Journal of Assisted Reproduction and Genetics

, Volume 35, Issue 6, pp 1005–1010 | Cite as

Obstetric and neonatal outcome following ICSI with assisted oocyte activation by calcium ionophore treatment

  • Ileana MateizelEmail author
  • Greta Verheyen
  • Hilde Van de Velde
  • Herman Tournaye
  • Florence Belva
Assisted Reproduction Technologies



Calcium ionophore treatment is being used in assisted reproductive technology (ART) for cases with previous low fertilization rate or total absence of fertilization after insemination by intracytoplasmic sperm injection or when a specific indication such as globozoospermia is present. As this technique is more invasive and differs from the physiological process of fertilization, a thorough investigation of the health of the children born following this procedure is required. We intent to report the medical outcome of all children conceived following calcium ionophore treatment in our IVF center.


One-armed descriptive study is performed to report the obstetrical and neonatal outcome of children born after using calcium ionophore treatment during the intracytoplasmic sperm injection procedure in our center.


A number of 237 cycles were included in this study, with 74 pregnancies reported, from which 47 children (31 singletons and 16 twin children) were born. No major malformations were detected in singletons. In twins, three children were diagnosed with major malformations. Minor malformations were present in seven singletons and in one twin.


In conclusion, our results regarding birth characteristics and congenital malformations are within the expected range but, although reassuring, should be interpreted with caution due to the small number of children included.


Assisted oocyte activation Calcium ionophore Malformations Neonatal outcome Obstetrical outcome 



The authors wish to thank the clinical embryologists and laboratory technologists from the Centre for Reproductive Medicine and to Andrea Buysse from the Centre of Medical Genetics.

Compliance with ethical standards

No additional informed consent was required. The study was approved by the Ethical Committee of the UZ Brussel (B.U.N. 143201732431).

Conflict of interest

The authors declare that they have no conflict of interest.


