Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Endometrial ablation: A Comparative Study between Hysteroscopic Resection and modified Thermal Balloon using Foley’s Catheter in The Treatment of Dysfunctional Menorrhagia Thesis Submitted for partial fulfillment of MD degree in Obstetrics and Gynecology BY Ayman Sobhy El-Gohary Assistant lecturer of Obstetrics and Gynecology Faculty of medicine – Benha University Under supervision of Prof. AHMED AHMED SALEM Professor of Obstetrics and Gynecology Faculty of medicine – Benha University Dr. MOHAMMED ABDEL-HADY MOHAMMED Assistant professor of Obstetrics and Gynecology Faculty of medicine – Benha University Dr. IBRAHIM IBRAHIM SWEDAN Lecturer of Obstetrics and Gynecology Faculty of medicine – Benha University Faculty of medicine Benha University 2016 ABSTRACT Abstract Study design: A randomized clinical prospective comparative study. Setting: The study was conducted in the Department of Obstetrics and Gynecology in Benha University between January 2014 and December 2015. Objective: To compare the efficacy and safety of endometrial ablation using Foley’s catheter with hysteroscopic endometrial resection in the treatment of dysfunctional menorrhagia. Patients and methods: The study comprised 100 premenopausal women with persistent intractable menorrhagia, selected under strict inclusion criteria. Patients were randomized into two equal groups of 50 patients each. Patients of the first group were treated by Foley’s catheter endometrial ablation (30 patients), while those of the other group were treated by hysteroscopic endometrial resection (50 patients). Pre and post-procedural quantification of menstrual blood was defined by pad count and self-assessment. Eighteen-month follow-up data were presented on all women and compared statistically. Results: Eighteen-month results indicated that both techniques significantly reduced menstrual blood flow with no clinically significant difference between the two groups. Success rates, as reflected by percent of patients who returned to normal bleeding or less, were comparable being 80% for the Foley’s catheter ablation group and 86.6% for the resection group. Procedural time was reduced significantly in the Foley’s catheter endometrial ablation group. Intra-operative complications occurred in three (8.5%) of the hysteroscopic resection patients, whereas no intra-operative complications occurred in the thermal balloon group. Postoperative complications were occurred in 3 patients in each group. Conclusion: Foley’s catheter endometrial ablation is as efficacious as hysteroscopic resection in the treatment of selected cases of menorrhagia. Keywords: Menorrhagia; Foley’s catheter; Hysteroscopic ablation; resectscope -2- LIST OF TABLES No. Page Description 1 13 Terminology of AUB, according to FIGO (2011) 2 14-15 Description of AUB, according to FIGO (2011) 3 16 PALM-COEIN classification of AUB 4 39 Types of distention media for hysteroscopy 5 75 The demographic and gynecological data in study groups 6 76 The operative time (min.), postoperative Hb drop (%) and hospital stay (Hrs.) in study groups. 7 79 Menstrual flow before and after treatment in Foley’s catheter group. 8 79 Menstrual flow before and after treatment in resection group. 9 80 Post treatment pattern in both groups at last visit (12 months). -3- LIST OF FIGURES No. Page Description 1 18 PBAC scoring system 2 19 The menstrual pictogram 3 43 Thermachoice system for endometrial ablation. 4 44 Cavaterm system for endometrial ablation. 5 44 Thermablate system (EAS) for endometrial ablation. 6 45 Novasure system for endometrial ablation. 7 45 Her Option system for endometrial ablation. 8 46 Microsulis system for endometrial ablation. 9 72 Foley’s catheter No. 18 French 10 73 The resectoscope elements. -4- LIST OF CHARTS No. Page Description 1 77 Intra and postoperative complications in Foley's catheter group. 2 78 Intra and postoperative complications in hysteroscopic resection group. 3 78 Intra and postoperative complications in study groups 4 81 Changes in the bleeding pattern, over time, after Foley’s catheter ablation. 5 82 Changes in the bleeding pattern, over time, after hysteroscopic resection. -5- LIST OF ABBREVIATIONS AAGL: Advancing Minimally Invasive Gynecology Worldwide. ACOG: American College of Obstetricians and Gynecologists. aPTT: activated partial thromboplastin time. ARDS: Adult respiratory distress syndrome. ASRM: American Society for Reproductive Medicine. AUB: Abnormal uterine bleeding. BMI: Body mass index. C: Celsius. CBC: Complete blood count. CHCs: Combined oral contraceptive. cm: centimeter. D&C: Dilatation and curettage. DMPA: Depomedroxy progesterone acetate. DUB: Dysfunctional uterine bleeding. EA: Endometrial ablation. F: French FCBEA: Foley’s catheter balloon endometrial ablation FDA: Food and Drug Administration. FIGO: International Federation of Gynecology and Obstetrics. GHz: Gigahertz. -6- Gn-RH: Gonadotropin releasing hormone. Hb: Hemoglobin. HMB: Heavy menstrual bleeding. Hrs: hours. HE: hyponatremic encephalopathy. IV: Intravenous LNG-IUS: Levonorgestrel releasing intrauterine system. MEA: microwave endometrial ablation. mEq: miliequilibrium. mg: milligram. min: minute. mm: millimeter MPA: Medroxy progesterone acetate. MRI: Magnetic Resonance Image. NaCl: Sodium Chloride NICE: National Institute for Health and Clinical Excellence. NS: No significant. NSAIDs: Nom steroidal anti-inflammatory drugs. OCP: Oral contraceptive pills. PBAC: Pictorial blood loss assessment chart. PCO: Polycystic ovary. PMS: Premenstural tension syndrome. -7- PT: Prothrombin time. RB: Roll ball RCTs: Randomized controlled trials. SIS: Saline infusion sonohysterography. SOGC: Society of Obstetricians and Gynecologists of Canada. TBEA: Thermal balloon endometrial ablation. TCRE: Transcervical endometrial resection. TVS: Transvaginal sonograpghy. UAE: Uterine artery embolization. UK: United Kingdom. Vs: versus. VWF: von Willebrand’s factor. W: Watt. -8- INTRODUCTION Heavy menstrual bleeding (HMB, also known as menorrhagia) is a significant cause of morbidity in premenopausal women. It is objectively defined as menstrual blood loss of more than 80 ml/cycle, or menstrual bleeding lasting longer than 7 days, over several consecutive cycles. However, in practice, the diagnosis is based on the woman's subjective assessment of blood loss (Munro et al., 2010). It is estimated that 1 in 20 women aged 30–49 years consults her general practitioner each year with HMB. Referrals for menstrual disorders account for about 20% of all referrals to specialist gynaecology services, placing a significant burden on secondary healthcare services (National Institute for Health and Care Excellence “NICE”, 2004). Heavy menstrual bleeding has adverse implications for quality of life. Women with HMB may have difficulties with daily activities such as work, social activities, hobbies and holidays. Many women report anxiety, depression, embarrassment and problems in their sex lives because of HMB. Anemia is also common amongst women with HMB, and this may further impair quality of life (Gokyildiz et al., 2013). The cause of HMB is not known in the majority of cases, in which no pelvic or organic pathology is identified. However, HMB may have structural organic causes such as fibroids, adenomyosis, polyps, infections, pre-cancerous conditions or hematological disorders (Frick et al., 2009). Diagnosis of HMB is complex and is usually based on subjective evaluation of blood loss by the affected individuals. The blood loss can be estimated using -9- pictorial blood-loss assessment charts (PBACs); this method takes into account the number of items of sanitary wear used and the degree of staining of each item. A PBAC score greater than 100 would normally indicate HMB. Although the 'gold standard' method of measuring blood loss is the alkaline haematin technique, which requires women to collect their used sanitary wear, this technique is rarely used outside research settings (The menorrhagia research group, 2004). Treatment of HMB aims to reduce menstrual loss and hence to improve the quality of life of the individuals. First-line treatment is drug therapy. The most commonly used drugs are tranexamic acid (an antifibrinolytic drug), mefenamic acid (a non-steroidal anti-inflammatory drug) and combined oral contraceptives. NICE recommend that drug treatment should be given for at least three cycles before considering another treatment option. Another alternative sometimes used before surgical intervention is a levonorgestrel-releasing intrauterine system (LNG-IUS) (NICE, 2004). Surgical treatment is usually offered to patients who do not respond to drug treatment. Hysterectomy is the only treatment for HMB that guarantees amenorrhoea, but it is associated with peri- and postoperative complications, including incontinence and other urinary problems, fatigue, infection, pelvic pain and sexual problems. Overall, 1 in 30 women suffers a major adverse event during or soon after the operation. Additionally, the procedure has a mortality rate of 0.4– 1.1 per 1000 operations. Hysterectomy is costly and has significant resource implications because it requires general anesthesia, long operating theatre times and a hospital stay of up to 7 days after the operation. Full recovery may take 1-3 months (Society of Obstetricians and Gynecologists of Canada “SOGC”, 2013) -10- Many women who are referred to secondary care for HMB will eventually undergo hysterectomy. It is estimated that HMB was the presenting complaint in about half of these cases. Furthermore, about half of all women who have a hysterectomy for HMB are believed to have a normal uterus removed (American College of Obstetricians and Gynecologists “ACOG”, 2013). First-generation endometrial ablation (EA) techniques were introduced almost 20 years ago as alternatives to hysterectomy. These techniques aim to reduce the menstrual bleeding by destroying (ablating) the entire thickness of the innermost layer of the uterus (the endometrium) and some of the underlying muscular layer (the myometrium) using electrical, thermal or laser energy. EA techniques do not guarantee amenorrhoea, but are less invasive and require fewer resources than hysterectomy. EA techniques are not suitable for women who wish to maintain fertility (Papadopoulos and Magos, 2007). The most widely used first-generation EA techniques are transcervical resection of endometrium (TCRE), using a loop diathermy electrode, and rollerball ablation (RB), using an electrode with a movable ball or cylinder. All firstgeneration EA techniques require direct visualisation of the endometrium using a hysteroscope. The success rates of these techniques depend heavily on the skills and experience of the operator (Deb et al., 2008). Possible perioperative adverse effects with the first generation EA techniques include electrosurgical burns, uterine perforation, hemorrhage, infection, and fluid overload (which may cause congestive cardiac failure, hypertension, hemolysis, coma and death) (Daniel et al., 2012). Second-generation EA techniques have been introduced with the aim of providing simpler, quicker and more effective treatment options for HMB -11- compared with first-generation EA techniques and hysterectomy. These techniques are less operator-dependent, but they rely heavily on the devices themselves to ensure safety and efficacy. Second-generation EA techniques include fluid-filled thermal balloon EA (TBEA), radiofrequency balloon EA, hydrothermal EA, 3D bipolar radiofrequency EA, microwave EA (MEA), diode laser hyperthermy, cryoablation and photodynamic therapy (Owusu-Ansah et al., 2006). The most frequently used second- generation EA techniques in clinical practice is fluid filled TBEA which do not require direct visualisation of the uterine cavity, and can be carried out under either local or general anaesthesia. It destroys the inner layers of the uterus by transferring heat from heated liquid within a balloon inserted into the uterine cavity. (Thermachoice, Thermablate EAS, and Cavaterm) are the 3 devices which have been approved by Food and Drug Administration (FDA) for TBEA. All involve an electronic controller, a single-use latex or silicone balloon catheter housing a heating element (Rishma, 2009). Although TBEA devices are safe, effective and easily used, they have the disadvantage of being expensive and unavailable in many centers, so the use of Foley’s catheter balloon in this study can be a cheap and available alternative to these devices in low resources countries. However, Foley’s catheter balloon has the disadvantage of absence of the control unit which allows proper setting and monitoring of temperature and pressure, thus the use of this simple technique will be assessed in this study (Azza, 2012). -12- Chapter (1): ABNORMAL UTERINE BLEEDING (AUB) Menstrual disorders are a common indication for gynecological visits among women of reproductive age. Heavy menstrual bleeding (HMB) affects up to 30% of these disorders (Pallavi et al., 2015). These complaints can affect life quality; result in time off work which may lead to hysterectomy (Frick et al., 2009). Abnormal uterine bleeding can be defined as any variation from the normal menstrual cycle which includes regularity and frequency changes of the menses, in flow duration, or in blood loss amount. Under the category of AUB, further definitions may be subdivided based on regularity, frequency, duration, volume, timing, and chronicity of the menstrual cycle (Munro, 2010). Standardized universal terminology is essential in the discussion of AUB. In 2011, the International Federation of Gynecology and Obstetrics (FIGO) Menstrual Disorders Working Group developed a new guideline for the terminology and descriptions related to this topic; as shown in table (1) and (2). This suggested nomenclature for AUB aims to simplify descriptions of this clinical presentation and eliminate terminology such as menorrhagia and metrorrhagia. The term menorrhagia should be replaced by heavy menstrual bleeding (HMB) and the term metrorrhagia should be replaced irregular menstrual bleeding (Munro et al., 2011). Table (1): Terminology of AUB, according to FIGO (2011) Volume Heavy Normal Light Regularity Irregular Regular Absent Frequency Frequent Normal Infrequent -13- Duration Prolonged Normal Shortened Other Intermenstrual Premenstrual Breakthrough Table (2): Description of AUB, according to FIGO (2011) Characteristic Terminology Description Volume Heavy menstrual bleeding Regularity Irregular menstrual bleeding Excessive menstrual blood loss which interfere with the women`s physical, emotional, social and material quality of life, A range of varying lengths of bleeding-free intervals >20 days within one 90-day reference period. Frequency (Normal = every 24-38 days) Duration (Normal = 3-8 days) Absent menstrual bleeding (amenorrhea) Infrequent menstrual bleeding No bleeding in a 90-day period Frequent menstrual bleeding Bleeding at intervals < 24 days (> 4 episodes in a 90-day period) Menstrual blood loss > 8 days in duration. Prolonged menstrual bleeding Shortened menstrual bleeding Irregular, Nonmenstrual Intermenstural Bleeding at intervals > 38 days apart (1 or 2 episodes in a 90-day period). Menstrual bleeding < 3 days in duration. Irregular episodes of bleeding, often light and short, occurring between otherwise fairy normal menstrual periods. Post-coital Bleeding post-intercourse. Pre-menstrual and post menstrual spotting Bleeding that may occur on regular basis > 1 days before or after the recognized menstrual period. -14- Bleeding outside Post-menopausal bleeding reproductive age Precocious menstruation Acute or chronic Acute AUB AUB Bleeding occurring > 1 year after menopause. Bleeding occurring before the age of 9 years. An episode of bleeding in a woman of reproductive age, who is not pregnant, that is of sufficient quality to require immediate intervention to prevent further blood loss. Bleeding that is abnormal in duration, volume, and/or frequency and has been present for most of the last 6 months Chronic AUB CAUSES OF AUB: In 2011, an international expert committee from the FIGO Menstrual Disorders Working Group has proposed a standardized classification system for AUB. This classification allows the characterization of more than one etiology in the same patient. The term “dysfunctional uterine bleeding” should be replaced by coagulopathy, ovulation disorder, or endometrial disorder. There are 9 main categories within the classification system which is named PALM-COEIN; as shown in table (3). The PALM side of the classification refers to structural causes that could be diagnosed by radiological imaging or biopsy. The COEIN side refers medical causes that could result in AUB (Munro et al., 2011). -15- Table (3): PALM-COEIN classification of AUB PALM-side (structural causes) COEIN-side (Non-structural causes) Polyps Coagulopathy Adenomyosis Leiomyomas -Submucous -other Malignancy & hyperplasia Ovulatory dysfunction Endometrial (primary disorder of mechanisms regulating local endometrial hemostasis) Iatrogenic Not yet specified DIAGNOSIS OF AUB: Assessment, history and physical examination will help to establish the cause of the abnormal bleeding, to direct further investigations, and to guide options for management. I. Assessment of heavy menstrual bleeding: The current ‘gold standard’ method of estimating blood loss is the alkaline hematin technique (Hallberg and Nilsson, 1964). Gannon et al. (1996) has been modified this method to simplify and fasten the process but all modifications require women to collect their used sanitary wear. This is subsequently treated to extract hemoglobin, which is then measured and related back to actual blood loss. This method is rarely used outside a research setting (Reid et al., 2000). Pictorial blood loss assessment chart (PBAC) is another method of estimating of the menstrual blood loss. This is a simple scoring system which was first introduced by Higham et al. (1990) as a visual representation of blood loss from which a numerical score is emerged. The chart composed of varieties of -16- diagrams representing lightly, moderately and heavily soiled tampons or towels. Moreover, passage of blood clots (size equated with that of UK coins) and flooding episodes were recorded (Fig. 1). A numerical scoring system was developed to estimate the blood loss amount. The scores assigned were 1 for each lightly stained tampon, 5 if moderately soiled and 10 if it was completely saturated with blood. The towels were given scores of 1, 5 and 20, with increased level of soiling. Small and large clots scored 1 and 5, respectively (The menorrhagia