To differentiate the specific types of embryo testing, PGT is divided into three subtypes, defined as:
- “PGT for aneuploidies” or PGT-A
PGT-A describes screening embryos for chromosome abnormalities, instead of its previous name ‘PGS’, PGT-A refers to testing embryos by counting the 46 chromosomes to look for extra or missing chromosomes (“aneuploidy”). PGT-A is used to select embryos that are the most likely to implant and result in a successful pregnancy. It also reduces the chance of having a child with extra or missing chromosomes, such as Down syndrome.
- “PGT for monogenic/single gene disorders” or PGT-M
PGT-M describes single-gene PGD. PGT-M is used to help individuals or couples reduce their risk to have a child with a known inherited disorder caused by mutations in a single gene (“monogenic”), such as cystic fibrosis or Huntington’s disease.
- “PGT for chromosome structural rearrangements” or PGT-SR.
PGT-SR is different from PGT-A. In these cases the chromosome abnormalities are hereditary due to one or both parents having a balanced chromosome “structural rearrangement” (such as translocations or inversions). PGT-SR reduces the risk of having a pregnancy or child with an unbalanced structural abnormality, which involves extra or missing genetic material and typically results in a pregnancy loss.
PGT-A
Because the leading cause of pregnancy loss is chromosomal abnormalities in the developing fetus, PGT-A can increase the chances of a successful pregnancy by identifying chromosomally normal embryos for transfer. This article will explain the details of what PGT-A testing is, who are good candidates, associated costs, and more!
- Fast Facts about PGT-A Testing
- What is PGT-A Testing?
- How is PGT-A Performed?
- PGT-A Testing Results
- Candidates for PGT-A Testing
- PGT-A Success Rate and Miscarriage Statistics
- How Much Does PGT-A Cost?
- Other Types of Genetic Testing
- The Bottom Line about PGT-A Testing
- What does the HFEA say?
Fast Facts about PGT-A Testing
- PGT-A stands for Preimplantation Genetic Testing for Aneuploidies and is an embryonic procedure done on IVF embryos that looks at the chromosomes inside the cells of an embryo.
- Embryos are classified with one of three potential results from PGT-A testing; euploid (normal), mosaic (partially normal, partially abnormal), and aneuploid (abnormal).
- As women get older, their chances of getting pregnant decrease. This is largely driven by the increased percentage of abnormal eggs and the resulting aneuploid embryos they produce.
- By identifying abnormal embryos, PGT-A can reduce the chance of miscarriage compare by selectively transferring embryos that have the correct number of chromosomes.
- By identifying the best embryo(s) for transfer (euploid or normal), PGT-A testing can increase the live birth rate per IVF embryo transfer. However, during PGT-A testing, some embryos may be identified as abnormal, which eliminates them from consideration for transfer. As such, it is unclear whether or not PGT-A increases the chance of a live birth per IVF egg retrieval.
- Other types of genetic testing can be performed if the intended parent(s) is at high risk of having a child with a specific genetic disease, or one or both parents has a known chromosomal abnormality.
What is PGT-A Testing?
PGT-A is an embryonic procedure done during the IVF Process that checks the number of chromosomes for each embryo prior to the embryo transfer portion of IVF treatment.
A normal embryo contains 23 pairs of chromosomes, for a total of 46 chromosomes (euploid). 23 chromosomes come from the sperm and 23 from the egg.
Twenty-two of these pairs (autosomes) look the same for both males and females. However, the 23rd pair (sex chromosomes) differ between males and females. This is because females have two X chromosomes in their cells, and males have an X and a Y chromosome in their cells.
The example below shows a normal, or euploid chromosomal count on the left and an abnormal chromosomal count on the right given chromosome 10 has 3 copies as opposed to the two it should have.
Embryos with more or less than 46 chromosomes (aneuploid) can cause IVF transfers to fail, pregnancy loss, or significant health problems for your child.
PGT-A testing can increase the chances for a successful IVF transfer by ensuring embryos have the correct number of chromosomes.
How is PGT-A Performed?
Step 1: Tissue Biopsy
The first step of PGT-A testing is performed after the ovarian stimulation, egg retrieval, fertilization, and embryo development stages of the IVF process. After embryos reach the blastocyst stage of development (approximately 5-7 days after fertilisation), a tissue biopsy is performed, and a small cell sample is taken from each embryo and frozen.
