When Prof Simon Fishel converses excitedly about a new piece of high-tech equipment, the world of assisted reproduction would be wise to take note. 

An internationally distinguished specialist in the field of fertility treatment, he has been at the forefront of many key scientific firsts in the field of embryology and infertility since his time on the team that assisted the birth of the first in vitro fertilisation (IVF) or ‘test tube’ baby in 1978.

The device inspiring the eminent embryologist’s rush of enthusiasm is a ‘super incubator’ called the embryoscope, a closed and controlled culture environment that allows for continuous monitoring and observation of up to 72 embryos at a time, using a microscope with built-in camera for automated time-lapse imaging. 

A number of separate studies have found that the embryoscope can increase the success rate of IVF by up to 20%, and can also achieve 15% higher survival of embryos than traditional incubators. 

The embryoscope has not only raised the bar for optimising the environment in which embryos develop, its time-lapse-enabled embryo assessment has also opened up unique opportunities to develop new parameters for future embryo scoring and selection. Many argue that it could offer the IVF industry a paradigm shift, leading to higher pregnancy success rates and improved value for clinics and patients. 

New model for embryo selection

Prof Fishel, who is managing director of the CARE Fertility Group, was in Dublin recently to promote a groundbreaking innovation that combines this time-lapse imagery and a new selection model, devised by him and his team at CARE Fertility clinics in the UK and Dublin, that predicts which embryos have the greatest potential for a successful pregnancy. Their research, published in the journal Reproductive BioMedicine Online, demonstrated a 56% uplift in live births, equivalent to a 78% live birth rate.

“I think it’s probably the most exciting breakthrough since I’ve been doing IVF and I’ve been doing IVF since the very beginning,” he tells Modern Medicine. “For me the embryoscope is one of the most exciting developments because it’s for all patients. 

“We have had lots of advances in IVF over the years that help particular types of patients – genetic testing or sperm injection, for example – but this is going to be useful for all patients because, irrespective of what treatment you’re having, you can give your embryos the best culture environment possible by putting them into the embryoscope.

“I call it the ‘super incubator’. Fundamentally, it is an incubator that provides the required ambient conditions for which embryos needs to grow. It maintains temperature, it controls the gas environment, and the beauty of this instrument is that it is a closed system; it doesn’t need to be opened at all during the culture of the embryos, which can be up to five or six days. It takes up to 12 embryos per patient, and up to six patients simultaneously, so it can take up to 72 embryos.

“While they’re in this protected environment, the embryos can be constantly monitored by a microscope. It’s a bit like having a camera on an embryo growing in the womb where it’s undisturbed, that’s very important. 

“It can focus through seven focal plains of the embryo and takes an image every 10 minutes or so, which is over 5,000 images displayed over a period of five days without disturbing the embryo, and these images can be projected onto whatever screen you want, a computer monitor or even your smartphone,” he explains.

In contrast, standard incubation requires the removal of the embryos from the incubator for assessment of embryo development, recording approximately six images over five days, basically ‘snapshot’ glimpses at defined time points in order to minimise disturbances to culture conditions. 

However, embryo development is a dynamic process and a wealth of information about embryo development history remains untapped.

Seeing new possibilities

“The embryologist can only get a subjective view of how the embryo is doing from a single static image. 

“What we now have are 5,000 images with objective parameters telling us what is happening to the embryo during its culture period. It’s revealing secrets to us about embryo development during the first five days after fertilisation that we never knew existed. 

“We’re seeing a single cell going to three cells without ever going to two cells, and a three or four cell reverting back to two cells or three cells, all of which we know are problematic now but we didn’t know existed at that level before. It’s quite staggering,” says Prof Fishel.

These time-lapse images allowed the CARE researchers to ‘screen’ embryos for delays at defined time points that could indicate risk of abnormalities in chromosomes. This non-invasive model for ploidy (a way to count chromosome sets) classification could then be used to select the low-risk embryos for implantation. 

“Why bother looking at chromosomes, why is that important? About 70% of embryos that are conceived naturally or through IVF don’t make babies – we’re not very efficient as a species – and the most common reason is because they have chromosomal abnormalities, also known as ‘aneuploidy’. 

“An embryo that ends up with three copies of chromosome 21, instead of the normal two, will develop Down’s syndrome, and three copies of chromosome 13 or 18 will go on and produce babies but with severe consequences – all the other chromosome errors will result as miscarriage or even failure to implant. 

“Given that it’s the largest single cause of IVF failure or miscarriage this becomes the most important element to try to discover in embryos.

“Until our discovery, we had no means to look at chromosomes except for a very expensive technology, an invasive procedure called embryo biopsy. 

“In routine IVF practice, embryologists worldwide could not differentiate between chromosomally viable and chromosomally abnormal embryos, and have been unwittingly and unintentionally transferring embryos that are not viable. 

“What we now have is a combination of time-lapse images and morphokinetic algorithms relating to ploidy, telling us objectively which embryos have the highest potential for live birth, down to the lowest potential for live birth,” he remarks.

Prof Fishel calls the new system Morphokinetic Algorithms to Predict Success (MAPS), and it is available to patients in Ireland at Beacon CARE Fertility, located in the Beacon Medical Campus in Dublin.

MAPS – what is it?

“Morphology is the shape or appearance of cells in the embryo. The time at which it reaches a particular stage is its kinetics, so embryos have to reach certain positions at certain times for us to give it a quality score, that’s morphokinetics. 

“Our time-lapse studies have revealed many secrets about the viability of embryos as they develop through the early stages, information we could never obtain by routine IVF culture. What we now know is that morphokinetics differ depending on whether the chromosomes were normal or abnormal,” he adds.

In a study of 69 couples at the CARE fertility clinic in Manchester, the researchers found that 11 babies were born from the low-risk group (61% success rate) compared to five from the medium-risk group (19% success rate) and none from those deemed high risk.

“We also found that, using our algorithms and the embryoscope, the data were holding up across an age range. 

“If we put back a euploid, which has a balanced set or sets of chromosomes, into an older woman, we saw a live birth rate that was similar to women of a younger age. 

“So, clearly that was the key problem for women approaching or into their 40s; it wasn’t the womb, it wasn’t hormones, it was the fact that they were producing eggs that were chromosomally abnormal. 

“In the 35 years I have been in this field this is probably the most exciting and significant development that can be of value to all patients seeking IVF,” stresses Prof Fishel. 

“Continuous incubation technology is more protective of the embryo, it is non-invasive and the fact that it is highly predictive of successful outcome suggests that we have a paradigm shift in the way IVF will be conducted in the future. 

“I have no doubt that the use of MAPS technology and further advances in time-lapse imaging will be of great benefit to all patients requiring IVF treatment.”