复发性流产患者自身免疫性抗体的变化研究

目的探讨自身免疫性抗体ACA、β2GP1-IgG/IgM、APE、aPS、TPOAb和TgAb与复发性流产(RSA)的关系.方法选取100例有复发性流产史未孕妇女为研究组,其中原发性RSA 62例,继发性RSA 38例,另选100例有正常妊娠史、未孕健康妇女为对照组,测定两组血清中ACA、β2GP1-IgG/IgM、APE、aPS、TPOAb和TgAb.比较2组中抗体的阳性率.结果研究组与对照组中ACA、β2GP1-IgG/IgM、APE、aPS/IgG、aPS/IgM、TPOAb和TgAb的抗体阳性率分别为8%、11%、41%、0%、0%、28%、24%和0%、0%、9%、0%、0%、6%、4%.aPS(IgG和IgM)在两组中比较差异无显著性,其余各项两组比较差异有显著性(P＜0.05).抗甲状腺抗体阳性者ACA、β2GP1-IgG/IgM及APE的阳性率分别为2.6%、7.9%和26.3%;抗甲状腺抗体阴性者ACA、β2GP1-IgG/IgM及APE的阳性率分别为4.3%、4.9%和24.7%,两组比较差异无显著性(P＞0.05).结论自身免疫性抗体与复发性流产有关,抗甲状腺抗体是复发性流产的独立危险因素.     

甲状腺自身抗体与复发性流产

摘要：甲状腺自身抗体是一种以自身甲状腺组织作为靶抗原的自身抗体,主要包括抗甲状腺过氧化物酶抗体、甲状腺球蛋白抗体及促甲状腺激素受体抗体,三者均是反映自身免疫性甲状腺疾病的特异指标。甲状腺自身抗体的存在可能与复发性流产有相关性,应对高危人群进行甲状腺自身抗体的筛查、早期诊断并及时给予治疗,可有效降低妊娠不良结局的发生。     

抗精子抗体、抗子宫内膜抗体及抗弓形虫抗体与反复自发性流产关系的研究

应用ELISA方法检测了186例自发性流产患者血清中抗精子抗体（AsAb）、抗子宫内膜抗体（EMAb）与抗弓形虫抗体（ATAb），并以56例正常育龄妇女作为对照。结果表明：反复自发性流产患者血清中AsAb、EMAb、ATAb阳性率分别为29．03％、38．71％和18．82％，而正常对照组的阳性率分别相应为1．79％、3．57％和1．79％（P＜0．01）。ATAb阳性率随流产次数的增加而增加（P＜0．05），AsAb阳性率随流产次数的增加而减少（P＜0．05）。流产时孕期＜90天者血清AsAb阳性率明显高于流产时孕期≥90天者（P＜0．05），EMAb阳性率与流产次数和流产时孕期之间无明显关系。本文结果提示：三种血清抗体ASAb、EMAb、ATAb与反复自发性流产密切相关，可能是造成自发性流产的重要因素，尤其在自发性流产的早期阶段。     

不孕症患者的自身免疫抗体分析

目的：探讨不孕症与患者自身免疫抗体的相关性。方法：采用酶联免疫吸附实验（ELISA）检测516例不孕症患者的血清抗精子抗体（ASAb）、抗卵巢抗体（AOAb）、抗子宫内膜抗体（EMAb）、抗绒毛膜促性腺激素抗体（hCGAb）及抗心磷脂抗体（ACAb）。选择125例正常妊娠妇女作为对照组．比较不孕症组与对照组5项抗体的阳性率。结果：不孕症组ASAb,AOAb,EMAb,hCGAb和ACAb的阳性率分别为26．7％,24．8％,25．2％,21．7％和21．3％。明显高于正常对照组4．8％,2．4％,1．6％,3．2％和1．6％（P均〈0．001）;5种抗体联合检测阳性率为38．2％,与分别单独检测这5项抗体的阳性率相比,差异均有统计学意义（P均〈0．05）。结论：ASAb,AOAb,EMAb,hCGAb和ACAb与不孕症有密切相关性,是引起不孕的重要原因。检测这5项抗体可作为不孕症病因诊断的一项指标。     

