Skip to main content
SpringerLink
Log in

Time-lapse imaging of morula compaction for selecting high‐quality blastocysts: a retrospective cohort study

  • Gynecologic Endocrinology and Reproductive Medicine
  • Published:
Archives of Gynecology and Obstetrics Aims and scope Submit manuscript

Abstract

Purpose

Before blastocyst development, embryos undergo morphological and metabolic changes crucial for their subsequent growth. This study aimed to investigate the relationship between morula compaction and blastocyst formation and the subsequent chromosomal status of the embryos.

Methods

This retrospective cohort study evaluated embryo development (n = 371) using time-lapse imaging; 94 blastocysts underwent preimplantation genetic testing for aneuploidy (PGT-A).

Results

The embryos were classified as fully (Group 1, n = 194) or partially (Group 2, n = 177) compacted. Group 1 had significantly higher proportions of good- and average-quality blastocysts than Group 2 (21.6% vs. 3.4%, p = 0.001; 47.9% vs. 26.6%, p = 0.001, respectively). The time from the morula stage to the beginning and completion of compaction and blastocyst formation was significantly shorter in Group 1 than in Group 2 (78.6 vs. 82.4 h, p = 0.001; 87.0 vs. 92.2 h, p = 0.001; 100.2 vs. 103.7 h, p = 0.017, respectively). Group 1 embryos had larger surface areas than Group 2 embryos at various time points following blastocyst formation. Group 1 blastocysts had significantly higher average expansion rates than Group 2 blastocysts (653.6 vs. 499.2 μm2/h, p = 0.001). PGT-A revealed a higher proportion of euploid embryos in Group 1 than in Group 2 (47.2% vs. 36.6%, p = 0.303).

Conclusion

Time-lapse microscopy uncovered a positive relationship between compaction and blastocyst quality and its association with embryo ploidy. Hence, compaction evaluation should be prioritized before blastocyst selection for transfer or cryopreservation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

Data availability

The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request. For further inquiries, please direct them to the corresponding authors.

References

  1. Nagy ZP, Shapiro D, Chang CC (2020) Vitrification of the human embryo: a more efficient and safer in vitro fertilization treatment. Fertil Steril 113:241–247. https://doi.org/10.1016/j.fertnstert.2019.12.009

    Article  CAS  PubMed  Google Scholar 

  2. Gardner DK, Meseguer M, Rubio C, Treff NR (2015) Diagnosis of human preimplantation embryo viability. Hum Reprod Update 21:727–747. https://doi.org/10.1093/humupd/dmu064

    Article  CAS  PubMed  Google Scholar 

  3. Hill MJ, Eubanks AE, Csokmay JM, Christy AY, Jahandideh S, DeCherney AH, Devine K, Levens ED, Connell MT (2020) Is transferring a lower-quality embryo with a good-quality blastocyst detrimental to the likelihood of live birth? Fertil Steril 114:338–345. https://doi.org/10.1016/j.fertnstert.2020.03.027

    Article  PubMed  Google Scholar 

  4. Park JK, Ahn SY, Seok SH, Chang EM, Kim JW, Kwak IP, Lee WS (2022) Does post-warming extended culture duration affect the clinical and obstetric outcomes of patients of advanced maternal age? A single-center study. J Korean Med Sci 37:e96. https://doi.org/10.3346/jkms.2022.37.e96

    Article  PubMed  PubMed Central  Google Scholar 

  5. Huang TT, Huang DH, Ahn HJ, Arnett C, Huang CT (2019) Early blastocyst expansion in euploid and aneuploid human embryos: evidence for a non-invasive and quantitative marker for embryo selection. Reprod Biomed Online 39:27–39. https://doi.org/10.1016/j.rbmo.2019.01.010

    Article  PubMed  Google Scholar 

  6. Coticchio G, Borini A, Zacà C, Makrakis E, Sfontouris I (2022) Fertilization signatures as biomarkers of embryo quality. Hum Reprod 37:1704–1711. https://doi.org/10.1093/humrep/deac123

    Article  PubMed  Google Scholar 

  7. Venturas M, Yang X, Sakkas D, Needleman D (2023) Noninvasive metabolic profiling of cumulus cells, oocytes, and embryos via fluorescence lifetime imaging microscopy: a mini-review. Hum Reprod 38:799–810. https://doi.org/10.1093/humrep/dead063

