Embryos classified as low-grade mosaic (

Abstract

Mosaic preimplantation embryos contain two or more cell lines with different chromosome content, the consequence of errors in chromosome segregation occurring during mitotic divisions. Recently the NGS was validated and implemented for PGS. There are several different platforms, with different resolutions, that can detect mosaicism to a different extent. Veriseq NGS (Illumina) that was used in our study, can detect mosaicism when aneuploidy is present in 20%-80% of TE cells biopsied from a blastocyst. The purpose of the present study was to retrospectively analyze 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. The molecular analyses were provided by Nexgenomics, LLC, Pasadena, CA. The platform used was the 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. 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. The patients generating the control group (only single euploid embryo transferred) were matched with the patients of the study group 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, by means of chorionic villus sampling or amniocentesis, to have a normal Karyotype. The results are summarized in Table 1. A total of 33 low mosaic embryos were transferred and they resulted in an overall live birth rate of 51.5%, similar to the live birth rate obtained from the transfer of euploid embryos (48.5%). No birth defects were reported.Table 1Comparison of the pregnancy outcomes of low rate mosaic and control embryos according to the mosaicism type and the chromosomes involved.Type of mosaicismSegmental*Single-Double1-12**Single-Double13-22***X-YComplexTotalControlsPAge38.8 ± 6.440.8 ± 6.936.3 ± 5.0-34.639.1 ± 6.439.3 ± 6.3NSN of transfer cycles13127013366NSEmbryos transferred13127013366NSEmbryos Implanted875-02039NSImplantation rate (IR)61.5%58.3%71.4%-060.6%59.1%NSAbortions111--37NSAbortion rate (AR)12.5%14.3%20%--15%17.9%NSDeliveries764-01732NSLive birth rate (LBR)53.8%50.0%57.1%-051.5%48.5%NS*Segmental: regarding a piece of chromosome**Single-Double 1-12: regarding one or two entire chromosomes from number 1 to number 12***Single-Double 13-22: regarding one or two entire chromosomes from number 13 to number 12-22 Open table in a new tab *Segmental: regarding a piece of chromosome **Single-Double 1-12: regarding one or two entire chromosomes from number 1 to number 12 ***Single-Double 13-22: regarding one or two entire chromosomes from number 13 to number 12-22 Our results indicate that low rate mosaic embryos have the same IR and LBR when compared to euploid embryos. Due to the low number of embryos in our study, further studies are required to verify this observation, but for clinical purposes, these embryos could be considered euploid. As far as we know this is the second study that provides data about the LBR of the mosaic embryos (Greco et al., 2015). A recent study (Munnè et al., 2017) concluded that, overall, mosaic embryos implant less and miscarry more than euploid embryos. However, embryos with >40% abnormal cells and complex mosaic embryos had the lower ongoing implantation rate. We transferred only one complex mosaic embryo and low rate mosaic embryos, which can explain the difference in our findings.