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Fibroids: New Options In Medical & Surgical Management

Linda D. Bradley MDProfessor SurgeryVice Chair Obstetrics and GynecologyDirector, Center For Menstrual Disorders, Fibroids & Hysteroscopic ServicesCleveland ClinicCleveland, Ohiobradlel@ccf.org

Disclosures

• Bayer, Ethicon Women’s Health: Consultant, Speaker

• Boston Scientific : Consultant

• Medscape: Advisory Panel

• OBG Management: Board

• Royalties for textbook, Hysteroscopy: Office Evaluation and Management of the Uterine Cavity, published by Elsevier 2009

• Royalties from Up to Date: Chapters Office Hysteroscopy and Operative Hysteroscopy 2013

• ACOG Practice Bulletin: Management of Abnormal Uterine Bleeding Associated with Ovulatory Dysfunction 2013. Honoraria

Objectives

• Outline the fibroid disease burden and rationale for individualizing clinical care

• List non-surgical procedural interventions for the treatment of uterine fibroids

• Describe surgical options for the treatment of uterine fibroids

• Outline emerging medical therapeutic options

Fibroids: An Equal Opportunity Problem

• The most common benign growths of fertile women– High prevalence– Significant health problems– Huge economic impact– Little known about etiology and pathophysiology

• Most common cause of hysterectomy worldwide

• Arise from smooth muscle cells

• Effect 80 % of women of reproductive age, but only 25% have clinical symptoms

• 25% have symptoms that impact activities of daily living or require treatment

• Approximately 600,000 hysterectomy procedures annually

• Approximately 125,000 myomectomies

• 1,000 deaths annually related to hysterectomy

• $2.2 billion dollars/year in USA

Leiomyomas: Sobering Statistics

• 3-fold increase relative risk and prevalence among women from the African diaspora– Higher disease burden– Earlier onset of symptoms– Larger in number and volume

• Risk factors include:– Early menarche– Late reproductive years– Heredity– Nulliparity– Obesity– Polycystic ovary syndrome– Diabetes– Hypertension

Walker CI, Stewart EA. Uterine fibroids; the elephant in the room. Science, 2005;1589-92

The Impact of Uterine Leiomyomas: A National Survey

• 968 women surveyed

• 3.6 years wait before seeking treatment

• 41 % saw > 2 health providers for diagnosis

• 28% missed work due to leiomyoma symptoms

• 24% believed that symptoms prevented career potential

• 79% expressed desire for treatment that does not involve invasive surgery

• 51% desired uterine preservation

• 43% wanting fertility preservation (women < 40 yrs)

Borah, B, Nicholson, W. Bradley, L, Stewart, E. The impact of uterine leiomyomas: a national survey of affected women. Am J Obstet Gynecol 2013;209:319, e 1-20.

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Fibroids

• International survey confined to assessment of bleeding and pain found:– Quality of life (QOL) indicators reveal that women are

impacted emotionally

–Fears about health

–Relationships

–Sexual functioning

–Body image

–Loss of control

–Hopelessness

Spies, JB et al. The UFS-QOL, a new disease-specific symptom and health-related qualityof life questionnaire for leiomyomata. Obstet Gynecol 2002:99:290-300.

Patient Choice: Decisions, Decisions

1. How do fibroids impact her quality of life?

2. Are the symptoms related to the fibroids?

3. What fibroid related symptoms bother her the most?

4. Does she want children?

5. Does she desire uterine conservation?

6. Do the symptoms require invasive treatment?

7. Are there anatomic factors that predispose her to treatment failures, recurrence of fibroids, or indicate adjunctive evaluation to ensure treatment success?

8. Are there medical or surgical risk factors that predispose her to anesthetic risks, surgical risks, or increase her risks surgical morbidity and mortality?

9. Gynecologist’s surgical expertise and access to interdisciplinary team consultation

10. What is the amount of convalescence needed for treatment?

Options?

