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Dysfunctional Uterine Bleeding and Uterine Fibroids- Commercial Medical Management Guideline Uterine Artery Embolization (UAE) Pinto et al. completed a randomized trial comparing UAE with hysterectomy. They concluded that UAE reduced abnormal bleeding in 86% of the patients and was associated with significantly shorter hospitalization and recovery time compared with hysterectomy. The total complication rate was higher for UAE than hysterectomy, although there were few major complications with UAE. Patient satisfaction was high for both procedures. (Pinto, 2003) Pron et al. completed a multicenter case series involving 555 patients evaluating fibroid uterine volume reduction, symptom relief and patient satisfaction following UAE. Their findings indicate that UAE reduced symptoms in the majority of patients as menorrhagia (83%), dysmenorrhea (77%) and bulk related urinary complaints were decreased (86%). They also noted that complications occurred in 44 patients (8%) including increased pain (26), eight patients required a hysterectomy, two had post procedure infections, one had vaginal bleeding and one had a prolapsed fibroid. The procedure could not be completed in 3 patients due to variant anatomy. Patient satisfaction was 91% and nearly half of the patients remained amenorrheic three months after the procedure. Hospital stays were 1.3 days and recovery time was an average of 10 days. (Pron, 2003b) Joffre et al.
There were no differences between the two methodologies. Complications occurred in 19 of the 100 study participants and included allergic reactions, pain with fibroid passage, urinary retention, hematoma, and one person had a pulmonary embolus. (Spies, 2004) Walker and Pelage concluded in their study of 400 patients that UAE reduced uterine volumes and improved symptoms, but 6% of the patients had treatment failure and required a hysterectomy. Other complications reported include permanent amenorrhea and chronic vaginal discharge. (Walker, 2002) Spies et al. reported a 5-year follow-up in 182 patients treated with UAE for leiomyomata. 73% continued to experience symptom control. 13.7% (25) had undergone hysterectomies, 4.4% (8) had undergone myomectomies, and 1.6% (3) had repeat embolizations. (Spies, 2005) Goodwin et al. compared results of UAE (n=149) with myomectomy (n=60) 6 months after procedure. Both groups experienced statistically significant improvements in menstrual bleeding and uterine volume as compared to menstrual bleeding and uterine volume pretreatment. When the two groups were compared to each other, there were no significant differences in bleeding improvement and uterine volume reduction. Patients who received UAE required fewer days off work, fewer hospital days and experienced fewer adverse events. (Goodwin, 2006) Mara et al. compared UAE to myomectomy in 63 women and followed-up for a mean of 17 months. Both methods were clinically successful in the majority of cases and were without a significant number of serious complications. (Mara, 2006) Siskin et al. compared UAE to hysterectomy in 146 women for treatment of fibroids. UAE was associated with greater sustained improvements in symptom severity and quality of life scores and with fewer complications than myomectomy.
MRI at 6-month follow-up demonstrated significant reductions in uterine and tumor volumes. (Siskin, 2006) Broder et al. completed a study of 97 women who had either a myomectomy or UAE. They concluded that women who had UAE were more likely than those who had myomectomy to require further invasive fibroid procedures 3-5 years postsurgery. Both procedures were effective in symptom control (92% for the UAE group and 90% for the myomectomy Dysfunctional Uterine Bleeding and Uterine Fibroids- Commercial Medical Management Guideline group). The satisfaction rate was higher in the UAE group.(Broder, 2002) Rasavi also studied 111 patients who had an UAE or a myomectomy. They concluded that the UAE was less invasive and safer than myomectomy with a shorter hospitalization, recovery time and duration of pain medication. UAE was also superior for control of menorrhagia, whereas myomectomy was superior for correction of mass/bulk effect. Both procedures were equal with respect to pain control. Of the patients who had complications, 11% were in the UAE group but 25% of the myomectomy patients had complications that were more serious and included blood transfusions, wound infections, ileus and adhesions. (Razavi, 2003) Goodwin et al. (2008) assessed the long-term clinical outcomes of uterine artery embolization across a wide variety of practice settings in 2112 patients with symptomatic leiomyomata. At 36 months after treatment, 1,916 patients remained in the study, and of these, 1,278 patients completed the survey. The primary measures of outcome were the symptom and health-related quality-of-life scores from the Uterine Fibroid Symptom and Quality of Life questionnaire. Mean symptom scores improved 41.41 points (P Agdi et al. (2008) evaluated intraabdominal adhesions after uterine artery embolization (UAE) in a case-control study of patients who underwent hysterectomy after UAE. The control group consisted of patients who underwent hysterectomy for uterine myoma in the same week. The study included 30 patients in the UAE group and 72 in the control group. In the UAE group, the diameter of the dominant myoma in patients with adhesions (11.3 +/- 1.9 cm) was larger than in those without adhesions (5.6 +/- 0.6 cm; P =.003; confidence interval, 1.9-8.5). The prevalence of adhesion in the UAE group (20%) was higher than in the control group (1.4%; P =.002; odds ratio, 17.2). The investigators concluded that UAE is associated with intraabdominal adhesion formation and that large myoma predisposes to adhesion formation.
