Exploring the increasing aneuploidy stress effects on embryo morphokinetic development: non-linear and stage-specific disruption in developmental timing.

purposeTo investigate how different forms of chromosomal imbalance affect human embryo morphokinetics, using a dataset of PGT-A tested embryos and a robust statistical framework that accounts for patient- and cycle-level variability.

methodsThis retrospective cohort study included 1303 embryos from 525 ICSI-PGT-A cycles from a single centre. Embryos were categorized by aneuploidy type as euploid, single, double, or complex (≥ 3) and further subtyped by chromosomal configuration. Developmental timings were extracted from time-lapse monitoring and compared using linear mixed-effects models with random intercepts for patient and treatment cycle. Estimated marginal means and pairwise contrasts were calculated for each morphokinetic parameter (tPB2 to tEB) and key developmental intervals (tSC → tB, tM → tEB).

resultsMorphokinetic behavior varied according to chromosomal load and aneuploidy type. Single aneuploidies, particularly monosomies, showed a biphasic delay pattern, with subtle slowing during early cleavage (tPNf-t2) and more pronounced divergence during blastulation (tSB-tEB). Double aneuploidies demonstrated partial early compensation followed by late-stage deceleration, suggesting non-additive or adaptive effects. Complex aneuploidies, and especially complex mosaic embryos, exhibited global and cumulative delays across nearly all stages, reflecting a progressive loss of developmental synchrony with increasing genomic imbalance.

conclusionThese findings support a dosage-dependent model of developmental disruption, in which the severity and timing of morphokinetic delay correlate with aneuploidy complexity in a stage-specific and non-linear manner. While not diagnostic on their own, time-lapse imaging may contribute to ploidy risk assessment and help identify embryos that could benefit from biopsy and further evaluation through PGT-A, particularly when integrated with clinical, biomarker, and genomic information.