The Role of Genetic Testing (PGT) in IVF

Beginning your fertility journey can feel overwhelming, with so much information and so many decisions to make. We understand the emotional weight you carry as you navigate the path to parenthood. At Izana, we are here to simplify the complex, offering clear, compassionate, and evidence based guidance every step of the way.

Preimplantation Genetic Testing, or PGT, is a powerful tool used in In Vitro Fertilization (IVF) to screen embryos for genetic abnormalities before implantation. It helps identify embryos with the highest potential for a successful pregnancy and a healthy baby, reducing the risk of miscarriage and certain genetic disorders.

• PGT screens embryos for chromosomal abnormalities and specific genetic conditions, improving IVF success rates.
• It encompasses PGT A for chromosomal counts, PGT M for single gene disorders, and PGT SR for structural rearrangements.
• The process involves an IVF cycle, embryo biopsy, genetic analysis, and selective embryo transfer.
• PGT is particularly beneficial for individuals with recurrent miscarriages, advanced maternal age, or known genetic risks.
• While offering significant advantages, it is important to discuss potential disadvantages and success rates with fertility specialists.

What is Preimplantation Genetic Testing (PGT)?

Preimplantation Genetic Testing (PGT) is a diagnostic technique performed on embryos created through In Vitro Fertilization (IVF), used to identify genetic abnormalities before an embryo is transferred to the uterus. It helps improve the chances of a healthy pregnancy by selecting embryos free from specific genetic conditions or chromosomal imbalances. This advanced testing provides valuable insights, empowering couples and their fertility specialists to make informed decisions.

What are the types of PGT?

There are three main types of PGT, each designed to detect different kinds of genetic issues in embryos. Understanding these distinctions is crucial for determining which test, if any, is right for your specific situation. Your fertility specialist will help you navigate this complex information.

PGT-A (Preimplantation Genetic Testing for Aneuploidy)

PGT A screens embryos for aneuploidy, which refers to an abnormal number of chromosomes. Humans typically have 46 chromosomes organized into 23 pairs. Having too many or too few chromosomes, such as in Down syndrome (Trisomy 21), can lead to implantation failure, miscarriage, or the birth of a child with a genetic condition.

PGT A is widely used to identify embryos with the correct number of chromosomes (euploid embryos), increasing the likelihood of a successful pregnancy. This is especially relevant for women of advanced maternal age, as the risk of aneuploidy increases significantly with age.

PGT-M (Preimplantation Genetic Testing for Monogenic Disorders)

PGT M is used to identify embryos affected by specific single gene disorders, also known as monogenic disorders. These conditions are caused by a mutation in a single gene and can be inherited from one or both parents.

Examples of conditions PGT M can detect include cystic fibrosis, sickle cell anemia, thalassemia, and Huntington's disease. If one or both partners are known carriers of a specific genetic mutation, PGT M can help prevent the transmission of that disorder to their child.

PGT-SR (Preimplantation Genetic Testing for Structural Rearrangements)

PGT SR is designed for couples where one partner carries a chromosomal structural rearrangement, such as a translocation or inversion. While the carrier themselves may be healthy, these rearrangements can lead to an unbalanced set of chromosomes in their offspring, resulting in recurrent miscarriages or birth defects.

PGT SR helps identify embryos that have inherited a balanced set of chromosomes, thus improving the chances of a successful and healthy pregnancy for these couples.

How does PGT work?

The PGT process is seamlessly integrated into an IVF treatment cycle. It involves several distinct stages, each requiring precision and expertise to ensure accurate results and optimal embryo selection.

IVF cycle & embryo creation

The journey begins with a standard IVF cycle. This involves ovarian stimulation to produce multiple eggs, followed by egg retrieval. The eggs are then fertilized with sperm in a laboratory setting to create embryos. These embryos are cultured for several days until they reach the blastocyst stage.

Embryo biopsy

Once embryos reach the blastocyst stage, a highly skilled embryologist performs a delicate embryo biopsy. This involves carefully removing a few cells (typically 5 to 10) from the trophectoderm, which is the outer layer of the blastocyst that will eventually form the placenta.

It is important to note that this biopsy is performed with extreme care to minimise any potential harm to the developing embryo. The inner cell mass, which forms the fetus, is not touched during this procedure.

Genetic testing of embryo cells

The biopsied cells are then sent to a specialized genetic laboratory for analysis. Depending on the type of PGT being performed (PGT A, PGT M, or PGT SR), different molecular techniques are used to examine the chromosomes or specific genes within these cells. The embryos themselves are cryopreserved (frozen) while awaiting the test results.

Results and embryo selection

Once the genetic test results are available, they are carefully reviewed by fertility specialists and genetic counselors. Euploid embryos (those with a normal chromosomal count for PGT A) or embryos free from specific genetic mutations (for PGT M and PGT SR) are identified as suitable for transfer. Your care team will discuss these results with you in detail, helping you understand their implications.

Who should consider PGT?