According to an evidence report prepared for the Agency for Healthcare Research and Quality (AHRQ), studies comparing uterine artery embolization (UAE) with other procedures reported procedure time and length of stay favoring UAE. However, the absence of key information on longer-term outcomes suggests that the evidence base is inadequate to comment on the relative risks and benefits of UAE versus hysterectomy or myomectomy. (AHRQ, 2007) American College of Obstetricians and Gynecologists (ACOG) ACOG issued a Practice Bulletin on uterine artery embolization (UAE). This bulletin states that UAE for the treatment of fibroids is contraindicated for women who wish to retain their childbearing function, although the procedure does appear to offer short-term symptom relief. (ACOG, 2004) In a separate practice bulletin, ACOG states that based on long- and short-term outcomes, uterine artery embolization is a safe and effective option for appropriately selected women who wish to retain their uteri. (ACOG, 2008) Magnetic resonance imaging (MRI)-guided cryoablation Searches of the medical literature revealed a paucity of data on magnetic resonance imaging (MRI)-guided cryoablation of fibroids. Two feasibility studies representing an ongoing, manufacturer-sponsored clinical trial on this specific technique that were conducted at the same study center were identified in the peer-reviewed literature. The first study consisted of 2 patients who were included in the second study. (Sewell, 2001; Cowan, 2002) The second published study is a prospective case series that evaluated the efficacy and safety of MRI-guided cryoablation of uterine fibroids in 9 symptomatic women whose disease was confirmed by clinical examination and MRI. The outcomes assessed included surgical time, postoperative fibroid volume, postoperative hemoglobin level, overall reduction in fibroid size, and complications.
Postoperative MRI findings were available for the patients for a period of 48 to 334 days after surgery.
While the preliminary data from a manufacturer-sponsored pilot study show that MRI-guided cryoablation of uterine fibroids can reduce the volume of uterine fibroids by an average of 65% as determined by serial MRI and improve patientreported symptoms over the short term, the procedure has been evaluated in very few patients, and the long-term outcomes and overall health benefits remain unknown. During this short-term study, none of the fibroids disappeared completely, Dysfunctional Uterine Bleeding and Uterine Fibroids- Commercial Medical Management Guideline and it remains unclear whether this would eventually occur. In the clinical trial, 3 of 9 (33%) patients experienced what the researchers described as important procedure-related complications. One patient developed persistent bleeding following laceration of a tumor blood vessel. The patient required emergent laparotomy and myomectomy. She recovered without complications but was ineligible for follow-up of the cryoablation procedure since her fibroids were removed.
Another patient sustained a mild peroneal nerve injury that resulted in a mild footdrop, which resolved at 4 months postoperatively. A third patient was observed for 24 hours due to nausea. No other serious complications were reported during follow-up.
Dohi et al. published a third study evaluating MRI-guided transvaginal cryotherapy to treat 8 uterine fibroids. They assessed the ratio of pre-treatment to post-treatment volume of the uterine fibroids as well as symptoms of anemia, abdominal pain and dysfunctional uterine bleeding. The mean ratio of reduction in uterine fibroid volume was 31.0% at 9months (0-75.0%). Symptoms caused by uterine fibroids improved in seven cases. There were no complications requiring surgical intervention ( Dohi, 2004).
Magnetic resonance imaging (MRI)-guided focused ultrasound ablation (FUA) Identified studies reported data from the manufacturer sponsored PMA trial. (Stewart, 2006; Hindley, 2004) The PMA trial considered quality of life and recovery of non-randomized patients who received either MRI-guided focused ultrasound (FUA) (n=109) or hysterectomy (n=83) to treat uterine fibroids. FUA treated patients were followed for 12 months and hysterectomy treated patients were followed for 6 months. At 12-month follow-up, 42 of 82 FUA treated patients maintained a 10 point score improvement.
