Preimplantation Genetic Testing for Aneuploidy (PGT-A testing) in IVF

What is Preimplantation Genetic Testing for Aneuploidy (PGT-A testing) in IVF?

Preimplantation Genetic Testing for Aneuploidy (PGT-A) in IVF involves testing embryos to check whether they have the expected number of chromosomes.

• Preimplantation Genetic Testing for Aneuploidy (PGT-A) is a screening test to check how many chromosomes an embryo has. Chromosomes are packages of DNA in each cell in our body. Embryos typically have 23 pairs of chromosomes (46 in total) in each cell.
• Euploid embryos have the expected number of chromosomes (46 chromosomes).
• Aneuploid embryos have too many or too few chromosomes. A missing chromosome is referred to as a monosomy (one copy), and an extra chromosome is referred to as a trisomy (three copies).
• Segmental aneuploidy is when only a specific segment or part of a chromosome is duplicated or deleted, rather than the whole chromosome.
• Aneuploid embryos are usually unable to lead to a successful pregnancy and can be associated with low pregnancy rates, miscarriage, or the birth of a baby with a chromosome condition. An example is Down syndrome (trisomy 21), a condition caused by an extra chromosome.
• Embryos with extra or fewer chromosomes are common. The percentage of embryos that are aneuploid increases with female age.
  • Among 30-year-olds, 20-30% are aneuploid.
  • Among patients over 40, more than 50% are aneuploid.
  • At 45 and older, over 90% are aneuploid.
• The PGT-A process requires taking 3-10 cells from an embryo which has 70-150 cells – this is called an embryo biopsy. All embryos are frozen while waiting for the PGT-A test results. The cells are taken from the outer layer of the embryo called the trophectoderm (see illustration below). These cells become the placenta in a pregnancy. The cells are analysed to determine whether they have the expected number of chromosomes.
• PGT-A was previously called preimplantation genetic screening (PGS) and is sometimes referred to as PGT.

Why might PGT-A improve IVF outcomes?

PGT-A is not intended to increase the chance of getting pregnant. It aims to reduce the chance of transferring an embryo with an extra or missing chromosome. This may:

• Reduce the chance of negative outcomes of aneuploid embryos, such as implantation failure, miscarriage, and the birth of a baby with a chromosome condition.
• Reduce the time and number of transfers it takes before the patient gets pregnant. In this way, it could help patients to get pregnant and have a baby faster.
• Reduce the costs of undergoing repeated embryo transfer cycles.

Why might PGT-A not improve IVF outcomes?

• PGT-A is not 100% accurate, and there is a small chance of an incorrect result, known as false positives or false negatives, leading to incorrect identification of euploid and aneuploid embryos. An incorrect result occurs in less than 5% of biopsies.
• PGT-A test result may come back as ‘inconclusive’. Sometimes the patient or clinic might decide not to transfer an ‘inconclusive’ embryo. If the embryo was actually euploid, the patient may lose an opportunity for a successful embryo transfer.
• Only a small sample of cells are taken from the embryo. While the accuracy of this result is usually high, it is possible that the sample of cells taken will not be an accurate reflection of the rest of the embryo. For example, the biopsy could happen to sample part of the embryo that is aneuploid, when the rest of the embryo is actually euploid.
• The cells of a blastocyst embryo are grouped into two parts: the inner cell mass and the trophectoderm (see Figure below). The trophectoderm cells will develop into the placenta. The inner cell mass will develop into the baby. The PGT-A process takes cells from the trophectoderm of the embryo, so that it does not disturb the cells that will go on to form the baby. However, these cells are not necessarily an accurate reflection of the cells in the inner cell mass. Studies have shown that a euploid or aneuploid PGT-A result on a trophectoderm biopsy sample is very likely to match the rest of the embryo. However, it is not possible to make this same prediction for a mosaic PGT-A result because the inner cell mass could be euploid, aneuploid, or mosaic.
• The embryo could be damaged during the biopsy process. This is more likely if the embryo is low grade (based on its morphology or shape), but may also occur in high grade embryos.
• Some embryos may not survive the freezing and thawing process required for PGT-A, reducing the number of suitable embryos for transfer. Approximately 2-5% of embryos do not survive the freezing and thawing process. However, it is important to remember that freezing and thawing embryos is a standard and widely used practice in IVF.

Who might consider PGT-A testing for IVF?

