ORIGINAL ARTICLE Embryology
Assisted oocyte activation is not
beneficial for all patients with a
suspected oocyte-related activation
F. Vanden Meerschaut*, D. Nikiforaki, S. De Gheselle, V. Dullaerts,
E. Van den Abbeel, J. Gerris, B. Heindryckx, and P. De Sutter
Department for Reproductive Medicine, Ghent University Hospital, De Pintelaan 185, B-9000 Ghent, Belgium
*Correspondence address. De Pintelaan 185, B-9000 Ghent, Belgium. Tel: +32(0)9-332-02-89; E-mail: email@example.com
Submitted on October 4, 2011; resubmitted on December 30, 2011; accepted on February 8, 2012
background: Despite the success of ICSI, total fertilization failure (TFF) still occurs in 1–3% of all ICSI cycles. ICSI followed by assisted
oocyte activation (ICSI-AOA) can restore fertilization, most efficiently in cases of sperm-related fertilization deficiency. The indication for
ICSI-AOA is less obvious when the capacity of the sperm to activate oocytes is considered normal, as proved by a heterologous ICSI
model, such as the mouse oocyte activation test (MOAT). In this study, we verified whether ICSI-AOA is beneficial for patients in
whom an oocyte-related activation deficiency is suspected.
methods: A prospective study was conducted including patients presenting with a history of TFF or low fertilization (LF) following con-
ventional ICSI in our centre (in-house cases, n ¼ 2) or elsewhere (out-house cases, n ¼ 12). In all cases a sperm deficiency was refuted by the
MOAT. In a next treatment cycle, ICSI-AOA was performed on half of the sibling metaphase II oocytes and conventional ICSI on the rest
(‘split ICSI-AOA cycle’). The main outcome parameters were fertilization, pregnancy and live birth rates.
results: Overall, ICSI-AOA was able to improve fertilization rates in couples with a suspected oocyte-related fertilization problem, with
a mean fertilization rate of 74.2% following ICSI-AOA compared with 43.5% following conventional ICSI (P , 0.001). Cumulative pregnancy
rate and live birth rate per cycle were 35.7 and 14.3%, respectively. Considering the out-house patients only, fertilization rates with ICSI-AOA
were higher in couples with previous TFF than with conventional ICSI (P , 0.001). Interestingly, for out-house patients who had experienced
low, but not zero, fertilization elsewhere, ICSI-AOA could not enhance the fertilization rate. For the two in-house patients, both suffering from
previous LF following conventional ICSI, the ICSI-AOA procedure enhanced the mean fertilization rate (25 versus 75%, respectively).
conclusions: For patients with a suspected oocyte-related activation deficiency, as diagnosed by a heterologuous ICSI model, the
indication for ICSI-AOA still remains debatable. Our data show that ICSI-AOA is very efficient in patients with a suspected oocyte-
related activation deficiency and previous TFF after conventional ICSI. In contrast, when there was a history of LF in another centre, one
should be careful and test the efficiency of ICSI-AOA on half of the sibling oocytes, because ICSI-AOA is not always beneficial for patients
with previous LF and a suspected oocyte-related activation deficiency. For these patients, a split ICSI-AOA cycle using sibling oocytes can
help to distinguish between a molecular oocyte-related activation deficiency and a previous technical or other biological failure. Moreover,
this split ICSI-AOA strategy enables us to set the appropriate strategy for future treatment cycles. Further research with larger groups of
patients is now required.
Key words: failed fertilization / oocyte activation deficiency / assisted oocyte activation / ionophore / mouse oocyte activation test
ICSI is used in two-thirds of the artificial reproduction technology
(ART) cycles in European fertility clinics (Mouzon et al., 2010). ICSI
was developed in the early 1990s and millions of couples suffering
from severe male infertility or previously failed IVF conceived by this
technique. On average, ICSI leads to fertilization rates of approximate-
ly 70–80% (Palermo et al., 2009). Unfortunately, total fertilization
& The Author 2012. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved.
