Clinical trial NCT00730886: ExAblate Treatment of Uterine Fibroids for Fertility Enhancement
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Uterine Fibroids, With Unexplained Infertility
Keywords: Uterine Fibroids
Unexplained Infertility
MRgFUS
ExAblate
Focused Ultrasound
Myomectomy
Lead sponsor: InSightec
Sponsor class: INDUSTRY
First posted: 2008-08-08
Enrollment: 2
Sex: FEMALE
Minimum age (years): 21
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

Female Partner

1. Able and willing to give consent
2. Able to attend all study visits.
3. At least one fibroid 3.0 cm or larger which is type 2 submucosal or intramural touching or abutting the cavity.
4. Able to communicate sensations during the ExAblate procedure.
5. Uterine fibroids, which are device accessible
6. Fibroids(s) clearly visible on non-contrast MRI. and with uniform enhancement with gadolinium
7. Age 21 to 40 (patients cannot be treated following their 41st birthday)
8. Patients with uterine cavitary distortion based on MRI images or ultrasound.
9. Premenopausal status
10. Normal pap smear and/or HPV testing within institutional guidelines
11. At least one ovary and at least one ipsilateral patent fallopian tube confirmed b hysterosalpingogram or laparoscopy.
12. Normal serum follicle-stimulating hormone and thyrotropin values on days 1-5 of the cycle
13. Length of 2 of the 3 most recent menstrual cycles between 24 and 35 days.
14. History of trying for pregnancy for at least 6 months
15. 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
16. Patient needs to demonstrate that she has already undergone testing and counseling in a fertility clinic or other medical office.

Male partner inclusion criteria

1. Age of male partner \< 55
2. At least 10 million total mobile sperm on semen analysis within last 6 months
3. 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:

1. Uterine size \> 16 weeks
2. Prior surgical intervention for fibroids (including UAE) except uncomplicated myomectomy (hysteroscopic, laparoscopic or abdominal) and MRgFUS.
3. Prior use of in vitro fertilization or other assisted reproductive technology
4. Previous treatment with gonadotropins or intrauterine inseminations
5. History of tubal surgery
6. History of oophorectomy
7. History of chemotherapy or radiation to the abdomen or pelvis
8. MRI showing only adenomyosis
9. Metallic implants that are incompatible with MRI
10. Severe claustrophobia that would prevent completion of procedure in MR unit
11. Patients with a BMI greater than 38.
12. Known intolerance to the MRI contrast agent (e.g. Gadolinium or Magnevist) including severe kidney disease
13. Individuals who are not able or willing to tolerate the required prolonged stationary prone position during treatment (approximately 3 hrs.)
14. Active pelvic inflammatory disease (PID)
15. Active local or systemic infection
16. Known or suspected pelvic carcinoma or pre-malignant conditions, including sarcoma and adenomatous hyperplasia
17. Dermoid cyst of the ovary anywhere in the treatment path
18. Extensive abdominal scarring that cannot be avoided by redirection of the beam (e.g., due to Caesarean section or repeated abdominal surgeries)
19. Undiagnosed vaginal bleeding
20. Patients having a contraindication to pregnancy.
21. Patients having a contraindication to surgery, including surgical myomectomy
22. Patients with type 0 submucosal fibroids.
23. More than 4 clinically significant fibroids \>2cm in mean diameters
24. Patients on dialysis.
25. Hematocrit \< 25
26. Hemolytic anemia
27. Patients with unstable cardiac status including:
28. Unstable angina pectoris on medication
29. Patients with documented myocardial infarction within six months of protocol entry
30. Congestive heart failure requiring medication (other than diuretic)
31. Patients on anti-arrhythmic drugs
32. Severe hypertension (diastolic BP \> 100 on medication)
33. Patients with cardiac pacemakers
34. 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)
35. Patients without uterine cavity distortion.

Male partner exclusion criteria

1. Prior use of in vitro fertilization of other assisted reproductive technology
2. Previous treatment intrauterine inseminations
3. History of chemotherapy or radiation to the abdomen or pelvis
4. History of vasovasectomy
5. History of varicocelectomy
6. History of pelvic-node dissection
7. Use of calcium-channel blocking medications

Primary outcomes:
measure: Live Birth Rate
timeFrame: Between the 3 and 9-month post-treatment visits
Secondary outcomes:
measure: Pregnancy Rate
timeFrame: Between the 3 and 15-month post-treatment visits
measure: Term Delivery Rate
timeFrame: Between the 3 and 15-month post-treatment visits
measure: Miscarriage Rate
timeFrame: Between the 3 and 15-month post-treatment visits
measure: Time to Conception
timeFrame: Post-treatment
measure: C-Section Rate
timeFrame: Post-treatment
measure: Uterine Fibroid Symptom and Health-Related Quality of Life Questionnaire (UFS-QOL)
timeFrame: Post-treatment
measure: Center for Epidemiologic Studies Depression Scale (CES-D)
timeFrame: Post-treatment
measure: Medical Outcomes Study 36-Item Short Form Survey
timeFrame: Post-treatment
measure: Health Care Costs
timeFrame: Post-treatment
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: UCLA
state: California
city: Smyrna
country: United States
facility: Atlanta Interventional Institute
state: Georgia
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Plano
country: United States
facility: Willowbend Health and Wellness
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia Health System
state: Virginia
Study officials:
References:
citation: Hanstede MM, Tempany CM, Stewart EA. Focused ultrasound surgery of intramural leiomyomas may facilitate fertility: a case report. Fertil Steril. 2007 Aug;88(2):497.e5-7. doi: 10.1016/j.fertnstert.2006.11.103. Epub 2007 Feb 8.
citation: Rabinovici J, David M, Fukunishi H, Morita Y, Gostout BS, Stewart EA; MRgFUS Study Group. Pregnancy outcome after magnetic resonance-guided focused ultrasound surgery (MRgFUS) for conservative treatment of uterine fibroids. Fertil Steril. 2010 Jan;93(1):199-209. doi: 10.1016/j.fertnstert.2008.10.001. Epub 2008 Nov 14.
citation: Bouwsma EV, Gorny KR, Hesley GK, Jensen JR, Peterson LG, Stewart EA. Magnetic resonance-guided focused ultrasound surgery for leiomyoma-associated infertility. Fertil Steril. 2011 Jul;96(1):e9-e12. doi: 10.1016/j.fertnstert.2011.04.056. Epub 2011 May 13.