{"paper_id":"188f7663-e11c-46c3-9a8b-f0323aa48d43","body_text":"Abnormal uterine bleeding (AUB), one of the\nmost common problems of reproductive age women,\naccounts for about 30% of outpatient gynecological\nvisits. AUB is defined as a heavy menstrual bleeding\nor an extra-menstrual bleeding ( 1 ,  2 ). Mahoney and\ncolleagues attributed 2.3% of hysterectomies and 25% of\ngynecological surgeries to bleeding. Endometrial ablation\ncan be used as a treatment for AUB in patients who have not\nresponded to medication, where the endometrial cavity is\nnormal and without sub-mucosal leiomyoma, endometrial hyperplasia, or malignancy. Different methods are used\nto ablate the endometrium, which generally differs in the\ntype of device, energy source, and endometrial ablation\nmechanism. These techniques include warm air balloon\nablation, intrauterine warm saline insertion, cryo-ablation\nwith a cryo-probe, microwave endometrial ablation, and\nthe use of radiofrequency electromagnetic energy ( 2 ,  3 ).\nEndometrial ablation with Cavaterm is considered as a safe\nsurgical procedure with minimal bleeding complications\nand systemic adverse events. This surgical approach\nbenefits from less technical proficiency and facilitates post-operative follow-up. Furthermore, the Cavaterm\nprocedure does not only take less time than most other\nalternative treatments, but also can be quickly learned\nby surgeons in training. There are several reports about\nsuccess rates and side effects of this approach, that makes\ncomparison difficult, particularly due to heterogeneity in\nimplementation methods and/or study populations with\ndifferent AUB background. A dual comparison between\nablation methods will be more informative for clinicians\nto select the best choice of therapeutic strategies. This\nexperimental study compares the efficacy, safety, and\ncomplications of endometrial ablation by the Cavaterm\nmethod with the hysteroscopy loop resection method to\ntreat abnormal uterine bleeding.\n\nThe present study is an open-label, randomized clinical\ntrial performed in the two hospitals, Shahid Akbarabadi\nand Hazrat Rasoul Akram hospitals, Tehran, Iran, from\nDecember 2019 to October 2020.\nThe study was approved by the Iran University of\nMedical Science Ethical Committee (IR.IUMS.FMD.\nREC.1398.437) and was registered retrospectively as\nIRCT20220210053986N1 in the Iranian registry of\nclinical trials on 2022/03/06.\nThe inclusion criteria were included:\n1. Non-nulliparous affected of 35 to 55 year age range\nwith a complaint of AUB\n2. No sign of malignancy in the pathology specimen that\nwas prepared by pipple or curettage\n3. Inadequate response drug therapy following of, an\nup to 18 months of oral contraceptive pills or various\nprogesterone drugs)\n4. Not trying to conceive (completion of fertility)\n5. Unwillingness for a hysterectomy due to various\nreasons [including patient dissatisfaction with the\nremoval of the uterus, high risk of surgery due to\nunderlying disease and high body mass index (BMI)].\n6. The exclusion criteria comprised grade 0 and 1\nsubmucosal myoma in the uterine ultrasound, uterine\ncavity distortion, and uterine size higher than 12\nweeks.\nPatients were randomly divided into two groups by\nsimple randomization using Excel software and using\nthe RAND function. Excel software creates a column of\n100 numbers, equal groups for Cavaterm group (n=50)\nand hysteroscopy group (n=50). The RAND function\ngenerated parallel columns contain of one hundred\nrandom numbers. After arranging the randomized\ncolumn, a random sequence was prepared, and patients\nwere divided into two groups, respectively. Four-digit\nunique codes were assigned to each participant to conceal\nthe allocation. The allocation codes were put in opaque\npockets and revealed to the surgery team one by one\nthrough the enrollment process.\nEndometrial destruction by the hysteroscopy method\nFirst, in eligible patients referred to a gynecological clinic\ndue to abnormal uterine bleeding, endometrial biopsy was\nperformed by pipple. If there was no atypia or malignancy\nsign, they were contained the criteria for endometrial\ndestruction by the method. In the hysteroscopy treatment\ngroup, in the operating room, after emptying the bladder,\nuterus, adnexa were examined bimanually. After ventilating\nthe normal saline dilation media system and white balance,\nthe lower vaginal valve was inserted and the anterior\nlip of the cervix was grasped with a tenaculum (Sialkot,\nPakistan). Endometrium was coagulated according to the\nstandard of destruction with a resectoscope (Storz Hamou\nEndomat Mod. 26331020) with a power of 50-150 watts,\ndepending on the size of the electrode, so that first the\nfundus, both cornea, the anterior wall, lateral wall and\nfinally the posterior wall were destroyed. In this method,\nit was tried to avoid the cervical mucosa destruction. The\nendometrium was coagulated to a depth of 5 mm underlying\nthe myometrial layer.