VaginalHysterectomy

– Laparoscopic– Robotic– Abdominal– Minimally invasive options

should be offered whenever clinically possible

• Uterine Artery Embolization

• MR Focused Ultrasound

• Hysteroscopic

• Medical therapy

• Multidisciplinary team?– Surgeons with vaginal

hysterectomy skills– Surgeons with advanced

laparoscopic skills– Surgeons with advanced robotic

skills– Surgeons with hysteroscopic

skills

– Surgeons with advanced abdominal surgical skills

– Interventional Radiologists

• Center of Excellence

• Dedicated surgical team

• Equipment

• Clinical trial

Goal: infarction and shrinkage of fibroidDifferential in vascularity between fibroid and normal uterine tissue makes selective fibroid infarction possible from a proximal uterine artery catheter position

Uterine Fibroid EmbolizationUFE: Pathologic Changes(Siskin, JVIR 1999; 891-894)

• Embolization results in ischemic infarction of the leiomyomata & decreased vascularity

• Normal myometrium is spared.

• Leiomyoma shrinks as result of hyaline degeneration.

• Degeneration continues for months to years.

• Both large and small leiomyomas infarcted

• Decreased uterine volume, hemorrhagic infarction

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Indications for UFE

• Standard–Symptomatic fibroids in reproductive

aged women who do not desire childbearing

–Recurrent uterine fibroids after other therapies

–Conditions contraindicating surgery

• Emerging–Adenomyosis

ACOG Practice Bulletin. Alternatives to Hysterectomy in the Management of Leiomyomas. August 2008,96: 387-400.

Contraindications to Uterine Fibroid Embolization

• Asymptomatic patient

• Postmenopausal patient

• Active infection, PID or vasculitis

• History of pelvic irradiation

• Life-threatening contrast allergy

• Renal failure or insufficiency

• Arteriovenous shunting

• Undiagnosed pelvic mass

• Pedunculated serosal fibroid (stalk < 3 cm)

• Pregnancy

• Uncorrected coagulation disorders

• Pt who would refuse hysterectomy for complications

Andrews RT. Patient Care and Uterine Artery Embolization for Leiomyomata. J Vasc Interv Radiol 2004;15:115-120.

The FIBROID RegistryEnrollment

• Initially, 3319 patients treated at 72 enrolling sites.– 3166 (95.4%) consented to Registry– Complete variables in 3005 (94.9%)

• Thirty-day follow-up complete in 2729 (90%)

• 2112 eligible for long-term follow-up.

• Six month follow-up completed in 1797 (85.1%).

• Twelve month follow-up completed in 1701 (83%).Worthington-Kirsch R. The Fibroid Registry for Outcomes Data (FIBROID) for Uterine Embolization. Obstet Gynecol 2005: 106:52-59.

Fibroid Registry Outcomes• 1.2% had surgical intervention for adverse event

– Most common was D&C for prolapsed fibroid

• 4.1% had complications within 30 days of discharge– 2.4% readmission rate for pain

• 3 hysterectomies performed within 30 days

• 5% patients had additional gynecologic procedures within 12 months– 1701 women had improved symptom and health-related

quality-of-life scores

–2.9% hysterectomy rate at 12 months

–9.5% other interventions

Worthington-Kirsch R. The Fibroid Registry for Outcomes Data (FIBROID) for Uterine Embolization. Obstet Gynecol 2005: 106:52-59.

Clinical OutcomeSummary of Published Case Series

• Menorrhagia:– Mean percent improved in 88% of patients (range

79% to 98%)

• Pain/pressure:– Mean percent improved in 71% of patients (range 64

to 98%)

• Mean leiomyoma volume reduction: Range: from 20% at 2 months; 60% at 12.3 months.

• Hysterectomies for complications: 8 (0.3%)

Dramatic Effects Over One Year

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Median Percentage Reductions in MBL at All Post-treatment Time Intervals

Months

Khaund A. et al., BJOG. 111(7):700-5, 2004.

