New Study Reassures on the Use of Assisted Oocyte Activation in ICSI Cycles

A recent study reports that the behavioral and neurodevelopment outcomes are normal in children born after assisted oocyte activation (AOA) using calcium ionophore in ICSI cycles. Touted to be the first study assessing the developmental outcome of children born following AOA, the preliminary findings are published in Reproductive BioMedicine Online.

Frauke Vanden Meerschaut from the Department for Reproductive Medicine, University Hospital Ghent, Belgium, and co-workers, assessed the neonatal and neurodevelopmental outcome of 21 children, aged 3-11 years (mean age 63.6 ± 21.07 months), born following AOA. The data were gathered by means of questionnaires, and the neurodevelopmental outcomes were assessed using the Reynell Developmental Language Scales or Clinical Evaluation of Language Fundamentals, Wechsler Preschool and Primary Scale of Intelligence or Wechsler Intelligence Scale for Children, and the Movement Assessment Battery for Children III. The behaviour of the children was evaluated using the Social Communication Questionnaire (SCQ), Teachers Report Form, and Child Behavior Checklist (CBCL).

The results showed that there were no major malformations at the time of birth; however, 14.3% of the toddlers reported birth defects, as assessed by different scales. The other key outcomes, which were all within the normal range, are listed below.

  • Cognitive development
  • Although the scores for language development were within the normal scale, younger children attained significantly more scores than those who were older. The disparity may be due to the fact that twins, who commonly score lesser for the language development tests than the singletons, were predominant in the older age group
  • Risk for autism spectrum disorders (ASD)
  • CBCL scores, which assessed any maladaptive behaviour (see table 01)

Table 01: Developmental and behavioural assessment scores of AOA children.

Maladaptive behavior screening CBCL (1.5–5 years)
Normal score <70
CBCL (6–18 years)
Normal score <70
TRF (1.5–5 years)
Normal score <70
TRF (6–18 years)
Normal score <70
Internalizing broadband 50.5 (42.7–58.2) (33–74) 38.4 (33.6–43.2) (33–50) 47.5 (41.3–53.7) (44–53) 43.5 (31.7–55.7) (37–52)
Externalizing broadband 47.6 (42.1–53.0) (35–60) 39.1 (35.0–43.2) (34–48) 44.8 (36.8–52.7) (38–49) 42.7 (40.9–44.1) (41–43)
Total score 48.6 (42.5–54.8) (30–63) 37.3 (32.0–42.5) (29–45) 45.5 (41.7–49.3) (44–49) 42.5 (32.1–52.9) (33–48)
Autism screening SCQ (≥2 years)
Normal score <15
Score 6.4 (4.5–8.3) (0–13)
Cognition tests WPPSI-III-NL
(≤7 years)
Normal score=100
(>7 years)
Normal score=100
Verbal IQ 102.8 (96.4–109.2) (77–129) 123
Performal IQ 105.0 (97.8–112.2) (74–142) 130
Full Scale IQ 104.2 (97.5–110.8) (85–144) 131
Language tests RTOS (<5 years)
Normal score=50
(>5 years)
Normal score=50
Receptive scale 82.0 (63.4–100.7)a (35.5–99) 32.5 (7.3–57.7)a (3.6–94.5)
Expressive scale 73.3 (49.4–97.2)b (30–99) 40.9 (16.6–65.2)b (7.1–88.5)
Total percentile score 78.2 (57.2–99.2)c (33.3–99.0) 40.1 (16.8–63.4)c (9.1–89.7)
Motor skills tests Movement ABC-II-NL
(3–6 years)
Normal score=50
Movement ABC-II-NL
(7–10 years)
Normal score=50
Manual dexterity 42.0 (24.4–58.7) (1–95) 56.5 (NA) (50–63)
Aiming and catching 43.8 (29.5–58.0) (2–95) 21.0 (NA) (5–37)
Balance 41.5 (25.1–57.9) (5–91) 77.0 (NA) (63–91)
Total percentile score 37.1 (22.3–52.0) (2–84) 50.0 (NA) (37–63)

Mean values (95% CI) (min – max) Normal scores: lesser than this cut-off value is considered normal (for maladaptive behaviour screening and autism) or the 50th percentile of the population (for motor skill assessment, language and cognition);
CBCL = Child Behaviour Checklist; TRF = Teachers Report Form WPPSI = Wechsler Preschool and Primary Scale of Intelligence; WISC = Wechsler Intelligence Scale for Children; RTOS = Reynell Developmental Language Scales; CELF = Clinical Evaluation of Language Fundamentals; Movement ABC-II-NL = Movement Assessment Bat-tery for Children III; NA = not applicable (n= 2); SCQ = Social Communication Questionnaire; a: P<0.01 between RTOS and CELF; b,c: P<0.05 between RTOS and CELF

Similar results with respect to the safety of AOA were found in an earlier study by Takisawa et al. (Fertility and Sterility, 2011), which compared the effect of oocyte activation by ionophore or strontium chloride in patients with reduced fertilization rate (<30%). The results demonstrated that the development and well-being of 22 infants were same at the time of their birth following both the AOA protocols.

With around 1–5% of ICSI cycles associated with total fertilization failure, AOA has been identified as one of the probable methods to overcome the problem (Kashir et al, Human Reproduction Update, 2010). Various artificial oocyte activating agents such as electrical pulses, strontium chloride, and calcium ionophore are used to overcome oocyte activating failures, among which ionophore is used more commonly.

It has been noted that artificial calcium ionophores do not accurately imitate the physiologically sperm-induced calcium oscillation pattern and their potential adverse effects on embryo development after the implantation is still unknown. Although the initial results of the current study are promising, long-term large multicentre research is warranted to validate the safety and effectiveness of AOA. Considering the small sample size, the study further emphasized that the evidence is insufficient to arrive at a conclusion on the long-term outcomes of AOA. Moreover, the researchers highlighted the importance of patient counselling in couples undergoing AOA on the enhanced risks of pregnancy complications and increased rate of obstetric interventions.


  • Vanden Meerschaut F, D’Haeseleer E, Gysels H, et al. Neonatal and neurodevelopmental outcome of children aged 3-10 years born following assisted oocyte activation. Reprod Biomed Online. 2014;28(1):54-63.
  • Takisawa T, Sato Y, Tasaka A, Ito Y, Nakamura Y, Hattori H. Effect of oocyte activation by calcium ionophore A23187 or strontium chloride in patients with low fertilization rates and follow-up of babies. Fertil Steril. 2011;96(3):S162.
  • Vanden Meerschaut F, Nikiforaki D, De Gheselle S, et al. Assisted oocyte activation is not beneficial for all patients with a suspected oocyte-related activation deficiency. Hum Reprod. 2012;27(7):1977-84.
  • 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(6):690-703.

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