Independent inner cell mass and trophectoderm morphology as non-invasive predictors of embryo euploidy in IVF

This study evaluates the independent correlation between inner cell mass (ICM) and trophectoderm (TE) grading with preimplantation genetic testing for aneuploidy (PGT-A) outcomes in embryos biopsied on Day 5 or Day 6 to determine whether morphology-based selection can serve as an alternative to PGT-A. A retrospective analysis of 1,292 embryos from patients undergoing IVF at a single academic center was conducted between October 2019 and March 2023. Blastocysts were graded using Society for Assisted Reproductive Technology (SART) morphology criteria, and biopsy results were categorized as euploid, aneuploid, mosaic, inconclusive, or low DNA. Maternal age (24-45 years) was analyzed both by SART age groups (< 35, 35-37, 38-40, 41-42, > 42) and in a multivariable logistic regression (euploid vs aneuploid) adjusting for age, biopsy day (Day 5 vs Day 6), inner cell mass (ICM), and trophectoderm (TE). Embryos with mosaic, inconclusive, or low-DNA results were excluded from inferential analyses. Statistical analysis was performed using the chi-square test (p < 0.05). Of the 1,292 embryos, 632 (48.9%) were euploid, 508 (39.3%) aneuploid, and 152 (11.8%) mosaic or inconclusive. Good ICM embryos had significantly higher euploidy rates than aneuploidy on both biopsy days (p < 0.001), while poor ICM embryos had higher aneuploidy rates (p < 0.001). Similarly, good TE embryos were more likely to be euploid than poor TE embryos (p < 0.001). Day 5 embryos had significantly higher euploidy rates than Day 6 embryos across all grading categories (p < 0.05). However, no statistical difference was found between Day 6 good ICM embryos and Day 5 fair ICM embryos (p = 0.1335), while Day 6 good TE embryos had higher euploidy than Day 5 fair TE embryos (p < 0.01). Euploidy declined stepwise across SART age groups. In the adjusted model, each additional year of maternal age after 35 lowered the odds of euploidy by ~ 6%. Both ICM and TE grades predict embryo euploidy, supporting the use of morphological assessment to optimize embryo selection and potentially reduce reliance on PGT-A.