Genetic Testing for IVF: PGT (formerly PGS & PGD)
Embarking on the journey of in vitro fertilization (IVF) can be an emotionally charged and transformative experience for individuals and families seeking to have children. In recent years, advances in reproductive technologies have introduced several types of genetic testing to make the process easier. One invaluable tool is called preimplantation genetic testing (PGT), which offers a wealth of possibilities for prospective parents. PGT is a biopsy to sample a few cells from embryos created through IVF before they are transferred back into the uterus. PGT can provide parents with a comprehensive understanding of their embryos, enabling informed decisions to greatly enhance the chances of a successful pregnancy and the birth of a healthy child. Another type of genetic testing is Carrier Screening, a series of blood tests performed on intended parents to assess whether they carry genes that might result in the birth of a baby with specific genetic conditions. This information helps individuals and families considering pregnancy to make considered decisions before attempting pregnancy on their own or with IVF. In this article, we will discuss:
- The intricacies of genetic testing for IVF
- The benefits of genetic testing
- The different types of PGT tests
- The considerations that individuals and families should bear in mind when considering this procedure
New Names for PGD and PGS Tests: Preimplantation Genetic Testing (PGT)
- The new name for all tests is Preimplantation Genetic Testing (PGT).
- When done for aneuploidies (abnormal number of chromosomes), it is PGT-A
- For monogenic/single gene defects, PGT-M
- For chromosomal structural rearrangements, it is PGT-SR.
What was called PGD is now PGT-M and what was called PGS is now PGT-A or PGT-SR. It will likely take several years for the new names to take hold, so it is important to be aware of both naming conventions now.
When Is PGT Recommended?
PGT is indicated in various situations to help increase the chances of a successful pregnancy and reduce the risk of certain genetic conditions. It is typically recommended in the following scenarios:
Advanced Maternal Age
A healthy human embryo typically contains 46 chromosomes. These chromosomes are organized into 23 pairs, with one set coming from each parent. Aneuploidy can lead to failed implantation, miscarriage, or certain genetic disorders (e.g., Down syndrome, Edwards syndrome, and Turner syndrome). PGT-A helps identify chromosomally normal embryos for transfer, increasing the chances of a successful pregnancy.
PGT-A testing is often recommended for women of advanced maternal age (typically 35 years or older) because the risk of aneuploidy in embryos increases with age. PGT-A generally tests for the number of chromosomes, specifically extra or missing chromosomes. It is most helpful for women in their late 30s or early 40s who have many embryos, helping them choose an embryo with a normal number of chromosomes to transfer into the uterus. If there is only a small number of embryos, the benefits of the test are usually outweighed by the disadvantages. In younger women (35 years or less) most embryos have a normal number of chromosomes and PGT has been shown not to be beneficial for most intended parents.
Although the topic remains controversial, it is important to acknowledge how PGT can be utilized for sex selection to achieve family balancing. While PGT raises numerous ethical considerations, it also presents prospective parents with the opportunity to prioritize their ultimate goal—a healthy and fulfilling family.
PGT-SR is specifically designed to detect structural abnormalities within individual chromosomes, such as translocations, inversions, deletions, or insertions. When there is an abnormality in these rearrangements, it can lead to developmental delays, learning disorders, physical challenges in children, or an increased risk of miscarriage during pregnancy. Choosing embryos that do not have structural rearrangements reduces the risk of miscarriage or chromosomal disorders in offspring.
Recurrent Pregnancy Loss
Prospective parents who have experienced multiple miscarriages or pregnancy losses may opt for PGT-A and PGT-SR testing to identify embryos with normal chromosome numbers and without structural rearrangements. This can improve the chances of a successful pregnancy. It is important to note that PGT cannot provide the answers for or prevent all miscarriages. It is often helpful to do genetic testing on tissue obtained after a second or third miscarriage to see if chromosome problems caused or contributed to the event.
