Evidence of Selection against Complex Mitotic-Origin Aneuploidy during Preimplantation Development.
Level 4 - case-series / case-control
Retrospective observational analysis of clinical preimplantation genetic screening biopsy data.
PubMed 26491874 · doi:10.1371/journal.pgen.1005601
What was done
The authors analyzed 24-chromosome preimplantation genetic screening results from 28,052 single-cell day-3 blastomere biopsies and 18,387 multi-cell day-5 trophectoderm biopsies across 6,366 in vitro fertilization cycles. They classified whole-chromosome abnormalities as meiotic or mitotic in origin using chromosomal signatures and evaluated associations with developmental stage, maternal age, and clinical referral indications.
What was found
The abstract does not report specific numerical rates, percentages, or effect sizes. Mitotic errors frequently involved multiple chromosome losses without bias toward maternal or paternal homologs. Unlike meiotic errors, mitotic errors were not significantly associated with maternal age. Controlling for maternal age, patients referred for previous in vitro fertilization failure had elevated rates of mitotic error, whereas patients referred for recurrent pregnancy loss had elevated rates of meiotic error.
Why it matters
The findings indicate that mitotic chromosome missegregation is a primary mechanism contributing to embryo loss prior to blastocyst formation and is uniquely associated with in vitro fertilization failure rather than maternal age.
Limits
Specific numerical rates, effect sizes, and confidence intervals are omitted from the abstract. The study is limited to an assisted reproduction cohort and may not reflect natural in vivo conceptions. Single-cell day-3 biopsies carry inherent sampling and technical limitations relative to multi-cell blastocyst biopsies.
Cited by
- contradicts In IVF, embryos failing to develop past day three into a blastocyst are typically attributed to sperm quality.