\nCavaterm method is based on rotating hot water with a\ntemperature of about 80°C at a constant pressure between\n240-230 mm Hg in a silicone balloon for 10 minutes. The\ncavaterm system (CAVATERMTM C-FACT04070101)\n(Veldana, Switzerland) consists of a disposable catheter\nwith an adjustable silicone balloon and a central unit. The\n10-minute treatment is a combination of heat, circulation\nand water pressure to coagulate the endometrium and the\nunderlying myometrial layer to a depth of 5 to 9 mm.\nOne surgeon with experience more than twelve years\nexperience did all Cavaterm, and another surgeon with\nmore than ten years of experience performed Hystroscopy\nablations.\nThe primary outcome was defined as changing the status\nof menstrual patterns in patients based on the International\nFederation of Gynecology and Obstetrics (FIGO)\nclassification. Other consequences and complications\nsuch as fever, infection and vaginal discharge, abdominal\npain, and number of surgical complications were asked\nduring the first hospitalization and the day after the\nprocedure. Patients’ satisfaction, menstrual pattern, and\nneed for hysterectomy in each study group were also\nasked one year in the subsequent visits and registered in\nthe researcher-made checklist for each patient directly.\nOverall satisfaction with the treatment was assessed and\nrecorded using the 5-point Likert scale ( 4 ).\nAll patients were visited two weeks after the interventions to evaluate immediate adverse\nevents, complications and also the time to recovery. Subsequent visits were done in the\nthird and 12 th  month after the surgery to assess the menstrual situation,\npatient satisfaction, and delayed complications.\nIn this study, to compare quantitative data between\nthe two groups, first the normal distribution of data\nwas assessed by the Kolmogorov-Smirnov test and\nthen independent t test and the Mann-Whitney test\nwere used, for parametric data and non-parametric data,\nrespectively. The Chi-square test was used to compare\ncategorical variables. A significance level of 0.05 was\nconsidered.\nA sample size of 50 patients in each group was calculated\nbased on the Brun’s results, one-tailed and with type one\nerror of 0.05 and power of 0.8.\n\nDuring 11 months, screening of 145 patients for eligibility\ncriteria led to 100 enrolled patients. Then, equal numbers\nof patients were randomly divided in each surgery group,\nCavaterm and hysteroscopy ( Fig.1 ). The demographic data\nof participants presented in  Table 1 . The U Mann Whitney\ntest result showed no significant difference between the two\ngroups in terms of age (P=0.072) and BMI (P=0.424). No\nsignificant difference was observed in parameters, including\ngravid, parities, abortion and a history of caesarian section,\nbetween our group.\nTable 2  shows the status of menstrual patterns of\nthe participants, before and after their intervention. A\ncomparison of menstrual status with the Chi-square\nmethod did not show a significant difference between the\ntwo groups before the intervention (P=0.36). Our results\nshowed that patients treated with the Cavaterm method\ndid not show a menometrorrhagia pattern. Only 4 cases of\nmenorrhagia have been observed in the Cavaterm group.\nIn contrast, in the hysteroscopy group, twelve menorrhagia\ncases experienced abnormal menstrual bleeding after the\nprocedure.\nStudy population and patients follow up.\nDemographic data of participants\nBMI; Body mass index.\nDistribution of menstrual pattern before and after interventions\nFailure cases were considered in which the patient’s\nmenstrual pattern was still abnormal. Considering this\ncriterion and by the cases specified in Table 2, 16 cases\nwere failed in our groups: Cavaterm group (n=4, 8.2%)\nand hysteroscopy group (n=12, 24%). This difference\nwas statistically significant, that indicates a higher\nsuccess of the Cavaterm approach in comparison with the\nhysteroscopy procedure [P=0.03, relative risk (RR)=1.63,\n95% confidence interval (CI): 1.13-2.36].