Step 2: Sample Shipping and Embryo Freezing
Next, the tissue samples are shipped to the genetics lab where testing will occur. Meanwhile, the embryos are frozen via vitrification, and they are stored until it is time for the frozen embryo transfer.
Step 3: PGT-A Chromosomal Analysis
After the tissue sample(s) reach the genetics lab, then the PGT-A chromosomal analysis is completed. During the analysis, embryos are screened for chromosomal abnormalities.
Step 4: The Genetics Report
After the analysis is completed, the genetics lab will send a genetics report detailing the status of each embryo, including the number of chromosomes, back to CRGW. One of our doctors will review the genetics report and share the results with the patient.
Step 5: Embryo Selection and Frozen Transfer
Based on the results outlined in the genetics report along with the input from the provider and patient, the embryologist will select the healthy embryo(s) for transfer. The selected embryo(s) will then be thawed for embryo transfer.
If there are remaining embryos, they will stay frozen and stored for use at a later time.
PGT-A Testing Results
PGT-A testing can produce three different types of results for reach embryo:
- Euploid (Normal) – All cells sampled from the embryo have 46 chromosomes
- Mosaic (Mixed) – some cells that were tested in the embryo are normal, some are abnormal.
- Aneuploid (abnormal) – all cells obtained from the biopsy had an abnormal number of chromosomes.
Euploid embryos are the most desired as they produce the greatest chance for a successful pregnancy. Mosaic embryos can have different proportions of abnormal cells. A low-level mosaic embryo has mostly normal cells and a lower percentage of abnormal cells. After euploid embryos have been transferred, or if all resulting embryos come back as mosaic or aneuploid, then mosaic embryos may be considered for transfer.
Research shows that although mosaic embryos result in inferior clinical outcomes compared to euploid embryos, they can result in healthy pregnancies and babies.
Candidates for PGT-A Testing
PGT-A testing can be completed by anyone undergoing an IVF procedure without known genetic diseases. That said, PGT-A is primarily recommended for females over 35 (especially if they have a history of failed IVF implantation or pregnancy loss).
If a patient is considered high risk for passing along a certain genetic disease to their offspring, or if they have a known chromosomal rearrangement, then a different type of genetic testing should be completed (PGT-M or PGT-SR).
Those with Female Partner 35 or Older
As women get older, the percentage of abnormal eggs they produce increases. Eggs with chromosomal abnormalities result in embryos with chromosomal abnormalities. Embryos with chromosomal abnormalities generally do not result in a live birth and thus an increase in maternal age usually results in a lower chance of getting pregnant.
As displayed in the figure below, the percentage of genetically abnormal embryos increases significantly after women reach the age of 35. Therefore, women over the age of 35 may wish to consider PGT-A testing, especially if they have a history of failed implantation or pregnancy loss.
As you would expect, since the percentage of abnormal (aneuploid) embryos increases with age, the percentage of normal euploid and mixed mosaic embryos produced also decreases as these are inversely proportional.
As previously mentioned, euploid embryos are the most desired and produce the highest rate of success per embryo transfer. However, mosaic embryos can also produce viable offspring. Since the proportion of euploid and mosaic embryos decreases over time, it makes sense that live birth rates also decrease as women age, but more on that below.
Fortunately, PGT-A testing can help increase the chances of successful implantation by ensuring that only high-quality embryos with the correct number of chromosomes are transferred.
Other Candidates
Other candidates for PGT-A testing are mainly those at a higher risk of producing irregular embryos, such as:
- Women suffering from recurrent pregnancy loss
- Women who have experienced repeated implantation failure
- Couples where the male partner has severe male factor infertility
PGT-A Success Rate and Miscarriage Statistics
As mentioned above, PGT-A has a powerful ability to see inside an embryo and determine if it has any major chromosomal abnormalities. Because pregnancy loss is often caused by these same genetic abnormalities, PGT-A certainly seems like it should have the ability to reduce pregnancy loss and overall success rates.
While incredibly promising, most data indicates it’s only beneficial for some patient populations and even that isn’t always conclusive. Because of this, it’s important to discuss the pros and cons of PGT-A with your reproductive endocrinologist.
PGT-A to Reduce Miscarriage Rates
Research has shown that abnormal embryos can significantly increase the chances of miscarriage.