血清CA125与抗子宫内膜抗体联合测定对子宫内膜异位症的诊断价值

目的 探讨血清CA125与抗子宫内膜抗体联合测定对于宫内膜异位症诊断的临床价值。方法 应用放射免疫法及酶联免疫吸附试验（ELISA）法测定44例子宫内膜异位症患者（EMT组）血清中CA125值及EMAb阳性情况，并与40例健康妇女对照组进行比较。结果 EMT组血清CA125值阳性率为61．4％（27／44），显著高于对照组5．0％（2／40），P〈0．05；EMT组抗子宫内膜抗体阳性率为65．9％（29／44），显著高于对照组7．5％（3／40），P〈0．05；联合测定EMT患者血清CA125值及抗子宫内膜抗体，其敏感性明显高于两者单独测定的敏感性。结论 血清CA125与抗子宫内膜抗体联合测定可提高子宫内膜异位症诊断的敏感性。     

甲状腺自身抗体与稽留流产关系的初步研究

目的探讨甲状腺自身抗体与稽留流产的关系。方法选择2013年1月至2014年12月于青岛市海慈医疗集团确诊为早期稽留流产的100例女性作为研究组,同期正常的100例早孕女性作为对照组,检测并比较两组患者血清中甲状腺过氧化物酶抗体(TPOAb)和甲状腺球蛋白抗体(Tg Ab)水平,分析其与早期稽留流产的关系。结果研究组TPOAb阳性率、Tg Ab阳性率均高于对照组(P0.05)。经对数转化后,研究组女性血清中TPOAb水平[(0.91±0.65)U/ml]高于对照组[(0.72±0.26)U/ml](P0.01),而研究组女性血清中Tg Ab水平与对照组比较,差异无统计学意义(P0.05)。经多因素Logistic分析,研究组女性TPOAb阳性率是对照组的4.129倍。结论甲状腺自身抗体阳性可能与稽留流产有关,TPOAb阳性为稽留流产的独立危险因素。     

抗β2糖蛋白1抗体与习惯性流产

目的 探讨抗β2 GP1抗体与习惯性流产间的关系。方法 选取122例有习惯性流产史未妊娠妇女为流产组，选取60名未妊娠正常生育育龄妇女为正常对照组，用酶联免疫法检测两组血清中抗β2 GP1抗体。结果 122例不明原因习惯性流产史的患者中，抗β2 GP1IgA、IgG、IgM型抗体阳性率分别为13．1％、9．0％和15．6％。这三型自身抗体阳性率均明显高于正常对照组，差别有显著性(P分别为P=0．009、P=0．011、P=0．003)。结论 对不明原因习惯性流产史的患者作抗β2 GP1抗体检测，将有助于病因的诊断。     

抗磷脂抗体与反复妊娠丢失的研究

目的 探讨抗磷脂抗体（antiphospholipid antibody，APA）与反复妊娠丢失（recurrent pregnancy loss，RPL）的关系。方法 选择不明原因的妊娠丢失妇女71例，并设正常对照60例，分别采用酶联免疫吸附法和活性部分凝血酶原时削法测定静脉血浆中抗磷脂抗体，包括抗心磷脂抗体（anticardlolipid antibody，ACL）和报疮抗凝物（luplls anlicoagulant，LA）。结果 RPL组APA、ACL、LA阳性率均高于正常对照组，差异有显著性（P〈0．05），RPL中胎死宫内的APA阳性率高达40％。结论 APA与RPL密切相关，以不明原因的胎死宫内为显著；对RPL妇女应常规筛查APA，并对APA阳性者进行预防性抗凝治疗以期提高妊娠成功率。     

