JBRA Assisted Reproduction 2025;29(Suppl.2 SBRA 2025):182
Poster Presentation
29^th Annual Congress of the SBRA. São Paulo/SP - Brazil, 2025
doi: 10.5935/1518-0557.20263906

P-170. Ovarian Hyperstimulation Syndrome in High Responders Undergoing a Dual-Trigger Protocol: A Systematic Review

Brunno Andrade Soares¹, Manuela Oliveira Poni Carvalho¹, Isadora Fernandes Gonçalves¹, Rívia Mara Lamaita¹

¹ Faculdade Ciências Médicas de Minas Gerais – Belo Horizonte – MG - Brasil

Objective: To evaluate, through a systematic review, the impact of the dual-trigger protocol compared with alternative triggers on the incidence of ovarian hyperstimulation syndrome (OHSS) and on major laboratory and clinical outcomes in high-responder women undergoing controlled ovarian stimulation.
Methods: A systematic search was conducted in PubMed/MEDLINE, Embase, CENTRAL, LILACS and SciELO through May 2025 using terms related to "GnRH agonist", "hCG", "dual trigger" and "ovarian hyperstimulation syndrome". Randomized clinical trials comparing the dual-trigger protocol (GnRH-a + low-dose hCG) with alternative protocols in women with high ovarian response were included. Outcomes assessed included: incidence of moderate/severe OHSS, number of oocytes retrieved, metaphase II (MII) oocyte rate, fertilization rate, implantation rate, biochemical and clinical pregnancy rates, clinical miscarriage rate and live birth rate.
Results: Three studies met the inclusion criteria, totaling 488 participants and 1,447 cycles analyzed. One study reported, in

212 cycles, that the fresh-transfer arm with GnRH-a plus intensified luteal support showed 8.6% moderate to severe OHSS, whereas the freeze-all group recorded no significant episodes (p<0.01). Another study including 71 patients observed an OHSS incidence of 3.8% in the dual-trigger group (GnRH-a + 1,000 IU hCG at trigger) and 9.7% in the late-hCG group, with no statistically significant difference but a trend toward lower risk with the dual trigger (p>0.05). The third study, in 205 cycles, demonstrated a dose-dependent relationship: groups exposed to up to 1,000 IU hCG did not present moderate/ severe OHSS, while exposures of 2,000 IU and 3,000 IU had incidences of 12.96% and 11.67%, respectively (p<0.05). Regarding laboratory outcomes, the mean number of oocytes retrieved was similar between protocols in two studies, with means of 18.5±7.1 vs. 19.4±7.8 for fresh and freeze-all cycles and 18.4±5.9 vs. 18.4±7.7 in the dual-trigger and late-hCG groups, respectively, without significant differences. Another study observed a higher number of oocytes in arms receiving 1,000 IU hCG (22.35±5.43) compared with GnRH-a alone (15.25±3.78; p=0.008). Fertilization and implantation rates showed non-significant differences in most studies, except Engmann et al., who reported an implantation rate of 57.6% in the late-hCG group vs. 44.7% in the dual-trigger group (p=0.44). For clinical outcomes, clinical pregnancy rates were 48.6% in fresh cycles vs. 54.8% in freeze-all cycles (p=0.41); clinical pregnancy rates of 57.7% vs. 71.0% (p=0.49) were observed in the dual-trigger and late-hCG groups, respectively, without statistical significance, and live birth rates of 53.8% vs. 61.3% (p=0.57). Clinical pregnancy rates varied from 52.4% to 61.1% according to hCG dose, without significance (p>0.05), and the clinical miscarriage rate was reduced to 0% in the 1,000 IU group vs. 22.7% in the arm without hCG (p=0.03).
Conclusion: The dual-trigger protocol has the potential to reduce the incidence of moderate to severe OHSS in high-responder women when combined with a low dose of hCG, without compromising oocyte yield or pregnancy outcomes. However, findings are heterogeneous and limited by the small number of trials, variations in hCG dosing and differences in luteal support regimens. Additional randomized clinical trials with larger samples and standardized protocols are needed to confirm the efficacy and safety of the dual trigger as a strategy to prevent OHSS and optimize outcomes in assisted reproduction.