research group, 2004). Higham et al. (1990) reported that when the PBAC was used as a diagnostic clinical tool, a score of 100 or more defined menorrhagia with a sensitivity and specificity of > 80%. Janssen et al. (1995) assessed the specificity, sensitivity, and negative and positive predictive values of PBACs at several cut-off points. Using a score of 185 as their cut-off point, the authors reported predictive values of negative and positive tests of 84.8%, and 85.9% respectively. The discriminatory power of PBAC as a diagnostic method was a matter of question. Reid et al. (2000) showed that, in a group of 103 women with menorrhagia; there was poor correlation between actual measured blood loss and PBAC score. The main 2 drawbacks for this score were that; the specific sanitary products that were used for the Higham technique are not now widely available, which may make it less accurate. Furthermore, methods that rely on directly or indirectly estimating blood loss from the effect on sanitary wear do not take account of blood loss during changing sanitary wear (Wyatt et al., 2001). -17- Another indirect method for assessing blood loss is the ‘menstrual pictogram’ (Fig. 2). It is similar to the PBAC but has 2 additional values for the modified charts, the first is that the score is calculated in milliliters and so, it is equal to the actual volume of blood lost. The second is the estimation of the blood loss during changing sanitary wear is considered. For these reasons, the menstrual pictogram appears to be an accurate and acceptable way of estimating menstrual blood loss for both research and clinical uses (The menorrhagia research group, 2004). Figure (1): PBAC scoring system -18- Figure (2): The menstrual pictogram -19- II. HISTORY: Assessing the amount, frequency, and regularity of bleeding, the presence of post-coital or intermenstrual bleeding, and any dysmenorrhea or premenstrual symptoms can help to differentiate between ovulatory from anovulatory bleeding or to diagnose anatomic causes such as cervical pathology or endometrial polyps. Ovulatory AUB is usually regular and is usually associated with dysmenorrhea and premenstrual symptoms while anovulatory bleeding, which is more common near menarche and the perimenopause, is usually irregular, heavy, and prolonged. It is more likely to be associated with endometrial hyperplasia and cancer (ACOG, 2013). Further history should include the following (SOGC, 2013): • Symptoms suggestive of anemia (i.e. pallor, headache, shortness of breath with activity). • Sexual and reproductive history (i.e. contraception, infertility, sexually transmitted diseases risk for pregnancy and desire for future pregnancy, cervical screening). • Symptoms suggestive of systemic causes of bleeding such as; coagulation disorders, hyperprolactinemia, and hypothyroidism. • Associated symptoms such as pelvic pain and vaginal discharge or odor. • A family history of inherited coagulation disorders, PCOS, or endometrial cancer. • A Past history of any co-existing conditions includes: cardiovascular problems thromboembolic disease, hormonally dependent neoplasm, or that; could affect options of treatment. Finally, a list of drugs that may interfere with ovulation or -20- otherwise be associated with bleeding should be obtained (anticoagulant, antidepressant, anti-psychotic, hormonal contraception, tamoxifen, corticosteroids, and herbs: ginseng) II. EXAMINATION: Physical examination should look for evidence of systemic disorders that can cause abnormal bleeding and should evaluate the abdomen, lower genital tract and pelvis to confirm the source of bleeding and to search for anatomical causes such as myomas or cervical polyps. General examination includes: vital signs (pulse, blood pressure, temperature, and respiratory rate), weight, thyroid, and skin (pallor, bruising, striae, hirsutism and petechiae). Abdominal examination should be done to exclude any mass, ascites, and hepato-splenomegally. Gynecological examination includes: inspection (vulva, vagina, cervix, anus and urethra), bimanual exam (uterus and adnexal mass), rectal exam (if bleeding from anus is suspected), uretheral exam (if bleeding from urethra is suspected) and testing (Pap smear and cervical cultures if risk for sexually transmitted infection) (NICE, 2007). III. INVESTIGATIONS: Investigations include the following: 1. Laboratory investigations: -21- Many laboratory investigations may be done including (Khrouf and Khaled, 2014): A complete blood count (CBC) is recommended if there is a history of HMB. If there is any possibility of pregnancy, serum beta subunit for human chorionic gonadotropin (β-HCG) should be carried out. Thyrotropin stimulating hormone (TSH) levels should be measured only if there are other symptoms or findings suggestive of thyroid disease. Testing for coagulation disorders should be done in patients who have a history of heavy bleeding beginning at menarche, a history of postpartum hemorrhage or hemorrhage with dental extraction, evidence of other bleeding problems, or a family history suggesting a coagulation disorder. There is no evidence that measurement of serum gonadotropins, estradiol, or progesterone levels is helpful in the management of AUB. 2. Transvaginal sonography (TVS): Transvaginal sonography (TVS) can diagnose the majority of anatomical abnormalities of the uterus and endometrium. In addition, pathologies of the myometrium, cervix, tubes, and ovaries can be assessed. This investigative method can help in the diagnosis of adenomyosis, leiomyomas, endometrial polyps, uterine anomalies, and endometrial thickening associated with hyperplasia and cancer. In a premenopausal woman, the normal endometrium varies in thickness according to the menstrual cycle from 4 mm in the follicular phase up to 16 mm in the luteal phase (Veena and Nermala, 2014). -22- 3. Saline infusion sonohysterography (SIS): Saline infusion sonohysterography (SIS) is a technique in which 5 to 15 mL of normal saline is introduced into the uterine cavity during TVS. So, it improves the diagnosis of intracavitary pathology. Especially in cases of endometrial polyps and myomas, SIS allows a greater discrimination of site and relationship to the uterine cavity. Although hysteroscopy is the gold standard, SIS is an easy, simple and safe technique for diagnosing of intracavitary pathologies. SIS can reduce the need for hysteroscopy but it is less sensitive (Sharma at al., 2013). 4. Magnetic resonance image (MRI): In patients with HMB, MRI is rarely used to evaluate the endometrium. However, it can be helpful in mapping the site of myomas in surgical planning and prior to uterine artery embolization. It can be used in assessing the endometrial cavity when TVS or other uterine imaging (i.e. congenital anomalies) is not conclusive (Kotdawala, 2013). 5. Hysteroscopy: Hysteroscopic evaluation for abnormal uterine bleeding is an option providing direct visualization of intra-cavitary pathology and facilitating directed biopsy (Van Dongen et al., 2007). 6. Endometrial biopsy: In women at risk of malignancy, endometrial biopsy is a minimally invasive method for endometrial evaluation. Sensitivity for malignancy is higher in postmenopausal women than in premenopausal women (Huang et al., 2007). -23- This biopsy can detect over 90% of endometrial cancers. However, it is a blind procedure and therefore it can miss a focal lesion; so, hysteroscopic directed biopsy is recommended in the cases of a focal lesion when is suspected on ultrasound (Huang et al., 2007). Indications for endometrial biopsy in women with AUB include (Lacey et al., 2010): Age > 40. Failure of medical treatment. Significant intermenstrual bleeding. Risk factors for endometrial cancer (BMI > 30 kg/m2, nulliparous, PCOs, and diabetes). 7. Dilatation and Curettage: Dilatation and curettage (D&C) is no longer used for the initial evaluation of the endometrium. The advantage of D&C is to add the endometrial assessment pathology in the diagnosis. The disadvantages of this procedure include; it is a blind procedure, with sampling errors and risks of complications similar to hysteroscopy (La Sala et al., 2011). TREATMENT OF AUB: I. MEDICAL TREATMENTS: In the treatment of women with AUB, once a detailed history, physical examination, and imaging studies are done and all significant structural causes are excluded, medical treatment is the first-line approach (Bradley and Gueye, 2016). -24- Treatment for any associated medical condition that can cause menstrual bleeding, such as hypothyroidism, should be started before to the addition of any medical drugs. Patients whom found to be anemic due to AUB, iron supplementation should be started immediately (Sweet et al., 2012). Regular menstrual bleeding can be treated effectively with both hormonal and non-hormonal options. Non-hormonal treatments such as non-steroidal antiinflammatory drugs and antifibrinolytics are used during menses to reduce the amount of blood loss (Ray and Ray, 2014). Irregular bleeding is most successfully treated with hormonal options which can regulate cycles, decreasing the episodes of heavy bleeding. combined hormonal contraceptives, Cyclic progestin and LNG-IUS are effective treatment in this group, allowing more predictable cycles while protecting the endometrium against unopposed estrogen and the risk of hyperplasia or cancer (Ray and Ray, 2014). Regard to any type of AUB, a patient- centered approach to the selection of a specific medical therapy is essential. Satisfaction and continuation of any given treatment will be affected not only by the efficacy, but also by the individual patient’s goals and tolerance of side effects. The decision to proceed with a trial of medical treatment should be based on a patient counseling, desire for future fertility or contraception, underlying medical disorders or contraindications, presence of dysmenorrhea, and bleeding severity (SOGC, 2013). II. SURGICAL TREATMENTS: Surgical treatment of AUB requires a detailed assessment of the underlying pathology and patient factors. The medical treatment of HMB is effective for many -25- patients, and treatment with the LNG-IUS may be comparable in results to any surgical options for improving the quality of life which is the ultimate goal of treatment and may occur through achieving amenorrhea or even eumenorrhea (NICE, 2007). The indications for surgery for women with AUB include (SOGC, 2013): Unresponsiveness to medical therapy. Side effects or contraindications for medical therapy. Severe anemia. Effect on quality of life. Associated uterine pathology (large uterine fibroids, endometrial hyperplasia). Surgical options include (ACOG, 2013): Dilation and curettage. Uterine artery embolization. Hysteroscopic polypectomy. Endometrial ablation. Myomectomy. Hysterectomy. Dilatation and curettage should be done as a primary diagnostic procedure when endometrial sampling or hysteroscopic evaluation is not possible in cases of severe acute bleeding refractory to medical therapy (SOGC, 2013). Uterine artery embolization (UAE) should only be performed for patient with symptomatic myomas who advised to have surgical treatment. Although, UAE early results are encouraging, no long-term data is existing. UAE is -26- contraindicated in patients with evidence of current genito-urinary infection and/or malignancy (Gupta et al., 2014). Myomectomy can be performed by laparotomy, laparoscopy, or hysteroscopy. The choice of surgery route depends on several factors including: the number, site and size of myomas, the patient age and desire for future fertility (Puchar et al., 2015). Hysterectomy is the definitive treatment for AUB. If hysterectomy is required, the least invasive route should be offered to patients to minimize morbidity and recovery time; such as, laparoscopic-assisted hysterectomy or vaginal hysterectomy (Neiboer, 2009). SPECIAL CONDITIONS FOR AUB: 1. Inherited bleeding disorders: Abnormal uterine bleeding is one of the most common manifestations of an inherited bleeding disorder. Up to 84% of patients with Von Willebrand’s disease are presented with HMB. These conditions should therefore always be considered on the differential diagnosis for abnormal bleeding (Committee on Adolescent Health Care; Committee on Gynecologic Practice, 2013). Von Willebrand’s disease is the most common inherited bleeding disorder, representing about 70% of cases. Other less common diagnoses include deficiencies in factor XI, VII, or XIII, carrier status for hemophilia A or B, and other inherited platelet function abnormalities (AC0G, 2009). -27- Despite all patients with AUB should have a CBC including platelet count, the need for a further coagulation investigation can be determined by a detailed history. The most important elements of this history include pattern and severity of the bleeding, past history and family history of bleeding conditions or HMB. (Sanders et al., 2012). Patients with bleeding disorders may present with different patterns of uterine bleeding at any age, but the majority will have heavy, regular, cyclic menstrual cycle since menarche. Up to 50% of adolescents presenting with severe bleeding at menarche will have a coagulopathy. Irregular or anovulatory bleeding is almost never caused by hemostatic abnormalities (Rodeghiero, 2008). Once structural uterine abnormalities have been excluded, initial investigations should include prothrombin time (PT), activated partial thromboplastin time (aPPT), and ferritin when anemia is suspected. Special investigations for von Willebrand’s disease (factor VIII level, vWF antigen, and vWF functional assay) can be requested by a family physician or gynecologist, but interpretation and final diagnoses often require hematological consultation (Altshuler and Hillard, 2014). Many of the treatments for HMB used among patients with normal coagulation can effectively be used among women with bleeding disorders. Regard to non-hormonal treatment, the exception is NSAIDS, which change platelet function, thus are contraindicated. Tranexamic acid can be used alone or with any hormonal treatment method to control menstrual bleeding among these patients (Weiss, 2012). Regarding hormonal treatment, the OCP and the LNG-IUS have both been recorded to decrease menstrual loss specifically among patients with inherited bleeding disorders (Silva et al., 2013). Also, Injected hormonal agents such as -28- DMPA and GnRH agonists can be used for these patients (Altshuler and Hillard, 2014). If the classical hormonal and non-hormonal treatments of AUB have failed, specific treatment including Desmopressin or factor replacement can be used. These treatments should only be considered by the hematologist. Desmopressin, which releases vWF from platelets, is used to treat bleeding in mild coagulation disorders. It can be administrated during menstruation intravenously, intranasally, or subcutaneously. For refractory cases, conservative surgical treatment, including different methods of endometrial destruction, can effectively and safely be performed (Leissinger et al., 2014). Hysterectomy, if needed, must be planned carefully along with a hematologist (Demer et al., 2005). 2. Adolescent: Although, the etiology of AUB in adolescence has a similar differential diagnosis to that of adult women; the relative proportion of causes differs. According to the PALM- COEIN Classification of AUB, the structural causes (adenomyosis, leiomyomas) are rare in adolescents (Benette and Gray, 2014). Abnormal uterine bleeding in adolescents is usually related to an immature hypothalamic-pituitary-ovarian axis. Within the first year following menarche, up to 85% of cycles may be anovulatory. The incidence of ovulatory cycles increases with time from menarche but by the fourth gynecologic year just over half (56%) will be ovulatory. So, for an adolescent presenting within the first few years of menarche, a focused history and investigations about the ovarian dysfunction is often the cause (Deligeoroglou et al., 2013). -29- The age at presentation is important when considering causes beyond an immature hypothalamic-pituitary- ovarian axis. Oligomenorrhea at the age of 15 is most suspected of persistent cycle irregularity and needs more assessment (Wilkinson and Kadir, 2010). Adolescents presenting with HMB at or close to menarche, particularly those who need admission, or blood transfusion, may have a bleeding disorder in up to 48% of cases (Mullin et al., 2015). Choice of treatment is based upon the underlying cause, the severity of the bleeding, and the side effect profile. All medical modalities, both non-hormonal and hormonal, can be applied safely to adolescents. A significant consideration is the need for contraception (Mullin et al., 2015). Combined hormonal contraception is considered an effective first line option for adolescent patients (Huguelet et al., 2015). Long-acting contraceptives (injectable progestin, progestin IUS) may be also may be considered as first line therapies in sexually active adolescents, as well as in non-sexually active adolescents with personal counseling (Lara-Torre, 2011). Danazol and GnRH agonists are not typically recommended for adolescents due to their side effects (Wilkinson and Kadir, 2010). Hysteroscopy, endometrial ablation, and hysterectomy have no role in the treatment of AUB in adolescents. Surgical intervention is limited only to the rare structural abnormality (e.g. polyp or myoma) that requires directed removal (Huguelet et al., 2015). -30- Chapter (2): Endometrial ablation Endometrial ablation (EA) is a procedure of removing the endometrium for cessation or decreasing the menstrual cycle in the treatment of AUB in selected patients who need future fertility. This procedure was indicated to treat HMB refractory or resistant to medical therapy provided that; not caused by structural uterine pathology (Bouzari et al., 2014). HISTORY: Endometrial ablation can be considered as one of the great success stories in gynecology. It has changed the treatment of HMB dramatically (Kumar et al., 2016). In (1976), Neuwirth described the first operative hysteroscopy which involved resection of submucos myoma using a modified urological resectoscope. However, endometrial destruction through the endocervical canal dates back to 1937. Moreover, in (1981), Goldrath described the Laser ablation, but lost its favor due to the cost and unreliability of the technique. Also, in (1983), DeCherney and Polan described endometrial ablation by loop electrode and rollerball (RB) using the electrosurgery via monopolar or bipolar radiofrequency (Zarek and Sharp, 2008). Since (1990), non-resectoscopic ablation techniques have been developed using different sources of energy to perform endometrial destruction, including heated liquid (either free circulating or within a balloon), tissue freezing, and radiofrequency electricity (Cooper at al., 2011). -31- INDICATIONS: Endometrial ablation is indicated in premenopausal women with HMB but in the following conditions (ACOG, 2008): Intolerance to or failure of medical therapy for AUB. No desire for future fertility is needed. Refuse or poor surgical fit for hysterectomy. CONTRAINDICATIONS: Absolute contraindications to EA include (SOGC, 2015): Pregnancy. Desire to preserve fertility. Known or suspected endometrial hyperplasia or cancer. Cervical cancer. Active pelvic infection. Specific contraindications related to non-resectoscopic techniques. CAUSES OF FAILURE: Causes of failure of EA include (Simon et al., 2015): Incomplete ablation, missing the upper uterine segment or sparing the region of cornue. Tubal endometriosis Prior tubal ligation (entrapped endometrium in Fallopian tubes during ligation). Preoperative dysmenorrhea. -32- In a study conducted by (El-Nashar et al, 2009), EA failure was defined as; persistent bleeding or pain after ablation that may require reablation or hysterectomy) and its incidence was from 16-30% at 5 years. Regardless any technique of EA, success rate varies from 73% to 85%. So, repeated ablation or hysterectomy is raised in cases of ablation failure. The clinical scenario for repeat ablation versus another approach should be discussed with the patients depending on the surgeon’s skill and expert. Patient’s consent must be obtained includes complete information, about possible complications for each scenario (Wortman et al., 2015). If repeat EA is indicated, a hysteroscopic approach using the resectoscope is recommended. However, the HydroThermAblator is an exception for the non- resectoscopic techniques in this condition (Glasser et al., 2009). The success rates for reablation have been reported to be about 55% to 60% (Wortman et al., 2015). Complication rates of repeat EA are significantly higher than primary ablation. In (2008), The American Society Reproductive Medicine (ASRM) reported that the risks of perforation, more fluid absorption, and bleeding have been reported to be in the order of 9.3% to 11% versus 2.05% for primary ablation. PREOPERATIVE CARE: I. Counseling: Patients must be counseled about the expectations outcomes from EA. There are two main items for counseling: -33- 1. EA is not a method of sterilization. Patients should be advised for use a permanent for contraception as severe maternal-fetal complications have been reported in pregnancies following EA (rupture uterus, fetal limb defects, and preterm labor) (Lo and Pickersgill, 2006). 