Effects of hydroxychloroquine sulfate combined with aspirin and enoxaparin sodium therapy on perinatal outcomes in patients with undifferentiated connective tissue disease-related recurrent miscarriage: a retrospective clinical study

BACKGROUND: To evaluate the association between triple therapy (hydroxychloroquine sulfate, aspirin, and enoxaparin sodium) and pregnancy outcomes in patients with undifferentiated connective tissue disease (UCTD)-related recurrent miscarriage (RM). METHODS: This retrospective cohort study included 135 pregnant women with recurrent miscarriage treated at a single center between January 2021 and August 2024. Patients were assigned to three groups according to treatment regimen: control group 1 (progesterone + enoxaparin sodium), control group 2 (aspirin + enoxaparin sodium), and the triple therapy group (hydroxychloroquine + aspirin + enoxaparin sodium). The primary outcome was live birth (≥ 28 weeks). Multivariable logistic regression analysis was performed to adjust for baseline differences using a parsimonious model including treatment group, maternal age, and gestational age at last pregnancy loss. RESULTS: In unadjusted analysis, the triple therapy group had a significantly higher live birth rate (95.6%) than the control group 1 (80.0%) and control group 2 (77.8%) (P = 0.028). The higher live birth rate was mainly driven by increased fetal survival, despite a numerically higher preterm birth rate. After adjustment for baseline differences, the association between triple therapy and live birth was attenuated and did not reach statistical significance, although the direction of effect remained consistent with the unadjusted analysis. No significant difference was observed between control group 2 and control group 1 in the adjusted analysis. Gestational age at last pregnancy loss was significantly associated with live birth, whereas maternal age was not. No increase in adverse reactions or differences in neonatal outcomes was observed among the groups. CONCLUSION: Triple therapy with hydroxychloroquine, aspirin, and enoxaparin sodium was associated with improved live birth outcomes in patients with UCTD-related recurrent miscarriage. However, this association was attenuated and did not remain statistically significant after adjustment for baseline differences. Given the retrospective design and limited sample size, further prospective studies are required to confirm these findings.