Uterine Fibroids
BS. Nguyễn Hồng Anh
KEY POINTS
1 Fibroids are very common; most are asymptomatic and can be managed expectantly.
2 There is no definite relationship between oral contraceptives and the presence of
fibroids.
3 First-degree relatives of women with fibroids have a 2.5 times increased risk of
developing fibroids.
4 The risk of having fibroids is 2.9 times greater in African American women than in
white women.
5 Women with fibroids are only slightly more likely to experience pelvic pain than
women without fibroids.
6 Rapid uterine growth is not well defined, and almost never indicates sarcoma in
premenopausal women; sarcomas are rare and more likely occur in postmenopausal
women with symptoms of pain and bleeding.
5347 Sonography is the most readily available and least costly imaging technique to
differentiate fibroids from other pelvic pathology; however, MRI permits more
precise evaluation of the number, size, and position of fibroids, including the
proximity to the endometrial cavity.
8 The presence of submucosal fibroids decreases fertility and removing them can
increase fertility; subserosal fibroids do not affect fertility and removing them does
not increase fertility; intramural fibroids may slightly decrease fertility, but removal
does not increase fertility.
9 Most fibroids do not increase in size during pregnancy.
10 For women who are mildly or moderately symptomatic with fibroids, watchful
waiting may allow treatment to be deferred, perhaps indefinitely.
11 As women approach menopause, watchful waiting may be considered because there
is limited time to develop new symptoms, and after menopause bleeding stops and
fibroids decrease in size.
12 Surgical treatment options include abdominal myomectomy, laparoscopic
myomectomy, laparoscopic radiofrequency ablation, hysteroscopic myomectomy,
endometrial ablation, and abdominal, vaginal, or laparoscopic hysterectomy.
13 An inability to evaluate the ovaries on pelvic examination is not an indication for
surgery.
14 Myomectomy should be considered as a safe alternative to hysterectomy, even for
those women who have large uterine fibroids and wish to retain their uterus.
15 Submucous fibroids, sometimes associated with increased menstrual bleeding or
infertility, often can be removed hysteroscopically.
16 Routine ultrasound follow-up is sensitive, and may detect many clinically
insignificant fibroids.
17 Uterine artery embolization (UAE) is an effective treatment for selected women
with uterine fibroids. The effects of UAE on early ovarian failure, fertility, and
pregnancy are unclear.
Fibroids (leiomyomas, myomas) are an important health care concern
because they are the most frequent indication for the performance of
hysterectomy, accounting for nearly 240,000 such procedures in the United
States (1). In comparison, approximately 30,000 myomectomies are performed
every year. Inpatient surgery for fibroids costs $2.1 billion per year in the United
States, and the cost of outpatient surgeries, medical and nonmedical costs, and
time away from work or family add significantly to these expenditures (2).
ORIGINS OF UTERINE FIBROIDS
Fibroids are benign, monoclonal tumors of the smooth muscle cells of the
myometrium and contain large aggregations of extracellular matrix composed of
535collagen, elastin, fibronectin, and proteoglycan (3).
Incidence
[1] Fibroids are remarkably common. Fine serial sectioning of uteri from 100
consecutive women subjected to hysterectomy discovered fibroids in 77%, some
as small as 2 mm (4). A random sampling of women aged 35 to 49, screened by
self-report, medical record review, and sonography, found that among African
American women by age 35 the incidence of fibroids was 60%, and it was over
80% by age 50 (Fig. 11-1). White women have an incidence of 40% at age 35 and
almost 70% by age 50 (5).
536537FIGURE 11-1 A: Age- and race-specific incidence of myomectomy, 1997, based on NIS
and U.S. Census Bureau estimates. B: Age- and race-specific incidence of hysterectomy
for fibroids, 1997, based on NIS and U.S. Census Bureau estimates. (From Health
Services/Technology Assessment Tests [HSTAT]. Available online at
http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=hstat1.section.48317.)
Etiology
Although the precise causes of fibroids are unknown, advances have been made
in understanding the molecular biology of these benign tumors and their
hormonal, genetic, and growth factors (6).
Genetics
Fibroids are monoclonal and are made up of concentric smooth muscle fibers and
fibrous connective tissue surrounded by a vascular pseudocapsule. Some authors
postulate that hypoxic conditions, perhaps associated with menstruation, induce
mutations in a single myometrial smooth muscle stem cell. Approximately 40% to
50% of fibroids display nonrandom and tumor-specific chromosome
rearrangements involving mostly deletions, duplications, and translocations of
chromosomes 6, 7, 12, and 14. These complex molecular changes affect energy
metabolism, extracellular matrix remodeling, and estrogen and progesterone
receptor status.
Growth factors, small proteins that act as signaling molecules, interact with
specific receptors on the cell surface and are important for the development of
fibroids. Transforming growth factor-β (TGF-β), basic fibroblast growth factor
(bFGF), vascular endothelial growth factor (VEGF), platelet-derived growth
factor (PDGF), and insulinlike growth factor (IGF) modulate cellular growth,
proliferation, and differentiation. The TGF-β family upregulates the synthesis of
many extracellular matrix components that increase the fibrous component of
fibroids. Proliferation of smooth muscle cells are induced by bFGF, which
promotes angiogenesis. Estrogen and progesterone influence fibroid development
by regulating growth factors and their signaling pathways. Fibroids may be
affected by environmental chemicals, which can increase or decrease estrogen
and/or progesterone receptors.
Genetic differences between fibroids and leiomyosarcomas (LMSs)
indicate that LMSs do not result from the malignant degeneration of
fibroids. Cluster analysis of 146 genes found that the majority are downregulated
in LMSs but not in fibroids or myometrium. Comparative genomic hybridization
did not find specific anomalies shared by fibroids and LMSs (7).
538Hormones
Estrogen and progesterone appear to promote the development of fibroids.
Fibroids are rarely observed before puberty, are most prevalent during the
reproductive years, and regress after menopause. Factors that increase overall
lifetime exposure to estrogen, such as obesity and early menarche, increase the
incidence. Decreased exposure to estrogen found with smoking, exercise, and
increased parity is protective (8).
Serum levels of estrogen and progesterone are similar in women with and
without clinically detectable fibroids. As a result of increased levels of aromatase
within fibroids, de novo production of estradiol is higher than in normal
myometrium (8). Progesterone is important in the pathogenesis of fibroids, which
have increased concentrations of progesterone receptors A and B compared with
normal myometrium (9,10). The highest mitotic counts are found in fibroids at the
peak of progesterone production (11). Gonadotropin-releasing hormone (GnRH)
agonists decrease the size of fibroids, but progestin given concurrently with
GnRH prevents a decrease in size (12).
