【作者】 李萍；

【导师】 孙雪梅； 赵晶；

【作者基本信息】 山东大学 ， 妇产科学， 2007， 硕士

【摘要】 研究背景异位妊娠(Ectopic Pregnancy，EP)是妇产科一种常见病、多发病，是妇科急腹症的一种，处理不及时或一旦破裂，可导致大出血等严重并发症发生，甚至危及患者生命。近年来国内外报道EP发生率呈上升趋势，随着人们保健意识的提高和诊疗技术的进步，80％以上的病人得以早期诊断，为其早期治疗方法的选择奠定了良好的基础，为保守治疗提供了条件。但是，在异位妊娠诊断和治疗过程中，监测指标为β-HCG和B超对附件区包块的动念观察，长期临床研究证明其价值有一定的局限性。因此，寻找一种更有价值和准确性较高的监测指标用于早期EP治疗方法的选择及药物治疗监测、并预测预后和结局成为目前EP研究的热点。国内外学者有研究发现，B超监测附件区包块血流显像结合血清β-HCG、PROG测定在EP的早期诊断中有其特异性和敏感性，是一种行之有效的方法，但在早期EP药物治疗中的作用研究尚少，因此，其联合监测在早期EP治疗方法的选择、药物治疗及其监测和预测预后及结局中作用的研究成为目前研究的热点，亦显得十分迫切。研究目的通过彩色多普勒血流显像(CDFI)对早期异位妊娠患者附件区包块血流指数收缩期峰值流速(PSV)、舒张末期流速(EDV)、阻力指数(RI)及血清人绒毛膜促性腺激素β亚单位(β-HCG)、孕酮(PROG)在药物治疗过程中的联合监测，观察其在药物治疗过程中的表现和变化规律，探讨其与早期异位妊娠药物治疗效果的关系，以期寻找一种能指导早期EP治疗方法选择及药物治疗监测的快捷、特异、敏感的方法，并成为能够进行药物治疗疗效评估、预后判断的有效指标；以期提高早期EP药物治疗的成功率，用于监测药物治疗效果，预测预后和结局，并完善随访指标。研究方法研究对象：收集山东省立医院计划生育综合科2005年10月～2007年3月门诊早期诊断或暂未明确诊断收住院进一步明确诊断后符合纳入标准的异位妊娠患者76例作为研究对象，根据最后的临床治疗结局将研究对象分为两组：A组为药物治疗组(46例)；B组为手术对照组(30例)。首先明确诊断后，对A组患者行药物治疗，治疗前和治疗后每次定期复查均行CDFI测定PSV、EDV、RI的具体值，并同时抽取静脉血，离心，吸取离心后的血清1ml立即进行β-HCG、PROG测定。对B组患者行手术治疗，并记录手术前超声结果及PSV、EDV、RI的具体数值和抽取清晨空腹血行血清β-HCG、PROG测定、手术情况和手术病理结果。1．本研究采用美国GE公司生产，型号为Voluson730Pro的彩色超声诊断仪，仪器设置为阴道超声检查程序，先二维常规扫查清晰显示子宫及附件区二维图像，然后用彩色多普勒观察并测定附件区包块血流显像的PSV、EDV、RI的具体值，最后作出超声诊断。2．血清β-HCG，PROG采用电化学发光法测定。3．所得数据应用SPSS11.5统计软件包进行统计学分析。正态分布资料用均数、标准差描述，两组均数间差别比较采用t检验(Student’s t-test)。P＜0.05为差别有统计学意义。4．监测数据以均数±标准差((?)±s)表示。5．将每次检查结果均对应列表，分别观察PSV、EDV、RJ和血清β-HCG，PROG在治疗前后的特征性变化及其变化趋势，并观察其与药物治疗效果的关系，用来预测早期EP的预后和结局。研究结果1．两组患者年龄、身高、体重、孕次、流产次数、停经天数、月经周期的比较，差别均无统计学意义(P＞0.05)。(见表1)2．异位妊娠患者药物治疗前、后PSV、EDV、RI及β-HCG、PROG测定在药物治疗过程中的特征性表现和变化规律：(1)特征性表现：药物治疗组治疗前PSV、EDV、RI、β-HCG、PROG的均值分别为：30.47±19.75cm／s，12.37±11.81cm／s，0.59±0.11，1868.44±2033.64mIU／ml，4.09±3.02ng／ml(见表3)。由此得出：异位妊娠患者彩色多普勒超声血流显像的特征性表现呈典型的低阻力血流频谱特征，即滋养层周围血流(见图6)。(2)特征性变化规律：药物治疗成功组患者治疗后第一～四次复查PSV、EDV、β-HCG、PROG均值呈明显的逐渐下降趋势，RJ均值呈逐渐递增趋势，分别为29.86±16.07cm／s～4.94±11.89cm／s，10.16±4.65cm／s～1.45±3.19cm／s，1851.95±1445.57mIU／ml～36.09±42.34mIU／ml，2.50±1.88ng／ml～2.55±3.05ng／ml；0.66±0.18～0.97±0.09，(见表3)。由此可见：随着药物治疗周期的逐渐递加，血β-HCG、PROG值不断下降和／或下降明显，包块处滋养动脉血流频谱阻力(RI)逐渐增加直至变成1，血流信号(PSV、EDV)逐渐减弱直至消失变为0。即：其血β-HCG、PROG值的变化与附件区包块血流指数PSV、EDV的变化呈正相关，而与阻力指数RI的变化呈负相关。(3)药物治疗成功组治疗前、后PSV、EDV、RI和β-HCG、PROG测定结果比较及其统计学分析：通过表4．1可见药物治疗前与治疗后第一次复查检查结果相比：血β-HCG、PROG和RI值的差异均有显著性(P＜0.05)；PSV、EDV值的差异无显著性(P＞0.05)。通过表4.2、4.3、4.4可见药物治疗前与治疗后第二、三、四次复查结果相比：PSV、EDV、RI、β-HCG、PROG动态变化水平相比，差异均有显著性(P＜0.05)，有统计学意义。3．两者联合监测的特征性变化规律：药物治疗组治疗后附件区包块处血流的血流指数PSV、EDV、RI随着血β-HCG和PROG的不断变化而呈现特征性变化。在46例行药物治疗的患者中(结果见表5)：(1)28例患者药物治疗后血β-HCG、PROG明显下降，RI逐渐变大，PSV、EDV逐渐变小。28例药物治疗均成功，成功率为100％。(2)12例患者药物治疗后血β-HCG、PROG无变化或者变化不大，RI逐渐变大，PSV、EDV逐渐变小。其中9例药物治疗成功，3例药物治疗失败转行手术治疗，成功率为75％。(3)6例患者药物治疗后血β-HCG、PROG不下降反而升高，砌变小，PSV、EDV反而变大。其中2例药物治疗成功，但是历时较长，4例药物治疗失败转行手术治疗，成功率为33.33％。4．药物治疗组与手术对照组治疗前PSV、EDV、RJ及β-HCG、PROG测定结果比较及其统计学分析(见表6)：两组治疗前PSV、EDV、RI、β-HCG、PROG水平相比，RI及β-HCG，PROG值的差异均有显著性(P＜0.05)；PSV、EDV值的差异无显著性(P＞0.05)。5．预测预后：血β-HCG、PROG与PSV、EDV、RI单独监测与联合监测预测EP预后的灵敏度和特异度分别为(见表7)，在预测EP预后上，联合监测血β-HCG、PROG与PSV、EDV、RI较单独监测其中任何一项或者单独的血清学指标与血流指数之间的联合监测的灵敏度和特异度均明显增高。