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Effect of A23187 ionophore treatment on human blastocyst development—a sibling oocyte study

  • Embryo Biology
  • Published:
Journal of Assisted Reproduction and Genetics Aims and scope Submit manuscript

Abstract

Purpose

To investigate whether treatment with commercially available ready-to-use A23187 ionophore (GM508-CultActive) improves embryo development outcome in patients with a history of embryo developmental problems.

Methods

This is a uni-center prospective study in which sibling oocytes of patients with embryos of poor quality on day 5 in the previous cycle were treated or not with CultActive.

Results

Two hundred forty-seven metaphase II (MII) oocytes from 19 cycles performed between 2016 and 2019 were included in the study. After ICSI, the sibling oocytes were assigned to the treatment group or to the control group, following an electronically generated randomization list. A number of 122 MII were treated with CultActive and 125 MII had no treatment and were assigned to the control group. No difference in fertilization rate (p = 0.255) or in the capacity of embryos to reach good quality on day 5 (p = 0.197) was observed between the two groups. The utilization rates defined as the number of embryos transferred or cryopreserved per mature oocyte (p = 0.438) or per fertilized oocytes (p = 0.299) were not significantly different between the treated group and the control group.

Conclusion

The results of the current study do not support the use of CultActive in cases with embryo developmental problems.

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References

  1. Saunders CM, Larman MG, Parrington J, Cox LJ, Royse J, Blayney ML, Swann K, Lai FA. PLC zeta: a sperm-specific trigger of Ca(2+) oscillations in eggs and embryo development. Development. 2002;129(15):3533–44.

    Article  CAS  PubMed  Google Scholar 

  2. Swann K, Larman MG, Saunders CM, Lai FA. The cytosolic sperm factor that triggers Ca2+ oscillations and egg activation in mammals is a novel phospholipase C: PLCzeta. Reproduction. 2004;127:431–9.

    Article  CAS  PubMed  Google Scholar 

  3. Yeste M, Jones C, Amdani SN, Patel S, Coward K. Oocyte activation deficiency: a role for an oocyte contribution? Hum Reprod Update. 2016;22(1):23–47. https://doi.org/10.1093/humupd/dmv040.

    Article  CAS  PubMed  Google Scholar 

  4. Whitaker M. Calcium at fertilization and in early development. Physiol Rev. 2006;86(1):25–88. https://doi.org/10.1152/physrev.00023.2005.

    Article  CAS  PubMed  Google Scholar 

  5. Jones KT. Intracellular calcium in the fertilization and development of mammalian eggs. Clin Exp Pharmacol Physiol. 2007;34(10):1084–9. https://doi.org/10.1111/j.1440-1681.2007.04726.

    Article  CAS  PubMed  Google Scholar 

  6. Schultz RM, Kopf GS. Molecular basis of mammalian egg activation. Curr Top Dev Biol. 1995;30:21–62. https://doi.org/10.1016/s0070-2153(08)60563-3.

    Article  CAS  PubMed  Google Scholar 

  7. Amdani SN, Jones C, Coward K. Phospholipase C zeta (PLCζ): oocyte activation and clinical links to male factor infertility. Adv Biol Regul. 2013;53(3):292–308. https://doi.org/10.1016/j.jbior.2013.07.005.

    Article  CAS  PubMed  Google Scholar 

  8. Yoon SY, Jellerette T, Salicioni AM, Lee HC, Yoo MS, Coward K, et al. Human sperm devoid of PLC, zeta 1 fail to induce Ca2+ release and are unable to initiate the first step of embryo development. J Clin Invest. 2008;118:3671–81. https://doi.org/10.1172/JCI36942.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  9. Heytens E, Parrington J, Coward K, Young C, Lambrecht S, Yoon SY, Fissore RA, Hamer R, et al. Reduced amounts and abnormal forms of phospholipase C zeta in spermatozoa from infertile men. Hum Reprod. 2009;24:2417–28. https://doi.org/10.1093/humrep/dep207.

    Article  CAS  PubMed  Google Scholar 

  10. Darwish E, Magdi Y. A preliminary report of successful cleavage after calcium ionophore activation at ICSI in cases with previous arrest at the pronuclear stage. Reprod Biomed Online. 2015;31(6):799–804. https://doi.org/10.1016/j.rbmo.2015.08.012.

    Article  CAS  PubMed  Google Scholar 

  11. Ebner T, Oppelt P, Wöber M, Staples P, Mayer RB, Sonnleitner U, Bulfon-Vogl S, Gruber I, Haid AE, Shebl O. Treatment with Ca2+ ionophore improves embryo development and outcome in cases with previous developmental problems: a prospective multicenter study. Hum Reprod. 2015;30(1):97–102. https://doi.org/10.1093/humrep/deu285.

    Article  CAS  PubMed  Google Scholar 

  12. Ducibella T, Huneau D, Angelichio E, Xu Z, Schultz RM, Kopf GS, Fissore R, Madoux S, Ozil JP. Egg-to-embryo transition is driven by differential responses to Ca(2+) oscillation number. Dev Biol. 2002;250(2):280–91.

    Article  CAS  PubMed  Google Scholar 

  13. Ozil JP, Huneau D. Activation of rabbit oocytes: the impact of the Ca2+ signal regime on development. Development. 2001;128(6):917–28.

