PGT-A may overestimate impact of embryo abnormalities

A common IVF 'add-on' – preimplantation genetic testing for aneuploidy (PGT-A) – may may overestimate the impact of embryo abnormalities, new research suggests.

A new imaging technique allowed scientists at the University of Cambridge to observe that some genetic errors appear later in embryo development than previously thought, and are present only in cells destined to become part of the placenta. This means that some embryos flagged as abnormal may still be viable, a discovery that could influence how fertility clinics select embryos for transfer in future.

'Having a baby through assisted conception can be very challenging,' said Professor Kathy Niakan, who led the study, which was published in Nature Biotechnology. 'Most embryos fail to develop or to implant, and even those that are good quality may not be transferred. Much more basic research is needed to inform future clinical practice.'

The researchers aimed to observe embryo development more precisely, since current tests do not fully capture the timing or the location of chromosomal errors that occur. In collaboration with the Francis Crick Institute, London, the researchers developed a live, high-resolution imaging method using fluorescent markers and microscopes, allowing them to watch embryos in three dimensions without damaging them.

Dr Ahmed Abdelbaki, first author of the study, said: 'This is the first time that this very gentle method, with much higher resolution, has been used. It meant that we could watch the embryos as they developed over a two-day period, the longest continuous time that this process has been observed.'

The researchers discovered that some chromosomal abnormalities arise after cells that would ordinarily go on to become the placenta – if the embryo were transferred to the womb and then continued to develop – have already diverged from cells that would ordinarily go on to become the fetus.

PGT-A is an 'add-on' to IVF treatment, and is often offered to older women or those with recurrent IVF failures. It seeks to improve chances of establishing and sustaining a pregnancy, by identifying chromosomally abnormal embryos which are less likely to result in a live birth if transferred to the womb. The method works by carefully removing a few cells from the outermost layer of the embryo, and testing these cells to check that they have the expected number of chromosomes.

The removed cells are taken to be representative of all the cells in the embryo. However, the new research adds to existing evidence that changes in the removed cells may not be present in those parts of the embryo that go on to become the fetus, therefore giving a potentially misleading picture of the embryo's overall viability. As a result, the study suggests, some embryos may be discarded unnecessarily, with potential consequences for patient outcomes and costs.

'The preliminary findings of this recent paper support the concept that the number of "aneuploid" embryos discarded due to errors in diagnosis and/or ignorance of biology is nothing short of scandalous, as many may have had the potential of being that desperately desired healthy child,' said Peter Braude, emeritus professor of obstetrics and gynaecology at King's College London, who was not involved in the study.

While the new imaging technique is unlikely to become a standard clinical test immediately, it provides important insights into early human development. The authors now hope to use a similar approach to see whether the inner cells of the embryo – the precursors of the cells of the fetus – can also develop chromosomal abnormalities later on during development.

The usefulness of PGT-A will be debated at this year's PET Annual Conference – What Does Genomics Mean for Fertility Treatment? – at a session entitled 'PGT-A as an IVF Add-On: 25 Years of Controversy'.

This is an in person only conference, taking place in central London on Wednesday 10 December 2025. Other sessions will explore issues including expanded carrier screening, polygenic risk scores and donor conception. Find out more and register here.