Chromosome 21 mosaic human preimplantation embryos predominantly arise from diploid conceptions

Objective: High rates of chromosomal mosaicism in human IVF embryos question the accuracy of preimplantation genetic diagnosis, and, with the majority of embryo transfers still resulting in no pregnancy, chromosomal mosaicism is likely to be a contributing factor to human IVF failure. The aim of this study was to investigate the origin and nature of chromosome 21 (Ch21) cell division errors in human IVF embryos. Design: Perform single cell Ch21 allelic profiling on human IVF embryos. Setting: Academic research environment. Patient(s): Women of advanced maternal age (> 35 yrs) (n = 65) undergoing infertility treatment; and amniocytes/chorionic cells from trisomy 21 pregnancies (n = 28). Intervention(s): Cells were analyzed by single cell allelic profiling. Main Outcome Measure(s): The origin and nature of cell division errors. Result(s): The vast majority of Ch21 mosaic embryos (similar to 80%) originated from diploid conceptions. In contrast, all fetal trisomy 21 originated from aneuploid conceptions. Increasing maternal age was significantly associated with aneuploid conceptions, meiotic cell division error, and adverse pregnancy outcome (P <.05). The mean daily FSH dose that produced embryos with normal Ch21 cell division was significantly lower than the mean daily FSH dose that produced embryos with mitotic Ch21 cell division errors (P <.01) and embryos with meiotic cell division errors (P <.05). Conclusion(s): Chromosomal mosaicism of Ch21 in human IVF embryos predominantly originate from diploid conceptions. Further understanding of chromosomal mosaicism with respect to IVF parameters, such as daily FSH dose, may eventually lead to improvements in IVF outcomes.