Abstract

Abstract Study question Among patients undergoing ovarian stimulation for ICSI, does dual trigger with hCG and GnRH agonist offer any benefit over mono trigger with hCG alone? Summary answer Dual trigger is associated with a higher number of mature oocytes without any impact on the pregnancy rate. What is known already In ART cycles, final oocyte maturation and resumption of meiosis are generally triggered by the administration of hCG as a surrogate for the natural LH surge. Several studies have investigated the role of a combination of a bolus of GnRH agonists and hCG to mimic the natural peak of endogenous LH and FSH, without clear answers regarding clinical benefit. A meta-analysis showed highernumbers of good-quality embryos and increased ongoing pregnancy rate after dual trigger and a recent systematic review demonstrated significantly higher live birth rate (LBR) per cycle after administration of dual trigger compared to hCG-only trigger. Study design, size, duration The study was a retrospective, single-centre cohort study. In this study, 8,525 ICSI cycles were included between January 2017 and April 2022 at a tertiary referral University Hospital. We included all patients undergoing ICSI in a GnRH antagonist ovarian stimulation cycle. The mono trigger consisted of recombinant or highly purified urinary hCG. In the dual trigger group, a bolus of GnRH agonist was combined with the hCG trigger. Participants/materials, setting, methods Our cohort of 8,525 cycles was divided into two groups: Group A, the mono trigger group, (7,022 cycles), and Group B, the dual trigger group (1503 cycles). Patients who underwent IVF, pre-implantation genetic testing, oocyte donation, and fertility preservation were excluded. Patients with uterine anomalies and endocrine disorders were also excluded, as well as patients who received a triptorelin-only trigger because of hyperresponse. Main results and the role of chance There was no difference in the mean age between the dual vs mono trigger cohorts (35.93 ± 4.90 vs 35.52±4.85). The most common indication for ART was male factor infertility in both groups (21.36% in group B vs 27.11% in group A). Stimulation was shorter in the dual trigger cohort (10.41 vs 12.08 p = 0.04). The total number of cumulus oocyte complexes (8.26±5.32 vs 7.45±4.68, p < 0.001), mature oocytes (6.39±4.15 vs 5.99±3.80, p = 0.006) and fertilized oocytes (4.79±3.59 vs 4.33±3.27, p = <0.001) was higher in the dual trigger group compared to those in the mono trigger group. Day 5 embryo transfer was more prevalent in the dual trigger group (46.07% vs 33,84%, p < 0.001). Embryo utilization rate was higher in group A (61.37% ±31.98) than in group B (53.47% ±30.91 p = <0.001). Ongoing regnancy rate was similar in both groups (27.29% in group A vs 27.08% in group B). Pearson chi2, Mann Whitney and logistic regression tests were used for the analysis. Limitations, reasons for caution In spite of the large sample, this study is retrospective and holds the possibility of unmeasured confounders. Wider implications of the findings Although a dual trigger may increase the number of mature oocytes, this does not translate into a higher pregnancy nor live birth rate. Reduced oocyte competence of the “surplus” oocytes may underlie this observation. Further research should identify specific subgroups that may benefit from dual trigger across meaningful outcome parameters. Trial registration number not applicable

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