Low-dose aspirin in unexplained recurrent pregnancy loss: A systematic review and meta-analysis.

INTRODUCTION: Recurrent pregnancy loss (RPL), defined as two or more consecutive pregnancy losses before 24 weeks of gestation, affects approximately 1%-2% of couples of reproductive ages. Despite comprehensive diagnostic work-up, up to 40%-50% of cases remain unexplained (uRPL). Low-dose aspirin (LDA) (50, 75, or 80 mg) administration during pregnancy has been proposed as a potential treatment to improve obstetric outcomes in women with uRPL. However, its efficacy in preventing pregnancy loss remains unclear. The aim of this systematic review and meta-analysis was to evaluate the efficacy of LDA administration on the pregnancy outcomes of women with uRPL. METHODS: We systematically searched for relevant studies in PubMed, Scopus, EMBASE, Google Scholar, and the Cochrane Library without language restriction from inception until April 2025. Randomized controlled trials (RCTs) that summarize the evidence regarding the effect of LDA on obstetric outcomes in women with uRPL were included. The counted data were analyzed using relative risk (RR) as the effect-size statistic, and each effect size was assigned its 95% confidence interval (CI). This study was conducted and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The primary outcome was the live birth rate (LBR), and secondary outcomes included preeclampsia and fetal growth restriction rates. RESULTS: Three RCTs were included, involving a total of 656 participants. No significant improvements were observed in terms of LBR in uRPL treated with daily administration of a 50-80 mg aspirin compared to untreated uRPL women (RR = 0.97, 95% CI, 0.90-1.04, p = 0.37). CONCLUSIONS: Our findings suggested that a 50-80 mg daily dose of aspirin does not improve the LBR of women with uRPL. Further studies, specifically RCTs using a 150 mg dose of aspirin in uRPL, are needed to clarify the efficacy of acetylsalicylic acid in preventing placental insufficiency-related pregnancy loss. PROSPERO REGISTRATION: CRD420251024932.