复发性流产合并甲状腺疾病的诊治

甲状腺疾病所致甲状腺功能异常是引起复发性流产的一个常见内分泌因素,近年来已成为内分泌学、生殖医学及围产医学领域研究和关注的热点之一。临床上常见的甲状腺疾病主要包括甲状腺功能亢进症、临床甲状腺功能减退症、亚临床甲状腺功能减退症及甲状腺自身免疫性疾病等。对于复发性流产合并甲状腺疾病的规范化诊治在业内尚未达成共识,故普遍存在诊断标准不一、用药不规范等现象。文章就复发性流产患者合并甲状腺疾病的诊治作一阐述。     

复发性流产的诊断与治疗

复发性流产的病因及相关因素 张建平教授 复发性自然流产（recurrent spontaneous abortion，RSA）是指与同一性伴侣连续遭受2次或2次以上在妊娠20周前的胎儿（体重≤500g）丢失者，是育龄妇女的常见病。从不同地区、不同阶层及不同年龄统计，自然流产的发生率约为15％～40％。2次或2次以上的流产患者约占生育期妇女的5％，而3次或3次以上者约占1％～2％。国内仍把3次或3次以上在妊娠28周之前的胎儿丢失称习惯性流产。     

甲状腺自身抗体与复发性流产关系的初步探讨

目的 研究抗甲状腺球蛋白抗体和抗甲状腺过氧化物酶抗体与复发性流产（RSA）之间的关系。方法 2004-08—2005—10选取山东省立医院妇产科门诊100例有复发性流产史非妊娠妇女为研究组，其中原发性RSA62例（原发性RSA组），继发性RSA38例（继发性RSA组），100例有正常妊娠史非孕健康妇女为对照组，化学发光免疫法测两组血清中的抗甲状腺抗体。结果 研究组血清中抗甲状腺球蛋白抗体和抗甲状腺过氧化物酶抗体的阳性率分别为：24％和28％，明显高于对照组的4％和6％（P〈0、05）。原发性与继发性RSA患者血清中抗体阳性率差异无显著性（P〉0、05）。结论 在复发性流产患者中，甲状腺自身抗体的阳性率增高，需进一步研究治疗后对妊娠结局的影响。     

原因不明复发性流产的诊治

复发性流产严重威胁人类的生殖健康,约50%患者病因不明,基于循证医学的诊断和治疗策略相对匮乏,是生殖医学中最困难的领域之一。文章重点阐述原因不明复发性流产的病因学和治疗研究现状及进展。     

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。     

原因不明复发性流产的诊治

复发性流产严重威胁人类的生殖健康,约50%患者病因不明,基于循证医学的诊断和治疗策略相对匮乏,是生殖医学中最困难的领域之一。文章重点阐述原因不明复发性流产的病因学和治疗研究现状及进展。     

免疫所致复发性流产和习惯性流产

自然流产指妊娠在 2 8周以前终止、胎儿体重在 10 0 0ｇ以下者 ,发生率为 15 %～ 2 0 %。如自然流产连续发生 2次或2次以上可称为复发性流产 ,发生率约 1% ;如连续发生 3次或 3次以上称为习惯性流产。近代生殖免疫研究表明 ,复发性流产和习惯性流产的病因 ,除染色体、解剖和内分泌异常外 ,约 5 0 %～ 6 0 %与免疫有关。其中约 1/ 3是与自身抗体特别是抗磷脂抗体有关 ,这部分患者可能是一种自身免疫疾病。另外约 2 / 3是原因不明 ,称之为原因不明性流产 ,被认为与孕期母体对胎儿父系抗原呈低识别和 (或 )低反应 ,以致无法产生足够的保护性抗…     

复发性流产的诊治现状与未来

复发性流产（recurrent spontaneous abortion, RSA）占妊娠总数的5%,是威胁女性身心健康的疑难病症,由于RSA病因存在复杂性和异质性,加之40%～50%以上的患者流产原因不明,给临床治疗带来极大的困难和盲目性。因此,RSA的规范化诊治是生殖健康领域亟待解决的重大问题［1-2］。 浏览更多请关注本刊微信公众号及当期杂志。     

复发性流产的诊治现状与未来

        复发性流产（recurrent spontaneous abortion, RSA）占妊娠总数的5%,是威胁女性身心健康的疑难病症,由于RSA病因存在复杂性和异质性,加之40%～50%以上的患者流产原因不明,给临床治疗带来极大的困难和盲目性。因此,RSA的规范化诊治是生殖健康领域亟待解决的重大问题［1-2］。 浏览更多请关注本刊微信公众号及当期杂志。     

