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Vacuolization in embryos on days 3 and 4 of in vitro development: Association with stimulation protocols, embryo
Longbin Chen1, Shuoping Zhang2, Yifan Gu1,2,3
1Institute of Reproductive and Stem Cells, School of Basic Medicine, Central South University, Changsha, China.
Insights
Embryo vacuolization on days 3 and 4 is linked to lower blastocyst formation but not pregnancy outcomes. However, excluding vacuolated cells during compaction may indicate a self-correction mechanism in embryo development.
Area of Science:
- Reproductive biology
- Embryology
- In vitro fertilization
Background:
- Vacuolization is a common phenomenon observed in human embryos during in vitro fertilization (IVF).
- The clinical significance of embryo vacuolization, particularly in the early cleavage stages (Days 3-4), remains incompletely understood.
- Understanding factors associated with vacuolization and its impact on embryo development and outcomes is crucial for improving IVF success rates.
Purpose of the Study:
- To investigate the association between embryo vacuolization on Days 3 and 4 and parent-related factors, stimulation protocols, embryo development, ploidy, and pregnancy outcomes.
- To determine if embryo vacuolization affects key developmental milestones such as blastocyst formation and quality.
- To explore the relationship between vacuolization, mosaicism, and potential self-correction mechanisms during embryo compaction.
Main Methods:
- Retrospective cohort study of 5,703 embryos from 611 patients undergoing preimplantation genetic testing (PGT) and time-lapse monitoring.
- Data collected from August 2017 to September 2021.
- Analysis of associations between vacuolization and various clinical and embryonic parameters.
Main Results:
- Embryo vacuolization on Days 3 and 4 correlated with higher LH levels on hCG trigger day and increased oocyte retrieval numbers.
- Vacuole-positive embryos showed significantly lower rates of blastocyst and good-blastocyst formation compared to vacuole-negative embryos.
- No significant differences were observed in euploidy, implantation, ongoing pregnancy, or live birth rates between vacuole-positive and negative embryos.
- Vacuole-positive blastomeres involved in compaction were associated with higher mosaicism rates, suggesting a potential exclusion mechanism.
Conclusions:
- Embryo vacuolization on Days 3 and 4 is associated with diminished blastocyst development potential.
- The exclusion of vacuolated cells during compaction may represent an embryo self-correction mechanism to reduce mosaicism.
- While vacuolization impacts early development, it does not appear to affect key reproductive outcomes like live birth rates.
Study Question:
Is vacuolization in embryos on Days 3 and 4 associated with parent-related factors, stimulation protocols, embryo development, embryo ploidy, pregnancy and neonatal outcomes?
Study Design Size Duration:
This is a retrospective cohort study that comprised 5,703 embryos from 611 patients who underwent preimplantation genetic testing and time-lapse monitoring of their embryos from August 2017 to September 2021.
Main Results:
Embryo vacuolization on Days 3 and 4 is associated with the LH level on the day of the hCG trigger and the number of retrieved oocytes. Compared to vacuole-negative embryos, the rates of blastocyst formation and good-blastocyst formation was significantly lower in vacuole-positive embryos. We observed no significant difference in the rates of euploidy, implantation, ongoing pregnancy, and live birth between vacuole-positive and vacuole-negative embryos. In vacuole-positive embryos, the embryos of which the vacuole-positive blastomeres were involved in embryo compaction exhibited significantly higher mosaicism rate compared with those of which the vacuole-positive blastomeres were not involved in embryo compaction.
Conclusion:
Vacuolization in embryos on Days 3 and 4 is associated with reduced blastocyst formation rate and high-quality blastocyst rate. Blastocysts had a low mosaicism rate if the vacuole-containing cells were rejected in compaction process, which supports the hypothesis that exclusion of abnormal blastomeres from compaction is a self-correction mechanism.
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