Med

ian

Per

cent

age

Red

uctio

n in

MB

L

3 6-9 12-24 24-36 36-48

0

-20

-40

-60

-80

-100

10 cm

Volume 50%

Diameter 21% 7.9 cm

15 cm

Volume 50%

Diameter 21% 11.9 cm

20 cmVolume 50%

Diameter 21%15.9 cm

Volume reduction of sphere= L xW x H x 0.5

IR Related Complications• Groin infection

• Groin hematomas

• Puncture site infection

• Arterial perforation by guide wire

• Thromboembolic

• Contrast allergy

• Contrast related renal failure

• Arteriovenous malformations

• Pseudoaneurysm

• Misembolization of abdominal vessels

• Radiation exposure

Approximately 1% procedurally related complications

UAE considerations in pregnancy

• Patients who have had UAE may have an increased risk of:

– Miscarriage

– Intrauterine growth restriction

– Abnormal placentation

– Malpresentation

– Postpartum hemorrhage

– Pre-term birth

A number of successful pregnancies have been reported after UAE, however there are risks in regard to pregnancy for this treatment option.

UFE: Potential Complications

• Pulmonary Embolism

• Need for gynecologic intervention <2.5%– prolapsing fibroids

– prolonged purulent drainage

– persistent pain

– heavy bleeding

• Infection– systemic infection

– endometritis

– pyometritis

• Misembolization of target vessels

• Premature ovarian failure– <1-2% in women <45– 2-5% in women >45

• Persistent post-procedural pain

• Premature ovarian failure

• Anorgasmia

• Death

• Delayed diagnosis of leiomyosarcoma

• UFE is proven effective with durable symptom control

• >500,000 UFE procedures worldwide

– 35,000 procedures performed per year in the United States

• 80-95% clinical success

– bleeding and bulk-related symptoms

• Clinical studies show equivalent symptom relief as compared to surgery

– with less recovery time and complications

• Minimally invasive

– < 23 hour hospital stay for most

– Increasingly 6-8 hr stay

• Return to normal activity in about 1-2 weeks

• Low complication rates

UFE Summary

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Uses focused ultrasound waves to non‐invasively heat targeted tissues to 60⁰‐ 65⁰C, causing coagulation and necrosis of the tissues without affecting surrounding/intervening tissues

Magnetic resonance imaging allowing precision in tumor definition, with real‐time MR thermometry that monitors treatment to achieve desired outcome

Focused Ultrasound for Uterine Fibroids

Courtesy of InSightec

Patient Selection for Focused UltrasoundGeneral screening guidelines

• Pre- or peri-menopausal women with symptomatic uterine fibroids

• Patient does not have contraindications for therapy

• Symptoms may include pressure, urinary frequency and/or bleeding

• Pre-screening by OB-Gyn shows no pregnancy or pelvic disease

– Pre-screening should include diagnosis of fibroids, standard pelvic exam to rule out other pelvic disease, cervical cancer and pregnancy.

– If suspected due to patient age and/or bleeding symptoms, malignancy ruled out using echo and/or hysteroscopy

• Screening US allowed for diagnosis of fibroids and confirmed limited-to-no calcifications

Patient selection – Fibroid Size

No limits to Fibroid Size

Practical considerations: Small Fibroids•4 mm cell must fit inside the fibroid•Very small fibroids do not cause strong symptoms•Practical min tumor size = 1 cm

Large Fibroids•Treatment time only limiting factor•Can be treated in multiple sessions•Consider GnRH analog pretreatment

Left: 11.6 x 9.1 x 11.1cm3 , 592 ml Right: 12.3 x 10.3 x 9.2 cm3, 599 ml

Dark fibroids before (top) and after (bottom) single session

Durability and Non-Perfused Volume (NPV)

Immediate Post- treatment Non- Perfused Volume (NPV) is important predictive factor for treatment durability

NPV

Enhanced T1wEnhanced T1w

200430% NPV

200750% NPV

2009100% NPV

ExAblate FDA Approvals

3 and 6 months follow-up

Improving Symptoms and Quality of Life

QoL improvements and 50% fibroid shrinkage in 6 months

Chief complaint: 48/F, heavy menstrual bleeding, bloating and frequent urination SSS 53.1 QoL: 58.6 2 large fibroids, 135 + 222 ml

Successful treatment: Post treatment NPV 68% & 86%

3 months follow-up: Shrinking fibroids: 85 + 132 ml Improving symptoms: SSS 34.4 QoL 84.5

6 months follow-up: Shrinking fibroids: 56 + 115 ml Improving symptoms: SSS 12.5 QoL 98.3

Baseline – 357 ml Post treatm. – 79% NPV

3 months – 61%6 months – 48%

Baseline              3 Months             6 Months

Correlation Between NPV% and Subsequent Alternative Treatment at 12 and 24 Months

Stewart EA, Gostout B, Rabinovici J, Kim HS, Regan L, Tempany CMC. Sustained relief of leiomyoma symptoms by using focused ultrasound surgery. Obstet Gynecol 2007; 110: 279–287.

