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Aims: Uterine fibroids are benign tumours that cause various complaints. These complaints may significantly compromise quality of life, necessitating a clinical intervention in 25–50% of the affected women. Hysterectomy, myomectomy or embolization may offer symptomatic relief, but are costly, include a recovery period, can cause serious side‐effects, sometimes fail to treat symptoms completely and are not always desired by patients. Ulipristal is a conservative long‐term treatment that has a fibroid‐volume decreasing effect, acceptable side‐effects while preserving fertility and may be an alternative to surgical alternatives. Currently, ulipristal is investigated by the European Medicine Agency and suspended from marketing authorization because it may cause drug‐induced liver injury (DILI). However, many drugs can cause severe DILI and prospective studies estimate 14–19 DILI cases/100 000 people. Methods: This overview will discuss the risk–benefit balance between ulipristal and DILI, describe the safety–efficacy balance of ulipristal and its alternative treatments and the arguments that led to the suspension of its marketing authorization. Results: Ulipristal may be associated with DILI resulting in a risk of severe liver injury in 1.5:100 000 patients and fatal liver injury in 0.1:100 000 patients. This risk needs to be weighed against the higher mortality risk of >1:1000 and higher incidence of severe complications after surgery. Conclusion: The DILI risk of ulipristal is considerably lower than that of other medicines that are not suspended, nor need additional safety measures. When evaluating drugs and drug safety, risks that apply to the alternative nonpharmacological treatment options should be taken into consideration. [ABSTRACT FROM AUTHOR]

The aims of this prospective diagnostic evaluation study were (i) to estimate the inter-observer agreement and reproducibility of real-time sonoelastography and real-time gray-scale ultrasound in the measurement of uterine and fibroid volumes; (ii) to evaluate the agreement between real-time gray-scale ultrasound, sonoelastography and magnetic resonance imaging with respect to these outcomes; and (iii) to evaluate the diagnostic accuracy of sonoelastography in the diagnosis of uterine pathology on stored sonoelastography and gray-scale cine loops. Women without a history of uterine pathology and with the diagnosis intrauterine fibroids or adenomyosis were included. All participants underwent gray-scale ultrasound, sonoelastography and magnetic resonance imaging. Compression sonoelastography was found to have high inter-observer and inter-method agreement for the measurement of uterine and fibroid volumes. The addition of sonoelastography to gray-scale ultrasound seems to be useful in the differentiation between fibroids, adenomyosis and normal uteri as reflected by an increase in accuracy and diagnostic agreement. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: To determine the effect of preference and treatment allocation on health-related quality of life (HRQOL) in patients in the randomized EMMY trial of hysterectomy versus uterine artery embolization (UAE) for symptomatic uterine fibroids. Study design: We invited 349 patients eligible for trial participation, of which 177 agreed to participate (the ‘randomized group’). Within the randomized group, patients were allocated to. UAE (n =88) or hysterectomy (n =89). The remaining 172 patients refused randomization and received the treatment of their preference (varying from hysterectomy to no treatment at all), of which 103 patients agreed to fill in questionnaires (the ‘preference group’). Patients’ treatment preferences and HRQOL were assessed at baseline and the patients were prospectively followed to evaluate HRQOL at 12 months after treatment. Results: At baseline, most patients in the randomized group preferred UAE: 115/177 (65%). In the preference group most patients preferred hysterectomy: 100/172 (58%). At 12 months there was no effect of having had the preferred treatment on HRQOL, neither in the randomized nor in the preference group. The randomized group improved significantly in both mental and physical health, compared to baseline. In the preference group, only mental health improved compared to baseline, while physical health did not improve significantly. Conclusions: In a randomized trial comparing UAE and hysterectomy for symptomatic fibroids, the pre-randomization preference for a specific treatment did not affect HRQOL. Trial participants improved better on physical HRQOL than women who refused to participate. [Copyright &y& Elsevier]

