Supplementary Material for: Efficacy of Double Trigger versus hCG Trigger Alone in GnRH-Antagonist Cycles: A Systematic Review and Meta-Analysis

Introduction
Triggering final oocyte maturation is a critical step in IVF-ET, especially for optimizing outcomes in patients with poor ovarian response or low oocyte maturation. The double trigger protocol, combining a GnRH agonist with hCG, has been proposed to enhance oocyte quality and improve reproductive outcomes compared to hCG alone. Our review aim to evaluate the efficacy of the double trigger compared to hCG-only trigger on reproductive outcomes in patients undergoing IVF-ET.
Methods
A systematic review and meta-analysis were conducted using PubMed, Scopus, and Google Scholar up to June 15, 2025. Studies comparing double trigger to hCG-only trigger were included. Outcomes such as the number of oocytes retrieved, MII oocytes, 2PN embryos, and day-3 top-quality embryos (TQEs) were analyzed using mean difference (MD), while clinical pregnancy rate was evaluated using odds ratio (OR). Risk of bias was assessed using RoB-2 and ROBINS-I tools. Meta-analysis was performed with a random-effects model in RevMan, and certainty of evidence was evaluated using GRADE. The review was registered with PROSPERO (CRD420251071480).
Results
Six studies involving a total of 352 patients were included. In poor ovarian responders, the double trigger protocol significantly increased the number of oocytes retrieved (MD 0.49; p = 0.02) and MII oocytes (MD 0.62; p = 0.005). Among normo-responders with low oocyte maturation, the double trigger significantly improved MII oocytes (MD 5.08; p = 0.03), 2PN embryos (MD 4.70; p < 0.0001), top-quality embryos (MD 1.46; p = 0.01), and clinical pregnancy rate (OR 5.75; p = 0.009).
Conclusion
The double trigger protocol may improve certain reproductive outcomes compared to hCG-only triggering, particularly among poor ovarian responders and normo-responders with low oocyte maturation. These findings suggest that double trigger could be considered as a potential personalized strategy in selected IVF populations, although further high-quality studies are needed to confirm its effectiveness.