FINAL OOCYTE MATURATION TRIGGER PROTOCOL IN POOR, NORMAL AND HIGH RESPONDERS: A SYSTEMATIC REVIEW AND NETWORK META-ANALYSIS OF LIVE BIRTH RATES, LABORATORY OUTCOMES AND ADVERSE EFFECTS

Oocyte maturation trigger prior to oocyte retrieval is a crucial component of ovarian stimulation. The objective is to perform a systematic review of the evidence and network meta-analysis to determine the efficacy and safety of the different final oocyte trigger protocols in poor, normal and high responders. Fresh and frozen embryo transfer cycles were analysed separately for clinical outcomes. MEDLINE, EMBASE, CINAHL, CENTRAL and ClinicalTrials.gov databases were searched until August 2022. Randomized controlled trials (RCTs) comparing at least two trigger protocols: hCG trigger, GnRH agonist trigger, dual trigger and double trigger with the antagonist regimen were included. The primary outcome was live birth (LBR) per participant. A network meta-analyses (NMA) was conducted and direct (DC) and indirect comparison (IC) were presented as weighted means difference (WMD) and risk ratio (RR) according to ovarian response groups (normal, high and poor response). 54 RCTs involving 5838 women were included in the analysis and were found to be at low risk of bias In normal responders, there is no difference in LBR with the GnRHa vs hCG (RR:1.11,95%CI:0.83-1.49;3 studies,430 women,I2=33%,low-certainty evidence, DC),dual trigger vs hCG(RR:1.14,95%CI:0.99-1.31;4 studies,1007 women,I2=33%,low-certainty evidence, DC),double trigger vs hCG(RR:0.53, 95%CI:0.27-1.06;(IC)),dual vs GnRHa (RR:0.97, 95%CI:0.70-1.34, IC),double vs GnRHa (RR:2.07, 95%CI:0.98-4.38, IC),dual vs double (RR:2.14, 95%CI:1.06-4.32;IC). In high responders, there is no difference in LBR with the GnRHa vs hCG (RR:1.04, 95%CI:0.84-1.29; 3 studies,178 women, I2=44%, low-certainty evidence, DC, dual trigger vs hCG (RR:1.82, 95%CI:1.25-2.67; 4 studies,117 women, I2=37%, low-certainty evidence, DC),double trigger vs hCG (RR:2.10, 95%CI:1.29-3.43, IC), dual vs GnRHa (RR:0.57, 95%CI:0.37-0.88, IC),double vs GnRHa (RR:0.49, 95%CI:0.29-0.88, IC),dual vs double (RR:0.87, 95%CI:0.64-1.18; 1 study,57 women, low-certainty evidence, DC). In poor responders, there may be a difference in LBR when comparing dual trigger to hCG (RR:1.12,95%CI:1.12-2.89 1 study,112 women, low-certainty evidence, DC). There was no significant difference in number of oocytes or miscarriage risks with the use of any triggers. OHSS rate was lowest with GnRH agonist trigger. There was no difference in LBR when comparing various trigger protocols in normal, high and poor responders.