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Nguyen Q, Sommer S, Greene B, Wrenzycki C, Wagner U, Ziller V (2018) Effects of opening the incubator on morphokinetics in mouse embryos. Eur J Obstet Gynecol Reprod Biol 229:64–69. https://doi.org/10.1016/j.ejogrb.2018.08.003

    Article  PubMed  Google Scholar 

  9. Lundin K, Park H (2020) Time-lapse technology for embryo culture and selection. Ups J Med Sci 125:77–84. https://doi.org/10.1080/03009734.2020.1728444

    Article  PubMed  PubMed Central  Google Scholar 

  10. Boucret L, Tramon L, Saulnier P, Ferré-L’Hôtellier V, Bouet PE, May-Panloup P (2021) Change in the strategy of embryo selection with time-lapse system implementation-impact on clinical pregnancy rates. J Clin Med 10:4111. https://doi.org/10.3390/jcm10184111

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Sainte-Rose R, Petit C, Dijols L, Frapsauce C, Guerif F (2021) Extended embryo culture is effective for patients of an advanced maternal age. Sci Rep 11:13499. https://doi.org/10.1038/s41598-021-92902-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Ezoe K, Miki T, Akaike H, Shimazaki K, Takahashi T, Tanimura Y, Amagai A, Sawado A, Mogi M, Kaneko S, Ueno S, Coticchio G, Cimadomo D, Borini A, Rienzi L, Kato K (2023) Maternal age affects pronuclear and chromatin dynamics, morula compaction and cell polarity, and blastulation of human embryos. Hum Reprod 38:387–399. https://doi.org/10.1093/humrep/dead001

    Article  PubMed  Google Scholar 

  13. Kim HJ, Park JK, Eum JH, Song H, Lee WS, Lyu SW (2021) Embryo selection based on morphological parameters in a single vitrified-warmed blastocyst transfer cycle. Reprod Sci 28:1060–1068. https://doi.org/10.1007/s43032-020-00349-6

    Article  PubMed  Google Scholar 

  14. Van de Velde H, De Vos A, Joris H, Nagy ZP, Van Steirteghem AC (1998) Effect of timing of oocyte denudation and micro-injection on survival, fertilization and embryo quality after intracytoplasmic sperm injection. Hum Reprod 13:3160–3164. https://doi.org/10.1093/humrep/13.11.3160

    Article  PubMed  Google Scholar 

  15. Park JK, Ahn SY, Seok SH, Park SY, Bang S, Eum JH, Kwak IP, Kim JW, Lee WS (2022) Clinical usability of embryo development using a combined qualitative and quantitative approach in a single vitrified-warmed blastocyst transfer: assessment of pre-vitrified blastocyst diameter and post-warmed blastocyst re-expansion speed. J Clin Med 11:7085. https://doi.org/10.3390/jcm11237085

    Article  PubMed  PubMed Central  Google Scholar 

  16. Alpha Scientists in Reproductive Medicine and ESHRE Special Interest Group of Embryology (2011) The Istanbul consensus workshop on embryo assessment: proceedings of an expert meeting. Hum Reprod 26:1270–1283. https://doi.org/10.1093/humrep/der037

    Article  Google Scholar 

  17. ESHRE Working Group on Time-Lapse Technology, Apter S, Ebner T, Freour T, Guns Y, Kovacic B, Le Clef N, Marques M, Meseguer M, Montjean D, Sfontouris I (2020) Good practice recommendations for the use of time-lapse technology. Hum Reprod Open 2020:hoaa008. https://doi.org/10.1093/hropen/hoaa008

  18. Kim MK, Park JK, Jeon Y, Choe SA, Lee HJ, Kim J, Chang EM, Kim JW, Lyu SW, Kim JY, Kwak IP, Lee WS, Yoon TK (2019) Correlation between morphologic grading and euploidy rates of blastocysts, and clinical outcomes in in vitro fertilization preimplantation genetic screening. J Korean Med Sci 34:e27. https://doi.org/10.3346/jkms.2019.34.e27

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Hur C, Nanavaty V, Yao M, Desai N (2023) The presence of partial compaction patterns is associated with lower rates of blastocyst formation, sub-optimal morphokinetic parameters and poorer morphologic grade. Reprod Biol Endocrinol 21(1):12

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Lensen S, Lantsberg D, Gardner DK, Sophian AD, Wandafiana N, Kamath MS (2022) The role of timing in frozen embryo transfer. Fertil Steril 118:832–838. https://doi.org/10.1016/j.fertnstert.2022.08.009

