Preimplantation Genetic Testing (PGT)

Preimplantation Genetic Testing (PGT) is a test that enables the detection of genetic disorders and the selection of healthy embryos that do not carry these abnormalities.

What is Preimplantation Genetic Testing (PGT)?

 

Preimplantation Genetic Testing (PGT) allows for the detection of genetic disorders in embryos before they are transferred to the uterus, enabling the selection and use of healthy embryos that do not carry these conditions. Commonly known among the public as a method for “eliminating bad genes,” the test actually works as follows: biopsies are taken from all embryos, and those identified as healthy are selected for transfer. No treatment is applied to the embryo itself. Currently, it is not legal anywhere in the world to treat embryos or even conduct research on embryos that will not be used. However, with the rapid advancements in genetic science, it is possible that in the near future this may change, and embryo treatments may become a topic of discussion.

When the indications for IVF and PGT testing are correctly determined, it is a highly effective method that helps families bring healthy babies into their homes. However, it cannot be used for selecting traits that are relatively complex to inherit, such as fetal abilities or eye color.

First and foremost, it should be stated that natural conception is always the preferred and healthiest form of pregnancy, as it occurs through natural processes. It is not appropriate to opt for IVF solely to achieve a “healthier” pregnancy when there is no risk. Every pregnancy carries risks, and no one can guarantee that your baby will be born 100% healthy. The same guarantee cannot be given for IVF pregnancies either. However, advanced pregnancy monitoring methods and detailed screenings conducted during pregnancy can significantly reduce the risk of disease.

The application of genetic testing in IVF is a relatively new development. Preimplantation Genetic Testing was first used in 1991 in a couple carrying an X-linked disease to check for the presence of a Y chromosome and select a female fetus. Since then, it has been used in many diseases such as sickle cell anemia, Tay-Sachs disease, Duchenne muscular dystrophy, and beta-thalassemia. Today, it can be successfully used for almost all diseases for which molecular diagnosis is available.

Can I have a perfect baby through IVF?

Can I conceive naturally but opt for IVF to ensure the baby is healthy?
Can I have a blue-eyed baby?
Can you eliminate all the bad genes?
Can I select an embryo that will be a good dancer?
Can I get a 100% guarantee by screening for all diseases?

If you have questions like these, we recommend you read this article.

For many families, PGT has been a source of hope. It has been successfully applied in families with the risk factors detailed below.

 

Who Should Undergo PGT? In Which Cases is PGT Recommended?

 

1. Couples Carrying Genetic Diseases:

If a couple is at risk of carrying a specific genetic disease, it is not appropriate to immediately say, “Let’s do PGT for this family.” Before planning IVF treatments, they must first consult a genetic center.

Questions to ask include:

  • What is the genetic disease in question?

  • Have genetic tests been performed?

  • Is preimplantation genetic testing necessary for this disease?

  • Is there another alternative method to consider?

  • Are there any other diseases for which the family is at risk?

These questions must be answered first. Before starting IVF, if the couple is a carrier of a genetic disease, identifying the specific variant they carry is the first step. IVF cannot be performed without identifying the variant known to be associated with the disease in the family. Preliminary studies are conducted to determine all the risks for the family, and then a tailored testing plan is created. Using the method called PGT-M (Monogenic), the genetic profiles of embryos are examined. This allows for the identification of embryos that carry the genetic disease, ensuring that only healthy embryos are transferred to the uterus.

2. Prevention of Recurrent Pregnancy Loss:

For families who have experienced recurrent pregnancy losses, particularly when maternal age is advanced, PGT-A can provide a chance for a healthy pregnancy. However, the causes of recurrent pregnancy loss must first be investigated.

3. Advanced Maternal Age:

As maternal age increases, the risk of chromosomal abnormalities also rises. In such cases, PGT-A can be used to assess chromosomal abnormalities in embryos. It is particularly recommended for women over the age of 35.

4. Structural Chromosomal Abnormalities:

In cases where one or both parents carry structural chromosomal rearrangements, PGT-SR (Structural Rearrangement) is used to examine the chromosomes of embryos.

5. Enhancing the Effectiveness of Fertility Treatments:

When combined with assisted reproductive techniques like in vitro fertilization (IVF), PGT can increase the chances of pregnancy by selecting healthy embryos. Therefore, it is recommended in cases of repeated IVF failures.

6. Severe Male Factor:

In families where a severe male factor is identified, the risk of chromosomal abnormalities is increased, and PGT-A is recommended.

7. Previous Pregnancy with Chromosomal Abnormalities:

Families should be thoroughly informed. Many changes detected in a pregnancy do not necessarily lead to a significantly increased risk in future pregnancies. Therefore, families should seek counseling from an experienced healthcare professional based on the specific change identified.