研究结论1．EP患者治疗前彩色多普勒超声血流显像的特征性表现：呈典型的低阻力血流频谱特征，为单相或双相，持续存在，频谱增宽，舒张期血流丰富的动脉血流，即滋养层周围血流(见图6)。2．EP患者药物治疗前、后PSV、EDV、RI及β-HCG、PROG测定在药物治疗过程中的特征性变化规律：随着药物治疗周期的逐渐递加，血β-HCG、PROG值不断下降和／或下降明显，其包块处滋养动脉血流频谱阻力(RI)逐渐增加至变成1，两者呈负相关；血流信号(PSV、EDV)逐渐减弱直至消失变为0，两者呈正相关。3．两者联合监测的特征性变化规律及其对预测预后和结局的意义：药物治疗组治疗后附件区包块处血流的血流指数PSV、EDV、RI随着血β-HCG和PROG的不断变化也呈现特征性的变化。(1)若药物治疗后血β-HCG、PROG明显下降，RI逐渐变大，PSV、EDV逐渐变小，则药物治疗基本均可成功。(2)若药物治疗后血β-HCG、PROG无变化或者变化不大，RI逐渐变大，PSV、EDV逐渐变小，则药物治疗成功的可能性较大，宜在严密监测下继续行药物治疗。(3)若药物治疗后血β-HCG、PROG不下降反而升高，RI变小，PSV、EDV反而变大，则药物治疗成功的可能性较小，不宜继续行药物治疗，宜尽快行手术治疗。4．在预测EP预后上，联合监测血β-HCG、PROG及PSV、EDV、RI的灵敏度和特异度分别为：84.78％，93.33％，较单独监测其中任何一项或者单独的血清学指标与血流指数之间的联合监测均明显增高。两者联合监测是一种方便、快捷、无创、敏感度及特异度较高的监测方法，为早期EP治疗方法的选择提供了可靠的依据，并可在药物治疗的疗效评估、预后及随访等方面发挥作用；有望成为药物治疗很好的监测和随访指标，并用于预测预后和结局。因此，两者联合监测在早期EP药物治疗中具有重要的价值和临床意义。更多还原

【Abstract】 BackgroundEctopic Pregnancy(EP)is not only a kind of common and frequently encountered disease but also a acute abdomen in the department of gynaecology and obstetrics.If we don’t deal with it in time or it once break suddenly can cause the big issue of blood wait serious complications occurrence,even endanger the sufferer’s life.The occurrence rate of EP in reports at home and abroad is rising in recent years.With the people’s consciousness for health protection rise and the technical progress of diagnosis and treatment,above eighty percent patients can be made a diagnosis in ordor to lay a good foundation for it can be cured in early days and for a choice of therapic method,so this could provide a condition for the conservative treatment of EP.But in the process of diagnosis and treatment of early ectopic pregnancy,the index is the dynamic observing of β - HCG and lump with Color Doppler ultrasound.The long-term clinical study proves that it’s value is restrict. Therefore,looking for a kind of more value and higher accuracy monitoring index sign for the choice for treatment method of EP,monitoring the conservative treatment of EP in early days and estimate the prognosis and termination of conservative treatment of earlier EP become a hot point in the existing study of EP.The domestic and foreign scholars has the research detection that they have their specificity and sensibility to combine monitoring blood flow display with color Doppler ultrasound with monitoring of β - HCG and PROG and the methods take their effect.But the research that their action in the conservative treatment of earlier EP was still little.Therefore, the study for combination of monitoring becomes a hot point in the existing study of EP.Moreover,it appears fairly stringent. ObjectiveTo observe the appearance and variety regularity by monitoring of the PSV,EDV,RI with Color Doppler ultrasound and determination of the conservative β - HCG,PROG in the drug treatment of early ectopic pregnancy and to approach the relationship between