GnRH agonist and hCG (dual trigger) versus hCG trigger for follicular maturation: a systematic review and meta-analysis of randomized trials

BACKGROUND: Traditionally, final follicular maturation is triggered by a single bolus of human chorionic gonadotropin (hCG). This acts as a surrogate to the naturally occurring luteinizing hormone (LH) surge to induce luteinization of the granulosa cells, resumption of meiosis and final oocyte maturation. More recently, a bolus of gonadotropin-releasing hormone (GnRH) agonist in combination with hCG (dual trigger) has been suggested as an alternative regimen to achieve final follicular maturation. METHODS: This study was a systematic review and meta-analysis of randomized trials evaluating the effect of dual trigger versus hCG trigger for follicular maturation on pregnancy outcomes in women undergoing in vitro fertilization (IVF). The primary outcome was the live birth rate (LBR) per started cycle. RESULTS: A total of 1048 participants were included in the analysis, with 519 in the dual trigger group and 529 in the hCG trigger group. Dual trigger treatment was associated with a significantly higher LBR per started cycle compared with the hCG trigger treatment (risk ratio (RR) = 1.37 [1.07, 1.76], I(2) = 0%, moderate evidence). There was a trend towards an increase in both ongoing pregnancy rate (RR = 1.34 [0.96, 1.89], I(2) = 0%, low evidence) and implantation rate (RR = 1.31 [0.90, 1.91], I(2) = 76%, low evidence) with dual trigger treatment compared with hCG trigger treatment. Dual trigger treatment was associated with a significant increase in clinical pregnancy rate (RR = 1.29 [1.10, 1.52], I(2) = 13%, low evidence), number of oocytes collected (mean difference (MD) = 1.52 [0.59, 2.46), I(2) = 53%, low evidence), number of mature oocytes collected (MD = 1.01 [0.43, 1.58], I(2) = 18%, low evidence), number of fertilized oocytes (MD = 0.73 [0.16, 1.30], I(2) = 7%, low evidence) and significantly more usable embryos (MD = 0.90 [0.42, 1.38], I(2) = 0%, low evidence). CONCLUSION: Dual trigger treatment with GnRH agonist and HCG is associated with an increased live birth rate compared with conventional hCG trigger. TRIAL REGISTRATION: CRD42020204452. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12958-021-00766-5.