微波子宫内膜去除术治疗月经过多的远期疗效及病理机制探讨
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摘要
前景和目的:
月经过多是生育年龄和更年期妇女的常见病,占月经不调就诊病人的2.7%,传统治疗方法是以缓解症状为主的药物治疗和诊刮,无效者需子宫切除,其手术病率高达40 % ,死亡率6/ 10 000～11/ 10 000,术后恢复期还有卵巢早衰、精神性性功能障碍等远期并发症。微波子宫内膜去除术(microwave endometial ablation,MEA)是一项近年来妇科领域新兴的微创技术[1],在治愈疾病同时能够保留子宫,不破坏盆底解剖,不影响卵巢内分泌功能,已成为替代子宫切除治疗月经过多的安全、有效的方法。其机制是将微波能源导入宫腔,通过热损伤,引起子宫内膜全层热凝固、变性、坏死及纤维化,导致治疗性Ashermann综合征,以减少月经量,减轻痛经,从而缓解月经过多症状[2]。其主要优点是简便、安全、快捷。
国内外已有大量文献报道MEA治疗月经过多的近期疗效、安全性、并发症等,但对于MEA术后的远期疗效、患者生活质量,术后宫腔形态改变,微波作用组织后产生热损伤的病理机制等方面的报道十分有限。同时MEA术后仍有一定的复发率及子宫切除率,由于其破坏组织深度有限,对子宫腺肌症患者疗效欠佳,术后仍有妊娠和发生子宫内膜癌的可能,如何降低复发率、提高治愈率及患者生活质量,减少并发症,这些都是困扰临床工作的问题。
本研究通过随访MEA术后患者的月经变化情况、生活质量评分等,探讨MEA治疗月经过多的远期疗效;并观察子宫内膜受微波作用后组织形态学及细胞病理学改变,评价MEA安全性及远期疗效的病理机制。
资料与方法
1、研究对象选择2000年1月～2008年8月本院因月经过多经药物治疗无效而行MEA治疗的患者共334例,完成术后1个月至术后8年临床症状的随访,术后6个月、2年、5年各评估一次患者的生活质量、性功能。患者年龄29～59岁,平均(42.32±5.47)岁。术后随机抽取53例患者行宫腔镜检查,并取子宫内膜做光镜及电镜检查。
2、手术指征及诊断月经过多诊断标准为因月经过多影响正常生活和缺铁性贫血导致慢性衰弱,月经评分(pictorial blood loss assessment chart, PBAC)>100分者。全部患者符合以下条件:(1)药物治疗无效;(2)6个月内子宫内膜病理检查已排除子宫内膜癌及癌前病变;(3)无生育要求;(4)子宫<10周大小,宫腔深度<12cm。
3、方法
3.1设备:MEA治疗仪(英国Microsulis公司生产的9.2GHz、功率为30W的全自动监控仪)、宫腔镜和液体膨宫机(德国WOLF)。
3.2 MEA治疗方法:(1)子宫内膜预处理:术前连续4周口服丹那唑400-800mg/d,或采用促性腺激素释放激素(GnRH-a),部分患者行负压吸宫薄化子宫内膜。(2)麻醉:采用静脉麻醉。(3)手术操作:取膀胱截石位,常规消毒铺巾,扩张宫颈至9号,微波探头连接数据探头,置于宫底,启动温控系统,45秒内,子宫内膜达治疗温度(70-80℃),微波探头自宫底开始缓慢、连续地由一侧宫角移向另一侧宫角,然后缓慢将探头退出,全部宫腔均匀加热,探头达到宫颈内口时退出,治疗结束。
3.3宫腔镜检查方法:使用5%葡萄糖液作膨宫介质,膨宫压力控制在18. 0～20. 0 kPa。进入宫腔后,分别观察宫腔及双侧宫角,特别记录有无残留子宫内膜、宫腔粘连、粘连的部位及程度等;同时记录患者当时的月经情况。宫腔镜下取子宫内膜做病理切片行光镜及电镜检查。
所有患者术前均签署手术同意书,并经过医院伦理委员会通过。
4、随访
4.1月经情况:手术后1、3、6个月门诊复查,以后每年发问卷1次或电话访问,填写术后调查表。随访内容包括月经评分、月经周期、经期、痛经的改变等。术前及术后第3个月检测血常规。术后按月经状况分成5种类型:(1)闭经(Amenorrhea);(2)点状出血(Spotting);(3)少经量的月经周期(Hypomenorrhea);(4)如正常经量的月经周期(Eumenorrhea);(5)月经如术前(The same)。手术成功:包括闭经、点状出血、少经量及正常经量月经这四种月经状况。
4.2生活质量及性功能问卷调查:采用国际女性性功能评估量表(brief index of sexual function for women ,BISF-W)和健康相关生存质量量表(short-form health survey , SF-36)测试患者术前及术后6个月、24个月、60个月的各项得分。
5、统计学方法:采用SPSS13.0软件进行统计分析。(1)计量资料采用均数和标准差进行描述,然后使用t检验(或者配对t检验)进行分析;计数资料采用频数、频率进行简单描述,使用卡方检验进行分析。(2)使用重复测量资料的方差分析比较不同时间段的评分变化情况。(3)使用Cox回归模型(生存分析方法)研究影响疗效及随访结局的因素,先进行单因素的分析,如果单因素的P小于0.30,则纳入模型进行多因素分析。所有检验水准α均为0.05。
结果
一、远期临床疗效评价
1、治疗前后月经变化情况比较
(1)月经评分比较。术前PBAC评分平均为169±51.27,术后6个月、12个月、24个月、60个月、96个月分别为35.05±34.04, 28.70±32.72, 26.55±31.87, 17.25±27.43, 16.50±25.72,与术前比较,评分均明显降低,差异有统计学意义(p均<0.05),术后6个月开始PBAC评分基本稳定,并维持于较低的水平。
2)治疗前后血红蛋白的变化情况。术前患者血红蛋白平均值为(107.08±22.23)g/L,术后3个月血红蛋白平均值为(131.73±13.62)g/L,p<0.05,差别有统计学意义。
3)术后月经状况。334例中,术后闭经127例,占49.7%;经血明显减少,表现为规律的少量月经者60例,占18.0%;点滴出血59例,占17.7%;月经量正常者20例,占6.0%;经量无变化,如术前者29例,占8.7%;手术总成功率91.3%(305/334)。
4)术后1年,2年,6～8年患者的闭经率分别为35.5%,40.1%及60.9%,手术成功率分别为89.1%、92.9%及93.5%。
2、治疗前后性功能及生活质量评分比较
1)生活质量8个分量表:术后6个月、24个月、60个月评分,均较术前升高,差异有统计学意义(P<0.05)。
(2)性功能7个分量表:术后6个月、24个月、60个月评分,均较术前升高,差异有统计学意义(P<0.05)。
3、MEA术后并发症
(1)334例患者中,术后宫颈管粘连2例,予以扩宫后症状消失;宫腔积血2例,均行子宫切除。MEA术后妊娠共2例,3例次,均为宫内妊娠。其中1例术后2次妊娠,3例均行人工流产术。术后2年1例子宫内膜不典型增生。
(2)MEA术后再次手术情况。334例中,共9例(2.7%)再次行MEA术。其中8例因治疗无效再次MEA,1例患者要求闭经再次MEA。术后行子宫切除33例,子宫切除率9.88%。子宫切除的原因分别为:子宫腺肌症14例(42.4%),MEA术后复发9例(27.3%),子宫肌瘤8例(24.2%),宫腔积血2例(6.1%)。
4、影响MEA疗效的可能因素
使用Cox回归分析方法对随访结局进行生存分析,结果显示:患者的年龄(P =0.011)、宫腔深度(P =0.001)、合并子宫腺肌症(P =0.003)、手术持续时间(P =0.000)有统计学意义,术前子宫内膜厚度、经期持续时间、合并宫内占位病变、术前药物预处理无统计学意义(P均>0.05)。
二、MEA术后组织及细胞病理学改变
1、大体形态学变化。共53例患者MEA术后行宫腔镜检查。术后3个月内宫腔内主要为坏死脱落的内膜组织,月经改变为不规则点滴出血;术后半年,宫腔内可见肉芽组织形成,月经为规律的少量月经或闭经;术后1年,宫腔为瘢痕组织覆盖,月经变化主要为闭经;术后2年以上,宫腔镜下可见不同形态的宫腔粘连。共28例患者发生宫腔粘连(52.8%),其中1例为宫颈管粘连,12例(22.6%)宫底局灶性粘连,11例(20.7%)形成筒状宫腔, 4例(7.5%)宫腔完全粘连、闭锁;这28例中,22例月经表现为闭经,3例为不规则的点滴出血,3例为规律的少量月经。
2、组织病理学变化:表现为急性坏死期及随后的慢性修复期。急性坏死期主要是术后1个月～3个月,光镜下见坏死组织分两层:内层为子宫内膜凝固性坏死,细胞崩解成碎片状;外层为浅层平滑肌细胞透明样变性,伴间质红细胞渗出,深肌层平滑肌细胞未见明显改变。慢性修复期发生于术后3个月,可见肉芽组织产生,胶原纤维形成,部分病例可见子宫内膜再生、新生血管形成。子宫内膜腺体可增生为多层,个别病例发生不典型增生。
3、组织超微结构变化:也表现为急性坏死期及慢性修复期。术后3个月内见子宫内膜上皮细胞变性坏死:细胞核固缩,核染色质浓缩,线粒体扩张、空化,嵴大部分溶解消失;浅层平滑肌细胞轻度变性、坏死,核染色质边集,粗面内质网轻度扩张;深层子宫平滑肌细胞变化不明显,细胞核较完整,可见核仁、核膜,线粒体、内质网结构完整。急性坏死期后随之发生慢性修复,见于术后3个月,组织破坏与慢性修复可能并存,并可伴随子宫内膜的再生,由于腺上皮再生能力强,子宫内膜可完整修复,达到完全再生,甚至出现不典型增生。
结论
1、MEA治疗月经过多远期疗效显著。
2、MEA对月经过多患者性功能、生活质量均有正向影响。
3、宫角残留岛状子宫内膜是术后复发的重要原因。年龄、合并子宫腺肌症是影响MEA手术远期成功率的主要因素。
4、MEA术后宫腔粘连程度逐渐加重,术后月经改变与宫腔形态变化密切相关。
5、高频微波可有效破坏子宫内膜达基底层,对子宫肌层无创伤。MEA术后病理学改变为急性坏死期及随后的慢性修复期,个别病例可伴随子宫内膜的再生。
Perspective and objective
Menorrhagia is a common gynaecological problem affecting all ages from reproductive years and the climacteric period, accounted for 2.7% outpatients of irregular menstruation. The management options vary from medical to surgical treatment. The initial approach to treating menorrhagia is using medicines or curettage which relieve symptoms. For patients whose bleeding cannot be controlled with hormones, abdominal hysterectomy which offered a permanent cure may be necessary. However, hysterectomy is associated with early ovarian failure, incontinence many years later, and a small mortality risk of 6/ 10 000～11/ 10 000. Microwave endometial ablation (MEA) offers a less invasive surgical alternative than hysterectomy for menorrhagia which is a software-controlled device designed to ablate the endometrial lining of the uterus, it doesn’t influence ovarian function by retaining the uterus and maintaining the integrity of cervix uteri and vagina. The aim of this technique is destroying the basal layer of the endometrium. This result in a therapeutic Ashermann’s syndrom, alleviating menstrual symptoms. It has emerged as an effective and safe alternative to hysterectomy for women with menorrhagia.The technique is quick, safe, simple to learn and perform.
