蛋白酶体亚基LMP 2在稽留流产的蜕膜和绒毛组织中的表达

目的探讨蛋白酶体亚基LMP-2在稽留流产中的作用。方法 用免疫组化方法研究LMP-2在201例稽留流产中的48例绒毛和45例脱膜与114例正常早孕人工流产中的56例绒毛和58例蜕膜中的表达。结果LMP-2在稽留流产的绒毛和蜕膜中的表达均低于正常早孕人工流产的绒毛和蜕膜,二者间的表达强度差异有统计学意义（P〈0.05）。结论 LMP-2在稽留流产中绒毛与蜕膜的表达减弱提示泛素-蛋白酶体通路介导的细胞蛋白降解参与调控滋养层细胞的生长过程。     

HIF-1α和VEGF在稽留流产患者血清和绒毛中的表达研究

目的探讨缺氧诱导因子(HIF)-1α和血管内皮生长因子(VEGF)在稽留流产患者血清和绒毛中的表达及二者的相关性。方法采用酶联免疫吸附试验和免疫组化SP法分别测定55例稽留流产患者(流产组)和45例正常早孕孕妇(对照组)血清和绒毛中HIF-1α和VEGF的表达水平。并将稽留流产组按有无明确原因分为有原因组和无原因组,同时根据胚胎死亡后稽留宫内时间分为<2周组、2～4周组和>4周组。结果流产组患者血清中HIF-1α和VEGF水平分别为(316.2±117.4)ng/L和(33.8±5.5)ng/L,对照组分别为(417.1±120.0)ng/L和(50.7±52.7)ng/L,两组比较,差异有统计学意义(P<0.05);流产组患者绒毛中HIF-1α和VEGF的表达量分别为3.0±2.1和3.6±1.9,对照组分别为6.2±3.4和6.8±3.6,两组比较,差异有统计学意义(P<0.05)。Pearson相关分析显示,流产组和对照组血清中HIF-1α和VEGF的表达成呈正相关(r=0.565,P<0.05;r=0.549,P<0.05),两组绒毛中HIF-1α和VEGF的表达呈正相关(r=0.352,P<0.05;r=0.457,P<0.05)。但稽留宫内时间<2周组、2～4周组和>4周组三组血清和绒毛中HIF-1α和VEGF的表达比较,差异均无统计学意义(P>0.05)。结论 HIF-1α和VEGF在血清和绒毛中的低表达可能是导致稽留流产的重要原因之一。     

Ang-2、VEGF在卵巢子宫内膜异位症中表达及相关性研究

目的:目的:探讨促血管生成素2(Ang-2)、血管内皮生长因子(VEGF)与血管生成的关系,及其在卵巢子宫内膜异位症(EMT)中表达的意义.方法:应用ElivisionTm plus免疫组化方法及体视学方法定量检测30例EMT患者的异位和在位内膜组织中Ang-2、VEGF和微血管密度(MVD)的表达,30例非EMT患者子宫内膜(卵巢囊性畸胎瘤)做为对照组.结果:Ang-2在EMT异位内膜组、在位内膜组和对照组中的平均光密度值分别为0.28±0.13、0.16±0.05及0.13±0.04,组间比较,差异均有高度统计学意义或统计学意义(P<0.01或P<0.05);VEGF的平均光密度值分别为0.32±0.08、0.47±0.12及0.39 4-0.14,组间比较,差异均有高度统计学意义或统计学意义(P<0.01或P<0.05);MVD的表达分别为41.58±14.72、31.30±19.89及20.70±16.17,组间比较差异具有高度统计学意义(P<0.01).Ang-2与VEGF以及Ang-2与MVD在EMT组中的表达呈明显正相关,而与对照组无明显相关性;VEGF与MVD在各组中表达均呈正相关.结论:Ang-2、VEGF过度表达可能与EMT的发生、发展密切相关.     

稽留流产绒毛中HIF-1α、VEGF和PLGF的表达及意义

目的:检测缺氧诱导因子-1α(HIF-1α)、血管内皮生长因子(VEGF)及胎盘生长因子(PLGF)在稽留流产(MA)绒毛组织中的表达,探讨3种因子在维持正常妊娠中的作用.方法:选取昆明市第一人民医院产科收治的MA患者36例(研究组)及行人工流产的正常早孕妇女28例(对照组).应用免疫组化法检测两组绒毛组织中HIF-1α、VEGF和PLGF的表达.结果:研究组绒毛水肿,细胞滋养细胞增生、数量增加,合体滋养细胞明显减少,甚至断裂消失.HIF-1 α、VEGF、PLGF在两组妇女绒毛滋养细胞的胞浆均有表达,但研究组HIF-1α、VEGF、PLGF的阳性表达率均低于对照组(16.67 vs 57.14％,66.67％ vs 100.00％,77.78％ vs 100.00％,P＜0.05).结论:HIF-1a、VEGF和PLGF与正常妊娠的维持有关,其表达异常可能导致MA.     