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Human Reproduction, Vol.27, No.7 pp. 1977–1984, 2012
Advanced Access publication on May 2, 2012doi:10.1093/humrep/des097
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Ebner T, Moser M, Sommergruber M, Jesacher K, Tews G. Complete
oocyte activation failure after ICSI can be overcome by a modified
injection technique. Hum Reprod 2004;19:1837–1841.
Eldar-Geva T, Brooks B, Margalioth EJ, Zylber-Haran E, Gal M, Silber SJ.
Successful pregnancy and delivery after calcium ionophore oocyte
activation in a normozoospermic patient with previous repeated failed
fertilization after intracytoplasmic sperm injection. Fertil Steril 2003;
Esfandiari N, Javed MH, Gotlieb L, Casper RF. Complete failed fertilization
after intracytoplasmic sperm injection—analysis of 10 years’ data. Int J
Fertil Womens Med 2005;50:187–192.
Flaherty SP, Payne D, Swann NJ, Mattews CD. Aetiology of failed and
abnormal fertilization after intracytoplasmic sperm injection. Hum
Flaherty SP, Payne D, Matthews CD. Fertilization failures and abnormal
fertilization after intracytoplasmic sperm injection. Hum Reprod 1998;
Goud PT, Goud AP, Van Oostveldt P, Dhont M. Presence and dynamic
redistribution of type I inositol 1,4,5-trisphosphate receptors in
human oocytes and embryos during in-vitro maturation, fertilization
and early cleavage divisions. Mol Hum Reprod 1999;5:441–51.
Goud PT, Goud AP, Leybaert L, Van Oostveldt P, Mikoshiba K,
Diamond MP, Dhont M. Inositol 1,4,5-trisphosphate receptor function
in human oocytes: calcium responses and oocyte activation-related
phenomena induced by photolytic release of InsP3are blocked by a
specific antibody to the type I receptor. Mol Hum Reprod 2002;
Heindryckx B, Van der Elst J, De Sutter P, Dhont M. Treatment option for
sperm- or oocyte-related fertilization failure: assisted oocyte activation
following diagnosticheterologous ICSI.HumReprod2005;20:2237–2241.
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;17:662–668.
Heytens E, Soleimani R, Lierman S, De Meester S, Gerris J, Dhont M, Van
der Elst J, De Sutter P. Reprod Biomed Online 2008;17:764–771.
Ito M, Shikano T, Oda S, Horiguchi T, Tanimoto S, Awaji T, Mitani H,
Miyazaki S. Difference in Ca2+ oscillation-inducing activity and
nuclear translocation ability of PLCZ1, an egg-activating sperm factor
candidate, between mouse, rat, human, and medaka fish. Biol Reprod
Kashir J, Heindryckx B, Jones C, De Sutter P, Parrington J, Coward K.
Oocyte activation, phospholipase C zeta and human infertility. Hum
Reprod Update 2010;16:690–703.
Kovacic B, Vlaisavljevic V. Configurationofmaternalandpaternalchromatin
and pertaining microtubules in human oocytes failing to fertilize after
intracytoplasmic sperm injection. Mol Reprod Dev 2000;55:197–204.
Kuczyn ´ski W, Dhont M, Grygoruk C, Grochowski D, Wołczyn ´ski S,
Szamatowicz M. The outcome of intracytoplasmic injection of fresh
randomized study. Hum Reprod 2001;16:2109–2113.
Liu J, Nagy Z, Joris H, Tournaye H, Smitz J, Camus M, Devroey P, Van
Steirteghem A. Analysis of 76 total fertilization failure cycles out of
2732 intracytoplasmic sperm injection cycles. Hum Reprod 1995;
Mansour R, Fahmy I, Tawab NA, Kamal A, El-Demery Y, Aboulghar M,
Serour G. Electrical activation of oocytes after intracytoplasmic
sperm injection: a controlled randomized study. Fertil Steril 2009;
Mouzon J, Goossens V, Bhattacharya S, Castilla JA, Ferraretti AP, Korsak V,
Kupka M, Nygren KG, Nyboe Andersen A. Assisted reproductive
technology in Europe, 2006: results generated from European
registers by ESHRE. European IVF-monitoring (EIM) Consortium, for
the European Society of Human Reproduction and Embryology
(ESHRE). Hum Reprod 2010;25:1851–1862.
