Preconception Hydroxychloroquine Therapy Restores Placental Function and Improves Pregnancy Outcomes in Obstetric Antiphospholipid Syndrome

AIMS: Obstetric antiphospholipid syndrome (OAPS), a representative autoimmune disorder driven by antiphospholipid antibodies (aPLs), afflicts 30% of patients with refractory to conventional antithrombotic treatment. Hydroxychloroquine (HCQ) offers adjunctive potential, yet its mechanistic action and critical treatment timing remain undefined. This study establishes the preventive efficacy of preconception HCQ initiation (HCQ-pre) and deciphers its fundamental rescue pathways in OAPS. RESULTS: Hippo/YAP and Wnt/β-catenin signaling. Murine OAPS models established that HCQ-pre restores placental perfusion (90% of control levels) by enhancing spiral artery remodeling-with diminished efficacy observed at post-conception administration-thereby attenuating hypoperfusion-induced hypoxic damage and improving pregnancy outcomes. INNOVATION AND CONCLUSIONS: 44, 748-769.