甲状腺自身抗体与复发性流产相关性的研究

目的:探讨甲状腺自身抗体(ATA)与复发性流产的相关性。方法:收集2013年8月—2014年4月于我院产科进行孕前检查,并符合入组条件的非妊娠期妇女,其中有复发性流产病史妇女92例,夫妻双方染色体检查未见异常,凝血功能相关检查无异常,为研究组;无复发性流产病史妇女226例,为对照组。检测2组对象甲状腺球蛋白抗体(Tg Ab)和甲状腺过氧化物酶抗体(TPOAb)的阳性率,Tg Ab(+)和(或)TPOAb(+)为ATA阳性。结果:1研究组中,年龄≥35岁及<35岁者的ATA阳性率分别为39.29%(11/28)和26.56%(17/64),差异无统计学意义(P>0.05);在对照组中则分别为25.00%(10/40)和18.28%(34/186),差异也无统计学意义(P>0.05),说明ATA在不同年龄阶段的状况相近。2研究组ATA阳性率为30.43%(28/92),高于对照组的19.47%(44/226),差异有统计学意义(P<0.05)。研究组TPOAb阳性率为30.43%(28/92),高于对照组的11.95%(27/226),差异有统计学意义(P<0.05)。研究组Tg Ab阳性率为7.61%(7/92),与对照组的7.52%(17/226)比较差异无统计学意义(P>0.05)。结论:ATA与复发性流产有关,尤其与TPOAb关系密切。     

妊娠丢失与抗磷脂抗体的关系

目的探讨妊娠丢失与抗磷脂抗体［ＡＰＡ,包括抗心磷脂抗体（ＡＣＡ）和狼疮抗凝抗体（ＬＡ）］的关系。方法对１２２例有不明原因妊娠丢失史的患者（研究组）和１００例正常非孕妇女（对照组）,分别采用酶联免疫吸附法和活性部分凝血酶原时间法,测定静脉血清中的ＡＰＡ。其中,研究组分为胚胎停育组（２８例）、死胎组（３１例）和复发性流产组（６３例）。结果整个研究组中ＡＰＡ、ＡＣＡ、ＬＡ的阳性百分比均高于对照组,与对照组相比,差异均有显著性（Ｐ＜０．０５～０．００１）。死胎组和复发性流产组此３项指标的阳性百分比分别与对照组比较,差异有显著性（Ｐ＜０．０５～０．００１）,而胚胎停育组与对照组相比,差异无显著性（Ｐ＞０．０５）。结论ＡＰＡ与妊娠丢失有关,尤其是复发性流产和死胎。因此,应对有不良孕产史的患者常规筛查ＡＰＡ,以利于尽早对因治疗。     

Lymphocyte immunotherapy and its probable mechanism in the maintenance of pregnancy in women with recurrent spontaneous abortion

Introduction Most women with alloimmune cause of recurrent spontaneous abortion (RSA) includes increased sharing of human leukocyte antigens (HLA) that may prohibit the mother from making anti-paternal cyto-toxic antibodies (APCA), anti-idiotypic antibodies (Ab2) and mixed lymphocyte reaction blocking antibodies (MLR-Bf). Overactivity of T helper-1 (Th-1) cytokines and natural killer (NK) cells have been also reported to be the major alloimmune cause of recurrent spontaneous abortion (RSA). It was revealed from extensive updated analysis of this subject that paternal lymphocytes immunotherapy may play a significant role in the prevention of alloimmune cause of fetal loss in women with RSA. These alloimmune parameters are found to be suppressed in successful immunotherapy, which is comparable to normal pregnancy.Review and discussion Various studies represented that paternal lymphocyte immunotherapy was attributed to the high expression of APCA, Ab2, MLR-Bf and inhibition of Th-1 pattern of cytokines and NK cell activity in women with alloimmune cause of RSA. Present updated randomized clinical trials demonstrated that women with RSA of study group who have been treated with paternal lymphocyte immunotherapy had more successful outcomes (68%) as compared to women with RSA of control group who either received autologous lymphocytes/third party lymphocytes/normal saline or no therapy (54%), (p<0.02). However, when the results of the randomized and nonrandomized studies were pooled together it was observed that 67% of women with RSA of study group who received paternal lymphocyte immunotherapy showed successful pregnancy outcome in comparison to 36% success in women with RSA of control group who either received autologous lymphocytes/third party lymphocytes/normal saline or no therapy (p<0.05).Conclusion These results advocate the role of paternal lymphocyte immunotherapy for the maintenance of pregnancy in women with RSA.     

