Abstract

Abstract Study question Could dual trigger increase oocyte yield and maturation rate in women of advanced maternal age (≥ 40) undergoing IVF? Summary answer Dual trigger does not result in higher oocyte yield or maturation rates compared to hCG monotrigger What is known already Advanced maternal age is related to poor ovarian response (POR) and remains a major therapeutic challenge in routine IVF practice, because of the association with low live birth rates and high cancellation rates. hCG is used at the end of controlled ovarian hyperstimulation as a surrogate LH surge to induce final oocyte maturation. Recently, the co-administration of GnRH agonist and hCG for final oocyte maturation (dual trigger) has been suggested to improve IVF outcome (by improving oocyte quantity and quality) in normal responders, while evidence in poor responders remains controversial. Study design, size, duration This is a retrospective cohort study including patients attending a private IVF clinic from 1st January 2018 until 1st June 2022. Participants/materials, setting, methods All women who underwent IVF/ICSI in antagonist protocol in our center were included. Patients may have undergone triggering of the final oocyte maturation either with 250mcg of rhCG or 0.2 mg of GnRH agonist. Mature oocytes were inseminated using ICSI. Main results and the role of chance In total, 2242 patients were included, 454 (20.2%) in the rhCG group and 1788 (79.8%) in the dual trigger group. There was no significant difference in female age [41.3 (1.12) vs 41.3 (1.19), p value 0.94]. Total stimulation units and duration were also comparable between groups. The number of oocytes and MII oocytes did not differ significantly between rhCG and dual trigger group [5.8 (4.1) vs 6.3 (4.7) and 4.7 (3.3) vs 4.9 (3.4), p = 0.15 and 0.49, respectively]. Maturation rates were similar 81.7% (22.4) and 79.8% (23.5), p = 0.15, as well as fertilization rates (defined as the number of oocytes fertilized divided by the total number of cumulus-oocyte complexes recruited) [57% (29.7) vs 58.8% (29.4), p value=0.2]. Embryo utilization rates (defined as the total number of embryos transferred and cryopreserved divided by the number of oocytes fertilized) were comparable between the two arms: 69.7% (34.2) vs 70% (33.9), p value =0.22. Multivariate Poisson regression analysis adjusting for relevant confounders (AMH, total stimulation units) showed that the type of triggering strategy (dual trigger vs rhCG) was not associated with either the number of MII oocytes (coefficient 0.2, p value=0.24) or maturation rates (coefficient -1.8, p value 0.12). Limitations, reasons for caution The main limitation is the retrospective design of our study, with an inherent risk of bias. Wider implications of the findings To the best of our knowledge, this is the largest study evaluating dual trigger strategy in advanced maternal age women. Our data demonstrate that dual trigger cannot improve the outcome of low prognosis women and should not be used as a panacea for all IVF patients. Trial registration number NA

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