359 patients, 2 years follow-up:

NPV of 60%: subsequent alternative treatment rate is

6% at 12 months and

13% at 24 months

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UF symptom relief after MRI focused UltrasoundTreatment

Months post-procedure

Patients available for follow-up

Symptom improvement

Improved No relief Worse

3 105 85.7% 13.3% 1%

6 99 92.9% 7.1% 0

12 89 87.6% 12.4% 0Gorny KR, Woodrum DA et al. Magnetic resonance–guided focused ultrasound of uterine leiomyomas: review of a 12-month outcome of 130 clinical patients. J Vasc Interv Radiol 2011

NPV increasing with learning curve and improved

techniques

• A close correlation exists between durability and NPV

• At 60% NPV durability similar to other treatments

• Current labeling guidelines allows for up to 100% treatment of fibroid volume

Elizabeth A. Stewart M.D., et al Focused Ultrasound Surgery of Uterine Leiomyomas Provides Sustained Relief of Leiomyoma Symptoms , Obstetrics & Gynecology Aug 1, 2007; 110 (2) ; Okada et al. Ultrasound in Obstet Gynecol 2009-Av. NPV ratio 46.6% (N=287) Leblang et al. AJR 2010-----Av. NPV ratio 55% (N=80). Trumm et al. Invest Radiol. 2013 Av. NPV 88%.

•Expected side-effects of FUS-therapy –Transitory

–30% patients may experience nausea, vomiting, leg and buttock pain, abdominal tenderness

–Less frequent, transitory –< 10% patients may experience swelling, abdominal cramping,

vaginal bleeding, urinary difficulty

–< 3% patients may experience first degree skin burns (skin redness) and general pelvic pain

• Very rare complications (< 1% patients)– Second and third degree skin burns

– Neuropathy < 0.1% (Taran 2009)

– Injury to abdominal/pelvic organs < 0.1% (Taran 2009)

MRgFUS Side Effects and Complications

Post ExAblate Pregnancies

Total number of pregnanciesMean ageAverage months to conception

Total deliveries- Of them vaginal

Elective pregnancy terminationSpontaneous miscarriageOngoing pregnanciesUnknown

Average baby weight at term delivery

117369

64 (55%) 59%

10 (9%)22 (19%)9 (8%)

12 (10%)

3.27 kg

Capmas et al., Lippincott Williams and Wilkins. Vol 25, No 4, Aug 2013.

Classification ofUterine Fibroids

How Big of an Intracavitary Fibroid Can You Tackle?

• Issues– Fluid absorption

– Visualization

– Myoma “chip”management

– Navigation within the uterine cavity

– Uterine walls collapsing

– Cervix

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Size of Intracavitary Lesion Determines Surgical Time

Surgery Time vs. Size*

• As diameter of myoma increases, volume increases cubically (v= 4/3r3 ), increasing operating time

• Surgeons should be aware of this dynamic and plan accordingly for overall procedure time

* Emanuel, MH. (2005). Presentation to Smith & Nephew

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Remember Volume: Size Matters

• 4/dr3

• 1 cm =1/2 cubic cm tissue

• 2 cm = 4 cubic cm tissue

• 3 cm = 14 cubic cm tissue

• 4 cm = 33 cubic cm tissue

As the size of the intra-cavitary lesion increases, the volume of resected tissue increasesexponentially.This effects length of surgery, complications ,amount of fluid used/absorbed, and ability to complete the surgery.

Hysteroscopic Fibroid Resection Outcome

Polena V, et al., Science Direct, EJOG, 130 (2007) 232-237.

