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Updated: May 4, 2026

Protocol for Human Blastoids Modeling Blastocyst Development and Implantation
Published on: August 10, 2022
The spatial arrangement of blastomeres at the 4-cell stage and IVF outcome
Goedele Paternot1, Sophie Debrock1, Diane De Neubourg1
1Leuven University Fertility Center, UZ Leuven, Gasthuisberg, Campus Gasthuisberg, Herestraat 49, 3000 Leuven, Belgium.
Abstract:
This study compared the developmental and implantation potential of tetrahedrally arranged versus non-tetrahedrally arranged 4-cell-stage embryos. If the cleavage planes of a 4-cell-stage embryo were perpendicularly orientated, blastomeres were defined as tetrahedrally arranged, while embryos with parallel-orientated cleavage axes were considered as non-tetrahedral embryos. The 4-cell-stage embryos (n=862) examined in this study were obtained from 299 patients aged <36 years. A total of 299 embryos were transferred as a single-embryo transfer on day 3. This study showed that tetrahedral embryos developed into a 8-cell-stage embryo on day 3 more frequently (307, 45% versus 42, 24%; P<0.0001) and also developed more frequently into good-quality embryos (461, 67% versus 67, 38%; P<0.0001) and into excellent-quality embryos (290, 42% versus 34, 19%; P<0.0001). Tetrahedral embryos had a significantly higher implantation potential (98, 38% versus 9, 21%; P=0.038), ongoing pregnancy rate (84, 33% versus 7, 16%; P=0.032) and live birth rate (84, 33% versus 7, 16%; P=0.032). In conclusion, tetrahedral 4-cell-stage embryos on day 2 developed into embryos of better quality on day 3 with a higher implantation potential and live birth rate compared with non-tetrahedral 4-cell-stage embryos. In this study, an additional characteristic of 4-cell-stage embryos has been evaluated. The aim of the study was to evaluate the spatial arrangement of blastomeres in a 4-cell-stage embryo. If the cleavage planes of a 4-cell-stage embryo were perpendicularly orientated (indicating that both axes meet a right angle), blastomeres were defined as tetrahedral arranged while the other embryos were considered as non-tetrahedral embryos. The 4-cell-stage embryos (n=862) examined in this study were obtained from 299 patients aged <36 years. A total of 299 embryos were transferred as a single-embryo transfer on day 3. This study showed that tetrahedral embryos developed into an 8-cell-stage embryo on day 3 more frequently (307, 45% versus 42, 24%; P<0.0001) and also developed more frequently into good-quality embryos (461, 67% versus 67, 38%; P<0.0001) and excellent-quality embryos (290, 42% versus 34, 19%; P<0.0001). Tetrahedral embryos had a significantly higher implantation potential (98, 38% versus 9, 21%; P=0.038), ongoing pregnancy rate (84, 33% versus 7, 16%; P=0.032) and live birth rate (84, 33% versus 7, 16%; P=0.032). In conclusion, tetrahedral 4-cell-stage embryos on day 2 developed into embryos of better quality on day 3 with a higher implantation potential and live birth rate compared with non-tetrahedral 4-cell-stage embryos.
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