Clinical study on circulating antisperm antibodies in women with recurrent abortion

Couples with a history of recurrent spontaneous abortions (RSA) were analyzed for circulating antisperm antibodies (Ab) with an enzyme-linked immunosorbent assay (ELISA), a Franklin-Dukes (F-D) and a sperm immobilization test(SIT). The three tests were positive in 31.5%, 25.9% and 18.5% for wives and 24.1%, 11.1% and 7.4% for husbands in RSA couples. There was a statistical significance (P less than 0.01) as compared with the control group. The ELISA method was found to be most sensitive, and the positive rate of antisperm antibodies in wives was higher than that in husbands. The Ab titer of RSA group varied within 1:8 approximately 1:512, with 60% above 1:32. The pregnant weeks (P greater than 0.05) did not seem to affect the antisperm Ab titer, nor did the aborting frequency. Our study suggests that antisperm Ab is one of the important causes of RSA in women.     

Role of antiphospholipid antibodies in 147 patients with spontaneous abortions and stillbirths: a retrospective and prospective analysis

Antiphospholipid antibodies (aPL) are a family of autoantibodies including lupus anticoagulant (LA), anticardiolipin antibodies (aCL), and ect. That appear to react with negatively charged phospholipids. These antibodies induce thrombosis and pregnancy complications including recurrent spontaneous abortions (RSA), recurrent stillbirth (SB), preeclampsia and intra-uterine growth retardation, although their exact pathogenic mechanisms remain poorly defined. The aim of this study was to investigate the frequency and the role of a aPL women with a history of RSA and SB due to positive aPL. The study included 147 women with a history of RSA and 48 women with a history of SB and to investigate the histological changes in the heams and stillborn fetuses in aCL positive women. We established that: 1, aCL were significantly increased in 62.2% (n = 92) in women with history of RSA and in 71% (n = 34) in women with history of SB; 2. aTr antibodies were positive in 22.7% (n = 5) in women with history of SB; 3. Tr activation status was increased in 77.3% (n = 17) in women with history of SB. CONCLUSION: The investigation of aPL in women with history of RSA and SB provides new insights into the disease and offers promise for prophylaxis and treatment in subsequent pregnancies.     

The prevalence of autoantibodies during third-trimester pregnancy complicated by hypertension or idiopathic fetal growth retardation.

Lupus anticoagulant, anticardiolipin, antinuclear, anti-deoxyribonucleic acid, antithyroglobulin, and antithyroid microsomal antibodies were assayed during third-trimester pregnancy (100 normal, 100 with complications). In spite of a normal activated partial thromboplastin time in all instances, lupus anticoagulant was further investigated by three additional procedures: tissue thromboplastin inhibition time, platelet neutralization procedure, and cephalin neutralization test. The prevalence of autoantibodies in pregnancies with hypertension reaches 16% (four with lupus anticoagulant, two with anticardiolipin, and two with antithyroid microsomal antibodies), which is significantly greater than that for idiopathic fetal growth retardation (2%) (one with lupus anticoagulant antibodies) and normal pregnancies (3%) (two with antithyroglobulin and one with autithyroid microsomal antibodies) (p less than 0.01). Autoantibodies were equally distributed between patients with gestational hypertension and those with preeclampsia. When compared with the 42 patients with hypertension and no autoantibodies, the eight patients with autoantibody had a more frequent history of fetal growth retardation (p less than 0.05), but there was no difference in the severity of hypertension, the frequency of obstetric complications, or the outcome of pregnancy. They did not require any specific treatment.     

Not every subseptate uterus requires surgical correction to reduce poor reproductive outcome

Objective

To evaluate whether hysteroscopic septoplasty should be performed in all women diagnosed with subseptate uterus.

Methods

In a prospective study, 138 patients diagnosed with subseptate uterus at the First Affiliated Hospital of Guangxi Medical University, Nanning, China, were enrolled between January 1, 2006, and March 1, 2011, and reproductive outcomes were compared among women who did and those who did not undergo hysteroscopic resection. Women were divided in 2 groups: group A comprised women with a history of recurrent spontaneous abortion (RSA), and was subdivided into control (A1) and surgery (A2) groups; group B comprised women with no history of poor reproductive outcomes, and was subdivided into control (B1) and surgery (B2) groups.

