What is Preimplantation Genetic Testing (PGT)? Methods and Clinical Success

Preimplantation Genetic Testing (PGT) is a sophisticated clinical procedure that allows for the screening of embryos—obtained through assisted reproductive technologies (ART)—for genetic diseases or chromosomal abnormalities before they are transferred into the uterus. While traditional In Vitro Fertilization (IVF) applications select embryos based solely on their microscopic morphology (appearance), PGT technology delves into the genetic code of the cells to identify the healthiest possible embryo for transfer. Assoc. Prof. Dr. Nazlı Korkmaz emphasizes that PGT is not only a method to prevent recurrent miscarriages but also a revolutionary procedure that prevents the transmission of severe hereditary diseases to future generations.

Physiological and Genetic Foundations of PGT

Human life begins with the union of 46 chromosomes—23 from the mother and 23 from the father. However, errors occurring during fertilization or the early division stages of the embryo can lead to numerical chromosomal abnormalities, known as "aneuploidy." These abnormalities can prevent the embryo from implanting in the uterus, or if implantation does occur, they may result in pregnancy loss or the birth of individuals with genetic disorders such as Down Syndrome.

The PGT process is performed on the 5th or 6th day of embryonic development in a laboratory setting (the blastocyst stage). A few cells are biopsied from the trophectoderm—the layer of the embryo that will eventually form the placenta. These cells are then analyzed using advanced Next-Generation Sequencing (NGS) methods without harming the embryo itself. This ensures that only chromosomally normal (euploid) embryos are selected for transfer, thereby maximizing the chances of a healthy pregnancy and live birth.

Types of PGT and Clinical Classification

In modern reproductive medicine, Preimplantation Genetic Tests are classified into three main categories based on the patient's medical history and specific needs:

1. PGT-A (Aneuploidy - Numerical Screening): This is the most frequently applied type of PGT. It involves screening all 24 chromosomes for numerical accuracy. It is particularly recommended for cases of advanced maternal age (over 35), recurrent IVF failures, or couples with a history of unexplained recurrent pregnancy loss, to identify embryos with the correct chromosomal count.

2. PGT-M (Monogenic - Single Gene Disorders): This test is performed to prevent the transmission of known single-gene disorders within a family (such as Thalassemia, Cystic Fibrosis, Spinal Muscular Atrophy - SMA, Sickle Cell Anemia, etc.) to the embryo. In this method, the specific gene region causing the disease is directly examined, and only healthy or carrier embryos (those who do not carry the risk of developing the disease) are selected.

3. PGT-SR (Structural Rearrangements): This is applied when one of the parents carries structural chromosomal abnormalities such as translocations or inversions. These structural imbalances can lead to embryos with missing or extra genetic material, resulting in pregnancy loss. PGT-SR identifies embryos that are free from these specific imbalances.

The PGT Application Process: A Step-by-Step Clinical Approach

The PGT process is seamlessly integrated with a standard IVF cycle. The procedure consists of the following stages:

• Ovarian Stimulation and Egg Retrieval (OPU): The expectant mother undergoes hormone therapy to stimulate the ovaries, and the matured eggs are retrieved.
• Fertilization (ICSI): The retrieved eggs are fertilized with the expectant father's sperm using the Intracytoplasmic Sperm Injection (ICSI) method.
• Embryo Culture: The fertilized embryos are monitored in a laboratory environment until the 5th day (blastocyst stage).
• Embryo Biopsy: Specialized embryologists take a cell sample from the outer layer (trophectoderm) without touching the inner cell mass (the part that will form the baby).
• Genetic Analysis and Freezing: While the samples are sent to the genetic laboratory, the embryos are vitrified (flash-frozen) using high-tech methods to be preserved during the analysis period.
• Healthy Embryo Transfer: Once the test results are finalized, the "best" embryo proven to be genetically normal is thawed and transferred into the mother's uterus.

Who Should Consider PGT? The Ideal Candidate Profile

In contemporary reproductive medicine, while PGT is not mandatory for every IVF patient, it is the key to success in the following scenarios:

• Expectant mothers aged 35 and older (due to chromosomal risks associated with oocyte aging).
• Couples with two or more failed IVF attempts.
• Individuals experiencing recurrent pregnancy loss (miscarriage).
• Cases where one partner has a known chromosomal rearrangement (e.g., translocation).
• Couples with a family history of hereditary single-gene disorders (SMA, Mediterranean Anemia, etc.).
• Couples who have previously had a child with a genetic disorder.

Advantages and Success Rates of PGT

The greatest advantage of PGT technology is that it shortens the "time to pregnancy" and significantly increases clinical success rates. In transfers performed without genetic screening, an embryo may appear morphologically perfect but still be genetically abnormal, leading to failure. When PGT is utilized:

• Live birth rates per pregnancy can reach levels of 70-80%.
• The risk of miscarriage is reduced from approximately 25% to levels as low as 5-10%.
• Single embryo transfer can be performed with confidence to avoid the risks associated with multiple pregnancies (twins/triplets).
• The risk of giving birth to a child with a genetic disorder is almost entirely eliminated.

Frequently Asked Questions (FAQ)

1. Does the PGT procedure harm the embryo? The biopsy is performed on the outer layer, avoiding the inner cell mass that develops into the fetus. When performed by experienced hands, the risk of harming the embryo's developmental or pregnancy potential is negligible.

2. Can the sex of the baby be determined with PGT? Technically, PGT can identify sex chromosomes (X and Y). However, according to the laws of the Republic of Turkey, sex selection is illegal unless there is a medical necessity (such as sex-linked genetic disorders).

3. Are PGT results 100% certain? PGT methods have a high accuracy rate of 98-99%. However, in rare cases, "mosaicism" (where an embryo has a mix of normal and abnormal cells) may occur. Therefore, standard prenatal screenings are still recommended for pregnancies achieved after PGT.

4. Can PGT-A and PGT-M be performed simultaneously? Yes. If a family has a known single-gene disorder and the mother is of advanced age, both disease screening (PGT-M) and chromosomal count screening (PGT-A) can be performed on the same embryo.

5. Is PGT a costly procedure? Since it involves additional genetic laboratory processes on top of standard IVF treatment, it increases the overall cost. However, when considering the emotional and financial burden of failed transfers or potential pregnancy losses, it is a highly efficient investment for eligible candidates.

6. Can PGT be performed on previously frozen embryos? Yes, frozen embryos can be thawed, biopsied, and re-frozen while waiting for the results. However, as this adds extra stress to the embryo, the risk-benefit ratio should be carefully evaluated by your physician.

The Preimplantation Genetic Testing process is not just a treatment aimed at the current pregnancy; it is a scientific assurance for the foundation of healthy future generations. With accurate diagnostic methods and meticulous laboratory work, the chance of becoming a parent without the shadow of genetic risks is higher than ever.

To embark on a healthy pregnancy journey and take the most accurate step by mapping the genetic blueprint of your embryos, you can plan personalized treatment protocols under the guidance of Assoc. Prof. Dr. Nazlı Korkmaz at our clinic in Ankara and improve your quality of life.