Humans, unlike rabbits, are inefficient breeders. Even a healthy couple trying to conceive has no more than a one-in-four chance of success in a cycle of unprotected intercourse. And among the subfertile - as many as one in six of the population - these odds are much less, and in some cases may be zero. While assisted conception will help many to conceive, more than half of treatment cycle may be unsuccessful.
The main reason for this reproductive inefficiency, and for miscarriages too, is thought to be chromosome imbalances (‘aneuploidies’) within the embryo, which rise in prevalence with advancing maternal age. These can result in disorders such as Down syndrome or Turner’s Syndrome, but also explain why success rates in IVF and natural conception decline with advancing maternal age, especially after the age of 35 when the prevalence of aneuploidy increases dramatically.
Reproductive scientists have tested embryos for aneuploidy for over 20 years using a technique known as PGT-A (supported by the HFEA) – as it is now well understood that aneuploidy is the most commonly recognized cause of pregnancy loss in humans. So, the strategy for IVF labs testing embryos in IVF is to identify and select for transfer to the uterus, only those without aneuploidy. That way, the risk of pregnancy loss will be much reduced. To date, it has been assumed that most of these aneuploidies are already present in eggs before they are fertilised, but new research has shown otherwise.
A new study published in Genome Medicine by researchers from London Women’s Clinic and Johns Hopkins University in the USA – well summarised in News Medical – has found that the natural development of embryos may be arrested at the very beginning of its growth cycle, immediately after the egg has been fertilised by a sperm cell, and thereby terminate cell division and embryonic growth. And this arrest of embryo development would inevitably thwart any prospect of pregnancy, whether natural or assisted with IVF. The researchers, who included London Women’s Clinic alumni Michael Summers and Alan Handyside, found it ‘surprising’ that most of these embryo arrests were coming not from errors at the time of egg formation, but from errors happening in cell divisions soon after fertilisation.
This is an important finding for IVF, where most embryos transferred to the uterus have been incubated for five or six days up to the blastocyst stage of their development. Studies show that results from blastocyst transfers are better than from transfers with younger embryos, but that only around one half of all embryos actually make it to the blastocyst stage. The other half experience embryo arrest at an early stage.
The latest London Women’s Clinic study, which may have important implications for the assessment of fertilised eggs in IVF, has now also found that the prevalence of aneuploidy among these arrested embryos is exceptionally high. Among almost 1000 embryos tested at an early stage, nearly half underwent developmental arrest because of genetic mishaps in their early development. This finding, say the researchers, may eventually help us find ways for more pregnancies to come to term in the fertility treatment process. So far, however, the study shows that aneuploidies, which frequently arise due to abnormalities in the first cell divisions after fertilisation, are the primary cause of arrest among IVF embryos.
What can be done to reduce the chances of miscarriage?
To combat the prevalence of aneuploidies where we can, at London Women’s Clinic we recommend PGT-A to our patients who are more likely to be impacted. The success rates we see for those who opt for IVF with PGT-A demonstrate the benefits of embryonic screening in the laboratory. ‘The appliance of PGT-A’, says Lead Embryologist in Genetics, Balsam Al Hashimi, ‘elevates overall success rates by selectively choosing the embryos with the best chances of implantation and survival.’
Professor Nick Macklon, Clinical Director of London Women’s Clinic states, ‘we see this selective approach yields positive outcomes particularly in women over 40 who are most affected by the impact of age on egg and embryo quality. But we also see the value of this additional selective method for other services across our clinic, including Egg Freezing, IVF using Donor Eggs and Surrogacy.’ People often ask how to choose the ‘right’ or the ‘best’ embryo/ gamete and it is these selective methods taken by our embryology team that best support this decision-making process.
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