Good embryos left behind: morphokinetic prioritization may penalize chromosomally competent embryos

Do morula compaction patterns and morphokinetic scoring systems accurately reflect chromosomal competence, or do they introduce bias that deprioritizes viable embryos?

This retrospective cohort study included 1711 blastocysts derived from 611 intracytoplasmic sperm injection cycles cultured in a time-lapse system. Embryos were classified according to KIDScore, morula compaction pattern [fully compacted morulae (FCM) versus partially compacted morulae with cells excluded from compaction from the outset (Exc-PCM)], and the Blastocyst Fragmentation Indicator (BFI). Chromosomal status was assessed using next-generation sequencing.

Embryos derived from Exc-PCM exhibited significantly slower developmental kinetics (standardized developmental interval between the 5-cell and blastocyst stages: 0.780 versus -0.216 for FCM; P < 0.001), and were disproportionately classified into the lowest morphokinetic category, namely KIDScore C (73.9% versus 25.5% for FCM). Despite this, euploidy rates were similar between Exc-PCM and FCM embryos (43.7% versus 43.4%, respectively). In multivariable models, blastocyst fragmentation was most strongly associated with euploidy [adjusted OR (aOR) 0.04 for combined inner cell mass and trophectoderm fragmentation versus no fragmentation; P < 0.001]. After adjustment, Exc-PCM embryos showed higher odds of euploidy than FCM embryos (aOR 1.56; P = 0.008). Within KIDScore C embryos, those without fragmentation (rated as 'no fragmentation' on the BFI) retained relatively high euploidy rates (50.0-66.7%).

Morphokinetic scoring systems based on developmental speed may introduce bias in embryo prioritization, particularly affecting embryos derived from PCM. Structural integrity, rather than developmental timing, may better reflect chromosomal competence. Integrating structural assessment may improve embryo prioritization strategies.