Standardising outcome reporting for clinical trials of interventions for heavy menstrual bleeding: Development of a core outcome set.

OBJECTIVE: To develop a core outcome set for heavy menstrual bleeding (HMB). DESIGN: Core outcome set (COS) development methodology described by the COMET initiative. SETTING: University hospital gynaecology department, online international survey and web-based international consensus meetings. POPULATION OR SAMPLE: An international collaboration of stakeholders (clinicians, patients, academics, guideline developers) from 20 countries and 6 continents. METHODS: Phase 1: Systematic review of previously reported outcomes to identify potential core outcomes. Phase 2: Qualitative studies with patients to identify outcomes most important to them. Phase 3: Online two-round Delphi survey to achieve consensus about which outcomes are most important. Phase 4: A consensus meeting to finalise the COS. MAIN OUTCOME MEASURES: Outcome importance was assessed in the Delphi survey on a 9-point scale. RESULTS: From the 'long list' of 114, 10 outcomes were included in the final COS: subjective blood loss; flooding; menstrual cycle metrics; severity of dysmenorrhoea; number of days with dysmenorrhoea; quality of life; adverse events; patient satisfaction; number of patients going on to have further treatment for HMB and haemoglobin level. CONCLUSIONS: The final COS includes variables that are feasible for use in clinical trials in all resource settings and apply to all known underlying causes of the symptom of HMB. These outcomes should be reported in all future trials of interventions, their systematic reviews, and clinical guidelines to underpin policy.

The significance of transcervical ultrasound-guided radiofrequency ablation in the treatment of symptomatic fibroids: results of an expert consensus from German-speaking countries.

Uterine fibroids are one of the most common diseases in female patients, lead mainly to bleeding disorders and lower abdominal pain, and reduce the chance of having children. In recent years we have seen a trend towards more and more pharmacotherapies and minimally invasive organ-preserving treatments. One novel and innovative procedure for an organ-preserving treatment of symptomatic uterine fibroids is the transcervical ultrasound-guided radiofrequency ablation (TRFA). TRFA has been used in Germany since 2013 and later found use in other German-speaking countries as well. There have now been more than 1200 TRFA treatments performed in Germany, Austria, and Switzerland. Experts from these three countries came together for a consensus meeting to analyze the significance of the procedure in the overall concept of the treatment of symptomatic uterine fibroids.

Pregnancy Outcomes After Transcervical Radiofrequency Ablation of Uterine Fibroids with the Sonata System.

Objective: To describe pregnancy outcomes in women who conceived after undergoing transcervical fibroid ablation (TFA) as treatment for symptomatic uterine fibroids. Materials and Methods: TFA was used to treat symptomatic uterine fibroids with radiofrequency energy, both under clinical trial protocol and commercial usage in hospitals in Europe, the United Kingdom, Mexico, and the United States. All women who reported pregnancies to their physicians after undergoing TFA with the Sonata® System and provided consent for use of their data were included. Results: There have been 36 pregnancies representing 20 deliveries among 28 women who were treated with TFA. Five women conceived more than once postablation, and four conceived as a result of assisted reproductive technology (ART). Outcomes include 8 vaginal deliveries, 12 Cesarean sections, 3 therapeutic abortions, and 8 first trimester spontaneous abortions (four occurring in a patient with a history of recurrent pregnancy loss and an immunologic disorder). Five women are currently pregnant, two of whom previously delivered after TFA. There were no 5-minute Apgar scores <7, and all neonates weighed >2500 g. All deliveries occurred at ≥37 weeks except for one delivery at 35 6/7 weeks. There were no uterine ruptures or abnormal placentation and no reports of postpartum hemorrhage or stillbirths. Ablated fibroids included transmural, submucous, and intramural myomata up to 7 cm in diameter. Conclusions: Normal pregnancy outcomes at term have occurred after TFA with the Sonata System, including in women with recurrent abortion and in those undergoing ART. There were no instances of low Apgar scores, low birthweight, stillbirth, postpartum hemorrhage, or uterine rupture (FAST-EU, NCT01226290; SONATA, NCT02228174; SAGE, NCT03 118037). (J GYNECOL SURG 38:207).