PURPOSE: Uterine artery embolization (UAE) is an emerging treatment for symptomatic uterine fibroid tumors. This study was performed to evaluate the periprocedural results of the UAE procedure and identify risk factors for technical failure, fever after UAE, pain, and other complications MATERIALS AND METHODS: As part of a multicenter, randomized trial to compare UAE versus hysterectomy in patients with symptomatic uterine fibroid tumors, 81 patients underwent UAE. Univariate and multivariate analyses were used to identify predictors for technical failure, postprocedural fever, complications as defined by the Society of Interventional Radiology (SIR), and pain scores RESULTS: The technical failure rate according to SIR guidelines was 5.3% (95% CI, 2.3%–10.1%). The procedural failure rate was 17.3% (95% CI, 9.8%–27.3%). Bilateral failure occurred in four of 81 patients and unilateral failure occurred in 10 of 81 patients. Technical failure occurred mainly as a result of difficult anatomy (3.7%) or absence of the uterine artery (3.1%). The overall complication rates were 28.4% during the patients'' hospital stay and 60.5% for the 6 weeks after discharge. The risk of technical failure was found to increase in the presence of a single fibroid tumor (odds ratio [OR], 6.21; 95% CI, 1.65–23.41; P = .007) and/or a small uterine volume (<500 cm3; OR, 10.8; 95% CI, 1.25–93.36; P = .03). The amount of embolization material was associated with the onset of fever after UAE (OR, 2.05; 95% CI, 1.09–3.87; P = .027), major complications (OR, 5.68; 95% CI, 2.05–15.75; P = .001), and high pain scores (OR, 1.97; 95% CI, 1.08–3.58; P = .027) CONCLUSIONS: The procedural failure rate for UAE was higher than those reported by others, mainly as a result of difficult anatomy and absence of a uterine artery in some cases. The risk of procedural failure was increased for patients with single fibroid tumors and/or small uterine volumes. A clear dose–effect response was revealed between the amount of embolization material used and the risk for postprocedural fever, major complications, and severe pain [Copyright &y& Elsevier]

Abstract: Uterine artery embolisation (UAE) is a new treatment for heavy menstrual bleeding caused by uterine fibroids. The EMMY trial evaluates the safety and efficacy of UAE in a randomised comparison to hysterectomy. Patients were included when they had uterine fibroids and menorrhagia and were eligible for hysterectomy. The primary endpoint is the elimination of menorrhagia after a 1-year follow-up period. Secondary endpoints comprise: effect on complaints of pain and pressure, quality of life issues, uterine volume reduction, effect on ovarian function and cost-effectiveness. 177 Patients were randomly assigned (1:1) to either UAE (n=88) or hysterectomy (n=89). The results of this trial will be presented at a later stage. UAE is already being performed on a regular basis, without profound evidence: no good quality randomised controlled trials have been conducted. This trial is the first to evaluate the value of UAE in clinical practice with a control group. Whether UAE can replace hysterectomy as treatment of first choice depends on the balance of efficacy, costs and quality of life. [Copyright &y& Elsevier]

Objectives: To investigate differences in volume and fibroid vascularity expressed in vascular index after three months of (pre-)treatment with leuprolide acetate (LPA) or ulipristal acetate (UPA).Study Design: Prospective pilot study of 23 premenopausal women with uterine fibroids. Patients who started with LPA or UPA and had at least one fibroid with a size between 3 and 12 cm, were included consecutively. Per patient one fibroid was evaluated. The ultrasound was performed at baseline and after three months using LPA or UPA using a standardized protocol. 