2. EA cannot guarantee amenorrhea. The aim of EA is to reduce the blood loss; amenorrhea, although possible, but cannot be confirmed (Isaacson, 2009). II. Endometrial preparation: Endometrial preparation can be considered preoperatively for 2 items; thinning of the endometrium and the use of prophylactic antibiotics. 1. Endometrial thinning: A thin endometrium can be achieved if the ablation is done in the first 2 days of post-menstrual phase, performing curettage before the procedure or administering of preoperative hormonal drugs; such as: progestogens, Danazol, and Goserelin (a gonadotropin-releasing hormone analogue, or GnRHa) (Sowter et al., 2014). It is well known that endometrial thinning will decrease operating time and reduce absorption of fluid used for uterine distension. In addition, it may also improve the long-term outcomes, including menstrual blood loss and dysmenorrhea. The drawbacks of endometrial thinning are related to hormonal therapy including their high cost and many side effects (Tan and Lethaby, 2013). A systematic review suggested that preoperative endometrial thinning using Goserelin and Danazol resulted in higher rates of amenorrhea at 12 and 24 months (Tan and Lethaby, 2013). -34- In another study conducted by Shawki et al. (2002) using a resectoscopic EA, amenorrhea rates at 12-month follow-up were 39% for endometrial preparation with Gn-RH agonists versus 34% for danazol, 26% for medroxyprogesterone acetate, and 18% for D&C. Preoperative endometrial thinning will depend on the product monograph for each individual device. For non-resectoscopic EA, Meta-analysis of a few randomized trials on second- generation devices (radiofrequency ablation and balloon devices), reported that no benefits have been achieved with the pretreatment endometrial thinning. Moreover, side effects were higher when hormonal therapies were used. On the controversy, for resectoscopic EA, preoperative endometrial thinning results in higher rates of amenorrhea, decreased fluid absorption, and shorter operative time (Sowter et al., 2014). Therefore, endometrial preparation can be used to ease resectoscopic endometrial ablation (EA) and can be considered for some non-resectoscopic techniques (Sowter et al., 2014). 2. The use of prophylactic antibiotics: No randomized control study recommended the routine use of antibiotic prophylaxis before EA by any technique (Thinkhamrop et al., 2007). Furthermore, observational data reveal an extremely low risk of infection (ACOG, 2009) III. Investigations: There are required investigations prior to EA include (SOGC, 2015): Pregnancy test. Papanicolaou test within previous 2 years. -35- Cervical cultures if clinically appropriate. Endometrial biopsy to exclude endometrial cancer. Assessment of uterine cavity for any anomalies or intracavitary pathology using TVS, SIS, or diagnostic hysteroscopy. POSTOPERATIVE CARE: Depending on the type of anesthesia used, patients are usually discharged within 1 to 3 hours after EA. They can resume their normal activities gradually, but are advised for (SOGC, 2015): No sexual intercourse for one week. Pain management with NSAIDs or opiates, and will usually resolve within 24 hours. Minimal pinkish discharge or mild vaginal bleeding is usual and can last up to several weeks following EA. Patients are instructed for seeking medical advice if they developed any fever, severe pain, or profuse vaginal bleeding (ASRM, 2008). Because it is often difficult to estimate the postoperative residual menstrual discharge and blood, the efficacy of the EA should be assessed at 6 and 12 weeks postoperatively (ASRM, 2008). TECHNIQUES: Endometrial resection/ablation is a method to destroy the basal endometrial layer to prevent future endometrial proliferation. Tissue destruction to a depth of 4 to 6 mm is needed to destroy this basal endometrial layer (Deb et al., 2008). -36- The first-generation techniques (Resectoscopic endometrial ablation) consist of targeted endometrial destruction under direct hysteroscopic visualization. These techniques included: laser ablation, electrosurgical endometrial resection by loop electrode or endometrial ablation by roll-ball (Deb et al., 2008). Resectoscopic EA offers many advantages. It permits an accurate assessment of uterine pathology with directed biopsies, documentation with photography, and concurrent treatment of associated intracavitary pathology. Also, it can be used in patients who have had previous EA or transmyometrial surgery (Hopkin et al., 2007). Despite their effectiveness, the first-generation methods had many disadvantages include: a requirement for a skilled and expert hysteroscopist, and a need for an operative room. Also, there have uncommon but serious complications including uterine perforation and fluid overload (Daniel et al., 2012). So, simpler alternatives have been established which nominated by; second-generation techniques (non- resectoscopic ablation) using a different energy sources to destroy the endometrial lining (Hopkin et al., 2007). The advantages of the second-generation techniques include: shorter operative time, needless for a specific training, and they can be done in the outpatient clinic (without anesthesia). They also help to avoid complications associated with the use of fluid distention media unlike first generation techniques while achieving similar results. For these reasons, non-resectoscopic procedures have become increasing in their popularity (Daniel et al., 2012). -37- I. Resectoscopic EA: Patients are placed in lithotomy position and the cervix is dilated to at least 10 mm. Most operative hysteroscopic systems involve a 9 mm (27 French) scope. Hysteroscopes are usually rigid, with using 12, 15, or 30 degrees of angulation. After uterine distension, the cavity is assessed for any endometrial lesions or abnormalities. Intrauterine landmarks (tubal ostia, internal cervical os, and/or the characteristic appearance of the endometrium) should be identified to confirm the successful entry of the cavity without created a false passage. Any focal lesions must be biopsied or resected. Endometrial polyps and small submucos myomas can be removed using the resectoscope; but larger (> 3 cm) myoma, resection will require a skillful and expert hysteroscopist (PerezMedina and Vallejo, 2011). The uterine walls can be ablated with the ball electrode or resected using the loop electrode while the rollerball is used exclusively at the fundus and ostial regions with a light touch technique applying no pressure to avoid their perforation. The electrode should always be visible, in contact with tissue, and moving toward the surgeon when activated. The treatment endpoint is a visual change in the endometrium to a yellow- brown honeycomb appearance which indicated that myometrial tissue has been reached. Prolonged activation of the electrode should not be done to prevent electrosurgical injuries. Also, the ablation beyond the cervico-uterine junction should be avoided fearing of cervical stenosis (Bradley, 2008). In (2013), the Advancing Minimally Invasive Gynecology Worldwide (AAGL) has stated hysteroscopic distention media as shown in table (4): -38- Table (4): Types of distention media for hysteroscopy. 1. Electrolytic solutions (Conductive): They are capable of conducting electricity, therefore cannot be used in conjunction with monopolar electrosurgical devices. They are recommended only for use in diagnostic cases and in operative cases in which mechanical, laser and bipolar energy is used. Per AAGL guidelines; the maximum fluid deficit for a patient should not exceed 2,500 ml. Normal Saline Isotonic Lactated Ringer’s Isotonic Protect against hyponatremia but can cause fluid overload which results in tachypnea, cerebral and pulmonary odema. 2. Non-electrolytic solutions (Non-conductive): They eliminate problems with electrical conductivity, but can increase the patient’s risk for hyponatremia and other specific complications. Use with monopolar energy. Per AAGL guidelines; the maximum fluid deficit for a patient should not exceed 1,000 ml. Glucose 5% Isotonic Glycine 1.5% Hypotonic Dextran 70 Hypertonic Mannitol 5% Isotonic Sorbitol 2.5%-5% Hypotonic Mannitol/Sorbitol mixture (Purisol) Hypotonic Contraindicated for patients with glucose intolerance. Metabolizes into ammonia and glycol, which can cross blood brain barrier causing dizziness, vomiting and coma. Also, may cause transient decrease in visual acuity and blindness. Complications include coagulation disorders, allergic reactions and adult respiratory distress syndrome (ARDS). Can crystallize on instruments, obstructing valves and channels. Has a diuretic effect; may cause hypotension and circulatory collapse. Metabolizes to fructose in the liver. Contraindicated for patients with fructose intolerance. Has the both hazards for Sorbitol and Mannitol. -39- II. Non-resectoscopic EA: Six devices are approved by FDA, using different energy sources for EA. They are listed in the following: Bipolar radiofrequency ablation (NovaSure). Cryotherapy (Her Option). Heated fluid freely circulated in the uterine cavity (Hydro ThermAblator). Fluid contained in a balloon (Thermachoice, Thermablate EAS, and Cavaterm). Future technologies such as the Aurora ablation system (radiofrequency energy and heated Argon gas forming plasma energy) have promising preliminary results (Sabbah et al., 2011). For safety and appropriate placement of intracavitary device, intraprocedural ultrasound guidance or pre- and post-procedural diagnostic hysteroscopy can be used. All the above technologies aim to achievement of coagulation that subsequently will lead to endometrial fibrosis. To obtain the maximum effect of this aim, 6 months are needed (Penninx et al., 2010). The choice from second generation technologies depends on the following (Kroft and liu, 2013): • Availability of scientific evidence. • Cost effectiveness. • Preference of the surgeon. Safety -40- Specifications of each of FDA devices are will be discussed in the following: Thermal balloon ablation (ThermaChoice, Thermablate EAS, and Cavaterm): For the ThermaChoice system (Fig. 2), a single-use silicon balloon-tipped catheter with a probe-hand piece measuring 5 mm diameter connected via a cable to a control unit. Within the balloon, the heating element is located, and a separate port attached to the hand piece permits the administration of 5% dextrose into the balloon. For activate the device, a minimum pressure of 150 mm Hg must be achieved; then, the fluid is heated to 87°C. Treatment time is 8 min. Finally, the balloon is deflated and removed (Sambrook et al., 2014). For Cavaterm system (Fig. 3), the catheter probe-hand piece measuring 9mm diameter, the fluid used is glycine 1.5%, the temperature is settled at 75°C, and the treatment time is 15 min (Alaily et al., 2003). For Thermablate system (EAS) (Fig. 4), the catheter probe-hand piece measuring 6 mm diameter, the fluid used is glycine 1.5%, the temperature is settled at 173°C, and the treatment time is 2 min. and 8 seconds (High temperature and short time) (Mangeshikar et al., 2003). All types of TBEA cannot be used on women with large or irregular uterine cavities because the balloon must be in direct contact with the uterine wall to cause ablation. Cavaterm is contraindicated for women whose uterine cavity is more than 10 cm long (from the internal os to the fundus), and Thermachoice for women whose uterine cavity is more than 12 cm long, and for those who have a latex allergy (NICE, 2004). -41- Bipolar energy ablation (NovaSure): The NovaSure (Fig. 5) includes a single-use 7.2-mm probe-hand piece that is attached to a based control unit. A bipolar mesh electrode is located at the end of the probe, covered by 2 extendable curved arms. The probe at 27.12 MHz causes the temperature of the basal endometrial layer to be raised to 50 -55°C allowing destroying 4-5 mm of the myometrium (Sabbah and Desaulniers, 2006). The probe is available in different lengths which allow the operator to set their manually according to the length of uterine cavity (assessed by uterine sound). In addition, NovaSure insufflates carbon dioxide; as a test for integrity of uterine cavity. The probe will not be activated automatically, if the cavity failed to pass this test. Moreover, NovaSure has a closed circuit for suction of any steam and blood derived, during the ablation phase (Elmardi et al., 2009). Cryoablation (Her Option): Her Option (Fig. 6) is the system for cryoablation of the endometrium. It includes a single-use 4.5-mm OD probe-hand piece which attached via a cable to a control unit. The probe is introduced in the uterine cavity, and when it is cooled to the temperature of less than -90°C, an elliptical ice ball will be formed. 2-4 "freeze" sites are typically needed for an optimal result. This procedure is done under abdominal ultrasonographic guidance. It allows a visual feedback for accurate treatment of the cavity but, extra personnel is always required (Dubak et al., 2000). -42- Microwave endometrial ablation (MEA) (Microsulis system): The microwave endometrial ablation device is called “Microsulis” system (Fig. 7). It includes an 8-mm probe which attached via a cable to a 9.2-GHz, 30-W control unit. When the device is introduced into the uterine cavity, a tissue temperature of 95°C at a depth of 6 mm will be achieved. The surgeon must move the probe from cornu to cornu all endometrium operated. The total treatment time is 1-4 minutes. The advantage of this system is that, a marker is located 4 cm from the probe tip to identify the cervicouterine junction and so, avoid cervical ablation. But, the disadvantage of this system that; the probe is too large for office use (Downes et al., 2007). Fig. 3: Thermachoice system for endometrial ablation. -43- Fig. 4: Cavaterm system for endometrial ablation. Fig. 5: Thermablate system (EAS) for endometrial ablation. -44- Fig. 6: Novasure system for endometrial ablation. Fig. 7: Her Option system for endometrial ablation. -45- Fig. 8: Microsulis system for endometrial ablation. COMPLICATIONS OF ENDOMETRIAL ABLATION I. Short term complications: 1. Pain, Nausea and vomiting: These are the most common adverse effects following EA which will generally resolve within 12 to 24 hours of the procedure (Lethaby et al., 2009). 2. Uterine perforation: It has been reported in 0.3% of non- resectoscopic EA and 1.3% of resectoscopic ablations. If uterine perforation is done during cervical dilatation or with the use of resectoscope (without electrosurgery), EA must be cancelled and the patient should be closely monitored for signs of intraperitoneal hemorrhage or visceral injury. If the -46- perforation occurs while using electrosurgery, abdominal exploration is mandatory to achieve hemostasis and exclude visceral injury (Sharp, 2012). 3. Perioperative hemorrhage: It has been reported in 1.2% of non- resectoscopic ablation and 3.0% of resectoscopic ablation. Immediate bleeding is usually due to cervical laceration or uterine perforation, while delayed bleeding is usually due to endometrial sloughing. In cases of late postoperative bleeding, coagulation studies should be performed especially if they were not done preoperatively (Lethaby et al., 2009). For acute hemorrhage, it may be managed with intrauterine Foley balloon tamponade or intracervical vasopressors injection (Sharp, 2012). 4. Hematometra: This complication has been reported in 0.9% of patients undergoing non-resectoscopic ablation and in 2.4 % of those undergoing resectoscopic ablation. Although intrauterine scarring is an aim of EA, hematometra will occur when endometrial areas are adherent and there is endometrial bleeding behind these occlusions. Hematometra should be suspected in a patient with a history of an EA and presents with cyclic pelvic pain despite of amenorrhea. It can be diagnosed by TVS and can be prevented by complete ablation of the uterine fundus, cornua, and tubal ostia and avoiding ablation of the cervico-uterine junction. Cervical stenosis or even hematometra are managed by hormonal suppression or cervical dilation with or without hysteroscopic adhesiolysis (SOGC, 2015). 