静脉注射免疫球蛋白对复发性流产活产率的影响

Effect of Intravenous Immunoglobulins on Live Birth Rate in Women of Recurrent Spontaneous Abortion

摘要: 目的：系统评价静脉注射免疫球蛋白(intravenous immunoglobulins, IVIG)治疗复发性流产(recurrent spontaneous abortion, RSA)的临床疗效。方法：检索Cochrane图书馆、PubMed、Embase、中国知网和维普数据库，查找有关IVIG治疗RSA的随机对照试验(randomized controlled trials, RCT)，检索范围为建库至2021年12月。按照纳入排除标准，由两名作者独立进行文献筛选并提取所需信息，采用Review Manager 5.3软件对所提取的数据进行分析。结果：本研究纳入10篇RCT，共496名RSA患者。IVIG治疗组活产率高于安慰剂组(60.57% vs 55.2%)，差异无统计学意义(RR = 0.88, 95% CI = 0.72~1.08, P = 0.23)。相对于原发性RSA患者，IVIG治疗对提高继发性RSA患者活产率有积极作用(RR = 1.05, 95% CI = 0.90~1.22, P = 0.03)。按照用药时机将RSA患者分为妊娠前与确定妊娠后IVIG治疗两个亚组进行分析，活产率在两种给药方案间无统计学差异(RR = 1.09, 95% CI (0.95~1.27), P = 0.06)。相比于妊娠后给药组(103/172 vs 101/168, RR = 1.00, 95% CI (0.84~1.18), P = 0.97)，在妊娠前给予IVIG治疗RSA患者活产率更高(46/74 vs. 37/82; RR = 1.38, 95% CI (1.03~1.86), P = 0.03)。将原发性RSA患者分为妊娠前与妊娠后给予IVIG治疗两个亚组进行分析，活产率在两种方案之间无统计学差异(RR = 0.88, 95% CI = 0.71~1.07, P = 0.45)。将继发性RSA患者分为妊娠前与妊娠后给予IVIG治疗两个亚组进行分析，活产率在两种方案之间无统计学差异(RR = 1.24, 95% CI = 0.98~1.57, P = 0.94)。结论：IVIG治疗RSA疗效尚不确定。相对于原发性RSA，IVIG治疗对提高继发性RSA患者活产率有积极作用。RSA患者在妊娠前给予IVIG治疗中获益。对于继发性RSA患者，妊娠前与妊娠后给予IVIG治疗，活产率无统计学差异。

Abstract: Objective: To evaluate the effectiveness of intravenous immunoglobulins (IVIG) in recurrent spon-taneous abortion (RSA) patients. Methods: Randomized controlled trials (RCTs) about IVIG for RSA were searched in the Cochrane Library, PubMed, Embase and the Chinese literature from CNKI and VIP. The search range was from the establishment of the database to December 2021. According to the inclusion and exclusion criteria, two authors independently conducted literature screening and extracted the required information. We undertook meta-analysis of aggregated data by using Re-view Manager 5.3 software. Results: Ten RCTs with a total of 496 patients were included in this study. The live birth rate in the IVIG group was higher than that in the placebo group (60.57% vs 55.2%), with no statistically significant difference (RR = 0.88, 95% CI = 0.72~1.08, P = 0.23). Sub-group analysis showed that IVIG may have a positive effect on live birth rate in secondary RSA pa-tients compared with patients with primary RSA (RR = 1.05, 95% CI = 0.90~1.22, P = 0.03). RSA pa-tients were divided into two subgroups of pre-pregnancy and post-pregnancy IVIG treatment ac-cording to medication timing. There was no significant difference in live birth rate between the two subgroups (RR = 1.09, 95% CI (0.95~1.27), P = 0.06). The results indicated that IVIG treatment be-fore conception may have beneficial effects (46/74 versus 37/82; RR: 1.38, 95% CI 1.03~1.86, P = 0.03) compared to first regimen given when the pregnancy was diagnosed (103/172 versus 101/168; RR: 1.00 95% CI 0.84~1.18, P = 0.97). Patients with primary RSA were divided into two subgroups receiving IVIG treatment before and after pregnancy. There was no significant difference in live birth rate between the two subgroups (RR = 0.88, 95% CI = 0.71~1.07, P = 0.45). Patients with secondary RSA were divided into two subgroups treated with IVIG before and after pregnancy. There was no significant difference in the live birth rate between the two subgroups (RR = 1.24, 95% CI = 0.98~1.57, P = 0.94). Conclusions: The efficacy of IVIG in the treatment of RSA patients is uncertain. Compared with primary RSA, IVIG treatment had a positive effect on improving the live birth rate for secondary RSA. IVIG treatment before conception may have beneficial effects on live birth in RSA patients. For secondary RSA, there was no statistically significance for outcome “live birth” between before pregnancy and after pregnancy.