Embryos classified as low-grade mosaic (

Abstract

The Preimplantation Genetic Diagnosis International Society (PGDIS) recommend the use of the high resolution next-generation sequencing (hr-NGS) that can detect mosaicism in excess of 20%. Therefore, embryos with less than 20% aneuploidy in the TE sample are considered as euploid and routinely transferred. Those over 80% as aneuploid and subsequently discarded. The 20-80% range as mosaic and transferred with caution, only in absence of euploid embryos. These cutoffs are currently debated. We recently reported the birth of 17 healthy babies from the transfer of 33 low grade (<50%) mosaic embryos with an overall live birth rate (LBR) and abortion rate (AR) similar to the LBR and AR obtained with euploid embryos (Rubino et al., 2018). The current study reports a grater number of cases. Retrospective analysis of the pregnancy outcome of replaced low rate mosaic embryos (20%-50% abnormal cells in the trophoctoderm biopsy) as diagnosed with the use of hr-NGS. This study included only patients that received a single embryo transfer of low rate mosaic embryos and for which the delivery of a newborn could be confirmed. NGS was performed by Nexgenomics, LLC, Pasadena by means of platform Veryseq NGS (Illumina). Nexgenomics position is to use an artificial cutoff of 50% to classify all the mosaicism events as normal or abnormal. Mosaicism <20% is considered not differentiable from technical noise. Low rate mosaic embryos were transferred when euploid embryos were not available. The patients of the study group were matched 1:2 with the patients of the control group (only single euploid embryo transferred) for age, embryo quality, use of an egg donor and/or gestational carrier and period of IVF treatment. All pregnancies that went to term were confirmed to have a normal karyotype. The results are summarized in Table 1. No birth defects were reported. We reported the birth of 33 babies with confirmed normal karyotype after the transfer of 55 low grade mosaic embryos. LBR and AR were similar to the ones obtained with the transfer of euploid embryos suggesting that low grade mosaic embryos (<50%) can have the same potential to give healthy newborn as euploid embryos and the PGDIS guidelines needs to be reconsidered. As far as we know this is the second study that provides data about the LBR of mosaic embryos (Greco et al., 2015). No deliveries were obtained from the transfer of complex mosaic embryos.Table 1Comparison of the pregnancy outcomes of low rate mosaic and control embryosType of mosaicismSegmental*Single-Double 1-12**Single-Double 13-22**X-YComplexTotalControlsAge38.8±6.440.8±6.936.3±5.049.136.2±4.039.1±6.439.3±6.3N of transfer cycles2215121555110Embryos transferred2215121555110Embryos Implanted16109113773Implantation rate (IR)72.3%66.7%75.0%-067.3%66.4%Abortions11101410Abortion rate (AR)6.3%10.0%11.1%--10.8%13.7%Deliveries1598103363Live birth rate(LBR)68.2%60.0%66.7%--60.0%57.3%*Segmental: regarding a piece of chromosome;**Single-double 1-12: regarding one of two entire chromosomes from number 1 to number 12;***Single-double 13-22: regarding one or two entire chromosomes from number 13 to number 22. Open table in a new tab