5. Post-ablation tubal sterilization syndrome: The rate of this complication is high. It has been reported to occur to about 10% after EA especially, in patients who have undergone tubal ligation prior to EA. The proposed cause is that bleeding from active endometrium trapped in the uterine -47- cornua which can be managed laparoscopically by excision of this tubal stumps or even hysterectomy (Mehra et al., 2011). 6. Pelvic infections and fever: It occurs in the immediate postoperative period in approximately 1% of patients who undergone EA. In a metaanalysis, the incidence of these complications included endometritis (1.4 to 2.0%), myometritis (0 to 0.9%), pelvic inflammatory disease (1.1%), and pelvic abscess (0 to 1.1%) (Sharp et al., 2012). 7. Burn: It may be occurred due to exposure of the vagina or vulva to hot fluid in hydrothermal ablation or rupture of any thermal balloon (Birdsell, 2010). 8. Complications related to distention media: There most common complications are fluid overload (for electrolytic fluid) and hyponatremia (for non-electrolytic fluid): A. Fluid overload: It is the main risk when using isotonic, electrolytic fluid such as, normal saline or Lactated Ringer’s solution which can be prevented by the following (Darwish et al., 2010): Pre-treatment hormonal suppression of the endometrium. Adherence to a strict protocol of fluid monitoring must be considered. Fluid input, output and deficits values must be reported to the surgeon and anesthesiologist. Intracervical injection of pressor drugs (vasopressin, epinephrine). Using a distension pressure less than that of the patient’s mean arterial pressure. -48- Excessive fluid absorption can be treated …………………according to the followings: (SOGC, 2015): Excess fluid deficit of 500 cc: The anesthesiologist and surgeons should be aware about this loss. At a fluid deficit of 1000 cc: The procedure should be completed rapidly as possible. Urinary Foley’s catheter must be inserted for accurate measurement of urine output, fluid restriction is obligatory and IV diuretic (e.g. furosemide) may be used. At a fluid deficit of 1500 cc: The procedure should be cancelled immediately, serum electrolyte values must be obtained and any abnormalities will be managed appropriately. Patient should be observed and managed for signs of fluid overloads such as; tachypnea, pulmonary edema, changes in level of consciousness, encephalopathy, and seizure activity. B. Hyponatremia: It is most common complication resulting from intravasation of large amounts of non-electrolytic fluid, which occurs when the ratio between serum sodium and circulating blood volume dips below normal levels. When intrauterine pressure exceeds mean arterial pressure, fluid absorption increases significantly. For every 100 mL absorption of non-electrolyte solution, serum sodium falls by 1 mEq (Berg et al., 2009). -49- Hyponatremia is especially problematic for premenopausal women, as they are at 25 time’s greater risk for and permanent brain damage than postmenopausal women. Estrogen and progesterone in pre-menopausal women inhibits sodium pump activity, which protects against cerebral edema. This pump serves to move osmotically-active sodium cations from the brain cells, thus reducing swelling (Glasser, 2005). Normal serum sodium is 135 to 145 mEq/L. Serum sodium less than 135mEq/L can result in hyponatremia which is categorized as the following (Paschopoulos et al, 2006): Mild (130 to 135mEq/L): Changes in mental status; disorientation, irritability, twitching, nausea, vomiting, tachypnea. Moderate (125 to 130mEq/L): Signs of impending pulmonary edema; moist skin and mucous membranes, pitting edema and polyuria. Severe (below to 125mEq/L): Vital sign changes including hypotension and bradycardia, anemia, jaundice, cyanosis, further encephalopathy hyponatremic encephalopathy (HE). When serum sodium falls below 115 mEq/L, brain stem herniation develops in the swelling brain’s attempt to equalize interstitial and intravascular osmotic pressures. Permanent brain damage, coma, or even death. -50- A panel of United States experts an issued guideline on the diagnosis, evaluation, and treatment of hyponatremia and recommended urgent correction by 4-6 mmol/L to prevent brain herniation and neurological damage from cerebral ischemia. Then, the correction of acute hyponatremia varies by symptom severity, as the following (Verbalis et al., 2013): Mild to moderate symptoms: 3% NaCl infused at 0.5–2 mL/kg/h. Severe symptoms: 100 mL of 3% NaCl infused intravenously over 10 min. can be repeated up to 3 times. II. Long term complications: Recurrent AUB after EA is one of the most common long term complications. It may be caused by endometrial regeneration, adenomyosis, or rarely, pre-malignant or malignant condition of the uterus. An endometrial biopsy should be carried out if more than 1 year has passed since the procedure but, because of dense intrauterine synechiae which might be developed following EA, endometrial biopsy may be not possible. In this situation, TVS can be used to exclude endometrial abnormality. Hysterectomy is indicated for both diagnostic and therapeutic purposes, if adequate sampling cannot be obtained while ultrasonic evidence of a thickened endometrium is revealed (Daub et al., 2015). Pregnancy after EA has been reported. Possible complications include: spontaneous abortion, preterm labor, premature rupture of membranes, abnormal placentation, intrauterine growth restrictions and intrauterine fetal death (McCausland and McCausland, 2007). -51- CLINICAL EFFECTIVNESS: I. EA versus LNG-IUS: The LNG-IUS is a simple treatment for patients with AUB. It is more costeffective than any surgical technique, including EA. A Cochrane review concluded that EA and LNG-IUS had similar patient satisfaction, although EA was associated with more decreasing in the menstrual blood. Importantly, during the first 6 months of its use, LNG- IUS may be associated with progestogenic side effects including irregular bleeding, breast tenderness, and headache (Kauntiz et al., 2009). II. EA versus Hysterectomy: In a review consists of 9 prospective randomized clinical trials, hysterectomy was associated with better results regarding pain control and bleeding (Matteson et al. 2012). In another study with 4 years’ follow-up; satisfaction rate was 98% of women in the hysterectomy group versus 85% in the EA group (Munro et al., 2011). However, hysterectomy was associated with longer hospital stay and a higher risk of complications. In a retrospective study with 11 years’ follow-up, stress urinary incontinence and pelvic floor repair associated with EA was lower than with hysterectomy (Bhattacharya et al., 2011). Also, the costs of EA may be about half that of hysterectomy in some countries (Longinotti et al., 2008). -52- III. THERMAL BALLON VERSUS HYSTEROSCOPIC RESECTION: National institute for Health and Care Excellence (NICE) released a guideline on 2004 by the name of “Fluid-filled thermal balloon and microwave endometrial ablation techniques for heavy menstrual bleeding”. This guideline included a systemic review comparing the thermal balloon endometrial ablation (TBEA) and trans-cervical endometrial resection (TCRE) or hysteroscopic roll-ball ablation (RB) in the treatment of HMB. Eleven studies were included in this review. The 1st study was done by Meyer et al. (1998). This study was a randomized controlled study to compare the clinical efficacy and safety of a TBEA with RB in the treatment of dysfunctional uterine bleeding. At the beginning of the study, 255 patients were included; 128 for TBEA and 117 for RB but the results were only for 239 patients; 125 for TBEA and 114 for RB. Outcome measures were menstrual bleeding, pre-menstrual tension syndrome, ability to work outside the home and patient satisfaction at 0, 3, 6 and 12 months. The authors concluded that; in the treatment of dysfunctional uterine bleeding, uterine balloon therapy was as efficacious as hysteroscopic rollerball ablation and may be safer. The 2nd study was done by Romer (1998). The study was a prospective randomized trial to compare between Cavaterm balloon coagulation (TBEA) versus roller-ball endometrium coagulation (RB) as; a therapy of recurrent menorrhagia. Total number of patients was 20 (10 for TBEA and 10 for RA). Outcome measure was satisfaction rate. Follow-up was up to 15 months. The author concluded that; Cavaterm was in comparison to the operative hysteroscopy as a simple method for endometrial coagulation, and could also be used by hysteroscopically inexperienced gynecologists with simple technical equipment. -53- The 3rd study was done by Gervaise et al. (1999). This study was a controlled study comparing the clinical efficacy and safety of a thermal uterine balloon system with hysteroscopic endometrial resection in the treatment of dysfunctional uterine bleeding. In all, 147 women were treated by two experienced gynecological surgeons: one performed 73 thermal balloon ablations and the other 74 endometrial resections. Outcome measures were amenorrhea, hypomenorrhea, eumenorrhea or elimination of dysmenorrhea. Follow up was done between 3-36 months. The authors concluded that; uterine balloon ablation appeared to be as efficacious as endometrial resection. The former was much easier to perform especially, by those with limited expertise in hysteroscopic surgery, and thus more widely applicable and safer. The 4th study was done by Bonger et al. (2000). This trial was a prospective cohort study comparing TCRE and hot-fluid balloon ablation in 152 patients suffering from menorrhagia and not responding to medical treatment. Between 1992 and 1994, all patients (75) had TCRE, whereas from 1995 onward, all patients (77) had balloon therapy. Outcome measures were surgical re-intervention, menstrual pattern, and patient satisfaction at 3,6,12 and 24 months. The authors concluded that; because endometrial ablation with a hot-fluid balloon seems to be as effective as endometrial resection, with a lower complication rate, balloon ablation might become the procedure of choice for endometrial ablation. The 5th study was done by Grainger et al. (2000). This study was a randomized controlled study to compare the clinical efficacy and safety of a thermal uterine balloon system (TBEA) with hysteroscopic rollerball ablation (RB) in the treatment of dysfunctional uterine bleeding. At the beginning of the study, 255 patients were included; 131 for TBEA and 124 for RB but the results were only 227 patients; 122 for TBEA and 105 for RB. Outcome measures were amount -54- of uterine bleeding, secondary complications, and adverse effects. The follow up was done at 1 week, 3 and 6 months, 1 and 2 years. The authors concluded that; endometrial ablation by both procedures was highly successful in avoiding hysterectomy and relieving symptoms of menorrhagia. Additional benefits were reduction in dysmenorrhea and premenstrual syndrome. The 6th study was done by Loffer (2001). The study was a multicenter, prospective, randomized study aiming to compare uterine balloon therapy (TBEA) and hysteroscopic roller-ball endometrial ablation (RB) with respect to efficacy and safety in treatment of menorrhagia. Total number of patients was 255. 131 patients had TBEA and other 124 had RB but, at 3 years data was only available for 124 patients (114 for TBEA, 100 for RB). Outcome measures were menstrual flow, menstrual symptoms and adverse effects. The Follow up was done at 1 week, 2, 6, 12 months and at 2 and 3 years. The authors concluded that; endometrial ablation with the ThermaChoice uterine balloon or rollerball continues at 3 years to be a successful method for treating menorrhagia, avoiding hysterectomy, decreasing dysmenorrhea and premenstrual symptoms, and improving quality of life. The 7th study was done by Soysal et al. (2001). The study was a prospective randomized trial to compare between endometrial roller ball ablation (RB) and thermal balloon ablation (TBEA) after pharmacological endometrial thinning. Total number of patients was 96 (48 for TBEA and 48 for RA). Outcome measures were blood loss, hemoglobin levels, operating time, pain post operation, future hysterectomy, amenorrhea, complications and satisfaction. Follow-up was up to 12 months. The authors concluded that; thermal balloon ablation under local anesthesia for myoma-induced menorrhagia provided significant similar reductions -55- in menstrual blood flow and increases in hemoglobin values with no intraoperative complication compared to roller ball endometrial ablation. The 8th study was done by Brun (2002). This study was a randomized controlled trial (RCT) to compare the efficacy and safety of Cavaterm thermal balloon endometrial ablation with hysteroscopic endometrial resection on 51 patients with menorrhagia unresponsive to medical treatment. 29 patients had Cavaterm (TBEA), 21 patients had TCRE and 1 patient was lost to follow-up. Outcome measures were bleeding status, adverse effects and patient satisfaction after 3 months only. The authors concluded that; Cavaterm thermal balloon ablation was as effective as hysteroscopic endometrial resection to treat menorrhagia, both resulting in a significant reduction in menstrual blood loss and high patient satisfaction. The 9th study was done by Loffer and Grainger (2002). The study was a multicenter, prospective, randomized study to compare uterine balloon therapy (TBEA) and hysteroscopic rollerball endometrial ablation (RB) in the treatment of menorrhagia. Total number of patients was 402 (202 for TBEA and 200 for RB). Outcome measures were menstrual status, dysmenorrhea, pelvic pain, satisfaction. Follow up was extended to 5 years. The authors concluded that; uterine balloon therapy was effective as, had less complication and of a shorter operative time than hysteroscopic rollerball ablation in the treatment of menorrhagia. The 10th study was done by Pellicano et al. (2002). The study was a prospective randomized trial to compare the satisfaction rate and the effectiveness of transcervical hysteroscopic endometrial resection (TCRE) and thermal destruction of the endometrium in the treatment of menorrhagia (TBEA). Total -56- number of patients was 82 (42 for TCRE and 40 for TBEA). Outcome measures were satisfaction rate, operative time, discharge time, complication rate, reintervention rate, and resumption of normal activity. Follow up was up to 2 years. The authors concluded that; thermal destruction of the endometrium for the treatment of menorrhagia should be considered as an effective therapeutic option because of its acceptability among patients, shorter operative time, and lower blood loss. The 11th study was done by Zon-Rabelink et al. (2003). The study was a prospective randomized trial to compare between two methods of endometrial ablation, hysteroscopic rollerball electrocoagulation (RB) and non-hysteroscopic uterine balloon thermal (TBEA) ablation (Thermachoice), regarding intra- and post-operative technical complications and safety aspects. Total number of patients was 139 (77 for TBEA and 62 for RA). Outcome measures were intra- and postoperative technical complications and safety aspects. Follow-up was up to 24 months. The authors concluded that; endometrial ablation by uterine balloon thermal ablation (Thermachoice) was a safe and simple non-hysteroscopic procedure In the analysis of this systemic review, the followings had been reported: Three TBEA studies reported changes in PBAC score. A study by Meyer et al. (1998) which compared TBEA with RB, reported that at 12 months, 73% of the TBEA and 70% of the RB group had normal bleeding levels, defined as a PBAC score of less than 100. Soysal et al. (2001) reported that 71% of the TBEA and 79% of the RB group had normal bleeding levels at 12 months, defined by a more criterion (that is, a PBAC score of less than 76). They reported mean PBAC scores of 41.1 in the TBEA group and 40.2 in -57- the RB group. Zon-Rabelink et al. (2003) did not report actual PBAC scores, but stated that these were significantly better for the TBEA group than for the RB group at 24 months (p = 0.01), although not at 6 or 12 months. This trial measured treatment success as a post-operative PBAC score of less than 185. 