Dual trigger vs. gonadotropin-releasing hormone agonist trigger for elective fertility preservation: a randomized controlled trial

Abstract

Objective: The study aimed to compare the efficacy, in terms of mature oocytes, of dual trigger vs. agonist alone in good-prognosis patients undergoing elective fertility preservation.

Design: Randomized, controlled, single-center, superiority clinical trial.

Subjects: A total of 109 women were enrolled in this study between October 2021 and April 2023 with a 1:1 allocation. Eligible patients were ≤40 years old, with an antral follicular count of <20 and antimüllerian hormone level of ≤3 ng/mL undergoing elective fertility preservation cycles.

Intervention: Controlled ovarian stimulation was performed using 225-300 IU/d of follitropin α or β or 15-20 μg of follitropin δ, tailored to ovarian reserve and weight. Luteinizing hormone surge was suppressed through a progestin-primed ovarian stimulation protocol, with oral administration of micronized progesterone (200 mg daily) from the beginning of ovarian stimulation until the trigger day. As soon as at least three follicles measuring ≥18 mm were observed by ultrasound, patients were randomization to the intervention group (triptorelin 0.2 mg + recombinant human chorionic gonadotropin 250 mcg) or the control group trigger with gonadotropin-releasing hormone agonist (GnRH-a) alone (triptorelin 0.2 mg).

Main outcome measures: The primary endpoint was the number of metaphase II (MII) oocytes retrieved after final oocyte maturation with dual trigger and GnRH-a trigger in patients undergoing elective fertility preservation.

Results: Overall, 109 patients were analyzed, 55 in the dual trigger group and 54 in the control arm (GnRH-a). No statistically significant differences were found regarding the total number of oocytes nor MII oocytes retrieved between the dual trigger and GnRH-a groups (9.22 ± 5.11 vs. 9.56 ± 5.16 [estimated mean difference, -0.34 {95% confidence interval, -2.29 to 1.61}] and 7.31 ± 4.63 vs. 7.94 ± 4.39 group [estimated mean difference, -0.64 {95% confidence interval, -2.07 to 0.80}], respectively). Likewise, no statistically significant differences were found regarding estradiol, progesterone, luteinizing hormone, and follicle-stimulating hormone levels on the day after the trigger. Notably, neither group exhibited any case of ovarian hyperstimulation syndrome.

Conclusion: In patients undergoing fertility preservation, adding human chorionic gonadotropin to GnRH-a for triggering final oocyte maturation is not superior to the administration of GnRH-a alone in terms of MII oocytes. Therefore, the selection of the trigger method should be based on both patients' and clinicians' preferences, with a focus on patients' safety and convenience.

Keywords: Final oocyte maturation; GnRH-agonist; MII oocyte; dual trigger; trigger.