Pulsations reveal which embryos have the best chance of success in IVF

A new method of predicting the chances an embryo will survive has shown promise in tests on mice and could one day be used on humans to boost IVF success rates, UK scientists have said.

Summary:

“Fertilization-induced cytoplasmic flows are a conserved feature of eggs in many species. However, until now the importance of cytoplasmic flows for the development of mammalian embryos has been unknown. Here, by combining a rapid imaging of the freshly fertilized mouse egg with advanced image analysis based on particle image velocimetry, we show that fertilization
induces rhythmical cytoplasmic movements that coincide with pulsations of the protrusion forming above the sperm head. We find that these movements are caused by contractions of the actomyosin cytoskeleton triggered by Ca2 + oscillations induced by fertilization. Most importantly, the relationship between the movements and the events of egg activation makes it possible to use the movements alone to predict developmental potential of the zygote.

In conclusion, this method offers, thus far, the earliest and fastest, non-invasive way to predict the viability of eggs fertilized in vitro and therefore can potentially improve greatly the prospects for IVF treatment”

The big picture:

Movements inside fertilised eggs created in IVF could provide a quick, non-invasive way to identify which to implant

Scientists have developed a technique that could significantly improve the success of IVF pregnancies by looking for telltale movements within fertilised eggs before they are implanted. The method could also cut the frequency of multiple births often associated with IVF, which are known to increase health risks both for the babies and their mothers.

In a normal cycle of IVF treatment, fertilised embryos are implanted after around three days in culture. Embryologists look for abnormalities in the eggs as an indicator of how well each is progressing and how successful a pregnancy might be.

Because of the uncertainties involved, several embryos are often implanted at once. This can lead to twins or triplets, which increases the potential health risks and risk of miscarriage.

Professor Magdalena Zernicka-Goetz of the University of Cambridge led a team of researchers to look for ways to assess fertilised embryos more effectively, allowing fewer embryos to be implanted. In her experiments on mice, she found that when a sperm entered an egg, the egg's jelly-like innards would start to pulsate soon afterwards.
"The pattern of those movements is predictive of whether the embryo will have successful developments throughout the entire pregnancy," said Zernicka-Goetz. "I believe this method has very important potential medical applications, as it provides a totally non-invasive and rapid way of making this prediction of which embryo will have successful and which will not have successful pregnancy."

Her findings were published recently in Nature Communications. Link: http://www.nature.com/ncomms/journal/v2/n8/pdf/ncomms1424.pdf


A spokesperson for the British Fertility Society said that egg quality was fundamental to the success of both natural conception and fertility treatments. "In IVF the selection of the 'best' embryo to replace remains key to live birth success, but clinical approaches to this are not sophisticated. This work adds to our understanding of how 'good' eggs may function in the mouse model."

The oscillations seen by researchers in the egg's cytoplasm – the jelly-like liquid inside the cell – is caused by the influx of calcium ions after an egg is fertilised. Zernicka-Goetz's team filmed the eggs in the hours after fertilisation and used a technique called particle image velocimetry (PIV) to measure the frequency of the movements. They then implanted the embryos and noted which ones led to successful pregnancies.

The cytoplasm in an unfertilised egg moves at around 4 nanometres per second, said Anna Ajduk, a postdoctoral researcher in Zernicka-Goetz's laboratory and an author on the research paper…But the oscillations speed up after fertilisation.

Those embryos that were most successful at creating pregnancies had cytoplasm moving at around 10-15nm per second, with waves of movement peaking every 10-30 minutes. "It's easy to identify embryos that will not develop well because they have low, low values," said Ajduk. "Everything above, they seem to cope relatively well."

Movements in human embryos would probably be similar to those seen in mouse eggs, said Ajduk, because of similarities in their biochemical properties and size. "Our method provides a way of assessing the potential on the second day because you just need a few hours to analyse the data and make the movie, and you will know. We can provide a really fast method of assessing embryos – potentially, the fastest available."

Zernicka-Goetz said she was discussing with IVF clinics to initiate trials involving human embryos and hoped it could be done within a few months. "Within a year's time we should know whether such movements are predictive of the successful development of human embryos," she added.

Dr Allan Pacey, an expert in reproductive biology at the University of Sheffield, said there were currently no satisfactory methods to predict which fertilised eggs would develop into good quality embryos, apart from waiting for several days to see what happens.

"Clearly the technique of performing PIV is complex and will need to be simplified or automated for use in a busy IVF lab. This is the biggest hurdle I anticipate that might prevent more people experimenting with this approach. But I hope they do, as we really need to develop something more technical than the 'watch and wait' approach we have currently."



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