While PGT can be a valuable tool, it is not recommended for everyone. Certain situations and risk factors make individuals and couples particularly good candidates for considering this advanced genetic testing:

• Advanced maternal age: Women over 35 have an increased risk of producing eggs with chromosomal abnormalities, such as aneuploidy.
• Recurrent miscarriage: Couples experiencing multiple miscarriages often have genetic factors contributing to pregnancy loss. PGT can help identify healthy embryos.
• Previous IVF failures: If previous IVF cycles have not resulted in a successful pregnancy, PGT can help rule out embryo chromosomal issues as a cause.
• Known carrier of a genetic disorder: If one or both partners carry a specific genetic mutation (e.g., cystic fibrosis, sickle cell anemia), PGT M can prevent passing it on.
• Known carrier of a chromosomal rearrangement: For individuals with translocations or inversions, PGT SR can identify embryos with balanced chromosome complements.
• Severe male factor infertility: In some cases, severe male factor infertility can be associated with an increased risk of chromosomal abnormalities in embryos.

Benefits of PGT

The advantages of incorporating PGT into an IVF cycle can be significant, offering hope and clarity to couples on their fertility journey. These benefits span both emotional and medical aspects of the process.

• Increased implantation rates: By transferring only genetically normal embryos, the chances of successful implantation are significantly improved.
• Reduced miscarriage rates: Many miscarriages are caused by chromosomal abnormalities. PGT helps avoid transferring such embryos, thereby lowering pregnancy loss.
• Higher live birth rates: Ultimately, the goal is a healthy live birth, and PGT contributes to this by selecting the most viable embryos.
• Reduced risk of multiple pregnancies: With higher success rates per embryo, the need to transfer multiple embryos is reduced, thereby lowering the risk of twins or triplets.
• Reduced risk of passing on genetic disorders: For carriers of specific conditions, PGT offers reassurance that their child will not inherit the disorder.
• Decreased emotional and financial burden of repeated IVF cycles: By improving the efficiency of IVF, PGT can potentially reduce the number of cycles needed.

The emotional impact of recurrent IVF failures or miscarriages is profound. PGT can help mitigate this by providing a clearer path forward, offering a sense of control and hope. For individuals navigating the complexities of their reproductive health, Izana provides science backed guidance and personalised support, helping you understand options like PGT.

Disadvantages and considerations of PGT

While PGT offers significant benefits, it is important to consider its potential drawbacks and complexities. Being fully informed about these aspects will help you make a decision that aligns with your values and circumstances.

• Cost: PGT adds an additional cost to the IVF cycle, which can be a significant factor for many couples.
• Risk of embryo damage: Although rare, the embryo biopsy procedure carries a small risk of damaging the embryo, potentially affecting its viability.
• No guarantee of pregnancy: PGT significantly improves success rates, but it does not guarantee a pregnancy or live birth. Other factors can still influence outcomes.
• Mosaicism: Some embryos may contain both normal and abnormal cells (mosaicism). Interpreting these results can be challenging, and their implications for pregnancy are still being researched.
• False positives or negatives: While highly accurate, there is a very small chance of an incorrect result, though these occurrences are rare.
• Ethical considerations: Some individuals may have ethical concerns about embryo selection based on genetic traits.
• Limited scope: PGT only tests for the specific genetic conditions or chromosomal abnormalities it is designed to detect and cannot screen for all possible birth defects or health issues.

It is crucial to have an open and honest discussion with your fertility specialist and a genetic counselor about these considerations. They can provide personalized advice based on your medical history and family planning goals.

PGT success rates

Understanding PGT success rates involves looking at improved implantation rates and reduced miscarriage rates, rather than a guarantee of pregnancy itself. The effectiveness of PGT is best viewed through the lens of selecting the healthiest embryos for transfer.

PGT A Success Rates (Percentage of euploid embryos leading to live birth per transfer)

Maternal Age	Live Birth Rate per Transfer (with PGT-A)	Source
Under 35	Approximately 60 70%	American Society for Reproductive Medicine (ASRM)
35 37	Approximately 50 60%	American Society for Reproductive Medicine (ASRM)
38 40	Approximately 40 50%	American Society for Reproductive Medicine (ASRM)
Over 40	Approximately 20 30%	American Society for Reproductive Medicine (ASRM)

These figures demonstrate that while PGT A significantly increases the likelihood of a successful pregnancy across all age groups compared to transferring un-tested embryos, maternal age remains a critical factor influencing overall live birth rates. It is important to discuss these statistics with your fertility specialist to set realistic expectations.

For PGT M and PGT SR, success is measured by the ability to identify and transfer an embryo free of the specific genetic condition or chromosomal rearrangement. Once a healthy embryo is identified, the subsequent pregnancy rates often align with those of PGT A for euploid embryos, adjusted for maternal age and other clinical factors.

Questions to ask your clinic

Being prepared with questions can empower you to have a productive discussion with your fertility specialist about PGT. Here are some practical questions to consider:

• Is PGT recommended for our specific situation, and if so, which type?
• What are the potential risks and benefits of PGT in our case?
• What is the additional cost of PGT, and are there any financing options available?
• What is your clinic's experience and success rate with PGT?
• How long does it take to get the PGT results, and what happens to the embryos during this time?
• How will mosaic embryos be handled and interpreted?
• Can you connect us with a genetic counselor to discuss the implications in more detail?
• What is the average number of embryos that make it to the blastocyst stage and are suitable for biopsy?

Sources

• American Society for Reproductive Medicine (ASRM)
• European Society of Human Reproduction and Embryology (ESHRE)
• Preimplantation Genetic Testing: A Review of the Current Practice. Front Cell Dev Biol. 2022;10:8900600.

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