Unexplained recurrent pregnancy loss (URPL), defined as two or more pregnancy losses without identifiable cause, affects approximately 2% of reproductive-aged women. Antinuclear antibodies (ANA) may disrupt maternal-fetal immune tolerance in URPL, but the prognostic value of ANA titres and effectiveness of immunomodulatory therapies like hydroxychloroquine (HCQ) remain uncertain. This multicentre prospective cohort study aims to establish a multicentre clinical cohort of ANA-positive women with URPL to investigate whether HCQ improves pregnancy outcomes and to examine the relationship between changes in ANA titres during pregnancy and live birth rates. Additionally, mechanistic exploration will use a large-scale autoantibody microarray with bioinformatics analysis. This multicentre prospective cohort study across three Chinese tertiary hospitals will recruit 720 ANA-positive URPL patients. Participants will receive either low-dose aspirin alone or low-dose aspirin in combination with HCQ, starting two months before conception. Treatment duration depends on ANA titres: discontinued if negative or < 1:80 at 20 weeks; continued if ≥ 1:160 until 38 weeks. Primary outcome is live birth rate. Autoantibody microarrays will compare profiles between 30 ANA-positive and 30 ANA-negative patients and assess HCQ effects. This study will provide prospective evidence on the effectiveness of HCQ in improving live birth rates among ANA-positive women with URPL. Findings may inform future therapeutic strategies and contribute to personalized management for this challenging condition. If HCQ demonstrates benefit, it could offer a readily applicable treatment option in clinical settings. Furthermore, autoantibody profiling may uncover mechanistic pathways and biomarker signatures associated with treatment response and pregnancy success. ChiCTR2500105183 (registration date 2025-06-30).
Ma et al. (Tue,) studied this question.