Results

The rates of pregnancy and term delivery were higher in group A2 than in group A1 (P < 0.05). The incidence of RSA and preterm delivery was higher in group A1 than in group A2 (P < 0.05). There was no difference in pregnancy rate, incidence of RSA, or preterm or term delivery between group B1 and group B2.

Conclusion

Hysteroscopic septoplasty significantly improved pregnancy outcomes in women with a history of RSA, but did not influence reproductive outcomes in women with no history of poor pregnancy outcomes.     

Adenosine deaminase activity and its isoenzyme pattern in women with recurrent spontaneous abortions

Normal pregnancy is characterized by suppressed cell-mediated immunity. Adenosine deaminase (ADA) is a purine metabolic enzyme enriched in trophoblast cells of the placenta. It is an early marker of trophoblast cell differentiation. Also, the activation of ADA gene expression in the placenta is crucial and essential for proper fetal development. The activity of ADA shows changes in diseases characterized by the alteration of cell-mediated immunity. The purpose of this study was to assess the possible role of the alteration of cell-mediated immunity in women with recurrent spontaneous abortions (RSA) as a cause of changes in tADA activity, and also to evaluate the extent of the contribution of ADA1 and ADA2 to changes of tADA activity in serum and peripheral blood lymphocytes (PBLs). We measured in serum and in PBLs activities of tADA, ADA1 and ADA2 of 25 married women with RSA (group A) and of 28 healthy non-pregnant women (group B). According to our results in women with RSA, mean serum tADA, ADA1 and ADA2 activities were significantly higher than those of non-pregnant women (p < 0.001, p < 0.05 and p < 0.05 respectively). In women with RSA, mean PBLs tADA, ADA1 and ADA2 activities were significantly higher than those of non-pregnant women (p < 0.001, p < 0.05 and p < 0.05 respectively). The findings of this study show a marked increase of serum and PBLs ADA activities, which is derived from an increase of ADA2 and ADA1 activity in women with RSA. These changes reflect cell-mediated immunological changes.     

History of biochemical pregnancy was associated with the subsequent reproductive failure among women with recurrent spontaneous abortion

Abstract

The aim of this study was to evaluate whether the presence of history of biochemical pregnancy (BP) was associated with clinical characteristics and the subsequent pregnancy outcome among women with recurrent spontaneous abortion (RSA). One-hundred and seventy-five RSA women with two or more clinical pregnancy losses were enrolled. The clinical characteristics were compared between 164 women with history of 0–1?BP (Group A) and 11 women with two or more BP (Group B). The frequency of previous pregnancy loss and history of in vitro fertilization and embryo transfer in Group B was higher than that in Group A; while frequency of secondary RSA in Group B was lower than Group A. The subsequent pregnancy outcome was assessed prospectively; and live-birth rate in Group A (72.9%) was higher (p?<?0.05) than that in Group B (41.7%). The incidence of reproductive failure (58.3%, p?<?0.05) and spontaneous abortion with normal chromosome (25.0%, p?=?0.050) in Group B was higher than those (27.1 and 5.9%, respectively) in Group A. RSA women with two or more BP had higher risk of reproductive failure and spontaneous abortion with normal chromosome together with lower chance of live-birth. The results of the present study involve important information and are helpful for clinical practitioners.     

Immune abnormalities in endometriosis compromising fertility in IVF-ET patients.

OBJECTIVE: To evaluate the incidence of immune abnormalities in patients with endometriosis and primary or secondary infertility. STUDY DESIGN: This study analyzed the incidence of alloantibodies and autoantibodies in 100 women with endometriosis and 62 patients with unexplained infertility without endometriosis who enrolled in an assisted reproduction program at the Colombian Fertility and Sterility Center from January 1, 1996, to May 30, 1997. The alloimmune status of the women was determined by testing for the presence or absence of antileukocyte antibodies. The autoimmune studies included antinuclear antibodies, antiphospholipid antibodies and lupus anticoagulant antibody. RESULTS: Negative titers of IgG antipaternal antibodies were identified in 34% of patients with primary infertility and in 34% of women with secondary infertility and a history of pregnancy losses. Positive titers of antinuclear antibodies were found in 27% (27/100) of the group of patients with endometriosis; of them, 30% (15/50) had primary infertility and 24% (12/50), secondary infertility. The average titer was 1/80. Forty-eight percent of the infertile patients (48/100) showed titers of antiphospholipid antibodies for IgG and IgM; 46% of these patients had primary infertility (23/50) and 50% (25/50), secondary infertility. This was significantly higher than in controls (P < .05). Two patients were positive for lupus anticoagulant antibody. In the group of patients with unexplained infertility without endometriosis, the incidence of antinuclear antibodies was 17.7% and of antiphospholipid antibodies, 30.6%. CONCLUSION: For women with endometriosis, alloimmune and autoimmune evaluation is recommended prior to their undergoing assisted reproduction in order to provide appropriate therapy for each case.     

