低分子肝素在人类辅助生殖技术获得妊娠后发生复发性流产患者中的临床研究

Clinical research of LMWH in therapy of women with RSA pregnant by ART

目的目前针对低分子肝素(LMWH)在人类辅助生殖技术(ART)获得妊娠后发生复发性流产(RSA)患者中的临床病例研究较少。文中旨在探讨LMWH在ART获得妊娠后发生RSA妇女中的临床应用研究。方法选择2010年1月至2016年2月于广东医科大学附属医院生殖医学中心进行ART治疗获得妊娠后发生RSA的患者126例。根据接受ART助孕治疗的病因不同,其中子宫输卵管造影提示至少有一侧输卵管为通畅的患者,接受宫腔内人工授精(IUI)助孕治疗;而有输卵管疾病体外受精-胚胎移植(IVF-ET)治疗。将同意采用LMWH治疗的60例患者按不同治疗方式分为LMWH+IUI组(接受IUI治疗)、LMWH+IVF-ET组(接受IVF-ET治疗),每组30例。将不同意采用LMWH治疗的66例患者分为IUI组(n=32)、IVF-ET组(n=34)。比较4组患者接受ART的妊娠成功率、抱婴率,再次发生RSA的妊娠时间、妊娠并发症的发病率等。同时观察LMWH使用过程中不良反应的发生情况。结果 LMWH+IUI组再次发生RSA的妊娠时间较IUI组显著增加[(82.67±9.10)d vs(48.17±8.68)d,P<0.05]。LMWH+IVF-ET组妊娠成功率、抱婴率较IVF-ET组显著升高[66.67%vs35.29%;85.00%vs 50.00%,P<0.05],2组再次流产的发生率、再次发生RSA的妊娠时间、妊娠期高血压疾病发生率差异亦有统计学意义(P<0.05)。LMWH+IUI组、LMWH+IVF-ET组孕4周血浆D二聚体(D2D)数值[(0.65±0.07)、(0.62±0.06)mg/L]低于IUI组、IVF-ET组[(0.76±0.12)、(0.77±0.06)mg/L],LMWH+IUI组孕6周D2D值低于IUI组、IVF-ET组,LMWH+IVF-ET组低于IVF-ET组(P<0.05)。4组患者的血浆D2D数值组内比较均随着孕周的增加而增加(P<0.05)。LMWH+IUI组、IUI组和LMWH+IVF-ET组孕4周凝血酶原时间(PT)含量[(12.53±0.38)、(12.38±0.65)、(12.47±0.58)s]较孕前[(12.33±0.52)、(12.30±0.68)、(12.22±0.64)s]、孕6周[(12.13±0.62)、(12.05±0.60)、(12.03±0.54)s]明显增高(P<0.05)。LMWH+IUI组、LMWH+IVF-ET组使用LMWH的60例患者中11例出现脐周注射部位的皮下小面积瘀青,发生率为18.33%(11/60)。仅2例患者出现皮下注射部位轻度疼痛不适感,发生率为3.33%(2/60)。结论 ART获得妊娠后发生RSA女性采用小剂量LMWH治疗安全有效。

Objective There are few studies on the appli- cation of low molecular weight heparin （LMWH） in the therapy of women with recurrent spontaneous abortion （RSA） pregnant by assis- ted reproductive technology （ART）. The article aimed to explore the clinical research of LMWH in therapy of women with RSA pregnant by ART. Methods 126 women with RSA pregnant by ART were enrolled and they were diagnosed and treated in Reproductive Medicine Center in the Affiliated Hospital of Guangdong Medical Univer- sity from January 2010 to February 2016. According to the patient＇s agreement on LMWH treatment, 60 patients in agreement with LMWH treatment were divided into 2 groups： LMWH＋IUI group（n = 30） and LMWH＋ IVF-ET group（n = 30）. 66 patients in disagree- ment with LMWH treatment were also divided into 2 groups： IUI group（n=32） and IVF-ET group（n=34）. Comparison was made in patients from 4 groups concerning pregnancy success rate, live birth rate, pregnancy time involving RSA and incidence of pregnancy complications. At the same time, the occurrence of adverse reactions during the use of LMWH was also observed. Results The preg- nancy time involving RSA in LMWH＋IUI group significantly increased compared with IUI group（ [ 82.67±9.10] d vs [ 48.17±8.68 ] d） （P〈0.05）. The pregnancy success rate and live birth rate in LMWH＋ IVF-ET group were both higher than those of IVF-ET group （66.7% vs 35.29%, 85.00% vs 50.00%）（P〈0.05） and significant difference was also found in the incidence of RSA, the pregnancy time involving RSA, and the morbidity of gestational hypertension between groups （P〈0.05）. The results of D2D at 4 weeks of pregnan- cy in LMWH＋IUI group（ [ 0.65±0.07] mg/L） and LMWH＋ IVF-ET group（ [ 0.625±0.06] mg/L） were lower than those of LMWH group （ [0.76±0.121 mg/L） and LMWH group（ [ 0.77±0.06 ] rag/L）. The result of D2D at 6 weeks of pregnancy in LMWH＋IUI group was lower than those of IUI group and IVF-ET group, and D2D in LMWH＋ IVF-ET group was lower compared with IVF-ET group（ P〈 0.05）. The results of D2D in all the four groups increased with the pregnancy weeks （P〈0.05）. The prothrombin time（PT） at 4 weeks of pregnancy in LMWH＋IUI group, IUI group and LMWH＋ IVF-ET group （ [ 12.53±0.38] s, [ 12.38±0.65] s, [ 12.47±0.581 s） was significantly higher at pre-pregnancy（ [ 12.33±0.52] s, [ 12.30±0.681 s, [ 12.22±0.641 s） and 6 weeks of pregnancy（ [ 12.13±0.62] s, [ 12.05±0.60 ] s, [ 12.03±0.54 ] s） （P〈 0.05）. Among 60 cases treated with LMWH, small area ecchymoma were found in 11 cases and the incidence was 18.33% （ 11/60）, only two cases reported with uncomfortable light pain in the location of subcutaneous injection. Conclusion Low-dose LMWH is safe and effective in the therapy of pregnant women with RSA through ART.