The pilot studies were focus on such aspects as short-period effectiveness, complications ,and safety of this system. But there were few reports on long-term clinical results , health-realated quality of life ,the hysteroscopic appearance of the uterine cavity and the incidence of postablation intrauterine adhensions after MEA, even fewer data were available regarding with thermal destruction and followed healing response to this type of tissue injury. At the same time, there was some definite incidence of postablative recurrence and hysterectomy after MEA, endometrial regrowth was seen in some post-ablation cases. Although rare, pregnancy and even endometrial cancer following endometrial ablation were possible. How to reduce the recurrence rate, increase the the cure rate and improve the quality of life, these are puzzled questions of clinical works.
We report the results of the change on the menstrual symptoms and the scores of health-realated quality of life, at eight years follow up, to explore the long-term effectiveness, the effects on health-realated quality of life of MEA, and also identify potential prognostic factors that will ensure successful menorrhagia treatment using MEA. We underwent outpatient hysteroscopy for assessment of the uterine cavity, and describe the pathologic effects and morphologic changes of thermal destruction of endometrium related to postablation time intervals, We sought to evaluate pathologic mechanism on the clinical efficiency and safety of this procedure.
Materials and methods
paticipants
From January 2000 to August 2008, 334 consecutive women who had undergone MEA, and who were followed up from 1 month to 8 years, sexual functioning and mental health were measured at 6 months, 2 years and 5 years, the median age was 42.32 years (range, 29 to 59 years). Fifty-three women underwent outpatient diagnostic hysteroscopy for assessment of the uterine cavity, subsequent endometrial sampling for light microscope and electron microscope.
Indication of the operation and the diagnosis of menorrhagia
Menorrhagia is defined as too much menstrual flow which influence normal life and chronic weekness as a result of iron deficiency anemia, a PBAC score (Pictorial Blood Assesment Charts) of 100 or higher was required. Women were eligible if they had heavy menstrual loss who were inefficient to medical treatments, no desire to have children bearing, no endometrial atypia on histopathologic examination 6 months before the ablation, and the uterus was not greater than 10 weeks’pregnancy size and 12 centimeter. Procedures
Some patients were given goserelin 3.6 mg or danazol to promote endometrial thinning, and underwent surgery 4 weeks later, another patients were given preoperative uterine curettage. Paticipants underwent ultrasonography for mesurement of endometrial thickness and identify of any fibroids in the endometrial cavity. For MEA procedure , a microwave probe of diameter 8 mm was inserted until the tip reached the uterine fundus. The footswitch was then activated. Once the temperature maintained at 75℃, the probe was moved slowly from side to side and withdrawn with the temperature maintained at 75℃-80℃. The technique effectively“paints”microwave energy with a maximum penetration of 6 mm over the whole surfuce of the uterine cavity. All procedures were done under intravenous anesthesia after cervical dilation to 9 mm.
Hysteroscopy was performed by using 5% glucose as the distending medium. The presence of residual endometrium and intrauterine adhesions was noted and their locations recorded. Menstrual patterns of the women at the time of assessment were also recorded, subsequent endometrial sampling for light microscope and electron microscope..
The study protocol was approved by the Clinical Research Ethics Subcommittee of Guang Dong province mother and children hospital, and written consent was obtained from each woman on recruitment.
Follow up
Clinical questionnaires assessing menstrual outcome which included PBAC score , menstrual cycle, dysmenorrhea and other changes were completed by participants. Hospital review was undertaken at 1, 3, 6 months , postal questionnaires or telephone interviews made every 1 year after operation. Routine blood test were made before and 3 months post-operation. Menstrual patterns were decribed as 5 types: (1) Amenorrhea; (2) Spotting; (3) Hypomenorrhea; (4) Eumenorrhea; (5) The same.
Sexual functioning measured by the 22-items Brief Index of Sexual Function for Women(BISF-W) and health-realated quality of life using the 36-Item Short-Form Health Survey(SF-36) was undertaken at 6 months, 2 years and 5 years after MEA. Statistical analysis
SPSS13.0 was used to analyze all the data. (1) Measurement data was described using mean and standard deviation, and then was analyzed by t-test or paired t-test. Categorical data was described using frequency or probability, and then was analyzed by Chi-square. (2) The scores in different times were analyzed by ANOVA of repeated measurement data. (3)In order to find out the influencing factors of survival time, Cox regression model was used. The variable with p value less than 0.3 in univariate model were entered into multi-variate model. All the significant was equal to 0.05. Results
Menstrual outcomes before and after MEA .
1. Menstrual score before and after MEA
(1) Menstrual blood loss by PBAC score before and in 6, 12, 24 ,60 and 96 months following MEA were 169±51.27 versus 35.05±34.04, 28.70±32.72, 26.55±31.87, 17.25±27.43, 16.50±25.72, respectively(P <0.05), PBAC score remained stable low-level from 6 months postoperation.
(2) Hemoglobin elevated from (107.08±22.23) g/ L preoperatively to (131.73±13.62)g/ L 3 months postoperatively , the difference was statistically significant (P < 0.05) .
(3) In all the 334 cases showed amenorrhea in 127 cases (49.7 %) , hypomenorrhea in 60 cases (18.0 %) , spotting in 59 cases (17.7 %), normal menstruation in 20 cases (6.0 %) and no improvement in 29 cases(8.7 %) , The total clinical effective rate was 91.3%.
(4)The amenorrhea rates and successful rates of 1-year,2-year and 6-8 years after MEA were 35.5%, 40.1% , 60.9%, and 89.1%, 92.9%, 93.5% respectively.
2.Sexual functioning and health-realated quality of life after MEA
7-Dimension of Sexual functioning and 8-Dimension of health-realated quality of life at 6 months, 24 months, 60 monthssignificantly improved after surgery, the difference was statistically significant (P <0.05).
3. Postoperative complications of MEA
In the 334 cases, 2 patients suffered endocervix adhesion which was disappeared by expanding the cervix. 2 women suffered intrauterine hematometra and required subsequent hysterectomy. 3 women were intrauterine pregnant after MEA and one of them had been pregnant twice. They all took artificial abortion finally. Atypical hyperplasia endometrium was found in one case 2 years after MEA.
4. Reoperation after MEA
In the 334 cases, 9 women (2.7%) had taken second operation after MEA. 8 of them were cured by MEA again because of the ineffective results for the first time. One woman required second MEA for amenorrhea. 33 women required subsequent hysterectomy with a rate of 9.88%, owing to adenomyosis (14 cases ,42.4%) , hysteromyoma (8 cases ,24.2%) , recurrent bleeding (9 cases ,27.3%), endometrial hematometra (2 cases ,6.1%).