8. Carriers of Cancer, Neurodegenerative Diseases, and Inherited Heart Diseases:

Families who carry variants associated with severe conditions that significantly impact life quality may not want their children to inherit these variants. In such cases, testing can be planned to select embryos that do not carry these variants.

9. HLA-Matched Sibling:

For families with a child who has leukemia or another disease requiring bone marrow transplantation, an HLA-matched sibling can be selected to provide stem cells when needed.

The Preimplantation Genetic Testing process can involve various psychological and emotional challenges. It is essential to provide families with accurate information. Therefore, couples considering PGT should seek detailed information and counseling from healthcare professionals.

 

What Methods Are Used in Preimplantation Genetic Testing (PGT)?

 

PGT analysis is performed using DNA obtained from either a day 3 blastomere biopsy or a day 5 trophectoderm biopsy. In a day 3 biopsy, a single cell is sent to the genetics center. In a day 5 biopsy, 5–9 cells are sampled. Except for certain special cases, the day 5 biopsy is preferred as it is considered more reliable. At our center, we also perform studies using the day 5 biopsy method. Since some time is required to complete the tests after a day 5 biopsy, the embryos are frozen.

The main methods used in Preimplantation Genetic Testing are:

PGT-M (Monogenic):

This method involves designing a family-specific test. Each family is treated as a unique project. Based on the mutation present in the family, a pre-analysis is conducted. The test is designed both to target the mutation and to identify specific “tracking markers” that distinguish between individuals who share or do not share the mutation. This allows for internal controls within the test. Using this custom-designed kit, embryos are analyzed, and healthy ones are selected. The study is conducted on DNA obtained from 5–9 cells taken from the embryo. Currently, only high-risk genes identified for the family are targeted for testing. Not all human genes are analyzed. Research is ongoing globally on using DNA from biopsies to analyze all genes, but it will take time before this becomes routine practice. At our center, we offer testing for the specific disease known in the family (the reason they come to us), as well as optional broad genetic screening of both partners before IVF (via whole exome sequencing—WES) to assess additional disease risks. If necessary, we can also identify and test for risky variants in 4–5 or more genes in embryos. These studies do not examine all genes in the embryo, but they significantly assess potential inherited diseases passed from parents, excluding new variants that may arise in the embryo itself.

PGT-A (Aneuploidy):

This method evaluates the chromosomal count in embryos. It is primarily used in cases of advanced maternal age, fertility issues, or recurrent pregnancy losses. Embryos with chromosomal abnormalities are identified, and healthy embryos are selected for uterine transfer.

PGT-SR (Structural Rearrangement):

This method is used when one or both parents carry structural chromosomal rearrangements. It examines structural chromosomal changes in embryos, and healthy embryos are selected for uterine transfer. In some cases, especially when the translocated chromosome segment is very small, additional markers may be identified, and supplementary tests may be planned to increase reliability.

These procedures are performed at our center using next-generation sequencing (NGS) technology.

 

How is Preimplantation Genetic Testing (PGT) Performed? What is the Process?

 

Preimplantation Genetic Testing (PGT) generally involves the following steps:

Egg Retrieval and Preparation:

During the IVF process, the woman receives an ovarian stimulation treatment. The higher the number of eggs retrieved, the greater the chance of obtaining healthy embryos. However, an excessive number of eggs can also create risks. This balance is managed by the IVF center. Sometimes, only a single embryo may be obtained in a cycle. In such cases, biopsies from a small number of embryos collected over several cycles are taken and frozen, increasing the chance of identifying a healthy embryo. Occasionally, standard ovarian stimulation protocols may fail, resulting in either too many or too few eggs. Underlying genetic variants (such as those in the FSHR gene) may contribute to these outcomes. In cases of unexpected results during IVF, contacting our center allows for necessary tests to be planned, and treatment durations and dosages can be adjusted based on the individual's genetic variants.

Embryo Development:

Fertilized eggs develop into embryos and are cultured in the laboratory for several days. Embryos are monitored until they reach a specific developmental stage.

Cell Biopsy:

Embryos are observed until they reach a certain stage of development. On day 5, a trophectoderm biopsy is taken and placed into special transport tubes with media provided by our center. After biopsy, embryos are frozen.

Genetic Analysis:

Biopsied cells are analyzed in the genetic laboratory. In PGT-M cases, it is determined whether the embryos carry a specific genetic disease. In PGT-A cases, the chromosomal count of the embryos is assessed.
Biopsies are sent to our center in special tubes. The initial processing is performed within these tubes to avoid losing any of the few cells. DNA is amplified using WGA (whole genome amplification). Once the entire genome is amplified, both the gene regions at risk in the family and potential chromosomal abnormalities can be examined. These methods are typically used sequentially: first, the target variants are assessed to identify healthy embryos, and then, among these, chromosomal disorders are screened. This approach helps avoid unnecessary costs.