Human fibroid tissue, grafted to immunodeficient mice, increased in size in
response to estradiol plus progesterone, but the growth was blocked by the
antiprogestin RU486 (12). The volume of grafted fibroid tissue decreased after
progesterone withdrawal. Treatment with estradiol alone did not increase the graft
size, but did induce expression of progesterone receptors and supported the action
of progesterone on the grafts (12).
Growth Factors
Growth factors, proteins, or polypeptides, produced locally by smooth muscle
cells and fibroblasts, appear to stimulate fibroid growth primarily by increasing
extracellular matrix (6). Many of these growth factors are overexpressed in
fibroids and either increase smooth muscle proliferation (TGF-β, bFGF), increase
DNA synthesis (epidermal growth factor [EGF], PDGF), stimulate synthesis of
extracellular matrix (TGF-β), promote mitogenesis (TGF-β, EGF, IGF, prolactin
[PRL]), or promote angiogenesis (bFGF, VEGF).
Risk Factors
Prospective, longitudinal studies characterize the factors that influence the
development of uterine fibroids (4,13,14). Although selection bias may limit
epidemiologic studies, risk factors are considered.
Age
The incidence of fibroids increases with age, 4.3 per 1,000 woman-years for 25
539to 29 year olds and 22.5 for 40 to 44 year olds. African American women develop
fibroids at an earlier age than white women (13).
Endogenous Hormonal Factors
Greater exposure to endogenous hormones, as found with early menarche
(younger than 10 years of age), increases and late menarche decreases the
likelihood of having uterine fibroids (14). Fibroids are smaller, less numerous,
and have smaller cells in hysterectomy specimens from postmenopausal women,
when endogenous estrogen levels are low (4,15).
Family History
[3] First-degree relatives of women with fibroids have a 2.5 times increased
risk of developing fibroids (26). Monozygous twins are reportedly hospitalized
for treatment of fibroids more often than heterozygous twins, but these findings
may be the result of reporting bias (27).
Ethnicity
[4] African American women have a 2.9 times greater risk of having fibroids
than white women, unrelated to other known risk factors (28). African American
women have fibroids develop at a younger age and have more numerous, larger,
and more symptomatic fibroids (29). It is unclear whether these differences are
genetic or result from known differences in circulating estrogen levels, estrogen
metabolism, diet, or environmental factors.
Weight
A prospective study found that the risk of fibroids increased 21% with each
10 kg increase in body weight, and with increasing body mass index (BMI)
(20). Similar findings were reported in women with greater than 30% body fat
(21). Obesity increases conversion of adrenal androgens to estrone and decreases
the sex hormone–binding globulin (SHBG). The result is an increase in
biologically available estrogen, which may explain the increase in fibroid
prevalence and/or growth.
Diet
Few studies examined the association between diet and the presence or growth of
fibroids (22). A diet rich in beef, other red meat, and ham increased the incidence
of fibroids, while a diet rich in green vegetables decreased this risk. These
findings are difficult to interpret because calorie and fat intake were not
measured.
540Exercise
Women in the highest category of physical activity (approximately 7 hours
per week) were significantly less likely to have fibroids than women in the
lowest category (less than 2 hours per week) (23).
Oral Contraceptives
[2] There is no definite relationship between oral contraceptives and the
presence of fibroids. An increased risk of fibroids with oral contraceptive use
was reported, but a subsequent study found no increased risk with the use or
duration of use (24,25). Studies in women with known fibroids who were
prescribed oral contraceptives showed no increase in fibroid growth (20,26). The
formation of new fibroids does not appear to be influenced by oral contraceptive
use (27).
Menopausal Hormone Therapy
For the majority of postmenopausal women with fibroids, hormone therapy
will not stimulate fibroid growth. If fibroids do grow, progesterone is likely
to be the cause (28). One study evaluated postmenopausal women with fibroids
who were given 2 mg of oral estradiol daily and randomized to 2.5 or 5 mg of
medroxyprogesterone acetate (MPA) per day (28). One year after starting
treatment, 77% of women taking 2.5-mg MPA had either no change or a decrease
in fibroids diameters and 23% had a slight increase. However, 50% of women
taking 5-mg MPA had an increase in fibroid size (mean diameter increase of 3.2
cm).
Postmenopausal women with fibroids treated with 0.625 of conjugated equine
estrogen (CEE) and 5-mg MPA were compared over 3 years to a similar group of
women not taking hormone therapy (29). By the end of the third year, only 3 of
34 (8%) treated and 1 of 34 (3%) untreated women had any increase in fibroid
volume over baseline (28). Postmenopausal women with known fibroids,
followed with sonography, were noted to have an average 0.5-cm increase in the
diameter of fibroid after using transdermal estrogen patches plus oral
progesterone for 12 months (29). Women taking oral estrogen and progesterone
had no increase in fibroid size (34).
Pregnancy
Increasing parity decreases the incidence and number of clinically apparent
fibroids (31–33). The remodeling process of the postpartum myometrium, a
result of apoptosis and dedifferentiation, may be responsible for the involution of
fibroids (34). Another theory postulates that the vessels supplying fibroids regress
during involution of the uterus, depriving fibroids of their source of nutrition (35).
541Smoking
Smoking reduces the incidence of fibroids. Reduced conversion of androgens to
estrone, caused by inhibition of aromatase by nicotine, increased 2-hydroxylation
of estradiol, and stimulation of higher levels of SHBG decrease bioavailability of
estrogen (36–38).
Tissue Injury
Cellular injury or inflammation resulting from an environmental agent, infection,
or hypoxia was proposed as a mechanism for initiation of fibroid formation (39).
Repetitive tissue injury to the endometrium and endothelium might promote the
development of monoclonal smooth muscle proliferations in the muscular wall.
Frequent mucosal injury with stromal repair (menstruation) may release growth
factors that promote the high frequency of uterine fibroids (39).
No increased incidence was found in women with prior sexually transmitted
infections, prior intrauterine device (IUD) use, or prior talc exposure (31). Herpes
simplex virus (HSV) I or II, cytomegalovirus (CMV), Epstein–Barr virus (EBV),
and chlamydia were not found in fibroids.
SYMPTOMS
Fibroids are almost never associated with mortality, but they may cause
morbidity and significantly affect the quality of life (40). Women who have
hysterectomies because of fibroid-related symptoms have significantly worse
scores on SF-36 quality-of-life questionnaires than women diagnosed with
hypertension, heart disease, chronic lung disease, or arthritis (40).
