Lodigiani Corrado, Di Micco Pierpaolo, Ferrazzi Paola, Librè Luca, Arfuso Veronica, Polatti Franco, Benigna Michela, Rossini Roberta, Morenghi Emanuela, Rota Lidia, Brenner Benjamin, Setti Paolo Emanuele Levi
Thrombosis Center, IRCCS Istituto Clinico Humanitas, Milan, Italy.
Womens Health (Lond). 2011 Jul;7(4):425-31. doi: 10.2217/whe.11.38.
Implantation failure is common in assisted reproduction techniques (ART). The role of low-molecular-weight heparin (LMWH) is a matter of debate as a potential factor to improve implantation.
To evaluate the pregnancy rate in patients with or without heparin administration.
MATERIALS & METHODS: We performed a retrospective observational analysis of patients with at least two IVF/intracytoplasmic sperm injection cycles with implantation failure, screened for inherited thrombophilia and submitted to further ART cycles with or without administration of LMWH. A total of 265 patients fulfilled the enrollment criteria. Of these 149 (56%) were primary infertile and 116 (44%) were secondary infertile. Their mean age was 36.3 ± 3.6 years. We analyzed basal FSH, smoking habit, gene variants for inherited thrombophilia (i.e., MTHFR C677T, prothrombin G202A10G and Factor V Leiden). The patients underwent 569 new ART cycles: 512 (90%) without and 57 (10%) with LMWH.
In total 105 clinical pregnancies were observed in 569 cycles (18.8%). The pregnancy rate was 17.19% (88/512) in patients not treated with LMWH and 29.52% (17/57) in the LMWH-treated group (p = 0.006). In women over 36 years of age the pregnancy rate was 15.53% (50/322) in nontreated versus 35.71% (10/28) in treated cycles (p = 0.007), while no difference was found in younger women. No statistical difference was found between the presence of inherited thrombophilia and pregnancy rate in treated and untreated cycles.
significantly higher pregnancy rate in patients with previous ART implantation failures was observed with LMWH. Our results confirm no relation among inherited thrombophilia and pregnancy rate in patients with previous IVF implantation failures. These findings should be confirmed by randomized controlled trials before use of LMWH for ART cycles is recommended.
植入失败在辅助生殖技术（ART）中很常见。低分子量肝素（LMWH）作为改善植入的潜在因素，其作用存在争议。
评估接受或未接受肝素治疗的患者的妊娠率。
我们对至少有两个体外受精/卵胞浆内单精子注射周期且植入失败的患者进行了回顾性观察分析，筛查遗传性血栓形成倾向，并在接受或不接受LMWH治疗的情况下进行进一步的ART周期。共有265名患者符合纳入标准。其中149名（56%）为原发性不孕，116名（44%）为继发性不孕。他们的平均年龄为36.3±3.6岁。我们分析了基础促卵泡激素、吸烟习惯、遗传性血栓形成倾向的基因变异（即亚甲基四氢叶酸还原酶C677T、凝血酶原G20210G和因子V莱顿）。患者进行了569个新的ART周期：512个（90%）未使用LMWH，57个（10%）使用LMWH。
在569个周期中共观察到105例临床妊娠（18.8%）。未接受LMWH治疗的患者妊娠率为17.19%（88/512），LMWH治疗组为29.52%（17/57）（p = 0.006）。36岁以上女性未治疗周期的妊娠率为15.53%（50/322），治疗周期为35.71%（10/28）（p = 0.007），而年轻女性未发现差异。在治疗和未治疗周期中，遗传性血栓形成倾向的存在与妊娠率之间未发现统计学差异。
观察到既往ART植入失败的患者使用LMWH后妊娠率显著更高。我们的结果证实既往IVF植入失败的患者中遗传性血栓形成倾向与妊娠率之间无关联。在推荐将LMWH用于ART周期之前，这些发现应通过随机对照试验加以证实。