5. Possible factor impacting the curative effect of MEA
Survival analysis of follow-up outcome was performed using Cox regression analysis. The results shows: Age (P=0.011), the depth of uterine cavity (P=0.001), adenomyosis (P=0.003), the duration of operation (P=0.000) are factors with statistical significance. However, endometrial thickness, the length of menstrual period before operation, complicating with intracavitary occupy lesion, preoperative medicine pretreatment have no statistical significance (P>0.05). Young age, complicating with adenomyosis, long operation time and deep uterine cavity all can increase the operation risk and influence the operation curative effect.
Pathological changes by thermal damage after MEA
1. Hysteroscopic appearance of the endometrial cavity following MEA. Second-look hysteroscopy at 3 months or less after ablation were always exhibited varied necrosis in the endometrium, destroyed endometrium and the debris were seen in the uterus. Most of them developed mimimal spotting during the menstural cycles. Grannulomatous reaction and fibrosis were present after 6 months postablation, the mestrual patterns of these women were regular reduction or cessation of mestrual flow. Post- hysteroscopy at 1 year after ablation showed fibrotic cavity, varied myofibrous scars can be seen. Most of the patients developed amenorrhea. All kinds of intrauterine adhensions were observed after 2 years or more postablation. Intrauterine adhesions were found in 28 women (52.8%); 1 had cervical adhesion(1.9%);12 had focal adhesions in the fundal area(22.6%);11 patients(20.7%) formed narrowed uterus which like a bucket ,whose endometrial cavity appeared totally scarred with bilateral stenotic ostia; 4(7.5%)had complete obliteration of the cavity. Of these 28 women, 22 had amenorrhea , 3 had spotting during menstruation and 2 had hypomenorrhea.
2. The results of observing HE staining section under light microscope: the pathological performance by thermal damage after MEA includes acute necrosis phase and subsequently chronic repair phase. The first phase often happened in one to three months postablation. Necrotic tissue could be divided into two layers: endometrium was coagulation necrosis, and the cells were disrupted into pieces in endothecium; superficial muscular layer underwent hyaloid degeneration accompanying with stromal inflammatory cells infiltrating in exothecium, while changes in deep muscle were not obvious. Chronic repair phase happened 3 months after ablation. It was observed that the necrotic tissue was thin with the formation of granulation tissue and collagen fiber. In some cases, regenerations of endometium and neovascularization could be found. 9 months after ablation, endometrial glands may be proliferated into multilayer with the appearance of cystic glandular hyperplasia and atypical hyperplasia.
3. The results of observing tissue ultrastructure under electron microscope: the ultrastructure changes after MEA also includes acute necrosis phase and chronic repair phase. In 3 months after ablation, the epithelial cells of endometrial glands were found degenerated and necrotic of different degree. Karyopyknosis, nuclear chromatin highly concentration, mitochondrion cavitation and extension, crista solution and disappearance partially could also be observed. Superficial muscle were lightly degenerated and necrotic. The nuclear chromatin slightly concentrated to the edge and the rough endoplasmic reticulum lightly extended. Deep muscle away from basal layer didn’t change obviously with complete nuclei in which the structures of nucleoli, nuclear membrane, mitochondria and endoplasmic reticulum were complete but the lysosome dilated slightly. Chronic repair phase following acute necrosis phase often happened 3 months postablation when tissue damage and chronic repair might coexist. In this phase, the endometrium may regenerate. Because of the high regenerated possibilities of epithelioglandular cells, the endometium could be repaired completely. As a result, it went to complete regeneration, even to atypical hyperplasia.
Conclusions
1.MEA in the treatment of menorrhagia is characterized by the marked long-term effectiveness.
2.Sexual functioning and health-realated quality significantly improved after surgery.
3.Incomplete removal of endometrium was the important factor in reducing the effiency , young age and adenomyosis showed significant increased risk of treatment failure.
4.Intrauterine adhensions aggravated gradually after MEA. Menstrual outcome is associated with postablation hysteroscopic appearance.
5. MEA can destroy the endometrium efficiently, reaching to basal layer. The pathological performance by thermal damage after MEA includes acute necrosis phase and subsequently chronic repair phase, some cases accompanied atypical hyperplasia.
月经过多是生育年龄和更年期妇女的常见病,占月经不调就诊病人的2.7%,传统治疗方法是以缓解症状为主的药物治疗和诊刮,无效者需子宫切除,其手术病率高达40 % ,死亡率6/ 10 000～11/ 10 000,术后恢复期还有卵巢早衰、精神性性功能障碍等远期并发症。微波子宫内膜去除术(microwave endometial ablation,MEA)是一项近年来妇科领域新兴的微创技术[1],在治愈疾病同时能够保留子宫,不破坏盆底解剖,不影响卵巢内分泌功能,已成为替代子宫切除治疗月经过多的安全、有效的方法。其机制是将微波能源导入宫腔,通过热损伤,引起子宫内膜全层热凝固、变性、坏死及纤维化,导致治疗性Ashermann综合征,以减少月经量,减轻痛经,从而缓解月经过多症状[2]。其主要优点是简便、安全、快捷。
国内外已有大量文献报道MEA治疗月经过多的近期疗效、安全性、并发症等,但对于MEA术后的远期疗效、患者生活质量,术后宫腔形态改变,微波作用组织后产生热损伤的病理机制等方面的报道十分有限。同时MEA术后仍有一定的复发率及子宫切除率,由于其破坏组织深度有限,对子宫腺肌症患者疗效欠佳,术后仍有妊娠和发生子宫内膜癌的可能,如何降低复发率、提高治愈率及患者生活质量,减少并发症,这些都是困扰临床工作的问题。
本研究通过随访MEA术后患者的月经变化情况、生活质量评分等,探讨MEA治疗月经过多的远期疗效;并观察子宫内膜受微波作用后组织形态学及细胞病理学改变,评价MEA安全性及远期疗效的病理机制。
资料与方法
1、研究对象选择2000年1月～2008年8月本院因月经过多经药物治疗无效而行MEA治疗的患者共334例,完成术后1个月至术后8年临床症状的随访,术后6个月、2年、5年各评估一次患者的生活质量、性功能。患者年龄29～59岁,平均(42.32±5.47)岁。术后随机抽取53例患者行宫腔镜检查,并取子宫内膜做光镜及电镜检查。
2、手术指征及诊断月经过多诊断标准为因月经过多影响正常生活和缺铁性贫血导致慢性衰弱,月经评分(pictorial blood loss assessment chart, PBAC)>100分者。全部患者符合以下条件:(1)药物治疗无效;(2)6个月内子宫内膜病理检查已排除子宫内膜癌及癌前病变;(3)无生育要求;(4)子宫<10周大小,宫腔深度<12cm。
3、方法
3.1设备:MEA治疗仪(英国Microsulis公司生产的9.2GHz、功率为30W的全自动监控仪)、宫腔镜和液体膨宫机(德国WOLF)。
3.2 MEA治疗方法:(1)子宫内膜预处理:术前连续4周口服丹那唑400-800mg/d,或采用促性腺激素释放激素(GnRH-a),部分患者行负压吸宫薄化子宫内膜。(2)麻醉:采用静脉麻醉。(3)手术操作:取膀胱截石位,常规消毒铺巾,扩张宫颈至9号,微波探头连接数据探头,置于宫底,启动温控系统,45秒内,子宫内膜达治疗温度(70-80℃),微波探头自宫底开始缓慢、连续地由一侧宫角移向另一侧宫角,然后缓慢将探头退出,全部宫腔均匀加热,探头达到宫颈内口时退出,治疗结束。
3.3宫腔镜检查方法:使用5%葡萄糖液作膨宫介质,膨宫压力控制在18. 0～20. 0 kPa。进入宫腔后,分别观察宫腔及双侧宫角,特别记录有无残留子宫内膜、宫腔粘连、粘连的部位及程度等;同时记录患者当时的月经情况。宫腔镜下取子宫内膜做病理切片行光镜及电镜检查。
所有患者术前均签署手术同意书,并经过医院伦理委员会通过。
4、随访
4.1月经情况:手术后1、3、6个月门诊复查,以后每年发问卷1次或电话访问,填写术后调查表。随访内容包括月经评分、月经周期、经期、痛经的改变等。术前及术后第3个月检测血常规。术后按月经状况分成5种类型:(1)闭经(Amenorrhea);(2)点状出血(Spotting);(3)少经量的月经周期(Hypomenorrhea);(4)如正常经量的月经周期(Eumenorrhea);(5)月经如术前(The same)。手术成功:包括闭经、点状出血、少经量及正常经量月经这四种月经状况。
4.2生活质量及性功能问卷调查:采用国际女性性功能评估量表(brief index of sexual function for women ,BISF-W)和健康相关生存质量量表(short-form health survey , SF-36)测试患者术前及术后6个月、24个月、60个月的各项得分。
