Molecular and Developmental Integrity Following Trophectoderm Biopsy: Evidence from Human and Mouse Models.

OBJECTIVE

To determine whether trophectoderm (TE) biopsy performed for preimplantation genetic testing induces molecular, epigenetic, or developmental perturbations in preimplantation embryos and subsequent placental development.

DESIGN

Comparative multi-omics investigation of human blastocysts combined with a murine embryo transfer model.

SUBJECTS: Surplus cryopreserved human euploid blastocysts donated to research and murine blastocysts that were either subjected to TE biopsy or no biopsy.

EXPOSURE: The impact of blastocyst-stage trophectoderm biopsy on transcriptomic, epigenomic, developmental, and/or placental outcomes.

MAIN OUTCOME MEASURES: Differential gene expression, imprinting methylation, whole-genome DNA methylation of inner cell mass (ICM) and TE, mitotic cell division mechanics, implantation rates, fetal and placental growth, placental methylation.

RESULTS

Trophectoderm biopsy was not associated with biologically meaningful molecular or epigenetic alterations in human blastocysts. Gene expression, imprinting methylation, global DNA methylation, and DNA budding/shedding were comparable between biopsied and non-biopsied embryos. In a murine model, biopsy had no effect on implantation rates, fetal or placental growth, placental methylome, or imprinting methylation status.

CONCLUSION

A comprehensive multi-omics assessment of human blastocysts, supported by developmental and placental analyses in a murine model, found no evidence that trophectoderm biopsy adversely affects early embryonic molecular regulation or subsequent developmental outcomes. These findings support the use of TE biopsy as a minimally invasive micro-manipulation procedure.