Wednesday August 10 2011
We cannot tell whether the method applies to humans
“A video technique that may significantly boost a woman’s odds of having a baby could soon be available,” according to the Daily Mail.
The news is based on research in mice that investigated what happens inside newly fertilised egg cells and how this relates to the success of in vitro fertilisation (IVF). In the experiments researchers looked for signs that would predict the successful development of the fertilised egg into a baby mouse after they were transferred into the womb. They found that when a sperm enters the egg, the internal liquid contents of the egg (cytoplasm) starts to move in a certain rhythmic pattern, and this pattern could be used to predict whether the embryo would develop to full term once implanted in the womb. Embryos that were considered to be of high quality based on their cytoplasmic movements were almost three times more likely to develop to full-term pregnancies than those graded as poor quality.
This study has demonstrated a potential way to identify the best embryos for IVF treatment in mammals, but it has important limitations. In particular, it used mouse sperm and eggs, and we cannot be certain that the results will be recreated in humans. While the results are certainly interesting, further experiments using human cells are needed to confirm these findings and assess any safety issues.
Where did the story come from?
The study was carried out by a collaboration of researchers at the Universities of Oxford and Cambridge, and was funded by the Wellcome Trust. The study was published in the peer-reviewed scientific journal Nature Communications.
The authors of this study declared filing a US patent on the techniques used in this research.
The headline featured in the Daily Mail is misleading when based on this study alone. It suggests that this was “a video technique that may significantly boost a woman’s odds of having a baby”, but we cannot be sure that the technique will be helpful in humans. The newspaper also said that the technique could be available soon, but again we cannot tell when it might be available. The article does not mention that the study was conducted using mice, not humans.
What kind of research was this?
This research was a laboratory and animal study using sperm and egg cells from mice, looking at what happens inside an egg immediately after fertilisation. Researchers then examined whether the properties of newly fertilised egg cells they observed related to the success of the fertilised egg after implantation in the womb.
Current IVF treatment involves fertilising eggs in the laboratory and picking the embryos that are considered to be the healthiest for transplantation into the mother’s womb, using selection criteria such as the number and shape of cells produced during the division process. However, the implantation of selected eggs using current methods does not always succeed, and multiple rounds of IVF can be required.
In this research, scientists tried to devise a new technique for identifying the embryos that are most likely to produce a successful pregnancy. It involved investigating whether specific movements of the cytoplasm in the egg cell shortly after fertilisation could predict which eggs had the best chance of leading to a successful pregnancy in mice. The cytoplasm is the collective term used to describe the thick liquid substance inside a cell and the various cell components floating within it.
This type of animal study is the best way to investigate the biology of fertilised eggs, initially. However, results shown in mice may not be recreated in humans due to their differences. Once findings have been confirmed in animals, further experiments using human cells are needed to confirm these findings in humans.
What did the research involve?
The researchers observed the cytoplasmic movements triggered when sperm entered mouse eggs (fertilisation) and how these related to the successful development of the embryo.
In order to do this they investigated how these internal movements were related to other cellular processes known to occur in the egg shortly after fertilisation. These include changes in calcium levels within the egg, in the shape of the egg and in the cytoskeleton (scaffold-like internal structures present in all cells). The researchers used time-lapse imaging and specialised microscopy techniques to visualise the flow of the cytoplasm inside the mouse egg. Both of these techniques were non-invasive so should not interfere with the development of the egg.
The researchers then looked to see whether the cytoplasmic movements could be used to predict the successful development of the fertilised egg in the periods both before and after it was implanted into the lining of the womb. The researchers fertilised 71 mouse eggs in the laboratory and recorded their cytoplasmic movements for four hours. They then grew the embryos in the lab for four days and measured the number of cells present after this time – an indicator of successful development. They also assessed whether the embryo developed to a specific stage of development known as the “blastocyst stage”, the point when an egg is ready for implantation into the womb.
Finally, based on their cytoplasmic movements, the researches categorised the IVF eggs as having “good” or “poor” developmental potential before they were implanted into the womb of a mouse to see if they developed to full term.
What were the basic results?
The research found that sperm entry into the mouse egg triggers “rhythmic cytoplasmic motions”. These movements had a specific direction at different stages of early development (the first four hours) of the fertilised egg. At the same time, they observed that the diameter of the newly fertilised egg changed in line with the rhythmic cytoplasmic motion.
In addition, the authors demonstrated that blocking the formation of the cytoskeleton (the dynamic scaffolding of the cell) blocked the observed cytoplasmic rhythms. This suggested that the cytoplasm was important for creating these rhythms.
The authors found that in almost all of the newly fertilised eggs the speed of the cytoplasmic movements were very closely linked to changing levels of calcium in the cell. However, they found that while calcium is important in to cytoplasmic movements it cannot trigger them by itself.
The researchers also found that embryos categorised as “high quality” (based on their cytoplasmic movements) developed to a specific stage of development five times more often than embryos scored as low quality (5/6 high quality embryos versus 1/6 low quality embryos).
High-quality embryos were found to be almost three times (2.77 times) more likely to develop to full term; that is, to the time of birth (21/24 high quality embryos vs. 6/19 low quality embryos).
How did the researchers interpret the results?
The researchers say that their new method offers the “earliest and fastest non-invasive way to predict the viability of eggs fertilised in vitro”. They go on to say that this “can potentially improve greatly the prospects for IVF treatment”.
This animal study was performed using mice sperm and egg cells. This study has identified an important pattern of cytoplasmic movement in newly fertilised eggs that is itself related to other important processes within the developing embryo, such as the behaviour of the cytoskeleton and calcium regulation. It also shows that assessing these movements before the newly fertilised egg is implanted into a female mouse can potentially predict the successful development of the embryo to full term.
While this study provides intriguing new findings it has the following limitations:
- This was a study using mouse sperm and eggs. We cannot assume that the results shown in mice can be recreated in humans due to the differences between mice and humans. Further experiments using human cells are needed to confirm these findings and assess any safety issues.
- The study did not assess whether there were any health or developmental problems within the embryos that reached full-term pregnancy. The safety of this procedure would have to be established before it could be considered for human cells.
This animal study introduces a new technique to potentially predict the best embryos for IVF treatment, but further study is needed in humans to confirm these findings and assess any safety issues.