Uterine Fibroids, With Unexplained Infertility
Conditions
Keywords
Uterine Fibroids, Unexplained Infertility, MRgFUS, ExAblate, Focused Ultrasound, Myomectomy
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.
Interventions
DEVICEExAblate 2000
Magnetic resonance image guided focused ultrasound (MRgFUS) for fibroid ablation
PROCEDUREMyomectomy
Invasive surgical procedure for fibroid removal
Sponsors
InSightec
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
21 Years to 40 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Live Birth Rate | Between the 3 and 9-month post-treatment visits |
Secondary
| Measure | Time frame |
|---|---|
| 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 |
| Pregnancy Rate | Between the 3 and 15-month post-treatment visits |
| 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 |
| Uterine Fibroid Symptom and Health-Related Quality of Life Questionnaire (UFS-QOL) | Post-treatment |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| ExAblate Treatment: All patients who received at least 10 therepeutic sonications with the ExAblate 2000 Magnetic resonance image guided focused ultrasound (MRgFUS) for fibroid ablation. | 2 |
| Myomectomy Treatment: All patients who had more than 15 grams of fibroid tissue excised. | 0 |
| Total | 2 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Physician Decision | 1 | 0 |
Baseline characteristics
| Characteristic | ExAblate Treatment: | Total |
|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 1 Participants | 1 Participants |
| Sex: Female, Male Female | 2 Participants | 2 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 1 / 2 | 0 / 0 |
| serious Total, serious adverse events | 1 / 2 | 0 / 0 |
Outcome results
Primary
Live Birth Rate
Time frame: Between the 3 and 9-month post-treatment visits
Population: enrollment in the clinical trial did not reach the target number of subjects needed to achieve target power and was insufficient to produce statistically reliable results.
Secondary
Center for Epidemiologic Studies Depression Scale (CES-D)
Time frame: Post-treatment
Population: enrollment in the clinical trial did not reach the target number of subjects needed to achieve target power and was insufficient to produce statistically reliable results.
Secondary
C-Section Rate
Time frame: Post-treatment
Population: enrollment in the clinical trial did not reach the target number of subjects needed to achieve target power and was insufficient to produce statistically reliable results.
Secondary
Health Care Costs
Time frame: Post-treatment
Population: enrollment in the clinical trial did not reach the target number of subjects needed to achieve target power and was insufficient to produce statistically reliable results.
Secondary
Medical Outcomes Study 36-Item Short Form Survey
Time frame: Post-treatment
Population: enrollment in the clinical trial did not reach the target number of subjects needed to achieve target power and was insufficient to produce statistically reliable results.
Secondary
Miscarriage Rate
Time frame: Between the 3 and 15-month post-treatment visits
Population: enrollment in the clinical trial did not reach the target number of subjects needed to achieve target power and was insufficient to produce statistically reliable results.
Secondary
Pregnancy Rate
Time frame: Between the 3 and 15-month post-treatment visits
Population: enrollment in the clinical trial did not reach the target number of subjects needed to achieve target power and was insufficient to produce statistically reliable results.
Secondary
Term Delivery Rate
Time frame: Between the 3 and 15-month post-treatment visits
Population: enrollment in the clinical trial did not reach the target number of subjects needed to achieve target power and was insufficient to produce statistically reliable results.
Secondary
Time to Conception
Time frame: Post-treatment
Population: enrollment in the clinical trial did not reach the target number of subjects needed to achieve target power and was insufficient to produce statistically reliable results.
Secondary
Uterine Fibroid Symptom and Health-Related Quality of Life Questionnaire (UFS-QOL)
Time frame: Post-treatment
Population: enrollment in the clinical trial did not reach the target number of subjects needed to achieve target power and was insufficient to produce statistically reliable results.