复发性流产的免疫学因素研究进展

复发性流产(recurrent spontaneous abortion,RSA)是指连续≥2次的自然流产,且常发生于同一妊娠月份,临床发病率约1%~5%。除美国妇产科医师协会(ACOG)、皇家妇产科医师学会(RCOG)已明确提出的病因如染色体异常、母体生殖道异常、母体内分泌异常、生殖道感染、血栓形成倾向等,约80%与免疫因素相关。近年来研究者根据免疫学发病机制将RSA分为自身免疫型和同种免疫型两大类,前者可能由于自身抗体针对内皮细胞、滋养细胞及种植前胚胎导致妊娠失败,后者则可能与母-胎界面免疫失衡有关。本文将分别从这2个方面就RSA免疫学发病机制进行综述。     

复发性流产与自身免疫性疾病

自身免疫性疾病（AID）是指机体产生高滴度自身抗体和（或）自身反应性淋巴细胞攻击相应的自身正常细胞和组织,导致组织器官损伤和功能障碍的综合征,是导致复发性流产（RSA）等妊娠并发症的重要原因。临床上常见的较易导致RSA的AID有：系统性红斑狼疮、抗磷脂综合征、干燥综合征、类风湿关节炎、系统性硬化症和未分化结缔组织病等。这些AID导致的RSA的治疗主要为小剂量免疫抑制剂联合抗凝治疗,且疗效肯定。     

复发性流产病因学研究进展

复发性流产（recurrent spontaneous abortion, RSA）一般指与同一配偶发生连续３次或３次以上的自然流产。近年来许多学者提出将连续发生2次的自然流产者纳入RSA的范畴,原因是连续发生2次自然流产后,再次妊娠的流产率可高达50%以上,要引起足够的重视。RSA的病因复杂,目前已知的病因有染色体异常、生殖道解剖异常、内分泌失调、感染性疾病因素、血栓前状态、自身免疫因素等。除此之外,临床上仍有至少40%以上的患者病因不明。由于RSA的病因复杂,造成了RSA的难治性,是目前基础与临床研究的难点与热点。     

复发性流产的内分泌因素

复发性流产是一种常见妊娠并发症,病因复杂多样,其中内分泌因素占8%～12%,文章主要就甲状腺功能异常、高催乳素血症、多囊卵巢综合征及代谢异常、糖尿病、黄体功能不全等内分泌因素进行综述,旨在为复发性流产的预防及治疗方面带来新的思考。     

复发性流产患者易栓症的筛查

复发性流产（RSA）为3次或3次以上妊娠28周之前的胎儿丢失,是临床上常见的妊娠并发症。RSA病因涉及多个方面,包括遗传、解剖、免疫、内分泌、易栓症等因素。易栓症指存在抗凝蛋白、凝血因子、纤溶蛋白等遗传性或获得性缺陷,或者存在获得性危险因素而具有高血栓栓塞倾向,分为遗传性与获得性两种类型。目前研究表明,易栓症与RSA存在相关性,重视RSA患者易栓症的筛查与诊断,并采取相应的措施,可在一定程度上提高患者的妊娠成功率。     

KDR gene polymorphisms and idiopathic recurrent spontaneous abortion

Objective: Process of angiogenesis is essential for successful gestation. Disruption in this pathway leads to various undesirable consequences in pregnancy such as recurrent spontaneous abortion (RSA). One of the most important genes involved in angiogenesis is kinase-insert domain-containing receptor (KDR). This study aimed to investigate the associations between two single-nucleotide polymorphisms (SNPs) of KDR gene, 1719A?>?T and 1192G?>?A, with idiopathic RSA in south-east Iran.

Methods: A total of 230 women, including 110 women with a history of at least two consecutive spontaneous miscarriages and 120 healthy women were recruited in this study. Genomic DNA was extracted from peripheral blood samples of participants using the Salting out method. The KDR 1719A?>?T and 1192G?>?A polymorphisms were genotyped by the standard amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) technique.

