Low molecular weight heparin or LMWH plus aspirin in the treatment of unexplained recurrent miscarriage with negative antiphospholipid antibodies: A meta-analysis of randomized controlled trial

Objective: Unexplained recurrent miscarriage (uRM) has caused serious distress to women of childbearing age, and effective treatment is particularly important. The aim of this meta-analysis is to compare the efficacy of low molecular weight heparin (LMWH) and LMWH combined with aspirin for uRM. Methods: Databases including PubMed, Web of Science, Embase, Scopus and the Cochrane Library databases were electronically searched to identify randomized controlled trials that reported the LMWH or LMWH combined with aspirin for women with uRM and negative antiphospholipid antibodies (aPL). The retrieval time is limited from inception to June 2021. Two reviewers independently screened literature, extracted data, and assessed risk bias of included studies. Meta-analysis was performed by using STATA 12.0 software. Results: A total of 7 studies involving 1849 patients were included. The meta-analysis results showed that compared with the control group, both LMWH and LMWH + aspirin interventions showed no substantial influence on miscarriage rate (LMWH: RR = 0.69, 95%CI: 0.34-1.39, P = 0.293, LMWH + aspirin: RR = 0.62, 95%CI: 0.30-1.27, P = 0.19) and the occurrence of pre-eclampsia (LMWH: RR = 1.1, 95%CI: 0.53-2.31, P = 0.792; LMWH + aspirin: RR = 1.49, 95%CI: 0.25-8.79, P = 0.662). LMWH therapy had no influence on the live births (RR = 0.99, 95%CI: 0.92-1.06, P = 0.72). Subgroup analysis showed that enoxaparin is not effective in women with uRM and negative aPL (miscarriage rate: RR = 0.82, 95%CI: 0.31-2.19, P = 0.695; pre-eclampsia: RR = 1.03, 95%CI: 0.46-2.33, P = 0.936). Conclusions: LMWH and LMWH combined with aspirin therapy cannot improve the pregnancy outcome of women with uRM and negative aPL. However, the above conclusions are still required to be verified through more RCTs due to the limited quantity of included studies. (C) 2021 Elsevier B.V. All rights reserved.