Time-lapse technique may boost success rate of IVF
“IVF advance triples couples' chances of having a baby”, The Daily Telegraph reports.
The innovation in question is actually based on an old imaging technique called time-lapse photography, where a camera is set to record a series of images at regular intervals. This technology is now available for monitoring the development of IVF embryos before they are transferred into the womb.
The researchers in this study developed a way of using the information collected to identify which embryos had a low or high chance of having an abnormal number of chromosomes (called aneuploidy). Aneuploidy can reduce the chances of embryos successfully implanting and resulting in a healthy live birth.
In this study, the researchers looked back at time-lapse imaging for embryos from 69 couples who had IVF. They wanted to know if their technique correctly identified embryos which were more likely to result in a pregnancy or live birth.
The time-lapse cameras allowed the researchers to potentially ‘screen’ embryos for risk of aneuploidy. From this, they would then be able to choose the low risk embryos for implantation.
The researchers found that 73% of the embryos their assessment would have classed as low risk resulted in a pregnancy at five to six weeks, and 61% resulted in a live birth. These rates were higher compared to the overall rate for all embryos (at any risk level), where the pregnancy rate was 42% and the live birth rate was 39%. However, it is important to restate that the new system was not used to intervene, so the results are based purely on observation.
While the results are promising, the technique is still in its early stages. Further research is needed to more widely test the technique and directly compare its results to standard methods.
Where did the story come from?
The study was carried out by researchers from CARE Fertility, an independent provider of fertility treatment and related services in the UK and Ireland. No sources of financial support were reported and the authors reported that they had no financial or commercial conflicts of interest.
The study was published in the peer-reviewed medical journal, Reproductive Biomedicine Online.
The study was well reported in the media, with BBC News coverage including an informative video to explain the technique.
However, potentially confusing figures are reported in other parts of the media.
The Times reported that the new technique “could give a 78% chance of success” while the Daily Mail reports that “Early trials show 78% of women having the test will have a healthy baby”.
The Guardian’s reporting suggests that “Doctors in Nottingham who devised the procedure say it could raise live birthrates at their clinic to 78%...” and this may be where this figure has come from.
However, this 78% figure does not come from the research paper itself, which reports that 61% of the low risk embryos successfully resulted in a live birth – not 78%.
What kind of research was this?
This study looked at whether the novel technique based on time-lapse images of IVF embryos might help select the embryos most likely to successfully produce a baby.
Until now, the researchers say that the vital decision about which IVF embryo should be selected and transferred into the mother’s womb is mainly based on between two and six observations of the developing embryo under the microscope.
To observe the embryo’s development, doctors have had to remove the culture dish containing the embryos from the very controlled environment of the incubator and place them under a microscope in the ambient air of the laboratory. This is usually only performed once a day to minimise disturbance to the embryo.
The authors of the study report that a major reason for IVF failure and miscarriage is that the implanted embryo has an abnormal number of chromosomes (aneuploidy). To accurately detect any chromosomal abnormality requires an invasive biopsy of the developing embryo, followed by genetic testing.
Currently it is not possible to reliably identify those embryos with an increased chance of aneuploidy with the normal microscopic observations of the embryo.
The current study tested a way of identifying the embryos at low risk of having abnormal numbers of chromosomal, using time-lapse imaging of the embryo. A relatively new system now allows doctors to obtain a stream of thousands of microscopic images of developing embryos (time-lapse images), without having to remove embryos from the incubator.
Using this system, the researchers previously found that embryos with an abnormal number of chromosomes take a different length of time to reach certain developmental stages than normal embryos. Based on this, they developed a method to identify those embryos at low, medium, and high risk of having an abnormal number of chromosomes.
In their current study, the researchers looked back at the results of IVF procedures where the embryos had been assessed using time-lapse imaging. They wanted to see if their method could identify those embryos which were more likely to go on to successfully implant, develop and be born.
It is important to note that the study did not actually use the method to select embryos for implantation – it only looked at what might have happened if the method had been used.
This is an appropriate first step for this type of research and, if the results are promising, the method would need to go on to be tested “for real” to select embryos, to see if it performed better than standard methods.
