Comparative efficacy of human chorionic gonadotropin alone versus dual trigger for oocyte maturation in advanced maternal age using the antagonist protocol: a randomized controlled trial

Abstract

Background: The dual trigger, combining a gonadotropin-releasing hormone agonist with hCG, is reported to improve number of mature oocytes, and cumulative live birth rates. However, few studies have focused on advanced-aged women, and the relationship between follicle size and MII oocyte retrieval rates in this group remains unclear. Methods: This randomized controlled trial enrolled 164 patients aged 35–42 years undergoing intracytoplasmic sperm injection (ICSI). Participants were randomized (1:1) to hCG-only or dual trigger. Final oocyte maturation was induced when ≥ 2 follicles reached 17 mm, with retrieval 35 h later. Oocytes were aspirated by follicle size (< 13 mm, 13–17 mm, > 17 mm). All mature oocytes underwent ICSI. Embryo transfer was performed in fresh or frozen-thawed cycles. The primary outcome was MII oocytes count; secondary outcomes were fertilization, implantation, pregnancy, live birth, and miscarriage rates. Results: Among 164 participants, 83 were in the hCG group and 81 in the dual trigger group. Baseline characteristics, ovarian response, and types and doses of stimulation medicines were statistically comparable. The mean number of MII oocytes was 6.07 ± 4.02 in the hCG group and 5.78 ± 3.62 in the dual trigger group (P = 0.62). Fertilization rates were similar between groups. Subgroup analysis by follicle size (< 13 mm, 13–17 mm, and > 17 mm) showed that follicles < 13 mm in the dual trigger group produced more mature oocytes and a significantly higher fertilization rate compared with hCG-only (40.71% vs. 32.65%, P = 0.08; 80.43% vs. 65.25%, P < 0.03). The implantation rate, chemical pregnancy rate, and clinical pregnancy rate were clinically higher in the dual trigger group (37.7% vs. 28.57%; 45.90% vs. 34.92%; 40.98% vs. 34.92%), although the differences were not statistically significant (P > 0.31, 0.27, 0.58, respectively). Ongoing pregnancy and live birth rates remained similar (P = 0.84). Conclusion: In advanced-aged patients, the dual trigger and hCG trigger protocols yielded comparable numbers of total oocytes and MII oocytes. However, subgroup analysis indicated that dual trigger may improve fertilization rates in smaller follicles. Although a trend toward higher chemical and clinical pregnancy rates was observed with dual trigger, ongoing pregnancy and live birth rates remained comparable between groups. Trial registration: This study was registered with the Thai Clinical Trials Registry (https://www.thaiclinicaltrials.org) on 15 March 2022 under the registration number TCTR20220315002.