Dual trigger versus GnRH-a trigger for elective fertility preservation. A randomized controlled trial.

Structured Abstract OBJECTIVE: The study aims 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 <20 and anti-Mullerian hormone ≤3 ng/ml undergoing elective fertility preservation cycles. INTERVENTION Controlled ovarian stimulation was performed using 225-300IU/day of follitropin alfa or beta or 15-20 μg of follitropin delta, tailored to ovarian reserve and weight. LH surge was suppressed through a progestin-primed ovarian stimulation protocol, with oral administration of micronized progesterone (200mg daily) from the beginning of ovarian stimulation until the trigger day. As soon as at least three follicles ≥ 18 mm were observed by ultrasound, patients were randomization to the intervention group (Triptorelin 0.2 mg + 250 mcg rhCG) or the control group trigger with GnRH-a alone (Triptorelin 0,2 mg). MAIN OUTCOME MEASURES The primary endpoint was the number of 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 ± 5.11vs.9.56 ± 5.16, (EMD-0.34 [95%CI: -2.29;1.61]) and 7.31 ± 4.63vs.7.94 ± 4.39 group (EMD -0.64 [95%CI: -2.07;0.80], respectively). Likewise, no statistically significant differences were found regarding estradiol, progesterone, LH and FSH levels on the day following the trigger. Notably, neither group exhibited any case of Ovarian Hyperstimulation Syndrome (OHSS). CONCLUSION In patients undergoing fertility preservation, adding hCG 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. TRIAL REGISTRATION NUMBER NCT04992468.