Embryo genetic testing: What is it and could it improve your chance of IVF success?
Accredited embryologist and all round IVF whizz, Kirsten explains what it means to have an embryo genetically tested, the benefits, the risks, who it might suit and importantly whether or not it’s likely to improve your chance of pregnancy.
In Vitro Fertilisation (IVF) is a primary treatment for many causes of infertility. Unfortunately even with IVF some patients will not be able to achieve or sustain a pregnancy. A leading cause for this is aneuploid embryos which are simply embryos with the wrong number of chromosomes. The majority of all embryos are genetically abnormal (about 50% overall). The chance of an aneuploid embryo increases with age.
Thanks to current technologies, embryos can be genetically tested before transfer in an attempt to increase success rates and reduce the risk of miscarriage due to chromosomal abnormality. However, recent studies show that this does not actually increase pregnancy rates. Let’s explore this further.
What is PGT-A?
PGT-A is Pre-implantation Genetic Testing for Aneuploidies. This was formally referred to as PGS, or Pre-implantation Genetic Screening. Embryos are created with an IVF cycle as usual:
Controlled ovarian hyper stimulation
Egg collection
Insemination with ICSI (some labs now are able to test IVF embryos)
Embryo culture
Suitable embryos are frozen until more embryos are available or embryos are biopsied and then frozen
Biopsied cells are sent for testing - the DNA of the cells are profiled for a genetic analysis
Test results will show which embryos are genetically normal (euploid) and can be used, or genetically abnormal (aneuploid) and need to be discarded.
Who is this suited to?
Recurrent implantation failure: one cause of multiple unsuccessful cycles may be that the embryos used so far have been abnormal, thus, genetic testing may be helpful.
History of losses: Chromosomal abnormalities are estimated to account for 70% of early miscarriages therefore, patients with a history of losses may be of benefit.
Older patients: The percentage of abnormal embryos increases with age, so older patients may benefit from having their embryos tested. 35 and over is considered to be ‘advanced maternal age’, however a 35 year old is expected to have a higher number of genetically normal embryos compared to a patient in her late 30s or early 40s; over the age of 42, over 80% of embryos are estimated to be abnormal. Genetic testing may be beneficial for this group of patients to deselect those embryos which should not be transferred.
Patients who carry a genetic disease: Patients may be aware prior to treatment that they carry a genetic disease, or may have had to terminate due to a genetic condition in the past. Having multiple embryos genetically tested allows for the exclusion of unsuitable embryos, with the aim of preventing a miscarriage or medical termination.
Benefits
Two of the main expressed benefits are the reduced risk of having a child with a genetic condition and a reduced risk of a chromosomal related miscarriage. As patients get older, the percentage of aneuploid embryo increases, therefore more embryos will be excluded after testing essentially decreasing the number of unsuccessful transfers.
Importantly, embryo quality and chromosomes are independent of each other. What we see sometimes is that with genetic testing, the order of embryos to thaw is changed, the ones we would have transferred first may be genetically abnormal. These embryos are not necessarily poor quality; they may appear absolutely perfect, therefore, where multiple embryos are available genetic testing may reduce the number of transfers needed to achieve pregnancy.
Interestingly, despite these conveyed benefits, studies have not proven to increase implantation rates. Data from the SART (Society for Assisted Reproductive Technology) and STAR (Single Embryo TrAnsfer of Euploid Embryos) studies both showed PGT was found to only help women over the age of 35 years, with implantation rates about 50% irrespective of maternal age indicating a benefit to older patients, but of no help to younger patients and potentially damaging.
Risks
Reliability
In the past, with genetic testing being performed on day 3 embryos with an array called Fluroscence in Situ Hibridisation (FISH), many embryos would incorrectly result as ‘normal’ because an abnormality was in a chromosome which was not part of the limited testing panel.
Current technologies involve a blastocyst biopsy, vitrification to cryopreserve the embryos and then genetic analysis by Next Generation Sequencing (NGS); this allows for assessment of all 23 pairs of chromosomes.
This procedure increases reliability but no test can be 100% accurate, meaning healthy embryos may potentially be discarded. Some embryos are ‘mosaic’ meaning they have a mixture of normal and abnormal cells. These are common and have been shown in many studies to result in healthy pregnancies; however, if these ‘abnormal’ cells are the ones that end up being biopsied, the embryo will end up with an ‘abnormal’ result and be discarded.
Damage to the embryo
There is a risk of damage to the embryo from the biopsy, but it also has to survive the freeze while awaiting test results and then the thaw when it’s time for embryo transfer. Unfortunately, some embryos despite testing as normal, just do not survive the biopsy, freezing and thawing processes. Therefore, there is a risk of perfectly normal/good quality embryos being discarded due to the testing process.
Incorrect diagnosis
Data from the STAR study mention above showed potential embryo wastage in both younger and older age groups and implied a loss of potential component embryos due to wrong diagnosis and/or biopsy related damage. The HFEA (Human Fertilisation and Embryology Authority) has listed PGT-A as RED on its traffic light system of IVF add-ons meaning there is no evidence to convey an increase in live birth rate.
The final word
Careful consideration with your specialist is required before determining what is suitable for your situation.
PGT-A is a great advance in scientific technology. Interestingly though, despite the potential benefits above, studies have not actually proven PGT-A to increase live birth rates. The Human Fertility and Embryology Authority explain that a reduction in miscarriage rates does not lead to an increase in live birth rates and that a reduction in available embryos after testing results may counter any benefit. It is important to note that the review that led to this decision (to make PGT-A red in the traffic light system) was based on live birth rate studies. However, the committee group acknowledge that there IS impact on reduction of miscarriage, particularly in the population of older patients.
As an example: a couple may test their embryos, and find all unsuitable for transfer, thus the transfer of aneuploid embryos that were destined to fail or miscarry has been avoided. However - we haven’t actually increased their chance of a live birth.
With multiple studies failing to show a benefit it is difficult to see the value, it is important to note that most patients do not need to have their embryos tested and their chance of success is good enough without it.
For those groups of patients that have not had success, suffered losses or carry genetic conditions, there are distinct benefits despite the risks involved. Careful consideration with your specialist is required before determining what is suitable for your situation.
You can find Kristen on instagram @ilikemyeggsfertilised
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