    Article  CAS  PubMed  Google Scholar 

  14. Malcuit C, Kurokawa M, Fissore RA. Calcium oscillations and mammalian egg activation. J Cell Physiol. 2006;206(3):565–73. https://doi.org/10.1002/jcp.20471.

    Article  CAS  PubMed  Google Scholar 

  15. Machaty Z. Signal transduction in mammalian oocytes during fertilization. Cell Tissue Res. 2016;363(1):169–83. https://doi.org/10.1007/s00441-015-2291-8.

    Article  CAS  PubMed  Google Scholar 

  16. Ozil JP, Banrezes B, Tóth S, Pan H, Schultz RM. Ca2+ oscillatory pattern in fertilized mouse eggs affects gene expression and development to term. Dev Biol. 2006;300(2):534–44. https://doi.org/10.1016/j.ydbio.2006.08.041.

    Article  CAS  PubMed  Google Scholar 

  17. Tóth S, Huneau D, Banrezes B, Ozil JP. Egg activation is the result of calcium signal summation in the mouse. Reproduction. 2006;131(1):27–34. https://doi.org/10.1530/rep.1.00764.

    Article  CAS  PubMed  Google Scholar 

  18. Ferrer-Buitrago M, Bonte D, De Sutter P, Leybaert L, Heindryckx B. Single Ca2+ transients vs oscillatory Ca2+ signaling for assisted oocyte activation: limitations and benefits. Reproduction. 2018;155(2):105–19. https://doi.org/10.1530/REP-17-0098.

    Article  Google Scholar 

  19. Gardner DK, Schoolcraft WB. In-vitro culture of human blastocysts. In: Jansen R, Mortimer D, editors. Towards reproductive certainty: fertility and genetics beyond 1999. Carnforth: Parthenon Press; 1999. p. 378–88.

    Google Scholar 

  20. De Munck N, Santos-Ribeiro S, Mateizel I, Verheyen G. Reduced blastocyst formation in reduced culture volume. J Assist Reprod Genet. 2015;32(9):1365–70. https://doi.org/10.1007/s10815-015-0541-z.

    Article  PubMed Central  PubMed  Google Scholar 

  21. Lv M, Dan Zhang D, He X, Chen B, Li Q, Ding D, Hao Y, Xue R, Ji D, et al. Artificial oocyte activation to improve reproductive outcomes in couples with various causes of infertility: a retrospective cohort study. Reprod Biomed Online. 2020;40(4):501–9. https://doi.org/10.1016/j.rbmo.2020.01.001.

    Article  CAS  PubMed  Google Scholar 

  22. Shebl O, Trautner PS, Enengl S, Reiter E, Allerstorfer C, Rechberger T, Oppelt P, Ebner T. Ionophore application for artificial oocyte activation and its potential effect on morphokinetics: a sibling oocyte study. J Assist Reprod Genet. 2021;38(12):3125–33. https://doi.org/10.1007/s10815-021-02338-3.

    Article  PubMed Central  PubMed  Google Scholar 

  23. Miller N, Biron-Shental T, Sukenik-Halevy R, Klement AH, Sharony R, Berkovitz A. Oocyte activation by calcium ionophore and congenital birth defects: a retrospective cohort study. Fertil Steril. 2016 1;106(3):590–6. https://doi.org/10.1016/j.fertnstert.2016.04.025

  24. Mateizel I, Verheyen G, Van de Velde H, Tournaye H, Belva F. Obstetric and neonatal outcome following ICSI with assisted oocyte activation by calcium ionophore treatment. J Assist Reprod Genet. 2018;35(6):1005–10. https://doi.org/10.1007/s10815-018-1124-6.

    Article  PubMed Central  PubMed  Google Scholar 

  25. Li B, Zhou Y, Yan Z, Li M, Xue S, Cai R, Fu Y, Hong et al. Pregnancy and neonatal outcomes of artificial oocyte activation in patients undergoing frozen-thawed embryo transfer: a 6-year population-based retrospective study. Arch Gynecol Obstet. 2019 Oct;300(4):1083–92. https://doi.org/10.1007/s00404-019-05298-3

  26. Moaz MN, Khattab S, Foutouh IA, Mohsen EA. Chemical activation of oocytes in different types of sperm abnormalities in cases of low or failed fertilization after ICSI: a prospective pilot study. Reprod Biomed Online. 2006;13(6):791–4. https://doi.org/10.1016/s1472-6483(10)61025-5.

    Article  CAS  PubMed  Google Scholar 

  27. Heindryckx B, De Gheselle S, Gerris J, Dhont M, De Sutter P. Efficiency of assisted oocyte activation as a solution for failed intracytoplasmic sperm injection. Reprod Biomed Online. 2008;17(5):662–8. https://doi.org/10.1016/s1472-6483(10)60313-6.

    Article  PubMed  Google Scholar 

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Acknowledgements

The authors wish to thank the clinical embryologists, medical doctors, and laboratory technologists of the Brussels IVF center from Universitair Ziekenhuis Brussel (UZBrussel).

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Correspondence to Ileana Mateizel.

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Mateizel, I., Santos-Ribeiro, S., Segers, I. et al. Effect of A23187 ionophore treatment on human blastocyst development—a sibling oocyte study. J Assist Reprod Genet 39, 1225–1232 (2022). https://doi.org/10.1007/s10815-022-02467-3

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  • DOI: https://doi.org/10.1007/s10815-022-02467-3

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