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The transfer of chromosomally 'abnormal' embryos can still result in pregnancy in IVF

ESHRE - Francesco Fiorentino

12 July 2017

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Geneva, 4 July 2017: IVF embryos whose cells have mixed chromosomal profiles - one normal, another abnormal - still have the potential to implant in the uterus and become a healthy pregnancy, according to a study presented today at the 33rd Annual Meeting of ESHRE. 

This pattern of embryonic mosaicism, which is characterised by the presence of two or more genetically distinct cell lineages, typically one with a chromosome abnormality and the other with a normal chromosome composition, has become a controversial topic in recent months, with debate over their potential viability. In the light of this latest study, which was performed by the GENOMA group and European Hospital IVF Center in Rome, Dr Francesco Fiorentino from the Molecular Genetics Laboratory of GENOMA, who will present today's study, said that its results "confirm that mosaic embryos can develop into healthy euploid [chromosomally healthy] newborns". 

This possibility was first raised by Dr Fiorentino's group and the European Hospital in a letter to the New England Journal of Medicine in November 2015, which described six healthy deliveries in a small series of 18 women for whom embryo screening had found no chromosomally normal (euploid) embryos.(1) Up to this point mosaic embryos were not usually transferred in IVF because they (like all other aneuploid embryos) were considered abnormal. Even in their NEJM letter, the Rome investigators noted that "it is reasonable to assume that mosaicism reduces the likelihood of success of IVF".

The bottom line of this latest study reported at ESHRE is that success or failure following the transfer of a mosaic embryo in IVF depends on the extent of the mosaicism and chromosomal abnormality (aneuploidy) in the embryo.

The study included 73 women for whom embryo screening following IVF had found no chromosomally normal embryos for transfer. Screening had, however, identified mosaic embryos in each of these patients, which were then offered for transfer. For the purpose of the study and assessment of development potential, these mosaic embryos were classified as having low (<50%) or high (>50%) degrees of aneuploidy.

Results of the study showed that pregnancy and delivery were indeed possible following the transfer of mosaic embryos. However, the transfers of mosaic embryos with a high percentage of chromosomally abnormal cells (≥50%) resulted in a live birth rate of 16.7%, with a miscarriage rate of 10%. In contrast, mosaic embryos with a lower aneuploidy percentage (<50%) resulted in a higher live birth rate of 39.5%, with miscarriage occurring in just 7.0% of the transfers. The difference between the two delivery rates was statistically significant, suggesting, said Dr Fiorentino, that "priority for transfer should be given to mosaic embryos with low levels of aneuploidy".

Dr Fiorentino said there are several reasons why an embryo with clearly detectable levels of aneuploidy might self-correct and develop into a healthy newborn. One reason, he explained, may be related to the fact that the aneuploid cells have a growth disadvantage or are simply eliminated by processes such as apoptosis. This may lead to a decline in number as the embryo develops, ultimately resulting in a normal fetus. 

However, he added that mosaic embryos may now be considered a "distinct category" in terms of potential to implant and develop, lying somewhere between euploid and fully aneuploid embryos. "Euploid embryos have a higher implantation potential than mosaic embryos," said Dr Fiorentino, "and because of this we suggest that mosaic embryos should only be transferred in women with no euploid embryos available. The transfer of euploid embryos, when available, results in higher implantation rates and a lower risk of miscarriage, and represents the preferred option for IVF patients."

Dr Fiorentino added that this finding - that mosaic embryos have the potential for implantation and pregnancy and may influence the clinical outcome of IVF - now suggests that all women may benefit from aneuploidy testing before embryo transfer.
 


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Date Added: 12 July 2017   Date Updated: 12 July 2017
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