Filming human embryos used for in vitro fertilisation (IVF) at an early stage in their development has allowed scientists to select those with the best chance of going on to develop into healthy babies with an accuracy of more than 93%.
Once the technique is available for use in IVF clinics it should eliminate the need to simultaneously implant several embryos into the uterus – a practice used to increase the chances of successful pregnancy. It could also prevent the problems associated with multiple pregnancy, which occurs when several of the implanted embryos go on to develop successfully.
Multiple pregnancies often lead to miscarriage or the need for foetal reduction – surgical removal of some of the developing foetuses. Nadya Suleman, an American known as ‘Octomom’ in the press, is an extreme example of what can happen if a large number of implanted IVF embryos are carried to term – she give birth to octuplets in 2009.
But the survival of Octomom and all eight of her children was extremely unusual. “Most women cannot carry more than two or three embryos to term – it’s very dangerous,” says Renee Reijo Pera, professor of obstetrics and gynecology at Stanford University, who led the study, published in the latest issue of Nature Biotechnology.
The researchers at Stanford and the University of Minnesota filmed 242 embryos developing over six days using microscopic time-lapse photography. They then analysed the images and found that three straightforward parameters gave a very accurate indication of whether each embryo would go on to become a blastocyst – a spherical mass of about 150 to 300 partially differentiated cells – after five or six days. Embryos which reach this stage usually go on to develop into healthy babies.
Successful embryos had an initial cytokinesis, or division of the cell’s cytoplasm, lasting between 0 and 33 minutes, a gap between first and second cell divisions lasting 7.8 – 14.3 hours, and an interval between second and third cell divisions of 0 – 5.8 hours. The pattern was so uniform that it was possible to automate the analytical process, using a computer algorithm to predict whether embryos would go on to develop successfully.
“We’ve often thought of [early embryonic development] as somewhat chaotic, but it’s very controlled,” says Reijo Pera.
The team released several videos, including the one above showing the development of normal (top) and abnormal (bottom) embryos.
This uniformity of the parameters bodes well for clinical use of the technique because the whole process can easily be automated without sacrificing accuracy. “The prediction they’re getting from the three parameters is really impressive. It’s certainly the best of the early indicators so far,” says John Carroll, professor of reproductive physiology at University College London.
Currently most clinics implant embryos three days after fertilisation, but until now methods to determine viability have been unreliable. Waiting until blastocysts have formed around day five or six is also problematic, as the extra time spent in vitro can affect the embryos’ genes. This new method allows a reliable guide to embryo viability on day two. “Success or failure is determined very early,” says Reijo Pera.
The next step will be a large-scale clinical trial, to be carried out by Auxogyn, a US company which has licensed the technology.
Before the publication of this study, remarkably little was known about the early development of human embryos. As well as the surprisingly uniform parameters of early development, the study also showed that success or failure is determined before the embryo’s genome has even been switched on, which happens around the third day, and is likely to be determined mainly by genetic material from the egg, suggesting viability is inherited from the mother. “This is a nice example of maternal messenger RNA driving early development,” says Carroll.
The researchers also examined gene expression profiles of both normal and abnormal embryonic cells and found that while successful embryos show a tight pattern of gene expression corresponding to different developmental stages, the profiles from abnormal cells were very variable. Individual cells within each embryo known as blastomeres were also seen to develop independently of one another – some surviving while others died off. “We had always thought the human embryo was a collection of cells acting in concert,” says Reijo Pera.