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Fertil Steril. 2017 Sep;108(3):468-482.e3. doi: 10.1016/j.fertnstert.2017.06.029.

Does the use of calcium ionophore during artificial oocyte activation demonstrate an effect on pregnancy rate? A meta-analysis.

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Department of Obstetrics and Gynaecology, Hillingdon Hospital, Uxbridge, United Kingdom.
Division of Surgery and Cancer, Institute of Reproductive and Developmental Biology, Imperial College London, London, United Kingdom. Electronic address:
Division of Surgery and Cancer, Institute of Reproductive and Developmental Biology, Imperial College London, London, United Kingdom.
Department of Obstetrics and Gynaecology, Chelsea and Westminster Hospital, Imperial College London, London, United Kingdom.
Department of Cardiothoracic Surgery, National Heart and Lung Institute, Imperial College London, London, United Kingdom.
Centre for Reproductive and Genetic Health, London, United Kingdom.



To study the effect, if any, of calcium ionophore as a method of artificial oocyte activation (AOA) on pregnancy outcomes and fertilization rates.


Meta-analysis of randomized controlled trials, prospective observational and retrospective trials, case reports, and a case-control trial.


University-affiliated teaching hospital.


Infertile couples undergoing fertilization treatment.


Use of calcium ionophore during AOA.


Odds ratio (OR) as the summary statistic for binary variables was used. Both a fixed and random effects model were applied. Subgroup analysis using quantitative methodology (risk of bias, metaregression) and graphical comparison (funnel plot) assessed statistical heterogeneity.


Fourteen studies were selected. AOA with calcium ionophore increased the overall clinical pregnancy rate (per ET; OR = 3.48; 95% confidence interval [CI], 1.65-7.37) and the live birth rate (OR = 3.33; 95% CI, 1.50-7.39). This effect of adding calcium ionophore was further demonstrated with fertilization, cleavage, blastocyst, and implantation rates. Subgroup analysis further supported our findings (studies where n > 10 in both arms; random and fixed effects models). A metaregression (beta = -.145) found that as the quality of the study increases, the effect of calcium ionophore is significantly more pronounced with regards to overall pregnancy rate.


AOA with calcium ionophore treatment after intracytoplasmic sperm injection (ICSI) results in a statistically significant improvement in fertilization, cleavage, blastulation, and implantation rates, as well as overall pregnancy and live-birth rates. The conclusion of this systematic review, demonstrating a strong effect of calcium ionophore use, is reassuring and promising, particularly for couples for whom ICSI alone yields poor fertilization rates.


In vitro fertilization; artificial oocyte activation; calcium ionophore; live birth; pregnancy

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