78% of women in the TBEA group and 76% of women in the TCRE group achieved this at 24 months. At 24 months, between 5% and 8% of patients who had undergone TBEA, and between 9% and 15% of those who had undergone TCRE or RB, were still experiencing HMB. At 60 months, these figures were 2% for the TBEA group and 1% for the TCRE or RB group. No trial reported statistically significant differences between the groups for recurrent HMB. Five TBEA studies by Romer (1998); Meyer et al. (1998); Gervaise et al. (1999); Bonger et al. (2000); and Soysal et al. (2001) reported amenorrhea as a clinical outcome. Amenorrhea at 12 months was reported in between 10% and 40% of women for TBEA and between 17% and 30% for TCRE/RB. These differences were statistically significant in only one study which was done by Meyer et al. (1998) (14% for TBEA versus 22% for RB, p < 0.05). At 36 months, 13% of women undergoing TBEA and 21% of women undergoing RB had amenorrhea, and at 60 months 10% of women undergoing TBEA and 14% of those undergoing RB had amenorrhea. Six TBEA studies reported patient satisfaction. Romer (1998); Meyer et al. (1998); Zon-Rabelink et al. (2003); Bonger et al. (2000); and Soysal et al. (2001) reported non- significant differences in patient satisfaction between TBEA and TCRE and/or RB groups The proportion of women who were satisfied or very satisfied with the treatment ranged between 79% and 100% -58- in TBEA groups, and between 54% and 100% in TCRE and/or RB groups at 12 months. On the contrary, Pellicano et al. (2002) reported statistically significant differences between the TBEA and the TCRE and/or RB groups. In this trial, 43% of women undergoing TBEA evaluated the treatment outcome as 'excellent' at 12 months compared with 24% of women undergoing TCRE and RB. These figures were 35% and 4% respectively at 24 months. The five studies by Meyer et al. (1998); Gervaise et al. (1999); Soysal et al. (2001); Pellicano et al. (2002); and Zon-Rabelink et al. (2003) consistently reported shorter procedure times for TBEA compared with TCRE and/or RB. Of these, the two studies by Meyer et al. (1998) and Gervaise et al. (1999) reported the percentages of operations that took less than 30 minutes. For TBEA these percentages were 65% and 100%, and for TCRE and RB they were 24% and 53% respectively. These differences were significant in both studies (p < 0.05). The mean operating times were between 11.5 and 24 minutes in the TBEA groups compared with between 37 and 45 minutes in the TCRE and/or RB groups. The differences were statistically significant in all studies. Six trials reported the proportion of women who required further intervention. These studies were performed by Meyer et al. (1998); Gervaise et al. (1999); Bonger et al. (2000); Soysal et al. (2001); Pellicano et al. (2002); and Zon-Rabelink et al. (2003). At 12 months, between 1% and 10% of women in the TBEA group required further interventions compared with between 2% and 16% in the TCRE and/or RB groups. In one study by Pellicano et al. (2002), 5% of women undergoing TBEA and 10% of -59- women undergoing TCRE plus RB had had an additional procedure, and these percentages rose to 6% and 15% respectively at 24 months. This difference in the repeat surgery rate was statistically significant (p < 0.01). Meyer et al. (1998) repeat procedures for 15 of the 76 women (19.7%) in the TBEA group (13 hysterectomies and two repeat ablations), compared with 9 of 71 women (12.7%) in the RB group (seven hysterectomies, two repeat ablations, and one dilatation and curettage) at 60 months. Other studies were conducted by many authors: Singh et al. (2000) carried out a study to evaluate the effectiveness and safety of a technique for thermal endometrial ablation. The study was carried out in three steps; step I on 10 fresh uterine specimens, step II on 14 intact uteri during hysterectomy and step III in 5 patients, two weeks prior to hysterectomy. For the technique, a Foley catheter No. 14F, which was inflated by a 30 ml 0.09% NaCl with a temperature of 100°C (boiling) and the fluid was placed inside the uterus for 9 min. Uterine cavity and serosal temperature was recorded during the procedure. Thermal injury was assessed by gross and histological examination of the specimens. The mean maximum endometrial cavity temperature was 91 degrees C whereas serosal temperatures in steps I and II were 34 degrees C and 35.9 degrees C respectively. None of the balloons ruptured in any of the steps and there were no complications. In 13 of 14 specimens in step II, there was a zone of hyperemia with a depth of 3 to 7 mm. The corresponding histological picture was extensive hemorrhage and fragmentation of glands throughout the endometrium including the cornual regions. Consistent findings were noted in step III in which all but one showed extensive coagulative necrosis of the whole of endometrium with edema of the underlying myometrium. There was a statistically significant positive -60- correlation between the volume of fluid injected and depth of hyperemia. The authors concluded that; this technique could be a simple, effective, inexpensive and safe alternative to hysteroscopic endometrial ablation. Brun et al. (2006) carried out a Multicenter randomized trial to compare the efficacy and safety of Cavaterm thermal balloon endometrial ablation with hysteroscopic endometrial resection among 51 women with menorrhagia unresponsive to medical treatment. Amenorrhea rates were 36% and 29% in the Cavaterm and the endometrial resection groups at 12 months, respectively (ns). Both treatments significantly reduced uterine bleeding. A subsequent hysterectomy for recurrent bleeding was performed in 2 women, both previously treated by resection. The rate of women reporting good or excellent satisfaction was 89% in the Cavaterm group and 79% in the resection group at 12 months. Discharge time was significantly lower in women treated by Cavaterm, although postoperative pain at 1 hour was higher. There were no major complications in either group. The conclusion was that; Cavaterm thermal balloon ablation was as effective as hysteroscopic endometrial resection to treat menorrhagia, both resulting in a significant reduction in menstrual blood loss and high patient satisfaction. Rishma (2009) conducted a retrospective analysis of 156 women with dysfunctional uterine bleeding who had completed childbearing and who underwent uterine balloon ablation therapy using the Thermachoice device to assess the safety and effectiveness of this technique; as a permanent treatment of DUB. Regard to results, 49% women had amenorrhea while 41 % had oligomenorhoea or eumenorrhoea. 90% were satisfied with the procedure. There were no major complications during this study. The author concluded that; Thermal balloon endometrial ablation is a simple, safe and effective technique for the permanent treatment of DUB in well selected case. -61- Regarding endometrial ablation by Foley’s catheter, Helal et al. (2010) conducted a prospective randomized controlled study to assess the efficacy of a modified Foley's catheter endometrial ablation in the treatment of abnormal uterine bleeding in low resource settings among 430 premenopausal women. The primary outcome measure was patient satisfaction regarding menstrual blood loss. Secondary measures included improvement in quality of life scores and failure rates. Only 303 patients were available for evaluation at 3-year follow up. 270/303 (89.1%) reported their satisfaction as indicated by reduction in days of menstrual flow per cycle (4.2 vs. 8.8 days, p < 0.0001). There was a significant improvement in quality of life scores (p < 0.0001). The rate of failure varies according to the interval of follow up from 15.6% at 6 months to 10.9% at 3 years. The authors concluded that; modified Foley's catheter endometrial ablation is a cost effective alternative to other thermal endometrial ablation techniques in the treatment of abnormal uterine bleeding in low resource settings. Another prospective randomized controlled study was performed by Azza (2012) to assess the efficacy and safety of endometrial thermal ablation by a technique using Foley’s catheter to treat cases with intractable menorrhagia and to compare between results with and without pre procedure curettage. Forty eight patients aged from 39 to 52 years complaining of menorrhagia not responding to treatment for at least 6 months were included in the study, pre ablation endometrial curettage was done for 24 randomly selected cases (group 1) and ablation without curettage for the other 24 cases (group 2). Outcome measures were patient’s satisfaction, menstrual outcome and hysteroscopic diagnosed scarred endometrium. This study showed a satisfaction rate of 83.3%, improvement in menstrual bleeding (79.2%) and hysteroscopic diagnosed scarring of the endometrium (75%). Cases in group 1 had a significantly higher satisfaction rate (95.8%) than in group 2 (70.8%) -62- and significantly lower incidence of persistent menorrhagia after ablation than cases in group 2 (4.2% versus 37.5%, respectively). Hysteroscopic diagnosed endometrial scarring was significantly higher in group 1 (91.7%) versus (53.8%) for group 2. The authors concluded that; endometrial thermal balloon ablation by a technique using Foley’s catheter was a safe, simple, cheap and effective procedure as an alternative to hysterectomy for treatment of menorrhagia in properly selected cases and pre ablation endometrial curettage increased the satisfaction rate and improved menstrual outcome. Another randomized clinical prospective comparative study to compare the efficacy and safety of a uterine thermal balloon system with hysteroscopic endometrial resection in the treatment of selected cases of menorrhagia was done by Ashraf and Gamal (2012). In this study, patients were randomized into two equal groups of 35 patients each. Patients of the first group were treated by uterine thermal balloon system (35 patients), while those of the other group were treated by hysteroscopic endometrial resection (35 patients). Quantification of preprocedural and post-procedural menstrual blood was defined by pad count and selfassessment. Twelve-month follow-up data were presented on all women and compared statistically. The results indicated that both techniques significantly reduced menstrual blood flow with no clinically significant difference between the two groups. Success rates, as reflected by percent of patients who returned to normal bleeding or less, were comparable being 82.8% for the balloon group and 91.4% for the resection group. Procedural time was reduced significantly in the uterine balloon therapy group. The authors concluded that; uterine thermal balloon therapy is as efficacious as hysteroscopic resection in the treatment of selected cases of menorrhagia. -63- Also, Naz et al. (2012) conducted a study to determine the efficacy of modified thermal balloon ablation using Foley’s catheter in the treatment of heavy menstrual bleeding. This study included 53 patients with heavy menstrual bleeding between 35 to 45 years of age. Main outcome measures were reduction in menstrual flow, amenorrhea, minor short term side effects and need of hysterectomy after failure of procedure. For results: 69% of patients had a reasonable reduction in menstrual blood flow, 12% had amenorrhea at the end of 6 months of follow up, 18% observed no change in bleeding pattern and underwent hysterectomy after failure of procedure and 6% patients complained of minor side effects like abdominal pain and endometritis. The authors concluded that; modified thermal balloon ablation with Foley’s catheter can be promising conservative management of heavy menstrual bleeding in resource poor settings. A brief report was done by (Api and Api, 2012) about using Foley’s catheter EA on 3 women with severe meno-metrorrhagia unresponsive to medical therapy. The aim of this report is to evaluate the effectiveness and safety of a new, simple and money-saving procedure, namely Foley catheter balloon endometrial ablation (FCBEA), for the treatment of DUB. For the technique, they used a Foley catheter of a size 18-F which was inflated by a 30 ml 0.09% NaCl with a temperature of 100°C (boiling) and the fluid was placed inside the uterus for 3 minutes for 3 times (9 min.). All the 3 women were achieved a complete amenorrhea for a 19 months follow-up period with no procedure-related complications except, a mild persistent watery discharge for 14-27 days; postoperatively. The authors concluded that; Foley catheter balloon ablation is a new method of EA, promising, safe and effective minimal invasive method for the treatment of abnormal uterine bleeding. A retrospective study by Bouzari et al. (2014) was conducted on 30 patients with menorrhagia who were unresponsive to hormone therapy or not candidates for -64- hysterectomy underwent endometrial ablation using Cavaterm. The aim of this study was to the analysis of the patient with menorrhagia subjected to operations of Cavaterm and explores its effectiveness and acceptability. Preoperative and postoperative PBAC Scoring System was used to assess menorrhagia. Outcome measures were amenorrhea rates, reduction of menstrual flow rates, and patients' satisfaction rates at 3, 6 and 12 months postoperative. After the follow-up, 36.7%, 43.3%, and 36.7% of women had a reduction in vaginal bleeding, respectively while amenorrhea rates were 56.7%, 50.0%, and 56.7%. The rate of women's reported good or excellent satisfaction was 93.3% in 12 months. During the follow-up period, no woman received a subsequent hysterectomy. The conclusion indicated that outcome with the Cavaterm was good for women with menorrhagia. The authors stated that, it was necessary to emphasize on lower operative and postoperative procedural risk and a deleterious effect on patients who were unresponsive to hormone therapy. COST EFFECTIVNESS: A meta-analysis was done by Kroft and Liu (2013) to assess the economic effect of the second-generation EA devices compared to first-generation for treatment of pre-menopausal menorrhagia. After full-text screening, 3 studies were included in the final qualitative synthesis after met eligibility criteria and (2 studies comparing first-generation with second-generation and 1 study comparing secondgeneration with second-generation). The two studies (Garside et al., 2004; Robert et al., 2011) comparing firstgeneration with second- generation devices were both cost-utility studies from United Kingdom while the single study (Bonger et al. 2005) comparing the -65- second- generation with second-generation itself (Novasure vs. Thermachoice) which was a cost-effectiveness study from Netherlands. The first cost-utility study was performed by Garside et al. (2004) comparing the thermal balloon with TCRE, TCRE+rollerball, and rollerball ablation using a model for a cohort of 1000 patients over a 10-year. The study found that; the thermal balloon was more cost effectiveness than all three types of first-generation ablation. The other cost-utility study was published by Robert et al., (2011) also, on 1000 women over 10 years to compare first-generation with second-generation ablation devices. This study concluded that; hysterectomy was more cost-effective than first-generation while the 2nd generation ablation was less cost than hysterectomy. SAFETY: Amso et al. (1998) assessed the safety aspects of thermal balloon therapy, and found that that up to 16 minutes of therapy can destroy the endometrium and the submucosal layers. The myometrium is only coagulated to a depth where full thickness necrosis or injury is unlikely. A review by Barrow et al. (1999) concluded that thermal balloon is the safest of all endometrial ablation methods on an outpatient basis. Also, Alestebi and Eksaknder (1999) did not encounter any complications when performing endometrial ablation using the thermal balloon. A multicenter, prospective, randomized study comparing thermal balloon ablation with endometrial resection for the treatment of AUB by Gervaise et al. -66- (1999), reported that; there were minimal postoperative morbidities with no intraoperative complications. Another prospective randomized trial on thermal destruction versus hysteroscopic transcervical endometrial resection for menorrhagia found less intraoperative blood loss and shorter operating time in the thermal destruction group (Pellicano et al., 2002). Lok et al. (2002) performed thermal balloon endometrial ablation on 30 women with menorrhagia in an outpatient setting and did not encounter any intraoperative complication. Mangeshikar et al. (2003), Alaily et al. (2003) confirmed these results. Ashraf and Gamal (2012) reported intra-operative complications occurred in 8.5% of the hysteroscopic resection patients, whereas no intra-operative complications occurred in the thermal balloon group when they compared the efficacy and safety of a uterine thermal balloon system with hysteroscopic endometrial resection in the treatment of selected cases of menorrhagia. Regard to Foley’s catheter endometrial ablation, Azza (2012) and Naz et al., (2012) reported minor side effects like abdominal pain and endometritis.. A meta-analysis published by Kroft and Liu (2013) found a decreasing in the rate of intraoperative and postoperative complications with second-generation systems compared to first-generation. Also, there was a decreasing in the operating time by 16.6 minutes, using the second-generation systems. However, there was no difference between first- and second- generation systems in the incidence of patients requiring further surgery during the follow-up period. -67- Vitagliano et al. (2014) conducted a longitudinal observational study to evaluate the postoperative pain after thermal balloon ablation for DUB compared with transcervical endometrial resection. 47 women were included in the study. They reported that; Pelvic pain was higher 1 and 4 hours after procedure in thermal balloon ablation group, and patients in the same group required more analgesic rescue dose. There were no complications such as uterine perforation, heavy blood loss or thermal injuries with both the procedures. So, the authors concluded that; TBEA appeared a more painful procedure than TCRE, both in the immediate postsurgical time and 30 days after surgery. TREATMENT FAILURE: Failure of treatment (EA) is defined by persistent of pain or bleeding after endometrial ablation that need re-ablation or hysterectomy. This definition was published by El-Nashar et al. (2009) when they conducted a study on 816 patients underwent endometrial ablation either by radiofrequency device or thermal balloon ablation. Also the authors described the factors of treatment failure which included: age before 45 years; parity equal or more than 5; previous tubal ligation; and history of dysmenorrhea. -68- PATIENTS AND METHODS TYPE OF THE STUDY: A prospective randomized controlled study. PLACE OF THE STUDY: Obstetrics and Gynecology Department in Benha university hospital. DURATION OF THE STUDY: Between January 2014 and December 2015. AIM OF THE STUDY: To compare the efficacy and safety of hysteroscopic endometrial ablation (resectoscopic using loop and roll-ball) with nonhysteroscopic technique (Foley’s catheter balloon) in the treatment of menorrhagia not responding to medical treatment. INCLUSION CRITERIA: The study included 100 premenopausal patients complaining of menorrhagia not responding to medical treatment for at least 6 months. Patients who met entry criteria were randomized to either the hysteroscopy or the Foley’s catheter group in a 1:1 allocation ratio (50 patients each) by the generation of a random numbers table. For quantification of menstrual blood, there are different methods. In our study, a prospective documentation of bleeding patterns was done by asking the patients to record menstrual frequency, number of pads used per day, and number of days of flow per cycle. These data were written in special sheet given to the patients. Also, side effects and need for further therapy were recorded. EXCLUSION CRITERIA: They included the followings: Patient needs further pregnancy. -69- Uterine depth > 12 cm. The presence of uterine scars (previous CS, myomectomy, etc.). Any intracavitary pathology as; submucous myoma, polyps or adhesions. Endometrial hyperplasia or malignancy. Active pelvic inflammatory disease (PID). Finally, patients with postmenopausal bleeding. METHODS: Informed written consent was obtained from all cases, and the study was approved by the local ethics committee. It was discussed during the consent process that EA was designed to reduce menstrual flow, not necessarily to eliminate it. Endometrial biopsy within the last 6 months is needed to exclude malignant or a typical lesion in the endometrium. All cases were subjected to full history taking of mainly menstrual pattern and severity of bleeding by recording the number of pads per day, duration of bleeding, presence of blood clots and manifestation of iron deficiency anemia. Clinical examination (general, abdominal and gynecological) and laboratory investigations (CBC, kidney function, liver function tests, and coagulation profile) were done for all patients. Transvaginal ultrasound (TVS) was done for all cases to rule out any pathology in uterus or adnexa and to measure endometrial thickness, if there was any doubt, SIS or diagnostic hysteroscopy was done to exclude uterine cavity abnormalities and endometrial lesions. -70- No pretreatment endometrial thinning regimens were used; however, ablation was timed to be performed in early follicular phase of the menstrual cycle (day 4-6). For all patients, EA was performed under general anesthesia. Prophylactic antibiotic was given at the start of the procedure. To reduce postoperative pain, all patients received indomethacin 100 mg rectal suppository immediately after the procedure. Technique of thermal balloon endometrial ablation by Foley’s catheter: 1. The patient was draped in the lithotomy position. 