5、统计学方法:采用SPSS13.0软件进行统计分析。(1)计量资料采用均数和标准差进行描述,然后使用t检验(或者配对t检验)进行分析;计数资料采用频数、频率进行简单描述,使用卡方检验进行分析。(2)使用重复测量资料的方差分析比较不同时间段的评分变化情况。(3)使用Cox回归模型(生存分析方法)研究影响疗效及随访结局的因素,先进行单因素的分析,如果单因素的P小于0.30,则纳入模型进行多因素分析。所有检验水准α均为0.05。
结果
一、远期临床疗效评价
1、治疗前后月经变化情况比较
(1)月经评分比较。术前PBAC评分平均为169±51.27,术后6个月、12个月、24个月、60个月、96个月分别为35.05±34.04, 28.70±32.72, 26.55±31.87, 17.25±27.43, 16.50±25.72,与术前比较,评分均明显降低,差异有统计学意义(p均<0.05),术后6个月开始PBAC评分基本稳定,并维持于较低的水平。
2)治疗前后血红蛋白的变化情况。术前患者血红蛋白平均值为(107.08±22.23)g/L,术后3个月血红蛋白平均值为(131.73±13.62)g/L,p<0.05,差别有统计学意义。
3)术后月经状况。334例中,术后闭经127例,占49.7%;经血明显减少,表现为规律的少量月经者60例,占18.0%;点滴出血59例,占17.7%;月经量正常者20例,占6.0%;经量无变化,如术前者29例,占8.7%;手术总成功率91.3%(305/334)。
4)术后1年,2年,6～8年患者的闭经率分别为35.5%,40.1%及60.9%,手术成功率分别为89.1%、92.9%及93.5%。
2、治疗前后性功能及生活质量评分比较
1)生活质量8个分量表:术后6个月、24个月、60个月评分,均较术前升高,差异有统计学意义(P<0.05)。
(2)性功能7个分量表:术后6个月、24个月、60个月评分,均较术前升高,差异有统计学意义(P<0.05)。
3、MEA术后并发症
(1)334例患者中,术后宫颈管粘连2例,予以扩宫后症状消失;宫腔积血2例,均行子宫切除。MEA术后妊娠共2例,3例次,均为宫内妊娠。其中1例术后2次妊娠,3例均行人工流产术。术后2年1例子宫内膜不典型增生。
(2)MEA术后再次手术情况。334例中,共9例(2.7%)再次行MEA术。其中8例因治疗无效再次MEA,1例患者要求闭经再次MEA。术后行子宫切除33例,子宫切除率9.88%。子宫切除的原因分别为:子宫腺肌症14例(42.4%),MEA术后复发9例(27.3%),子宫肌瘤8例(24.2%),宫腔积血2例(6.1%)。
4、影响MEA疗效的可能因素
使用Cox回归分析方法对随访结局进行生存分析,结果显示:患者的年龄(P =0.011)、宫腔深度(P =0.001)、合并子宫腺肌症(P =0.003)、手术持续时间(P =0.000)有统计学意义,术前子宫内膜厚度、经期持续时间、合并宫内占位病变、术前药物预处理无统计学意义(P均>0.05)。
二、MEA术后组织及细胞病理学改变
1、大体形态学变化。共53例患者MEA术后行宫腔镜检查。术后3个月内宫腔内主要为坏死脱落的内膜组织,月经改变为不规则点滴出血;术后半年,宫腔内可见肉芽组织形成,月经为规律的少量月经或闭经;术后1年,宫腔为瘢痕组织覆盖,月经变化主要为闭经;术后2年以上,宫腔镜下可见不同形态的宫腔粘连。共28例患者发生宫腔粘连(52.8%),其中1例为宫颈管粘连,12例(22.6%)宫底局灶性粘连,11例(20.7%)形成筒状宫腔, 4例(7.5%)宫腔完全粘连、闭锁;这28例中,22例月经表现为闭经,3例为不规则的点滴出血,3例为规律的少量月经。
2、组织病理学变化:表现为急性坏死期及随后的慢性修复期。急性坏死期主要是术后1个月～3个月,光镜下见坏死组织分两层:内层为子宫内膜凝固性坏死,细胞崩解成碎片状;外层为浅层平滑肌细胞透明样变性,伴间质红细胞渗出,深肌层平滑肌细胞未见明显改变。慢性修复期发生于术后3个月,可见肉芽组织产生,胶原纤维形成,部分病例可见子宫内膜再生、新生血管形成。子宫内膜腺体可增生为多层,个别病例发生不典型增生。
3、组织超微结构变化:也表现为急性坏死期及慢性修复期。术后3个月内见子宫内膜上皮细胞变性坏死:细胞核固缩,核染色质浓缩,线粒体扩张、空化,嵴大部分溶解消失;浅层平滑肌细胞轻度变性、坏死,核染色质边集,粗面内质网轻度扩张;深层子宫平滑肌细胞变化不明显,细胞核较完整,可见核仁、核膜,线粒体、内质网结构完整。急性坏死期后随之发生慢性修复,见于术后3个月,组织破坏与慢性修复可能并存,并可伴随子宫内膜的再生,由于腺上皮再生能力强,子宫内膜可完整修复,达到完全再生,甚至出现不典型增生。
结论
1、MEA治疗月经过多远期疗效显著。
2、MEA对月经过多患者性功能、生活质量均有正向影响。
3、宫角残留岛状子宫内膜是术后复发的重要原因。年龄、合并子宫腺肌症是影响MEA手术远期成功率的主要因素。
4、MEA术后宫腔粘连程度逐渐加重,术后月经改变与宫腔形态变化密切相关。
5、高频微波可有效破坏子宫内膜达基底层,对子宫肌层无创伤。MEA术后病理学改变为急性坏死期及随后的慢性修复期,个别病例可伴随子宫内膜的再生。
Perspective and objective
Menorrhagia is a common gynaecological problem affecting all ages from reproductive years and the climacteric period, accounted for 2.7% outpatients of irregular menstruation. The management options vary from medical to surgical treatment. The initial approach to treating menorrhagia is using medicines or curettage which relieve symptoms. For patients whose bleeding cannot be controlled with hormones, abdominal hysterectomy which offered a permanent cure may be necessary. However, hysterectomy is associated with early ovarian failure, incontinence many years later, and a small mortality risk of 6/ 10 000～11/ 10 000. Microwave endometial ablation (MEA) offers a less invasive surgical alternative than hysterectomy for menorrhagia which is a software-controlled device designed to ablate the endometrial lining of the uterus, it doesn’t influence ovarian function by retaining the uterus and maintaining the integrity of cervix uteri and vagina. The aim of this technique is destroying the basal layer of the endometrium. This result in a therapeutic Ashermann’s syndrom, alleviating menstrual symptoms. It has emerged as an effective and safe alternative to hysterectomy for women with menorrhagia.The technique is quick, safe, simple to learn and perform.
The pilot studies were focus on such aspects as short-period effectiveness, complications ,and safety of this system. But there were few reports on long-term clinical results , health-realated quality of life ,the hysteroscopic appearance of the uterine cavity and the incidence of postablation intrauterine adhensions after MEA, even fewer data were available regarding with thermal destruction and followed healing response to this type of tissue injury. At the same time, there was some definite incidence of postablative recurrence and hysterectomy after MEA, endometrial regrowth was seen in some post-ablation cases. Although rare, pregnancy and even endometrial cancer following endometrial ablation were possible. How to reduce the recurrence rate, increase the the cure rate and improve the quality of life, these are puzzled questions of clinical works.
We report the results of the change on the menstrual symptoms and the scores of health-realated quality of life, at eight years follow up, to explore the long-term effectiveness, the effects on health-realated quality of life of MEA, and also identify potential prognostic factors that will ensure successful menorrhagia treatment using MEA. We underwent outpatient hysteroscopy for assessment of the uterine cavity, and describe the pathologic effects and morphologic changes of thermal destruction of endometrium related to postablation time intervals, We sought to evaluate pathologic mechanism on the clinical efficiency and safety of this procedure.
Materials and methods
paticipants
From January 2000 to August 2008, 334 consecutive women who had undergone MEA, and who were followed up from 1 month to 8 years, sexual functioning and mental health were measured at 6 months, 2 years and 5 years, the median age was 42.32 years (range, 29 to 59 years). Fifty-three women underwent outpatient diagnostic hysteroscopy for assessment of the uterine cavity, subsequent endometrial sampling for light microscope and electron microscope.
Indication of the operation and the diagnosis of menorrhagia
Menorrhagia is defined as too much menstrual flow which influence normal life and chronic weekness as a result of iron deficiency anemia, a PBAC score (Pictorial Blood Assesment Charts) of 100 or higher was required. Women were eligible if they had heavy menstrual loss who were inefficient to medical treatments, no desire to have children bearing, no endometrial atypia on histopathologic examination 6 months before the ablation, and the uterus was not greater than 10 weeks’pregnancy size and 12 centimeter. Procedures
Some patients were given goserelin 3.6 mg or danazol to promote endometrial thinning, and underwent surgery 4 weeks later, another patients were given preoperative uterine curettage. Paticipants underwent ultrasonography for mesurement of endometrial thickness and identify of any fibroids in the endometrial cavity. For MEA procedure , a microwave probe of diameter 8 mm was inserted until the tip reached the uterine fundus. The footswitch was then activated. Once the temperature maintained at 75℃, the probe was moved slowly from side to side and withdrawn with the temperature maintained at 75℃-80℃. The technique effectively“paints”microwave energy with a maximum penetration of 6 mm over the whole surfuce of the uterine cavity. All procedures were done under intravenous anesthesia after cervical dilation to 9 mm.