The Uterine Fibroid Symptoms and Quality of Life (UFS-QOL) questionnaire was used to assess uterine fibroid symptoms. Stewart et al. reported the mean symptom severity scores for the FUA patients at 12-months compared to baseline were 38.8 versus 61.1, respectively. By 12- month follow-up, 23 of 82 evaluable FUA patients had sought alternative treatment for fibroids. (Stewart, 2006) Limitations of these studies include short follow-up, no comparison of FUA to other minimally invasive technologies intended to treat uterine fibroids and preserve uterine structure and function, the subjective nature, measurement, and interpretation of principal outcomes, small sample size, and the incomplete reporting of results.
According to an evidence report prepared for the Agency for Healthcare Research and Quality (AHRQ), the strength of evidence for MRI-guided ultrasound ablation of fibroids is weak. (AHRQ, 2007) National Institute for Clinical Excellence (NICE) Magnetic Resonance Image-guided Transcutaneous Focused Ultrasound for Uterine Fibroids: The NICE guidance document stated that Current evidence on the safety and efficacy of magnetic resonance image guided focused ultrasound ablation for uterine fibroids is such that this procedure should only be used with special arrangements for consent and for audit or research. The guidance also indicates that patients should be told about the uncertainties of the procedure's safety and efficacy and that future research should look at long-term outcomes.
(NICE, 2007) Additional Product Information Endometrial cryoablation (ECA): Her Option™ Uterine Cryoblation Therapy™ System (American Medical Systems Gynecology Inc) (American Medical Systems acquired CryoGen Inc.); Accuprobe®ThermaChoiceTM Uterine Balloon Therapy System (Gynecare, a division of Ethicon Inc.), CavatermTM System (Wallsten Medical, SA), and the Hydro ThermAblatorTM (BEI Medical Systems).
Levonorgestrel-releasing intrauterine device (LNG-IUD): MIRENA© (Berlex Laboratories Inc.) Radiofrequency endometrial ablation (RFA): NovaSureTM Global Endometrial Ablation (GEA) System, NovaSureTM Dysfunctional Uterine Bleeding and Uterine Fibroids- Commercial Medical Management Guideline Impedance Controlled Endometrial Ablation System (Novacept Inc., purchased by Pfizer) Uterine artery embolization (UAE): Gelfoam® (Pharmacia and Upjohn, Kalamazoo MI), Gel Spheres® (Biocure, Inc.), Contour SE™ Microspheres, Boston Scientific Corp.), Maxistat™ PVA Foam Embolization Particles (Surgica Corp.), Embosphere® and EmboGold™ Microspheres (BioSphere Medical Inc., MENISCAL ALLOGRAFTS) Trufill™ PVA Particles (Cordis Neurovascular, Inc.) and Ivalon® Embolization Particles (Ivalon).
Magnetic resonance imaging (MRI)-guided focused ultrasound (FUA) : ExAblate 2000; Signa 1.5T Magnetic Resonance System; Signa 3T Magnetic Resonance System, Cryo-Hit(TM) System, (Galil Medical Ltd, Washington, DC); Signa Profile/i Magnetic Resonance System (GE Medical Systems Inc.) References and Resources Resources Abbott J, Hawe J, Hunter D, Garry R. A double-blind randomized trial comparing the Cavaterm and the NovaSure endometrial ablation systems for the treatment of dysfunctional uterine bleeding. Fertil Steril. 2003;80(1):203-208.
Agency for Healthcare Research and Quality (AHRQ) Viswanathan, M, Hartmann, K, McKoy, N, Stuart, G, Rankins, N, Thieda, P, Lux, L, Lohr, KN. Management of Uterine Fibroids: An Update of the Evidence. Evidence Report/Technology
Assessment No. 154. AHRQ Publication No. 07-E011. Rockville, MD: July 2007. Available at:
http://www.ahrq.gov/downloads/pub/evidence/pdf/uterupdate/uterup.pdf. Accessed April 2009.
Agdi M, Valenti D, Tulandi T. Intraabdominal adhesions after uterine artery embolization. Am J Obstet Gynecol. 2008 Nov;199(5):482.e1-3.
American College of Obstetricians and Gynecologists. ACOG Practice Bulletin. Clinical Management Guidelines for Obstetrician-Gynecologists. Management of Anovulatory Bleeding. Number 14, March 2000.
American College of Obstetricians and Gynecologists (ACOG) [website]. ACOG news release. ACOG issues opinion on