2. Sterilization of vulva, vagina and cervix was carefully done using gauze soaked with povidone iodine solution. 3. Two Simm’s speculums were introduced in into the vagina. The cervix was grasped with a multiple toothed vollesullum. Uterine sounding was done. Then, cervical dilation was performed till number 6 Hegar. 4. Foley’s catheter number 18Fr/CH (latex silicon coated, Ultramed) (Fig. 9), with a capacity of 30–50 ml was tested for possible leak and risk of rupture by inflation of about 20 ml boiling saline then deflation and the tip of the catheter was cut just above the balloon to allow the inflated balloon to fit well close to the uterine fundus. 5. The Foley’s catheter was inserted gently into the uterine cavity and inflated by a variable volume of boiling saline 0.9% as much as the uterine cavity capacity permits till resistance to add more fluid is reached under maintained moderate pressure. -71- 6. For safety, a vaginal gauze pack was placed around the catheter to protect against accidental balloon leak or rupture. 7. Maintenance of temperature was done by frequent changing of the boiled saline every 3 minutes by a new boiling saline and the procedure was continued for 9 minutes then the balloon was deflated and removed. Fig. 9: Foley’s catheter No. 18 French Technique of resectoscopic endometrial ablation: 1. The patient was draped in the lithotomy position. 2. Sterilization of vulva, vagina and cervix was carefully done using gauze soaked with povidone iodine solution. 3. Two Simm’s speculums were introduced in into the vagina. The cervix was grasped with a multiple toothed vollesullum. Uterine sounding was done. Then, cervical dilation was performed till number 9 Hegar dilator. -72- 4. The resectocope elements (passive handle, 4 mm Hopkins II telescope with an angle 30°, continuous flow outer sheath, and 26 French in the whole size) (Karl Storz, Germany) were inserted (Fig. 10). 5. Uterine distention was done by the gravity method using a nonconductive, low viscosity solution (Glycine, 1.5 %). The fluid balance was recorded and monitored continuously. 6. After exclusion of the uterine cavity for any focal lesion, the uterine walls were ablated using monopolar diathermy by the loop electrode with the direction of the ablation towards the surgeon when activated. 7. The uterine walls near tubal ostia were ablated using the roll ball (fearing of increase risk of perforation due to thin endometrium). 8. The procedure endpoint was a visual change in the endometrium to a yellow- brown honeycomb appearance which indicated that the myometrial tissue has been reached. Then, the resectoscopic elements were removed. Fig. 10: The resectoscope elements. -73- For both groups, the operating time was measured from the initiation of anesthesia to the end of the procedure. Any intra-or postoperative complications were recorded. Then, the patient was discharged in the same day. All patients were assessed postoperatively at 3, 6, and 12 months. Follow up of all patients in the outpatient clinic with a subjective assessment of clinical outcomes including patients’ satisfaction, menstrual outcome and occurrence of amenorrhea, hypomenorrhea, euomenorrhea and persistent or increasing menorrhagia. -74- RESULTS No patients were lost to follow-up. The demographic data and gynecological histories of the 100 patients treated either by the Foley’s catheter technique or hysteroscopic resection demonstrated no significant differences in age, body mass index (BMI), duration of menorrhagia, pads/cycle, uterine cavity depth, and position; as shown in table (5). Table (5): The demographic and gynecological data in study groups Foley’s catheter group Hysteroscopic resection group P (n=50) (n=50) value Mean Range n (%) (+SD) Mean Range n (%) (+SD) Age (years) 46.4 (4.9) BMI (kg/m2) 30.7 (6.6) 25.2-40.3 32.1 (7.3) 28.1-49.6 NS 9.4 (7.3) 10.4 (7.9) NS Years with 40-52 44.6 (5.2) 2-12.0 40-49 NS 1.4-10.4 menorrhagia Pads/cycle 86 ± 40.4 Uterine cavity 10.4 (1.0) 81 ± 41.7 4.0-10.5 11.1 (1.2) NS 6.0-12.0 NS depth (cm) Uterine position (AVF/RVF) AVF = 43 (86%) AVF = 41 (82%) NS RVF =7 (14%) -75- RVF =9 (18%) Procedure time was significantly less for the Foley’s catheter group, compared with mean operative time of in the hysteroscopic resection group (p<0.05); as shown in table (6). Intra-operative bleeding indicated by hemoglobin (HB) drop postoperatively was higher among the hysteroscopy group, but the difference was not significant statically; as shown in table (6). Hospital stay after operation was longer in hysteroscopy group and it was statistically significant (p<0.05); as shown in table (6). Table (6): The operative time (min.), postoperative Hb drop (%) and hospital stay (Hrs.) in study groups Foley’s catheter group (n=50) Hysteroscopic resection group (n=50) Mean (+SD) Range Mean (+SD) Range Operative time (min.) 15.5 + 3.5 15-20 30.5+8.6 24-37 <0.05* Hb drops (%) 0.8 + 0.3 0.2-0.9 1.2+1 0.5-1.6 NS Hospital stay (Hrs.) 8 +2 6-10 14+8 8-20 <0.05* NS= non-significant. -76- P value There were no intra-operative complications in the Foley’s catheter group. However, we had 3 intra-operative complications in the hysteroscopy group (6%), 2 cases (4%) with fluid overload, and 1 (2%) patient with cervical lacerations; as shown in chart (1) and (2). Postoperatively, 3 cases of endometritis were attributed to the Foley’s catheter group (6%) and all cases responded to oral antibiotic therapy. For hysteroscopy group, there were 2 cases (4%) developed endometritis (also, resolved with oral antibiotics) and 1 case (2%) had a delayed adverse event with hematometra (resolved with D&C); as shown in chart (1) and (2). Regard to intra and postoperative complications, there was no statically significant difference between Foley’s catheter and hysteroscopic resection groups; as shown in chart (3). Chart (1): Intra and postoperative complications in Foley's catheter group Endometritis 6% No complication 94% -77- Chart (2): Intra and postoperative complications in hysteroscopic resection group Endometritis Fluid overload 4% 4% Hematometra 2% Cervical laceration 2% no complication 88% Chart (3): Intra and postoperative complications in study groups 12% 10% 8% 6% Hysteroscopic resection group 4% Foley"s catheter group 2% 0% -78- There was significant reduction in the menstrual flow after treatment as evidenced by reduction in number of pads/day, days/cycle, and pads/ cycle in both groups; as shown in tables (7) and (8). Table (7): Menstrual flow before and after treatment in Foley’s catheter group Pre treatment Post treatment P value Mean (+SD) Range Mean (+SD) Range Pads/day (n=50) 12 + 2.5 6-15 4.5+2.3 0-10 <0.05* Days/cycle (n=50) 11.2 + 5.7 10-21 4.3+2.3 0-12 <0.05* Pads/cycle (n=50) 134.4+48 60-224 26.4+20.8 0-72 <0.05* Table (8): Menstrual flow before and after treatment in resection group Pre treatment Post treatment P value Mean (+SD) Range Mean (+SD) Range Pads/day (n=50) 11.9 + 2.3 6-19 5+1.5 0-11 <0.05* Days/cycle (n=50) 12.3 + 4.4 9-26 4+2.9 0-10 <0.05* Pads/cycle (n=50) 143.7 + 50 54-213 24.2+22.8 0-78 <0.05* -79- Regard to post treatment menstrual flow changes, although the difference between both groups was not statistically significant, there was a significant greater percentage of patients in the hysteroscopy group (40.0%) compared with the uterine balloon therapy group (20.0%) were amenorrheic at their 12-month follow up (p<0.05). Percent of patients with hypomenorrhea, eumenorrhea, and menorrhagia (failed treatment) in both treatment arms of the study were comparable; as shown in table (9). The success rates, defined as percent of patients who had eumenorrhea or less 12 months after treatment, were 86% for the Foley’s catheter group and 92% for the hysteroscopy group. Success rates were clinically comparable and not statistically different among the two groups; as shown in table (8). Table (9): Post treatment pattern in both groups at last visit (12 months) Foley’s catheter group (NO. and %) Hysteroscopic resection group P value (NO. and %) Amenorrhea 7 (14%) 14 (28%) <0.05* Hypomenorrhea 10 (20%) 9 (18%) NS Eumenorrhea 26 (52%) 23 (46%) NS Menorrhagia 7 (14%) 4 (8%) NS Success rate 43 (86%) 46 (92%) NS -80- Furthermore, repeated measures analysis of variance demonstrated no difference between the two treatment arms (Foley’s catheter & hysteroscopic resection group) in bleeding pattern variability at 3, 6, and 12 months after the procedure; as shown in chart (4) and (5). Regard to Foley’s catheter group; at 3,6, and 12 months follow up: Amenorhea was recorded in 5 (10%), 6 (12%) and 7 (14%) patients, respectivly while hypomenorhea was recorded in 6 (12%), 9 (18%) and 10 (20%) patients, respectivly. Eumenorrhea was recorded in 34 (68%), 29 (58%) and 26 (52%) patients, respectivly. Finally, menorrhagia (failed treatment) was recorded in 5 (10%), 7 (14%) and 7 (14%) patients, respectivly; as shown in chart (4). Chart (4): Changes in the bleeding pattern, over time, after Foley’s catheter ablation. 60 50 40 menorrhagia Eumenorrhea 30 Hypomenorrhea 20 Amenorrhea 10 0 3 month 6 month 12 month -81- Regard to hysteroscopic resection group; at 3,6, and 12 months follow up: Amenorhea was recorded in 11 (12%), 13 (15%) and 14 (16%) patients, respectivly while hypomenorhea was recorded in 8 (16%), 8 (16%) and 9 (18%) patients, respectivly. Eumenorrhea was recorded in 27 (54%), 25 (50%) and 23 (46%) patients, respectivly. Finally, menorrhagia (failed treatment) was recorded in 4 (8%) at the all 3 times; as shown in chart (5). Chart (5): Changes in the bleeding pattern, over time, after hysteroscopic resection 60 50 40 menorrhagia 30 Eumenorrhea Hypomenorrhea 20 Amenorrhea 10 0 3 month 6 month 12 month Treatment failure was occurred in 11% women who suffered from continued menorrhagia, remaining dissatisfied with their bleeding pattern. The failure rate was 8% (n = 4) for endometrial resection and 14% (n = 7) for Foley’s catheter treatment. All these patients were managed surgically by, abdominal hysterectomy. -82- DISCUSSION If medical therapy is unsuccessful in the treatment of DUB, D&C may be curative but it is only a temporary solution. Although hysterectomy is curative, it may be associated with a 40% morbidity rate and 10 per 10,000 mortality rate (Ashraf and Gamal, 2012) As a result, other surgical intervention for menorrhagia has been developed. Endometrial ablation is one of the simplest, safest and most promising alternatives for treatment of menorrhagia in the era of minimal invasive surgery (Singh et al. 2000). Uterine thermal balloon therapy (TBEA) was developed to simplify the procedure of EA with an efficacy that parallels to classical hysteroscopic methods (Singer, 1994). Thermal balloon ablation devices which used are Thermachoice, Cavaterm and Thermablate systems. Although they are safe, effective and easily used, they have the disadvantage of being expensive and unavailable in many centers, so the use of Foley’s catheter balloon in this study was a cheap and available alternative to these devices. However, Foley’s catheter balloon has the disadvantage of absence of the control unit which allows proper setting and monitoring of temperature and pressure, thus the use of this simple technique should be only used in low resources countries (Azza, 2012). Failure or success of TBEA is multi factorial; increased age, shorter of uterine depth and maintaining adequate pressure inside the balloon can predict a successful treatment. However, the outcome is not affected by parity, uterine volume and endometrial thickness (Shamash and Sayed, 2004). -83- Neuwirth et al. (1994); reported a success rate of 83% used hot 5% dextrose in a latex balloon. First generation techniques reported successful results in 61.5-90% of patients (O’Connor and Magos, 1996; Overton et al. 1997) while TBEA reported success rate in 80-97% (Meyer et al., 1998; and Feitoza et al. 2003). Regarding Foley’s catheter ablation, the data obtained by Singh et al. (2000) were encouraging about its safety and efficacy although the number of patients was small in their study. Api and Api (2012) confirmed these results in a brief report in only 3 cases with intractable menorrhagia. Helal et al. (2010) reported 89.1% of satisfaction in 303 patients when they conducted a prospective randomized controlled study to assess the efficacy of a modified Foley's catheter EA in the treatment of AUB in low resource settings; as indicated by reduction in menstrual flow days per cycle (4.2 Vs. 8.8 days, p < 0.0001). There was a significant improvement in scores of life quality (p < 0.0001). Another prospective randomized controlled study conducted by, Azza (2012) to assess the efficacy and safety of EA by a technique using Foley’s catheter to treat cases with intractable menorrhagia showed a satisfaction rate (83.3%), improvement in menstrual bleeding (79.2%) and hysteroscopic diagnosed endometrial scarring (75%). Also, Naz et al. (2012) conducted a study included 53 patients to determine the efficacy of EA by Foley’s catheter in the treatment of HMB. They reported that 69% of patients had a reduction in menstrual blood flow and 12% had amenorrhea at the end of 6 months of follow up. The authors concluded that; EA by Foley’s catheter had promising results for the conservative management of HMB in low resource settings. -84- For pre-ablation endometrial thinning, Bongers et al. (2002) advised hormonal suppression drugs or endometrial curettage before thermal ablation; as they believed that thick endometrium prevents a deep intramural coagulative effect, thereby limiting to basal layer damage. Azza (2012) agree with this advice; when she reported a significantly higher satisfaction rate (95.8 vs. 70.8%), a significantly lower incidence of persistent menorrhagia (4.2% versus 37.5%) and a significantly higher hysteroscopic diagnosed endometrial scarring (91.7% vs. 53.8%) in patients who underwent pre ablation endometrial curettage than without, respectively. On the contrary, this assumption was not confirmed by many authors (Lissak et al. 2003; and Garza-Leal et al., 2010); as they reported that endometrial thinning did not affect the outcome of TBEA. Moreover, in a study performed by Amso et al. (2002, patients who had D&C experienced statistically more failures which is difficult to explain, and the performance of this procedure before TBEA can be used only to exclude occult malignancy. In our study, success of EA was defined as subjective reduction of menses to eumenorrhea or less. We achieved success rates of 86% and 92% in Foley’s catheter ablation and the hysteroscopic resection groups respectively which were not statically different between the 2 groups. Those rates were consistent across 3 occasions of follow up in the first year. Statistically significant differences were found only between pre-treatment and post-treatment menstrual flow in both treatments’ arms (p<0.05). Although, the following studies used another thermal balloon rather than Foley’s catheter, our results were comparable to those obtained by Meyer et al. (1998) whom recorded success rates between 80.2% to 84.3% for TBEA and -85- hysteroscopic resection groups respectively with significant reduction in menstrual flow and duration before and after treatment (p<0.0001). The higher success rates recorded in other studies, reaching up to 97% and the cause might be due to the longer periods of follow up (3 years) (Singer et al, 1994; Garry, 1995; and Overton and Maresh, 1995). In a study conducted by, Brun et al. (2006) using Cavaterm system; amenorrhea rates were 29% and 36% in the endometrial resection and thermal balloon groups at 12 months, respectively. Both treatments significantly reduced menstrual blood loss. The authors concluded that; TBEA was as effective as hysteroscopic endometrial resection to treat menorrhagia, both resulting in a significant reduction in menstrual blood loss and high patient satisfaction. Regard to post treatment menstrual flow changes, we recorded a significant greater percentage of patients in the hysteroscopy group (40.0%) compared with the uterine balloon therapy group (20.0%) that were amenorrheic at their 12-month follow up (p<0.05). However, Percent of patients with hypomenorrhea, eumenorrhea, and menorrhagia (failed treatment) in both treatment study groups were comparable. So, postoperative amenorrhea was not a key endpoint because patients undergoing any form of EA should not predict this result. The main goal for most menorrhagic women is to be returned to normal menstrual flow or less. If any patient expecting amenorrhea, she should choose hysterectomy, as this is the only procedure that can guarantee such a result. Frankly, although amenorrhea rates were statistically higher among the hysteroscopic ablation patients, no statistical difference in the results between the two groups as regards hypomenorrhea or eumenorrhea. -86- Treatment failure is defined; as persistent bleeding after procedures. In our study, 11% women suffered from continued menorrhagia remaining dissatisfied with their bleeding pattern. The failure rate was 8% (n = 4) for endometrial resection and 14% (n = 7) for Foley’s catheter treatment. All these patients were managed surgically by, abdominal hysterectomy. Helal et al. (2010) reported that; 18% of patients had no change in bleeding pattern and underwent hysterectomy after EA by Foley’s catheter and the failure rate varies according to the interval of follow up from 15.6% at 6 months to 10.9% at 3 years. In a study conducted by EL-Nashar et al. (2009), they described predictors of treatment failure which included: age younger than 45 