Term Delivery in an Infertile Patient after Transcervical Radiofrequency Fibroid Ablation and Assisted Reproductive Technology.

Background: Transcervical radiofrequency (RF) ablation of uterine fibroids is an incisionless procedure to treat nonpedunculated uterine fibroids, including those that are not amenable to operative hysteroscopy. However, its safety and effectiveness regarding fertility and fecundity have not been established, including among women with infertility. Case: A 38-year-old nullipara with infertility since 2008 and a recent complaint of refractory dysmenorrhea in association with a uterine fibroid underwent transcervical RF ablation with the Sonata® System (Gynesonics, Redwood City, CA) to treat the symptomatic myoma. Unsuccessful assisted reproduction (intracytoplasmic sperm injection/embryo transfer) as confirmed by negative pregnancy testing had been attempted 1 month preablation, and a second embryo transfer after thawing the previously cryopreserved pronuclei was performed 7 months postablation. Results: RF ablation with the Sonata System resulted in a 68% reduction in fibroid volume noted on sonography 2 months post-treatment along with resolution of the patient's dysmenorrhea. No residual fibroid was noted on sonography 7 months postablation. A second attempt at assisted reproduction produced an uncomplicated pregnancy that resulted in vacuum-assisted vaginal delivery of a liveborn infant at term weighing 3670 g with Apgar scores of 91/105/1010. Pelvic sonography 4 months postpartum an unremarkable uterus, again, with no evidence of a fibroid remnant. Conclusions: This is the first report of a pregnancy and delivery in an infertile couple who underwent transcervical RF ablation of a uterine fibroid followed by assisted reproduction.

Transcervical Fibroid Ablation (TFA): Update on Pregnancy Outcomes.

Background/Objectives: Transcervical fibroid ablation (TFA) is an incisionless method to treat symptomatic uterine fibroids. While safety regarding future pregnancy remains to be established, TFA does not preclude the possibility of pregnancy, and a previous 36-patient case series of post-TFA pregnancies reported normal outcomes. That prior series did not include postmarket cases in the United States, as the Sonata® System was initially cleared and used in Europe. This is a substantive update of known pregnancies with the Sonata System since June 2011, and includes pregnancies in Europe, Mexico, and the US. Methods: TFA was carried out under both clinical trial and postmarket use to treat symptomatic uterine fibroids. All post-TFA pregnancies reported by physicians with their patient's consent were included. Results: 89 pregnancies and 55 deliveries have occurred among 72 women treated with the Sonata System. This includes 8 women who conceived more than once after TFA. Completed pregnancies (n = 62 women) include 19 vaginal deliveries, 35 Cesarean sections, 5 therapeutic abortions, 1 ectopic pregnancy, and 1 delivery by an unknown route. Ten pregnancies are ongoing. Mean birthweight was 3276.7 ± 587.3 g. Ten women experienced 18 first-trimester spontaneous abortions (SAbs), with 10 of the 18 SAbs (55.6%) occurring between two patients with a history of recurrent abortion. The SAb rate was 22.8%, inclusive of these two patients, and 10.1% if they were excluded as outliers. There were no instances of uterine rupture, placenta accreta spectrum, or stillbirth. Conclusions: This case series, the largest to date for any hyperthermic ablation modality, suggests that TFA with the Sonata System could be a feasible, safe treatment option regarding eventual pregnancy in women with symptomatic uterine fibroids.

Radiofrequency Ablation for Adenomyosis.