Mean follow-up period = 3.3 years (40 months). *Hysterectomy performed for obstetrical reason was not considered as a failure. n = 235

Results Number %

Success 186 94.4

Failure 11 5.6

Repeat myomectomy 4 2.0

Hysterectomy 4* 2.0

Recurrence of symptoms 4 2.0

Hysteroscopic Myomectomy for Abnormal Uterine Bleeding

Average Success (NoCases, Follow-up, Follow-up Study Further

no. % Time, months surgery), %

Polena et al. 235 84 40 94.4

Wamsteker et al. 51 93.3 20 93.3

Emanuel et al. 285 94 46 85.5

Cravell et al. 196 86.2 73 82.2

Marziani et al. 84 97 36 80.9

Kuzel et al. 45 100 48 100

Hart et al. 194 100 27 79

Munoz et al. 120 100 36 88.5

Brooks et al. 90 100 6 91

Derman et al. 177 100 108 83.9

Percentage of Patients Treated with Hysteroscopic Myomectomy Stratified by Intramural Extension and Completeness of Removal

Incomplete removalComplete removal

Type 0 Type 1 Type 20

20

40

60

80

100

Per

cen

tag

e

97

3

90

10

61

39

Van Dongen H, et al., Acta Obstet et Gynecologica, 2006;85: 11463-1467

1 175 (74.5%) 2 1.4

2 41 (17.4%) 3 7.3

3 or more 19 (8%) 1 5.3

Type of fibroids*0 26 (11%) 0 0.01 45 (19%) 2 4.42 164 (70%) 4 2.4

Weight of fibroids (g)<3 137 (58.3%) 2 1.53-10 81 (34.5%) 3 3.7>10 11 (4.7%) 1 9.1>15 6 (2.5%) 0 0.0

Number, Type, Weight of Fibroids and Operative Complications

Polena V, et al., Science Direct, EJOG, 130 (2007) 232-237.

*The Classification is based on the fibroid with the deepest intramural extension. n = 235

Number of Operativefibroids Number complications %

Indications for Endometrial Ablation

• Patient-perceived heavy menstrual bleeding

• Disabling uterine bleeding

• Non-responder to aggressive medical management

• Poor surgical risk for hysterectomy

• Patient wishes to preserve uterus

• Patient does not want children

Failure or intolerance of medical therapy and anemiaare important considerations, they are not prerequisites for the procedure.

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Contraindications• Endometrial hyperplasia

• Uterine prolapse

• Enlarged uterus (more than 12 cm cavity)– Intramural fibroids > 3 cm– Leiomyomas with majority intracavitary component

• Multiple fibroids/mullerian anomalies

• Intracavitary fibroids > 3 cm

• Diffuse adenomyosis

• Prior transmural leiomyoma

• Chronic pelvic pain

• Genital malignancy

• Acute PID

• Women expecting 100% amenorrhea

• Desires future childbearing

Comparative Summary

Longinotti. et al., Obstetrics and Gynecology.

Data not based on a head-to-head clinical study.

Patients Patients with Patients ExperiencingPatient-Reported Experiencing Normal Levels Reduction inComparisons* Amenorrhea at 12 Mos. or Less Dysmenorrhea (Pain)

Gynecare Thermachoice® III(1) 37% 81% 89%

NovaSure®(2) 36% 78% 63%

Her Option®(3) 22% 67% 76%

HTA System®(4) 35% 68% N/A

Endometrial Ablation

• Rates of subsequent surgery following endometrial ablation has varied among studies:– English study (comprehensive national data set)

– 114,910 had endometrial ablation

– 16.7% had subsequent procedure within 5 years

– Higher rate of surgery with younger age

Women < 35 had adjusted hazard ration 2.83 or 27%

compared to women > 45 had 10.4% further surgery

1/6 women had further surgery after endometrial ablation

Risk decreases with age

The presence of uterine fibroids increased the risk of further surgery

Bansi-Matharu, L. Rates of subsequent surgery following endometrial ablation among English Women with menorrhagia: population-based cohort study. BJOG 2013;120:1500-1507.

Endometrial Ablation

• Rates of subsequent surgery following endometrial ablation has varied among studies:– English study

–114,910 had endometrial ablation

–Age strongest risk factor for further surgery

–Less than 10% of women >45 had further surgery within 5 yrs, compared to 31% women < 35 had further surgery

Bansi-Matharu, L. Rates of subsequent surgery following endometrial ablation among English Women with menorrhagia: population-based cohort study. BJOG 2013;120:1500-1507.

