Objective

Current opinion on the superiority of fondaparinux versus low molecular-weight heparin (LMWH) in treating recurrent miscarriage is controversial. This meta-analysis aimed to comprehensively compare the pregnancy outcomes and adverse events in patients with recurrent miscarriage receiving fondaparinux versus LMWH.

Methods

EMBASE, PubMed, Cochrane, China National Knowledge Internet (CNKI), Wanfang Database, and China Science and Technology Journal Database (CQVIP) databases were searched for articles reporting fondaparinux versus LMWH in treating recurrent miscarriage till June 10, 2022. Inclusion criteria for study screening were: (i) randomized, controlled trials (RCT), non-randomized controlled studies, or observational studies; (ii) patients aged over 18 years; (iii) patients with recurrent miscarriage during gestation period; (iv) patients in the experimental/observational group who received FD, and patients in the control group who received LMWH; (v) studies involving at least one outcome of interest for the current analysis. Exclusion criteria were: (i) systematic reviews, meta-analyses, case reports, or animal studies; (ii) duplicated studies; (iii) incomplete or inconsistent data. Quality assessment was conducted with Newcastle-Ottawa Scale criteria or Cochrane Collaboration. Data of live birth, abortion, birth weight, fetal growth restriction (FGR), and adverse events were extracted and synthesized.

Results

Six eligible studies (4 observational studies and 2 RCTs) with 321 patients receiving fondaparinux and 546 patients receiving LMWH were enrolled. Live birth (relative risks (RR) = 1.05, 95% confidence interval (CI) = 0.97 ∼ 1.14, P = 0.217), abortion (RR = 0.73, 95% CI = 0.50 ∼ 1.08, P = 0.113), birth weight (weighted mean difference = 167.20, 95% CI = −236.89 ∼ 571.30, P = 0.417), and FGR (RR = 0.95, 95% CI = 0.25 ∼ 3.59, P = 0.942) were of no difference between patients receiving fondaparinux and LMWH. Regarding adverse events, the incidence of ecchymosis (RR = 0.11, 95% CI = 0.03 ∼ 0.46, P = 0.002) and skin reaction at injection site (RR = 0.15 95% CI = 0.05 ∼ 0.44, P = 0.001) were lower in patients receiving fondaparinux compared with those receiving LMWH, while that of thrombocytopenia (RR = 0.45, 95% CI = 0.09 ∼ 2.14, P = 0.315), vagina bleeding (RR = 1.03, 95% CI = 0.62 ∼ 1.71, P = 0.646), and oral mucosa hemorrhage (RR = 1.08, 95% CI = 0.33 ∼ 3.51, P = 0.899) did not vary between these patients receiving these two treatments. However, most studies were conducted in China, which could induce regional and ethnic bias.

Conclusion

Fondaparinux is attributable to fewer adverse events and similar pregnancy outcomes compared with LMWH in patients with recurrent miscarriage.