Comment on “Dual Trigger vs. Gonadotropin-Releasing Hormone Agonist Trigger for Elective Fertility Preservation: A Randomized Controlled Trial”

Under normal physiologic conditions, maturation of oocytes is triggered by a surge in luteinizing hormone (LH); in cases where assisted reproductive technology is used, human chorionic gonadotropin (hCG), gonadotropin-releasing hormone agonist (GnRH-a), or a combination of the two (dual trigger) can be used to trigger oocyte maturation. Recently, GnRH antagonist protocols have been more commonly used, which consist of a single bolus of GnRH-a administered 36 hours before retrieval. This method reduces the risk of ovarian hyperstimulation syndrome (OHSS) as well as a surge of follicle-stimulating hormone (FSH). Dual trigger has also been recently introduced, which combines GnRH-a and an hCG bolus before retrieval, which is designed to enhance oocyte and embryo quality; previous literature has shown more mature oocytes and improved embryo quality with the dual trigger compared with hCG alone, but recent studies have not confirmed this finding. This study was designed to compare the efficacy of dual trigger vs. GnRH-a alone in good-prognosis patients undergoing elective fertility preservation.

This was a randomized, controlled, superiority clinical trial conducted between October 2021 and April 2023. Inclusion criteria were patients undergoing ovarian stimulation for elective fertility preservation, age 40 or under, antral follicular count (AFC) <20, and antimüllerian hormone of 3 ng/mL or less. Exclusion criteria were fertility preservation for medical reasons, AFC 20 or greater, polycystic ovary syndrome, FSH level 20 or greater, body mass index <18.5 or >30, and history of untreated autoimmune, endocrine, or metabolic disorders. The primary outcome for this study was the number of metaphase II (MII) oocytes retrieved after final maturation with dual trigger or GnRH-a trigger. Secondary outcomes included the total number of oocytes retrieved, the endocrine profile on the day after trigger, and the incidence of OHSS.

The final analysis included 109 patients, with 55 randomized to the dual-trigger group (group A) and 54 to the GnRH-a group (group B). Baseline characteristics were similar between groups. The mean duration of stimulation and gonadotropin dose was similar between groups, as was the number of oocytes retrieved. No significant differences were found in the number of MII oocytes retrieved, and there were no cases of OHSS in this study. Hormone profiles before and after the trigger were also similar between groups.

These results indicate that there were no significant differences in outcomes when using a dual trigger compared with GnRH-a alone, meaning that the addition of hCG does not improve outcomes in this population. This is consistent with previous literature, though this study is the first randomized controlled trial to assess differences between these 2 treatments. Based on recent evidence and the evidence from this trial, it does not appear that a dual trigger confers enough benefit to justify increased cost and patient burden in good-prognosis patients. Future research should assess these outcomes in a more heterogenous population, including among patients who are not considered good-prognosis patients, as well as patients who are not undergoing elective fertility preservation. In addition, these findings should be confirmed in other LH suppression protocols to take into account previous literature surrounding the GnRH antagonist protocol.

(Summarized from Donno V, Neves AR, García-Martinez S, Rodriguez I, Polyzos NP. Dual trigger vs. gonadotropin-releasing hormone agonist trigger for elective fertility preservation: a randomized controlled trial. Fertil Steril . 2026;125(3):488-495. doi:10.1016/j.fertnstert.2025.09.016).