Murase Y, Araki Y, Mizuno S, Kawaguchi C, Naito M, Yoshizawa M,
Araki Y. Pregnancy following chemical activation of oocytes in a
couple with repeated failure of fertilization using ICSI: case report.
Hum Reprod 2004;19:1604–1607.
Nasr-Esfahani MH, Deemeh MR, Tavalaee M. Artificial oocyte activation
and intracytoplasmic sperm injection. Fertil Steril 2010;94:520–526.
Palermo GD, Neri QV, Takeuchi T, Rosenwaks Z. ICSI: where we have
been and where we are going. Semin Reprod Med 2009;27:191–201.
Parrington J, Davis LC, Galione A, Wessel G. Flipping the switch: how a
sperm activates the egg at fertilization. Dev Dyn 2007;236:2027–2038.
Rawe VY, Olmedo SB, Nodar FN, Doncel GD, Acosta AA, Vitullo AD.
Cytoskeletal organization defects and abortive activation in human
oocytes after IVF and ICSI failure. Mol Hum Reprod 2000;6:510–516.
Rybouchkin A, Dozortsev D, Pelinck MJ, De Sutter P, Dhont M. Analysis of
the oocyte activation capacity and chromosomal complement of
roundheaded human spermatozoa by their injection into mouse
oocytes. Human Reprod 1996;11:2170–2175.
Saunders CM, Larman MG, Parrington J, Cox LJ, Royse J, Blayney LM,
Swann K, Lai FA. PLC zeta: a sperm-specific trigger of Ca(2+)
oscillations in eggs and embryo development. Development 2002;
Shen S, Khabani A, Klein N, Battaglia D. Statistical analysis of factors
affecting fertilization rates and clinical outcome associated with
intracytoplasmic sperm injection. Fertil Steril 2003;79:355–360.
Swain JE, Pool TB. ART failure: oocyte contributions to unsuccessful
fertilization. Hum Reprod Update 2008;14:431–446.
Tesarik J, Mendoza C. In vitro fertilization by intracytoplasmic sperm
injection. Bioessays 1999;21:791–801.
Tesarik J, Mendoza C, Greco E. The activity (calcium oscillator?)
responsible for human oocyte activation after injection with round
spermatids is associated with spermatid nuclei. Fertil Steril 2000;
Tesarik J, Rienzi L, Ubaldi F, Mendoza C, Greco E. Use of a modified
intracytoplasmic sperm injection technique to overcome sperm-borne
and oocyte-borne oocyte activation failures. Fertil Steril 2002;
Vanderheyden V, Wakai T, Bultynck G, De Smedt H, Parys JB, Fissore RA.
Regulation of inositol 1,4,5-trisphosphate receptor type 1 function
during oocyte maturation by MPM-2 phosphorylation. Cell Calcium
van Loendersloot LL, van Wely M, Limpens J, Bossuyt PMM, Repping S,
van der Veen F. Predictive factors in in vitro fertilization (IVF): a
systematic review and meta-analysis. Human Reprod Update 2010;
Yanagida K. Complete fertilization failure in ICSI. Hum Cell 2004;
Yanagida K, Katayose H, Yazawa H, Kimura Y, Sato A, Yanagimachi H,
Yanagimachi R. Successful fertilization and pregnancy following ICSI
and electrical oocyte activation. Hum Reprod 1999;14:1307–1311.
Yanagida K, Morozumi K, Katayose H, Hayashi S, Sato A. Successful
pregnancy after ICSI with strontium oocyte activation in low rates of
fertilization. Reprod Biomed Online 2006;13:801–806.
Meerschaut et al.
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