  1. 1.
    Johnson LN, Sasson IE, Sammel M, Dokras A, et al. Does intracytoplasmic sperm injection improve the fertilization rate and decrease the total fertilization failure rate in couples with well-defined unexplained infertility? A systematic review and meta-analysis. Fertil Steril. 2013;100:704–11.CrossRefPubMedGoogle Scholar
  2. 2.
    Yeste M, Jones C, Amdani SN, Patel S, Coward K. Oocyte activation deficiency: a role for an oocyte contribution? Hum Reprod Update. 2016;22:23–47.CrossRefPubMedGoogle Scholar
  3. 3.
    Jones KT. Intracellular calcium in the fertilization and development of mammalian eggs. Clin Exp Pharmacol Physiol. 2007;34:1084–9.CrossRefPubMedGoogle Scholar
  4. 4.
    Murugesu S, Saso S, Jones BP, et al. Does the use of calcium ionophore during artificial oocyte activation demonstrate an effect on pregnancy rate? A meta-analysis. Fertil Steril. 2017;108:468–82.CrossRefPubMedGoogle Scholar
  5. 5.
    Sfontouris IA, Nastri CO, Lima ML, et al. Artificial oocyte activation to improve reproductive outcomes in women with previous fertilization failure: a systematic review and meta-analysis of RCTs. Hum Reprod. 2015;30:1831–41.CrossRefPubMedGoogle Scholar
  6. 6.
    Van Blerkom J, Cohen J, Johnson M. A plea for caution and more research in the ‘experimental’ use of ionophores in ICSI. Reprod BioMed Online. 2015;30:323–4.CrossRefPubMedGoogle Scholar
  7. 7.
    Ozil JP, Banrezes B, Tóth S, et al. Ca2+ oscillatory pattern in fertilized mouse eggs affects gene expression and development to term. Dev Biol. 2006;15:534–44.CrossRefGoogle Scholar
  8. 8.
    Vanden Meerschaut F, Nikiforaki D, Heindryckx B, et al. Assisted oocyte activation following ICSI fertilization failure. Reprod BioMed Online. 2014;28:560–71.CrossRefGoogle Scholar
  9. 9.
    D'Haeseleer E, Vanden Meerschaut F, Bettens K, et al. Language development of children born following intracytoplasmic sperm injection (ICSI) combined with assisted oocyte activation (AOA). Int J Lang Commun Disord. 2014;49:702–9.CrossRefPubMedGoogle Scholar
  10. 10.
    Miller N, Biron-Shental T, Sukenik-Halevy R, et al. Oocyte activation by calcium ionophore and congenital birth defects: a retrospective cohort study. Fertil Steril. 2016;106:590–6.CrossRefPubMedGoogle Scholar
  11. 11.
    Capalbo A, Ottolini CS, Griffin DK, et al. Artificial oocyte activation with calcium ionophore does not cause a widespread increase in chromosome segregation errors in the second meiotic division of the oocyte. Fertil Steril. 2016;105:807–14.CrossRefPubMedGoogle Scholar
  12. 12.
    Bonduelle M, Liebaers I, Deketelaere V, et al. Neonatal data on a cohort of 2889 infants born after ICSI (1991-1999) and of 2995 infants born after IVF (1983-1999). Hum Reprod. 2002;17:671–94.CrossRefPubMedGoogle Scholar
  13. 13.
    Heindryckx B, De Gheselle S, Gerris J, et al. Efficiency of assisted oocyte activation as a solution for failed intracytoplasmic sperm injection. Reprod BioMed Online. 2008;17:662–8.CrossRefPubMedGoogle Scholar
  14. 14.
    Belva F, De Schrijver F, Tournay H, et al. Neonatal outcome of 724 children born after ICSI using non-ejaculated sperm. Hum Reprod. 2011;26:1752–8.CrossRefPubMedGoogle Scholar
  15. 15.
    Santella L, Dale B. Assisted yes, but where do we draw the line? Reprod BioMed Online. 2015;31:476–8.CrossRefPubMedGoogle Scholar
  16. 16.
    Borges E, de Almeida Ferreira Braga DP, de Sousa Bonetti TC, et al. Artificial oocyte activation using calcium ionophore in ICSI cycles with spermatozoa from different sources. Reprod BioMed Online. 2009;18:45–52.CrossRefPubMedGoogle Scholar
  17. 17.
    Montag M, Köster M, van der Ven K, et al. The benefit of artificial oocyte activation is dependent on the fertilization rate in a previous treatment cycle. Reprod BioMed Online. 2012;24:52152–5256.CrossRefGoogle Scholar
  18. 18.
    Ebner T, Köster M, Shebl O, et al. Application of a ready-to-use calcium ionophore increases rates of fertilization and pregnancy in severe male factor infertility. Fertil Steril. 2012;98:1432–7.CrossRefPubMedGoogle Scholar
  19. 19.
    Ebner T, Montag M, Oocyte Activation Study Group, et al. Live birth after artificial oocyte activation using a ready-to-use ionophore: a prospective multicentre study. RBMOnline. 2015;30:359–65.Google Scholar
  20. 20.
    Nikiforaki D, Vanden Meerschaut F, de Roo C, et al. Effect of two assisted oocyte activation protocols used to overcome fertilization failure on the activation potential and calcium releasing pattern. Fertil Steril. 2016;105:798–806.CrossRefPubMedGoogle Scholar
  21. 21.
    Belva F, Bonduelle M, Roelants M, et al. Semen quality of young adult ICSI offspring: the first results. Hum Reprod. 2016;31:2811–20.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Centre for Reproductive MedicineVrije Universiteit Brussel (VUB), Universitair Ziekenhuis Brussel (UZ Brussel)BrusselsBelgium
  2. 2.Centre for Medical GeneticsVrije Universiteit Brussel (VUB), Universitair Ziekenhuis Brussel (UZ Brussel)BrusselsBelgium

Personalised recommendations