    Article  PubMed  Google Scholar 

  21. Venturas M, Shah JS, Yang X, Sanchez TH, Conway W, Sakkas D, Needleman DJ (2022) Metabolic state of human blastocysts measured by fluorescence lifetime imaging microscopy. Hum Reprod 37:411–427. https://doi.org/10.1093/humrep/deab283

    Article  CAS  PubMed  Google Scholar 

  22. Bebbere D, Coticchio G, Borini A, Ledda S (2022) Oocyte aging: looking beyond chromosome segregation errors. J Assist Reprod Genet 39:793–800. https://doi.org/10.1007/s10815-022-02441-z

    Article  PubMed  PubMed Central  Google Scholar 

  23. Haas J, Meriano J, Bassil R, Barzilay E, Zilberberg E, Casper RF (2019) Developmental potential of slow-developing embryos: day-5 morulae compared with day-5 cavitating morulae. Fertil Steril 111:105–111. https://doi.org/10.1016/j.fertnstert.2018.08.053

    Article  PubMed  Google Scholar 

  24. Coticchio G, Barrie A, Lagalla C, Borini A, Fishel S, Griffin D, Campbell A (2021) Plasticity of the human preimplantation embryo: developmental dogmas, variations on themes and self-correction. Hum Reprod Update 27:848–865. https://doi.org/10.1093/humupd/dmab016

    Article  PubMed  Google Scholar 

  25. Coticchio G, Lagalla C, Sturmey R, Pennetta F, Borini A (2019) The enigmatic morula: mechanisms of development, cell fate determination, self-correction and implications for ART. Hum Reprod Update 25:422–438. https://doi.org/10.1093/humupd/dmz008

    Article  CAS  PubMed  Google Scholar 

  26. Ivec M, Kovacic B, Vlaisavljevic V (2011) Prediction of human blastocyst development from morulas with delayed and/or incomplete compaction. Fertil Steril 96:1473–1478.e2. https://doi.org/10.1016/j.fertnstert.2011.09.015

  27. Lagalla C, Tarozzi N, Sciajno R, Wells D, Di Santo M, Nadalini M, Distratis V, Borini A (2017) Embryos with morphokinetic abnormalities may develop into euploid blastocysts. Reprod Biomed Online 34:137–146. https://doi.org/10.1016/j.rbmo.2016.11.008

    Article  CAS  PubMed  Google Scholar 

  28. Lagalla C, Coticchio G, Sciajno R, Tarozzi N, Zacà C, Borini A (2020) Alternative patterns of partial embryo compaction: prevalence, morphokinetic history and possible implications. Reprod Biomed Online 40:347–354. https://doi.org/10.1016/j.rbmo.2019.11.011

    Article  CAS  PubMed  Google Scholar 

  29. Tao J, Tamis R, Fink K, Williams B, Nelson-White T, Craig R (2002) The neglected morula/compact stage embryo transfer. Hum Reprod 17:1513–1518. https://doi.org/10.1093/humrep/17.6.1513

    Article  PubMed  Google Scholar 

  30. Yang H, Liu Y, Niu W, Yang Z, Wang Y, Jin H, Li G (2023) Correlation study of male semen parameters and embryo aneuploidy in preimplantation genetic testing for aneuploidy. Front Endocrinol (Lausanne) 13:1072176. https://doi.org/10.3389/fendo.2022.1072176

    Article  PubMed  Google Scholar 

  31. Capalbo A, Rienzi L, Cimadomo D, Maggiulli R, Elliott T, Wright G, Nagy ZP, Ubaldi FM (2014) Correlation between standard blastocyst morphology, euploidy and implantation: an observational study in two centers involving 956 screened blastocysts. Hum Reprod 29:1173–1181. https://doi.org/10.1093/humrep/deu033

    Article  PubMed  Google Scholar 

  32. Shi W, Zhou H, Chen L, Xue X, Shi J (2022) Live birth rate following frozen-thawed blastocyst transfer is higher in high-grade day 6 blastocysts than in low-grade day 5 blastocysts. Front Endocrinol (Lausanne) 13:1066757. https://doi.org/10.3389/fendo.2022.1066757

    Article  PubMed  Google Scholar 

  33. Ueno S, Uchiyama K, Kuroda T, Okimura T, Yabuuchi A, Kobayashi T, Kato K (2020) Establishment of day 7 blastocyst freezing criteria using blastocyst diameter for single vitrified-warmed blastocyst transfer from live birth outcomes: a single-center, large cohort, retrospectively matched study. J Assist Reprod Genet 37:2327–2335. https://doi.org/10.1007/s10815-020-01882-8