Hysteroscopy was performed by using 5% glucose as the distending medium. The presence of residual endometrium and intrauterine adhesions was noted and their locations recorded. Menstrual patterns of the women at the time of assessment were also recorded, subsequent endometrial sampling for light microscope and electron microscope..
The study protocol was approved by the Clinical Research Ethics Subcommittee of Guang Dong province mother and children hospital, and written consent was obtained from each woman on recruitment.
Follow up
Clinical questionnaires assessing menstrual outcome which included PBAC score , menstrual cycle, dysmenorrhea and other changes were completed by participants. Hospital review was undertaken at 1, 3, 6 months , postal questionnaires or telephone interviews made every 1 year after operation. Routine blood test were made before and 3 months post-operation. Menstrual patterns were decribed as 5 types: (1) Amenorrhea; (2) Spotting; (3) Hypomenorrhea; (4) Eumenorrhea; (5) The same.
Sexual functioning measured by the 22-items Brief Index of Sexual Function for Women(BISF-W) and health-realated quality of life using the 36-Item Short-Form Health Survey(SF-36) was undertaken at 6 months, 2 years and 5 years after MEA. Statistical analysis
SPSS13.0 was used to analyze all the data. (1) Measurement data was described using mean and standard deviation, and then was analyzed by t-test or paired t-test. Categorical data was described using frequency or probability, and then was analyzed by Chi-square. (2) The scores in different times were analyzed by ANOVA of repeated measurement data. (3)In order to find out the influencing factors of survival time, Cox regression model was used. The variable with p value less than 0.3 in univariate model were entered into multi-variate model. All the significant was equal to 0.05. Results
Menstrual outcomes before and after MEA .
1. Menstrual score before and after MEA
(1) Menstrual blood loss by PBAC score before and in 6, 12, 24 ,60 and 96 months following MEA were 169±51.27 versus 35.05±34.04, 28.70±32.72, 26.55±31.87, 17.25±27.43, 16.50±25.72, respectively(P <0.05), PBAC score remained stable low-level from 6 months postoperation.
(2) Hemoglobin elevated from (107.08±22.23) g/ L preoperatively to (131.73±13.62)g/ L 3 months postoperatively , the difference was statistically significant (P < 0.05) .
(3) In all the 334 cases showed amenorrhea in 127 cases (49.7 %) , hypomenorrhea in 60 cases (18.0 %) , spotting in 59 cases (17.7 %), normal menstruation in 20 cases (6.0 %) and no improvement in 29 cases(8.7 %) , The total clinical effective rate was 91.3%.
(4)The amenorrhea rates and successful rates of 1-year,2-year and 6-8 years after MEA were 35.5%, 40.1% , 60.9%, and 89.1%, 92.9%, 93.5% respectively.
2.Sexual functioning and health-realated quality of life after MEA
7-Dimension of Sexual functioning and 8-Dimension of health-realated quality of life at 6 months, 24 months, 60 monthssignificantly improved after surgery, the difference was statistically significant (P <0.05).
3. Postoperative complications of MEA
In the 334 cases, 2 patients suffered endocervix adhesion which was disappeared by expanding the cervix. 2 women suffered intrauterine hematometra and required subsequent hysterectomy. 3 women were intrauterine pregnant after MEA and one of them had been pregnant twice. They all took artificial abortion finally. Atypical hyperplasia endometrium was found in one case 2 years after MEA.
4. Reoperation after MEA
In the 334 cases, 9 women (2.7%) had taken second operation after MEA. 8 of them were cured by MEA again because of the ineffective results for the first time. One woman required second MEA for amenorrhea. 33 women required subsequent hysterectomy with a rate of 9.88%, owing to adenomyosis (14 cases ,42.4%) , hysteromyoma (8 cases ,24.2%) , recurrent bleeding (9 cases ,27.3%), endometrial hematometra (2 cases ,6.1%).
5. Possible factor impacting the curative effect of MEA
Survival analysis of follow-up outcome was performed using Cox regression analysis. The results shows: Age (P=0.011), the depth of uterine cavity (P=0.001), adenomyosis (P=0.003), the duration of operation (P=0.000) are factors with statistical significance. However, endometrial thickness, the length of menstrual period before operation, complicating with intracavitary occupy lesion, preoperative medicine pretreatment have no statistical significance (P>0.05). Young age, complicating with adenomyosis, long operation time and deep uterine cavity all can increase the operation risk and influence the operation curative effect.
Pathological changes by thermal damage after MEA
1. Hysteroscopic appearance of the endometrial cavity following MEA. Second-look hysteroscopy at 3 months or less after ablation were always exhibited varied necrosis in the endometrium, destroyed endometrium and the debris were seen in the uterus. Most of them developed mimimal spotting during the menstural cycles. Grannulomatous reaction and fibrosis were present after 6 months postablation, the mestrual patterns of these women were regular reduction or cessation of mestrual flow. Post- hysteroscopy at 1 year after ablation showed fibrotic cavity, varied myofibrous scars can be seen. Most of the patients developed amenorrhea. All kinds of intrauterine adhensions were observed after 2 years or more postablation. Intrauterine adhesions were found in 28 women (52.8%); 1 had cervical adhesion(1.9%);12 had focal adhesions in the fundal area(22.6%);11 patients(20.7%) formed narrowed uterus which like a bucket ,whose endometrial cavity appeared totally scarred with bilateral stenotic ostia; 4(7.5%)had complete obliteration of the cavity. Of these 28 women, 22 had amenorrhea , 3 had spotting during menstruation and 2 had hypomenorrhea.
2. The results of observing HE staining section under light microscope: the pathological performance by thermal damage after MEA includes acute necrosis phase and subsequently chronic repair phase. The first phase often happened in one to three months postablation. Necrotic tissue could be divided into two layers: endometrium was coagulation necrosis, and the cells were disrupted into pieces in endothecium; superficial muscular layer underwent hyaloid degeneration accompanying with stromal inflammatory cells infiltrating in exothecium, while changes in deep muscle were not obvious. Chronic repair phase happened 3 months after ablation. It was observed that the necrotic tissue was thin with the formation of granulation tissue and collagen fiber. In some cases, regenerations of endometium and neovascularization could be found. 9 months after ablation, endometrial glands may be proliferated into multilayer with the appearance of cystic glandular hyperplasia and atypical hyperplasia.
3. The results of observing tissue ultrastructure under electron microscope: the ultrastructure changes after MEA also includes acute necrosis phase and chronic repair phase. In 3 months after ablation, the epithelial cells of endometrial glands were found degenerated and necrotic of different degree. Karyopyknosis, nuclear chromatin highly concentration, mitochondrion cavitation and extension, crista solution and disappearance partially could also be observed. Superficial muscle were lightly degenerated and necrotic. The nuclear chromatin slightly concentrated to the edge and the rough endoplasmic reticulum lightly extended. Deep muscle away from basal layer didn’t change obviously with complete nuclei in which the structures of nucleoli, nuclear membrane, mitochondria and endoplasmic reticulum were complete but the lysosome dilated slightly. Chronic repair phase following acute necrosis phase often happened 3 months postablation when tissue damage and chronic repair might coexist. In this phase, the endometrium may regenerate. Because of the high regenerated possibilities of epithelioglandular cells, the endometium could be repaired completely. As a result, it went to complete regeneration, even to atypical hyperplasia.
Conclusions
1.MEA in the treatment of menorrhagia is characterized by the marked long-term effectiveness.
2.Sexual functioning and health-realated quality significantly improved after surgery.
3.Incomplete removal of endometrium was the important factor in reducing the effiency , young age and adenomyosis showed significant increased risk of treatment failure.
4.Intrauterine adhensions aggravated gradually after MEA. Menstrual outcome is associated with postablation hysteroscopic appearance.
5. MEA can destroy the endometrium efficiently, reaching to basal layer. The pathological performance by thermal damage after MEA includes acute necrosis phase and subsequently chronic repair phase, some cases accompanied atypical hyperplasia.
引文
1. Sculpher MJ, Dwyer N, Byford S et al. Randomised trial comparing hysterectomy and transcervical endometrial resection: Effect on health related quality of life and costs two years after surgery. Br J Obset Gynaecol 1996,103:142–149.
2. Hill DJ, Maher P. Intrauterine surgery using electrocautery. Aust NZ J Obstet Gynaecol , 1990 ,30 :145-146.
3.罗喜平.微波子宫内膜去除术的临床应用.中华妇产科杂志,2001,36:636-637.
4. Cahan WG, Brockunier A Jr. Cryosurgery of the uterine cavity. Am J Obstet Gy- necol , 1967 , 99 :138-153.
5. Goldrath MH, Fuller TA,Segal S. Laser photovaporization of endometrium for the treatment of menorrhagia. Am J Obstet Gynecol ,1981 , 140 :14-19.
6. DeCherney A, Polan ML. Hysteroscopic management of intrauterine lesions and intractable uterine bleeding. Obstet Gynecol , 1983 , 61 :392-397.
7. Vancaille TG. Electro coagulation of the endometrium with the ball - end resectoscope. Obstet Gynecol , 1989 , 74 :425-427.
