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使用肿瘤坏死因子抑制剂和静脉注射免疫球蛋白进行治疗可提高复发性自然流产女性的活产率。

Treatment with tumor necrosis factor inhibitors and intravenous immunoglobulin improves live birth rates in women with recurrent spontaneous abortion.

作者信息

Winger Edward E, Reed Jane L

机构信息

Alan E. Beer Center for Reproductive Immunology & Genetics, San Francisco, CA, USA.

出版信息

Am J Reprod Immunol. 2008 Jul;60(1):8-16. doi: 10.1111/j.1600-0897.2008.00585.x. Epub 2008 Apr 1.

Abstract

PROBLEM

The purpose of this study was to investigate whether treatment with tumor necrosis factor (TNF) inhibitors combined with intravenous immunoglobulin (IVIG) increases live birth rates among women with recurrent spontaneous abortion (RSA) concurrently treated with anticoagulants (AC).

METHOD OF STUDY

Seventy-five pregnancies in patients with a history of RSA were retrospectively evaluated. The population was divided into three groups: group I: 21 patients treated with AC (anticoagulants), group II: 37 patients treated with AC and IVIG, and group III: 17 patients treated with AC, IVIG and the TNF inhibitor Etanercept (Enbrel) or Adalimumab (Humira). In groups II and III, IVIG was administered at least once during the cycle of conception and/or at least once after a positive pregnancy test. In group III, either Adalimumab or Etanercept was administered by subcutaneous injection according to standard protocols. Statistical analysis of pregnancy outcome was performed using Fisher's exact test.

RESULTS

Patient populations in the three treatment groups were similar in terms of age, past miscarriages, inherited thrombophilia and autoimmunity. The live birth rate was 19% (4/21) in group I, 54% (20/37) in group II, and 71% (12/17) in group III. There was significant improvement in pregnancy outcome in group II versus group I (P = 0.0127) and in group III versus group I (P = 0.0026). The live birth rate in group III compared to group II was not significantly different (P = 0.3723). Side effects of AC, IVIG and TNF inhibitor treatment were minimal in these patients, and no birth defects were identified in their offspring.

CONCLUSION

In women with RSA, addition of either IVIG or a TNF inhibitor + IVIG to the AC regimen appears to improve live birth rates compared to the treatment with AC alone. The positive effect of IVIG and TNF inhibitor therapy on pregnancy outcome merits further study in prospective clinical trials.

摘要

问题

本研究的目的是调查肿瘤坏死因子(TNF)抑制剂联合静脉注射免疫球蛋白(IVIG)治疗是否能提高同时接受抗凝剂(AC)治疗的复发性自然流产(RSA)女性的活产率。

研究方法

回顾性评估了75例有RSA病史患者的妊娠情况。将研究对象分为三组:第一组:21例接受AC(抗凝剂)治疗的患者;第二组:37例接受AC和IVIG治疗的患者;第三组:17例接受AC、IVIG以及TNF抑制剂依那西普(恩利)或阿达木单抗(修美乐)治疗的患者。在第二组和第三组中,IVIG在受孕周期至少给药一次和/或在妊娠试验呈阳性后至少给药一次。在第三组中,根据标准方案通过皮下注射给予阿达木单抗或依那西普。使用Fisher精确检验对妊娠结局进行统计分析。

结果

三个治疗组的患者在年龄、既往流产史、遗传性血栓形成倾向和自身免疫方面相似。第一组的活产率为19%(4/21),第二组为54%(20/37),第三组为71%(12/17)。与第一组相比,第二组的妊娠结局有显著改善(P = 0.0127),与第一组相比,第三组也有显著改善(P = 0.0026)。第三组与第二组的活产率相比无显著差异(P = 0.3723)。这些患者中AC、IVIG和TNF抑制剂治疗的副作用最小,其后代未发现出生缺陷。

结论

在RSA女性中,与单独使用AC治疗相比,在AC治疗方案中添加IVIG或TNF抑制剂+IVIG似乎能提高活产率。IVIG和TNF抑制剂疗法对妊娠结局的积极作用值得在前瞻性临床试验中进一步研究。

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