Characteristics of Patients Undergoing Hysterectomy for Failed Endometrial Ablation

• Pelvic pain-22%

• Recurrent heavy menstrual periods 43%

• Pelvic pain and heavy menses 35%

• Surgical findings at hysterectomy:– Endometriosis --68%

– Leiomyomata--64%

– Adenomyosis 43%

Probability of Hysterectomy by Endometrial Ablation Technique: Life-Table Method

Longinotti. et al., Obstetrics and Gynecology.

Years after Endometrial Ablation

0 1 2 3 4 5 6 7 8

Pro

babi

lity

of H

yste

rect

omy

(%)

0

10

20

30

Overall

First generation

Hydrothermal

Radiofrequency

Thermal balloon

Unclassified

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Why Minimally Invasive Surgery?

• Decreased scarring

• Better cosmesis

• Decreased pain

• Short hospital stay

• Faster return to normal activities

• Overall decreased morbidity

• Cost

Vaginal Hysterectomy

• Original minimally invasive hysterectomy– Least expensive– Better cosmesis

–No abdominal incision– Shorter operating time than laparoscopic or

abdominal approach– Minimal equipment– Shorter hospital stay– Faster recovery– Decreased pain– Back to work sooner– Otherwise operative outcomes and post operative

pain the same as laparoscopic approach

Benefits and Disadvantages of Laparoscopic Approach to Hysterectomy

• Reduce time to return to normal activities

• Decreases post-operative pain

• Decreased febrile episodes or unspecified infections

• Decreased hospital stay

• Better quality of life at six weeks and four months (compared to abdominal hysterectomy)

• More expensive

• Takes more time to perform

• Longer learning curve

• Higher rate of urinary system injury than abdominal (not compared to vaginal approach)

Garry, R. et. al. EVALUATE hysterectomy trial: a multicentre randomised trial comparingAbdominal, vaginal and laparoscopic methods of hysterectomy. Health Technol Assess2004:8:154.

Laparoscopic Vaginal Hysterectomy (LAVH)

• Classified by Garry et. al.– Upper supporting structures are detached laparoscopically

– Uterine vessel ligation– Cervical cuff dissection– Vaginal cuff closure are performed vaginally

• This method increases candidacy for vaginal approach, especially if adnexal pathology and adhesions can be treated prior to the vaginal approach

Laparoscopic Hysterectomy (LH)

• Includes laparoscopically detaching the uterine body from supporting tissue and ligating all vascular pedicles through the laparoscopic approach

• Closure of the vaginal cuff is performed vaginally

• This technique is helpful in women with little uterine descensus, more obese, or who have broad uterine segment fibroids, thus improving the success of vaginal approach to hysterectomy

Total Laparoscopic Hysterectomy (TLH)

• Complete laparoscopic approach to hysterectomy

• Includes total laparoscopic detachment of the uterus from surrounding structures, ligation of uterine vessels, laparoscopic closure of vaginal cuff and suspension

• More often utilized:– in menopausal women, – nulliparity, – obesity, – tethering of the uterus from

prior C/Section, – lack of descensus– Permits treatment of

endometriosis, extensive adhesive disease

• Requires

–Advanced laparoscopic skills

–Knot tying

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Single Port or Single Incision Laparoscopy

• Single transumbilical 2-3 cm incision used for placement of multi channel devices– Advantages

–Decreased number of abdominal incisions–Reduced post operative pain– Improved cosmetic result

• Limitations includes– Visualization and triangulation of instruments– Close proximity of camera and instruments handles makes

procedure technically challenging– Difficult to deal with unsuspected pelvic findings– Cost is greater than traditional laparoscopic approach

Escobar, PF. Robotic-assisted laparoendoscopic single-site surgery in gynecology: initialReport and technique. J Minim Invasive Gynecol 2009;16:589-561.

New Innovations in Gynecology

•$1.7 million/robot•$125,000 annual

maintenance fee•$ 2,000 per surgerysingle use instrument

3 yrs ago 0.5% hysterectomiesperformed robotically, now 10%

Robotic Hysterectomy

• Laparoscopic access

• 3-D high definition with 10 fold magnification improves visualization

• Articulated instruments decreases tremor

• Improves ease of knot tying, however decreases haptic feedback

• Requires skilled bedside assistant and surgical team

• $960 million-$1.9 billion will be added to health care system if robotic surgery is used for all hysterectomies

Liu, H. Robotic convention laparoscopic surgery for benign Gynecologic disease: CochraneDatabase Syst Rev 2012;2: CD008978.

