MATERIALS AND METHODS
adenomyosis, malignancy, fibroids, loss of menstrual blood
FIBROID, PELVIC INFLAMMATORY DISEASE, ADVERSE EVENTS, BLEEDING, INTRAOPERATIVE COMPLICATION, UTERINE FIBROID, ADENOMYOSIS, FIBROIDS, REGRESSION, BLOOD, COMPLICATIONS
The present study is an open, randomized, parallel multicenter trial comparing two uterine‐saving fibroid treatments with ethics approval from the Coventry and Warwickshire National Research Ethics Service Committee (Reference: 11/WM/0149). It was approved by the UK National Research Ethics Service and the research department at each participating hospital.The participants were recruited from 29 participating hospitals across the UK. Following a full clinical assessment and imaging to confirm the presence of fibroids, the patients were invited to the study if the assessing clinician felt the patient would benefit from either myomectomy or UAE. A trial‐approved member of the local team would then approach the patient at a later date and provide written information on the study. Patients who consented to take part were given a baseline questionnaire. The majority of the participants had magnetic resonance imaging (MRI) scans to map the fibroids. Patients were randomized if they met all the inclusion criteria and none of the exclusion criteria.The inclusion criteria were as follows: women with symptomatic fibroids who did not wish to have a hysterectomy, but who were prepared to accept one in an emergency; women suitable for, and accepting of, either myomectomy or UAE; women for whom the clinical team were uncertain as to which treatment was indicated; and women who provided written informed consent.The exclusion criteria were as follows: women who refused a hysterectomy, even if an intraoperative complication made this an advisable procedure; women with recent or ongoing pelvic inflammatory disease; women with significant adenomyosis, as identified by transvaginal ultrasound or MRI (women with concurrent adenomyosis were eligible if fibroids were believed to be the predominant cause of their symptoms); women with a positive pregnancy test just before consent; postmenopausal women, defined as more than 1 year since the last menstrual period; women with suspected malignancy; women aged under 18 years; women who were unable to provide informed consent because of incapacity (as defined by the Mental Capacity Act 200555 or the Adults with Incapacity (Scotland) Act 200056); non‐English‐speaking women for whom translation or interpretation facilities were insufficient to guarantee informed consent; and women who had previously undergone myomectomy via a laparotomy or had previously undergone embolization.A sample size of 250 participants was estimated to have a power of 90% (at a two‐sided alpha level of 0.05) to detect a moderate‐sized difference between the groups (i.e., 0.55 of a standard deviation in the primary outcome).The analysis of the primary outcome was performed in accordance with the intention‐to‐treat (ITT) principle. Statistical analyses were computed on complete observed data and all randomized participants at all assessment times through the imputation of missing responses. Repeated‐measures linear regression models, including data at all time points, were used to estimate least‐square mean differences (with 95% two‐sided CIs) in the primary outcome at 2 years. The model included participant, treatment group, baseline score, time, interaction between time and treatment group, and the minimization variables. Participants were included in the complete case analysis if they had at least one response at any of the three assessment time points. In the analysis that took missing responses into account, multiple imputation was performed with the use of the Markov chain Monte Carlo method, which assumed a joint multivariate normal distribution. The imputation model was consistent with the analysis model.For the primary outcome, a Several sensitivity analyses for the primary outcome were also performed, including the following: the inclusion of time as a continuous linear predictor, assuming no interaction with treatment; the addition of a parameter for the treating hospital; and a per‐protocol analysis, including only those who received the allocated treatment. Some questionnaires were incomplete and, therefore, an additional sensitivity analysis used available subscale scores to generate an overall score.For the 4‐year data, continuous outcomes were analyzed by adding responses at this time point to the aforementioned regression models. For time to first pregnancy and time to first further procedure for treatment of fibroids, a Cox proportional hazard model was carried out, adjusting for the minimization variables. Kaplan–Meier plots were produced, in which women were censored if they had withdrawn, were lost to follow‐up, or had undergone a hysterectomy.The treatment effect on the primary outcome in pre‐specified subgroups that matched the minimization variables were analyzed involving adding the subgroup‐by‐treatment group interaction parameters to the linear regression model. All analyses were performed using SAS software version 9.4 (SAS Institute, Inc.,).Participants were randomized to undergo myomectomy or UAE in a 1:1 ratio. The stratification variables were used for the minimization details of the fibroids and whether the woman desired pregnancy. The demographic and clinical criteria were requested for each randomized participant. These procedures were performed according to the local guidelines and clinician's preference.The primary outcome was participant‐reported health‐related quality of life domain of the Uterine Fibroid Symptom and Quality of Life (UFS‐QOL) tool, which combines the assessment of symptoms as well as quality of life.Blood tests were obtained at baseline, along with various demographic and clinical criteria. Patients were allocated to treatment, either myomectomy or UAE, following the randomization process. These procedures were performed according to the local guidelines and clinician's preference.Secondary outcomes included loss of menstrual blood using the Pictorial Bleeding Assessment Chart (PBAC), pregnancy and related outcomes, patient acceptability, length of hospital stay, further treatments, assessment of ovarian reserve by measuring FSH, AMH, luteinizing hormone, serious adverse events, and complications.