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Genetics: Why investing in basic embryology research must be a priority - 01/03/2021

Darren K Griffin, Professor of Genetics, and Alan R Thornhill, Professor of Reproductive Genetics at University of Kent, School of Biosciences lift the lid on why investing in basic embryology research must be a priority.

In-vitro fertilisation (IVF), responsible for the birth of more than 5 million babies, is now considered a routine procedure. We assume that, because it’s routine, it’s also usually successful. However, the majority of the time, IVF is unsuccessful. Because of the relatively low success rate of IVF, new treatments and technologies have been and are continuing to be developed. One of these technologies is preimplantation genetic testing (PGT).

The most common, known reason behind IVF failure is chromosomal abnormality in the embryo. PGT was tailored to detect this, and one branch of PGT is now known as preimplantation genetic testing for aneuploidy (PGT-A) and is available as an ‘add-on’ to IVF. Aneuploidy includes viable conditions such as Down’s syndrome, but in some cases may instead result in pregnancy loss, congenital abnormality, infertility and, importantly, IVF failure. PGT-A allows for the selection and transfer of euploid (normal/non-aneuploid) embryos, which may improve the IVF outcomes by reducing risk. As the risk of generating aneuploid embryos increases with maternal age and/or other factors such as recurrent miscarriage, PGT-A is typically aimed at these higher-risk couples.

In recent years, testing for chromosomal aneuploidies is performed via next-generation sequencing (NGS), which is sensitive enough to detect the presence of euploid and aneuploid cells in the same embryo (so-called ‘mosaicism’). Whilst the detection of mosaicism may allow embryologists to make more refined embryo-selection decision, some view it as a distraction which could lead to the unnecessary disposal of mosaic embryos, some of which could potentially go on to result in chromosomally-normal live-births.

This argument against PGT-A has caused passionate and polarise debate within the IVF community regarding whether the technology should be used at all. However, many IVF practitioners believe that, in the right hands, using the right methods for the right patients, that PGT-A can be beneficial, and this is supported by recent randomised clinical trials (RCTs), observational studies, and large validated national datasets.


Despite the polarity, what both sides can agree on is the need for more research. The mechanisms of how mosaicism arises in the embryo are poorly understood, despite leading to a range of adverse outcomes, including miscarriage, stillbirth, and severe genetic disease in new-borns. Mosaicism applies not only to IVF embryos, but to a significant proportion of naturally conceived foetuses too, and thus the scope of the impact of such research is relevant to us all.

Through in-depth basic research and comparison with model systems (e.g. mouse, pig, cattle) and basic questions not only relevant to PGT-A specifically but to IVF in general (and to naturally conceived foetuses) could be addressed more deeply.

In addition to these basic research studies, more well-designed RCTs are needed, using real-world conditions, some of which stratify patient groups (for example, comparing advanced maternal age versus recurrent implantation failure versus recurrent pregnancy loss etc.).

Ushering in further basic embryological research begins a domino effect of establishing a greater understanding of aneuploidy and mosaicism which can only result in improved patient management and thus, improved outcomes for couples. This research is of particular importance as, with increasingly older couples wishing to begin or add to their family, aneuploidy is one of the most significant genetic problems in reproduction in our time.

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