The relationship between chromosomal mosaicism and maternal age in embryos TESTED WITH Next Generation Sequencing (NGS) platform

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Introduction Chromosomal mosaicism refers to the presence of two or more cell lines with a differentchromosome content in an individual or tissue sample. Besides aneuploidy, the use of highresolution NGS for Pre-implantation Genetic Diagnosis (PGS) detects the presence of mosaicism introphectoderm biopsies. The transfer of mosaic embryos has been shown to result in lowerimplantation rates and higher miscarriage rates as compared to euploid transfer. This study aims to evaluate whether there is an association between mosaicism and maternal ageand the clinical pregnancy and implantation rate of mosaic embryos transfer. Materials and Method A retrospective observational study of 533 blastocyst-stage embryos analysed by NGS from IVFcycles from Sunfert International Fertility Centre over the course of 2015 to 2016 was performed. Ofthose analysed, 197 blastocysts were transferred. The clinical outcome obtained after the transfer ofwhole chromosomal mosaic embryos was compared with those resulting from a control group 190euploid blastocysts. Blastocyst-stage embryos underwent biopsy and trophectoderm cells were extracted for aneuploidyscreening using IIlumina NGS protocol. Mosaic information for each chromosome was obtained. Forthis study, only whole chromosomal mosaicism was considered; segmental mosaicism wascategorized as euploid embryos. These embryos were further stratified by maternal age group. Result The transfer of mosaic embryos resulted in higher clinical pregnancy rate (60% vs 57.5%) andimplantation rate (57% vs 52.9%) compared to euploid embryos. In our series, no miscarriage wasreported in this group of patients. Conclusion In concordance with most published studies, we found that mosaicism is not associated withadvanced maternal age. Unlike aneuploidy which arises from meiotic error, mosaicism on the otherhand is caused by impaired mitotic chromosome segregation which does not appear to increase withadvancing maternal age. Therefore, while there is a direct relationship between advanced maternalage and aneuploidy, age is not a contributor to mosaicism. Contrary to the experience of other groups, we have observed similar rate of implantation in mosaicembryo transfers as compared to euploid embryo transfers. This may be the consequence of thesmall sample size of mosaic embryos transfer (<10% of total blastocysts transferred) in our series. Similarly, no miscarriage was reported. PGS in its current form does have limitations. Implantation rates can potentially be further improvedby developing a clearer understanding of the impact of mosaic embryos. Chromosomal mosaicism refers to the presence of two or more cell lines with a differentchromosome content in an individual or tissue sample. Besides aneuploidy, the use of highresolution NGS for Pre-implantation Genetic Diagnosis (PGS) detects the presence of mosaicism introphectoderm biopsies. The transfer of mosaic embryos has been shown to result in lowerimplantation rates and higher miscarriage rates as compared to euploid transfer. This study aims to evaluate whether there is an association between mosaicism and maternal ageand the clinical pregnancy and implantation rate of mosaic embryos transfer. A retrospective observational study of 533 blastocyst-stage embryos analysed by NGS from IVFcycles from Sunfert International Fertility Centre over the course of 2015 to 2016 was performed. Ofthose analysed, 197 blastocysts were transferred. The clinical outcome obtained after the transfer ofwhole chromosomal mosaic embryos was compared with those resulting from a control group 190euploid blastocysts. Blastocyst-stage embryos underwent biopsy and trophectoderm cells were extracted for aneuploidyscreening using IIlumina NGS protocol. Mosaic information for each chromosome was obtained. Forthis study, only whole chromosomal mosaicism was considered; segmental mosaicism wascategorized as euploid embryos. These embryos were further stratified by maternal age group. The transfer of mosaic embryos resulted in higher clinical pregnancy rate (60% vs 57.5%) andimplantation rate (57% vs 52.9%) compared to euploid embryos. In our series, no miscarriage wasreported in this group of patients. In concordance with most published studies, we found that mosaicism is not associated withadvanced maternal age. Unlike aneuploidy which arises from meiotic error, mosaicism on the otherhand is caused by impaired mitotic chromosome segregation which does not appear to increase withadvancing maternal age. Therefore, while there is a direct relationship between advanced maternalage and aneuploidy, age is not a contributor to mosaicism.