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Abstract Introduction Analyses of miscarriage products indicate that the majority of aneuploidies in early developing embryos derive from errors occurring during maternal meiosis and the paternal contribution is less than 10%. Our aim was to assess the aneuploidy (mainly monosmies) frequencies at the earliest stages of embryo development, 3 days following fertilization during In vitro fertilization (IVF) treatments and to elucidate their parental origin. Later, we compared monosomies rates of day 3 to those of day 5 as demonstrated from Preimplantation Genetic Testing for Structural chromosomal Rearrangement (PGT-SR) results. Methods For a retrospective study, we collected data of 210 Preimplantation Genetic Testing for Monogenic Disorder (PGT-M) cycles performed between years 2008 and 2019.This study includes 2083 embryos, of 113 couples. It also included 432 embryos from 90 PGT-SR cycles of other 45 patients, carriers of balanced translocations. Defining the parental origin of aneuploidy in cleavage stage embryos was based on haplotypes analysis of at least six informative markers flanking the analyzed gene. For comprehensive chromosomal screening (CCS), chromosomal microarray (CMA) and next generation sequencing (NGS) was used. Results We inspected haplotype data of 40 genomic regions, flanking analyzed genes located on 9 different chromosomes.151 (7.2%) embryos presented numerical alterations in the tested chromosomes. We found similar paternal and maternal contribution to monosomy at cleavage stage. We demonstrated paternal origin in 51.5% of the monosomy, and maternal origin in 48.5% of the monosomies cases. Conclusion In our study, we found equal parental contribution to monosomies in cleavage-stage embryos. Comparison to CCS analyses of PGT-SR patients revealed a lower rate of monosomy per chromosome in embryos at day 5 of development. This is in contrast to the maternal dominancy described in studies of early miscarriage. Mitotic errors and paternal involvement in chemical pregnancies and IVF failure should be re-evaluated. Our results show monosomies are relatively common and may play a role in early development of ART embryos.

Introduction: A 33-year-old infertile patient presented with two early miscarriages in a spontaneous pregnancy and a pregnancy achieved by intrauterine insemination, respectively. She subsequently had nine failed IVF cycles. Despite the fact that >10 oocytes were retrieved in each cycle, all were characterized by abnormal fertilization demonstrated by the presence of only one pronucleus (IPN) and nonextraction of the secondnd polar body when examined 9-20 h following either standard insemination or intracytoplasmic sperm injection (ICSI). About 50% of these embryos further cleaved by day 3 post fertilization. While embryo transfer was performed in all cycles, no pregnancy was achieved. The aim was to analyse the genetic composition of oocytes and embryos in this patient in order to provide counselling regarding prognosis and treatment options. Materials/Methods: In her last cycle, ICSI was performed for all 10 oocytes. All first polar bodies (PB) were biopsied and analysed by fluorescence in-situ hybridization (FISH) probes for chromosomes 13, 18, 21, X and Y. In addition, all cleaving embryos were subjected to blastomere biopsy, followed by FISH analysis, as above. Since none of the embryos were found to be euploid, they were further subjected to single cell PCR analysis using a panel of highly polymorphic markers from different chromosomes (6, 7, 17, 19, X and Y). Results: FISH analysis of the first PB demonstrated normal segregation of chromosomes in meiosis 1. FISH analysis of single blastomeres from five cleaving embryos demonstrated three diploid and two mosaic triploid embryos. However, haplotype analysis demonstrated that all embryos including the diploid ones, had two sets of maternal alleles. Conclusion: We conclude that the diploid embryos represent parthenogenetic activation of a diploid oocyte. Furthermore, since ICSI was performed, the triploid embryos must have resulted from fertilization of a diploid oocyte by a single spermatozoon. Thus the abnormality detected in this case results from failure to extrude the second PB. Although abnormality of the spermatozoa has not been ruled out, this most likely represents failure in the oocyte activation machinery leading to incompetence of the oocyte to complete meiosis II as well as to decondense the sperm nucleus into the male pronucleus. [ABSTRACT FROM AUTHOR]