People who have experienced

• Older female age
• Recurrent implantation failure
• Recurrent miscarriage

Does PGT-A testing in IVF work? What the evidence says

Cumulative outcomes from multiple embryo transfers

It is unclear whether PGT-A affects the overall chance having a baby from multiple embryo transfers, both fresh and frozen. Only three trials followed up the participants for multiple embryo transfers. The evidence is considered very low-quality because the studies reported very different results and the results are imprecise. In addition, the studies had important design limitations: the studies did not test all the embryos in the PGT-A group, and they did not follow participants for all relevant embryo transfers. This doesn’t reflect how PGT-A is typically done in real-life practice, where all embryos are usually tested and all euploid embryos are transferred.

PGT-A may decrease the overall chance of getting pregnant from multiple embryo transfers. Two trials followed up participants for multiple embryo transfers. The evidence is considered low quality because the studies did not test all the embryos in the PGT-A group, and they did not follow participants for all relevant embryo transfers. This doesn’t reflect how PGT-A is typically done in real-life practice, where all embryos are usually tested and all euploid embryos are transferred.

It may seem surprising that PGT-A appears to decrease the overall chance of getting pregnant from multiple embryo transfers. It may be because the existing studies did not use an optimal design, or it may be because PGT-A really doesn’t offer any benefit for these outcomes. See ‘why might PGT-A not improve IVF outcomes’ above.

Outcomes from the first embryo transfer of an IVF cycle

When considering just the first embryo transfer of an IVF cycle, it is unclear whether PGT-A affects the chance of having a baby, however it appears to have no effect on the chance of getting pregnant. PGT-A does appear to reduce the chance of miscarriage. This is based on the results of seven trials; the evidence is rated as moderate quality because the studies mostly included younger participants who had many good-quality embryos. This may not represent the typical group of people offered PGT-A in Australia, as it is often used by older people with fewer embryos.

It may seem surprising that PGT-A appears to have no effect on the chance of getting pregnant from IVF. It may be because the existing studies did not use an optimal design, or it may be because PGT-A really doesn’t offer any benefit for these outcomes. See ‘why might PGT-A not improve IVF outcomes’ above.

Side effects of PGT-A

Side effects are not usually relevant for lab-based optional extras like PGT-A.

However, each additional handling step in the IVF lab, including the biopsy of an embryo, adds some level of potential risk. There is a very small chance of damaging the embryo during the biopsy procedure.

Risks of PGT-A testing and long-term outcomes

There are no known risks or long-term harms related to taking a biopsy of the embryo for PGT-A.

PGT-A requires a frozen embryo transfer. Compared to a fresh embryo transfer, some types of frozen embryo transfer where medication is used thicken the uterine lining, may be associated with some risk. These are risk related to a frozen transfer, rather than PGT-A itself.

Compared to a fresh embryo transfer, PGT-A and frozen embryo transfer may be associated with an increased risk of

• Pre-eclampsia and other hypertensive disorders of pregnancy
• High birthweight or babies that are larger than normal at birth

Compared to a fresh embryo transfer, PGT-A and frozen embryo transfer may be associated with a reduced risk of

• Ovarian hyperstimulation syndrome (OHSS).

This is based on data from randomised controlled trials and input from IVF specialists. Possible risks of harm and long-term outcomes are often not reported in randomised trials and therefore it is unknown whether PGT-A poses any other risk of harm to the IVF patient or the embryo/baby.

Earlier versions of PGT-A technology have been used in Australia since approximately 2004. PGT-A using Next-Generation Sequencing has been used in Australia since 2014, and approximately 60,000 IVF cycles have used PGT-A with next-generation sequencing.

Cost of PGT-A testing in IVF

PGT-A usually costs between $500-1,000 AUD per embryo, which includes the cost to biopsy and test the embryo. In Australia, there is currently no Medicare rebate for PGT-A (although PGT-M and PGT-SR are covered by Medicare).

Cost information is indicative only, costs can vary from clinic to clinic and depending on different circumstances.

Practical considerations about PGT-A testing

• PGT-A is often considered when patients have multiple embryos, as it aims to help prioritise which embryos to transfer first. For people with few embryos, it may not be as useful for decision making.
• Some patients may not have any embryos suitable for biopsy. Different IVF clinics will have different criteria that they apply to decide whether embryo biopsy is a suitable or possible option, and some embryos may not meet this criteria.
• All embryos must be frozen while waiting for the PGT-A test results, which means a fresh embryo transfer is not possible unless an untested embryo is transferred, or a tested embryo that was created in a previous cycle is transferred. Because of this, PGT-A adds time to the IVF cycle and results in a delay of about 1-2 months. Some Australian clinics send the embryo biopsy overseas for PGT-A analysis, while the embryo remains frozen at the clinic.
• PGT-A is available in all states in Australia, however there are restrictions on who can access PGT-A in WA.

Unsure about some of the terms we have used? Use our glossary to understand scientific or unfamiliar terms.