Determining parental origin of embryo aneuploidy: analysis of genetic error observed in 305 embryos derived from anonymous donor oocyte IVF cycles

Background: Since oocyte donors are typically young and believed to be a source of highly competent gametes, donor oocyte IVF is considered to be an effective treatment for diminished ovarian reserve. However, the aneuploidy rate for embryos originating from anonymously donated oocytes remains incompletely characterized. Here, comprehensive chromosomal screening results were reviewed from embryos obtained from anonymous donor-egg IVF cycles to determine both the aneuploidy rate and parental source of the genetic error. To measure this, preimplantation genetic screening (PGS) data on embryos were retrospectively collated with parental DNA obtained before IVF for chromosome-specific assessments. This approach permitted mitotic and meiotic copy errors to be differentiated for each chromosome among all embryos tested, thus providing information on the parental source of embryo aneuploidy (i.e., from the anonymous egg donor vs. sperm source). Results: 305 embryos generated for 24 patients who began IVF treatment in 2013. For oocyte donors (n = 24), mean (+/- SD) age was 24.0 +/- 2.7 years (range = 20-29). For embryos with full chromosomal reporting (n = 284), euploidy was present in only 133 (46.8%). Considering all embryo chromosomes, the average error rate was 18%. 133 of 151 observed embryo aneuploidies (88.1%) were attributable to an oocyte donor source. Among all aneuploid embryos (n = 151), chromosomal errors from both genetic parents (i.e., oocyte donor and sperm source) were present in 57%. The average correlation coefficient across all pairs of chromosomal abnormalities (r = 0.60) suggests that chromosomes tend to have multiple and simultaneous errors (complex aneuploidy) even when oocytes from young donors are used. Conclusion: These data show that even when young donors provide oocytes for IVF, the probability of embryo aneuploidy remains high. The oocyte donor appears to make an important contribution to embryo aneuploidy even when her age is <30 yrs. If these findings are confirmed with larger, prospective studies, the routine integration of PGS with donor oocyte IVF cycles to identify single euploid embryos for transfer should be considered.