Triggering Oocyte Maturation in IVF Treatment in Normal Responders: a Systematic Review and Network Meta-Analysis

OBJECTIVE To compare efficacy and safety of hCG, GnRH agonist, dual, and double triggers in predicted normal responders undergoing ovarian stimulation and IVF DESIGN A systematic review and network meta-analysis of randomized controlled trials (RCTs). DATA SOURCES RCTs indexed in PubMed, MEDLINE, EMBASE, clinical trial registries and Cochrane Database of Systematic Reviews up to December 2023. STUDY SELECTION AND SYNTHESIS Twelve high-integrity RCTs comprising 1,931 women were included, which compared hCG trigger to GnRH agonist trigger, dual trigger, and double trigger. Statistical analysis was performed using STATA version 16. MAIN OUTCOMES Key outcomes included clinical pregnancy rates (CPR), live birth rates (LBR), number of oocytes, number of mature oocytes, miscarriage rate and rates of ovarian hyperstimulation syndrome (OHSS). RESULTS The network meta-analysis for CPR were relative risk (RR) 1.13 (95% Confidence Interval (CI):0.80-1.60) for hCG versus GnRH agonist trigger, RR 1.23 (95% CI:0.92-1.65) for hCG versus dual trigger, RR 0.38 (95% CI:0.21-0.69) for hCG versus double trigger, RR 1.09 (95% CI:0.70-1.70) for GnRH agonist versus dual trigger and 0.34 (95% CI:0.17-0.67) for GnRH agonist versus double trigger and RR 0.31 (95%CI:0.16-0.60) for double versus dual trigger. Dual trigger demonstrated the highest SUCRA (85.1%), indicating superior efficacy for clinical pregnancy rates. For LBR, while connectivity was limited, the RR was 1.31 (95% CI: 1.00-1.70) for dual versus hCG trigger, and RR 1.60 (95% CI: 1.05-2.43) for dual versus GnRH agonist trigger. OHSS rates were significantly lower with the GnRH agonist compared to hCG trigger (RR 0.56, 95% CI: 0.19-1.75). There were no randomized controlled trials reporting OHSS rates with the use of dual or double trigger. No significant differences were observed in the number of oocytes retrieved, mature oocytes, or miscarriage rates among the trigger protocols. CONCLUSION AND RELEVANCE The findings indicate that there is no evidence to suggest that using GnRH agonist, dual, or double protocols is superior to hCG trigger in improving clinical pregnancy rates. While live birth rates may benefit from dual trigger, results are limited by available RCTs. Larger, multicentre trials are needed for further evaluation of live birth rates and understanding of long-term outcomes.