    Article  PubMed  PubMed Central  Google Scholar 

  34. Hur C, Nanavaty V, Yao M, Desai N (2023) The presence of partial compaction patterns is associated with lower rates of blastocyst formation, sub-optimal morphokinetic parameters and poorer morphologic grade. Reprod Biol Endocrinol 21:12. https://doi.org/10.1186/s12958-023-01059-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Venturas M, Yang X, Kumar K, Wells D, Racowsky C, Needleman DJ (2021) Metabolic imaging of human cumulus cells reveals associations among metabolic profiles of cumulus cells, patient clinical factors, and oocyte maturity. Fertil Steril 116:1651–1662. https://doi.org/10.1016/j.fertnstert.2021.07.1204

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Richani D, Dunning KR, Thompson JG, Gilchrist RB (2021) Metabolic co-dependence of the oocyte and cumulus cells: essential role in determining oocyte developmental competence. Hum Reprod Update 27:27–47. https://doi.org/10.1093/humupd/dmaa043

    Article  CAS  PubMed  Google Scholar 

  37. Guo YH, Liu Y, Qi L, Song WY, Jin HX (2021) Can time-lapse incubation and monitoring be beneficial to assisted reproduction technology outcomes? A randomized controlled trial using day 3 double embryo transfer. Front Physiol 12:794601. https://doi.org/10.3389/fphys.2021.794601

    Article  PubMed  Google Scholar 

  38. Zhao J, Yan Y, Huang X, Sun L, Li Y (2019) Blastocoele expansion: an important parameter for predicting clinical success pregnancy after frozen-warmed blastocysts transfer. Reprod Biol Endocrinol 17:15. https://doi.org/10.1186/s12958-019-0454-2

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The authors thank the other CHA Fertility Center Gangnam embryologists and physicians who contributed significantly to this project. This research was supported by a grant from the Korean Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI) funded by the Ministry of Health and Welfare, Republic of Korea (grant number: HI21C1560020021).

Funding

This work was supported by a grant from the Korean Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI) funded by the Ministry of Health and Welfare, Republic of Korea (grant number: HI21C1560020021).

Author information

Author notes

  1. Jae Kyun Park and Yunmi Jeon have contributed equally to this work.

Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Fertility Center of CHA Gangnam Medical Center, CHA University School of Medicine, 566 Nonhyeon-ro, Gangnam-gu, Seoul, 06135, Korea

    Jae Kyun Park, Yunmi Jeon, Soyoung Bang, Ji Won Kim, In Pyung Kwak & Woo Sik Lee

Authors
  1. Jae Kyun Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yunmi Jeon
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Soyoung Bang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ji Won Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. In Pyung Kwak
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Woo Sik Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

JW Kim and WS Lee: project development and manuscript writing/editing. JK Park: data collection and analysis, and manuscript writing/editing. YM Jeon, SY Bang, and IP Kwak: data collection and analysis, and manuscript writing. All authors contributed to revising the manuscript and approved the final version.

Corresponding authors

Correspondence to Ji Won Kim or Woo Sik Lee.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethics approval

All procedures conducted in the study adhered to the ethical standards set by the Institutional Review Board of CHA Gangnam Medical Center (GCI 2023-07-010-001), following the 1964 Helsinki Declaration and its subsequent amendments, or equivalent ethical standards.

Consent to participate

The requirement of participant consent was waived owing to the study’s retrospective nature and the utilization of medical records.

Research involving human participants and/or animals

All procedures conducted in the study adhered to the ethical standards set by the institutional and national research committee, following the 1964 Helsinki Declaration and its subsequent amendments, or equivalent ethical standards.

Informed consent

The requirement of participant consent was waived owing to the study’s retrospective nature and the utilization of medical records.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

404_2024_7461_MOESM1_ESM.docx

Supplementary file1 Online Resource 1 Examples of morphologic compaction patterns. a Fully compacted morula; b partially compacted morula (DOCX 96 kb)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Park, J.K., Jeon, Y., Bang, S. et al. Time-lapse imaging of morula compaction for selecting high‐quality blastocysts: a retrospective cohort study. Arch Gynecol Obstet (2024). https://doi.org/10.1007/s00404-024-07461-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s00404-024-07461-x

Keywords

Search

Navigation