Triggering of ovulation for GnRH-antagonist cycles in normal and low ovarian responders undergoing IVF/ICSI: A systematic review and meta-analysis of randomized trials

Abstract

Objective: To conduct a systematic review andmeta-analysis of all randomized controlled trials (RCTs) that investigated whether dual triggering [a combination of gonadotropin-releasing hormone (GnRH) agonist and human chorionic gonadotropin (hCG)] of final oocyte maturation can improve the number of oocytes retrieved and clinical pregnancy rate in low or normal responders undergoing in-vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles using a GnRH-antagonist protocol.

Study design: Studies up to October 2022 were identified from PubMed, Scopus, Cochrane Library and Web of Science. The risk of bias of included studies was assessed. Dichotomous outcomes were reported as relative risks (RR), and continuous outcomes were reported as weighted mean differences (WMD) with 95% confidence intervals (CI). The primary outcomes were number of oocytes retrieved, number of mature [metaphase II (MII)] oocytes, clinical pregnancy rate and ongoing pregnancy rate; other IVF outcomes were considered as secondary outcomes.

Results: Seven studies were identified, and 898 patients were eligible for inclusion in this meta-analysis. The results showed that the number of oocytes retrieved [WMD = 1.38 (95% CI 0.47-2.28), I² = 66%, p = 0.003, low evidence], number of MII oocytes [WMD = 0.7 (95% CI 0.35-1.05), I² = 42%, p < 0.0001, moderate evidence], number of embryos [WMD = 0.68 (95% CI 0.07-1.3), I² = 67%, p = 0.03, low evidence] and number of good-quality embryos [WMD = 1.14 (95% CI 0.35-1.93), I² = 0%, p = 0.005, moderate evidence] in the dual trigger group were significantly higher than in the hCG trigger group. The results of the ovarian response subgroup analysis showed significant differences in all of these outcomes in normal responders, and no differences in any of the outcomes in low responders, except for the number of MII oocytes. In low responders, clinical pregnancy rates may be improved in the dual trigger group [RR = 2.2 (95% CI 1.05-4.61), I² = 28%, p = 0.04, low evidence].

Conclusion: Dual triggering by GnRH agonist and hCG improved oocyte maturity and embryo grading for normal responders in GnRH-antagonist cycles. Dual triggering for final oocyte maturation may improve clinical pregnancy rates in low responders.

Keywords: GnRH agonist; Meta-analysis; Randomized trial; Systematic review; hCG.