8.夏恩兰.宫腔镜手术的进展与前景.中华妇产科杂志,1997 , 32 :259.
9. Phipps JH, Lewis BV, Roberts T, et al . Treatment of functional menorrhagia by radiofrequency-induced thermal endometrial ablation.Lancet ,1990, 335 :374-376.
10. Jack SA, Cooper KG. Microwave endometrial ablation: an overview.Rev Gynaecol Practice, 2005, 5: 32 - 38.
11. Sharp NC, Cronic N, Feldberg I ,et al. Microwaves for menorrhagia: a new fast technique for endometrial ablation. Lancet, 1995, 346:1003-1004.
12. Hodgson DA , Feldberg IB ,Sharp N ,et al. Microwave endometial ablation :devolopment, clinical trials and outcomes at three years .Br J Obstet Gynecol ,1999 ,106:684-694.
13. Cooper KG, Bain C, Lawrie L, et al. A randomised comparison of microwave endometrial ablation with transcervical resection of the endometrium; follow up at a minimum of five years. BJOG, 2005, 112:470-475.
14. Anderson TL, Cooper JM, Fortin CA, et al. Microwave endometrial ablation vs. rollerball electroablation for menorrhagia: a multicenter randomized trial. J Am Assoc Gynecol Laparosc, 2004 ,11:394-403.
15. Garside R, Stein K, Wyatt K, et al. The effectiveness and cost-effectiveness of microwave and thermal balloon endometrial ablation for heavy menstrual bleeding: a systematic review and economic modelling. Health Technol Assess 2004,8: iii1–iii155.
16. Huang MC, Chen CP, Su TH, et al.The safety and efficacy of microwave endometrial ablation after endometrial curettage without hormonal pretreatment.Taiwan J Obstet Gynecol. 2007 ,46:152-156.
17. Rubin G, Wortman M, Kouides PA. Endometrial ablation for von Willebrand disease-related menorrhagia-experience with seven cases[ J ]. Haemophilia, 2004, 10: 477-482.
18.王惠兰,张霞,陈素琴,等.微波子宫内膜去除术治疗异常子宫出血的临床观察.中华妇产科杂志,2005,40:435-438.
19. Qian Y, Gan N, Zhou J, et al. Microwave endometrial ablation for menorrhagia in patients with systemic disorders. Int J Gynaecol Obstet, 2005 ,91:32-35.
20. Pakin DE. Microwave endometrial ablation(MEA): a safe technique? Complication data from a prospective series of 1400 cases .Gynaecol Endosc ,2000, 9:385-386.
21. Feldberg IB , Cronic NJ . A 9.2 GHz microwave application for the treatment of menorrhagia . IEEE MTT-S Dig ,1998, 2:755-758.
22.董晓瑜,王惠兰,韩翠欣,等.微波子宫内膜去除术前刮宫内膜预处理的临床及实验研究.中国微创外科杂志,2007,7:307-309.
23. Arthur M, McCausland AM, McCausland VM. Freqnency of symptomatic corneal hematonetra and postablation tubal sterilization syndrome after total rollerball endometrial ablation: A 10-year follow-up. Am J obster Gynecol, 2002,186:1274-1283.
24. Lo JS, Pickersgill A. Pregnancy after endometrial ablation: English literature review and case report. J Minim Invasive Gynecol, 2006, 13:88-91.
25. Palep-Singh M, Angala P, Seela R, et al. Impact of microwave endometrial ablation in the management of subsequent unplanned pregnancy. J Minim Invasive Gynecol, 2007 ,14:365-366.
26. Sagiv R, Ben-Shem E, Condrea A, et al. Endometrial carcinoma after endometrial resection for dysfunctional uterine bleeding. Obstet Gynecol, 2005 ,106:1174-1176.
27. Magos AM , Baumann R, Lockwood GM , et al. Experience with the first 250 endometrial resection for menorrhagia. Lancet, 1992, 337: 1074.
28. Bae IH, Pagedas AC, Barr CA , et al. Retrospective analysis of 305 consecutive cases of endometrial ablation and partial endomyometrial resection. J Am Asso s Gyneco lL aparo sc, 1996, 3: 549.
29. Wortmann M , Daggett A. Hysteroscopic endometrial resection: a new technique for treatment of menorrhagia.Obstet Gyneco l, 1994, 83: 295.
30. Tulandi T. Images in reproductive medicine. Endometrial cavity after microwave endometrial ablation. Fertil Steril, 2000, 73:598-601.
31.罗喜平.微波子宫内膜去除术后宫腔影像观察.广东医学,2004,25:155-156.
32.陈玉清,姚书忠,刘栋擎.采用高频微波技术治疗月经过多病理机制的探讨.中山大学学报,2005,26:219-222.
33. Donnez J , Vilos G, GannonMJ , et al. Goserelin acetate (zoladex) plus endometrial ablation for dysfunctional uterine bleeding : a 3-year follow-up evaluation.Fertil Steril , 2001, 75 : 620-622.
34. Bongers MY, Mol BW, Brolmann HA. Prognostic factors for the success of thermal balloon ablation in the treatment of menorrhagoia.Obstet Gynecol, 2002 , 99: 1060-1066.
35. Vilos CA ,Vilos EA, Pendlev L. Endometrial ablation with a thermal balloon for treatment of menorrhagia. J Am Assos Gynecol Laparosc, 1996, 3: 549.
36. Higham J M, O′Brien PM, Shaw RW. Assessment of menstrual blood loss using a pictorial chart [ J ]. Br J Obstet Gynecol , 1990 , 97 : 734-739.
37. Mazer NA, Leiblum SR, Rosen RC. The Brief Index of Sexual Functioning for Women (BISF-W): a new scoring algorithm and comparison of normative andsurgically menopausal populations. Menopause, 2000,7:350-363.
38. Jenkinson C, Coulter A, Wright L.Short form 36(SF36) health survey questionnaire:normative data for adults of working age. BMJ, 1993,306:1437-40.
39. Korn A P. Endometrial cryoablation and thermal ablation [J].Clin Obstet Gynecol , 2000 ,43 : 575.
40. Dovnes E , O’Donovan P. Microwave endometrial ablation in the management of menorrhagia : current status[J ].Curr Opin Obstet Gynecol , 2000 ,12 :293.
41. United States Food and Drug Administration. MAUDE Database.United States Food and Drug Administration MAUDE database, July 24, 2003, 2004.
42. Milligan MP , Etotowo GA. Microwave endometrial ablation for menerrhagia. J Obstet Gynecol , 1999 , 19 :496-499.
43. Neis KJ , Brandner P. Adenomyosis and endometrial ablation Gynaecol Endosc ,2000 , 99: 141-145.
44. Francisco T , Pablo G, Alicia U. Morphological changes in hysterectomies after endometrial ablation. Hum Reprod, 1999,14:1473-1477.
45. Davis JR, Maynard KK, Brainard CP, Purdon TF, Sibley MA, King DD. Effects of thermal endometrial ablation. Clinicopathologic correlations. Am J Clin Pathol 1998,109:96–100.
46. Colgan TJ, Shah R, Leyland N. Post-hysteroscopic ablation reaction: a histopathologic study of the effects of electrosurgical ablation. Int J Gynecol Pathol 1999,18:325–331.
47. Neuwirth RS. Gynecologic surgery and adhesions prevention. Asherman’s syndrome. Prog Clin Biol Res 1993;381:187–190.
48. Goldrath MH. Hsteroscopic endometrial ablation. Obstet Gynaecol Clin North Am 1995,22:559-572.
49. Cooper JM, Brady RM. Late complication of operative hysteroscopy. Obstet Gynecol Clin North Am, 2000,27:367-374.
1.罗喜平.微波子宫内膜去除术的临床应用.中华妇产科杂志,2001,36:636-637.
2. Jack SA, Cooper KG. Microwave endometrial ablation: an overview.Rev Gynaecol Practice, 2005, 5: 32 - 38.
3. Sharp NC, Cronic N, Feldberg I ,et al. Microwaves for menorrhagia: a new fast technique for endometrial ablation. Lancet, 1995, 346:1003-1004.
4. Hodgson DA , Feldberg IB ,Sharp N ,et al . Microwave endometial ablation :devolopment ,clinical trials and outcomes at three years .Br J Obstet Gynecol ,1999 ,106:684-694.
5. Cooper KG, Bain C, Parkin DE. Comparison of microwave endometrial ablation and transcervical resection of the endometrium for treatment of heavy menstrual loss: a randomized trial. Lancet ,1999,354(9193):1859-1863.
6. Cooper KG, Bain C, Lawrie L, et al. A randomised comparison of microwave endometrial ablation with transcervical resection of the endometrium; follow up at a minimum of five years. BJOG, 2005 ,112(4):470-475.
7. Anderson TL, Cooper JM, Fortin CA, et al. Microwave endometrial ablation vs. rollerball electroablation for menorrhagia: a multicenter randomized trial. J Am Assoc Gynecol Laparosc, 2004 ,11(3):394-403.
8. Henshaw R,Coyle C ,Low S, et al.A retrospective cohort study comparing microwave endometrial ablation with levonorgestrel-releasing intrauterine device in the management of heavy menstrual bleeding. Aust NZ J Obstet Gynecol ,2002, 42(2):205-209.
