Dual trigger improves the pregnancy rate in fresh in vitro fertilization (IVF) cycles compared with the human chorionic gonadotropin (hCG) trigger: a systematic review and meta-analysis of randomized trials

Abstract

Propose: The purpose of this study was to assess whether the implementation of a "dual trigger" approach, utilizing gonadotropin-releasing hormone agonist (GnRHa) and human chorionic gonadotropin (hCG) in the GnRH antagonist protocol for in vitro fertilization (IVF), leads to improved pregnancy outcomes compared to the conventional hCG trigger alone. Previous meta-analyses have not provided sufficient evidence to support the superiority of the dual trigger over the hCG trigger in fresh or frozen embryo transfer cycles. Thus, a systematic review and meta-analysis of randomized trials were conducted to provide a comprehensive evaluation of the impact of the dual trigger on pregnancy outcomes in fresh or frozen embryo transfer cycles.

Method: A systematic review and meta-analysis of randomised controlled trials (RCTs) were conducted. We searched the Medline and Embase databases for articles up to 2023 by using search terms: "dual trigger," "GnRHa," "hCG," "IVF." Eligible RCTs comparing the dual trigger with the hCG trigger were included. The primary outcome was the live birth rate (LBR) per cycle. The secondary outcomes were the number of oocytes retrieved, number of mature oocytes retrieved, implantation rate, biochemical pregnancy rate, CPR, miscarriage rate and ovarian hyperstimulation syndrome (OHSS) rate per started cycle We compared the oocyte maturation and pregnancy outcomes in the dual trigger and hCG trigger groups. In patients undergoing fresh embryo transfer (ET) and frozen-thawed ET, we also conducted a subgroup analysis to evaluate whether dual trigger improves the clinical pregnancy rate (CPR).

Results: We included 10 randomised studies, with 825 participants in the dual trigger group and 813 in the hCG trigger group. Compared with the hCG trigger, dual trigger was associated with a significant increase in the LBR per cycle (odds ratio (OR) = 1.61[1.16, 2.25]), number of oocytes retrieved (mean difference [MD] = 1.05 [0.43, 1.68]), number of mature oocytes retrieved (MD = 0.82 [0. 84, 1.16]), and CPR (OR = 1.48 [1.08, 2.01]). Subgroup analyses revealed that dual trigger was associated with a significantly increased CPR in patients who received fresh ET (OR = 1.68 [1.14, 2.48]). By contrast, the dual trigger was not associated with an increased CPR in the patient group with frozen-thawed ET (OR = 1.15 [0.64, 2.08]).

Conclusion: The dual trigger was associated with a significantly higher number of retrieved oocytes, number of mature oocytes, CPR, and LBR in IVF than the hCG trigger. The beneficial effect for fresh ET cycles compared with frozen-thawed ET might be associated with increased endometrial receptivity.

Relevance: After dual trigger, delaying ET due to the concern of endometrial receptivity might not be needed.

Keywords: Dual trigger; GnRH agonist; Meta-analysis; Randomised trials; Systematic review; hCG.

Fig. 1

PRIZMA diagram

Fig. 2

Meta-analysis of studies reporting the following outcomes. A Number of retrieved oocytes; B Number of mature oocytes retrieved; C Biochemical pregnancy rate per cycle; D Clinical pregnancy rate per cycle; E Implantation rate per cycle; F Miscarriage rate per cycle; G Live birth rate per cycle

Fig. 3

Subgroup analysis for clinical pregnancy rate after fresh ET and frozen–thawed ET. A Clinical pregnancy rate after fresh ET. B Clinical pregnancy rate after frozen–thawed ET

Fig. 4

Results of the risk-of-bias analysis

Fig. 5

Funnel plot of the included studies for live birth rate

Fig. 6

GRADE pro

Fig. 7

OHSS rate

Fig. 8

Subgroup analysis: meta-analysis for the following outcomes in patients with poor ovarian response or advanced age. A Number of oocytes retrieved; B Number of mature oocytes retrieved; C Biochemical pregnancy; D Clinical pregnancy; E Implantation rate; F Clinical pregnancy rate after fresh ET