复发性自然流产患者封闭抗体的检测与临床应用

复发性自然流产（recurrent spontaneous abortion,RSA）是常见的妊娠并发症,发生率为0.4%-5%,导致RSA的原因复杂,除染色体、解剖、内分泌、感染、自身抗体的产生外,多与封闭抗体（blocking antibodies BA）缺乏有关。正常孕产妇血清中封闭抗体（BA）主要是针对胚胎HLA-Ⅱ抗原和滋养层淋巴细胞交叉抗原即TLX抗原产生的Ig-G抗体,     

封闭抗体与复发性自然流产的研究进展

复发性自然流产(RSA)是妊娠期妇女常见的并发症,在育龄妇女中发病较常见,导致RSA的原因复杂主要涉及到染色体、解剖、内分泌、感染、自身抗体等多方面因素,其中大多数与免疫因素有关.近年来封闭抗体(APLA)与RSA之间的关系得到了越来越多研究者的关注.APLA缺乏是导致RSA的免疫学因素之一,因而具有重要的临床意义.     

配偶淋巴细胞免疫治疗反复自然流产91例分析

目的探讨反复自然流产患者,运用配偶淋巴细胞免疫治疗后,体内封闭抗体水平的变化及其临床疗效.方法对确诊为封闭抗体缺乏的RSA患者91例,用分离的配偶淋巴细胞,皮内注射法免疫治疗3～5疗程,治疗前后运用流式细胞仪测定患者体内封闭抗体水平.结果 91例RSA患者经免疫治疗后,体内封闭抗体的水平显著提高,抗配偶CD3%、抗配偶CD4%、抗配偶CD8%,分别由治疗前的-1.32±0.98、-1.39±0.80、-0.96±0.54上升为0.99±0.74、1.01±0.64、0.75±0.49(P＜0.05);妊娠成功80例,成功率为87.9%(80 / 91).结论配偶淋巴细胞免疫治疗,可以提高患者体内封闭抗体水平,有助于妊娠成功.     

加强免疫治疗反应不良的RSA患者的疗效评价

目的：评价加强免疫对淋巴细胞免疫治疗反应不良RSA患者的疗效。方法：以封闭抗体流式细胞术选择抗CD3-BE和抗CD4-BE低于O％的母-胎免疫识别低下型RSA患者行配偶淋巴细胞体外诱生后免疫、高于O％者行配偶淋巴细胞直接免疫，对第一疗程反应不良的RSA患者行加强免疫治疗，复测封闭抗体指标以评价其效果。结果：母-胎免疫识别低下型RSA经配偶淋巴细胞免疫后封闭抗体水平仍呈下降趋势的患者，经第二疗程配偶淋巴细胞加强免疫后，封闭抗体水平明显升高，而经配偶淋巴细胞直接免疫者虽然封闭效率明显升高，其它指标均无明显改善。结论：对配偶淋巴细胞免疫疗法反应不良的RSA患者需进行第二疗程配偶淋巴细胞加强免疫，以配偶淋巴细胞体外诱生后免疫治疗为佳。     

反复自然流产患者经配偶淋巴细胞免疫治疗后外周封闭抗体水平变化

反复自然流产(Recurrent spontaneous abortion,RSA)的发病原因除少数为生殖内分泌、染色体及生殖器官解剖学异常外,多因免疫调节异常所致.根据免疫病因分类可将RSA分为母-胎免疫识别低下型、母-胎免疫识别过度型、母-胎免疫紊乱型[1],其中,以封闭抗体(Blocking antibody,BA)缺乏为主要特征的母-胎免疫识别低下型最常见.     

母-胎免疫识别低下型反复自然流产配偶淋巴细胞免疫疗法的改进

比较配偶淋巴细胞诱生后与非诱生免疫疗法 ,对于母 胎免疫识别低下型反复自然流产 (RSA )的临床疗效 ,并分析其疗效机制。 194例母 胎免疫识别低下型RSA患者随机分成 2组 ,分别采用经体外诱生的或未经体外诱生的配偶淋巴细胞对其进行皮内多点注射免疫治疗。分别观察随后的妊娠结局、封闭抗体水平。经配偶淋巴细胞免疫后 ,体外诱生的淋巴细胞免疫组妊娠成功率为 90 0 % ;未经体外诱生的淋巴细胞免疫组妊娠成功率为 84 8%。对于封闭抗体各项指标分析结果显示 ,配偶淋巴细胞皮内免疫能有效促进RSA患者封闭抗体及其抗独特型抗体水平的升高 ;经体外诱生的配偶淋巴细胞免疫疗法能显著提高RSA患者外周血抗CD3 BE的水平。配偶淋巴细胞皮内免疫疗法通过刺激封闭抗体的产生 ,改善随后的妊娠预后 ,配偶淋巴细胞经体外诱生后作为免疫原 ,通过升高抗CD3封闭抗体水平 ,有助于改善妊娠预后。     

