Sonographic Features of Fibroids Before and During Non-surgical Therapy and/or Expectant Management

Study Overview
=================
Brief Summary
-----------------
Rationale: 20-30% of women of reproductive age have leiomyomas, causing symptoms like dysmenorrhea and pelvic pain which both effect quality of life.[1-4] The natural behaviour of uterine fibroids is to grow between 7 to 84% in 3 to 12 months.[5-7] Non-surgical options to treat uterine fibroids are non-hormonal or hormonal medical therapies and minimally invasive interventional radiologic techniques. Exogenous hormone exposure including COC, POP or Mirena give in conflicting literature minimal growth to 60% volume shrinkage. [8, 9]] Selective progesterone receptor modulators (SPRM) eg. Esmya and GnRH-analogues intent to reduce fibroids volume after several months; GnRH-agonists provide a 31-63% shrinkage and less frequently applied GnRH-antagonists 14.3 - 42.7%.[10-16] Esmya gives a volume reduction varying between 10 to 48%.[17] Radiological technique like embolization decreases dominant fibroid volume with 40-70%.[1, 18-22] UAE fails in case of devascularized or minimal vascularized fibroids.[23] Ablation techniques show shrinkage up to a maximum of 90% depending e.g. which treatment.[24-41] Clear prognostic models to predict the effect on fibroid related symptoms and volume reduction are lacking. We postulate higher vascularity to be related to 1) larger fibroid growth during the natural course or during exogenous hormonal exposure; 2) more effective shrinkage during progestogens, GnRH-analogues, SPRM and UAE; but 3) less effective after ablation therapy. Objectives: To study the value of sonographic features including vascularity in the prediction of fibroids' volume change at follow-up during their (1) natural course or (2) long-term use of exogenous hormone exposure; after initiation of (3) SPRM or GnRH-analogues treatment or (4) exogenous hormonal exposure; or after (5) embolization or (6) ablation therapy. Study design: Observational cohort study during 5 years in the outpatient clinic. Patientselection: Women ≥18 years with 1 to 3 fibroids with a maximal diameter ≥ 3cm and ≤ 10cm diagnosed on ultrasound examination, planned for expectant or non-surgical management. Study objectives: The primary outcome is volume reduction after 3 to 12 month depending on the study group. The secondary outcome include UFS-QOL, EQ-5D score, PBAC, hemoglobin level, treatment failure rate and (re)intervention rate. Nature and extent of the burden and risks associated with participation, benefit and group relatedness: No risks are associated with the participation of this observational study since the outcome measures include vaginal ultrasound, questionaires and a hemoglobin test. These measurements are also applied in daily practice, the burden for the patient is time. Extra in the context of the study are questionnaires which last a maximum of 5-15 minutes. The treatment considering the fibroid(s) is independent of this research.

Official Title
-----------------
Sonographic Features of Fibroids Before and During Non-surgical Therapy and/or Expectant Management

Conditions
-----------------
Fibroid Uterus

Intervention / Treatment
-----------------
* Other: Questionnaire


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 1 to 3 fibroids maximal diameter ≥1.5 cm and ≤ 10 cm diagnosed on ultrasound examination with informed consent planned for expectant management or non-surgical management in the follwing groups: Women with uterine fibroids without treatment (during natural course); Women with uterine fibroids using exogenous hormone exposure for at least 3 months: e.g. COC, POP, DP or LNG-IUD; Women with uterine fibroids before and after/during treatment with SPRMs or GnRH-analogues; Women with uterine fibroids before and after/during treatment with exogenous hormones; Women with uterine fibroids before and after embolization; Women with uterine fibroids before and after ablation therapy*. In case of embolization or ablation: inclusion in case of multiple fibroids is allowed, if ≥ 1 fibroid is accessible for transvaginal ultrasound. Exclusion Criteria: Any fibroid treatment in the last 3 months in case of (3) SPRMs or GnRH-analogues (except for exogenous hormone exposure) or (1) no treatment Age < 18 years Fibroids not accessible for transvaginal ultrasonography Suspicion for malignancy Postmenopausal Severe adenomyosis Pregnancy Contra-indication for the planned treatment Use of aromatase inhibitors or tamoxifen Infertility treatment with use of clomifene and/or follicle-stimulating hormone Breastfeeding

