Large Intra-Age Group Variation in Chromosome Abnormalities in Human Blastocysts

Abstract

Research Question: Is maternal age only a gross predictor of chromosome abnormalities in human embryos? Design: Here, we evaluated the less-studied variation in chromosome abnormality rates in embryos of patients within the same age group. Patients undergoing IVF and PGD for chromosomal abnormalities in ~127 different IVF clinics were included. PGT-A analysis was performed by a single reference laboratory using array CGH or NGS. To get an estimate of the range of abnormalities observed, the aCGH and NGS data were studied both independently and together. Results: The overall results showed the typical increase in aneuploidy rates with advancing maternal age (AMA) but extensive variability within each age group. Conclusions: Increasing aneuploidy with maternal age has been demonstrated in live births, unborn fetuses, IVF embryos and oocytes. In contrast, post-meiotic and other abnormalities that might lead to mosaicism, polyploidy and haploidy, are commonplace (around 30%), regardless of maternal age. Here we conclude that age is only a gross predictor of chromosome abnormalities in IVF embryos. In contrast to the existing standard of offering PGT-A to AMA patients, the high rate and extreme variation of chromosomal abnormalities in human embryos may warrant PGT-A for further IVF cycles even in younger age groups, especially if a history of increased levels of aneuploidy is evident. Furthermore, better indicators are needed to determine which patients are at a higher risk of producing increased levels of aneuploid embryos.