Efficacy of the combined administration of low dose aspirin and low molecular weight heparin in unexplained recurrent miscarriages with occasional antiphospholipid antibody positivity: A case report and literature review

Background: Recurrent miscarriage (RM), defined as three or more miscarriages, is estimated to occur in 1–3% of couples trying to conceive. Although several established causes of RM have been reported, the causes for half of all cases remain unexplained. Occasional antiphospholipid antibody (aPL)-positivity not diagnosed as antiphospholipid syndrome (APS) could be a risk factor for unexplained RM. However, no established treatment has been documented for patients with occasional aPL-positivity. Case presentation: This patient with unexplained infertility underwent in vitro fertilization (IVF) and experienced three continuous miscarriages, including chemical pregnancy. The general screening for RM detected only aPL-IgG. However, the negative result obtained by the retest 12 weeks later suggested the case as an unexplained RM with occasional aPL-positivity not diagnosed with APS. Low-dose aspirin (LDA; enteric-coated aspirin tablet, 100 mg once daily) as an anticoagulant was administered on the day of embryo transfer (ET) and continued until a successful clinical pregnancy was determined. Although implantation was achieved with this intervention, a successful clinical pregnancy could not be achieved. Thereafter, low-molecular-weight heparin (LMWH; 10,000 IU every 12 h) and LDA (enteric-coated aspirin tablet, 100 mg once daily) were administered everyday starting on the day of ET and continued till 14 and 28 weeks of gestation, respectively. On day 16 post-ET, the serum β-human chorionic gonadotropin concentration was elevated to 2562.0 IU/L, and an ultrasound confirmed the pregnancy. The patient successfully completed the course of pregnancy and delivered a viable female neonate (3010 g) at 40 weeks and 3 days of gestation. Conclusions: This case demonstrated that the combination therapy of LMWH and LDA led to a successful pregnancy and live birth in a patient with occasional aPL-positivity but not APS. However, further clinical trials are required to confirm the efficacy of the combined therapy of LMWH and LDA in patients with unexplained RM associated with occasional aPL-positivity.