Concordant mtDNA heteroplasmy between trophectoderm and inner cell mass supports blastocyst-stage PGT-mt for m.14487T>C.

PURPOSE: Is blastocyst-stage trophectoderm (TE) biopsy informative for preimplantation genetic testing of the mitochondrial DNA (mtDNA) variant m.14487 T > C (MT-ND6), by providing heteroplasmy estimates representative of the inner cell mass (ICM), within a combined PGT-A/PGT-mt workflow?

METHODS

Single IVF/ICSI cycle study in one carrier woman; six blastocysts were obtained and underwent day 5-6 TE biopsy followed by combined PGT-A and targeted mtDNA heteroplasmy assessment.

RESULTS

Six blastocysts underwent combined PGT-A/PGT-mt (day 5, n = 2; day 6, n = 4). PGT-A classified three embryos as euploid, two as aneuploid, and one as mosaic. PGT-mt showed a bimodal distribution of m.14487 T > C heteroplasmy: three embryos were < 18% (11.4-13.5%) and three were > 70% (73.2-99.6%); only one embryo met the predefined transfer criteria (euploid; 11.4% heteroplasmy). After warming and embryo fractionation, heteroplasmy estimates from the original TE biopsy and the corresponding post-warming embryo fraction (the remaining TE, ICM, or combined TE + ICM) were closely concordant, with only small paired differences.

CONCLUSION

These findings provide variant-specific evidence that blastocyst TE biopsy can be representative of the ICM for m.14487 T > C, supporting combined PGT-A/PGT-mt at the blastocyst stage. Nevertheless, given the possibility of heteroplasmy shifts later in development, prenatal diagnosis and postnatal follow-up remain advisable when a heteroplasmic embryo is transferred.