9. Wallage S , Cooper KG, Graham WG, et al.A randomized control trial comparing the acceptability of local anaesthesia plus or minus sedation and general anaesthesia for microwave endometrial ablation. Br J Obstet Gynecol, 2003,110:799-807.
10. Jack SA, Cooper KG, Seymour J,et al. A randomised controlled trial of microwave endometrial ablation without endometrial preparation in the outpatient setting: patient acceptability, treatment outcome and costs. BJOG, 2005 ,112(8):1109-1116.
11.董晓瑜,王惠兰,韩翠欣,等.微波子宫内膜去除术前刮宫内膜预处理的临床及实验研究.中国微创外科杂志,2007,7(4):307-309.
12. Huang MC, Chen CP, Su TH, et al.The safety and efficacy of microwave endometrial ablation after endometrial curettage without hormonal pretreatment.Taiwan J Obstet Gynecol. 2007 ,46(2):152-156.
13. Garside R, Stein K, Wyatt K, et al. The effectiveness and cost-effectiveness of microwave and thermal balloon endometrial ablation for heavy menstrual bleeding: a systematic review and economic modelling. Health Technol Assess 2004;8(3): iii1–iii155.
14. Rubin G, Wortman M, Kouides PA. Endometrial ablation for von Willebrand disease-related menorrhagia-experience with seven cases[ J ]. Haemophilia, 2004, 10 (5) : 477-482.
15.王惠兰,张霞,陈素琴,等.微波子宫内膜去除术治疗异常子宫出血的临床观察.中华妇产科杂志,2005,40(7):435-438.
16. Qian Y, Gan N, Zhou J, et al. Microwave endometrial ablation for menorrhagia in patients with systemic disorders. Int J Gynaecol Obstet, 2005 ,91(1):32-35.
17. Pakin DE. Microwave endometrial ablation(MEA): a safe technique? Complication data from a prospective series of 1400 cases .Gynaecol Endosc ,2000,9(6):385-386.
18. Feldberg IB , Cronic NJ . A 9.2 GHz microwave application for the treatment of menorrhagia . IEEE MTT-S Dig ,1998, 2:755-758.
19.董晓瑜,王惠兰,韩翠欣,等.微波子宫内膜去除术的安全性及其相关因素研究.中国实用妇科与产科杂志,2006,22(3):206-208.
20. Francisco T , Pablo G, Alicia U. Morphological changes in hysterectomies after endometrial ablation. Hum Reprod, 1999,14:1473-1477.
21.陈玉清,姚书忠,刘栋擎.采用高频微波技术治疗月经过多病理机制的探讨.中山大学学报,2005,26(2):219-222.
22. Arthur M, McCausland AM, McCausland VM. Freqnency of symptomatic corneal hematonetra and postablation tubal sterilization syndrome after total rollerball endometrial ablation: A 10-year follow-up. Am J obster Gynecol, 2002,186:1274-1283.
23. McCausland AM, McCausland VM. Long-term complications of endometrial ablation: cause, diagnosis, treatment, and prevention. J Minim Invasive Gynecol, 2007 ,14(4):399-406.
24. Lo JS, Pickersgill A. Pregnancy after endometrial ablation: English literature review and case report. J Minim Invasive Gynecol, 2006 ,13(2):88-91.
25. Xia EL, Li TC, Yu D, et al. The occurrence and outcome of 39 pregnancies after 1621 cases of transcervical resection of endometrium. Hum Reprod, 2006,21:3282-3286.
26. Palep-Singh M, Angala P, Seela R, et al. Impact of microwave endometrial ablation in the management of subsequent unplanned pregnancy. J Minim Invasive Gynecol, 2007,14(3):365-366.
27. Margolis MT,Thoen LD, Boike GM. Asymptomatic endometrial carcinoma after endometrial ablation. Int J Gynecol Obstet, 1995,51:255-258.
28. Sagiv R, Ben-Shem E, Condrea A, et al. Endometrial carcinoma after endometrial resection for dysfunctional uterine bleeding. Obstet Gynecol, 2005 ,106(5 ):1174-1176.
29. Tulandi T. Images in reproductive medicine. Endometrial cavity after microwave endometrial ablation. Fertil Steril, 2000, 73:598-601.
30.罗喜平.微波子宫内膜去除术后宫腔影像观察.广东医学,2004,25(2):155-156.
31. Kooy J, Taylor NH, Healy DL, et al. Endothelial cell proliferation in the endometrium of women with menorrhagia and in women following endometrial ablation. Hum Reprod, 1996,11:1067-1072.
32. National Institute for Clinical Excellence. Fluid-filled thermal balloon and microwave endometrial ablation for heavy menstrual bleeding. London: National Institute for Clinical Excellence, 2004 [Technology Appraisal Guidance No. 78].
2. Hill DJ, Maher P. Intrauterine surgery using electrocautery. Aust NZ J Obstet Gynaecol , 1990 ,30 :145-146.
3.罗喜平.微波子宫内膜去除术的临床应用.中华妇产科杂志,2001,36:636-637.
4. Cahan WG, Brockunier A Jr. Cryosurgery of the uterine cavity. Am J Obstet Gy- necol , 1967 , 99 :138-153.
5. Goldrath MH, Fuller TA,Segal S. Laser photovaporization of endometrium for the treatment of menorrhagia. Am J Obstet Gynecol ,1981 , 140 :14-19.
6. DeCherney A, Polan ML. Hysteroscopic management of intrauterine lesions and intractable uterine bleeding. Obstet Gynecol , 1983 , 61 :392-397.
7. Vancaille TG. Electro coagulation of the endometrium with the ball - end resectoscope. Obstet Gynecol , 1989 , 74 :425-427.
8.夏恩兰.宫腔镜手术的进展与前景.中华妇产科杂志,1997 , 32 :259.
9. Phipps JH, Lewis BV, Roberts T, et al . Treatment of functional menorrhagia by radiofrequency-induced thermal endometrial ablation.Lancet ,1990, 335 :374-376.
10. Jack SA, Cooper KG. Microwave endometrial ablation: an overview.Rev Gynaecol Practice, 2005, 5: 32 - 38.
11. Sharp NC, Cronic N, Feldberg I ,et al. Microwaves for menorrhagia: a new fast technique for endometrial ablation. Lancet, 1995, 346:1003-1004.
12. Hodgson DA , Feldberg IB ,Sharp N ,et al. Microwave endometial ablation :devolopment, clinical trials and outcomes at three years .Br J Obstet Gynecol ,1999 ,106:684-694.
13. Cooper KG, Bain C, Lawrie L, et al. A randomised comparison of microwave endometrial ablation with transcervical resection of the endometrium; follow up at a minimum of five years. BJOG, 2005, 112:470-475.
14. Anderson TL, Cooper JM, Fortin CA, et al. Microwave endometrial ablation vs. rollerball electroablation for menorrhagia: a multicenter randomized trial. J Am Assoc Gynecol Laparosc, 2004 ,11:394-403.
15. Garside R, Stein K, Wyatt K, et al. The effectiveness and cost-effectiveness of microwave and thermal balloon endometrial ablation for heavy menstrual bleeding: a systematic review and economic modelling. Health Technol Assess 2004,8: iii1–iii155.
16. Huang MC, Chen CP, Su TH, et al.The safety and efficacy of microwave endometrial ablation after endometrial curettage without hormonal pretreatment.Taiwan J Obstet Gynecol. 2007 ,46:152-156.
17. Rubin G, Wortman M, Kouides PA. Endometrial ablation for von Willebrand disease-related menorrhagia-experience with seven cases[ J ]. Haemophilia, 2004, 10: 477-482.
18.王惠兰,张霞,陈素琴,等.微波子宫内膜去除术治疗异常子宫出血的临床观察.中华妇产科杂志,2005,40:435-438.
19. Qian Y, Gan N, Zhou J, et al. Microwave endometrial ablation for menorrhagia in patients with systemic disorders. Int J Gynaecol Obstet, 2005 ,91:32-35.
20. Pakin DE. Microwave endometrial ablation(MEA): a safe technique? Complication data from a prospective series of 1400 cases .Gynaecol Endosc ,2000, 9:385-386.
21. Feldberg IB , Cronic NJ . A 9.2 GHz microwave application for the treatment of menorrhagia . IEEE MTT-S Dig ,1998, 2:755-758.
22.董晓瑜,王惠兰,韩翠欣,等.微波子宫内膜去除术前刮宫内膜预处理的临床及实验研究.中国微创外科杂志,2007,7:307-309.
23. Arthur M, McCausland AM, McCausland VM. Freqnency of symptomatic corneal hematonetra and postablation tubal sterilization syndrome after total rollerball endometrial ablation: A 10-year follow-up. Am J obster Gynecol, 2002,186:1274-1283.
24. Lo JS, Pickersgill A. Pregnancy after endometrial ablation: English literature review and case report. J Minim Invasive Gynecol, 2006, 13:88-91.
25. Palep-Singh M, Angala P, Seela R, et al. Impact of microwave endometrial ablation in the management of subsequent unplanned pregnancy. J Minim Invasive Gynecol, 2007 ,14:365-366.
