT-A allows detecting abnormalities in the chromosomal makeup of the embryo before transfer into the uterus. Its benefits include:

• Reducing the number of unsuccessful transfers.
• Reducing the risk of miscarriages.
• Increasing the chances of pregnancy for at-risk patients.
• Reducing the risk of multiple pregnancies.
• Minimizing the risk of birth of a child with a chromosomal disorder.

Chromosomal abnormalities can occur spontaneously, even in healthy individuals. With age, the risk of embryonic aneuploidy increases in women. On average, the frequency of these abnormal embryos is between 48% and 90%, depending on reproductive age. It is important to note that aneuploid embryos do not visually differ from healthy embryos, which is why genetic screening is particularly necessary.

PGT-A is performed to detect Down syndrome, Edwards syndrome, Patau syndrome, Prader-Willi syndrome, Turner syndrome, Klinefelter syndrome, and others. In our clinic, all 23 pairs of chromosomes are examined, allowing for the selection of a chromosome-normal embryo.

When is PGT-A indicated?

• Chromosomal diseases in the family.
• Women over 35 years of age.
• Couples who have experienced IVF failures.
• Men over 40 years of age.
• Poor sperm morphology results.
• History of early pregnancy losses.

PGT-M — monogenic disease screening test

This method determines the genetic status of the embryo regarding a specific monogenic disease. It is recommended when there is a risk of transmitting a particular disorder to the offspring.

PGT-M is indicated in the following cases:

• Both partners are carriers of an autosomal recessive disease (e.g., cystic fibrosis).
• The woman is a carrier of a sex-linked disorder (e.g., Duchenne muscular dystrophy).
• One partner suffers from a dominant autosomal pathology (e.g., Huntington's disease).
• There is a mutation associated with hereditary oncogenic syndromes (e.g., BRCA1/2).
• There is a history of pregnancy or birth of a child with a genetic mutation.

PGT-M requires the development of a unique test that considers the mutation and neighboring chromosome regions. For this, DNA samples from both partners are necessary.

PGT-SR — structural chromosome rearrangement detection test

PGT-SR is performed when rearrangements are detected in a couple’s karyotype. These modifications may include:

• Translocations (movement of a chromosome segment).
• Deletions (loss of a segment).
• Duplications.

If the rearrangement is balanced, the carrier shows no symptoms, but it can be transmitted to offspring and lead to miscarriages or severe pathologies in the child.

Testing methods:

• NGS (Next Generation Sequencing) to detect missing or extra chromosomes.
• Karyomapping, which allows diagnosing balanced anomalies.

Rearrangements can be hereditary or occur spontaneously. Many carriers only discover them during conception problems.

Importance of PGT in infertility treatment

Preimplantation genetic tests (PGT-A, PGT-M, PGT-SR) are key to IVF success. They help minimize risks, reduce the time to achieve pregnancy, and ensure the birth of a healthy child. In our blog, we discussed the topic: « What you need to know about preimplantation genetic testing (PGT-A)? »