Selection of Healthy Embryos:

Based on the genetic analysis results, genetically healthy embryos are identified. These embryos are selected for transfer to the uterus.

Embryo Transfer:

Healthy embryos are transferred into the woman’s uterus, initiating the pregnancy process.

The PGT process requires precise techniques and equipment to determine the accuracy of the genetic analysis and whether embryos are healthy. This process involves a range of ethical, medical, and emotional challenges, and couples are strongly encouraged to collaborate with a genetic counselor and receive thorough information.

 

What Diseases Can Preimplantation Genetic Testing (PGT) Diagnose?

 

A) For Chromosomal Disorders (PGT-A and PGT-SR)

PGT-A is used to screen for all chromosomal aneuploidies or large segmental deletions and duplications.

Using the FISH method, aneuploidy of specific chromosomes can be investigated. The advantage of FISH is that it can be performed on day 3 biopsies without the need to freeze the embryo. Since the procedure can be done quickly, healthy embryos can be identified and transferred immediately. However, FISH uses a single cell from the biopsy and relies on special fluorescent probes that bind only to certain chromosomes, which limits its reliability. While FISH was previously used to investigate common chromosomal anomalies, it has largely been abandoned in most centers today due to its low reliability.

Currently, next-generation sequencing (NGS)-based methods are used. With minimal amounts of DNA, these methods allow for the detection of all numerical chromosomal abnormalities in the embryo. For this, 5–9 cells are obtained from a day 5 biopsy, subjected to WGA (whole genome amplification), and the resulting DNA is used to assess either the chromosomal count (PGT-A) or, if needed, specific chromosomal segmental losses or gains (PGT-SR).

PGT-SR is used to screen for smaller chromosomal deletions and duplications than those typically detected by PGT-A. It is a higher-resolution, more detailed platform, making it the preferred method for small structural changes.

If the translocated chromosomal segment carried by the parents is small, PGT-SR is planned. In some cases, additional markers identified from the family may be required, and combined analyses with other molecular methods may be necessary.

ESHRE (2018) recommendations for PGT-A are as follows:

  • Advanced maternal age

  • Recurrent implantation failure

  • Recurrent pregnancy loss

  • Severe male factor (SMF)

  • Previous pregnancy with a chromosomal abnormality

Patients with these indications can contact our center for detailed information. If tests or treatments other than IVF are required, we will guide them accordingly. If there is another underlying cause for pregnancy loss, unless that issue is resolved, pregnancies achieved through IVF may also result in miscarriage.
It is important to remember that humans are not made up of a single gene. We all have differences and predispositions to certain diseases due to variations in our approximately 20,000 genes. No two patients are the same. This is why personalized medicine is so important—it increases treatment success. For appropriate method selection and counseling, please contact our center.

 

B) For Single-Gene Disorders (PGT-M)

The PGT-M method is used for families affected by or carrying a single-gene disorder.

Conditions include:

  • Autosomal recessive and dominant disorders,

  • X-linked disorders,

  • Late-onset diseases,

  • HLA typing applications,

  • Variants related to cancer predisposition in the parents,

  • Risks for neurodegenerative diseases and hereditary heart conditions.

Testing can be performed for one or more genetic disorders that carry a recurrence risk in the family.

In our country, the rate of consanguineous marriages is quite high. While statistical studies report a rate of around 26% for consanguineous marriages in Turkey, considering marriages between individuals from the same village—where we have observed high genetic similarity in genetic tests—the actual rate in certain regions is known to be much higher than reported figures. Among couples who have a consanguineous marriage, approximately 30% carry the same disease-causing variant for at least one condition, while the rate of carrying multiple mutations is estimated to be around 7-10%. Considering the 30% chance of a mutation in consanguineous marriages, the probability of having an affected child per pregnancy is around 7.5%.

Therefore, when providing counseling to couples in consanguineous marriages, it is critical to obtain thorough clinical information from the family and inform them about the testing process. If comprehensive broad gene panels (see: Pregnarisk) are performed before IVF, PGD can be planned based on the results of these tests. The risks associated with consanguinity can be significantly reduced.

For appropriate method selection, please contact our center.

Important Note: The risk to the fetus in PGT can never be reduced to zero anywhere in the world. Therefore, pregnancy monitoring must continue, and families should be informed about prenatal diagnosis based on the specific disease characteristics.

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