L26/P-018 Do elevated sperm DNA fragmentation levels affect neonatal outcomes after ICSI in good-prognosis cycles?

Abstract Study question In singleton pregnancies conceived through ICSI in good-prognosis couples, does elevated sperm DNA fragmentation influence pregnancy course and neonatal outcomes compared with normal DNA fragmentation? Summary answer Elevated sperm DNA fragmentation was not associated with adverse pregnancy or neonatal outcomes following ICSI in good-prognosis cycles using blastocyst culture and frozen embryo transfer. What is known already Elevated sperm DNA fragmentation (SDF) has been linked to impaired embryo development, implantation failure, and increased miscarriage risk. Experimental data suggest a potential influence of sperm DNA integrity on trophectoderm development and placentation, raising concerns regarding hypertensive disorders, fetal growth restriction, preterm delivery, and congenital anomalies. However, clinical evidence evaluating pregnancy course and neonatal safety following ART in the context of elevated SDF remains limited and inconsistent, particularly in well-controlled, good-prognosis cycles. Study design, size, duration This retrospective cohort study included ICSI cycles performed between 2013 and 2024 at a single ART centre. Only self-gamete, non-PGT cycles were evaluated. Couples were stratified according to sperm DNA fragmentation index (DFI) measured using the sperm chromatin structure assay (SCSA). Pregnancy and neonatal outcomes were compared between elevated and normal SDF groups following standardized ART protocols in good-prognosis cycles. Participants/materials, setting, methods Men aged <40 years with DFI >30% constituted the elevated SDF group, while those with DFI <15% as controls. Only autologous ICSI cycles resulting in singleton pregnancies were included. All cycles involved extended blastocyst culture, freeze-all strategy, and frozen embryo transfer under uniform protocols. Cycles with fresh transfers, multiple gestations, or major obstetric complications were excluded. Outcomes assessed included miscarriage, preterm delivery, hypertensive disorders of pregnancy, fetal growth abnormalities, congenital anomalies, and neonatal birth weight. Main results and the role of chance Given the hypothesised associations between elevated sperm DNA fragmentation (SDF) and impaired blastocyst development, reduced implantation, increased miscarriage, and potential placental/ fetal complications, neonatal and perinatal outcomes were carefully evaluated. Despite these concerns, no adverse pregnancy or neonatal outcomes were observed in cycles with elevated SDF. Mean birth weight was comparable between the elevated and normal SDF groups (2.7kg vs 2.8kg; p = 0.95), with no increased risk of low birth weight (odds ratio [OR]∼1.05,95% CI 0.72–1.54). Rates of preterm delivery—often considered a surrogate for placental dysfunction—were similar (30% vs 37%; p = 0.10; OR ∼0.74, 95% CI 0.51–1.08). Congenital anomalies occurred infrequently and did not differ between groups (2.0% vs 3.0%; p = 0.48;OR ∼0.66, 95% CI 0.27–1.61). Miscarriage rates were also comparable (10.0% vs 9.1%; p = 0.73). Importantly, no increased incidence of pregnancy complications suggestive of placental insufficiency—including hypertensive disorders, fetal growth restriction, or adverse neonatal outcomes—was detected in the elevated SDF group. Overall, when good-quality blastocysts and frozen embryo transfer protocols were used, elevated SDF did not translate into measurable adverse effects on pregnancy course, fetal development, or neonatal health. These findings support reassurance during counselling and suggest that raised SDF alone may not warrant additional interventions aimed at improving obstetric or neonatal outcome. Limitations, reasons for caution The retrospective design and restriction to good-prognosis cycles limit generalizability. Neonatal follow-up was limited to early outcomes, and residual confounding cannot be excluded. Findings should be interpreted cautiously when extrapolating to poor-prognosis populations. Wider implications of the findings These findings provide reassurance regarding pregnancy and neonatal safety in good-prognosis ICSI cycles with elevated SDF. They support individualized counselling and caution against routine additional interventions aimed solely at preventing obstetric or neonatal complications in this population. Prospective studies are needed to validate these observations in higher-risk cohorts. Trial registration number No