不同疗法对封闭抗体缺乏所致复发性流产的临床观察

目的观察五子颗粒、主动免疫疗法及五子颗粒联合主动免疫3种疗法对反复自然流产(RSA)患者封闭抗体转阳及妊娠的影响。方法将125例在我院产前诊断中心就诊的RSA患者随机分成中药治疗组38例,免疫治疗组(主动免疫治疗)41例,联合治疗组(主动免疫治疗+服用中药)46例。中药组采用五子颗粒制剂治疗,免疫治疗组采用主动免疫方法治疗,联合治疗组在主动免疫治疗基础上,辅以中药联合治疗,免疫治疗每月1次,3次为1个疗程,并观察其封闭抗体转阳情况及妊娠结局。结果 125例患者均完成治疗后,联合治疗组封闭抗体总转阳率为89.1%,高于中药治疗组(68.4%)和免疫治疗组(73.1%),差异有统计学意义(P0.05);中药治疗组妊娠成功率(71.1%)与免疫治疗组(70.7%)相比差异无统计学意义(P0.05),联合治疗组妊娠成功率91.3%,优于单一治疗的中药治疗组和免疫治疗组,差异有统计学意义(P0.05)。结论中药联合主动免疫治疗有效提高封闭抗体缺乏所致复发性流产患者的BA阳性率及再次妊娠成功率,是一种比较有效的治疗方案。     

封闭抗体与反复自然流产的研究进展

封闭抗体缺乏是导致反复自然流产的免疫学因素之一,本文对何为封闭抗体、封闭抗体与复发性自然流产有何关系做一阐述。     

封闭抗体的抗独特型抗体在反复自然流产中的应用价值

为了观察在反射自然流产（ＲＳＡ）中独特型抗体－抗独特型抗体网络的作用，分别测定正常生育组、原发性ＲＳＡ、继发性ＲＳＡ的封闭抗体效率（Ａｂ１）和抗独特型抗体（Ａｂ２），以及原发性ＲＡＳ免疫治疗前后Ａｂ２的变化。结果发现：正常生育组的Ａｂ２分别为７．５３％和１０．７０％；而原发性ＲＳＡ分别为－５５．５１％和－４２．６８％；继发性ＲＳＡ则分别为２９．９８％和－３０．００％，免疫治疗前后，原发性ＲＳＡ患者     

习惯性流产患者的淋巴细胞免疫治疗

反复习惯性流产（reeurent or repetitive spontaneous abortion,RSA）是指连续发生了3次或3次以上的自然流产。发生率为0．4％～1．0％,原因复杂,有解剖、内分泌、遗传、感染等原因,其中有40％～80％的患者原因不明,考虑与免疫有关,而封闭抗体（blocking antibody,BA）的缺乏是RSA的重要原因之一。我院自2003年9月始,利用丈夫淋巴细胞皮内注射,治疗原因不明的自然流产44例,治愈率达73．8％。收到良好的效果,现报道如下。     

Intravenous immunoglobulin treatment of women with multiple miscarriages.

Eleven women who had previously experienced four to eight unexplained fetal losses (median 6.0 fetal losses/woman) were treated in their next pregnancy with individualized doses of pooled intravenous immunoglobulins. Nine women (82%) delivered healthy infants subsequent to the treatment. Prior to treatment, the pregnant patients had a significantly (P less than 0.05) increased median level of complement C3 neodeterminants in the blood compared with a group of 33 normal first trimester pregnant women. This may be a sign of increased turnover of complement in these women.     