The detection of anti-beta2-glycoprotein I antibodies is associated with increased risk of pregnancy loss in women with threatened abortion in the first trimester

OBJECTIVE: This study was designed to evaluate whether the detection of serum antiphospholipid autoantibodies may be useful in predicting pregnancy outcome in women with threatened abortion in the first trimester. STUDY DESIGN: A group of 77 pregnant women of between 8 and 12 weeks' gestation with vaginal bleeding was tested for serum antiphospholipid, lupus anticoagulants, anticardiolipin, antinuclear antibodies, and anti-beta2-glycoprotein I antibodies, and was followed up until the spontaneous end of pregnancy. A control group composed of 15 healthy women with uncomplicated gestation was tested contemporarily for the same antibody panel. RESULTS: Of the 77 patients with threatened abortion, 32 (41.5%) progressed to deliver at term and 45 (58.5%) experienced early pregnancy loss. Among the antibodies evaluated, only anti-beta2-glycoprotein I was significantly more frequent in those women whose pregnancy resulted in spontaneous abortion (22/45, 49%) than in those who progressed to term (6/32, 19%) or in the control group (2/15, 13%; p=0.004). This difference was specific to the IgM isotype (p=0.001). After adjustment by multivariate analysis, the odds ratio for pregnancy loss associated with a positive beta2-glycoprotein I antibody test was 5.18 (p=0.001). CONCLUSION: The detection of anti-beta2-glycoprotein I antibodies is associated with an increased risk of pregnancy loss in women with threatened abortion in the first trimester.     

Butyrylcholinesterase activity and lymphocyte subpopulations in peripheral blood of Kuwaiti women experiencing recurrent spontaneous abortion

This study has evaluated the hypothesis that activity of the detoxifying enzyme butyrylcholinesterase (BuChE) correlates with levels of serum anti-cardiolipin antibodies (ACA) and T lymphocytes in peripheral blood of women experiencing recurrent spontaneous abortion (RSA). Peripheral venous blood from 16 non-pregnant, RSA-afflicted women and 8 healthy non-pregnant women was analyzed for frequency of T lymphocyte subpopulations by two-color flow cytometry and for serum BuChE using butyrylthiocholine iodide/spectrophotometry. RSA-afflicted women with high serum ACA, but not those with normal ACA levels, exhibited significantly increased percentages of CD4+CD25+ cells (p<0.01) and CD4+HLA-DR+ cells (p<0.05) relative to healthy women. CD4+CD25+(high) cells were significantly lower (p<0.05), while CD4+CD25+(low) cells were significantly higher (p<0.01), in women with elevated ACA compared to healthy women and to RSA women with normal ACA. Relative to healthy, non-pregnant subjects, serum BuChE activity in RSA patients was elevated, both for those with normal ACA (p<0.001) and elevated ACA levels (p<0.01). Among healthy controls, a significant positive correlation was observed between frequency of CD3+NK cells and BuChE activity (p<0.01), but not for RSA-afflicted subjects. A positive correlation between BuChE activity and frequency of CD4+CD25+ cells, as well as CD4+CD25+(high) cells, was observed in the RSA-afflicted subject group with elevated ACA (p<0.05), which may be related to induction of BuChE by toxic metabolites resulting from pathogenic T cell activity. It is concluded that, among RSA patients, high serum ACA correlates with elevated levels of activated T cells and reduced CD4+CD25+(high)/CD4+CD25+(low) cells in comparison to healthy women or those afflicted with RSA but with normal ACA. BuChE activity is observed to be elevated in RSA patients irrespective of serum ACA status.