Adenomyosis is a common benign gynecologic condition characterized by ectopic endometrial glands and stroma in the myometrium causing pain (dysmenorrhea) and abnormal uterine bleeding. New interventional techniques have been introduced over recent years. This study evaluates the treatment success and side effects of radiofrequency ablation. An electronic literature search in the PubMed, Scopus, and ScienceDirect databases was carried out on the outcomes of pain reduction and, secondarily, on abnormal uterine bleeding, reintervention, reproductive outcome, imaging outcome, and complications. There was a mean decrease in dysmenorrhea pain scores by -63.4 ± 9.0% at 12 months. Data on other outcome parameters were sparse. No major complications were reported. Radiofrequency ablation represents a promising minimally invasive and organ-preserving treatment in patients with symptomatic adenomyosis. It is associated with clinically meaningful improvement of adenomyosis-related pain in the short term.

Normal spontaneous vaginal delivery after transcervical radiofrequency ablation of uterine fibroids: a case report.

Transcervical radiofrequency ablation of uterine fibroids was performed on a patient in Germany, who subsequently conceived. This is the first report of a normal spontaneous vaginal delivery after fibroid ablation with the Sonata® System.

A New Paradigm for Uterine Fibroid Treatment: Transcervical, Intrauterine Sonography-Guided Radiofrequency Ablation of Uterine Fibroids with the Sonata System.

PURPOSE OF REVIEW: This article provides the current evidence related to transcervical radiofrequency ablation of uterine fibroids under integrated intrauterine sonography guidance (the Sonata System). RECENT FINDINGS: Published data on the treatment of fibroids with the Sonata System has demonstrated significant median reductions in total (73.3%) and perfused (73.3%) uterine fibroid volume, menstrual bleeding (72.3%), symptom severity (62.5%), and improvements in health-related quality of life (127%) at 12 months post-ablation. A clinical trial under an FDA Investigational Device Exemption is in progress. SUMMARY: The Sonata System is a promising treatment modality for uterine fibroids. As an incisionless, minimally invasive treatment that does not require general anesthesia or hospitalization, it has the potential for redefining the current paradigm for management of symptomatic fibroids.

The FAST-EU trial: 12-month clinical outcomes of women after intrauterine sonography-guided transcervical radiofrequency ablation of uterine fibroids.

The FAST-EU Trial was designed to establish the effectiveness and confirm the safety of transcervical intrauterine sonography-guided radiofrequency ablation with the VizAblate™ System in the treatment of symptomatic uterine fibroids. This was a multicenter, prospective, single-arm trial involving academic and community hospitals in the United Kingdom, the Netherlands, and Mexico. Women with qualifying uterine fibroids and heavy menstrual bleeding underwent intrauterine sonography-guided transcervical radiofrequency ablation (RFA) with the VizAblate System; anesthesia was individualized. Patients were required to have up to five fibroids from 1 to 5 cm in diameter. The primary trial endpoint was the percentage change in perfused fibroid volume, as assessed by contrast-enhanced MRI at 3 months by an independent core laboratory. Secondary endpoints, evaluated at 6 and 12 months, included safety, percentage reductions in the Menstrual Pictogram (MP) score, and the Symptom Severity Score (SSS) subscale of the Uterine Fibroid Symptom-Quality of Life (UFS-QOL) questionnaire, along with the rate of surgical reintervention for abnormal uterine bleeding and the mean number of days to return to normal activity. Additional assessments included the Health-Related Quality of Life (HRQOL) subscale of the UFS-QOL, nonsurgical reintervention for abnormal uterine bleeding, anesthesia regimen, patient satisfaction, and pain during the recovery period. An additional MRI study was performed at 12 months on a subgroup of patients. Fifty patients (89 fibroids) underwent transcervical radiofrequency ablation with the VizAblate System. At 3 and 12 months, perfused fibroid volumes were reduced from baseline by an average of 68.1 ± 28.6 and 67.4 ± 31.9 %, respectively, while total fibroid volumes were reduced from baseline by an average of 54.7 ± 37.4 and 66.6 ± 32.1 %, respectively (all P < .001 compared with baseline; Wilcoxon signed-rank test). At 12 months, mean MP score and SSS decreased by 53.8 ± 50.5 and 55.1 ± 41.0 %, respectively; the mean HRQOL score increased by 277 ± 483 %. There were four surgical reinterventions (8 %) within 12 months. This is the first report of the 12-month follow-up for patients in the FAST-EU Trial. In concert with previously reported 3- and 6-month endpoint data, the 12-month results of the FAST-EU Trial suggest that in addition to substantially reducing the perfused and total volume of targeted uterine fibroids, the VizAblate System is safe and effective through 12 months in providing relief of abnormal uterine bleeding associated with submucous, intramural, and transmural fibroids.

