What makes a good embryo?
Alison Campbell, Director of Embryology at CARE Fertility, answers patients’ most common questions about what makes a good embryo, including common factors that affect embryo quality and how they are assessed.
How do you assess what is a ‘good’ embryo? What technology is used to assess embryo quality?
The way we assess embryo quality has significantly improved over the past few years, with great technological advancements allowing us to analyse embryos in our IVF laboratories in even more detail and with more certainty than ever before.
Traditionally, embryologists would assess embryo quality by looking down a microscope and subjectively assessing an embryo based on their number of cells, how smooth and even those cells are, and whether or not there is any fragmentation (bits of cells that have broken off, which generally is not a good sign). This traditional method of assessing embryos is effective, but we can now use much more sophisticated tools to choose the best embryo for transfer and increase the chances of success.
Why do embryos fragment and how does it affect the chance of success?
Dr Sue Montgomery, Laboratory Manager at CARE Manchester, discusses why embryos fragment, and what we can do to give you your best chance of success.
In standard IVF, we would usually carry out this traditional assessment of embryos once a day, opening up the incubator and very carefully taking out the embryos to look at them under the microscope. One of the more advanced methods we have for embryo assessment is time-lapse imaging, where a photo is taken of the developing embryo every five to ten minutes throughout the whole period we have them in our care in the IVF laboratory, all without removing them from the optimum environment of their incubator. We use the vast amounts of data gathered from this time-lapse imaging to assess the embryos’ morphokinetics: how they look (their morphology) and they way they move and their behaviours (kinetics). With the ‘live feed’ of time-lapse imaging, we can continuously assess both these sets of information throughout the embryos’ whole developmental journey.
How does time-lapse technology help to select the best embryo for transfer?
The development of this advanced embryo analysis technology has been a very exciting journey. Eight or nine years ago, we started collecting all these images taken by our time-lapse incubators, and we looked at the data collected and compared the images of embryos which developed to a healthy, live birth to images of the embryos which sadly did not. A data analysist then investigated this huge amount of data and found that there were differences between these sets of embryo images, and that’s how we developed CAREmaps: our unique algorithm which helps us determine, much more subjectively than traditional methods, which embryos are actually good quality, whether they appear to be or not.
Does time-lapse embryo assessment lead to higher success rates?
There has been lots of work published about whether time-lapse embryo imaging assessment, like CAREmaps, improves the chances of success and the answer is yes, definitely. We have published work in peer-review journals, and even in a textbook! It is very difficult to give precise figures on how CAREmaps improves the pregnancy success rate as every patient, their medical history, and their treatment is different, but, in general, the average uplift is around 20% - that’s a relative increase, such as an improvement from 40% to 50% (not twenty percentage points). That is a significant improvement!
Fertility breakthroughs and the future of embryology
Sam Duffy, Senior Clinical Embryologist at CARE Manchester and co-author of a world-first study by CARE scientists about the success of time-lapse imaging, talks about how CAREmaps was developed and how it can improve chances of IVF success, as well as her thoughts on the future of embryology.
How do IVF clinics grade embryos?
There are many different systems that IVF clinics use to grade their embryos, and each IVF laboratory will pick the best embryo based on their embryo grading system. The important thing is that your embryologist keeps you updated on your embryos, and they will talk to you about the quality of each of your embryos, why we’re choosing the embryo we have, and the chances of success for all your embryos.
The thing about embryo grading is that when we look at an embryo, we can only see how it looks at that exact moment in time. It could have looked different two hours before, and get a completely different grading, and it could look completely different again in another two hours. That’s where time-lapse imaging comes in and makes a big difference, as we can see the whole development process.
Of course, not everyone chooses to use time-lapse imaging, but we can still use our experience from CAREmaps. What we’ve learned from our time-lapse imaging is that we don’t necessarily need to take an embryo out of its incubator every day and assess it for the sake of it; the most important grading is the one we do right at the end of its culture, when it’s ready for transfer. This is one of the reasons why we felt confident implementing our ‘Do Not Disturb’ policy during COVID-19, where we leave your embryos to develop in their specially-designed culture medium for five days without disturbing them. This ensures that the embryos are kept safe, continuously in the optimum environment of their culture medium, until they are ready for transfer, while minimising dish handling and footfall in the laboratory. Crucially, we still assess the embryos when they are ready for transfer, and that grading will help us to determine which embryo will give you your best chance of success.
What to expect when resuming fertility treatment during COVID-19
Dr Mark Wilcox, CARE Fertility’s Group Medical Director, explains what to expect at every stage of your fertility treatment during this ‘new normal’.
How does genetic testing help assess embryos?
Looking at an embryo’s morphokinetics unfortunately does not tell us what is going on in its DNA – and this is where genetic testing comes in. With PGT-A genetic testing, we can find that an embryo that seems magnificent-looking can actually have an abnormal number of chromosomes.
To explain, to give the best chance of success, we need to create an embryo with chromosomes from each the egg and the sperm, which form 23 pairs of chromosomes. In humans, aneuploidy (an irregular number of chromosomes) is, strangely, quite a common phenomenon, and aneuploidy is one of the greatest causes of miscarriage.
