Profiling mitochondrial DNA variant segregation during human preimplantation development: a prerequisite to preimplantation genetic testing for mitochondrial DNA-related disorders.

This article investigates the feasibility of preimplantation genetic testing for mitochondrial DNA (mtDNA) disorders (PGT-mt) at early compaction (Day 4) and blastocyst stages (Day 5 or 6) of human embryo development. The study analyzed 112 embryos carrying pathogenic mtDNA variants and 28 control embryos, assessing heteroplasmy levels in single cells from cleavage, early compaction, and blastocyst stages. Results indicate that pathogenic mtDNA variants segregate evenly among blastomeres at Day 3 and Day 4, and between trophectoderm (TE) and inner cell mass (ICM) at the blastocyst stage, supporting the representativity of TE biopsies for PGT-mt. However, some intercellular variation in heteroplasmy was observed in single TE cells, suggesting that biopsies should include 5–10 cells to ensure accuracy. The study concludes that while PGT-mt is feasible at these later stages, prenatal diagnosis remains recommended due to possible shifts in mutant load during subsequent development.