Adjunct low-molecular-weight heparin to improve live birth rate after recurrent implantation failure: a systematic review and meta-analysis

background: Poor fertility outcomes in womenwith recurrent implantation failure (≥RIF) present significant challenges in assisted reproduction, and various adjuncts, including heparin, areused for potential improvement in pregnancy rates.Weperformed this systematic reviewand meta-analysis to evaluate the effect of low-molecular-weight heparin (LMWH) on live birth rates (LBRs) and implantation rates (IRs) in women with RIF and undergoing IVF. methods: Studies comparing LMWH versus control/placebo in women with RIF were searched for on MEDLINE, EMBASE, Cochrane Library, conference proceedings and databases for registered and ongoing trials (1980–2012). Statistical analysis was performed using Review Manager 5.1. The main outcome measure was LBR per woman. results: Two randomized controlled trials (RCTs) andonequasi-randomized trialmet the inclusion criteria.One study includedwomenwith at least one thrombophilia (Qublan et al., 2008) and two studies included women with unexplained RIF (Urman et al., 2009; Berker et al., 2011). Pooled risk ratios inwomenwith≥3RIF (N 1⁄4 245) showed a significant improvement in the LBR (risk ratio (RR) 1⁄4 1.79, 95% confidence interval (CI) 1⁄4 1.10–2.90, P 1⁄4 0.02) and a reduction in the miscarriage rate (RR 1⁄4 0.22, 95% CI 1⁄4 0.06–0.78, P 1⁄4 0.02) with LMWH compared with controls. The IR for ≥3 RIF (N 1⁄4 674) showed a non-significant trend toward improvement (RR 1⁄4 1.73, 95% CI 0.98–3.03, P 1⁄4 0.06) with LMWH. However, the beneficial effect of LMWH was not significant when only studies with unexplained RIF were pooled.