Prospective parents with a known family history of genetic disorders may choose PGT-M testing to screen embryos for specific genetic conditions. This allows for the selection of embryos free from the identified genetic disorder. If carrier screening is conducted, the results may indicate the presence of recessive disorders in the parents that could be passed on to the child or dominant disorders that will be passed on; these are conditions that will be specifically tested for during PGT-M.
Common conditions for which PGT-M is performed include cystic fibrosis, muscular dystrophy, and hemophilia. PGT-M also offers hope for prospective parents who have a child with diseases like leukemia and require a hematopoietic cell transplant. When there are no suitable matches within the family, embryos can undergo HLA typing, allowing the transfer of embryos that are a match for the affected sibling. Cord blood from the IVF pregnancy can then be utilized for the transplant procedure.
The decision to undergo PGT testing is highly personal and should be made in consultation with healthcare professionals, including genetic counselors and fertility specialists.
Carrier screening describes genetic testing performed on an individual who does not have any overt physical finding for a genetic disorder but may have one variant allele within one or more genes associated with a diagnosis. Carrier screening is performed on prospective parents before they become pregnant, either by trying on their own or undergoing IVF. It involves assessing the carrier status of the parents for specific recessive disorders, even if they do not exhibit any signs or symptoms of the disorders themselves.
Carrier screening can now be done for many genes, even hundreds, at one time using Next Generation Sequencing (NGS). This is called expanded carrier screening (ECS). Other important terms include:
- PGT-P: preimplantation genetic testing for polygenic risk.
- Polygenic risk scores (PRS): the results of the findings of PGT-P tests.
- PRS: An estimate of an individual’s risk of developing an adult-onset, multifactorial condition by looking at the combination of specific genetic variants. This type of testing commonly identifies variants of unknown significance (VUS).
- VUS: A change in a gene’s DNA sequence that has an unknown effect on a person’s health. There is usually not enough information about a VUS to know whether it increases a person’s risk of developing a disease, such as cancer.
Deciding on PGT and Carrier Screening
By identifying whether they carry a mutation in a particular gene associated with a recessive disorder, potential parents can make informed decisions about family-building and explore options such as genetic testing of the embryos during IVF.
PGT and carrier screening are very important advances in clinical medicine. However, these technologies are not perfect or comprehensive for all diseases, and we still have incomplete understanding of some findings. It is essential for everyone to consider carefully whether and how to use PGT and carrier screening, and to do so in consultation with a genetic counselor.
How Long Does PGT Testing Take?
The duration of genetic testing for IVF can vary depending on the specific type of testing and the laboratory conducting the analysis. In general, the process can take several weeks to complete. PGT-A typically takes around 1-2 weeks, while PGT-M and PGT-SR may require 2-4 weeks or longer, depending on the complexity of the genetic analysis involved.
To accommodate the time required for PGT testing, IVF treatments almost always involve freezing and storing the embryos for several weeks while the sample of cells (about 3 to 8) that have been biopsied from them are tested. After the biopsy results are received, parents can choose the best embryo for transfer and doctors can perform a frozen embryo transfer (FET).
Potential Risks of PGT
PGT carries several risks, including:
- A small chance of false positives or false negatives, leading to incorrect diagnoses of the embryo’s genetic condition.
- The invasive nature of PGT, which involves removing cells from the embryo for analysis, poses a risk of potential damage to the embryo during the biopsy process.
- The biopsy itself may decrease embryo viability, although the risk is generally low.
- PGT has limitations in genetic screening and can only target specific conditions. It may not detect all possible genetic disorders or variations, including complex conditions.
- Ethical concerns arise from discarding embryos based on their genetic characteristics, raising debates about “designer babies” and the ethical value attributed to certain genetic traits.
The Process of Genetic Testing for IVF
During PGT, a specialized biopsy technique is used to extract a small sample of cells from the outer layer of the embryo, known as the trophectoderm. This process allows for the collection of an adequate amount of genetic material for analysis while ensuring the embryo’s viability for future transfer.