What did the research involve?
This study looked at the treatment outcomes for 88 embryos from 69 couples who attended the CARE Fertility clinic in Manchester between April 2011 and December 2012, and who had a known outcome from their IVF.
This meant that they knew if transfer of the embryo(s) had resulted in:
- failed implantation – where the woman had a negative pregnancy test
- clinical pregnancy – defined as the presence of a developing embryo with a heart beat at between six and eight weeks of pregnancy
- a live birth – identified through the mother completing a clinic delivery outcome form, which according to regulations is reported to the UK Human Fertilisation and Embryology Authority
The researchers excluded cases where two embryos were implanted but did not both have the same outcome, as they would not be able to tell which embryo had which outcome.
The egg cells collected from the women had been fertilised using intra-cytoplasmic sperm injection (ICSI), where a single sperm is injected directly into the egg. The fertilised eggs were then placed into the time-lapse incubator for culturing and imaging for five to six days.
The inbuilt microscope took images of the fertilised egg cell every 20 minutes. The image-analysis software recorded the precise timing of developmental events as they occurred. The embryos had been selected using standard existing methods before being transferred into the womb (that is, not using the new risk assessment method).
The researchers used this previously collected data model to assess the embryos, and grade whether the embryos were at low, medium or high risk of having an abnormal number of chromosomes. They then looked at what proportion of each of these three groups of embryos had achieved clinical pregnancy and live birth, and if this differed between the groups.
What were the basic results?
The researchers found that of the 88 embryos they assessed, 33 were at low risk for having an abnormal number of chromosomes, 51 at medium risk, and four at high risk.
Overall, 42% of the embryos successfully implanted and had a fetal heart beat at five to six weeks.
Among the low risk embryos, almost three-quarters (73%) successfully implanted and had a fetal heart beat at five to six weeks, compared to a quarter (25.5%) of medium risk embryos and no high risk embryos.
This meant that the 73% figure for low risk embryos is a relative increase of 74% compared with the rate for all embryos (42%) – what the media has translated as a ‘74% chance of successful pregnancy’.
The researchers had data on whether or not women had a live birth for 46 of the embryos (18 low risk, 26 medium risk, two high risk). The rest of the pregnancies had not reached term during the study period.
Overall, 39% of the embryo transfers resulted in a live birth. Among the low risk embryos, 61% resulted in a live birth. Among medium risk embryos, 19% resulted in live birth. None of the high risk embryos resulted in a live birth.
Therefore, the 61% figure for low risk embryos is a relative risk increase of 56% compared with the rate for all embryos (39%) – this is where media reports of the ‘increasing live birth rates to above 50%’ come from.
How did the researchers interpret the results?
The researchers say that their risk classification model using time-lapse imaging introduces a non-invasive way of selecting the embryos that are at a low risk of having an abnormal number of chromosomes. They say that this can result in higher likelihood of successful pregnancy and live birth.
Conclusion
This study reports on a new technique using ‘time-lapse imaging’ to non-invasively identify the IVF embryos least likely to have abnormal numbers of chromosomes.
An embryo having an abnormal number of chromosomes is one of the reasons IVF can be unsuccessful.
By looking back at the results of previous IVF procedures, the study showed that embryos identified as being low risk using the new method were the most likely to result in a live birth.
To date, IVF techniques rely on removing the embryo from the incubator about once daily over the course of five to six days to view its development under the microscope. As such, current methods only allow for a few static images which cannot give a reliable indication of whether an embryo has chromosome abnormalities, and also disturb the developing embryo. To select the best embryo for implantation, biopsies of the embryo have to be taken to examine the genes. The new technique potentially offers a non-invasive way to assess the risk of chromosome abnormality using detailed time-lapse images.
The results of this study are promising, but there are some limitations:
- It only assessed the outcomes for only 69 couples who received care at one fertility service. Larger numbers of embryos would ideally need to be assessed to confirm the results. Ideally, prospective studies comparing this new technique with standard techniques would also be carried out.
- The researchers note that their methods and results may not be directly transferable to other laboratories or other types of patient populations.
The technique, while potentially promising, is still in an early stage of development.
