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A study published in Nature Biotechnology looks at live imaging of late-stage preimplantation human embryos.
Prof Peter Braude, Emeritus Professor of Obstetrics and Gynaecology, King’s College London, said:
“Debate on the efficacy, reliability, and appropriateness of embryo testing (PGT-A) has been raging for nearly 30 years. Advances in genomics have revealed a high frequency of mosaicism within some embryos making the clinical search for ‘euploid’ embryos less certain. This genetic testing was not against a background of abnormal children after IVF, but perhaps more frequent miscarriages.
“This paper confirms that mosaicism may be a normal feature of early embryo in mice and more so in humans, and explains the confined placental mosaicism not infrequently found in CVS samples and placentae.
“The preliminary findings of this recent paper supports 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.
“It has also stimulated a whole new level of patient and physician anxiety with a created need for counselling as to what should be done with mosaic embryos not appreciated previously and transferred or discarded with impunity.”
Dr Emma Lucas, Lecturer in Reproductive Medicine, Division of Clinical Medicine, School of Medicine & Population Health, Faculty of Health, University of Sheffield, said:
Is this good quality work and do the claims in the press release accurately reflect the paper? –
“Yes. This is a renowned group, and the methods and results are well-described in the paper, and the press release is accurate and informative.”
Is this a scientifically significant advance in our understanding of embryo development in IVF?
“Yes, it is. This elegant approach to imaging the embryo has supported the observation of events taking place in the late preimplantation stage that were not previously possible to observe.”
Is it very basic research or can we draw conclusions that will inform IVF clinics?
“This is fundamental research, but that is not to say it can’t inform practice in IVF clinics. A large number of in vitro produced embryos which are tested for chromosomal abnormalities will be discarded on the basis of the results. Previous research has shown that a high proportion of these embryos would go on to result in a successful live birth, and this paper confirms that cells in the outer layer of the embryo remain viable even when they acquire these changes. The other important issue highlighted in this paper is that longer time in vitro does increase the risk of these changes occurring, so that may inform decision-making about when to transfer embryos back to the mother.”
There is a debate about whether IVF ‘add ons’ are worth what patients pay – in money and hope – has this paper got anything to say about these?
“Not addressed directly in the paper, but I suspect this research could contribute to further debate on that topic.”
Does the paper also add evidence that is new about the timing of embryo transfer?
“Not directly, but by identifying that these changes can still occur at later timepoints than previously thought this provides support for reducing the time in culture which is a known risk for the occurrence of these chromosomal errors.”
Prof Alison Campbell, Chief Scientific Officer, Care Fertility and Honorary Professor, University of Kent, said:
“This research is exciting and brilliantly conducted.
“It involved live cell imaging and provided insights into the types of spontaneous errors which occur during cell divisions of the preimplantation human embryo, at a stage which has not been studied this way before. It allowed scientists to visualise errors occurring and study the location and dynamics of them. It does not tell us whether we can prevent them or the impact they may have on the developing embryo.
“We already know that early human embryos often contain cells impacted by errors and that the more affected cells there are, the less likely the embryo will result in a successful pregnancy.
“We also know that such errors in chromosome numbers (aneuploidies), are more severe if they originated in the egg or the first cell divisions, rather than later ones – where this novel research has focused.
“For specific patients, many fertility clinics offer preimplantation genetic testing for aneuploidy (PGT-A) whereby they remove (biopsy) a few cells from the embryo to test for errors in chromosome numbers, often caused by cell division errors. This testing is performed to help select embryos with the highest potential for IVF success and reduce the chance of miscarriage; which the clinical studies largely support. I don’t see this current research impacting current clinical treatment for patients yet either in terms of PGT-A or the optimal day of embryo transfer.
“Whether this new research can help advance practices in the IVF lab remains to be seen but collaboration between researchers and clinical scientists, and patient donation of supernumerary human embryos (from fertility treatments), is essential to continue to improve our knowledge and help further improve outcomes for fertility patients.”
Professor Dagan Wells, Professor of Reproductive Genetics, University of Oxford and Director, Juno Genetics, said:
“The results of the research from Cambridge are very interesting, but don’t actually tell us much about the value of methods such as preimplantation genetic testing for aneuploidy (PGT-A). Understanding the true value of IVF add-ons, such as PGT-A, can only be determined through clinical studies.
“While no medical test can ever be 100% perfect, recent research using the latest PGT-A methods indicates that the result obtained is usually highly predictive of the fate of the embryo. When PGT-A classifies an embryo as abnormal, due to the detection of an incorrect number of chromosomes in a sample of cells, these embryos have greatly reduced chances of producing a successful pregnancy. In one recent clinical study the viability of more than one hundred embryos with an abnormal PGT-A result was determined – none succeeded in producing a baby. This suggests that the losses and duplications of whole chromosomes detected by PGT-A are almost always lethal to the embryo.