缺氧诱导因子(HIF)-1a在稽留流产、患者绒毛中的表达

目的:探讨缺氧诱导因子-1α(HIF-1α)在稽留流产中的作用.方法:经B超及β-hCG动态监测证实为稽留流产患者50例,其中不明原因组30例,有原因组20例;根据胚胎停止发育后稽留宫内时间不同又分为A组,B组和C组,分别为胚胎停止发育≤2周、3-4周和≥5周.选取同时期经B超证实为活胎,因非意愿妊娠在门诊要求行人工流产的早孕妇女20例为对照组.应用免疫组织化学方法比较各组绒毛组织中HIF-1a的表达.结果:HIF-1a的表达主要位于绒毛滋养细胞胞浆和胞核:与正常早孕妇女绒毛组织相比较,稽留流产患者绒毛组织中HIF-1α表达明显降低(P＜0.05):但A、B、C组间HIF-1α表达无统计学差异(P＞0.05).结论:HIF-1α在绒毛组织中的低表达可能是导致稽留流产的原因之一.     

绒毛中表皮生长因子受体和血管内皮生长因子的表达对早孕绒毛血管生成的影响及与稽留流产的关系

目的探讨表皮生长因子受体(EGFR)、血管内皮生长因子(VEGF)的表达对早孕绒毛血管生成的影响及与早孕稽留流产的关系。方法应用免疫组织化学方法检测30例稽留流产(稽留流产组)及30例早孕人工流产(早孕人工流产组)绒毛EGFR、VEGF的表达及绒毛的微血管密度(MVD),并分析相关因子的相关性。结果稽留流产组绒毛的MVD(7.03±1.72)比早孕人工流产组(14.74±1.66)显著降低(P0.01)。稽留流产组绒毛的EGFR表达水平(0.42±0.14)表达比早孕人工流产组(0.49±0.07)低(P0.05),稽留流产组绒毛的VEGF表达水平(0.47±0.12)表达比早孕人工流产组(0.60±0.12)低(P0.01)。Pearson相关分析显示在早孕人工流产绒毛及稽留流产绒毛中EGFR与VEGF的表达呈正相关,EGFR的表达与MVD呈正相关,VEGF表达与MVD呈正相关。结论绒毛组织中EGFR和VEGF的表达与绒毛血管生成状况密切相关,EGFR和VEGF低表达参与了稽留流产的绒毛血管的形成障碍。     

血清抑制素A和激活素A浓度与稽留流产的关系研究

目的:了解抑制素A、激活素A在孕妇孕早期血清中的表达水平,探讨抑制素A、激活素A预测早期妊娠稽留流产的价值.方法:选择于我院行门诊产前检查的孕6～10周孕妇1000例为研究对象,采用ELISA法于孕6～8周或孕8～10周测定其血清抑制素A和激活素A的浓度水平,并追踪至孕13周,了解妊娠情况.对其中继续正常妊娠和发生稽留流产的孕妇的血清抑制素A、激活素A的浓度水平进行比较,并比较两者的临界值、敏感性和特异性.结果:无论在孕6～8周还是在孕8～10周,正常妊娠组血清抑制素A、激活素A水平均明显高于稽留流产组,差异有高度统计学意义(P＜0.01).检测血清抑制素A的临界值为＜230 ng/L,其预测孕早期稽留流产的敏感性为84.8％,特异性为77.4％;检测血清激活素A的临界值为＜162 ng/L,其预测孕早期稽留流产的敏感性为85.0％,特异性为88.7％.两者敏感性和特异性比较,差异无统计学意义(P＞0.05).结论:血清抑制素A、激活素A作为预测孕早期稽留流产的手段是可行的,且具有较高的敏感性和特异性,两者的诊断效能无优越性差别.     