\nThe time to return to daily activities was compared in our\ngroups with an independent sample t test. The Cavaterm\ngroup with a mean ± SD of 2.61 ± 1.3 days was significantly\ndifferent from the hysteroscopy group with a mean ± SD\nof 2.1 ± 1.12 days, P=0.06. Also, the comparison of time\nto return to work activity in the two groups was compared\nwith the independent t test. The Cavaterm group with a\nmean ±SD of 2.67 ± 1.29 days reported a longer time to\nreturn to work than the hysteroscopy group with a mean ± SD of 1.78 ± 1.26 days, which was statistically significant\nP=0.01.\nOut of 12 cases of treatment failure in the hysteroscopy\ngroup, six patients (50%) required hysterectomy after\nthe initial intervention, which one of them was a member\nof the Cavaterm group (25%). This difference was not\nstatistically significant (P=0.395). In the Cavaterm group,\nnone of the successfully treated patients were needed a\nhysterectomy approach, but in the hysteroscopy group,\none person was needed this surgery. Without considering\nmentioned treatment success, no significant difference\nin the need for hysterectomy after endometrial ablation\nwas observed in our participants ( Table 3 ).\nThe level of satisfaction, classified into the 5 Likert\nscores, including excellent, good, average, bad and\nvery bad, that the Cavaterm group showed 67.3, 12.2,\n12.2, 0 and 8.2%, respectively, while the hysteroscopy\ngroup displayed 54, 4, 18, 8 and 16% rate, respectively.\nComparison of satisfaction scores in the two groups based\non the Likert scores (excellent=5, 1=very bad) represented\nthat satisfaction with the intervention with Cavaterm\n(mean ± SD=4.3 ± 1.21) compared to hysteroscopy (mean\n± SD=3.7 ± 1.56) was higher which was statistically\nsignificant with P=0.04.\nThe intervention complications showed that the rate\nof spots, bloody discharge and malodor discharge was\nsignificantly higher in the Cavaterm group. In contrast,\npostoperative dysmenorrhea is more common in the\nhysteroscopy group ( Table 3 ).\nComparison of complications between two groups of the study\nData are presented as number (%).  †  ; Chi square test was performed.\n\nUsing Cavaterm or hysteroscopy, this study compared\nthe success rate and complications of two treatments for\nendometrial ablation in the AUB patients. Our results\nshowed that the success of the Cavaterm method in the\ntreatment of AUB and the menstrual pattern change one\nyear after surgery (91.2%) was significantly higher than\nthe hysteroscopy method (76%). On the other hand,\ndespite adverse events including spotting, malodor\nvaginal discharge and supra pubic pain, participants’\nsatisfaction with uterine bleeding was higher than\nendometrial ablation one year after Cavaterm intervention\nin comparison with hysteroscopy. In addition, the chance\nof hysterectomy in the first-year post-intervention in the\nCavaterm group was 25%, which was lower than the\nhysteroscopy ablation group, although this difference was\nnot statistically significant compared to this percentage\nin hystroscopy group (50%). No serious adverse events\n(including perforation, sepsis, prolonged hospitalization,\nor death) were observed in both intervention groups.\nThe reported success rates for these two methods in\nprevious interventional and observational studies are\nlargely consistent with our results. Most of these studies\nhave considered the ultimate success of ablation in\nachieving amenorrhea status for patients ( 4 - 9 ). However,\nin some cases, achieving normal menstrual patterns or\nhypomenorrhea has also been considered as a success in\nthese interventions ( 5 ).\nSmith et al. conducted a comparative clinical trial\nbetween Cavaterm and bipolar ablation in a 5-year\nfollow-up, they observed a 60% success rate for Cavaterm\nablation while in their bipolar group reached 62%, the\nhighest reported results of the success of the Cavaterm\nmethod. They considered achieving amenorrhea as\na success rate ( 6 ). This ratio is equivalent to 56% in\nquarterly and one-year follow-up in the Bouzari et al.