3D scans were evaluated using VOCAL software to calculate outcomes of volume, vascular index (VI) without shell ("shell off") and of the inner shell.Results: Four patients in the LPA group were additionally excluded from analyses due to insufficient quality of 3D scans. In the ten remaining patients (pre-)treated with LPA both volume and vascular indices of the fibroid reduced significantly after three months from a median of 224.3 cm3 (IQR 338.0) to 124.8 cm3 (IQR 186.1) (p = 0,05); median VI fibroid (shell off) reduced from 4.30 (IQR 4.72) to 0.93 (IQR 1.54) (p = 0,05); and VI inner capsule from 6.34 (IQR 7.51) to 1.28 (IQR 2.13) (p = 0,05). After UPA (n = 9) changes in fibroid volume and vascular indices did not reach statistical significance. Volume reduced from 248.5 cm3 (IQR 271.9) to 140.7 cm3 (IQR 209.4) (p > 0,05); median VI fibroid (shell off) from 2.97 (IQR 3.81) to 2.90 (IQR 4.82) (p > 0,05); and VI inner capsule from 2.56 (IQR 7.48) to 2.89 (IQR 4.83) (p > 0,05). A strong positive correlation was found between the VI of the fibroid (shell off) at baseline with the volume change after three months of LPA use (LPA r = 0.636, p = 0.048, 95% CI = -0.03 - 1.00).Conclusion: In this pilot study we observed a consistent and statistically significant decrease in VI and fibroid volume after three months of LPA treatment in patients with uterine fibroids. The decrease in fibroid volume and VI was less consistent after UPA use. The strong correlation between the VI at baseline and volume reduction, may in theory be used to predict the volume reduction after LPA. [ABSTRACT FROM AUTHOR]

Background: Since 1995 uterine artery embolization has been described as an alternative for hysterectomy in patients with symptomatic fibroids. Many studies including several randomized controlled trials established uterine artery embolization as a valuable treatment. These randomized controlled trials reported outcomes in terms of health-related quality of life, clinical outcomes, efficacy, and cost-effectiveness after 1, 2, and 5 years of follow-up.Objective: The purpose of this study was to compare clinical outcome and health-related quality of life 10 years after uterine artery embolization or hysterectomy in the treatment of heavy menstrual bleeding caused by uterine fibroids in a randomized controlled trial.Study Design: In all, 28 Dutch hospitals recruited patients with symptomatic uterine fibroids who were eligible for hysterectomy. Patients were 1:1 randomly assigned to uterine artery embolization or hysterectomy. The outcomes assessed at 10 years postintervention were reintervention rates, health-related quality of life, and patient satisfaction, which were obtained through validated questionnaires. Study outcomes were analyzed according to original treatment assignment (intention to treat).Results: A total of 177 patients were randomized from 2002 through 2004. Eventually 81 uterine artery embolization and 75 hysterectomy patients underwent the allocated treatment shortly after randomization. The remaining patients withdrew from the trial. The 10-year questionnaire was mailed when the last included patient had been treated 10 years earlier. The mean duration of follow-up was 133 months (SD 8.58) accompanied by a mean age of 57 years (SD 4.53). Questionnaires were received from 131 of 156 patients (84%). Ten years after treatment, 5 patients underwent secondary hysterectomy resulting in a total of 28 of 81 (35%) (24/77 [31%] after successful uterine artery embolization). Secondary hysterectomies were performed for persisting symptoms in all cases but 1 (for prolapse). After the initial treatment health-related quality of life improved significantly. After 10 years, generic health-related quality of life remained stable, without differences between both groups. The urogenital distress inventory and the defecation distress inventory showed a decrease in both groups, probably related to increasing age, without significant differences between study arms. Satisfaction in both groups remained comparable. The majority of patients declared being (very) satisfied about the received treatment: 78% of the uterine artery embolization group vs 87% in the hysterectomy group.Conclusion: In about two thirds of uterine artery embolization-treated patients with symptomatic uterine fibroids a hysterectomy can be avoided. Health-related quality of life 10 years after uterine artery embolization or hysterectomy remained comparably stable. Uterine artery embolization is a well-documented and less invasive alternative to hysterectomy for symptomatic uterine fibroids on which eligible patients should be counseled. