Beyond PGT: Integrating Genetic, Morphological and Functional Assessment of the Human Embryo

Preimplantation Genetic Testing for Aneuploidies (PGT-A) is widely applied in assisted reproduction to assess the chromosomal status of blastocysts and support embryo prioritization for transfer. However, clinical studies highlight a persistent limitation: a substantial proportion of euploid embryos still fail to achieve sustained implantation or result in early pregnancy loss. Chromosomal constitution alone does not reflect the full biological potential of an embryo. Furthermore, routine clinical practice faces unresolved diagnostic dilemmas, including how to prioritize embryos with mosaic or segmental aneuploidies, how to minimize the potential impact of trophectoderm biopsy on embryo viability, and how to interpret the concordance and clinical significance of cell-free DNA-based results obtained through non-invasive PGT (niPGT). Opening this biological “black box” requires investigating the non-chromosomal determinants of embryo developmental competence, implantation, and pregnancy maintenance.This Research Topic aims to advance embryo assessment beyond binary chromosomal classification by establishing multi-modal evaluation frameworks. By integrating genetic status with functional cellular competence and advanced phenotypic characterization, this collection seeks to identify actionable biomarkers of embryo developmental and reproductive potential. We aim to bring together clinical embryologists, reproductive endocrinologists, geneticists and molecular biologists to investigate how metabolic dynamics, mitochondrial function, and epigenetic stability influence developmental competence alongside genomic status. Ultimately, the goal is to translate these biological insights into more comprehensive and clinically applicable embryo assessment strategies that may improve embryo prioritization, shorten time to pregnancy, and support more effective single-embryo transfer decisions.This collection focuses on the biological and clinical integration of genetic, morphological, and functional parameters for the assessment of human preimplantation embryo competence.We welcome submissions addressing, but not limited to, the following themes:•  Biological and cellular determinants of implantation failure and early pregnancy loss following euploid embryo transfer•  Functional biomarkers of embryo competence including metabolomic and secretomic profiling of spent culture media, embryo metabolism, mitochondrial function, and mtDNA-related biomarkers•  Clinical management, transfer prioritization, and reproductive outcomes of mosaic and segmental aneuploid embryos•  Analytical validity and clinical concordance of non-invasive PGT (niPGT) using blastocoel fluid or spent culture medium•  Epigenetic and cellular effects of ovarian stimulation protocols, culture conditions, and vitrification/cryo-storage on embryo viability•  Multi-parameter scoring models combining genetic, phenotypic, and functional readouts to refine embryo prioritizationEditor Dr. Christian Simon Ottolini is a shareholder in GenEthYX S.r.l. The other Topic Editor, Dr. Stefano Canosa, declares no competing interests with regard to the Research Topic subject Topic editors: Stefano Canosa, Christian Ottolini Source: https://www.frontiersin.org/research-topics/86707/beyond-pgt-integrating-genetic-morphological-and-functional-assessment-of-the-human-embryo