years; parity of 5 or greater; previous tubal ligation; and history of dysmenorrhea. In our study, although the length of post-ablation follow-up was limited to 12 months, such improvements in menstrual bleeding had been achieved in other studies with 3 years or longer follow up. Ahonkallio et al. (2008) reported that with a long term follow up (5 years), 76% of patients were satisfied with TBEA which can be considered as a good result. Also, in a long follow up study by, Helal et al. (2010), they reported a reduction in the number of days per cycle and the long term improvement in dysmenorrhea at 12, 24 and 36 months. At 6 months following this procedure, 18.4% of patients were amenorrheic, 41.6% were hypomenorrhoeic, 14.4% had spotting and 15.6% reported no improvement and underwent hysterectomy. At 3year follow up, the rate of amenorrhoea, hypomenorrhoea and spotting were 17.2, 37; 20.1%, respectively. For all patients, general anesthesia was chosen as the method of anesthesia in our study. This was done to target the operative techniques results to unify the -87- inclusion criteria. However, uterine thermal balloon therapy can be done with paracervical block which is an advantage that may decrease cost and intraoperative complications (Penninx et al., 2009). In our study, procedure time and hospital stay were significantly less for the Foley’s catheter group, compared with hysteroscopic resection group. These results were also agreed with those by Gervaise et al., (1999) and Ashraf and Gamal (2012). We recorded intra- operative complications in 6% of hysteroscopic resection No intra- operative complications were recorded in the balloon group. Delayed complications were recorded in 6% of patients in both groups. Those figures are comparable to those of recorded by Meyer et al. (1998.) The American Association of Laparoscopists reported a complication rate of 4.4% for operative hysteroscopy (Hulka et al., 2008). Also, Helal et al. (2010) reported that 6% patients complained of minor side effects like abdominal pain and endometritis after Foley’s catheter ablation. However, several complication rates ranging from 5 to 10% have been documented (Arieff and Ayus, 1993; Brook et al., 1993; and Garry et al., 1995). The pitfall in our study may be the absence of long term follow up, so several studies with longer follow up are needed to be performed. -88- SUMMARY TYPE OF THE STUDY: A prospective randomized controlled study. PLACE OF THE STUDY: Obstetrics and Gynecology Department in Benha university hospital. DURATION OF THE STUDY: Between January 2014 and December 2015. AIM OF THE STUDY: To compare the efficacy and safety of hysteroscopic endometrial ablation (resectoscopic using loop and roll-ball) with nonhysteroscopic technique (Foley’s catheter) in the treatment of menorrhagia not responding to medical treatment. INCLUSION CRITERIA: The study included 100 premenopausal patients complaining of menorrhagia not responding to medical treatment for at least 6 months. Patients who met entry criteria were randomized to either the hysteroscopy or the Foley’s catheter group in a 1:1 allocation ratio (50 patients each) by the generation of a random numbers table. For menstrual blood quantification, there are several methods. In our study, a prospective documentation of bleeding patterns was achieved by asking he patients to report number of pads used per day and number of days of flow per cycle. These data were written in special sheet forms given to the patients assigned for trial entry. They were queried as to menstrual volume and frequency, side effects, and need for further therapy. -89- EXCLUSION CRITERIA: They included the followings: Patient needs further pregnancy. Uterine depth > 12 cm. The presence of uterine scars (previous CS, myomectomy, etc.). Any pathology distorting the uterine cavity as; submucous fibroids, intrauterine polyps or adhesions. Endometrial hyperplasia or malignancy. Active pelvic inflammatory disease (PID). Finally, patients with postmenopausal bleeding. METHODS: Informed written consent was obtained from all cases, and the study was approved by the local ethics committee. It was emphasized during the informed consent process that these modalities of treatment were designed to reduce menstrual flow, not necessarily to eliminate it. Endometrial biopsy within the last 6 months is needed to exclude malignant or a typical lesion in the endometrium. All cases were subjected to full history taking of mainly menstrual pattern and severity of bleeding by recording the number of pads per day, duration of bleeding, presence of blood clots and manifestation of iron deficiency anemia. Clinical examination (general, abdominal and gynecological) and laboratory investigations (CBC, kidney function, liver function tests, and coagulation profile) were done for all patients. Transvaginal ultrasound (TVS) was done for all cases to rule out any pathology in uterus or adnexa and to measure endometrial thickness, if there was -90- any doubt, SIS or diagnostic hysteroscopy was done to exclude uterine cavity abnormalities and endometrial lesions. No pretreatment endometrial thinning regimens were used; however, ablation was timed to be performed in early follicular phase of the menstrual cycle (day 4-6). All patients were operated under general anesthesia. Prophylactic antibiotic was given at the start of the procedure. To reduce postoperative cramping, all patients received indomethacin 100 mg rectal suppository immediately after the procedure. For both groups, the operating time was measured from the initiation of anesthesia to the end of the procedure. Any intra-or postoperative complications were recorded. Then, the patient was discharged in the same day. All patients were assessed postoperatively at 3, 6, and 12 months. Follow up of all patients in the outpatient clinic with a subjective assessment of clinical outcomes including patients’ satisfaction, menstrual outcome and occurrence of amenorrhea, hypomenorrhea, euomenorrhea and persistent or increasing menorrhagia. RESULTS: No patients were lost to follow-up. The demographic data and gynecological histories of the 100 patients treated either by the Foley’s catheter technique or by hysteroscopic resection demonstrated no significant differences in age, body mass index (BMI), duration of menorrhagia, pads/cycle, uterine cavity depth, and position. Procedure time (min.) and hospital stay (hrs.) was significantly less for the Foley’s catheter group, compared with hysteroscopic resection group (p<0.05). -91- Intra-operative bleeding indicated by hemoglobin (HB) drop post-operatively was higher among the hysteroscopy group, but the difference was not significant statically; as the following Foley’s catheter group (n=50) Hysteroscopic resection group (n=50) Mean (+SD) Range Mean (+SD) Range Operative time (min.) 15.5 + 3.5 15-20 30.5+8.6 24-37 <0.05* Hb drops (%) 0.8 + 0.3 0.2-0.9 1.2+1 0.5-1.6 NS Hospital stay (Hrs.) 8 +2 6-10 14+8 8-20 <0.05* P value There were no intra-operative complications in the Foley’s catheter group. However, we had 3 intra-operative complications in the hysteroscopy group (6%), 2 cases (4%) with fluid overload, and 1 (2%) patient with cervical lacerations. Postoperatively, 3 cases of endometritis were attributed to the Foley’s catheter group (6%) and all cases responded to oral antibiotic therapy. For hysteroscopy group, there were 2 cases (4%) developed endometritis (also, resolved with oral antibiotics) and 1 case (2%) had a delayed adverse event with hematometra (resolved with D&C). Regard to the intra and postoperative complications, there was no statically significant difference on patients who underwent Foley’s catheter ablation or hysteroscopic resection. -92- There was significant reduction in the menstrual flow after treatment as evidenced by reduction in number of pads/day, days/cycle, and pads/ cycle in Foley’s catheter group; as the following: Pre treatment Post treatment P value Mean (+SD) Range Mean (+SD) Range Pads/day (n=50) 12 + 2.5 6-15 4.5+2.3 0-10 <0.05* Days/cycle (n=50) 11.2 + 5.7 10-21 4.3+2.3 0-12 <0.05* Pads/cycle (n=50) 134.4+48 60-224 26.4+20.8 0-72 <0.05* Also, there was significant reduction in the menstrual flow after treatment as evidenced by reduction in number of pads/day, days/cycle, and pads/ cycle in Foley’s catheter group; as the following: Pre treatment Post treatment P value Mean (+SD) Range Mean (+SD) Range Pads/day (n=50) 11.9 + 2.3 6-19 5+1.5 0-11 <0.05* Days/cycle (n=50) 12.3 + 4.4 9-26 4+2.9 0-10 <0.05* Pads/cycle (n=50) 143.7 + 50 54-213 24.2+22.8 0-78 <0.05* -93- Regard to post treatment menstrual flow changes, although the difference between both groups was not statistically significant, there was a significant greater percentage of patients in the hysteroscopy group (40.0%) compared with the uterine balloon therapy group (20.0%) were amenorrheic at their 12-month follow up (p<0.05). Percent of patients with hypomenorrhea, eumenorrhea, and menorrhagia (failed treatment) in both treatment arms of the study were comparable. The success rate was defined as percent of patients who had eumenorrhea or less 12 months after treatment. This rate was 86% for the Foley’s catheter group and 92% for the hysteroscopy group. Success rates were clinically comparable and not statistically different among the two groups; as the following: Foley’s catheter group (NO. and %) Hysteroscopic resection group P value (NO. and %) Amenorrhea 7 (14%) 14 (28%) <0.05* Hypomenorrhea 10 (20%) 9 (18%) NS Eumenorrhea 26 (52%) 23 (46%) NS Menorrhagia 7 (14%) 4 (8%) NS Success rate 43 (86%) 46 (92%) NS Furthermore, repeated measures analysis of variance demonstrated no difference between the two treatment arms (Foley’s catheter & hysteroscopic -94- resection group) in bleeding pattern variability at 3, 6, and 12 months after the procedure. Regard to Foley’s catheter group; at 3,6, and 12 months follow up: Amenorhea was recorded in 5 (10%), 6 (12%) and 7 (14%) patients, respectivly while hypomenorhea was recorded in 6 (12%), 9 (18%) and 10 (20%) patients, respectivly. Eumenorrhea was recorded in 34 (68%), 29 (58%) and 26 (52%) patients, respectivly. Finally, menorrhagia (failed treatment) was recorded in 5 (10%), 7 (14%) and 7 (14%) patients, respectivly. These results were demonstrated in the following charts: 60 50 40 menorrhagia Eumenorrhea 30 Hypomenorrhea 20 Amenorrhea 10 0 3 month 6 month 12 month Regard to hysteroscopic resection group; at 3,6, and 12 months follow up: Amenorhea was recorded in 11 (12%), 13 (15%) and 14 (16%) patients, respectivly while hypomenorhea was recorded in 8 (16%), 8 (16%) and 9 (18%) patients, respectivly. Eumenorrhea was recorded in 27 (54%), 25 (50%) and 23 -95- (46%) patients, respectivly. Finally, menorrhagia (failed treatment) was recorded in 4 (8%) at the all 3 times. The results were demonstrated in the following charts: 60 50 40 menorrhagia 30 Eumenorrhea Hypomenorrhea 20 Amenorrhea 10 0 3 month 6 month 12 month Treatment failure was occurred in 11% women who suffered from continued menorrhagia, remaining dissatisfied with their bleeding pattern. The failure rate was 8% (n = 4) for endometrial resection and 14% (n = 7) for Foley’s catheter treatment. All these patients were managed surgically by, abdominal hysterectomy. -96- COCLUSIONS AND RECOMMENDATIONS Foley's catheter endometrial ablation is as efficacious as to hysteroscopic resection in the treatment of persistent menorrhagia (failed medical treatment). It has similar results, easy, simple and need no experience. Large series studies and evaluation of clinical response for a longer period are advised to be performed. The pitfall in our study is the small number of cases (100) and absence of long term follow up (only 12 months). -97- REFERENCES Advancing Minimally Invasive AAGL Practice Report: Gynecology Practice Guidelines Worldwide (AAGL). for the Management of Hysteroscopic Distention Media: (Replaces Hysteroscopic Fluid Monitoring Guidelines. J Am Assoc Gynecok Laparosc. 2000; 7:167-168.). J Minim Invasive Gynecol. 2013; 20:137-48. Ahonkallio S, Martikainen S and Santala M. Endometrial thermal balloon ablation has a beneficial long-term effect on menorrhagia. Acta Obstet Gynecol. 2008; 87:107-10. Alaily AB Auld BJ and DiabY. Endometrial ablation with the Cavaterm balloon. J Obstet Gynaecol. 2003; :231:51-54. Alestebi FA and Ekskander VG. Thermal balloon endometrial ablation to treat menorrhagia in high risk surgical candidates. J Am Assoc Gynecol Laparosc. 1999; 6:4:435-9. Altshuler AL and Hillard PJ. Menstrual suppression for adolescents. Curr Opin Obstet Gynecol. 2014; 26:323-31. American College of Obstetricians and Gynecologists (ACOG). ACOG practice bulletin No. 104: antibiotic prophylaxis for gynecologic procedures. Obstet Gynecol. 2009 May. 113(5):1180-9. American College of Obstetricians and Gynecologists (ACOG). ACOG committee opinion no. 557: Management -98- of acute abnormal uterine bleeding in non-pregnant reproductive-aged women. Obstet Gynecol. 2013; 121:891-6. American College of Obstetricians and Gynecologists (ACOG). Committee on Adolescent Health Care; American College of Obstetricians and Gynecologists Committee Gynecologic Practice. ACOG Committee Opinion No. 451: Von Willebrand’s disease in women. Obstet Gynecol 2009:114:1439-43. American Society for Reproductive Medicine (ASRM). Indications and options for endometrial ablation. Fertil Steril 2008; 90: 237-240. Amso NN, Stabinsky S and McFaul. J Am Assoc Gynecol Laparosc. 2002, 9:429-35. Api M and Api O. Foley catheter balloon endometrial ablation: successful treatment of three cases. J Pak Med Assoc. 2012; 62;3:284-6. Arieff AL and Ayus JC. Endometrial ablation complicated by fatal hyponatremic encephalopathy. JAMA. 1993; 270:1230-32. Ashraf TA and Gamal M. Uterine thermal balloon ablation versus hysteroscopic endometrial resection in treatment of menorrhagia. Gynecol Obstet. 2012; 2:136. Azza A. Endometrial thermal balloon ablation by a simple technique using Foley’s catheter with or without pre ablation endometrial curettage to treat cases with intractable menorrhagia. MEFS. 2012; 17:116-21. Barrow C. Ballon ‘Endometrial ablation as a safe alternative to hysterectomy’. AORN J. 1999; 80:83-6. -99- Bennett AR and Gray SH. What to do when she's bleeding through: the recognition, evaluation, and management of abnormal uterine bleeding in adolescents. Curr Opin Pediatr. 2014; 26:413-9. Berg A, Sandvik L, Langebrekke A and Istre O. A randomized trial comparing monopolar electrodes using glycine 1.5% with two different types of bipolar electrodes (TCRis, Versapoint) using saline, in hysteroscopic surgery. Fertil Steril. 2009; 91:1273-8. Bhattacharya S, Middleton LJ, Tsourapas A, Lee AJ, Champaneria R, Daniels JP and et al. Hysterectomy, endometrial ablation and Mirena® for heavy menstrual bleeding: a systematic review of clinical effectiveness and cost- effectiveness analysis. Health Technol Assess. 2011; 15:iii–xvi–1-252. Birdsell DC, Mattatall F, Rosengarten AM and Watson SD. Vulvar burn: a complication of hysteroscopic endometrial ablation. J Obstet Gynaecol Can. 2010; 32:1021-2. Bongers MY, Mol BW and Brolmann HA. Prognostic factors for the success of thermal balloon ablation in the treatment of menorrhagia. Obstet Gynecol. 2002; 99:6:1060-66. Bongers MY, Mol BW, Dijkhuizen FP and Brolmann HA. Is balloon ablation as effective as endometrial electroresection in the treatment of menorrhagia? J Laparoendosc Adv Surg Tech A. 2000; 10:85–92. Bongers MY, Van Der Bourdrez P, Steeg JW, Heintz A, Brolmann H, and Mol BJ. Thermal endometrial ablation in dysfunctional uterine bleeding: an economic comparison of bipolar ablation and balloon ablation. Gynecol Surg. 2005; 2:271-77. -100- Bouzari Z, Yazdani S, Azimi S and Delavar M. Thermal Balloon Endometrial Ablation in the Treatment of Heavy Menstrual Bleeding. Med Arch 2014; 68: 411-13. Bouzari Z, Yazdani S, Azimi S and Delavar M. Thermal Balloon Endometrial Ablation in the Treatment of Heavy Menstrual Bleeding. Med Arch. 2014; 68:6:411-13. Bradley LD and Gueye NA. The medical management of abnormal uterine bleeding in reproductive-aged women. Am J Obstet Gynecol. 2016; 214:3144. Bradley LD. Hysteroscopy: Office Evaluation and Management of The Uterine Cavity. Linda D. Bradley and Tommaso Falconi (editors). MOSBY ELSEVIER (Publisher). 1st edition. 2008; 18:201-22. Brooks PG, Clouse J and Morris LS. Hysterectomy vs. resectoscopic endometrial ablation for the control of abnormal uterine bleeding. A costcomparative study. J Reprod Med. 1994; 39:55-60. Brun JL. French randomised comparative multicentre study of Cavaterm™ versus resection in patients with meorrhagia: interim results. Morges, Switzerland: Wallsten Medical SA; 2002. Cirilli AR and Cipot SJ. Emergency evaluation and management of vaginal bleeding in the nonpregnant patient. Emerg Med Clin North Am. 2012; 30:991-1006. Committee on Adolescent Health Care and Committee on Gynecologic Practice. Committee Opinion No.580: von Willebrand’s disease in women. Obstet Gynecol. 2013; 122:1368-73. -101- Cooper K, Lee A, Chien P, Raja E, Timmaraju V and Bhattacharya S. Outcomes following hysterectomy or endometrial ablation for heavy menstrual bleeding: retrospective analysis of hospital episode statistics in Scotland. BJOG. 2011; 118(10):1171–9. Darwish AM, Hassan ZZ, Attia AM, Abdelraheem SS and Ahmed YM. Biological effects of distension media in bipolar versus monopolar resectoscopic myomectomy: a randomized trial. J Obstet Gynaecol Res. 2010; 36:810-17. Daub CA, Sepmeyer JA, Hathuc V, Sakala MD, Caserta MP, Clingan MJ and et al. Endometrial Ablation: Normal Imaging Appearance and Delayed Complications. AJR Am J Roentgenol. 2015; 205:451-60. Deb S, Flora K AND Atiomo W. A survey of preferences and practices of endometrial ablation/resection for menorrhagia in the United Kingdom. Fertil Steril 2008; 90:1812-7. DeCherney A, Polan ML. Hysteroscopic management of intrauterine lesions and intractable uterine bleeding. Obstet Gynecol. 1983; 61:392-97. Deligeoroglou E, Karountzos V and Creatsas G. Abnormal uterine bleeding and dysfunctional uterine bleeding in pediatric and adolescent gynecology. Gynecol Endocrinol. 2013; 29:74-8. Demers C, Derzko C, David M, Douglas J; Society of Obstetricians and Gynecologists of Canada. Gynaecological and obstetric management of women with inherited bleeding disorders. SOGC Clinical Practice Guidelines, No 163, July 2005. J Obstet Gynaecol Can 2005; 27:707-32. -102- Dobak JD, Willems J, Howard Endometrial cryoablation with R, Shea C ultrasound and Townsend visualization in DE. women undergoing hysterectomy. J Am Assoc Gynecol Laparosc. 