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to compare the 2 years’ efficiency of uterine artery embolization (UAE) with hysterectomy in the treatment of menorrhagia caused by uterine fibroids in a randomized controlled trial. Study Design: Twenty-eight Dutch hospitals recruited patients with uterine fibroids and menorrhagia, who were eligible for hysterectomy. Patients were randomized to UAE or hysterectomy. The primary endpoint was if UAE could avoid a subsequent hysterectomy in at least 75% of cases. Secondary endpoints were changes in pain, bulk-related complaints, and uterine and dominant fibroid volume reduction. Results: One hundred seventy-seven patients were randomized to UAE (n = 88) or hysterectomy (n = 89). Two years after treatment 23.5% of UAE patients had undergone a hysterectomy. There were no significant differences in improvement compared to baseline in pain and bulk-related complaints. Uterine and dominant fibroid volume reduction in UAE patients was 48.2% and 60.5%, respectively. Conclusion: UAE is a valuable alternative treatment for symptomatic uterine fibroids. Nevertheless, when patients seek for certainty on the cessation of bleeding problems, a hysterectomy remains the treatment of choice. [Copyright &y& Elsevier]

Objectives: Transcervical resection of myoma (TCRM) is a widely implemented treatment for submucous fibroids. The aim of this study is to evaluate the effect of TCRM on menstrual bleeding, fibroid related symptoms and quality of life and hemoglobin (Hb) levels.Study Design: A prospective cohort study was conducted in three teaching hospitals and two academic hospitals in the Netherlands. Patients with HMB (PBAC score > 150) and submucous fibroids (type 0, 1, 2, 3, 4 and hybrid type 2-5) scheduled for TCRM were eligible. At baseline and 3 months after TCRM a Trans Vaginal Ultrasound (TVU) was performed and a Hb sample was taken. Patients filled out the Pictorial Blood Assessment Chart (PBAC) and the Uterine Fibroid Symptom and Quality of Life (UFS-QOL) questionnaire at baseline and up to 6 months after surgery. Primary outcome was improvement in PBAC score 6 months after surgery. Secondary outcomes were improvement in PBAC score and Hb level 3 months after surgery and UFS-QOL scores 3 and 6 months after surgery.Results: 126 patients were included and 104 were operated. PBAC were obtained from 98 patients. Six months after surgery, 56.6% of patients went from HMB to normal menstrual bleeding (PBAC < 150). A significant reduction in median PBAC scores of 427 (IQR 198 - 1392) (p <.0001) was found (86% improvement). UFS-QOL scores were obtained from 91 patients. Symptom severity improved from a median of 54 on a scale of 100 (IQR 44-66) at baseline to 22 (IQR 9-41) after 6 months (p <.0001) (59% improvement). Health related quality of life (HRQOL) improved from a median score of 44 on a scale of 100 (IQR 33-62) to 89 (IQR 67-97) 6 months after surgery (p <.0001) (102% improvement).Conclusion: TCRM significantly reduces the amount of menstrual bleeding, severity of fibroid related symptoms and improves HRQOL in patients with submucous fibroids. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To study the diagnostic value of three-dimensional gel instillation sonography (3D GIS) in addition to two-dimensional (2D) GIS in the assessment of intrauterine abnormalities. Secondly, the clinical value of 3D GIS in the planning for hysteroscopic procedures was evaluated. Study design: A prospective cohort study was performed from 2008 till 2010. All women with a suspected intrauterine abnormality on 2D GIS suitable for hysteroscopic resection or with recurrent postmenstrual bleeding were planned for a hysteroscopic procedure. Diagnostic accuracy tests were calculated for the detection of fibroids and polyps with both histology and hysteroscopy as the reference standard. For the assessment of type and size of fibroids hysteroscopy was used as the reference standard. We compared the planning for type of hysteroscopy based on 2D GIS findings with the combined 2D–3D GIS findings. Results: In total 110 patients were analysed. In comparison to histology, addition of 3D GIS did not change sensitivity or specificity substantially in the discrimination between fibroids and polyps. In comparison to hysteroscopy, sensitivity increased for detecting fibroids and polyps, without major interference with the specificity. Despite an improved accuracy after the addition of 3D GIS, the planning for hysteroscopic procedures did not improve substantially. Conclusion: In daily practice, the addition of 3D GIS to 2D GIS improved the accuracy for the detection of polyps and fibroids compared to hysteroscopy, but only marginally improved the planning of hysteroscopic procedures, and therefore the clinical relevance seems to be limited. [Copyright &y& Elsevier]

