IVF embryo testing technique used commonly may overestimate abnormalities; Cambridge study

A study at the University of Cambridge has found that a widely used test to assess embryo viability for in vitro fertilisation may incorrectly classify embryos as abnormal, after researchers observed that chromosomal errors can arise later in development than has been previously believed

A study at the University of Cambridge, United Kingdom, has suggested that a commonly used test employed by fertility clinics to assess embryo viability may overestimate the number of embryos with abnormalities. The findings indicate that the test may detect errors in cells that later go on to become the placenta rather than a foetus. Some embryos created for in vitro fertilisation (IVF) treatment are therefore discarded at an early stage when they could have been viable.

The research team from the Loke Centre for Trophoblast Research, working with colleagues from the Francis Crick Institute, St Pancras, London, has used a novel real-time imaging technique to observe human embryo development at high resolution. The results reveal that chromosomal abnormalities can occur at a much later stage of development than previously believed.

When an egg becomes the zygote following its fertilisation by a sperm, it divides repeatedly as each cell copies the parental DNA. This process produces a hollow ball of cells called a blastocyst. At around six days following fertilisation, the blastocyst implants itself into the uterus’ lining with its outer layer forming the placenta and its inner cells becoming the foetus.

Assisted conception techniques such as IVF have become increasingly common but success rates have remained low. Before embryo transfer, many clinics test for chromosomal abnormalities known as aneuploidy, in which some cells contain an incorrect number of chromosomes. When these abnormalities are detected, embryos are deemed to be non-viable and discarded. Pre-implantation genetic testing for aneuploidy is typically offered to older women and to patients who have experienced recurrent miscarriages or a number of IVF failures. Its reliability, however, has long been questioned.

“Having a baby through assisted conception can be very challenging,” said Professor Kathy Niakan, director of the Loke Centre for Trophoblast Research and co-chair of Cambridge Reproduction.

“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 and improve the rates of [successful] assisted conception,” she said.

To gain clearer insight into early embryo development, Professor Niakan’s team developed a high-precision imaging method to observe embryos live and in three dimensions without damaging them. The approach involved tagging DNA inside the cell nucleus with a fluorescent protein and observing development with light-sheet microscopy also called selective plane illumination microscopy.

“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,” said Dr Ahmed Abdelbaki, a postdoctoral researcher at the Loke Centre and first author of the study.

“The design of the microscope allows for multiple embryos to be watched simultaneously and from both sides.

“This has allowed the team to catch events that have previously been missed. It’s a proof of the power of direct observation to uncover unexpected findings in human biology,” added Professor Ben Steventon from the Department of Genetics at the University of Cambridge, and a co-author.

The research has revealed that abnormal cell divisions can begin at a surprisingly late stage of human development.

“We were extremely surprised to discover that abnormal cell divisions can happen from scratch at a very late stage of human development.

“It was only by using a new imaging technique that it was possible to see this happening,” Professor Niakan said.

In 13 embryos analysed, around 10% of cells displayed chromosomal abnormalities. These appeared to arise when DNA was incorrectly copied during cell division, for example when chromosomes failed to separate properly or when a cell divided into three rather than two.

Given that these errors occurred relatively late in development, they were confined to the outer layer of the blastocyst, which forms the placenta. It is from this layer that samples for pre-implantation genetic testing are typically taken, suggesting that current tests may misclassify otherwise healthy embryos that are enclosed by the blastocyst.

Professor Niakan’s group is now investigating whether similar late-arising abnormalities can occur in the inner layer of the blastocyst which becomes the foetus.

All embryos used in the study were donated by families who had already enjoyed successful pregnancies following IVF treatment at Bourn Hall Clinic, Cambridge, or at a Create Fertility IVF clinic at other locations in the UK.

For further reading please visit: 10.1038/s41587-025-02851-1