2000; 7:1:89-93. Downes E, Yasmin R and Flemming R. Microwave endometrial ablation: development and clinical application. Surg Technol Int. 2007; 16:142-6. Dutton C, Ackerson L and Phelps-Sandall B. Outcomes after rollerball endometrial ablation for menorrhagia.Obstet Gynecol. 2001; 98;1:35-39. Elmardi A, Furara S, Khan F and Hamza M. NovaSure impedance controlled system for endometrial ablation: the experience of the first UK reference centre. J Obstet Gynaecol. 2009; 29:5:419-22. El-Nashar SA, Hopkins MR and Creedon DJ. Prediction of treatment outcomes after global endometrial ablation. Obstet Gynecol. 2009; 113:97-106. Farquhar C and Brown J. Oral contraceptive pill for heavy menstrual bleeding. Cochrane Database Syst Rev. 2009; 4:2. Feitoza S, Gebhart J, Gostout B, Wilson B and Cliby W. Efficacy of thermal balloon ablation in patients with abnormal uterine bleeding. Am J Obstet Gynaecol. 2003; 189:453-57. Frick KD, Clark MA, Steinwachs DM, Langenberg P, Stovall D, Munro MG and et al. Financial and quality-of-life burden of dysfunctional uterine bleeding among women agreeing to obtain surgical treatment. Women’s Health Issues 2009; 19:70-78. -103- Gannon MJ, Day P, Hammadieh N and Johnson N. A new method for measuring menstrual blood loss and its use in screening women before endometrial ablation. Br J Obstet Gynaecol. 1996; 103:1029-33. Garry R, Shelley-Jones D, Mooney P and Phillips G. Six hundred endometrial laser ablations. Obstet Gynecol. 1995; 85:24-9. Garside R, Stein K, Wyatt K, Round A and Pitt MA. Cost-utility analysis of microwave and thermal balloon endometrial ablation techniques for the treatment of heavy menstrual bleeding. BJOG. 2004; 111:1103-14. Garza-leal G, Pena A, Donovan A, Cash C, Romanowski C, Ilie B and et al. Clinical evaluation of a third generation thermal uterine balloon therapy system for menorrhagia coupled with curettage. J Minimally Invasive Gynecol. 2010; 1:82-90. Gervaise A, Fernandez H, Capella-Allouc S, Taylor S, La Vieille S, Hamou J and et al. Thermal balloon ablation versus endometrial resection for the treatment of abnormal uterine bleeding. Hum Reprod.1999; 14:2743-7. Glasser M. Hysteroscopy: Managing and minimizing operative complications. OBG Management. 2005; 17:42-57. Glasser MH, Heinlein PK and Hung Y-Y. Office endometrial ablation with local anaesthesia using the HydroThermAblator system: comparison of outcomes in patients with submucous myomas with those with normal cavities. J Minim Invasive Gynecol 2009; 16:700-7. Gokyildiz S, Aslan E, Beji K, and Mecdi M. The Effects of Menorrhagia on Women’s Quality of Life: A Case-Control Study. ISRN Obstetrics and Gynecology.2013; 2013:7. -104- Grainger DA, Tjaden BL, Rowland C and Meyer WR. Thermal balloon and rollerball ablation to treat menorrhagia: two-year results of a multicenter, prospective, randomized, clinical trial. J Am Assoc Gynecol Laparosc. 2000; 7:175-9. Gupta JK, Sinha A, Lumsden MA and Hickey M. Uterine artery embolization for symptomatic uterine fibroids. Cochrane Database Syst Rev. 2014; 12:5073. Hallberg L and Nilsson L. Determination of menstrual blood loss. Scand J Clin Lab Invest. 1964; 16:244-8. Hansen BB, Dreisler E and Stampe Sørensen S. Outcome of repeated hysteroscopic resection of the endometrium. J Minim Invasive Gynecol 2008; 15:704–6. Hawe J, Abbot J and Hunter D. A randomized controlled comparing the Cavaterm endometrial ablation system with the ND:YAG laser for the treatment of dysfunctional uterine bleeding. BJOG. 2003;110:4:350-57. Higham JM, O’Brien PMS and Shaw RW. Assessment of menstrual blood loss using a pictorial chart. Br J Obstet Gynaecol. 1990; 97:734-9. Hopkins MR, Creedon DJ, El-Nashar SA, Brown DL, Good AE and Famuyide AO. Radiofrequency global endometrial ablation followed by hysteroscopic sterilization. J Minim Invasive Gynecol. 2007; 14:494-501. Huang GS, Gebb JS, Einstein MH, Shahabi S, Novetsky AP and Goldberg GL. Accuracy of preoperative endometrial sampling for the detection of high-grade endometrial tumors. Am J Obstet Gynecol 2007; 196:243. -105- Huguelet PS, Buyers EM, Lange-Liss JH and Scott SM. Treatment of acute abnormal uterine bleeding in adolescents: what are providers doing in various specialties?. J Pediatr Adolesc Gynecol. 2015; 15:1083-88. Hulka JF, Peterson HA, Phillips JM and Surrey MW. Operative hysteroscopy: American Association of Gynecologic Laparoscopists’ 1993 Membership Survey. J Am Assoc Gynecol Laparosc. 2008; 2:131-32. Janssen CA, Scholten PC and Heintz AP. A simple visual assessment technique to discriminate between menorrhagia and normal menstrual blood loss. Obstet Gynecol. 1995; 85:977-82. Kaunitz AM, Meredith S, Inki P, Kubba A, Sanchez-Ramos L. Levonorgestrelreleasing intrauterine system and endometrial ablation in heavy menstrual bleeding: a systematic review and meta-analysis. Obstet Gynecol 2009; 113:1104–16. Khrouf M and Khaled T. Diagnosis and Management of Formerly Called “Dysfunctional Uterine Bleeding” According to PALM-COEIN FIGO Classification and the New Guidelines. J Obstet Gynaecol India. 2014; 64: 388-93. Kotdawala P, Kotdawala S, and Nagar N. Evaluation of endometrium in perimenopausal abnormal uterine bleeding J Midlife Health. 2013; 4:16-21. Kroft J and Liu G. First- versus second-generation endometrial ablation devices for treatment of menorrhagia: a systematic review, meta-analysis and appraisal of economic evaluations. J Obstet Gynaecol Can. 2013; 35:1010-9. Kumar V, Chodankar R, Gupta JK. Endometrial ablation for heavy menstrual bleeding. Womens Health (Lond Engl) 2016; 12:45-52. -106- La Sala GB, Blasi I and Gallinelli A. Diagnostic accuracy of sonohysterography and transvaginal sonography as compared with hysteroscopy and endometrial biopsy: a prospective study. Minerva Ginecol 2011; 63:421. Lacey JV, Sherman ME, Rush BB, Ronnett BM, Ioffe OB, Duggan MA and et al. Absolute risk of endometrial carcinoma during 20-year follow-up among women with endometrial hyperplasia. J Clin Oncol 2010; 28:788-9. Lara-Torre E, Spotswood L, Correia N and Weiss PM. Intrauterine contraception in adolescents and young women: a descriptive study of use, side effects, and compliance. J Pediatr Adolesc Gynecol 2011; 24:39-41. Leissinger C, Carcao M, Gill JC, Journeycake J, Singleton T and Valentino L. Desmopressin (DDAVP) in the management of patients with congenital bleeding disorders. Haemophilia. 2014; 20:158-67. Lethaby A, Augwood C, Duckitt K and Farquhar C. Nonsteroidal antiinflammatory drugs for heavy menstrual bleeding. Cochrane Database Syst Rev 2007; 4:4. Lissak A, Fruchter O and Mashiach S. Immediate versus delayed treatment of perimenopausal bleeding due to benign causes by thermal balloon ablation. J Am Assoc Gynecol Laparosc. 1999; 2:145-50. Loffer FD and Grainger D. Five-year follow-up of patients participating in a randomized trial of uterine balloon therapy versus rollerball ablation for treatment of menorrhagia. J Am Assoc Gynecol Laparosc. 2002; 9:429-35. Loffer FD. Three-year comparison of thermal balloon and rollerball ablation in treatment of menorrhagia. J Am Assoc Gynecol Laparosc. 2001; 8:48-54. -107- Lok IH, Chan M and Tam WH. Patient-controlled sedation for outpatient thermal balloon endometrial ablation. J Am Assoc Gynecol Lapparosc. 2002; 9:4:436-41. Longinotti MK, Jacobson GF, Hung Y-Y and Learman LA. Probability of hysterectomy after endometrial ablation. Obstet Gynecol 2008; 112:1214-20. Magos AL, Baumann R, Turnbull AC. Transcervical resection of endometrium in women with menorrhagia. BMJ 1989; 298:1209-12. Mangeshikar PS, Kapur A and Yackel DB. Endometrial ablation with a new thermal balloon system. J Am Assoc Gynecol Lapparosc. 2003; 10:1:27-32. Matteson KA, Abed H, Wheeler TL, Sung VW, Rahn DD, Schaffer JI and et al. A systematic review comparing hysterectomy with less-invasive treatments for abnormal uterine bleeding. J Minim Invasive Gynecol 2012; 19:13-28. McCausland AM and McCausland VM. Long-term complications of endometrial ablation: cause, diagnosis, treatment, and prevention. J Minim Invasive Gynecol. 2007; 14:399-406. Mehra N, Farshid S, Lamba M and Singh SS. Post-ablation tubal sterilization syndrome. J Obstet Gynaecol Can. 2011; 33:1085. Meyer WR, Walsh BW, Grainger DA, Peacock LM, Loffer FD and Steege JF. Thermal balloon and rollerball ablation to treat menorrhagia: a multicenter comparison. Obstet Gynecol. 1998; 92:98-103. Middleton LJ, Champaneria R, Daniels JP, Bhattacharya S, Cooper KG, Hilken NH and et al. Hysterectomy, endometrial destruction, and -108- levonorgestrel releasing intrauterine system (Mirena) for heavy menstrual bleeding: systematic review and meta-analysis of data from individual patients. BMJ 2010; 341:c3929. Mullins TL, Miller RJ and Mullins ES. Evaluation and Management of Adolescents with Abnormal Uterine Bleeding. Pediatr Ann. 2015; 44:21822. Munro MG, Dickersin K, Clark MA, Langenberg P, Scherer RW, Frick KD and et al. The Surgical Treatments Outcomes Project for Dysfunctional Uterine Bleeding: summary of an Agency for Health Research and Qualitysponsored randomized trial of endometrial ablation versus hysterectomy for women with heavy menstrual bleeding. Menopause 2011; 18:445-52. Munro MG, Critchley HO, Broder MS, Fraser IS; FIGO Working Group on Menstrual Disorders. FIGO classification system (PALM-COEIN) for causes of abnormal uterine bleeding in nongravid women of reproductive age. Int J Gynaecol Obstet. 2011; 113:3-13. Munro MG. Abnormal uterine bleeding. Cambridge: Cambridge University Press; 2010. National Institute for Health and Clinical Excellence (NICE). Clinical guideline CG78: Fluid-filled thermal balloon and microwave endometrial ablation techniques for heavy menstrual bleeding.. 2004; 78:1-31. National Institute for Health and Clinical Excellence (NICE). Clinical guideline CG44: heavy menstrual bleeding. London: Royal College of Obstetricians and Gynecologists. 2007; 15:7. -109- Naz M, Irshad F, Zafar H, Fatima U. Efficacy of modified thermal balloon ablation in heavy menstrual bleeding. JUMDC. 2012; 3:2:1-5. Neuwirth R, Duran M, Singer A, MacDonald R and Bolduc L. The endometrial ablator: A new instrument. Obstet Gynecol. 1994; 3:792-96. Nieboer TE, Johnson N, Lethaby A, Tavender E, Curr E, Garry R and et al. Surgical approach to hysterectomy for benign gynaecological disease. Cochrane Database Syst Rev 2009; 3:36-72. O’Connor H and Magos A. Endometrial resection for the treatment of menorrhagia. N Engl J Med. 1996; 335:151-56. Overton C, Hargreaves J and Maresh M. A national survey of the complications of endometrial destruction for menstrual disorders: the MISTLETOE study Minimally Invasive Surgical Techniques – Laser, EndoThermal or Endoresection. Br J Obstet Gynaecol. 1997; 104:1351-39. Owusu-Ansah R, Gatongi D and Chien PF. Health technology assessment of surgical therapies for benign gynaecological disease. Best Pract Res Clin Obstet Gynaecol. 2006; 20:841-79. Pallavi C, Dhamangaonkar K, Anuradha A and Archana Saxena. Levonorgestrel intrauterine system (Mirena): An emerging tool for conservative treatment of abnormal uterine bleeding. J Midlife Health. 2015; 6:26-30. Papadopoulos NP and Magos A. First-generation endometrial ablation: roller-ball vs loop vs laser. Best Pract Res Clin Obstet Gynaecol. 2007; 21:915-29. -110- Paschopoulos M, Polyzos NP, Lavasidis LG, Vrekoussis T, Dalkalitsis N and Paraskevaidis E. Safety issues of hysteroscopic surgery. Ann N Y Acad Sci. 2006; 1092:229-34. Pellicano M, Guida M, Acunzo G, Cirillo D, Bifulco G and Nappi C. Hysteroscopic transcervical endometrial resection versus thermal destruction for menorrhagia: a prospective randomized trial on satisfaction rate. Am J Obstet Gynecol. 2002; 187:545-50. Penninx JP, Mol BWJ, Engels R, van Rumste MM, Kleijn C, Coks CA and et al. Bipolar radiofrequency endometrial ablation compared with hydrothermablation for dysfunctional uterine bleeding: a randomized controlled trial. Obstet Gynecol. 2010; 116:819-26. Penninx JP, Mol BY and Bongers MY. Endometrial ablation with paracervical block. J Reprod Med; 2009; 54:617-20. Perez-Medina T and Vallejo MR. Diagnostic and Operative Hysteroscopy. Tirso Perez-Medina and Enrique Cayuela Font (editors). JAYPEE (Publisher). 2nd edition. 2011; 13:138-45. Puchar A, Feyeux C, Luton D and Koskas M. Therapeutic management of uterine fibroid tumors. Minerva Ginecol. 2015; [Epub ahead of print]. Ray S and Ray A. Non-surgical interventions for treating heavy menstrual bleeding (menorrhagia) in women with bleeding disorders. Cochrane Database Syst Rev. 2014; 11:338. Reid PC, Coker A and Coltart R. Assessment of menstrual blood loss using a pictorial chart: a validation study. Br J Obstet Gynaecol. 2000; 107:320-2. -111- Rishma DP. Thermal Balloon Endometrial Ablation in Dysfunctional Uterine Bleeding J Gynecol Endosc Surg. 2009; 1:1:31–33. Roberts T, Tsourapas A, Middleton LJ, Champaneria R, Daniels JP, Cooper KG and et al. Hysterectomy, endometrial ablation, and levonorgestrel releasing intrauterine system (Mirena) for treatment of heavy menstrual bleeding: cost effectiveness analysis. BMJ. 2011; 342. Rodeghiero F. Management of menorrhagia in women with inherited bleeding disorders: general principles and use of desmopressin. Haemophilia. 2008; 14:1:21-30. Romer T. Therapy of recurrent menorrhagia - Cavaterm balloon coagulation versus roller-ball endometrium coagulation- a prospective randomized comparative study. Zentralbl Gynakol. 1998; 120:511–14. Sabbah R and Desaulniers G. Use of the NovaSure Impedance Controlled Endometrial Ablation System in patients with intracavitary disease: 12month follow-up results of a prospective, single-arm clinical study. J Minim Invasive Gynecol. 2006; 13:5:467-71. Sabbah R, Laberge P, Fortin C, Thiel J, Garza-Leal J and Fullop T, et al. A multi-center, single-arm, international clinical study of the safety and efficacy of the AURORA endometrial ablation system. Preliminary clinical results. J Minim Invasive Gynecol 2011; 18:82. Sambrook AM1, Elders A and Cooper KG. Microwave endometrial ablation versus thermal balloon endometrial ablation (MEATBall): 5-year follow up of a randomised controlled trial. BJOG. 2014; 121:6:747-53. -112- Sanders S, Purcell S, Silva M, Palerme S and James P. Relationship between diagnosis and intervention in women with inherited bleeding disorders and menorrhagia. Haemophilia. 2012; 18:273-6. Shaamash HA and Sayed EA. Prediction of successful menorrhagia treatment after thermal balloon endometrial ablation. J Obstet Gynaecol Res. 2004; 30:3: 210–16. Sharma M, Shubham J, Akash S, Oby N, Rakesh K and Meenu B. Role of saline infusion sonography in abnormal uterine bleeding. Int J Reprod Contracept Obstet Gynecol. 2013; 2:533-38. Sharp HT. Endometrial ablation: postoperative complications. AJOG 2012; 207:242-47. Shawki O, Peters A and Abraham-Hebert S. Hysteroscopic endometrial destruction, optimum method for preoperative endometrial preparation: a prospective, randomized, multicenter evaluation. JSLS 2002; 6:23-7. Silva CD, Geraldes F and Silva IS. Levonorgestrel intrauterine system as a treatment option for severe menorrhagia in adolescent with type III von Willebrand disease. BMJ Case Rep. 2013; 1:33-88. Simon RA, Quddus MR, Lawrence WD and Sung CJ. Pathology of endometrial ablation failures: a clinicopathologic study of 164 cases. Int J Gynecol Pathol. 2015; 34:245-52. Singer A, Almanza R, Gutierrez A, Haber G and Bolduc LR. Preliminary clinical experience with a thermal balloon endometrial ablation method to treat menorrhagia. Obstet Gynecol. 2000; 83: 732-34. -113- Singh KC, Sengupta R, Agarwal N and Misra K. Thermal endometrial ablation: a simple technique. Acta Obstet Gynecol Scand. 2000; 79:1:54-9. Society Of Obstetricians and Gynecologists of Canada (SOGC). Clinical practice guideline. Abnormal Uterine Bleeding in Pre-Menopausal Women. JOGC 2013; 35:1-28. Society Of Obstetricians and Gynecologists of Canada (SOGC). Clinical practice guideline. Endometrial ablation in the management of abnormal Uterine Bleeding. JOGC 2015; 37(4):362-376. Sowter MC, Lethaby A and Singla AA. WITHDRAWN: Pre- operative endometrial thinning agents before endometrial destruction for heavy menstrual bleeding. Cochrane Database Syst Rev. 2014; 7: 11-24. Soysal ME, Soysal SK and Vicdan K. Thermal balloon ablation in myomainduced menorrhagia under local anesthesia. Gynecol Obstet Invest. 2001; 51:128-33. Sweet MG, Schmidt-Dalton TA, Weiss PM and Madsen KP. Evaluation and management of abnormal uterine bleeding in premenopausal women. Am Fam Physician. 2012; 85:35-43. Tan YH and Lethaby A. Pre-operative endometrial thinning agents before endometrial destruction for heavy menstrual bleeding. Cochrane Database Syst Rev 2013; 11:10-41. The Menorrhagia Research Group. Quantification of menstrual blood loss. REVIEW The Obstetrician & Gynaecologist. 2004; 6:88-92. -114- Thinkhamrop J, Laopaiboon M and Lumbiganon P. Prophylactic antibiotics for transcervical intrauterine procedures. Cochrane Database Syst Rev 2007; 3:37-56. Ulmsten U, Cartensen H and Falconer C. The safety and efficacy of MenoTreat, a new balloon device for thermal endometrial ablation. Acta Obstet Gynecol Scand. 2001; 80:1:52-57. Van Dongen H, de Kroon CD, Jacobi CE, Trimbos JB and Jansen FW. Diagnostic hysteroscopy in abnormal uterine bleeding: a systematic review and meta-analysis. BJOG 2007; 114:664-75. Veena BTand Nirmala SH. Role of Transvaginal Sonography and Diagnostic Hysteroscopy in Abnormal Uterine Bleeding J Clin Diagn Res. 2014; 8:0608. Verbalis JG, Goldsmith SR, Greenberg A, Korzelius C, Schrier RW, Sterns RH and et al. Diagnosis, evaluation, and treatment of hyponatremia: expert panel recommendations. Am J Med. 2013; 126:1:1-42. Vitagliano A, Bertin M, Conte L, Borgato S, Leggieri C and Fagherazzi S. Thermal balloon ablation versus transcervical endometrial resection: evaluation of postoperative pelvic pain in women treated for dysfunctional uterine bleeding. Clin Exp Obstet Gynecol. 2014; 41:4:405-8. Weiss JA. Just heavy menses or something more? Raising awareness of von Willebrand disease. Am J Nurs. 2012; 112:38-44. Wilkinson JP and Kadir RA. Management of abnormal uterine bleeding in adolescents. J Pediatr Adolesc Gynecol 2010; 23(6):22–30. -115- Wortman M, Cholkeri A, McCausland AM and McCausland VM. Lateonset endometrial ablation failure--etiology, treatment, and prevention. J Minim Invasive Gynecol. 2015; 22:323-31. Wyatt KM, Dimmock PW, Walker TJ and O’Brien PMS. Determination of total menstrual blood loss. Fertil Steril. 2001; 76:125-31. Zarek S and Sharp HT. Global endometrial ablation devices. Clin Obstet Gynecol. 2008; 51:167-75. Zon-Rabelink I. Rollerball versus Thermachoice. 10th Congress of the European Society for Gynaecological Endoscopy. Proceedings 2001; 11-14. -116-