VEGF、ENS、MVD在子宫腺肌病中的表达及意义

目的探讨血管内皮生长因子（VEGF）、内皮抑素（ENS）及微血管密度（MVD）在子宫腺肌病（AM）中的表达及意义。方法采用SP免疫组织化学方法检测51例AM患者在位及异位子宫内膜和40例正常子宫内膜组织中VEGF、ENS的表达及MVD值。结果VEGF、ENS、VEGF／ENS、MVD在AM异位内膜中的表达均明显高于正常内膜及在位内膜（P〈O．05）;VEGF、ENS、VEGF／ENS、MVD在对照组中的表达均为分泌期高于增殖期（P〈0．05）,在位内膜中VEGF、Ⅵ1GF／ENs、MVD的表达仍为分泌期高于增殖期（P〈O．05）,但ENS在增殖期与分泌期的表达差异无统计学意义,失去周期性（P〉0．05）,异位内膜VEGF、ENS、vEGF／ENS、MVD在增殖期与分泌期的表达差异均无统计学意义,均失去周期性变化（P〉0．05）;VEGF、vEGF／ENS与MVD分别呈正相关（r=0．36、r=0．43,P〈0．05）,ENS与MVD的表述呈负相关（r=0．22,P％0．05）。结论VEGF、MVD、ENS在子宫腺肌病异位、在位内膜中呈高表达,提示局部血供丰富和新生血管形成可能与子宫腺肌病的发病有关。     

血管内皮生长因子受体2在子痫前期患者胎盘中的表达及其意义

目的探讨子痫前期患者胎盘中血管内皮生长因子受体2（KDR）的表达与胎盘血管病变的关系,研究子痫前期的发病机制。方法对中国医科大学附属第二医院2004年1至11月间收治的重度子痫前期患者22例、轻度子痫前期患者20例和同期正常妊娠妇女20例,采用免疫组化SP法检测其胎盘中KDR的表达情况,记数胎盘间质的平均微血管密度（MVD）值。结果子痫前期重度患者胎盘中KDR的表达显著低于轻度患者和正常孕妇（P〈0.01）,子痫前期轻度组较正常对照组KDR表达明显降低（P〈0.05）。子痫前期重度组患者胎盘中MVD值明显低于轻度组和正常对照组（P〈0.01）,子痫前期轻度组较正常对照组MVD值降低（P〈0.05）。子痫前期患者和正常孕妇胎盘中KDR表达与MVD值的变化呈显著正相关（r=0.855,P〈0.01）。结论KDR表达水平降低可能参与引起胎盘血管发育不良,从而导致子痫前期的发生和发展。     

Th1／Th2型细胞因子在药物流产绒毛和蜕膜组织中的表达

目的了解米非司酮药物流产局部绒毛、蜕膜组织中Th1／Th2型细胞因子的表达,进一步探讨药物流产发病机制。方法Th1／Th2型细胞因子以白介素-2（Interleukin-2,IL-2）、干扰素-γ（Interferon gamma,INF-γ）／白介素-4（Interleukin-4,IL-4）、白介素-10（Interleukin-10：IL-10）为代表,采用原位杂交及免疫组化方法对40例药物流产患者绒毛和蜕膜中IL-2、INF-γ、IL-4、IL-10的表达进行检测（实验组）,利用计算机CMIAS系统,表达指标以阳性数密度（N／S）计算,并与40例正常人工流产的绒毛和蜕膜组织比较（对照组）。结果原位杂交显示实验组绒毛组织IL-2、INF-γ、IL-4、IL-10分别为[（0．003±0．001）、（0．0027±0．0007）、（0．0±0．0）、（0．031±0．008）],与对照组[（0．0027±0．001）、（0．0028±0．0007）、（0.0±0．0）、（0．042±0．011）]比较,IL-10差异有统计学意义（P〈0．05）。蜕膜组织实验组IL-2、INF-γ、IL-4、IL-10[（0.0±0.0）、（0.0±0．0）／（0．029±0．010）、（0．028±0．010）]与对照组[（0.0±0．0）、（0．0±0．0）／（0．031±0．005）、（0．032±0．006）]比较,差异无统计学意义（P〉0．05）。免疫组化结果显示与原位杂交一致。结论绒毛组织Th1／Th2型细胞因子与流产有关,蜕膜组织Th1／Th2型细胞因子与药物流产无关,绒毛组织Th1／Th2平衡失调是米非司酮导致流产的机制之一。     

Transcervical embryoscopy in missed abortion

Purpose: The present study was conducted to determine the usefulness of transcervical embryoscopy in diagnosing localized and systemic defects in embryonic morphogenesis of missed abortions.Methods: The study population consisted of 24 women with the final diagnosis of missed abortion. Prior to the instrumental evacuation of the uterus a rigid hysteroscope was passed transcervically into the amniotic cavity to obtain a detailed view of the embryo. Karyotyping was attempted in all cases included in this study.Results: An embryo could be visualized in 19 cases. Ten embryos showed multiple developmental defects.Conclusions: In cases of early failure of pregnancy, embryoscopy permits visualization of the embryo in utero, unaffected by the damage usually caused by its instrumental evacuation or spontaneous passage. This technique can be a helpful tool for pathologists and geneticists in enhancing their understanding of human embryonic malformations, but more importantly, it improves clinical care and follow-up, especially in cases of repeated abortions.     

