Uterine Fibroids: An introduction

Shannon Laughlin-Tommaso, MD MPH

Fibroid Center & Minimally Invasive Gynecologic Surgery
Mayo Clinic, Rochester
July 10-11, Silver Springs, MD

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Disclosures
• No financial disclosures or conflicts of interest
• Co-investigator, Clinical study to evaluate safety
of ExAblate Model 2100 System for
Symptomatic Uterine Fibroids
• (Sponsored by InSightec)
• Co-investigator, FIRSTT trial (Comparing UAE
and FUS)
• Co-investigator, Study of environment, lifestyle
and fibroids

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Objectives
• Discuss the biology, epidemiology, and impact
of fibroids
• Describe the clinical presentation and effects on
quality of life
• Provide an overview of the medical and
minimally invasive fibroids therapies

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What are fibroids?
• Benign smooth muscle cell tumor: “leiomyoma”
• Bulky fibrous physiologically active extracellular
tissue (collagen): “fibroids”
• Arise from single cell & are monoclonal
• But, a single uterus can have multiple
independent tumors
• Most common reproductive tumor in women

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What are fibroids?
• Hormonally dependent
• Menarche  menopause
• Estrogen, progesterone and aromatase
receptors in fibroid tissue
• Chromosomal abnormalities are common (40%)
• Trisomy 12
• T(12;14)
• Deletions of 7q, 3q, 1p

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How do leiomyosarcomas differ?
• Rare, fatal tumors with 4 histologic patterns:
• Nuclear atypia
• Mitotic activity
• Necrosis
• High cellularity
• Fibroid variants may have one of the above but
not all
• Usually benign course

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Fibroids grow at different rates
• Fibroids in same uterus grow (or shrink) at
different rates
• Range of growth: -89% to +138% in 6 months
(median +9%)
• For black women: growth continued at same
rate up to menopause
• For white women: growth rate slowed after
age 45

Peddada et al, PNAS, 2008

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Fibroid are common
• Symptomatic fibroids: estimated 25%
• Pathology specimens: ~80%
• Ultrasound-screening studies: up to 80% by
age 50
• Incidence differs between white and black
women
• Studies of self-reported fibroids: 9 (white) -
34 (Black)/1000 woman-yrs
Cramer and Patel 1990; Marshall et al 1997;
Wise et al, 2006; Baird et al, 2003

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Public Health Impact of Fibroids
• 400,000 new cases per year1
• Myomectomy
• >30,000 per year in US
• Direct & indirect costs: $30,206-$39,2072
• Hysterectomy
• 600,000 per year in US
• 40% for fibroids
• Direct & indirect costs: $31,559- $42,6192
• Health disparity: black>>white women3,4

1Hartmann et al, 2006, 2Carls et al, 2008; 3Viswanathan, 2007

4Eltoukhi et al, 2013

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How do women present clinically?
• Menstrual cramps and
pain
• Heavy menstrual bleeding
& anemia
• Problems with fertility or
pregnancy
• Bladder or bowel
symptoms

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Black women are disproportionately
affected
• More symptoms
• 40% report menstrual pain and cramps
• 3-fold increased risk of anemia
• 2.4x risk of hysterectomy
• Nearly 7-fold risk of myomectomy
• Higher uterine weights
• More fibroids & larger volume

Eltoukhi et al, 2013, Wechter et al, 2011

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Fibroids affect quality of life
• Relationship impacts:
• 14% childcare, 15% friends, 22% partner
• Work:
• 29% missed work days
• 24% reported lost potential
• 27% unable to do part of their job
• 12% feared losing their job
• 15% could not travel

Stewart et al, 2013

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Fibroids affect quality of life
• Fears about fibroids:
• 77% growth
• 53% cancer
• 25% unable to become pregnant (twice as
high in African American women than white)
• Concerns about treatments:
• 81% invasiveness
• 64% sexuality
• 49% wanted fertility sparing option (70% v.
30%) Stewart et al, 2013

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Fibroid evaluation
• Pelvic exam
• Ultrasound
• Endometrial biopsy
• Blood counts

• Pelvic MRI
• ?Hysteroscopy

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When do we treat fibroids?
• Fibroids that are symptomatic at any age can
be treated
• Imaging will help
• Options: treat symptoms vs. treating fibroids
• Fertility issues:
• Submucosal fibroids
• Intramural fibroids>5 cm
• Treatments that optimize future fertility:
• MRgFUS
• Myomectomy
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When do we not treat fibroids?
• Asymptomatic or an incidental finding
• Rapid growth without symptoms
• Postmenopausal*