Immunology: Prognostic significance of maternal DR histocompatibility types in Danish women with recurrent miscarriages

In a previous case-control study of women with unexplained recurrentmiscarriages we reported that the frequency of women positivefor each of the two histocompatibility (HLA) types HLA-DR1,Br and HLA-DR3 was increased in a subset of patients with ahistory of four or more miscarriages. In the present study weexamined whether the increased frequency of the two HLA typesin this subset of patients indicated that they would resultin a poor pregnancy prognosis. We related pregnancy outcomesto the mothers' HLA-DR type in a prospective study of a well-defined,closely supervised group of 94 women with unexplained recurrentmiscarriages who had achieved intra-uterine pregnancy in thecourse of one of two prospective placebo-controlled trials concerningthe efficacy of immunotherapy. Of the patients who were HLA-DR1,Br and/or HLA-DR3 positive 62% miscarried their next pregnancycompared with 29% of the patients negative for the two HLA types[relative risk of miscarriage in the former group = 2.2 (P <0.002)unadjusted, and 1.8 (P = 0.025) when adjusted for the numberof previous miscarriages]. The results suggest that Danish womenwith unexplained recurrent miscarriages who are positive forHLA-DR1, Br and/or -DR3 display a poorer pregnancy outcome thanpatients negative for these types.     

妊娠4～9周孕妇血清雌二醇变化与妊娠结局的关系

目的探讨妊娠4～9周孕妇血清雌二醇（E2）变化与妊娠结局的关系。方法选择在本院就诊的妊娠4～9周的孕妇,根据孕妇妊娠结局分为正常妊娠组和胚胎停育组,正常妊娠组又根据有无复发性流产病史者分为两组,各组按孕周又分为6个亚组。采用化学发光分析法检测各组孕妇血清E2水平,并进行比较分析。结果正常妊娠组妊娠4～9周孕妇每周血清E2水平随妊娠周数增加而增加,有复发性流产病史的患者和无复发性流产的患者各孕周E2水平的变化差异无统计学意义（P〉0.05）;而胚胎停育组随孕周增加呈下降趋势。与正常妊娠组的相应孕周两两比较胚胎停育组各个孕周孕妇血清E2水平相应均数显著偏低（P〈0.05）。结论胚胎停育孕妇各孕周血清E2水平均显著下降,提示E2可能是维持早期妊娠的重要因素之一。     

尿LH试纸对流产妇女恢复排卵时间影响的临床研究

目的利用尿LH试纸、基础体温(BBT),B型超声(USS)方法监测流产后妇女排卵时间,研究人工流产与药物流产对恢复排卵时间的影响。方法选择本院门诊进行流产的妇女共124例,分为人工流产组和药物流产组,利用尿LH半定量检测试纸测定,BBT测定、和USS监测排卵恢复时间。结果人工流产组(61例)和药物流产组(63例)间年龄、孕次、初潮年龄等差异均无统计学意义(P0.05);124例患者中5例失访,结合BBT、月经中期监测尿LH试纸、USS方法三者可靠的监测排卵;两组患者排卵恢复时间在各个月经周期的分布秩和检验表明两组分布有显著差异(P0.05),药物流产组排卵恢复时间明显滞后于人工流产组。结论药物流产较人工流产患者排卵恢复时间延迟,这可能与药物流产改变患者体内内环境有关系。     

A prospective study of the incidence, time of appearance and significance of anti-paternal lymphocytotoxic antibodies in human pregnancy

The incidence and natural history of serum anti-paternal cytotoxic antibody (APCA) in normal pregnancy and spontaneous abortion was investigated prospectively in 306 women (64 primigravidae and 242 multigravidae), in order to establish whether serum APCA is a useful screening test in the diagnosis, treatment and prognosis for patients with recurrent pregnancy loss. Pre-pregnancy, serial pregnancy and post delivery serum samples were tested against partner's lymphocytes, using a microdroplet lymphocytotoxicity assay. The incidence of serum APCA in the 256 pregnancies successfully completed was 32%, compared with 10% amongst the 50 pregnancies ending in spontaneous abortion. The lower incidence of positive APCA tests in unsuccessful pregnancies was explained by our finding that positive APCA tests are related to the gestational age of the pregnancy and are rarely demonstrable before 28 weeks gestation. Since APCA usually disappears between pregnancies, its usefulness as a diagnostic test for immunotherapy against recurrent abortion should be questioned.     

Vaccination Against Spontaneous Abortion in Mice by Preimmunization With an Anti-diotypic Antibody

ABSTRACT: CBAE/J females mated with DBA/2 display a high level of fetal wastage which can be corrected by anti-Balb/c vaccination. A batch of CBA/J anti-(CBA/J anti-Balb/c) antiserum was raised. This serum was characterized as anti-idiotypic by various techniques, including a solid-phase radioimmunoassay. Such a serum proved to confer protection against resorbtions when injected into CBA/J mice mated with DBA/2. However, the kinetics of the effect pointed to the need for administration in early pregnancy for successful protection. The significance of these data, and the possible mechanism(s) by which the serum acts, are discussed.     