Of course, we wouldn’t wish to transfer an embryo which could lead to a miscarriage, which is where PGT-A genetic testing comes in. In recent years, we’ve been able to take a few cells from an embryo, usually at blastocyst stage (on day 5 or 6 of development) when it has over 100 cells – it can easily space a few! So, we very carefully take just a couple of cells and send them to our specialist genetic testing laboratory, where they will count the number of chromosomes and report back to us on each embryo’s unique genetic makeup. Basically, telling us which embryos have the normal number of chromosomes and which are aneuploid.
What is embryo mosaicism and how does it affect embryo quality?
Sometimes, the genetics lab will tell us than an embryo is mosaic: where there is just a little bit extra of a chromosome, not a whole copy, meaning that some cells are euploid (have a normal number of chromosomes) and some are aneuploid. As scientists, we don’t really know what causes this mosaicism, but we do grade mosaic embryos as ‘high-level’ or ‘low-level’. The research and literature about this from around the world – which is always expanding – would suggest that embryos with low-level mosaicism have a reasonable chance of a health, live birth. High-level mosaic embryos will have a much lower chance. However, it is important to remember that every mosaicism is different, and if you have PGT-A testing which shows some embryos are mosaic, we will offer you an appointment with one of our specialist genetic counsellors to discuss your options.
Who is PGT-A suitable for?
PGT-A is not suitable for everyone. Generally, we would recommend PGT-A genetic testing for women over the age of 37, as we know that aneuploidy is more common in advanced maternal age. We might also recommend PGT-A to patients who have experienced recurrent implantation failure. Having said that, some women who have just the one embryo like to check its number of chromosomes to avoid the risk of miscarriage. Others might think that they only have the one embryo, and they want to give it a chance. It is a completely personal choice.
Why should I consider PGT-A in my IVF treatment?
Rob Smith, Clinic Director of CARE London and advanced embryology practitioner, explains who might benefit from PGT-A, the genetic testing process, what you should consider before genetic testing, and the success rates of IVF treatment with PGT-A.
How can women improve their egg quality?
Of course, the main thing that will impact embryo quality is the quality of the egg and sperm. A woman is born with all the eggs she will ever have, and the number and quality of these eggs is genetically determined, and decreases over the years. However, the environment the eggs are growing in can be improved by lifestyle factors, just like any other cell in the body. Take a look at our top tips for improving fertility for how you can increase your chances of success at home. Overall, we can’t change the quality of the eggs collected, but, working with what we have and using the most advanced fertility technologies and techniques, we will do everything possible to give you your best chance of having a baby.
Unlike women, who are born with all the eggs they’ll ever have, men continuously make sperm from puberty, although (as you might expect) age does also have an impact on the quality of sperm. If our male diagnostic fertility tests identify an issue with your sperm, there are many tools in our toolbox which we can use to identify the best sperm for treatment and help successfully fertilise your eggs.
One of these methods is ICSI, which was developed by CARE’s Founder and Head of Research and Development, Professor Simon Fishel, in 1990. Also known as, intracytoplasmic sperm injection, this is a really phenomenal technique; as opposed to normal IVF, where the egg and sperm are put together in a petri dish, with ICSI we directly inject a single sperm into the centre of the egg, so overcoming that physical barrier between the egg and the sperm. We would generally recommend ICSI for those with low sperm count or poor sperm quality.
Can freezing embryos affect their quality?
Patients often worry that something will happen to their precious gametes and embryos, and we always reassure them of the robust protocols we have in place in our cryolabs to keep all your frozen eggs, sperm and embryos safe. We continuously monitor the temperature and the liquid nitrogen levels of our cryopreservation tanks, and the cryolab is regularly checked by embryologists.
When it comes to success rates, IVF using previously-frozen eggs has a very comparable success rate to fresh eggs – almost exactly the same. In addition, the thaw survival rate of embryos at CARE last year was 98.5%, so you can be reassured that almost all embryos at CARE will survive the entire freeze-thaw process.
Does the time of embryo transfer impact the chances of IVF success?
The number of days an embryo has developed before transfer does impact its chances of success. For example, a day 5 embryo would have a better chance of success than a day 3 embryo. There are a few reasons for this, the first being that the longer we leave the embryos to development, the more data we have to analyse. Also, if an embryo were going to fail on day 3, 4 or 5 we wouldn’t know that on day 3, but by day 5 we’re choosing from a selection of potentially stronger embryos.
In addition to this, the synchronicity of the window of implantation is better with a day 5 transfer. To explain, for women conceiving naturally, an embryo will be travelling down the tube on around day 3, and only arrive in the uterus to meet the endometrium when it is at around day 5 of development, by which stage the endometrium is prepared for the embryo to implant. So, if we transfer on day 3, the embryo has to sit around for a few days – which it wouldn’t naturally do – as the endometrium isn’t receptive. In many ways, it can therefore be better for an embryo to stay in the excellent incubators that we have in our IVF laboratories, and then transfer the embryo on day 5 when the environment of the endometrium is more optimised to receive the embryo.
Overall, be assured that we gather information all the time to assess your embryos, and we are constantly fine-tuning our practices based on research, data and all our experience to give you your best chance of success. Your need for family is at the heart of everything we do – please get in touch with us to find out how we can help you.