\n( 7 ) study, which is a retrospective cross-sectional study\nperformed in the Cavaterm patients in the Babol, Iran. A\n5-year follow-up, Kleijn et al. ( 8 ) reported amenorrhea\n(32%) in their Cavaterm group. Karimi-Zarchi et al. ( 9 ),\nevaluate the long-term outcome of endometrial ablation\n(EA) therapy with a Cavaterm Thermal Balloon in\npatients with AUB and showed prevalence of amenorrhea\nwas 41.2%. Penezic et al. ( 10 ) to determine long-term\npatient satisfaction after thermal balloon EA 7 to 10 years\npostoperatively in a population previously surveyed at\nthe Penn State Milton S. Hershey Medical Center at 1 to\n5 years postoperatively and observed 58% amenorrhea\nover 7 to 10 years. In the study of Hokenstad et al. ( 11 ),\nthe ratio of amenorrhea following EA in patients without\na history of ovulation dysfunction was 13.8%, which is\nconsistent with the results of the present study.\nHowever, other comparative studies have conflicting\nresults, for example Brun et al. ( 12 ) reported a 36%\nsuccess rate for Cavaterm, while hysteroscopy group\nshowed a 29% success rate. The results obtained in other\nstudies are contradictory ( 13 ). The study of Ajao et al.\n( 14 ) reported 29.7% amenorrhea and 27.2% amenorrhea\nin a cohort study. Amenorrhea rates were also similar in\nboth. The high risk (HR) cohort had a higher proportion of women with cardiac disease (27.1 vs. 6.7%, P<0.001)\nand more women with nongynecologic cancer (12.3 vs.\n2.9%, Fisher exact test, P<0.001). Nonetheless, EA had\ncomparable efficacy in both the HR and low risk (LR)\ncohorts with a 5-year failure rate of 11.7 and 14.8%\n(P=0.659). It seems that the differences in the success\nrate of amenorrhea in these studies are due to patient\nselection methods and differences in surgical techniques.\nThe higher amenorrhea rate in the Cavaterm group might\nbe due to its homogenous circumambient ablative ability\nin comparison with focal intervention in the hysteroscopy\nablation.\nIn general, regarding the amenorrhea rate following\nhysteroscopic ablation, which is lesser than 50%, leads to\nthe conclusion that EA by both methods is not a good choice\nfor women who prefer postoperative amenorrhea ( 15 ).\nEA success was considered as an AUB cessation\n(conversion to amenorrhea or eumenorrhea) in the present\nstudy, this value in two methods of ablation by Cavaterm\nor hysteroscopy was 91.8 and 76%, respectively, which is\nalso a statistically significant difference and demonstrates\nthe better performance of the Cavaterm method. Bouzari et\nal. ( 7 ) also defined the success of Cavaterm as improving\nthe bleeding status and reported its rate in the quarter\nand six months as 92.5 and 93.5%, respectively. Their\nresult is consistent with the present study. The success\npercentage of Cavaterm in the study of Karimi-Zarchi et\nal. ( 9 ) was about 94% after 6 month follow up that was\nhigher than present study. In a same direction a 7-year\nsuccess proportion for the Penezic et al. ( 10 ) study was\n91.5%. Brun et al. ( 12 ) reported a 87% success rate of\nthe hysteroscopy degrading treatment, which is somewhat\nhigher than the present study. Similar results have been\nsuggested by Ajao et al. ( 14 ), and Hokenstad et al. ( 11 ),\n85 and 87% respectively.\nThe treatment failure rate leading to hysterectomy\nfollowing treatment with Cavaterm has different reports.\nThe Bouzari et al. ( 7 ) one-year follow-up study did not\nreport any hysterectomy, but this number was about 2%\nin Karimi-Zarchi et al. study ( 9 ), 12.9% in Kleijn et al.\n( 8 ) study and 21.6% in the Penezic et al. ( 10 ) study. We\nreported a 25% failure in the Cavaterm group which is\nconsistent with what was mentioned. It seems that the\ndifference in the number of reports is affected by the\nduration of follow-up of patients, which in these four\nstudies was one year, about two years, 5 years and 7 years,\nrespectively. The reports of the articles mentioned that\nthe patients' satisfaction after treatment is incomparable\nin many cases due to the satisfaction assessment method.\nIn a Cochran review article, the postoperative satisfaction\nwith different methods is almost equal and comparable,\nbut another meta-analysis found patients’ satisfaction\nwith thermal methods higher than other methods ( 16 ),\nthat was consistent with our results.\nThe main limitation of our study was the impossibility of\nlong-term follow-up due to lack of access to them and the\nimpossibility of standardizing the long-term evaluation of\npostoperative outcomes. It is suggested to consider longterm follow-up in future studies.\n\nCavaterm ablation is accompanied by a higher success\nrate of amenorrhea and patient satisfaction compared with\nhysteroscopy ablation. Major adverse events will not be\nexpected frequently.","source_license":"public-domain-us","license_restricted":false}