Of 116 women with fibroids larger than 5 cm on sonographic examination and
uterine size greater than 12 cm on pelvic examination, 42% were satisfied with
their initial level of symptoms, including stress, bleeding, and pain (41). Most of
the 48 women who chose to have treatment within 1 year were more likely to
have higher scores on bleeding and pain scales and be more concerned about their
symptoms. Most women chose myomectomy (n = 20), hysterectomy (n = 15), or
hysteroscopic myomectomy (n = 4), and symptom scores improved markedly
during the 7.5 months (mean) of follow-up.
Abnormal Bleeding
The association of fibroids with heavy menstrual bleeding is not clearly
established. Therefore, other possible etiologies, including coagulopathies
such as the von Willebrand disease, should be considered in a woman with
heavy menstrual bleeding (42).
542Type 0 and 1 fibroids have been associated with anemia. Of 1,665 women
having office hysteroscopic evaluation for heavy menstrual bleeding, 259 women
had a submucous fibroid diagnosed; 63 were type 0, 110 type 1, and 52 were type
2 (25 were not documented). Hemoglobin concentrations below 12 were
significantly associated with submucous fibroids and most strongly correlated
with type 0 fibroids (43).
Another study found that women with fibroids used 7.5 pads or tampons on the
heaviest day of bleeding compared with 6.1 pads or tampons used by women
without fibroids (44). Women with fibroids larger than 5 cm had slightly more
gushing and used about 3 more pads or tampons on the heaviest day of bleeding
than women with smaller fibroids.
Pain
[5] Women with fibroids are only slightly more likely to experience pelvic
pain than women without fibroids. Transvaginal sonography (TVS) was
performed on a population-based cohort of 635 non–care-seeking women with an
intact uterus to determine the presence of uterine fibroids (45). Dyspareunia,
dysmenorrhea, or noncyclic pelvic pain was measured by visual analog scales.
The 96 women found to have fibroids were only slightly more likely to report
moderate or severe dyspareunia or noncyclic pelvic pain and had no higher
incidence of moderate or severe dysmenorrhea than women without fibroids.
Neither the number nor the total volume of fibroids was related to pain. However,
women who present for clinical evaluation for fibroid-associated pain may be
different from those in the general population (45).
Fibroid degeneration may cause pelvic pain. As fibroids enlarge, they may
outgrow their blood supply, with resulting cell death (46). Types of degeneration
determined both grossly and microscopically include hyaline degeneration,
calcification, cystic degeneration, and hemorrhagic degeneration. The type of
degeneration appears to be unrelated to the clinical symptoms (46). Pain from
fibroid degeneration is often successfully treated with analgesics and observation.
Torsion of a pedunculated subserosal fibroid may produce acute pelvic pain that
requires surgical intervention (47).
Urinary Symptoms
Fibroids may cause urinary symptoms, although few studies examined this
association. Following uterine artery embolization (UAE) with a 35% reduction in
the mean uterine volume, frequency and urgency were greatly or moderately
improved in 68% of women, slightly improved in 18%, and unchanged or worse
in only 14% (48). This finding suggests that increased uterine volume
543associated with fibroids is related to urinary symptoms.
Fourteen women with large fibroids and urinary symptoms were given six
monthly injections of GnRH agonist (GnRH-a) with a resulting 55% decrease in
uterine volume (49). Following therapy, urinary frequency, nocturia, and urgency
decreased. There were no changes in urge or stress incontinence as measured by
symptoms or urodynamic studies. It is not clear whether these findings are related
to a decrease in uterine volume or to other effects of GnRH treatment.
NATURAL HISTORY OF FIBROIDS
Most fibroids grow slowly. A prospective, longitudinal study of 72
premenopausal women (38 African American, 34 white) using computer analysis
of serial MRI found that the median growth rate was 9% over 12 months (13).
Multiple fibroids in the same individual were found to have highly variable
growth rates, suggesting that growth results from factors other than hormone
levels. After age 35, growth rates declined with age for white women but not for
African American women, which likely explains the increased fibroid-related
symptoms noted in African American women. Seven percent of fibroids regressed
over the study period. Continued follow-up of these women is planned and may
provide a better understanding of this issue.
Rapid Fibroid Growth
[6] In premenopausal women, “rapid uterine growth” almost never indicates
the presence of uterine sarcoma. One study found only 1 sarcoma among 371
(0.26%) women operated on for rapid growth of presumed fibroids (50). No
sarcomas were found in the 198 women who had a 6-week increase in uterine size
over 1 year, which is the definition of rapid growth that was used in the past.
Uterine Sarcoma
Women found to have uterine sarcoma are often clinically suspected of
having a pelvic malignancy (50,51). Women with pain and bleeding and who
are closer to menopause or postmenopausal may have a rare sarcoma. Of
nine women found to have uterine sarcomas, all were postmenopausal and
eight were admitted with abdominal pain and vaginal bleeding (51). All eight
had presumed gynecologic malignancies: uterine sarcoma in four, endometrial
carcinoma in three, and ovarian cancer in one. One additional woman had surgery
for prolapse and a sarcoma was found incidentally (51).
The Surveillance, Epidemiology, and End Results (SEER) database identified
13,089 patients diagnosed with uterine sarcoma in the period from 2000 to 2012.
544The mean age of patients with sarcomas was 68 for carcinosarcoma; 55 for LMS;
54 for stromal sarcoma; and 59 for adenosarcoma (52). A literature review found
a mean age of 36 years in women subjected to myomectomy (50).
DIAGNOSIS
Pelvic Examination
Clinically significant subserosal and intramural fibroids can usually be
diagnosed by pelvic examination based on findings of an enlarged,
irregularly shaped, firm, and nontender uterus. Uterine size assessed by
bimanual examination, even for most women with BMI greater than 30, correlates
well with uterine size and weight at pathologic examination (53). Routine
sonographic examination is not necessary when the diagnosis is almost certain. A
definite diagnosis of submucous fibroids often requires saline-infusion
sonography (SIS), hysteroscopy, or magnetic resonance imaging (MRI) (54).
Fibroid Location
The FIGO fibroid classification system categorizes submucous, intramural,
subserosal, and transmural fibroids.