Robotic Surgery

Robotically assisted hysterectomy offered no better clinical outcomes than traditional laparoscopic surgery over a 3-year period

Added an average of $2000 to the cost of the operation

Wright, JD et al. Robotically assisted vs laparoscopic hysterectomy among women with benign gynecologic diseaseJAMA 2013:309:689-698.

ACOG Statement

“ Robotic hysterectomy is best used for unusual and complex clinical conditions in which improved outcomes over standard minimally invasive approaches have been demonstrated”

Radiofrequency Volumetric Thermal Ablation of Fibroids

• Volumetric tissue ablation

• Guided by laparoscopic ultrasound

• Treatment effect is limited to the fibroid —spares the myometrium

• Treats uterine fibroids in all locations

• An outpatient procedure

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Radiofrequency Volumetric Thermal Ablation of Fibroids with Acessa

• Combines three basic gynecologic skills:– Laparoscopy: Two trocars, no special suturing skills

– Ultrasound: Laparoscopic ultrasound probe scans and manipulates

– Probe placement under ultrasound guidance: RF probe easily seen on ultrasound

The Acessa Handpiece

Reduction in MBL: 103.6 mL (p <.001)

Days to normal activity: 7 – 10 days

Device‐related adverse events: 3.6%

Two serious (pelvic abscess; sigmoid serosal tear)

Three non‐serious events 

Baseline to 12 Month Results

63

Mean Uterine and Fibroid Volume Measured by MRI (cm3)

Tranexamic acid: An Excellent Option for Women with Ovulatory Heavy Menstruation

• Indication– Tranexamic acid tablets are indicated for the treatment of

cyclic (ovulatory) heavy menstrual bleeding

– Can be prescribed in the presence of fibroids

• Contraindication– Can not use with hormonal contraception

– Prior history of DVT, MI, stroke, or pulmonary embolism

*

MBL Levels Reduced Consistently Across all Cycles Studied

3‐cycle6‐cycle

Tranexamic acid 3900 mg/d (n=112)  MBL 169mL

Placebo (n=67)Baseline MBL 154mL

Tranexamic acid 3900 mg/d(n=115)  MBL 172.3mL

Placebo (n=72)Baseline MBL 153mL

*P<0.05 3‐cycle study

**P<0.05 6‐cycle study

***

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Tranexamic Acid

• Tranexamic acid first-line, non-hormonal, non-surgical therapy for cyclic heavy menstrual bleeding

• Significant reductions in MBL across treatment cycles– 39% (65 mL) and 38% (66 mL) reductions in two pivotal trials (P

< 0.001 vs. 5% (7 mL) and 12% (18 mL) for placebo)

– Study population represents a broad range of patients seen in clinical practice

• Significantly reduced limitations on physical, social, and leisure activities (P < 0.05 vs. placebo)

• For the management of HMB without structural or histological abnormalities, or in the presence of small fibroids1

• High concentrations of LNG suppresses proliferation of uterine leiomyoma cells and promotes cell apoptosis

• Reduces menstrual blood loss in women with fibroid-related heavy menses and increases hemoglobin but not fibroid regression

• LNG-IUS has proven to be highly effective, reducing average MBL by as much as 90%2,3

• It can take up to 6 months to be fully effective and break-through bleeding may occur particularly during the first 3 cycles of use1

• Releases 20 g of levonorgestrel every 24 hrs

• Decreases amount of menstrual blood loss

Levonorgestrel Intrauterine System (LNG-IUS)

1. NICE. Heavy Menstrual Bleeding. Guideline 44. 2007.2. Fraser. Drug Saf. 2008;31:275–82.3. Roy. Drug Saf. 2004;27:75–90.

Medical Therapy With the Levonorgestrel Intrauterine System Reduces Heavy Uterine Bleeding

Men

stru

al b

lood

los

s (m

L)

Fedele L, et al. Fertil Steril. 1997;68:426-429; Soysal S, Soysal ME. Gynecol Obstet Invest. 2005;59:29-35.

