Abstract Study question Standard-dose dual trigger (SDT) and low-dose dual trigger (LDT) could improve the number of oocytes, blastocysts and euploid blastocysts or not compared with hCG trigger. Summary answer LDT increased the number of oocytes and blastocysts but not euploid blastocysts among high ovarian responders, while SDT cannot help poor to normal ovarian responders. What is known already For low and normal responders, hCG trigger was recommended by the ESHRE guidelines for ovarian stimulation for in vitro fertilization (IVF) /intracytoplasmic sperm injection (ICSI) in 2020. For high responders, this guideline recommended gonadotropin-releasing hormone agonist (GnRH-a) as the first-choice treatment. While recent studies showed that SDT could increase the number of oocytes and blastocysts to achieve equivalent or better pregnancy outcomes among poor and normal ovarian responders. And LDT was designed to prevent severe ovarian hyperstimulation syndrome (OHSS) while guaranteeing embryo quality among high responders by previous studies. Study design, size, duration This retrospective cohort study was performed at the Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital from July 2018 to December 2021. A total of 2,649 IVF-PGT cycles involving 2,275 patients were analyzed, of which 2,270 cycles had complete baseline data. A total of 1,131, 715, and 424 cycles were included in the hCG trigger, SDT, and LDT groups, respectively. Participants/materials, setting, methods Patients who were triggered by SDT(triptorelin acetate 0.2 mg and rhCG 250 µg), LDT(triptorelin acetate 0.2 mg and rhCG 125 µg or hCG 2,000 IU), and hCG (rhCG 250 µg) with GnRH-antagonist stimulation protocol in IVF-PGT cycles were enrolled. The number of oocytes retrieved, blastocysts, and euploid blastocysts were compared as primary endpoints. Propensity score matching (PSM) was used to control for confounding factors of retrospective study. Main results and the role of chance The SDT and hCG groups had a comparable number of oocytes retrieved (11.0 [7.0, 16.0] vs. 11.0 [7.0, 15.0], p = 0.580), blastocysts (2.0 [1.0, 3.0] vs. 2.0 [1.0, 3.0], p = 0.517), and euploid blastocysts (1.0 [0.0, 2.0] vs. 1.0 [0.0, 2.0], p = 0.383) after PSM. LDT increased the number of oocytes retrieved (19.0 [14.0, 25.0] vs. 16.0 [12.0, 21.0], p < 0.001) and blastocysts (3.0 [2.0, 6.0] vs. 3.0 [2.0, 5.0], p = 0.001), but not euploid blastocysts (2.0 [1.0, 3.0] vs. 1.0 [1.0, 3.0], p = 0.111), compared with the hCG trigger after PSM. Limitations, reasons for caution This was a single-center retrospective cohort study. The baseline characteristics of SDT and LDT differed from those of the hCG group because of clinical decision preferences. PSM was used to control for these effects and generate a balanced cohort. Pregnancy outcomes after embryo transfer has not been assessed yet. Wider implications of the findings The hormone change curve induced by LDT is more similar to the natural cycle. Probably LDT could also benefit poor to normal ovarian responders in IVF/ICSI cycles. And LDT might help in fresh embryo transfer cycles because of its advantage on endometrial receptivity. Trial registration number the National Natural Science Foundation of China (Grant No.82171626)
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