Type 0—intracavitary (e.g., a pedunculated submucosal fibroid entirely within the
cavity)
Type 1—less than 50% of the fibroid diameter within the myometrium
Type 2—50% or more of the fibroid diameter within the myometrium
Type 3—abut the endometrium without any intracavitary component
Type 4—intramural and entirely within the myometrium, without extension to
either the endometrial surface or to the serosa
Type 5—subserosal at least 50% intramural
Type 6—subserosal less than 50% intramural
Type 7—subserosal attached to the serosa by a stalk
Type 8—no involvement of the myometrium; includes cervical lesions, those in the
round or broad ligaments without direct attachment to the uterus, and
“parasitic” fibroids
Transmural fibroids are categorized by their relationship to both the
endometrial and the serosal surfaces, with the endometrial relationship noted
545first, for example, types 2 to 3 (Table 11-1; Fig. 11-2) (55).
Table 11-1 FIGO Leiomyoma Classification System
SM—
submucosal
0 Pedunculated intracavitary
1 <50% intramural
2 ≥50% intramural
O—other 3 Contacts endometrium; 100% intramural
4 Intramural
5 Subserosal ≥50% intramural
6 Subserosal <50% intramural
7 Subserosal pedunculated
8 Other (specify, e.g., cervical, parasitic)
Hybrid
leiomyomas
(impact both
endometrium
and serosa)
Two numbers are listed separated by a hyphen. By
convention, the first refers to the relationship with the
endometrium while the second refers to the relationship to
the serosa. One example is given below.
2–
5
Submucosal and subserosal, each with less than half the
diameter in the endometrial and peritoneal cavities,
respectively.
46FIGURE 11-2 FIGO leiomyoma classification system.
Fibroid Variants
A number of benign uterine smooth muscle tumors have been defined according
to histologic criteria issued by the World Health Organization. Mitotically active
leiomyoma is defined by the presence of 10 to 15 mitoses/10 high-power fields
(hpf) and may be seen in patients who are pregnant or are using exogenous
hormones.
Increased cellularity, higher than that of nearby myometrium, is defined as a
cellular leiomyoma. Taran et al. reported a series of women treated for cellular
leiomyomas and 2 of 99 patients (2%) had recurrent disease (56). One study
suggested that cellular leiomyomas exhibiting chromosome 1p deletions, a
genetic alteration found in LMS, may be clinically more aggressive and require
more intense surveillance (57).
Leiomyoma with bizarre nuclei (also called atypical or symplastic) shows
scattered large atypical cells. Ly et al. described 34 patients with atypical
leiomyomas undergoing hysterectomy and 4 had recurrent disease (12%) (58).
Smooth muscle tumors of uncertain malignant potential (STUMP) show
atypical histologic features that range between leiomyoma and LMS, uncertain
types of necrosis, the presence of focal or diffuse cytologic atypia but the mitotic
count is less than 10/10 hpf, the presence of coagulative tumor necrosis but
mitosis is less than 10/10 hpf, and cellular tumors with more than 15 mitoses/10
hpf. Rarely STUMPs, mostly those that are p53 and p16 positive, have been
547found to exhibit malignant potential to develop a low-grade LMS (not highgrade). Guntupalli et al. reported a series of 41 patients with STUMPs: three
(7.3%) had recurrence (all local and distant) after undergoing a total abdominal
hysterectomy, and one of the recurrences was an LMS (59).
LMSs exhibit hypercellularity, diffuse moderate-to-marked nuclear atypia, a
high mitotic rate (≥10/hpf), and tumor cell necrosis. LMS is an aggressive cancer
and has a poor prognosis caused by early hematogenous spread, even in earlystage disease. The 5-year survival for stage I LMS is 61% and for stages III and
IV is about 30%. Pritts et al. published a rigorous meta-analysis of 133 studies of
women having surgery for presumed fibroids and determined that the prevalence
of LMS was 1 in 1,960, or 0.051% (60). The Agency for Healthcare Research and
Quality (AHRQ) of the U.S. Department of Health and Human Services updated
the analysis, added 91,294 more surgeries, and calculated a prevalence of LMS of
1 in 1,429 (0.07%) cases of surgery for presumed fibroids (61).
There is no reliable method of preoperative diagnosis of LMS available and it
is difficult to differentiate this disease from benign fibroids.
Imaging
For symptomatic women, consideration of medical therapy, noninvasive
procedures, or surgery often depends on an accurate assessment of the size,
number, and position of fibroids. TVS, SIS, hysteroscopy, and MRI were all
performed on 106 women scheduled for hysterectomy and the findings were
compared to pathologic examination (54). [7] Submucous fibroids were best
identified with MRI (sensitivity 100%, specificity 91%). Identification was about
equal with TVS (sensitivity 83%, specificity 90%), SIS (sensitivity 90%,
specificity 89%), and hysteroscopy (sensitivity 82%, specificity 87%). MRI is not
technique dependent and has low interobserver variability for diagnosis of
submucous fibroids, intramural fibroids, and adenomyosis when compared with
TVS, SIS, and hysteroscopy (62,63).
The presence of adenomyosis is associated with junctional zone thickness of
more than 15 mm (or 12 mm in a nonuniform junctional zone). Focal, not welldemarcated, and high- or low-intensity areas in the myometrium correlate with
adenomyosis (65).
MRI allows evaluation of the number, size, and position of submucous,
intramural, and subserosal fibroids and can evaluate their proximity to the
bladder, rectum, and endometrial cavity. MRI helps define what can be expected
at surgery and may help the surgeon avoid missing fibroids during surgery (66).
For women who wish to preserve fertility, MRI to document location and position
relative to the endometrium may be helpful prior to hysteroscopic, laparoscopic,
or abdominal myomectomy.
548[7] Sonography is the most readily available and least costly imaging
technique to differentiate fibroids from other pelvic pathology. It is
reasonably reliable for evaluation of uterine volume less than 375 cc and
containing four or fewer fibroids (62). Sonographic appearance of fibroids can
be variable, but often they appear as symmetrical, well-defined, hypoechoic, and
heterogeneous masses. Areas of calcification or hemorrhage may appear
hyperechoic, while cystic degeneration may appear anechoic. SIS utilizes saline
inserted into the uterine cavity to provide contrast and better defines submucous
fibroids (62).
Imaging of Uterine Sarcomas
The preoperative diagnosis of LMS may be possible. Diagnosis with total
serum lactate dehydrogenase (LDH) and LDH isoenzyme 3 measurements along
with gadolinium-enhanced diethylenetriamine pentaacetic acid (Gd-DTPA)
dynamic MRI was reported to be highly accurate (66). MRI images are taken
during the arterial phase, between 40 and 60 seconds after infusion of gadolinium.