0

100

200

300

400

Before treatment

3 6 12Months of use

Range of normal blood

loss

Uterine Fibroids: LNG-IUS for Symptom Relief

• Before-after study; 67 women with uterine leiomyomas who chose LNG-IUS for contraception

• Menstrual blood loss reduced 84%

• Hemoglobin and ferritin significantly increased

• By 3 months, 10 of 14 women with painful menses reported improvement

• Volume of uterus and fibroids decreased

• Only 6 of 67 women discontinued LNG-IUS over 12 month study.

Grigorieva V, et al. Fertil Steril 2003;79:1194-1198.

GnRH Agonist• FDA approved in 1999

• GnRHa stimulates the receptor and leads to down-regulation effectively causing hypogonadism and induces a state of hypoestrogenism

• Suppresses cell proliferation and induces apoptosis– Leads to decreased expressions of:

– mitogenic factors– decreased angiogenic growth factors– decreased platelet derived factors

• Clinical efficacy– Shrinks fibroids 50% of volume– Improves fibroid related symptoms– Improves pre and post operative anemia in anemic patients– Reduced duration of stay in hospital– Blood loss and rate of vertical skin incision reduced for myomectomy and

hysterectomy

• Treatment limited to 3-6 months– Fibroids resume pre-treatment size after discontinuation of therapy

• Side effects– Hot flashes, vaginal dryness, decrease in bone mineral density

Mifepristone (RU-486)• Synthetic steroid with antiprogesterone and

antiglucorcorticoid activity synthesized from precursor norethindrone

• Binds competitively and inhibits progesterone receptors

• Suppresses prolactin in leiomyomas and myometrium

• Regulates amino acid transporter system which plays a role in proliferation

• Clinical efficacy– Phase I, II, III trial completed utilizing Mifepristone 2.5mg-50 mg/day– All tested doses decreased uterine volume up to 50%

– However 5-10 mg dose associated with low-grade endometrial hyperplasia

– Also associated with less hypoestrogenic side effects

• Mifepristone 2.5 mg– Approves leiomyoma specific quality of life indicators– Reduces leiomyoma size– No evidence of endometrial hyperplasia

13

Asoprisnil• First selective progesterone receptor modulator

• Inhibits the expression of growth factors

• Inhibits proliferation and induces apoptosis of cultured leiomyoma cells

• Reduces collagen deposits in ECM– High degree of receptor and tissue selectivity

– High-binding affinity for progesterone receptors

– moderate affinity for glucocorticoid receptor,

– low affinity for androgen receptor,

– no binding affinity for estrogen or mineralocorticoid receptors

• Clinical efficacy– Phase II and III trials completed

– In doses of 25 mg, Asoprisnil reduces uterine volume by 36% after 12 wks of therapy

– Reduction in bloating and pelvic pressure

– Associated with follicular phase estrogen and minimal hypoestrogenic complaints

– Moderately reduced uterine artery flow

Ulipristal Acetate• Synthetic steroid derived from 19-

norprogesterone, – A selective progesterone receptor modulator that binds to

progesterone receptors.

– The binding and antagonist potency with glucocorticoid receptor is reduced compared to mifepristone

– Exerts anti-proliferative, pro-apoptotic, and anti-fibrotic actions on leiomyoma cells

• Clinical efficacy– Phase I, II trial have been completed

• Reduces uterine volume

• Controls uterine bleeding

• Improves quality of life

Ulipristal Acetate Compared to Leuprolide

• Donnez, et al– After 13 wks, Ulipristal controlled uterine bleeding in 91%

of 96 women who received ulipristil 5 mg/day and and uterine volume decreased 21%

– Compared to 92% of 98 women who took 10 mg/day AND uterine volume decreased 12%

–Compared to19% of 48 women who took placebo who had improvement of uterine bleeding and 3% increase in uterine volume.

Summary

• Fibroids size, number, and location often determine clinical symptoms and treatment options

• Individualize clinical care pathways

• Determine patient preference for therapy

• Collaborate with interventional radiology

• Embrace concepts integral to the Center of Excellence success