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

Objective: To study the effect, if any, of calcium ionophore as a method of artificial oocyte activation (AOA) on pregnancy outcomes and fertilization rates. Design: Meta-analysis of randomized controlled trials, prospective observational and retrospective trials, case reports, and a case-control trial. Setting: University-affiliated teaching hospital. Patient(s): Infertile couples undergoing fertilization treatment. Intervention(s): Use of calcium ionophore during AOA. Main Outcome Measure(s): 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. Result(s): 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. Conclusion(s): 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. (C) 2017 by American Society for Reproductive Medicine.