Sarcomas have increased vascularity and show increased enhancement with
gadolinium, while degenerating fibroids have decreased perfusion and exhibit
decreased enhancement. Using LDH measurements and Gd-DTPA, a study of 87
women with uterine fibroids, 10 women with LMSs, and 130 women with
degenerating fibroids reported 100% specificity, 100% positive predictive value,
100% negative predictive value, and 100% diagnostic accuracy for LMS (Fig. 11-
3).
A form of MRI functional imaging called diffusion-weighted imaging (DWI)
has been used to distinguish between malignant and benign tumors. Malignant
lesions have higher cellularity and nuclear area, which restrict water diffusion as
measured by the apparent diffusion coefficient (ADC). Sixteen patients with
uterine LMSs and 26 patients with degenerating fibroids confirmed by surgery
and pathology underwent MRI and DWI. The mean ADC in LMSs was
significantly lower than that in degenerating fibroids. The sensitivity and
specificity were 100% and 90%. Other studies show conflicting results and DWI
needs further investigation (67).
FERTILITY
[8] The presence of submucous fibroids decreases fertility rates and
removing them increases fertility rates. Subserosal fibroids do not affect
fertility rates but removing them does increase fertility. Intramural fibroids
may slightly decrease fertility, but removal does not increase fertility (68). A
meta-analysis of the effect of fibroids on fertility and the effect of myomectomy
549on fertility found that submucous fibroids that distort the uterine cavity appear to
decrease fertility, with ongoing pregnancy/live birth rates decreased by about 70%
(relative risk [RR] 0.32; 95% confidence interval [CI], 0.12–0.85) (68). Resection
of submucous fibroids slightly increased fertility relative to infertile controls
without fibroids (ongoing pregnancy/live birth rate, RR 1.13; 95% CI, 0.96–1.33).
FIGURE 11-3 MR images. A: Degenerating fibroid. Left to right. Pre-enhanced T1
image, T2 image, and no enhancement on T1 Gd-DTPA at 60 seconds. B:
Leiomyosarcoma. Left to right. Pre-enhanced T1 image, T2 image (arrow to dorsal part of
tumor), and enhancement of dorsal part of tumor (arrow) on T1 Gd-DTPA at 60 seconds.
(From Goto A, Takeuchi S, Sugimura K, et al. Usefulness of Gd-DTPA contrastenhanced dynamic MRI and serum determination of LDH and its isozymes in the
differential diagnosis of leiomyosarcoma from degenerated leiomyoma of the uterus. Int J
Gynecol Cancer 2002;12:354–361.)
Several studies have described the role of HOXA10 and HOXA11 transcription
factors on uterine factor infertility associated with endometrial receptivity. In
normal endometrium, BMP-2 upregulates HOXA10 expression. This process is
550absent in endometrial cells of women with submucous fibroids. The result is
altered decidualization and inhibition of embryo implantation and decreased
uterine factor fertility (69).
Analysis of studies that routinely used hysteroscopy to confirm clear
nondistortion of the cavity by intramural fibroids found ongoing pregnancy/live
birth rates were not significantly different compared to controls (RR 0.73; 95%
CI, 0.38–1.40) (66). Removal of intramural or subserosal fibroids did not improve
ongoing pregnancy/live birth rates (RR 1.67; 95% CI, 0.75–3.72). Another study
evaluated pregnancy rates for 102 women undergoing ovarian stimulation—intrauterine insemination (OS-IUI) for unexplained infertility and who had at least one
documented fibroid and a normal uterine cavity determined by hysterosonography
or hysterosalpingogram. No differences were observed in conception and live
birth rates in women with non–cavity-distorting fibroids and those without
fibroids (70).
Myomectomy may involve operative and anesthetic risks, risks of infection
or postoperative adhesions, a slight risk of uterine rupture during
pregnancy, an increased likelihood that a cesarean section will be
recommended for delivery, plus the expense of surgery and time for
recovery. Therefore, until intramural fibroids are shown to decrease and
myomectomy to increase fertility rates, surgery should be undertaken with
reluctance (68). Randomized studies are needed to clarify the RRs and benefits
of surgical intervention.
FIBROIDS AND PREGNANCY
Incidence of Fibroids During Pregnancy
The prevalence of fibroids among pregnant women is 18% in African
American women, 10% in Hispanic women, and 8% in white women, based
on first trimester sonography (71). Mean size of the fibroids was 2.5 cm.
Clinical examination detects 42% of fibroids greater than 5 cm during pregnancy,
but only 12.5% when they are less than 5 cm (72).
Effect of Pregnancy on Fibroids
[9] Most fibroids do not increase in size during pregnancy. Pregnancy has a
variable, and unpredictable, effect on fibroid growth, likely dependent on
individual differences in fibroid gene expression, circulating growth factors, and
fibroid-localized receptors (72,73). A prospective study of 36 pregnant women
with a single fibroid discovered during routine first trimester sonographic
screening and examined by sonography at 2- to 4-week intervals found that 69%
of the women had no increase in fibroid volume throughout pregnancy (73). In
551the 31% of women noted to have an increase in volume, the greatest increase
occurred before the 10th week of gestation. There was no relationship between
initial fibroid volume and fibroid growth during gestational periods. A reduction
in fibroid size toward baseline measurements was observed 4 weeks after
delivery.
Fibroid Degeneration During Pregnancy
In women noted to have fibroids during pregnancy, clinical symptoms and
sonographic evidence of fibroid degeneration occur in about 5% (74). Among 113
women followed during pregnancy with serial sonography, 10 (9%) developed
anechoic spaces or coarse heterogeneous patterns consistent with fibroid
degeneration. Seven of 10 women had severe abdominal pain requiring
hospitalization, consistent with clinical symptoms of degeneration. No
sonographic changes were noted in the other 103 women, and only 11.7% had
similar abdominal pain. A small study of women with fibroid-associated pain
during pregnancy found use of ibuprofen shortened the hospital stay and
decreased the rate of readmission (75).
Influence of Fibroids on Pregnancy
Very rarely does the presence of a fibroid during pregnancy lead to an
unfavorable outcome. Research was conducted on large populations of pregnant
women examined with routine second trimester sonography with follow-up care
and delivery at the same institution (76,77). In a study of 12,600 pregnant women,
the outcomes of 167 women with fibroids were no different with regard to the
incidence of preterm delivery, premature rupture of membranes, fetal growth
restriction, placenta previa, placental abruption, postpartum hemorrhage, or
retained placenta (76). Cesarean section was more common among women with
fibroids (23% vs. 12%).
