Rated red for increasing chances of having a baby for most fertility patients

Rated green for reducing the chances of miscarriage for most fertility patients

What is PGT-A?

PGT-A (previously known as preimplantation genetic screening or PGS) involves checking embryos for abnormalities in the number of chromosomes. Embryos with missing or extra chromosomes (known as aneuploid embryos) have less chance of developing into a baby or, less commonly, may result in a baby being born with a genetic condition. Embryos with the correct chromosome number are known as euploid. PGT-A is therefore offered to some patients as a treatment to help identify euploid embryos and avoid transferring aneuploid embryos. To perform PGT-A, embryologists remove several cells (a biopsy), from the embryo, which are then tested to assess the number of chromosomes they contain. The biopsy result is used to reflect the embryo as a whole. The embryo can still develop with fewer cells, if the removal of cells is done carefully.

Sometimes, the result is reported as mosaic, which means the embryo contains both euploid and aneuploid cells. The proportion of euploid and aneuploid cells can impact the chance of successful outcome if the embryo is transferred. Mosaic embryos may have a lower chance of pregnancy but there are reports of healthy live births after a transfer of a mosaic embryo. There are concerns that mosaic embryos may be discarded if PGT-A analysis looks at only the portion of cells from the embryo that all happen to be aneuploid, when they also contain normal cells and may be able to result in a live birth. Clinics may have different practices regarding testing, reporting and transfer of embryos reported as mosaic so it is important to discuss this with your clinic.

Risks of PGT-A

PGT-A does not carry any additional known risks for the person undergoing fertility treatment. However, PGT-A is known to carry some risks for the embryo:

• Although current PGT-A techniques are mostly very accurate, the test may give the wrong result (it may miss an abnormality or detect one that isn’t there).
• If a test result is not accurate, healthy embryos may be discarded, meaning you may have fewer embryos for transfer.
• In some cases viable embryos could be discarded. This is because not all embryos may be suitable for biopsy, or because embryos are reported as mosaic. Mosaic embryos may have a lower chance of pregnancy but there are reports of healthy live births after a transfer of a mosaic embryo.
• It is also possible that no embryos may be suitable if chromosomal abnormalities are detected in all the embryos tested. This would mean that although PGT-A can reduce the chances of miscarriage, it may not translate to an increased chance in having a baby.
• Embryos can continue to develop successfully after a few cells have been removed, however, removing cells from the embryo may damage it and prevent it from successfully developing.

If you have any questions about the safety and risks, your clinic will be able to discuss whether a treatment add-on would be safe for you to use considering your specific medical history and circumstances.

Evidence

PGT-A is now mostly carried out at the blastocyst stage on day five or six. There is no evidence from randomised controlled trials (RCTs) that PGT-A carried out at this stage is effective at improving your chances of having a baby for most patients undergoing IVF. As it is a selection tool, PGT-A often reduces the number of embryos available for transfer.

There is some evidence that suggests PGT-A may be beneficial for reducing the rate of miscarriage. The evidence that PGT-A can reduce the rate of miscarriage in certain groups of women, particularly older women or women with a history of miscarriage, is a secondary outcome, meaning it was not the main aim of this research, so the study was not designed to investigate the effect of PGT-A on miscarriage rate, which may make these secondary results less reliable. For this reason, it is important to discuss your individual circumstances with your doctor. It is important to keep in mind that this reduction in the rate of miscarriage does not remove the chance of having a miscarriage entirely, as there are other reasons this may occur other than aneuploidy. The NHS page on miscarriage has further information on this. Reducing the chance of miscarriage may also not increase your chance of having a baby and using PGT-A may decrease the chance of having a baby as it often reduces the number of embryos available for transfer.

For some patients, PGT-A may shorten the time to pregnancy (by avoiding a series of embryo transfers). However, the evidence shows that the time to achieving pregnancy for most patients may be longer due to the additional time taken to carry out this test.

Aria’s view

We have, and will continue to offer PGT-A at Aria to selected patients where it may be of benefit. Performing testing on an embryo, does not make the embryo any better so this technique will not change the chances of a livebirth. There may be scenarios where screening can ensure we choose the most appropriate embryo and avoid subsequent failed cycles.

The HFEA’s current stance on PGT-A is in contrast with our own experience and results which show that by performing PGT-A and transferring euploid embryos clinical pregnancy rates (CPR) are increased. Looking at all patients undergoing frozen embryo transfer (own eggs), for 2021-2022 the clinical pregnancy rate per embryo transfer was 41.4% (58/140, all ages combined). For the same period of time, the clinical pregnancy rate per embryo transfer in frozen transfers with PGT-A tested embryos was 51.1% (67/131). The differences between both groups were more significant for patients over 38 years of age: 26% (12/46) vs 51.3% (37/72). We believe that the evidence shows that when used correctly in particular patient groups, PGT-A can be of a significant benefit by reducing the amount of cycles needed to achieve a successful ongoing pregnancy. By reducing the time it takes to achieve this ‘end result’, the impact of treatment both emotionally and physically is alleviated considerably. We do not believe the way we practice PGT-A can worsen time to pregnancy as described by the HFEA.

Recent data also suggests that mosaic embryos give livebirth rates similar to euploid embryos (Capalbo et al, 2021). At Aria we report mosaic embryos and have successfully transferred some with good clinical outcomes (reported together with out PGT-A results on our website. Our patients can access Genetic Counselling to improve their understanding of mosaicism and understand their options ahead of transferring them. With regard to the risk of embryos being incorrectly classified as abnormal, a large study confirmed that no embryos (tested blindly) that were genetically abnormal led to a successful pregnancy. Furthermore, the increased accuracy of testing we now use has increased the proportion of embryos deemed “euploid” and we believe has minimised any risks of error (Tiegs et al, 2021). It is always our intention to provide you with safe effective treatment, personalised to your needs. Further information on PGT-A is available.