ExAblate Treatment of Uterine Fibroids for Fertility Enhancement

Study Overview
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Brief Summary
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The objective of this trial is to evaluate the efficacy and safety of the ExAblate 2000 system for enhancement of fertility in women with non-hysteroscopically resectable uterine fibroids, who are diagnosed with unexplained infertility. Uterine fibroids are fairly common in women of child-bearing age. An evidence based review supported removing fibroids that distort the uterine cavity to increase pregnancy rates and decrease the rates of miscarriage. Some fibroids can be removed hysteroscopically which is minimally invasive, with low morbidity. However, removal of fibroids within the uterine wall require more invasive surgical procedures (e.g., myomectomy), with increasing morbidity risks including, but not limited to, infection, blood loss and postoperative uterine adhesions. ExAblate is approved by FDA for the treatment of uterine fibroids; however, its use in patients seeking pregnancy is considered experimental. Accumulated evidence suggests there are no significant complications from the procedure in women seeking pregnancy as with existing fibroid therapies; however, these data are based on a small number of patients. This study will evaluate fertility enhancement following ExAblate treatment or myomectomy, in women with unexplained infertility and who have non-hysteroscopically resectable uterine fibroids.

Official Title
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A Randomized Study to Evaluate the Effectiveness and Safety of ExAblate Surgery Compared With Myomectomy for the Enhancement of Fertility Following Treatment of Uterine Fibroids in Women Seeking Pregnancy

Conditions
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Uterine Fibroids, With Unexplained Infertility

Intervention / Treatment
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* Device: ExAblate 2000
* Procedure: Myomectomy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female Partner Able and willing to give consent Able to attend all study visits. At least one fibroid 3.0 cm or larger which is type 2 submucosal or intramural touching or abutting the cavity. Able to communicate sensations during the ExAblate procedure. Uterine fibroids, which are device accessible Fibroids(s) clearly visible on non-contrast MRI. and with uniform enhancement with gadolinium Age 21 to 40 (patients cannot be treated following their 41st birthday) Patients with uterine cavitary distortion based on MRI images or ultrasound. Premenopausal status Normal pap smear and/or HPV testing within institutional guidelines At least one ovary and at least one ipsilateral patent fallopian tube confirmed b hysterosalpingogram or laparoscopy. Normal serum follicle-stimulating hormone and thyrotropin values on days 1-5 of the cycle Length of 2 of the 3 most recent menstrual cycles between 24 and 35 days. History of trying for pregnancy for at least 6 months Documentation of ovulation using urine LH testing, serum LH testing, serum progesterone > 4 ng/dl or endometrial biopsy showing secretory endometrium in a cycle between 24 and 35 days Patient needs to demonstrate that she has already undergone testing and counseling in a fertility clinic or other medical office. Male partner inclusion criteria Age of male partner < 55 At least 10 million total mobile sperm on semen analysis within last 6 months Use of donor sperm which includes at least 10 million total mobile sperm, for female candidates who otherwise meet eligibility criteria (e.g., single women, etc) Exclusion Criteria: Uterine size > 16 weeks Prior surgical intervention for fibroids (including UAE) except uncomplicated myomectomy (hysteroscopic, laparoscopic or abdominal) and MRgFUS. Prior use of in vitro fertilization or other assisted reproductive technology Previous treatment with gonadotropins or intrauterine inseminations History of tubal surgery History of oophorectomy History of chemotherapy or radiation to the abdomen or pelvis MRI showing only adenomyosis Metallic implants that are incompatible with MRI Severe claustrophobia that would prevent completion of procedure in MR unit Patients with a BMI greater than 38. Known intolerance to the MRI contrast agent (e.g. Gadolinium or Magnevist) including severe kidney disease Individuals who are not able or willing to tolerate the required prolonged stationary prone position during treatment (approximately 3 hrs.) Active pelvic inflammatory disease (PID) Active local or systemic infection Known or suspected pelvic carcinoma or pre-malignant conditions, including sarcoma and adenomatous hyperplasia Dermoid cyst of the ovary anywhere in the treatment path Extensive abdominal scarring that cannot be avoided by redirection of the beam (e.g., due to Caesarean section or repeated abdominal surgeries) Undiagnosed vaginal bleeding Patients having a contraindication to pregnancy. Patients having a contraindication to surgery, including surgical myomectomy Patients with type 0 submucosal fibroids. More than 4 clinically significant fibroids >2cm in mean diameters Patients on dialysis. Hematocrit < 25 Hemolytic anemia Patients with unstable cardiac status including: Unstable angina pectoris on medication Patients with documented myocardial infarction within six months of protocol entry Congestive heart failure requiring medication (other than diuretic) Patients on anti-arrhythmic drugs Severe hypertension (diastolic BP > 100 on medication) Patients with cardiac pacemakers Patients planning to use adjuvant therapies post (ExAblate or Myomectomy) procedures to improve the chance of conception within 9 months of study treatment will be excluded from study (note: candidates relying on donor sperm and artificial insemination to conceive between months 3 and 9 post-treatment are allowed to participate, provided they meet all eligibility criteria) Patients without uterine cavity distortion. Male partner exclusion criteria Prior use of in vitro fertilization of other assisted reproductive technology Previous treatment intrauterine inseminations History of chemotherapy or radiation to the abdomen or pelvis History of vasovasectomy History of varicocelectomy History of pelvic-node dissection Use of calcium-channel blocking medications

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Non-invasive procedure for fertility enhancement (i.e., ExAblate treatment) | Device: ExAblate 2000<br>* Magnetic resonance image guided focused ultrasound (MRgFUS) for fibroid ablation<br>|
| Active Comparator: 2<br>Invasive surgical procedure for fertility enhancement (i.e., myomectomy) | Procedure: Myomectomy<br>* Invasive surgical procedure for fibroid removal<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Live Birth Rate |  | Between the 3 and 9-month post-treatment visits | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pregnancy Rate |  | Between the 3 and 15-month post-treatment visits | 
| Term Delivery Rate |  | Between the 3 and 15-month post-treatment visits | 
| Miscarriage Rate |  | Between the 3 and 15-month post-treatment visits | 
| Time to Conception |  | Post-treatment | 
| C-Section Rate |  | Post-treatment | 
| Uterine Fibroid Symptom and Health-Related Quality of Life Questionnaire (UFS-QOL) |  | Post-treatment | 
| Center for Epidemiologic Studies Depression Scale (CES-D) |  | Post-treatment | 
| Medical Outcomes Study 36-Item Short Form Survey |  | Post-treatment | 
| Health Care Costs |  | Post-treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Uterine Fibroids, Unexplained Infertility, MRgFUS, ExAblate, Focused Ultrasound, Myomectomy