The other study of 15,104 pregnancies, including 401 women with fibroids,
found no increased risk of premature rupture of membranes, operative vaginal
delivery, chorioamnionitis, or endometritis (77). However, there were increased
risks of preterm delivery (19.2% vs. 12.7%), placenta previa (3.5% vs. 1.8%), and
postpartum hemorrhage (8.3% vs. 2.9%). Cesarean section was again more
common (49.1% vs. 21.4%). A small retrospective study found an association
between retroplacental fibroids and placental abruption; 8 of 14 women with
retroplacental fibroids developed abruption compared with 2 of 79 women
without retroplacental fibroids (78).
Fetal injury attributed to mechanical compression by fibroids is uncommon. A
search of the PubMed database from 1980 to 2010 revealed one case of fetal head
552anomalies with fetal growth restriction, one case of a postural deformity, one case
of a limb reduction, and one case of fetal head deformation with torticollis (79–
82).
Any decision to perform a myomectomy in order to prevent problems
during pregnancy should take into account the risks of surgery, anesthesia,
postoperative adhesions, and an increased likelihood of subsequent cesarean
delivery, along with concerns about discomfort, expense, and time away from
work or family.
Rupture of Myomectomy Scar During Pregnancy
Following abdominal myomectomy, uterine rupture during pregnancy
appears to be a rare event.
Trial of labor after myomectomy is associated with a 0.47% risk of uterine
rupture. Eleven studies that included 1,034 pregnancies and 756 viable (≥24
weeks) deliveries found 7 uterine ruptures after myomectomy (0.93%); the rate
was 0.47% (2/426) in women undergoing trial of labor after myomectomy and
1.52% (5/330) in women before the onset of labor. Five of the seven uterine
ruptures occurred before 36 weeks. Size, number, and positions of removed
fibroids or the type of myometrial closure was not available to determine specific
risk factors for rupture. The 0.47% rate of rupture for women with a trial of labor
after myomectomy is similar to the 0.5% to 1% risk of rupture for trial of labor
after previous cesarean delivery (83).
Operative techniques, instruments, and energy sources used during
laparoscopic myomectomy may differ from those employed during laparotomy. A
study of 19 published and unpublished cases of uterine rupture during pregnancy
following laparoscopic myomectomy found that almost all cases involved
deviations from standard surgical technique as described for abdominal
myomectomy (84). In 7 cases, the uterine defect was not repaired; in 3 cases it
was repaired with a single suture; in 4 cases it was repaired with only one layer of
suture; and in 1 case only the serosa was closed. In only 3 cases was a
multilayered closure employed. In 16 of the cases, monopolar or bipolar energy
was used for hemostasis.
Although definite conclusions and recommendations regarding appropriate
technique for laparoscopic myomectomy must await proper study of myometrial
wound healing, it appears prudent for surgeons to adhere to time-tested
techniques developed for abdominal myomectomy, including multilayered
closure of myometrium (for other than superficial uterine defects) and limited use
of electrosurgery for hemostasis. Even with ideal surgical technique, individual
wound-healing characteristics may predispose to uterine rupture.
553TREATMENT
The development of new treatments for fibroids is slow, perhaps because many
women with fibroids are asymptomatic, fibroids are benign, and mortality is very
low (84). If offered hysterectomy as a first, and sometimes only, treatment
option, some women choose to accommodate to symptoms and stop seeking
treatment. This may lead physicians to underestimate the true impact of the
condition, despite the fact that women who have hysterectomies as a result of
fibroid-related symptoms have significantly worse scores on SF-36 quality-of-life
questionnaires than women diagnosed with hypertension, heart disease, chronic
lung disease, or arthritis (40).
After an exhaustive review of the medical literature published between 1975
and 2000, with evaluation of 637 relevant articles and careful study of 200
articles, the authors found no satisfactory answers to fundamental questions about
fibroid treatments (86). Women and their physicians need information on which
to base decisions regarding possible treatments.
This section summarizes the literature regarding the management of fibroids.
Treatment options include observation, medical therapy, hysteroscopic
myomectomy, laparoscopic myomectomy, hysterectomy, UAE, and focused
ultrasound.
Watchful Waiting
Not having treatment for fibroids rarely results in harm, except for women
with severe anemia from fibroid-related heavy menstrual bleeding or
hydronephrosis from ureteric obstruction from a massively enlarged fibroid
uterus. Predicting future fibroid growth or onset of new symptoms is not possible
(84). During observation, the average fibroid volume increases 9% per year with a
range of −25% to +138% (87). A nonrandomized study of women with uterine
size 8 weeks or greater who chose watchful waiting found that 77% of women
had no significant changes in the self-reported amount of bleeding, pain, or
degree of bothersome symptoms at the end of 1 year (88). Furthermore, mental
health, general health, and activity indexes were also unchanged. Of the 106
women who initially chose watchful waiting, 23% opted for hysterectomy during
the course of the year.
[10] Therefore, for women who are mildly or moderately symptomatic with
fibroids, watchful waiting may allow treatment to be deferred, perhaps
indefinitely. [11] As women approach menopause, watchful waiting may be
considered, because there is limited time to develop new symptoms and after
menopause, bleeding stops and fibroids decrease in size (15). Although not
specifically studied, the incidence of hysterectomy for fibroids declines
554considerably after menopause, suggesting that there is a significant decline in
symptoms.
Medical Therapy
Nonsteroidal Anti-Inflammatory Medication
Nonsteroidal anti-inflammatory drugs (NSAIDs) were not shown to be
effective for the treatment of heavy menstrual bleeding in women with
fibroids. A placebo-controlled, double-blind study of 25 women with
menorrhagia, 11 of whom had fibroids, found a 36% decrease in blood loss
among women with idiopathic heavy menstrual bleeding, but no decrease in
women with fibroids. No other studies examined this treatment (89).
Tranexamic Acid
Tranexamic acid is a synthetic antifibrinolytic medication which can be used for
the management of menorrhagia at a dosage of 1.3 g, three times a day for 3 to 5
days during menstrual bleeds. A pooled analysis of two randomized, doubleblind, placebo-controlled, parallel-group studies of women with heavy menstrual
bleeding and fibroids found mean menstrual blood loss was significantly (p
<0.001) reduced compared with placebo maintained across three treatment cycles
(90). Adverse events included headache (55%) and nausea (15%). The results of
this analysis may not be generalizable to women with markedly enlarged fibroids
that require surgical management.
Gonadotropin-Releasing Hormone Agonists
Treatment with GnRH-a decreases uterine volume, fibroid volume, and bleeding.