“It has also been shown that it is rare for embryos with a normal set of chromosomes, as revealed by PGT-A, to gain chromosome abnormalities later. This means that risks of a pregnancy having the wrong number of chromosomes should be very low when embryos classified ‘normal’ by PGT-A are transferred to IVF patients. In turn, this is expected to lower risks of miscarriage and certain genetic problems such as Down syndrome, caused by the embryo having an incorrect number of chromosomes.
“One of the most important considerations when offering PGT-A to IVF patients is that only modern, well-validated methods should be used. Additionally, there should be a focus on detecting chromosome abnormalities that affect all of the cells in the sample taken from the embryo. The abnormalities seen in the Cambridge study only affect a minority of the cells. Embryos made up of a mixture of normal and abnormal cells are said to be ‘mosaic’. It has been known for many years that mosaic embryos typically have good chances of producing healthy babies. They are frequently transferred to patients and are not routinely discarded.
“In theory, it is possible that a patch of chromosomally abnormal cells could be sampled from a mosaic embryo that has normal cells elsewhere, potentially fooling the PGT-A analysis into thinking the embryo is entirely abnormal. This appears to be the basis for the concern raised by the researchers from Cambridge. However, studies where individual embryos have been sampled and tested multiple times have shown that, in reality, such errors are rare.
“Taken together, multiple clinical studies using modern PGT-A methods have provided increasingly encouraging data concerning its value for patients undergoing IVF treatment. Data generated from studies conducted in the laboratory environment can provide fascinating biological insights, but care is needed in extrapolating such findings to clinical situations.”
Professor Darren K Griffin, GriffinLore Ltd and Honorary Professor University of Kent, UCL, Kasetsart University, said:
“First of all, this is outstanding work, as would be expected from such an excellent group. The technique for labelling embryos and detecting aneuploidy has the potential for wide application. The issue of the mechanisms of chromosome segregation in human embryos is fascinating and this paper is genuinely a seminal one in the field.
“Where the press release falls a little short however is its exposition of a sentence that appears in the discussion, namely “Our findings underscore the urgent need to reassess the clinical utility of PGT-A as its widespread use may be limiting the transfer of viable embryos.” Also, its estimates of the levels of chromosome abnormality in human blastocysts are somewhat out of date compared to what is now being realised from recent research. Work out of the Universities of Maastricht and Leuven are now providing strong evidence that around 80% (and possibly up to 100%) of human embryos have some sort of mitotic chromosome error (often amidst chromosomally normal cells). What we have known for some time is that, when PGT-A detects aneuploidy in 100% of the cells biopsied, the likelihood is that the error arose in the gamete (sperm or egg) and the chances of the embryo developing to a live birth are near zero. Moreover, the chances of pregnancy loss are near trebled. When a “mosaic” result (i.e. some cells normal, some cells aneuploid) is returned, then there is a good chance that the embryo will indeed develop to a live birth, albeit with a slightly lower success rate. Modern methods of detection can now differentiate mitotic from meiotic (those arising in the egg/sperm) errors.
“While, the work of this paper does indeed help inform the work of IVF clinics performing PGT-A, in many ways its great value is providing independent and corroborating evidence for what we already knew (or at least think we did). As for PGT-A “limiting the transfer of viable embryos” I’m afraid that this statement is a little out of date in relation to modern practice. Nowadays, when mosaicism is detected (i.e. the mitotic errors reported in this study) then embryo transfer can be considered (though perhaps deprioritised). In the past, this was not the case. As for the “urgent need to reassess the clinical utility of PGT-A” – this is already occurring through the work of the Human Fertilisation and Embryology Authority (HFEA) scientific and clinical advances advisory committee (SCAAC). This paper will undoubtedly be discussed in such a forum, but in the light of much other well established evidence also.
“Finally, this leads to the issue of IVF “add-ons” – what some would consider a less than complimentary term. The HFEA SCAAC (who deal with “add-ons”) now recommends the use of PGT-A for the reduction of the chances of miscarriage. While PGT-A is currently not believed to improve “cumulative live birth rate” (i.e. will the couple/patient have a healthy baby eventually if they keep trying), evidence from well-designed non-selection trials indicate that the live birth rate per embryo transfer is significantly improved through the use of PGT-A. For many patients, by not opting for PGT-A, they run the risk of delayed time to pregnancy and increased cost of additional embryo transfers. In monetary terms alone, patients therefore need to balance the cost of PGT-A cycles with the cost of potential extra embryo transfers – these costs will vary from clinic to clinic.”
‘Live imaging of late-stage preimplantation human embryos reveals de novo mitotic errors’ by Abdelbaki, A et al. was published in Nature Biotechnology at 10:00 UK time on Thursday 23rd October 2025.
DOI: 10.1038/s41587-025-02851-1
Declared interests
Prof Dagan Wells: Director, Juno Genetics (a company that provides genetic testing services for IVF clinics, including PGT).
Prof Darren K Griffin: Several collaborations and consultancies with IVF clinics and diagnostic labs performing PGT-A.
Prof Alison Campbell: Minor shareholder in Care Fertility.
Dr Emma Lucas: I have no COIs.
For all other experts, no reply to our request for DOIs was received.