Intravenous immunoglobulin and idiopathic secondary recurrent miscarriage: a multicentered randomized placebo-controlled trial
Intravenous immunoglobulin and idiopathic secondary recurrent miscarriage: a multicentered randomized placebo-controlled trial
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DOI：
10.1093/humrep/deq179
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发表时间：
2010-09-01
影响因子：
6.1
通讯作者：
Liao, Chuanhong
中科院分区：
文献类型：
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作者：
Stephenson, Mary D.;Kutteh, William H.;Liao, Chuanhong
特发性继发性复发性流产可能与产妇对后续妊娠的异常免疫反应有关。静脉注射免疫球蛋白（IVIG）已经在随机对照试验（rct）中进行了研究，结果相互矛盾。因此，建议进行决定性的试验。我们进行了一项研究者发起的、多中心、随机、双盲、安慰剂对照试验，比较IVIG和生理盐水在特发性继发性复发性流产患者中的应用，特发性继发性复发性流产定义为至少有一次持续妊娠史，随后连续三次或更多原因不明的流产。受试者接受IVIG 500 mg/kg或等量生理盐水。在预计下一次月经后的14-21天进行孕前注射。根据妊娠记录，受试者每4周接受相同的输注，直至妊娠18-20周。主要结局是持续妊娠至少20周。共纳入82例患者，其中47例为指数妊娠。所有正在进行的妊娠均导致活产。因此，IVIG组活产率为70%(16/23)，对照组为63%(15/24)，差异有统计学意义（P = 0.760）；优势比（OR） 1.37[95%可信区间（CI） 0.41-4.61]。仅包括临床妊娠（妊娠6周时胚胎有心脏活动），活产率相等，分别为94%（16/17）和（15/16）（P < 0 0.999）；或1.07 （95% ci 0.06-18.62）。评价IVIG治疗特发性继发性复发性流产的随机对照试验（rct）荟萃分析显示，IVIG组活产率为70%(31/44)，对照组为62% (28/45)(P = 0.503)；普通OR为1.44 （95% CI 0.59-3.48）。这是迄今为止在特发性继发性复发性流产妇女中评估IVIG的最大的随机对照试验；没有发现治疗效果。将我们的研究结果与之前的两项随机对照试验相结合的荟萃分析也显示，使用ivig治疗没有显著效果。
Idiopathic secondary recurrent miscarriage may be associated with an abnormal maternal immune response to subsequent pregnancies. Intravenous immunoglobulin (IVIG) has been studied in randomized controlled trials (RCTs) with conflicting results. Therefore, a definitive trial was proposed.We conducted an investigator-initiated, multicentered, randomized, double-blinded, placebo-controlled trial comparing IVIG with saline in women with idiopathic secondary recurrent miscarriage, defined as a history of at least one prior ongoing pregnancy followed by three or more consecutive unexplained miscarriages. Subjects received either IVIG 500 mg/kg or the equivalent volume of normal saline. Preconception infusions were administered 14-21 days from the projected next menstrual period. With documentation of pregnancy, the subject received the same infusion every 4 weeks until 18-20 weeks of gestation. The primary outcome was an ongoing pregnancy of at least 20 weeks of gestation.A total of 82 patients enrolled, of whom 47 had an index pregnancy. All ongoing pregnancies resulted in live births. Therefore, the live birth rates were 70% (16/23) in the IVIG group and 63% (15/24) in the control group (P = 0.760); odds ratio (OR) 1.37 [95% confidence interval (CI) 0.41-4.61]. Including only clinical pregnancies (embryo with cardiac activity at 6 weeks of gestation), the live birth rates were equivalent, 94% (16/17) and (15/16), respectively (P > 0.999); OR 1.07 (95% CI 0.06-18.62). Meta-analysis of randomized controlled trials (RCTs) evaluating IVIG for idiopathic secondary recurrent miscarriage revealed live birth rates of 70% (31/44) in the IVIG group and 62% (28/45) in the control group (P = 0.503); common OR 1.44 (95% CI 0.59-3.48).This is the largest RCT to date in which IVIG was evaluated in women with idiopathic secondary recurrent miscarriage; no treatment benefit was found. The meta-analysis, which combined our study results with two prior RCTs, also showed no significant effect of treatment with IVIG.ClinicalTrials.gov NCT00606905.