The benefits of GnRH-a are limited by side effects and risks associated with longterm use (91,92). Monthly GnRH-a given for 6 months reduced fibroid volume by
30% and total uterine volume by 35% (91). Reduction in the uterine size occurs
mostly within the first 3 months of treatment (92). Heavy menstrual bleeding
responds well to GnRH-a; 37 of 38 women had resolution by 6 months.
Following discontinuation of GnRH-a, menses returns in 4 to 8 weeks and uterine
size returns to pretreatment levels within 4 to 6 months (93). In this study 64% of
women remained asymptomatic 8 to 12 months after treatment.
Side effects occur in 95% of women treated with GnRH-a (89). Seventy-eight
percent experience hot flushes, 32% vaginal dryness, and 55% have transient
frontal headaches. During 6 months of treatment only 8% of women discontinued
GnRH-a because of the side effects. Arthralgia, myalgia, insomnia, edema,
emotional lability, depression, and decreased libido are reported. The
hypoestrogenic state induced by GnRH-a causes significant bone loss after 6
555months of therapy (94).
In an effort to reduce side effects, inhibit bone loss, and allow long-term use of
GnRH-a, low doses of estrogen and progestins may be added while continuing
GnRH-a. A study of long-term use of GnRH-a over 6 years found a wide range of
reduction in bone density among women and no difference in bone loss between
groups given estrogen and progestin versus those treated with GnRH-a alone
(95).
Gonadotropin-Releasing Hormone Agonist as Temporary Treatment for
Perimenopausal Women
Women in late perimenopause who are symptomatic from uterine fibroids may
consider short-term use of GnRH-a. Thirty-four perimenopausal women with
symptomatic fibroids were treated with GnRH-a for 6 months, 12 of whom
required repeat treatment 6 months after discontinuation of the medication (96);
31 women avoided surgery; 15 women went into natural menopause. Although
not specifically studied, add-back therapy might be considered in this setting.
Gonadotropin-Releasing Hormone Antagonist
The immediate suppression of endogenous GnRH by daily subcutaneous injection
of the GnRH antagonist ganirelix results in a 29% reduction in fibroid volume
within 3 weeks (97). Treatment is accompanied by hypoestrogenic symptoms.
When long-acting compounds are available, a GnRH antagonist might be
considered for medical treatment prior to surgery.
Progesterone-Mediated Medical Treatment
The reduction in uterine size following treatment with the progesterone-blocking
drug mifepristone is similar to that found with GnRH-a (98). A prospective,
randomized controlled trial of mifepristone treatment found a 48% decrease in the
mean uterine volume after 6 months (99). Mifepristone blocks progesterone, and
the unopposed exposure of the endometrium to estrogen may lead to endometrial
hyperplasia. A systematic review found endometrial hyperplasia in 10 of 36
(28%) women screened with endometrial biopsies (100).
Ulipristal Acetate
Ulipristal acetate (UPA) is a selective progesterone receptor modulator with pure
antagonist activity. UPA modulates the progesterone signaling pathway and
promotes remodeling of the extracellular matrix and reduction of collagen
synthesis. UPA is effective for controlling bleeding and reducing the size of
fibroids, while increasing the quality of life. The largest study included 451
women with symptomatic uterine fibroids, uterine size less than 16 weeks, and
556heavy menstrual bleeding (101). Women received four repeated 12-week
treatment courses of daily UPA, 5 or 10 mg, given orally. Both doses led to
amenorrhea, usually within 1 week, in ≥70% of women and bleeding was
controlled in ≥73%. Hemoglobin levels increased over the first two treatment
courses and were maintained during follow-up.
By the fourth treatment course, approximately 80% of women had more than
25% reduction in the volume of the three largest fibroids. Patients had significant
improvement in pain and quality of life and reached scores reported for healthy
individuals. Six cases of hyperplasia were observed, all of which returned to
normal endometrium during the study.
Adverse events included headache and hot flushes in 11% of women, almost all
of which were mild or moderate. Levels of E2 remained well above
postmenopausal levels, suggesting that bone mineral density will not be adversely
affected by ulipristal.
Progesterone-Releasing Intrauterine Device
The levonorgestrel-releasing intrauterine system (LNG-IUS) may be a
reasonable treatment for selected women with fibroid-associated heavy
menstrual bleeding.
Evidence from a systematic review of 11 studies of premenopausal women
with uterine fibroids using LNG-IUS concluded that they significantly reduced
menstrual blood loss and increased hemoglobin and ferritin levels, but did not
decrease the fibroid volume. Device expulsion rates were 15.4% with fibroids
larger than 3 cm, but only 6.3% with fibroids smaller than 3 cm and unrelated to
fibroid location (102).
Alternative Medicine Treatment
A nonrandomized, nonblinded study compared fibroid growth in 37 women
treated with Chinese medicine, body therapy, and guided imagery to 37 controls
treated with NSAIDs, progestins, or oral contraceptive pills (103). After 6
months, sonographic evaluation demonstrated that fibroids stopped growing or
shrank in 22 of 37 (59%) women treated with Chinese medicine compared to 3 of
37 (8%) controls. Although symptoms responded equally well in both groups,
satisfaction was higher in the Chinese medicine group. Participants actively
sought alternative therapy and assessment of satisfaction may reflect selection
bias.
An uncontrolled study reported treatment of 110 women with fibroids smaller
than 10 cm with the Chinese herbal medicine kuei-chih-fu-ling-wan for at least 12
weeks (104). Clinical and sonographic evaluation found complete resolution of
fibroids in 19% of women, a decrease in size in 43%, no change in 34%, and an
557increase in 4%. Heavy menstrual bleeding improved in 60 of 63 (95%) women
and dysmenorrhea improved in 48 of 51 (94%). Fifteen of the 110 (14%) women
chose to have a hysterectomy during the 4 years of the study.
SURGICAL TREATMENT OPTIONS
[12] Surgical treatment options include abdominal myomectomy,
laparoscopic myomectomy, laparoscopic radiofrequency ablation,
hysteroscopic myomectomy, endometrial ablation, and abdominal, vaginal,
or laparoscopic hysterectomy.
Serious medical conditions, such as severe anemia or ureteral obstruction,
often need to be addressed surgically. Pain from fibroid degeneration is usually
successfully treated with analgesics until symptoms resolve, but if severe the
patient may opt for surgery. Torsion of a pedunculated subserosal fibroid may
produce acute pain that requires surgical intervention. Surgical intervention may
be indicated in women with fibroids associated with heavy menstrual bleeding,
pelvic pain or pressure, urinary frequency, or incontinence that compromises the
quality of life (105).