Objective: Uterine fibroids are the most common benign tumours in women of the reproductive age. Symptoms of heavy menstrual bleeding, abdominal discomfort and infertility may seriously affect a woman's quality of life. Uterine artery embolization is a safe and effective alternative treatment to hysterectomy or myomectomy for symptomatic uterine fibroids. Which treatment provides the highest quality of life, least complications, symptom reduction and least chance intervention, has not been established and might depend on strict patient selection. This study aims to identify which specific subgroups benefit most of each treatment by analyzing individual participant data derived from randomized controlled trials of women undergoing embolization or surgical treatment. This study will primarily assess the effectiveness of both treatment groups by evaluating the effect on quality of life of embolization in comparison to surgery on specific patient and fibroid characteristics and the possible need for re-intervention for fibroid-related symptoms.Data Sources: PubMed/MEDLINE, Embase and The Cochrane Library were searched up to August 2020.Study Eligibility Criteria: We will collect individual participant data from randomized controlled trials that studied clinical and procedural outcomes of premenopausal women with symptomatic uterine fibroids, who were randomized between uterine artery embolization and surgery.Study Appraisal and Synthesis Methods: Individual participant data from all eligible trials will be sought and analysed according to intention-to-treat principle. Risk of Bias will be done by using version 2 of the Cochrane tool for Risk of Bias in randomized trials. Subgroup analyses to explore the effect of e.g. age, fibroid characteristics and fibroid complaints will be performed, if data is available. This individual patient data meta-analysis will be analysed according to a one-stage model. [ABSTRACT FROM AUTHOR]

Objectives: Fibroids are the most common benign tumours found in the uterus and can cause various symptoms. In 20-50 % of the women, an intervention is required. When conservative options fail, invasive options such as hysterectomy, uterine artery embolization or myomectomy are eligible options. Ulipristal acetate (UPA) was launched as the sole available long term pharmaceutical treatment, with the potential to avoid surgery. It is suggested that UPA improves quality of life, reduces symptoms and fibroid volumes. However, UPA is an expensive medicine, is possibly associated with liver injury and has never been directly compared to surgical treatment. The aim of this trial is to compare UPA to surgical treatment on both effectiveness and cost-effectiveness. Primary outcome is the reduction in symptom severity scores (part of the Uterine Fibroid Symptom and Quality of Life questionnaire) at 24 months of follow-up compared to baseline. Secondary outcomes include quality of life, societal costs, societal participation, liver function variation, patient satisfaction and preference. Outcomes will be analysed according to intention-to-treat principle.Study Design: The MYOMEX-2 trial is an open-label, multicentre, non-inferiority randomized controlled trial. Patients are pre-menopausal women with symptomatic fibroids eligible for surgical treatment (hysterectomy, myomectomy or UAE). Fibroid symptoms may comprise (but are not limited to) heavy menstrual bleeding, bulk symptoms or pain. Patients are randomised 2:1 in a parallel group design between two treatment arms: 119 patients in the UPA group and 60 patients in the surgery group. Follow up comprises of online questionnaires, outpatient visits and phone appointments on several follow up moments, up to 24 months after surgery or start UPA.Registration Details: MYOMEX-2 trial; protocol version 4, date 22-02-2019; NTR6860; NL62638.029.18. All items from the World Health Organization Trial Registration Data Set are provided in the online supplementary file (Appendix-B). [ABSTRACT FROM AUTHOR]

