Preimplantation Genetic Testing: What is PGT?

Preimplantation Genetic Testing (PGT) is the process of screening embryos obtained using assisted reproductive techniques for genetic diseases or chromosomal irregularities before they are transferred into the uterus. While in traditional in vitro fertilization applications, embryos are selected only based on their microscopic morphology (appearance), PGT technology allows the selection of the healthiest embryo by delving into the genetic code of the cells. Assoc.Dr. Nazlı Korkmazemphasizes that the PGT method not only prevents recurrent miscarriages, but also is a revolutionary procedure that prevents the transmission of serious genetic diseases to future generations.

Physiological and Genetic Basis of PGT

Human life begins with the union of a total of 46 chromosomes, 23 of which come from the mother and 23 from the father. However, errors occurring during fertilization or in the first division stages of the embryo can lead to chromosome number disorders called "aneuploidy". These disorders may prevent the embryo from attaching to the uterus, and even if it does, it may cause the pregnancy to end in miscarriage or the birth of individuals with genetic diseases such as Down Syndrome.

In reproductive health evaluation, age, infertility duration, ovarian reserve, sperm parameters and uterine-tube factor should be considered together [1][3].

The PGT process is performed on the 5th or 6th day of the embryo developed in a laboratory environment (blastocyst stage), by taking several biopsies from the trophectoderm cells of the embryo that will form the placenta in the future. These cells are examined with advanced technology sequencing methods (NGS - Next Generation Sequencing) without damaging the embryo itself. In this way, the chance of pregnancy is maximized by transferring only chromosomally normal (euploid) embryos.

PGT Types and Clinical Classification

Today, Preimplantation Genetic Tests are classified under three main headings according to the patient's medical history and needs:

Protocol selection in in vitro fertilization and assisted reproductive treatments should be individualized, taking into account ovarian response and safety risks [1][2].

1. PGT-A (Aneuploidy - Numerical Screening):It is the most commonly applied type of PGT. All 24 chromosomes in the embryo are digitally scanned. It is used to find the embryo with the correct chromosomal number, especially in couples with advanced maternal age (over 35 years of age), recurrent in vitro fertilization failures or a history of unexplained miscarriage.

2. PGT-M (Monogenic - Single Gene Diseases):It is performed to prevent the transfer of single gene diseases known in the family (Thalassemia, Cystic Fibrosis, Spinal Muscular Atrophy - SMA, Sickle Cell Anemia, etc.) to the embryo. In this method, the gene region that directly causes the disease is examined and only healthy or carrier (not at risk of disease) embryos are selected.

3. PGT-SR (Structural Rearrangements):It is applied if one of the parents has structural disorders such as translocation or inversion in their chromosomes. These structural imbalances lead to missing or excess genetic material in the embryo, resulting in pregnancy losses. With PGT-SR, embryos without this imbalance are detected.

PGT Application Process: Step-by-Step Clinical Approach

The PGT process is integrated with a standard in vitro fertilization (IVF) treatment. The process consists of the following stages:

Prior attempts, comorbidities, and pregnancy goal should be evaluated in detail before starting treatment [1].

• Egg Development and Collection (OPU):With the hormone treatment given to the expectant mother, the ovaries are stimulated and the matured eggs are collected.
• Fertilization (ICSI):The collected eggs are fertilized with the sperm of the prospective father by microinjection method.
• Embryo Culture:Fertilized embryos are monitored in the laboratory environment until the 5th day (blastocyst stage).
• Embryo Biopsy:Expert embryologists take a cell sample from the outer wall of the embryo without touching its inner cell (the part that will form the baby).
• Genetic Analysis and Freezing:While the samples are sent to the genetics laboratory, the embryos are frozen and stored using high technology (vitrification).
• Healthy Embryo Transfer:After the test results come in, the "best" embryo, which is proven to be genetically normal, is thawed and transferred to the mother's uterus.

Who is PGT Recommended for? Ideal Candidate Profile

In modern reproductive medicine, although PGT is not mandatory for every IVF patient, it is the key to success in the following cases:

Embryo transfer, genetic evaluation or additional laboratory applications may not be necessary for every patient; The decision should be made based on the individual clinical picture [2][3].

• Expectant mothers aged 35 and over (due to chromosomal risks due to egg aging).
• Couples who have had two or more unsuccessful in vitro fertilization attempts.
• Those who experience recurrent pregnancy losses (Miscarriages).
• One of the spouses has a known chromosomal disorder (Translocation, etc.).
• Those with a family history of hereditary single gene disease (SMA, Mediterranean Anemia, etc.).
• Couples who had children with genetic disorders in previous pregnancies.

Advantages and Success Rates of PGT

The biggest advantage of PGT technology is that it shortens the pregnancy period and increases clinical success. In transfers without genetic screening, even if the embryo looks very good morphologically, it may be genetically defective, resulting in failure. When PGT is performed;

• The live birth rate per pregnancy can reach up to 70-80%.
• The risk of miscarriage decreases from 25% to 5-10%.
• In order to reduce the risk of multiple pregnancy (twins/triplets), single and healthy embryo transfer can be done safely.
• The risk of giving birth to children with genetic diseases is almost completely eliminated.

Frequently Asked Questions (FAQ)

1. Does PGT procedure damage the embryo?The biopsy is performed from the outer layer of the embryo, without touching the inner cell mass that will form the baby. When done in experienced hands, the risk of harming the development of the embryo or pregnancy potential is negligible.

2. Can the gender of the baby be determined with PGT?Technically, with PGT, the sex chromosomes (X and Y) of the embryo can be seen. However, according to the laws of the Republic of Türkiye, it is not legal to choose gender unless there is a medical necessity (genetic diseases that are transmitted depending on gender).

3. Are PGT results 100% accurate?PGT methods have a high accuracy rate of 98-99%. However, in rare cases, "mosaicism" (some cells of the embryo are normal and some are abnormal) may occur. For this reason, standard prenatal screenings are also recommended for pregnancies achieved after PGT.

4. Can PGT-A and PGT-M be performed at the same time?Yes, if there is a known single gene disease in the family and the mother is older, both disease screening (PGT-M) and chromosome number screening (PGT-A) can be applied to the same embryo.

5. Is PGT a costly procedure?It increases the cost because it involves genetic laboratory processes in addition to standard in vitro fertilization treatment. However, considering both the financial and moral burden caused by unsuccessful transfers and possible pregnancy losses, it is a very productive investment in suitable candidates.

6. Can PGT be performed on frozen embryos later?Yes, previously frozen embryos can be thawed and biopsied and frozen again to wait for the results. However, since this procedure may be a source of extra stress for the embryo, the benefit-loss balance should be carefully evaluated by the physician.

The Preimplantation Genetic Testing process is not only a treatment targeting the current pregnancy, but a scientific assurance that lays the foundations of healthy generations. With accurate diagnostic methods and meticulous laboratory studies, the chance of becoming a parent without being overshadowed by genetic risks is higher than ever.

To start a healthy pregnancy journey and take the right step by creating the genetic map of your embryos, Assoc. Prof. in our clinic in Ankara. Dr. With the help of Nazlı Korkmaz, you can plan treatment protocols specific to you and improve your quality of life.

References

• [1] NICE NG257 - Fertility problems: assessment and treatment- Current clinical guidance for infertility evaluation, treatment options and IVF approach.
• [2] ESHRE - Ovarian Stimulation for IVF/ICSI- Ovarian stimulation, monitoring and personalization recommendations during the IVF/ICSI process.
• [3] ASRM - Definition of infertility: a committee opinion- Expert committee opinion on the definition of infertility and the timing of application for treatment.