Because PGT-A allows you to selectively transfer embryos with a normal genetic profile, the odds of pregnancy loss are generally much lower.
The figure below is an illustration of (from Cooper Genomics) data on how PGT-A testing decreased the rate of miscarriage across age groups – particularly notable is the data as one gets closer to and beyond 40.
That said, the results aren’t always so clear. While a 2018 committee report confirms the above and shows data that PGT-A testing reduces miscarriages, a large 2019 study found no difference.
Given the conflicting data, it’s hard to draw definitive conclusions. That said, most experts lean on the side of caution and appreciate PGT-A as a valuable tool.
Miscarriage can cause both physical and emotional stress for the intended parent(s) and waste valuable time in the pursuit of bringing a child into the world. By decreasing the chances of miscarriage, PGT-A may help protect from the stresses of miscarriage, the amount of time it takes to get pregnant, and as we will see below, increase the success rates of IVF embryos transfers.
PGT-A and Success Rates
A 2015 meta analysis that reviewed several small studies found a benefit in the overall success rate when using PGT-A. Two other studies conducted in 2016 and 2017 found an increase in success rates with PGT-A, but only in females older than 37.
From 2014 to 2017, Cooper Genomics collected data of blastocyst biopsies and transfers. As you can see from the figure below, PGT-A testing and its ability to identify the best embryos resulted in increased live birth rates for women across all age groups. The disparity between live birth rates for IVF without PGT-A and IVF with PGT-A grows noticeably as the female ages.
In 2019, a large study supported a similar notion and found that while there was no difference when using PGT-A testing across ages 25-35, success rates increased from 37.2% to 50.8% in the 35-40-year-old group.
More Issues with PGT-A Success Rate Data
Although the data above seems significant, there are other variables that must be considered. Since PGT-A testing identifies the best embryo(s) for transfer, it makes sense that the live birth rate per transfer would be higher. However, this doesn’t mean the live birth rate per IVF retrievals is higher. In fact, PGT-A actually has the possibility of decreasing the chance of pregnancy per IVF cycle.
A study was conducted between 2012 and 2016 to measure the effects of PGT-A testing on IVF with ICSI success rates for women between the ages of 36 and 40. Of the 396 women that were enrolled in the study, 205 had embryo testing, 191 did not.
After one year, 50 of the 205 (24%) of the women in the PGT-A testing group had a live birth, compared to 45 of the 191 (24%) in the group without PGT-A testing. While there was no statistical difference in the live birth rates between the two groups the number of embryos transferred was significantly lower for the embryo testing group as was the miscarriage rate.
This study highlights the fact that PGT-A testing can result in viable embryos being mistakenly discarded. There are two ways embryos can be mistakenly discarded.
Embryos may be able to correct themselves
While it isn’t yet conclusive, some evidence suggests that mosaic embryos can self-correct and over time, develop into a euploid embryo. Mosaic chromosome abnormalities are common in early human embryos and research has shown mosaic embryos can result in healthy pregnancies.
In a study published by the American Study for Reproductive Medicine (ASRM), 32 women elected to have at least one mosaic embryo transferred. 11 women (34%) had successful pregnancies which resulted in healthy babies.
A non-representative biopsy sample
Another issue that could cause embryos to be mistakenly discarded is due to a non-representative sample being taken from the embryo. Most biopsies only take 5 or so cells compared to 300 or so cells that exist in the embryo in the blastocyst stage. Interestingly one study found that you’d need at least 27 cells from a biopsy to be confident that the biopsy matched the rest of the embryo. The problem is that taking this many cells could fatally damage the embryo.
The below graphic illustrates this problem.
In the example above, the Inner Cell Mass (the part of the embryo that becomes the baby) is normal, and the trophectoderm (the outer ring where the biopsy is taken from ) is mosaic. The example becomes worse if only abnormal cells are removed from what is truly a mosaic embryo with a 100% normal ICM during the biopsy; the PGT-A testing would misclassify the embryo as abnormal and would thus be discarded.
How Much Does PGT-A Cost?
Please see our price lists for current pricing.
What does the HFEA say about PGTa?
The HFEA has a traffic light system for treatment ‘add ons’. You can read about their view on PGTa here. Remember that this is a their view on PGTa and not PGTm or PGTsr.