Tony Gordon: Do Whole-Chromosome Aneuploid Embryos Make Healthy Live Births?

Tony Gordon, Senior Director of Clinical Strategy and Market Development at CooperSurgical Fertility Solutions, shared on LinkedIn:

“Do whole chromosome aneuploid (WCA) embryos make healthy live births? This is a well-discussed subject and I posted about our small dataset earlier this year.

However, in a recent landmark Fertility and Sterility publication, Manuel Viotti, PhD, HCLD from the International Registry of Mosaic Embryo Transfer IRMET (26 IVF centres/PGT-A labs over 10years), reported on the outcome of 168 WCA transfers (111 without knowledge of the PGT-A result, aka non-selection), which resulted in no live births.

Others have written on LinkedIn (for instance, co-author Jamie Grifo) about this paper and how important these findings are to show the specificity (in correctly reporting aneuploidy) of PGT-A.

So I’ll try to highlight a few points other than the main message of Viotti et al. – that WCA don’t make healthy live births. Hopefully the IRMET paper puts this question to bed.

In Viotti et al there were 8 transfers of live-birth trisomy embryos: 5 T21,1 T18 and 2 sex chromosomal aneuploidies (SCA), which resulted in no live births and a termination.

We know from prenatal cytogenetics that many live birth trisomy’s (T13/T18/T21) end in pregnancy loss.

However, we don’t know how many embryos at the PGT stage identified as containing a live birth trisomy result in early loss (implantation failure/biochem loss) and how many will end up in a syndromic live birth.

Although the n=8 is small, it’s striking how none of these embryos result in a live birth. Even across five T21, a genotype that can clearly result in a syndromic live birth, all resulted in pregnancy loss.

The other aspect of Viotti et al that are particularly of interest to me is the data on the transfer of segmental abnormalities (SA). 82 SA were transferred, resulting in a 17% live birth rate.

This is clearly far less than euploid transfer LBR (around 1/3) or even all except the most complex mosaic aneuploidies. Our recent paper showed that (via multiple re-biopsies of whole copy SA) SA are a diverse range of chromosomal aberrations (dels/dups/inversions/ring/isochromosomes) and unstable chromosomes – the ‘intrachromosomal effect’.

Many questions are yet to be answered with regard to SA outcomes, such as, which subset of SA results in live births and which don’t? We need far more data.

There is certainly far more research to undertake here!

One last point: the rebiospsy of just 7 SA embryos, displayed euploid results, so these were effectively mosaic SA, but only one of these resulted in a live birth.

This was highlighted to me by my great colleague Jenna Miller. Although the ‘n’ is small, mosaic SA result in a LBR per ET similar to euploid cells and hence you might expect to see more LB from 7 mosaic SA. Again we need more data here.

This is such a great paper. It provides very clear results on the outcomes of WCA and at the same time raises so many interesting SA questions. Congrats to the IRMET team!”

Title: Multicenter Assessment of Outcomes After Intended or Non-selective Transfer of Whole Chromosome and Segmental Aneuploid Embryos

Authors: Manuel Viotti, Svetlana Madjunkova, Andria Besser, Francesca Spinella, IRMET Consortium, Sharyn Stock-Myer, Hayden Homer, Iulian Roman, Pavel Yakovlev, Nikolay Kornilov, Christine Wechsberg, Mariana A. Jimenez, Amber R. Cooper, Murat Cetinkaya, Semra Kahraman, Mary Carney, Caroline McCrae, Sergio Vaccari, Peter C. Klatsky, Nam D. Tran, Andrea R. Victor, Frank L. Barnes, Caroline McCaffrey, James Grifo, Clifford Librach, Christo G. Zouves, Mitko Madjunkov

You can read the Full Article in Fertility and Sterility.

Title: Segmental aneuploidy in human embryos is frequently mosaic with evidence of meiotic origin: insights from trophectoderm and inner cell mass analyses

Authors: Balsam Al Hashimi, Nick Macklon, Kamal Ahuja, Elena Linara-Demakakou, Bhavna Raikundalia, Sioban SenGupta, Tony Gordon, Darren K. Griffin

You can read the Full Article in Fertility and Sterility.

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