them and the effect of drug treatment for EP.Accordingly,we can look for a simple,fast,sensitive and specific method of the choice for treatment method and the monitoring in the drug treatment of early EP.And then,it hope to become a effective index for follow-up and monitoring and be used for an estimate the prognosis and termination of earlier EP,in order to raise the achievement ratio in drug treatment of earlier EP,to be be used for monitoring the effect of drug treatment and an estimate the prognosis and termination of earlier EP,and then consummate the follow-up indexes. MethodsResearch object:From October 2005 to March 2007, serum samples of the out-patient service examined a patient in early days and accept a hospitalization or the out-patient service didn’t examine a patient to accept a hospitalization definitely temporary to examine a patient further and definitely behind were collected and done the medicine cure at the planned parenthood comprehensive section of Shandong Provincial Hospital.There were 76 cases that meet the above criteria altogether.They were divided into two groups.the A group is a drug treatment group (46 cases) and the B group is a operation group (30 cases) .First make a conclusive diagnosis and then give the A group a medicine treatment.It should be determined PSV,EDV,RI with transonogram and β-HCG,PROG. Give the B group a treatment of operation and it should be determined PSV,EDV,RI with transonogram and β-HCG,PROG before the treatment. The color Doppler is made in GE company of American. It’s pattern number is Voluson730Pro.The installation of instrument is a vaginal transonogram checking program.First,to display the two-dimensional pictures of uterus and appendix clearly using two-dimensional and conventional way to sweep.Then,to determine the value of PSV,EDV and RI with the color Doppler in the appendix.Finally,to make a ultraphonic diagnosis.The blood samples of PROG and β-HCG were determined by automatic electrochemiluminescence analyzer.The data was analyzed by SPSS 11.5 for windows statistical package.Data of normal distribution were described with mean.The comparison of the difference of means of two groups was processed by Student’s t-test.It meant significant if P<0.05. Results1.There was no significant difference on age,height,weight,gravidity,abortion times,menelipsis weeks,menstrual cycle between the two groups(P>0.05). (table 1)2.The distinctive appearance and variety regularity of PSV,EDV,RI and |3 -HCG,PROG in the process of drug treatment before and after being given medicine treatment:(1)The value of PSV,EDV,RI and β-HCG,PROG were 30.47±19.75,12.37±11.81,0.59±0.11,1868.44±2033.64,4.09±3.02 before given medicine treatment in the drug treatment group. We could arrive at a conclusion that the distinctive appearance of blood flow display for EP patients is a kind of typical,low and spectral resistance blood frequency characteristic.I.e.It is circum-trophoblastic blood.