Results: For the case group, frequencies of 2.73%, 30% and 67.27% were observed for AA, AT and TT genotypes in1719A?>?T SNP, respectively, and the genotype frequencies for controls were equal to AA?=?3.33%, AT?=?32.5% and TT?=?64.17%. Distribution of genotypes in 1192G?>?A SNP in the case group was 79.1%, 19.1% and 1.8% for GG, AG and AA, respectively, whereas the corresponding values for the controls were GG = 80%, AG = 20% and AA = 0. No significant difference was found between the case and control groups based on the frequency of KDR gene polymorphisms with the susceptibility to RSA.

Conclusions: There is no association between these two SNPs of KDR gene and the susceptibility to RSA in women from south-east Iran.     

复发性流产的抗凝治疗

复发性流产部分患者是由于妊娠期生理性和病理性的血液高凝状态常导致胎儿丢失。合理应用低分子肝素和阿司匹林等抗凝药物能有效改善此类患者的母胎结局,在复发性流产治疗中发挥重要作用。     

不明原因复发性流产免疫学发病机制的研究进展

复发性流产发生率为1%~5%,其中40%~60%原因不明,称为不明原因复发性流产(unexplained recurrent spontaneous abortion,URSA)。近年研究表明,URSA的发生与免疫失衡关系密切,又称为同种免疫型复发性流产。本文论述URSA免疫学的发病机制、诊断、治疗的最新研究进展,重点论述了发病机制中免疫失衡方面的研究进展。     

T regulatory markers expression in unexplained recurrent spontaneous abortion

Objective: To evaluate expression of glucocorticoid-induced tumor necrosis factor receptor (GITR), cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and IL-10 in peripheral blood mononuclear cells (PBMCs) of 20 women with unexplained recurrent spontaneous abortion (URSA) compared to 20 normal non-pregnant women (NNP) during luteal phase in the window of implantation.

Methods: Quantitative real-time PCR (qRT-PCR) was performed using the Taqman method for expression of GITR and SYBR Green method for expression of CTLA-4 and IL-10.

Results: Expression of CTLA-4 in the NNPs (median; interquartile range; 3; 1.8–10) was significantly higher than the URSAs (0.72; 0.26–3.81, p?=?0.015). Expression of GITR in the NNPs (53; 10–139) was significantly higher than the URSAs (6; 3–27, p?=?0.005). However, IL-10 expression in the URSAs was significantly higher than the NNPs, did not meet a significant value. A significant correlation was found between CTLA-4 and GITR expression in the study population (p?=?0.0001).

Conclusions: Expression of CTLA-4 and GITR were significantly down-regulated in the URSAs compared to NNPs at the window of implantation, which shows the essential role of Treg cells in creating an immunological privileged site for fetus as an allograft at the maternal–fetal interface by high expression levels of CTLA-4 and GITR during a normal pregnancy.     

The value of hysteroscopy in diagnosis of chronic endometritis in patients with unexplained recurrent spontaneous abortion

Objectives

We performed this study in order to investigate the role of chronic endometritis (CE) in unexplained recurrent spontaneous abortion (RSA) and to determine the correlation between hysteroscopic and histologic findings of CE in patients with unexplained RSA. We also tried to find out the relation between CE and primary vs. secondary RSA.

Study design

One hundred and forty-two consecutive patients with unexplained RSA and 154 fertile women were enrolled in this study. All the patients and controls underwent hysteroscopy and, at the same time, endometrial biopsy. CE was suspected when hysteroscopy revealed signs of focal or diffuse endometrial hyperemia or endometrial endopolyps (less than 1 mm in size). Histopathologic diagnosis of CE was based on superficial stromal edema, increased stromal density, and pleomorphic stromal inflammatory infiltrate dominated by lymphocytes and plasma cells. Results were compared between cases and controls as well as those with primary (n = 61) and secondary (n = 81) RSA.

Results

Patients with RSA had a significantly higher incidence of CE both hysteroscopically (67.6% vs. 27.3%; p < 0.0001) and pathologically (42.9% vs. 18.2%; p < 0.0001). The sensitivity, specificity, positive predictive value and negative predictive value of hysteroscopy in the diagnosis of CE were found to be 98.4%, 56.23%, 63.5% and 97.82% respectively. Patients with secondary RSA had a higher prevalence of CE both pathologically (83.9% vs. 45.9%; p < 0.0001) and hysteroscopically (58.1% vs. 24.6%; p < 0.0001).

Conclusion

CE is associated with unexplained RSA. Hysteroscopy, with high sensitivity and acceptable specificity, is suitable for the diagnosis of CE in those with unexplained RSA. CE should be taken into consideration in those with secondary unexplained RSA.