P-246 Independent inner cell mass and trophectoderm morphology as non-invasive predictors of embryo euploidy in in vitro fertilization

Study question

Do independent inner cell mass (ICM) and trophectoderm (TE) morphology provide a non-invasive method to predict embryo euploidy in in vitro fertilization (IVF)?

Summary answer

ICM and TE grades independently predict euploidy, supporting a non-invasive tool to refine embryo selection and reduce reliance on preimplantation genetic testing for aneuploidy (PGT-A).

What is known already

Despite several advancements in assisted reproductive technology, pregnancy rates are still significantly lagging. Embryo morphology is one of the key predictors of IVF outcomes, with embryo ICM and TE grades being critical components of blastocyst evaluation. While some data showed a correlation between TE grading and embryo euploidy, data on ICM grading’s predictive value is limited. PGT-A, despite its growing use, is costly, invasive, and prone to inaccuracies, raising the need for alternative selection methods.

Study design, size, duration

This retrospective cohort study analyzed 1,292 embryos biopsied for PGT-A at a single academic center between October 2019 and March 2023. Society for Assisted Reproductive Technology (SART) criteria were utilized to grade all embryos prior to vitrification. Patient information was anonymized before analysis.

Participants/materials, setting, methods

Embryos from patients aged 24–45 years were included. All patients underwent IVF using gonadotropin-releasing hormone (GnRH) antagonist protocols followed by HCG or GnRH agonist trigger injection and oocyte retrieval within 34-36 hours. ICM and TE of embryos that reached blastocyst stage were graded using SART criteria. PGT-A categorized embryos as euploid, aneuploid, or other (mosaic, inconclusive, low DNA). Chi-square tests assessed associations between morphology and euploidy rates, with statistical significance set at p < 0.05.

Main results and the role of chance

Day 5 embryos had higher euploidy rates than Day 6 embryos, particularly among fair and poor-quality ICM and TE grades which reached statistically significant differences (p < 0.05). Good ICM grades were associated with higher euploidy rates (67% on Day 5, 63% on Day 6), whereas poor ICM grades showed predominantly aneuploid outcomes (64% and 77%, respectively). Similarly, good TE grades had higher euploidy rates (69% on Day 5, 67% on Day 6), while poor TE grades were linked to higher aneuploidy (53% and 76%, respectively).

Euploidy rates declined significantly as ICM and TE grades worsened. For Day 5 embryos, the euploidy rate was 67%, 53%, and 36% for good, fair, and poor ICM, respectively. This trend was also observed for TE with euploidy rates of 69%, 51%, and 47%. A similar decline was observed for Day 6 embryos with ICM euploidy rates of 63%, 42%, and 23%, respectively, and TE euploidy rates of 67%, 42%, and 23%. In addition, Day 6 embryos with good TE grades had higher euploidy rates than Day 5 embryos with fair TE grades (p = 0.0114), but this was not observed for ICM (p = 0.1335).

Limitations, reasons for caution

The retrospective nature and single-center design may limit generalizability. Although live birth outcomes were not analyzed, we focused on the association between ICM/TE grading and euploidy. Future prospective studies could further refine morphology-based decision-making for embryo selection, limiting the need for invasive procedures and potentially reducing IVF costs.

Wider implications of the findings

This study supports independent ICM and TE grading as a cost-effective tool for embryo selection. Embryo transfer could follow this sequence: Day 5 good ICM/TE, Day 6 good ICM/TE, Day 5 fair ICM/TE, Day 6 fair ICM/TE, Day 5 poor ICM/TE, and finally Day 6 poor ICM/TE.

Trial registration number

No