(graph 6)(2)From the first to the fourth rechecked value of PSV,EDV,RI and β-HCG,PROG were 29.86±16.07cm/s ～ 4.94±11.89cm/s,10.16±4.65cm/s ～ 1.45±3.19cm/s,1851.95±1445.57mIU/ml ～ 36.09±42.34mIU/ml,2.50±1.88ng/ml ～ 2.55±3.05ng/ml;0.66±0.18～0.97±0.09(table 3)after given medicine treatment in the succeed drug treatment group.We could arrive at a conclusion that in the therapic cycle increased progressively,the RI of the blood is increased to land the signal of the blood(PSV,EDV)is weaken to zero gradually with the constant variance of β-HCG,PROG are decreased.That is to say, the relationship between the variance of β-HCG,PROG and PSV,EDV is positive correlation.the relationship between the variance of β-HCG,PROG and RI is negative correlation.(3)Through comparing the metered results and the analysis in statistics of PSV,EDV,RI and β-HCG,PROG in the drug treatment group before and after being given medicine treatment:We could arrive at a conclusion that there were significant difference between the value of before being given medicine treatment and the first rechecked value(P<0.05)except the PSV,EDV in the two groups(P>0.05)by the table 4.1.We could arrive at a conclusion that there were significant difference between the value of before being given medicine treatment and the second, third and fourth rechecked value (P<0.05) by the table 4.2,4.3 and 4.4.3.The distinctive variety regularity for combination of monitoring:the circum-trophoblastic blood in the appendix of EP patients after given medicine treatment in the succeed drug treatment group takes on distinctive variance with the constant variance of β-HCG,PROG.In the 46 cases for drug treatment(table 5):(1)There are 28 cases their value of β-HCG and PROG is decreased obviously,the value of RI is increased and the value of PSV,EDV is shrink gradually.Their drug treatment were all succeed and the achievement ratio is 100%. (2)There are 12 cases their value of β-HCG and PROG is invariant or with modicus variance,the value of RI is increased and the value of PSV,EDV is shrink gradually.After given drug treatment, among them 9 cases were succeed,3 cases were failed and the achievement ratio is 75%.(3)There are 6 cases their value of β-HCG and PROG is increased,the value of RI is decreased and the value of PSV,EDV is increased on the contrary.After given drug treatment,among them 2 cases were succeed,4 cases were failed and the achievement ratio is 33.33%.4.Through comparing the metered results and the analysis in statistics of PSV,EDV,RI and β-HCG,PROG before treatment in the drug treatment group and the operation group:There were significant difference between the two groups(P<0.05)except the PSV and EDV in the two groups(P>0.05).5.Estimate the prognosis and termination:The sensibility and specificity of the solitary and conjoined monitoring of PSV,EDV,RI and