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| natural course<br>To study the value of sonographic features including vascularity in the prediction of fibroids' volume change at follow-up during their (1) natural course or (2) long-term use of exogenous hormone exposure; after initiation of (3) SPRMs or GnRH-analogues treatment or (4) exogenous hormonal exposure; or after (5) embolization or (6) ablation therapy . Primary outcome: Natural behaviour - 1 year | Other: Questionnaire<br>* Extra in the context of the study are questionnaires which last a maximum of 5-15 minutes. The treatment considering the fibroid(s) is independent of this research. the Also the outcome measures include vaginal ultrasound, questionaires and a hemoglobin test. These measurements are applied in daily practice, as standard care.<br>|
| during long-term use of exogenous hormone exposure<br>To study the value of sonographic features including vascularity in the prediction of fibroids' volume change at follow-up during their (1) natural course or (2) long-term use of exogenous hormone exposure; after initiation of (3) SPRMs or GnRH-analogues treatment or (4) exogenous hormonal exposure; or after (5) embolization or (6) ablation therapy . Primary outcome: Long-term exogenous hormonal exposure - 1 year | Other: Questionnaire<br>* Extra in the context of the study are questionnaires which last a maximum of 5-15 minutes. The treatment considering the fibroid(s) is independent of this research. the Also the outcome measures include vaginal ultrasound, questionaires and a hemoglobin test. These measurements are applied in daily practice, as standard care.<br>|
| Selective progesterone receptor modulators treatment or GnRH-analogues treatment<br>To study the value of sonographic features including vascularity in the prediction of fibroids' volume change at follow-up during their (1) natural course or (2) long-term use of exogenous hormone exposure; after initiation of (3) SPRMs or GnRH-analogues treatment or (4) exogenous hormonal exposure; or after (5) embolization or (6) ablation therapy . Primary outcome: SPRMs or GnRH-analogues - 3 months | Other: Questionnaire<br>* Extra in the context of the study are questionnaires which last a maximum of 5-15 minutes. The treatment considering the fibroid(s) is independent of this research. the Also the outcome measures include vaginal ultrasound, questionaires and a hemoglobin test. These measurements are applied in daily practice, as standard care.<br>|
| after initiation exogenous hormonal exposure<br>To study the value of sonographic features including vascularity in the prediction of fibroids' volume change at follow-up during their (1) natural course or (2) long-term use of exogenous hormone exposure; after initiation of (3) SPRMs or GnRH-analogues treatment or (4) exogenous hormonal exposure; or after (5) embolization or (6) ablation therapy . Primary outcome: Initiation of exogenous hormonal exposure - 1 year | Other: Questionnaire<br>* Extra in the context of the study are questionnaires which last a maximum of 5-15 minutes. The treatment considering the fibroid(s) is independent of this research. the Also the outcome measures include vaginal ultrasound, questionaires and a hemoglobin test. These measurements are applied in daily practice, as standard care.<br>|
| embolization therapy<br>To study the value of sonographic features including vascularity in the prediction of fibroids' volume change at follow-up during their (1) natural course or (2) long-term use of exogenous hormone exposure; after initiation of (3) SPRMs or GnRH-analogues treatment or (4) exogenous hormonal exposure; or after (5) embolization or (6) ablation therapy . Primary outcome: Embolization - 6 months | Other: Questionnaire<br>* Extra in the context of the study are questionnaires which last a maximum of 5-15 minutes. The treatment considering the fibroid(s) is independent of this research. the Also the outcome measures include vaginal ultrasound, questionaires and a hemoglobin test. These measurements are applied in daily practice, as standard care.<br>|
| ablation therapy<br>To study the value of sonographic features including vascularity in the prediction of fibroids' volume change at follow-up during their (1) natural course or (2) long-term use of exogenous hormone exposure; after initiation of (3) SPRMs or GnRH-analogues treatment or (4) exogenous hormonal exposure; or after (5) embolization or (6) ablation therapy . Primary outcome: Ablation therapy - 6 months | Other: Questionnaire<br>* Extra in the context of the study are questionnaires which last a maximum of 5-15 minutes. The treatment considering the fibroid(s) is independent of this research. the Also the outcome measures include vaginal ultrasound, questionaires and a hemoglobin test. These measurements are applied in daily practice, as standard care.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Volume change | Three directions on 2D ultrasound in centimeters. | Baseline, 3 and 12 months, in embolization and ablation group after 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Questionnaire Utreine Fibroid Specific Quality of Life | UFS-Qol. Total health-related quality of life (29 items, 29-145 points). Or seven subscales: 'symptom severity' (8 items, 8-40 points), 'concern' (5 items, 5-25 points), 'activities' (7 items, 7-35 points), 'energy/mood' (7 items, 7-35 points), 'control' (5 items, 5-25 points), 'self-conscious' (3 items, 3-15 points), 'sexual function' (2 items, 2-10 points). The higher, the lower the quality of life. | Baseline, 3, 12 and 24 months, in embolization and ablation group after 6 months | 
| Questionnaire EuroQol 5 Dimensions | EQ-5D. Range 0 - 1. The higher, the lower the quality of life. | Baseline, 3, 12 and 24 months, in embolization and ablation group after 6 months | 
| Questionnaires Picterial Bloodloss Assessment Chart | PBAC. Range 0 to no maximum. PBAC > 150 is heavy menstrual bleeding. The higher, the more bloodloss. | Baseline, 3, 12 and 24 months, in embolization and ablation group after 6 months | 
| Questionnaire re-intervention rate | Percentage of patients who underwent re-intervention (e.g. embolization, operation, etc) for their fibroid(s) in follow-up period. Range: 0-100%, the higher, the more re-interventions. | Baseline, 3, 12 and 24 months, in embolization and ablation group after 6 months | 
| Questionnaire treatment failure rate | Percentage of patients who started additional treatment (e.g. medication, etc) for their fibroid(s) in follow-up period. Range: 0-100%, the higher, the more treatment failures. | Baseline, 3, 12 and 24 months, in embolization and ablation group after 6 months | 
| Haemoglobin | According to local protocol, standard care, mmol/L (range 0-20). A lower haemoglobin level corresponds with more menstrual bloodloss and/or anemia. | Baseline, 3 and 12 months, in embolization and ablation group after 6 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
fibroid, power doppler, vascularization