Leicester Fertility Centre, University Hospitals of Leicester, Leicester LE1 5WW, UK.
Hum Reprod Update. 2013 Nov-Dec;19(6):674-84. doi: 10.1093/humupd/dmt032. Epub 2013 Aug 2.
BACKGROUND Poor fertility outcomes in women with recurrent implantation failure (≥ RIF) present significant challenges in assisted reproduction, and various adjuncts, including heparin, are used for potential improvement in pregnancy rates. We performed this systematic review and 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) and one quasi-randomized trial met the inclusion criteria. One study included women with 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 in women with ≥ 3 RIF (N = 245) showed a significant improvement in the LBR (risk ratio (RR) = 1.79, 95% confidence interval (CI) = 1.10-2.90, P = 0.02) and a reduction in the miscarriage rate (RR = 0.22, 95% CI = 0.06-0.78, P = 0.02) with LMWH compared with controls. The IR for ≥ 3 RIF (N = 674) showed a non-significant trend toward improvement (RR = 1.73, 95% CI 0.98-3.03, P = 0.06) with LMWH. However, the beneficial effect of LMWH was not significant when only studies with unexplained RIF were pooled. The summary analysis for the numbers needed to be treated with LMWH showed that approximately eight women would require treatment to achieve one extra live birth. CONCLUSIONS In women with ≥3 RIF, the use of adjunct LMWH significantly improves LBR by 79% compared with the control group; however, this is to be considered with caution, since the overall number of participants in the studies was small. Further evidence from adequately powered multi-centered RCTs is required prior to recommending LMWH for routine clinical use. This review highlights the need for future basic science and clinical research in this important field.
在反复着床失败（≥RIF）的女性中，生育能力差会给辅助生殖带来重大挑战，肝素等各种辅助药物也被用于提高妊娠率。我们进行了这项系统评价和荟萃分析，以评估低分子肝素（LMWH）对接受体外受精（IVF）的 RIF 女性的活产率（LBR）和着床率（IR）的影响。
我们在 MEDLINE、EMBASE、Cochrane 图书馆、会议记录和注册及正在进行的试验数据库中搜索比较 LMWH 与 RIF 女性的对照/安慰剂的研究。使用 Review Manager 5.1 进行统计分析。主要观察指标为每位女性的活产率。
两项随机对照试验（RCT）和一项准随机试验符合纳入标准。一项研究纳入了至少有一项血栓形成倾向的女性（Qublan 等人，2008 年），两项研究纳入了不明原因的 RIF 女性（Urman 等人，2009 年；Berker 等人，2011 年）。在至少有 3 次 RIF 的女性（N=245）中，汇总风险比显示 LMWH 治疗组的活产率显著提高（风险比（RR）=1.79，95%置信区间（CI）=1.10-2.90，P=0.02），流产率降低（RR=0.22，95%CI=0.06-0.78，P=0.02）。在至少有 3 次 RIF 的女性（N=674）中，IR 有改善的趋势，但无统计学意义（RR=1.73，95%CI 0.98-3.03，P=0.06）。然而，当仅纳入不明原因 RIF 的研究进行汇总分析时，LMWH 的有益效果并不显著。LMWH 治疗需要的人数分析显示，大约需要治疗 8 名女性才能多获得一个活产。
在至少有 3 次 RIF 的女性中，与对照组相比，辅助使用 LMWH 可使 LBR 显著提高 79%；然而，由于研究的总参与者人数较少，这一结果应谨慎考虑。在推荐 LMWH 常规临床应用之前，还需要来自足够多的多中心 RCT 的进一步证据。本综述强调了在这一重要领域进行未来基础科学和临床研究的必要性。
