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.