Long Term Outcomes, Pathologic Mechanism Following Microwave Endometrial Ablation

Perspective and objectiveMenorrhagia 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 methodspaticipantsFrom 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 menorrhagiaMenorrhagia 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. ProceduresSome 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 upClinical 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 analysisSPSS13.0 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. ResultsMenstrual 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 MEA7-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 MEAIn 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 MEAIn 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 MEASurvival 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 MEA1. 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.Conclusions1.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.