Title: A multicentre randomised controlled trial comparing laparoscopic supra-cervical hysterectomy with second generation endometrial ablation for the treatment of heavy menstrual bleeding (HEALTH)
Funder: Chief Scientist Office, Scotland

Abstract: A pragmatic multicentre randomised controlled trial comparing laparoscopic supra-cervical hysterectomy with second generation endometrial ablation for the treatment of heavy menstrual bleeding. Health technologies being assessed: The two interventions which are evaluated in this trial are used in secondary care to treat women with heavy menstrual bleeding (HMB) resistant to medical treatment, including the Levonorgestrel Intrauterine System (LNG-IUS). The trial will take place within designated NHS hospitals with the appropriate expertise to perform either procedure. The proposed surgical procedures will be standardised by means of pre-agreed protocols. Endometrial ablation (EA) aims to treat HMB by destroying the endometrium (lining of the womb). EA techniques currently used in the UK are known as second generation procedures and include thermal balloon endometrial ablation (Thermachoice and Cavaterm) and Novasure® (Hologic Inc) which significantly reduces menstrual loss and results in complete cessation of bleeding in 40 to 50% of women. Hysterectomy, defined as surgical removal of the uterus, offers definitive treatment for HMB, but is invasive and carries a risk of complications. Unlike conventional hysterectomy, laparoscopic supra-cervical hysterectomy (LASH), a more recent form of hysterectomy, involves removal of the upper part of the uterus or the body containing the uterine cavity lined by specialised tissue known as endometrium which bleeds during menstruation. The operation which is performed by means of keyhole surgery is minimally invasive, quick, relatively easy to learn, and has low morbidity, short hospital stay (under 24 hours) and rapid recovery time. Unlike conventional hysterectomy the cervix is not removed, thus obviating the need for prolonged and complex surgery involving dissection of tissue around the cervix. This extra step, necessary for the removal of the cervix, can lead to serious complications such as injury to surrounding structures such as the ureters and major pelvic blood vessels. Following LASH, most women will cease to have periods although light menstrual loss can occur in 5-10% of cases. As the cervix is retained, cervical smears are still required. Setting: Fifteen acute hospital settings within the UK where gynaecological surgeons routinely perform both procedures. Target population: Women < 50 years of age, with HMB, in whom medical treatment has failed and who are eligible for endometrial ablation. Exclusion criteria: infertility, plans to conceive, endometrial atypia, uterine cavity size above 11 cm, women with submucous fibroids > 2 cm distorting the uterine cavity, women at high risk of complications from contraindications to anaesthesia or laparoscopic surgery (e.g. bowel adhesions or previous midline laparotomy). Measurement of costs and outcomes The co-primary outcomes will be: a) Patient reported satisfaction, measured on a six point Likert scale (from totally satisfied to totally dissatisfied) at 12 months and b) Menorrhagia multi-attribute scale (MMAS), a condition-specific tool for heavy menstrual bleeding (Pattison et al, 2011) at 12 months. Twelve months was chosen since maximum benefit of the intervention will be perceived and any peri-operative period complications will have been resolved. The primary economic outcome will be the incremental cost (to the health service) per QALY gained. Patient reported: MMAS at 6 months; patient reported satisfaction at 6 months; acceptability of procedure measured at 6 weeks; severity of post operative pain using a pain Numerical Rating Scale (NRS) measured at 1-14 days and at 6 weeks, symptom diary days 1 to 14 (including analgesic use); generic health related quality of life (SF-12, EQ-5D 3-L) measured at baseline, 6 and 12 months; and Sexual Activity Questionnaire (SAQ) at baseline, 6 and 12 months. In addition, all women will be asked to consent to long-term follow-up to determine need for further gynaecological surgery using routine Hospital Episode Statistics for England and Wales and Information Services Division (ISD) data for Scotland. It is anticipated that the relative incidence of subsequent gynaecological surgery (beyond 12 months) may be a key driver of longer term cost-effectiveness. While these data will not be analysed within the proposed study period, we have included costs to set up the record linkage for future use.

Lay abstract: Heavy menstrual bleeding (HMB) affects approximately 1.5 million women in England and Wales, prompts 1 in 20 women of reproductive age to consult their general practitioners and accounts for 20% of gynaecology outpatient referrals. It causes significant distress to women and leads to a measurable reduction in quality of life. Initial treatment involves the use of drugs, including the combined oral contraceptive pill, as well as a hormone impregnated intrauterine contraceptive device. However, these can fail in some women and a significant proportion will need surgical treatment. Endometrial ablation, which involves removal of the lining of the womb using heat energy, has emerged as the most popular form of surgery to reduce menstrual blood loss. ‘First generation’ ablation techniques, which were performed under direct vision, have now been replaced by ‘second generation’ procedures which are easier and quicker to perform. Recent research has shown that conventional hysterectomy, which involves removal of the womb (including the cervix) through a surgical incision is superior to first and second generation endometrial ablation in relieving symptoms and is also more cost-effective. It is however, more invasive and associated with a higher risk of complications. Unlike other forms of hysterectomy, laparoscopic supracervical hysterectomy or ‘LASH’ is performed as a keyhole procedure. It requires less extensive surgery as only the part of the uterus which contributes to menstrual bleeding is removed, it is quick, relatively easy to learn with fewer complications, short, often ‘day case’ hospital stay and rapid recovery time. It could thus offer women and surgeons the benefit of hysterectomy with the minimal invasiveness of endometrial ablation. We have assembled a multidisciplinary research team comprising clinical and methodological experts in order to carry out a large multicentre randomised controlled trial comparing second generation endometrial ablation with laparoscopic supracervical hysterectomy in women with HMB. The trial will provide information on which treatment is the most effective in terms of symptom relief, side effects, acceptability and costs.

Research activity codes: 6.4 SURGERY
Health categories: REPRODUCTIVE HEALTH AND CHILDBIRTH