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Treatment options for bleeding
• NSAIDs
• Tranexamic acid
• Contraceptive hormones (estrogen-progestin
or progestin alone)
• Mirena IUD
• Endometrial ablation

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Medical options for fibroids and bleeding
• Leuprolide acetate:
• GnRH agonists/antagonists
• Controls bleeding
• Shrinks fibroids
• Ulipristal acetate:
• Selective progesterone-receptor modulator
• Controls bleeding in >90% of women
• Shrinks fibroids
• Not available for use in US currently

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Minimally Invasive Treatments

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Uterine
Artery
Embolization

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UAE: how it works
• Catheter placed in common femoral artery
• Travels through anterior internal iliac to uterine
arteries
• Position confirmed with angiography
• Embolic agents (polyvinyl alcohol particles)
• Compression on incision to reduce hematoma

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UAE: Candidates
• UAE has a more global treatment
• Relative cut-off of 10 cm
• No active genitourinary infection/ malignancy
• No severe vascular disease (limits vessel
access)
• No iodine contrast allergy
• Good renal function
• Hysteroscopically resectable SM fibroids

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UAE: Details
• 2-3 hour procedure under fluoroscopy
• Overnight stay for pain control
• Incision in groin

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UAE: risks
• Amenorrhea: 3% if <40yrs, 40% if >50 yrs
• Markers of ovarian reserve have shown lower
ovarian function after UAE compared with
myomectomy
• Also found with hysterectomy
• Postembolization syndrome: pain, nausea,
vomiting, leukocytosis, malaise

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Symptom Relief from UAE
• Menorrhagia: 83% improved
• Dysmenorrhea: 77% improved
• Urinary frequency: 86% improved
• 91% satisfaction
• Fibroid volume reduced 42% at 3 months
• Symptoms unrelated to volume reduction

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Pregnancies after UAE
• 164/555 desired fertility (? 35 trying at 1 year)
• 24 pregnancies
• 18 live births – 4 preterm
• 3 abnormal placentations
• 23/102 desired fertility
• 61% pregnancy rate
• 2 miscarriages
• 13 went to term without complication
Pron et al, Obstet Gynecol, 2005;Firouznia et al, AJR, 2009

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MRgFUS: how it works
• FDA approved in 2004
• Focused ultrasound beam
• Temperature highest in focal spot
• Non-target areas relatively safe
• MRI:
• Mapping of fibroids & beam
guidance
• Thermal monitoring
• Treatment effect

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MRgFUS: Candidates?
• Few large fibroids
• Accessible by FUS
• Relative cut-off at 10 cm in
diameter
• No metal or scars
• Good renal function due to
Gadolinium use

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MRgFUS: Details

• ~3 hour treatment, possible 2 days in a row

• Done under IV sedation/pain medications and
with urinary catheter
• Outpatient (goes home same day)
• Requires minimal pain medication
prescriptions
• No incisions/ no radiation

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MRgFUS: Risks
• Skin burns: resolved with procedural changes
• Inflammation of subcutaneous fat and muscle
• Mainly asymptomatic
• Bowel injury
• Paresthesias:
• Sonicate 4cm from bony structures
• Generally spontaneously resolve

Hesley et al. Ultrasound Q, 2008

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Symptom relief from MRgFUS
• Symptoms lowest at 3 months
• Symptom severity score dropped by 50%
• 91% have symptom relief at 12 months
• Probability of another procedure:
• The more volume you treat, the better the
outcome
• ~20% at 2 years with 50% treated
• ~20% at 4 years with unrestricted treatment
Stewart et al. Obstet Gynecol 2007
Fennessy et al. Radiology 2007

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MRgFUS: fertility-sparing option
• Observational studies only
• 54 pregnancies
• 51% delivered at term, 33% miscarried
• High vaginal delivery rate
• No distinct patterns of complications
• Success with in vitro fertilization after MRgFUS
• Counsel women on the risks that are known
and unknown
Rabinovici, Fertil Steril, 2010

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Summary
• Fibroids are common and costly
• African-American women are disproportionately
affected
• Symptomatic fibroids can be treated,
asymptomatic fibroids can be left alone
• There are many alternatives to hysterectomy
that are durable and effective

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Questions?

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