Platelet function, coagulation and fibrinolysis during termination of missed abortion and missed labor by PGF2 alpha and oxytocin

In cases of missed abortion and missed labor, labor was induced by PGF2 alpha i.a., i.v. and by oxytocin infusion. Platelet function (methods of Born and Breddin), the coagulation system and fibrinolysis have been studied within the three groups. Using PGF 2 alpha i.v., the initially increased platelet aggregation showed a tendency to become normal. There was no manifestation of activation of the coagulation system. Fibrinolytic activity showed a slight increase during PGF2 alpha i.v. No essential changes in platelet function, coagulation and fibrinolytic system were found after i.a. injection of PGF2 alpha. When inducing labor by oxytocin i.v., both the coagulation and the fibrinolytic system were slightly activated and platelet aggregation increased. The results and their clinical importance for hemostasis as well as therapeutic consequences are discussed.     

Intracervical instillation of PGE2-gel in patients with missed abortion or intrauterine fetal death

A single intracervical instillation of prostaglandin E2 (1.0 mg or 0.5 mg in viscous gel) was given to dilate the cervix before dilatation and evacuation in patients with missed abortion or intrauterine fetal death in late pregnancy. The 1.0-mg dose of PGE2 gave more prominent cervical dilatation in early pregnancy. In late pregnancy 1.0 mg PGE2 induced labor in the majority of patients and with shorter induction delivery time than in patients given 0.5 mg PGE2. There was no uterine hypertonus and no patients complained of gastrointestinal symptoms. We conclude that intracervical instillation of 1.0 mg of PGE2 in viscous gel is a safe and effective method both for dilating the cervix before dilatation and evacuation and as a method of inducing labor in patients with intrauterine fetal death.     

Clinical features of missed abortion

RATIONALE: There is no general agreement concerning the definition of missed abortion which remains one of the most commonly encountered pregnancy complication of an extremely variable clinical picture. AIM OF THIS STUDY: The analysis of the clinical symptoms of missed abortion. SETTING: Academic Medical Center. MATERIALS AND METHODS: Consecutive 50 women with non-viable pregnancy from 7 to 22 weeks, diagnosed by clinical examination, ultrasonography and serum beta-HCG evaluation were studied. RESULTS: In 92% of the missed abortion cases a vaginal spotting was observed before the diagnosis was established. The average period of the estimated retention of the products of conception was 2.8 weeks. In only one patients this period exceeded 8 weeks. The reverse correlation was established between the gravidity of a patient and the period of asymptomatic retention of the non-viable conception products in uterus. The obtained results confirm that the onset of vaginal bleeding does not reflect the moment of embryonal/fetal death.     

Induction of labor in patients with missed abortion and fetal death in utero with protaglandin E2 suppositories

Labor was successfully induced in 20 patients with a diagnosis of missed abortion or intrauterine fetal death (IUFD) by intravaginal administration of prostaglandin E2 suppositories. Fifteen patients delivered with the prostaglandin alone while a concomitant oxytocin infusion was employed to augment contractions in the other five patients. The mean induction-delivery time was 9.80 hours; nulliparous patients delivered in a mean time if 7.78 hours, parous patients in a mean time of 12.29 hours. The uterus appeared to be sensitive to the PGE2 stimulation in all patients and all were delivered completely without the need for surgical intervention. Fifty per cent of patients were delivered within 8 hours and 80 per cent by 12 hours. The side effects associated with prostaglandin administration--vomiting, diarrhea, and temperature elevation--were well tolerated and therapy did not have to be terminated in any patient. The administration of PGE2 vaginal suppositories offers an effective and safe technique for the induction of labor in patients with IUFD. Labor can be induced with PGE2 suppositories as soon as the diagnosis of IUFD is confirmed, which eliminates the need for waiting until spontaneous labor occurs.     

Management of missed abortion in private practice

There is diversity of opinion concerning the proper management of missed abortion. Both conservative treatment with spontaneous evacuation of the uterus and surgical evacuation have their advocates.In a personal series of 11 cases of missed abortion, 10 terminated spontaneously and the patients were then curetted. One pregnancy was interrupted by curettage. This was the only morbid patient of the group. There was no afibrinogenemia, infection, or maternal death.No attempt is made to draw conclusions since there are so few patients. On the other hand the conservative management of missed abortion may be a good choice for the private practitioner because it is traditional and offers him protection if complications arise. This view is advanced despite the fact that valuable reproductive time is wasted.