Ulipristal acetate is increasingly used for several clinical indications, like emergency contraception and pre-treatment of uterine fibroids. It has mixed progesterone agonist and antagonist effects in the myometrium and endometrium. Due to its progesterone antagonistic effect, an unopposed estrogen effect could occur which could cause (pre-)malignant lesions in the endometrium. Several studies have been performed to evaluate this possible increased risk for endometrial malignancies when using ulipristal acetate. The specific spectrum of morphological changes due to ulipristal acetate, named progesterone receptor modulator associated endometrial changes (PAEC), occurs to be reversible after discontinuing ulipristal acetate. In this systematic review we provide a detailed overview of the literature on histopathological endometrial changes and imaging characteristics of the endometrium in ulipristal acetate users. We performed an extensive search in Embase.com, Wiley/Cochrane Library and PubMed in accordance with the prisma guidelines. All studies published as full papers in peer reviewed journals using ulipristal acetate reporting on endometrial changes were included, independent of clinical indication, dosage taken and duration of therapy. No language restrictions were applied. Ten studies with a total of 1450 participants were included. Seven were randomized clinical trials and three prospective cohort studies. A quality assessment of all included studies was performed. In only five of ten studies an endometrial biopsy was performed during treatment. All of these studies described specific histological non-physiological endometrial changes (PAEC) due to ulipristal acetate, varying from 41 to 78.8% of all patients. Three of these studies also performed follow-up biopsies after discontinuing ulipristal acetate. The percentage of PAEC decreased from 62% to 0%, 78.8% to 0% and from 59% to 6-7% after the treatment period. In six of 1450 women (0.4%) endometrial hyperplasia was reported during or after ulipristal acetate use. Five were simple hyperplasia, one biopsy showed simple atypical endometrial hyperplasia that resolved into benign secretory endometrium by the end of the treatment. One case of endometrial adenocarcinoma was reported, however this does not seem to be related to ulipristal acetate use, since it was already present at the baseline biopsy. In eight of ten studies a transvaginal ultrasound or MRI was performed at any moment to assess the endometrial thickness before, during and after treatment. Most studies showed a transient increase of endometrial thickness during treatment, which returned to normal within a few weeks after discontinuing ulipristal acetate. Based on the literature found in this systematic review, follow-up after a maximum of four courses of ulipristal acetate did not report any non-reversible (pre-)malignant lesions of the endometrium. Most studies focused on short term use of ulipristal acetate and their follow-up period was limited. Therefore, we believe more information concerning long term (intermittent) use is needed before it can be concluded that its use is completely safe. [ABSTRACT FROM AUTHOR]

Objectives The volume of a fibroid uterus before performing hysterectomy is typically estimated through bimanual examination and confirmed by ultrasonography. This study compares estimated volumes by bimanual examination and ultrasound examination with MRI and actual volumes obtained from histopathology, as gold standards. Study design We used data from a previous prospective randomized multi-center trial that compared hysterectomy and uterine artery embolization (UAE) for the treatment of symptomatic fibroids. All patients underwent bimanual vaginal examination and pelvic ultrasonography. Those women randomized to UAE received a pelvic MRI. For women randomized to hysterectomy, the exact uterine volume was based on histopathologic examination. We compared the calculated volumes based on ultrasound parameters and estimated volume based on bimanual examination with either the calculated volumes of the pelvic MRI parameters or the calculated volume based on the exact weight during histological examinations. Results Our study demonstrated poor agreement between ultrasound and bimanual examination compared with exact volume during histopathologic examination and MRI-based volume. The agreement within the patient group with uterine volume >233 g and >747 g was fair to good. For those women with a uterine volume between 233 and 747 g, the agreement was poor when comparing bimanual estimates with volume obtained from MRI or histolopathologic examination. Within this volume group, the agreement on uterine volume between ultrasound and MRI or histopathologic examination was fair. Conclusions Our study shows that uterine volume as estimated by ultrasound and bimanual examination can be used for small or large uteri. For uteri with an intermediate volume, bimanual examination and ultrasound are less reliable. [ABSTRACT FROM AUTHOR]