Here is an overview of the genetic testing process during an IVF cycle:
Consultation with a Fertility Specialist
Patient counseling is an essential step in the PGT process, ensuring informed decision-making. If carrier screening is indicated, it will take place prior to starting the IVF cycle.
The person providing the eggs receives medication to stimulate the production of multiple eggs within their ovaries.
The eggs are surgically retrieved from the parent’s ovaries using a minor procedure performed under anesthesia.
The eggs are fertilized with sperm in a laboratory dish to create embryos.
Around the fifth or sixth day of embryo development, during the blastocyst stage, a small number of cells are removed from each embryo for genetic testing. The biopsy samples are then shipped to the lab for testing.
The embryos are cryopreserved for frozen embryo transfer (FET). A FET is required when preimplantation genetic testing is requested.
Once the biopsy samples are received at the lab, the extracted cells undergo genetic analysis to identify any abnormalities or specific genetic conditions.
The embryos are assessed based on genetic testing results, and the healthiest is chosen for transfer. Almost always only a single embryo is transferred (called SET) when an embryo has been tested and is euploid (normal number of chromosomes). This is done to limit the chance of multiple pregnancy, which carries a higher risk for both the mother and babies.
The selected embryo is transferred into the parent’s uterine lining using a thin catheter.
How Much Does PGT Cost?
The cost of PGT can vary depending on several factors, including:
- Fertility clinic
- Type of PGT (PGT-A, PGT-SR, or PGT-M)
- Number of genetic disorders being screened
- Number of embryos being tested
- Additional services or tests included in the package.
Carrier Screening is an additional cost. Some Fertility Clinics offer bundled IVF packages that include PGT-A testing.
PGT-A and PGT-SR Test Costs
The average cost of PGT-A ranges from $2,250 to $4,000 per cycle. This includes the biopsy of embryos, laboratory processing, and the analysis of the chromosomes to identify any aneuploidies or abnormalities in the number of chromosomes.
PGT-SR typically costs more than PGT-A due to the additional complexities involved in detecting structural rearrangements within individual chromosomes. The cost of PGT-SR can range from $5,000 to $7,000 or more per cycle, including the specialized testing techniques required to identify specific structural abnormalities.
PGT-M Test Cost
The cost range for PGT-M (Preimplantation Genetic Testing-Monogenic) can vary depending on the specific genetic disorder tested for and the number of mutations that need to be analyzed.
On average, the cost of PGT-M falls between $7,000 and $12,000 per cycle. This cost includes the biopsy of embryos, laboratory processing, and the analysis of specific gene mutations to identify any genetic disorders or abnormalities the embryos may carry.
This price can be influenced by the complexity of the genetic disorder being tested, as well as the number of specific mutations that need to be examined.
What Is the Cost of Carrier Screening?
The cost of carrier screening can vary depending on several factors, including insurance coverage and the specific tests performed. In certain cases, individuals with insurance may be able to undergo carrier screening for as little as $100. Note that the cost can range up to $2,000 or more, particularly when additional tests or panels are included.
The Cost of IVF, Medications, and Other Services and Procedures
In addition to the PGT costs, factor in the cost of the IVF procedure (ovarian stimulation, egg retrieval, embryo transfer), fertility medications, consultation fees, and any other required laboratory or diagnostic tests. These costs can vary significantly.
PGT Consultation with a Fertility Specialist
PGT empowers individuals and families with vital information about the health and genetic makeup of embryos, allowing them to make informed decisions and significantly improve their chances of a successful pregnancy. While PGT offers numerous benefits, it is crucial to approach this process with careful consideration and consultation with fertility experts.
Consulting with a fertility specialist provides an opportunity to discuss the benefits, limitations, and implications of carrier screening, expanded carrier screening, and each type of PGT test. The specialist will also address any concerns or questions raised by patients, ensuring a clear understanding of all potential outcomes and the role of genetic testing in their journey towards starting or expanding their family.
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