Transcervical, intrauterine ultrasound-guided radiofrequency ablation of uterine fibroids with the VizAblate® System: three- and six-month endpoint results from the FAST-EU study.

This was a prospective, longitudinal, multicenter, single-arm controlled trial, using independent core laboratory validation of MRI results, to establish the effectiveness and confirm the safety of the VizAblate® System in the treatment of symptomatic uterine fibroids. The VizAblate System is a transcervical device that ablates fibroids with radiofrequency energy, guided by a built-in intrauterine ultrasound probe. Fifty consecutive women with symptomatic uterine fibroids received treatment with the VizAblate System. Patients had a minimum Menstrual Pictogram score of 120, no desire for fertility, and met additional inclusion and exclusion criteria. The VizAblate System was inserted transcervically and individual fibroids were ablated with radiofrequency energy. An integrated intrauterine ultrasound probe was used for fibroid imaging and targeting. Anesthesia was at the discretion of each investigator. The primary study endpoint was the percentage change in perfused fibroid volume, as assessed by contrast-enhanced MRI at 3 months. Secondary endpoints, reached at 6 months, included safety, percentage reductions in the Menstrual Pictogram (MP) score and the Symptom Severity Score (SSS) subscale of the Uterine Fibroid Symptom-Quality of Life questionnaire (UFS-QOL), along with the rate of surgical reintervention for abnormal uterine bleeding and the mean number of days to return to normal activity. Additional assessments included the Health-Related Quality of Life (HRQOL) subscale of the UFS-QOL, medical reintervention for abnormal uterine bleeding, and procedure times. Fifty patients were treated, representing 92 fibroids. Perfused fibroid volumes were reduced at 3 months by an average of 68.8 ± 27.8 % (P < 0.0001; Wilcoxon signed-rank test). At 6 months, mean MP and SSS scores decreased by 60.8 ± 38.2 and 59.7 ± 30.4 %, respectively; the mean HRQOL score increased by 263 ± 468 %. There were two serious adverse events (overnight admissions for abdominal pain and bradycardia, respectively) and no surgical reinterventions. These 6-month results suggest that the VizAblate System is safe and effective in providing relief of abnormal uterine bleeding associated with fibroids, with appropriate safety and a low reintervention rate.

Radiofrequency ablation for treatment of symptomatic uterine fibroids.

The use of thermal energy-based systems to treat uterine fibroids has resulted in a plethora of devices that are less invasive and potentially as effective in reducing symptoms as traditional options such as myomectomy. Most thermal ablation devices involve hyperthermia (heating of tissue), which entails the conversion of an external electromagnetic or ultrasound waves into intracellular mechanical energy, generating heat. What has emerged from two decades of peer-reviewed research is the concept that hyperthermic fibroid ablation, regardless of the thermal energy source, can create large areas of necrosis within fibroids resulting in reductions in fibroid volume, associated symptoms and the need for reintervention. When a greater percentage of a fibroid's volume is ablated, symptomatic relief is more pronounced, quality of life increases, and it is more likely that such improvements will be durable. We review radiofrequency ablation (RFA), one modality of hyperthermic fibroid ablation.