26. Sagiv R, Ben-Shem E, Condrea A, et al. Endometrial carcinoma after endometrial resection for dysfunctional uterine bleeding. Obstet Gynecol, 2005 ,106:1174-1176.
27. Magos AM , Baumann R, Lockwood GM , et al. Experience with the first 250 endometrial resection for menorrhagia. Lancet, 1992, 337: 1074.
28. Bae IH, Pagedas AC, Barr CA , et al. Retrospective analysis of 305 consecutive cases of endometrial ablation and partial endomyometrial resection. J Am Asso s Gyneco lL aparo sc, 1996, 3: 549.
29. Wortmann M , Daggett A. Hysteroscopic endometrial resection: a new technique for treatment of menorrhagia.Obstet Gyneco l, 1994, 83: 295.
30. Tulandi T. Images in reproductive medicine. Endometrial cavity after microwave endometrial ablation. Fertil Steril, 2000, 73:598-601.
31.罗喜平.微波子宫内膜去除术后宫腔影像观察.广东医学,2004,25:155-156.
32.陈玉清,姚书忠,刘栋擎.采用高频微波技术治疗月经过多病理机制的探讨.中山大学学报,2005,26:219-222.
33. Donnez J , Vilos G, GannonMJ , et al. Goserelin acetate (zoladex) plus endometrial ablation for dysfunctional uterine bleeding : a 3-year follow-up evaluation.Fertil Steril , 2001, 75 : 620-622.
34. Bongers MY, Mol BW, Brolmann HA. Prognostic factors for the success of thermal balloon ablation in the treatment of menorrhagoia.Obstet Gynecol, 2002 , 99: 1060-1066.
35. Vilos CA ,Vilos EA, Pendlev L. Endometrial ablation with a thermal balloon for treatment of menorrhagia. J Am Assos Gynecol Laparosc, 1996, 3: 549.
36. Higham J M, O′Brien PM, Shaw RW. Assessment of menstrual blood loss using a pictorial chart [ J ]. Br J Obstet Gynecol , 1990 , 97 : 734-739.
37. Mazer NA, Leiblum SR, Rosen RC. The Brief Index of Sexual Functioning for Women (BISF-W): a new scoring algorithm and comparison of normative andsurgically menopausal populations. Menopause, 2000,7:350-363.
38. Jenkinson C, Coulter A, Wright L.Short form 36(SF36) health survey questionnaire:normative data for adults of working age. BMJ, 1993,306:1437-40.
39. Korn A P. Endometrial cryoablation and thermal ablation [J].Clin Obstet Gynecol , 2000 ,43 : 575.
40. Dovnes E , O’Donovan P. Microwave endometrial ablation in the management of menorrhagia : current status[J ].Curr Opin Obstet Gynecol , 2000 ,12 :293.
41. United States Food and Drug Administration. MAUDE Database.United States Food and Drug Administration MAUDE database, July 24, 2003, 2004.
42. Milligan MP , Etotowo GA. Microwave endometrial ablation for menerrhagia. J Obstet Gynecol , 1999 , 19 :496-499.
43. Neis KJ , Brandner P. Adenomyosis and endometrial ablation Gynaecol Endosc ,2000 , 99: 141-145.
44. Francisco T , Pablo G, Alicia U. Morphological changes in hysterectomies after endometrial ablation. Hum Reprod, 1999,14:1473-1477.
45. Davis JR, Maynard KK, Brainard CP, Purdon TF, Sibley MA, King DD. Effects of thermal endometrial ablation. Clinicopathologic correlations. Am J Clin Pathol 1998,109:96–100.
46. Colgan TJ, Shah R, Leyland N. Post-hysteroscopic ablation reaction: a histopathologic study of the effects of electrosurgical ablation. Int J Gynecol Pathol 1999,18:325–331.
47. Neuwirth RS. Gynecologic surgery and adhesions prevention. Asherman’s syndrome. Prog Clin Biol Res 1993;381:187–190.
48. Goldrath MH. Hsteroscopic endometrial ablation. Obstet Gynaecol Clin North Am 1995,22:559-572.
49. Cooper JM, Brady RM. Late complication of operative hysteroscopy. Obstet Gynecol Clin North Am, 2000,27:367-374.
1.罗喜平.微波子宫内膜去除术的临床应用.中华妇产科杂志,2001,36:636-637.
2. Jack SA, Cooper KG. Microwave endometrial ablation: an overview.Rev Gynaecol Practice, 2005, 5: 32 - 38.
3. Sharp NC, Cronic N, Feldberg I ,et al. Microwaves for menorrhagia: a new fast technique for endometrial ablation. Lancet, 1995, 346:1003-1004.
4. Hodgson DA , Feldberg IB ,Sharp N ,et al . Microwave endometial ablation :devolopment ,clinical trials and outcomes at three years .Br J Obstet Gynecol ,1999 ,106:684-694.
5. Cooper KG, Bain C, Parkin DE. Comparison of microwave endometrial ablation and transcervical resection of the endometrium for treatment of heavy menstrual loss: a randomized trial. Lancet ,1999,354(9193):1859-1863.
6. Cooper KG, Bain C, Lawrie L, et al. A randomised comparison of microwave endometrial ablation with transcervical resection of the endometrium; follow up at a minimum of five years. BJOG, 2005 ,112(4):470-475.
7. Anderson TL, Cooper JM, Fortin CA, et al. Microwave endometrial ablation vs. rollerball electroablation for menorrhagia: a multicenter randomized trial. J Am Assoc Gynecol Laparosc, 2004 ,11(3):394-403.
8. Henshaw R,Coyle C ,Low S, et al.A retrospective cohort study comparing microwave endometrial ablation with levonorgestrel-releasing intrauterine device in the management of heavy menstrual bleeding. Aust NZ J Obstet Gynecol ,2002, 42(2):205-209.
9. Wallage S , Cooper KG, Graham WG, et al.A randomized control trial comparing the acceptability of local anaesthesia plus or minus sedation and general anaesthesia for microwave endometrial ablation. Br J Obstet Gynecol, 2003,110:799-807.
10. Jack SA, Cooper KG, Seymour J,et al. A randomised controlled trial of microwave endometrial ablation without endometrial preparation in the outpatient setting: patient acceptability, treatment outcome and costs. BJOG, 2005 ,112(8):1109-1116.
11.董晓瑜,王惠兰,韩翠欣,等.微波子宫内膜去除术前刮宫内膜预处理的临床及实验研究.中国微创外科杂志,2007,7(4):307-309.
12. Huang MC, Chen CP, Su TH, et al.The safety and efficacy of microwave endometrial ablation after endometrial curettage without hormonal pretreatment.Taiwan J Obstet Gynecol. 2007 ,46(2):152-156.
13. Garside R, Stein K, Wyatt K, et al. The effectiveness and cost-effectiveness of microwave and thermal balloon endometrial ablation for heavy menstrual bleeding: a systematic review and economic modelling. Health Technol Assess 2004;8(3): iii1–iii155.
14. Rubin G, Wortman M, Kouides PA. Endometrial ablation for von Willebrand disease-related menorrhagia-experience with seven cases[ J ]. Haemophilia, 2004, 10 (5) : 477-482.
15.王惠兰,张霞,陈素琴,等.微波子宫内膜去除术治疗异常子宫出血的临床观察.中华妇产科杂志,2005,40(7):435-438.
16. Qian Y, Gan N, Zhou J, et al. Microwave endometrial ablation for menorrhagia in patients with systemic disorders. Int J Gynaecol Obstet, 2005 ,91(1):32-35.
17. Pakin DE. Microwave endometrial ablation(MEA): a safe technique? Complication data from a prospective series of 1400 cases .Gynaecol Endosc ,2000,9(6):385-386.
18. Feldberg IB , Cronic NJ . A 9.2 GHz microwave application for the treatment of menorrhagia . IEEE MTT-S Dig ,1998, 2:755-758.
19.董晓瑜,王惠兰,韩翠欣,等.微波子宫内膜去除术的安全性及其相关因素研究.中国实用妇科与产科杂志,2006,22(3):206-208.
20. Francisco T , Pablo G, Alicia U. Morphological changes in hysterectomies after endometrial ablation. Hum Reprod, 1999,14:1473-1477.
21.陈玉清,姚书忠,刘栋擎.采用高频微波技术治疗月经过多病理机制的探讨.中山大学学报,2005,26(2):219-222.
22. Arthur M, McCausland AM, McCausland VM. Freqnency of symptomatic corneal hematonetra and postablation tubal sterilization syndrome after total rollerball endometrial ablation: A 10-year follow-up. Am J obster Gynecol, 2002,186:1274-1283.
23. McCausland AM, McCausland VM. Long-term complications of endometrial ablation: cause, diagnosis, treatment, and prevention. J Minim Invasive Gynecol, 2007 ,14(4):399-406.
24. Lo JS, Pickersgill A. Pregnancy after endometrial ablation: English literature review and case report. J Minim Invasive Gynecol, 2006 ,13(2):88-91.
25. Xia EL, Li TC, Yu D, et al. The occurrence and outcome of 39 pregnancies after 1621 cases of transcervical resection of endometrium. Hum Reprod, 2006,21:3282-3286.
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