Abstract

Abstract Study question Does Intracytoplasmic Sperm Injection (ICSI) improve reproductive outcomes in patients with non-male factor infertility undergoing Frozen-Thawed Embryo Transfer (FET) treatment? Summary answer ICSI showed slightly improved clinical outcomes compared to IVF, but was associated with higher preterm birth rates and low birthweight when twins were born. What is known already The use of ICSI has seen a significant surge globally, particularly in Europe and the USA, as a solution for fertilization failure resulting from male factor infertility. FET presents a viable option for those considering additional children. Numerous studies have investigated the effectiveness of ICSI in couples with non-male factor infertility undergoing fresh embryo transfer in ovarian stimulation cycles. However, there is a dearth of evidence demonstrating whether ICSI, compared to conventional IVF (cIVF), could influence reproductive outcomes in couples with non-male factor infertility undergoing FET treatment. Study design, size, duration This retrospective cohort study included 10,143 cycles from 6,206 couples who underwent FET at the Third Affiliated Hospital of Zhengzhou University between January 2016 and September 2022. Participants/materials, setting, methods Patients were categorized into two groups based on the insemination methods used for the transferred embryos. Patients were excluded if : 1) Embryos were biopsied and tested; 2) Oocytes had been vitrified; 3) Embryos were derived from donor oocytes, AOA treatment, or rescue ICSI; 4) Embryos that were not transferred; and 5) They had undergone fresh embryo transfer. PSM at a ratio of 1:1 was utilized to ensure comparability of reproductive outcomes. Main results and the role of chance Post-PSM, the general characteristics were comparable across both groups. The clinical pregnancy rates (37.6% vs 40.0%, P = 0.311), miscarriage rates (21.4% vs 23.1%, P = 0.597), and live birth rates (28.2% vs 30.4%, P = 0.329) exhibited no significant disparity post-PSM between the two groups. Notably, a marginally elevated live birth rate was observed in the ICSI group when blastocysts were transferred to the women (39.8% vs 48.3%, P = 0.050). However, the GEE models indicated that ICSI did not enhance the likelihood of clinical pregnancy, miscarriage, and live birth relative to IVF in women with non-male factor infertility. Following adjustments for variables, ICSI yielded consistent OR values [1.14(0.92-1.42), P = 0.241; 1.08(0.72-1.61), P = 0.703; and 1.16(0.92-1.46), P = 0.220, respectively]. The perinatal outcomes were similar between the two grousps. However, a significantly higher incidence of preterm birth was observed in the ICSI group compared to the cIVF group (20.0% vs 12.5%, P = 0.026). While pregnancy complications were comparable between the two groups, neonates born as twins in the ICSI group exhibited significantly reduced live birth-weight [2520.8(572.9) vs 2691.9(423.7), P = 0.043] and birth length [47.5(2.8) vs 48.5(2.3), P = 0.031]. Correspondingly, the rate of low birthweight was significantly higher in the ICSI group (38.9% vs 21.0%, P = 0.025). Limitations, reasons for caution The retrospective design may lead to selection bias among the included patients. The use of ICSI in ART has been strictly regulated in our country, limiting the sample size and potentially reducing the statistical power. Wider implications of the findings The value of ICSI should be thoroughly discussed with patients with non-male factor infertility before ovarian stimulation. Further research is needed to better understand the impact of ICSI on reproductive and neonatal outcomes in this population. Trial registration number 2021YFC2700602

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