p-HCG,PROG that used to estimate the prognosis and termination of earlier EP were(table 7).Based on them, we could arrive at a conclusion that the sensibility and specificity of conjoined monitoring of PSV,EDV,RI and β-HCG,PROG are more higher than the solitary monitoring in estimate the prognosis and termination of earlier EP. Conclusions1 .The distinctive appearance a of PSV,EDV,RI before being given medicine treatmentlt is a kind of typical,low and spectral resistance blood frequency characteristic.It is monophasic or diphase, persistent exist,it’s frequency spectrum is widen and the blood in diastolic phase is affluent.I.e.It is circum-trophoblastic blood.2.In the therapic cycle increased progressively,the RI of the blood is increased to land the signal of the blood(PSV,EDV)is weaken to zero gradually with the constant variance of β-HCG,PROG are decreased.That is to say, the relationship between the variance of β-HCG,PROG and PSV,EDV is positive correlation, the relationship between the variance of β-HCG,PROG and RI is negative correlation.3.The distinctive variety regularity for combination of monitoring and the significance:the circum-trophoblastic blood in the appendix of EP patients after given medicine treatment in the succeed drug treatment group takes on distinctive variance with the constant variance of β-HCG,PROG.(1)If the value of β-HCG and PROG is decreased obviously,the value of RI is increased and the value of PSV,EDV is shrink gradually,drug treatment were mainly succeed.(2)If the value of β-HCG and PROG is invariant or with modicus variance,the value of RI is increased and the value of PSV,EDV is shrink gradually,the possibility of successful drug treatment is biggish and they could be kept going to be geiven drug treatment under the rigorous monitoring.(3)If the value of β-HCG and PROG is increased, the value of RI is decreased and the value of PSV,EDV is increased on the contrary,the possibility of successful drug treatment is min.They were unsuitable for being geiven drug treatment and should be carried on a operation as soon as possible.4.In estimate the prognosis and termination of earlier EP, the sensibility and specificity of conjoined monitoring of PSV,EDV,RI and β-HCG,PROG are 84.78 % ,93.33 % .they are more higher than the solitary monitoring.The conjoined monitoring of PSV,EDV,RI and β-HCG,PROG is a convenience,fast,atraumatic,the sensitivity and specificity higher monitor method.It provid alternations of the treatment method for earlier EP that based on it.It also produces a marked effect in estimating the curative of medicine treatment,prognosis and follow-up.Then it hope to become a good index for follow-up and monitoring and be used for an estimate the prognosis and termination of earlier EP.Therefore,the conjoined monitoring of PSV,EDV,RI and β-HCG,PROG have important value and clinical meaning in medicine treatment of earlier EP.更多还原