未生育女性人群中流产与乳腺癌的关系的Meta分析

目的通过系统评价及Meta分析未生育女性流产与乳腺癌的相关性。方法根据纳入和排除标准,检索Cochrane图书馆、Pub Med数据库(时间截止至2014年6月)关于未生育女性流产和乳腺癌关系的临床队列和病例对照研究文献,运用STATA软件对文献中提供的效应值(RR或OR)及95%采用固定效应模型进行合并。结果最终纳入文献13篇。Meta分析结果显示,在未生育女性人群中,流产与乳腺癌发生率之间无统计学意义,RR=0.98,95%CI为[0.89,1.08],P0.05,并且流产次数与乳腺癌的发生并无多大关系。其中人流与乳腺癌关系,自然流产与乳腺癌关系的RR及95%CI分别为0.96[0.88,1.04],P0.05和1.01[0.88,1.14],P0.05。结论在未生育女性人群中,流产并不增加乳腺癌的发生率,且随着流产次数的增加,乳腺癌发生的风险并不升高。     

Specialist contraceptive counselling and provision after termination of pregnancy improves uptake of long-acting methods but does not prevent repeat abortion: a randomized trial

BACKGROUND: One in four abortions in the UK is undertaken for women who have had one before. Women undergoing abortion in Edinburgh were targeted for improved contraceptive advice and provision in this randomized trial. METHODS: Between November 2001 and May 2002, women recruited at assessment for abortion were randomized at admission to receive specialist contraceptive advice and enhanced provision (316 women) or standard care (297 women). Randomization was based on the week of admission. Contraceptive use 16 weeks after abortion was assessed by questionnaire and subsequent abortions by review of the hospital records 2 years later. RESULTS: Women receiving specialist advice and enhanced provision were more likely to leave the hospital with contraception (271 versus 115, P < 0.001), which was more likely to be a long-acting method (141 versus 78, P < 0.001) than women receiving standard care. Four months later, there was no significant difference in contraceptive prevalence or continuation, but women in the intervention group were more likely to be using contraceptive implants (32 versus 6, P < 0.001). Two years later, 14.6% of women in the intervention group (44/302) and 10% of controls (27/268) had undergone another abortion in the same hospital (P = 0.267). CONCLUSIONS: Specialist contraceptive advice and enhanced provision had a short-lived effect on contraceptive uptake and increased the use of long-acting methods but did not appear to reduce repeat abortions.     

继发免疫性不孕与终止妊娠方式间的关系

目的 :分析免疫性因素与终止妊娠方式间的相关性。方法 :对 2 0 6例非自然流产组、72例自然流产组人群进行抗精子抗体 (AsAb)、抗子宫内膜抗体 (EmAb)和抗心磷脂抗体 (ACL)检测 ,AsAb检测采用试管一玻片凝集试验 ,EmAb、ACL采用ELISA法 ,并以 4 5例正常生育妇女 (对照组 )作对照。结果 :生殖免疫性抗体为终止妊娠后引起继发不孕的主要原因之一( 4 1 75 % ) ;非自然流产组EmAb的产生率和自然流产组相比无差异性 (P >0 0 5 ) ,非自然流产组和自然流产组与正常生育组相比 ,免疫抗体的产生均有显著性差异 (P <0 0 0 1)。药物流产组EmAb的产生率高于人工流产组 (P <0 0 5 ) ;药物流产十清宫术组中EmAb的产生率最高 ( 6 2 5 0 % )。免疫性抗体的产生与流产次数多少不成比例。结论 :生殖免疫性抗体为终止妊娠后引起继发不孕的主要因素之一 ,药物流产方式EmAb的产生率高于人工流产组 ;免疫性抗体的产生与流产次数多少无关     

药物流产与人工流产对未婚产妇心理健康的影响及对策研究

目的探讨药物流产与人工流产对未婚产妇心理健康的影响及相关对策。方法在唐山市第三医院(2008年1月～2009年12月)做流产的未婚妊娠妇女中随机抽取362例,其中进行药物流产的为145例,人工流产的为217例。采用症状自评量表(SCL-90)进行施测。结果采取药物流产或人工流产的未婚产妇与全国常模相比,除强迫和精神病性外,其余因子均具有显著差异(t=1.18,P0.05;t=0.76,P0.05)。人工流产与药物流产的SCL-90分数有显著差异(t=2.01,P0.05)。结论药物流产和人工流产对未婚产妇的心理健康均具有不良影响,相较于药物流产,人工流产对未婚产妇的心理健康伤害更大。