PREDICTING EMBRYO QUALITY IN WOMEN OF ADVANCED MATERNAL AGE: DOES THE RELATIVE IMPORTANCE OF INNER CELL MASS VERSUS TROPHECTODERM MORPHOLOGY DIFFER FROM YOUNGER COHORTS?

Abstract

Background. Blastocyst morphology remains the best broadly used non-invasive predictor of implantation potential. “Inner cell mass (ICM) and trophectoderm (TE)” grades are recognized to carry prognostic information, but whether their relative predictive weight is modified by maternal age is unclear. Objective. To determine whether the relative importance of ICM versus TE morphology for predicting euploidy and live birth differs between “women of advanced maternal age (AMA, ≥35 years)” and younger women. Methods. We analysed 5,620 biopsied blastocysts across four age strata (<35, 35–37, 38–40 and ≥41 years) and 1,370 single euploid blastocyst transfers. Gardner “ICM and TE grades were related to euploidy (preimplantation genetic testing for aneuploidy, PGT-A) and to live birth” using stratified multivariable logistic regression, likelihood-ratio interaction tests and ROC analysis. Results. Euploidy declined with age (60.8% to 20.3%). TE grade was the dominant morphological predictor of euploidy at every age (adjusted odds ratio [aOR] for TE-A vs B ≈ 2.0; AUC 0.62–0.63), with no age interaction (p = 0.462); ICM added little (AUC 0.52–0.54). For live birth the pattern reversed with age: TE-A predicted live birth in younger women (aOR 2.70) but lost significance by ≥41 years, whereas the ICM effect strengthened (ICM-A aOR rising to 2.86 and ICM C aOR falling to 0.07 at ≥41 years). The age × ICM interaction for live birth was highly significant (p <0.001), as was the age × TE interaction (p = <0.001). ICM discrimination for live birth rose from AUC 0.54 (<35) to 0.73 (≥41), while TE fell from 0.62 to 0.45. Conclusions. The relative prognostic importance of ICM and TE morphology is age-dependent. TE grade best predicts the chromosomal (euploidy) axis irrespective of age, whereas ICM grade becomes the more informative predictor of “live birth in women of advanced maternal age”. Age-specific weighting of morphological parameters may improve embryo selection and counselling in older patients.