Abdominal myomectomy was long employed as a conservative treatment for
uterine fibroids, and much of the literature predates the use of prospective,
randomized controlled trials. Although myomectomy is stated to relieve
symptoms in 80% of women, there is scant literature documenting its efficacy and
many large series have not reported data for relief of symptoms following surgery
(105–107). A prospective, nonrandomized study comparing myomectomy with
UAE did report that 75% of women in the myomectomy group had a significant
decrease in symptom scores after 6 months (108).
Back pain may, on occasion, be related to the presence of fibroids, but other
possible causes should be considered. [13] Inability to evaluate the ovaries on
pelvic examination is not an indication for surgery (109). There is no evidence
that pelvic examination increases early detection or decreases the mortality
related to ovarian cancer, and sonography can be used to evaluate the adnexa
should symptoms develop. Recent evidence that most serous “ovarian” cancers
have a tubal origin makes early sonographic diagnosis particularly unlikely.
Treating Preoperative Anemia
In women with significant preoperative anemia, intravenous iron infusions,
epoetin, and GnRH agonists have been used to increase hemoglobin levels. A
randomized study of women with heavy menstrual bleeding and Hb levels <9.0
g/dL who were scheduled to have surgery received iron either intravenously
(based on the calculated total iron deficit, 3 times a week for 3 weeks) or orally
558(80 mg/day of oral iron protein succinylate daily). The mean increase in
hemoglobin was higher in the intravenous iron group than the oral group (3.0 vs.
0.8 g/dL) and there were no severe adverse events in either group (110). A
randomized study showed that the use of epoetin, a recombinant form of
erythropoietin, 250 IU/kg (approximately 15,000 U) per week for 3 weeks prior to
elective surgery increased hemoglobin concentrations by 1.6 g/dL and
significantly reduced transfusion rates when compared to controls (111). GnRH-a
may be used preoperatively to stop abnormal bleeding, with a resultant increase of
hemoglobin concentration. One study of women with fibroids and mean
hemoglobin concentrations of 10.2 g who were randomized to GnRH-a plus oral
iron or placebo plus oral iron found that after 12 weeks, 74% of the women
treated with GnRH-a and iron had hemoglobin greater than 12 g compared with
46% of the women treated with only iron (112).
Abdominal Myomectomy
[14] Myomectomy should be considered a safe alternative to hysterectomy.
Victor Bonney, an early advocate of abdominal myomectomy, stated in 1931 that
“The restoration and maintenance of physiologic function is, or should be, the
ultimate goal of surgical treatment.”
Case-controlled studies suggest that there may be less risk of intraoperative
injury with myomectomy when compared with hysterectomy (113). A
retrospective review of 197 women who had myomectomies and 197 women who
underwent hysterectomies with similar uterine size (14 vs. 15 weeks) found
operating times were longer in the myomectomy group (200 vs. 175 minutes), but
estimated blood loss was greater in the hysterectomy group (227 vs. 484 mL)
(113). The risks of hemorrhage, febrile morbidity, unintended surgical procedure,
life-threatening events, and rehospitalization were no different between groups.
However, 26 (13%) women in the hysterectomy group suffered complications,
including 1 woman with bladder injury, 1 with ureteral injury, 3 bowel injuries, 8
with ileus, and 6 with pelvic abscesses. In contrast, complications occurred in 11
(5%) of the myomectomy patients, including 1 woman with bladder injury, 2 with
reoperation for small bowel obstruction, and 6 with ileus.
Hysterectomy, without oophorectomy, may have a more lasting adverse effect
on ovarian reserve than myomectomy. Serum AMH was significantly lower 3
months following hysterectomy compared with the preoperative level. Following
myomectomy, serum AMH was similar to the preoperative level 3 months after
surgery (114).
Myomectomy may be considered even for those women who have large
uterine fibroids and wish to retain their uterus. A study of 91 women with
uterine size larger than 16 cm (range 16 to 36 cm) reported 1 bowel injury, 1
559bladder injury, and 1 reoperation for bowel obstruction, but no women had
conversion to hysterectomy (115). The cell saver, which is a device used to
collect blood intraoperatively and reinfuse, was used in 70 women, and only 7
required homologous blood transfusion. A retrospective cohort study by Iverson
et al. compared 89 women having abdominal hysterectomy for fibroids (mean
uterine size 15 cm) to abdominal myomectomy in 103 women (mean uterine size
12 cm) (116). Although selection bias was likely, the hysterectomy group
suffered two ureteral, one bladder, one bowel, and one nerve injury and two
reoperations for bowel obstruction, while there were no visceral injuries in the
myomectomy group. A review of 6 observational studies, which included the
patients from the Iverson study, found that among the 1,520 women with uterine
size up to 18 weeks, there was no difference in morbidity between those having
an abdominal myomectomy compared with those having an abdominal
hysterectomy (117).
Cesarean Section and Concurrent Myomectomy
In carefully selected women, myomectomy may be safely accomplished at the
time of cesarean section by experienced surgeons. One series reported 25
women with removal of 84 fibroids (2 to 10 cm) at the time of cesarean section
without the need for cesarean hysterectomy (118). Estimated blood loss was 876
mL (range 400 to 1,700 mL) and 5 women required blood transfusion. Another
study compared 111 women who had myomectomy at the time of cesarean
section with 257 women with fibroids who were not subjected to myomectomy
during cesarean section (119). Only one of the women in the myomectomy group
required transfusion and none required hysterectomy or embolization. There were
no differences in mean operative times, incidence of fever, or length of hospital
stay between the two groups. Although the cases were likely selected carefully,
the authors concluded that, in experienced hands, myomectomy might be safely
performed in selected women during cesarean section.
Surgical Technique for Abdominal Myomectomy
Managing Blood Loss
Available surgical techniques allow safe removal of even large fibroids.
Tourniquets or vasoconstrictive agents may be used to limit blood loss.
Vasopressin, an antidiuretic hormone, causes constriction of smooth muscle in the
walls of capillaries, small arterioles, and venules.
Significant reductions in blood loss during myomectomy have been found in
several interventions: vaginal misoprostol (−98 mL); intramyometrial vasopressin
(−246 mL); intravenous tranexamic acid (−243 mL); a Foley catheter secured
560around the cervix (−240 mL), and a polyglactin suture placed around both the
cervix and infundibulopelvic ligaments (−1,870 mL) (120). A significant
reduction in the need for blood transfusion has been shown while using
vasopressin and tourniquets, but not for misoprostol or tranexamic acid. There are
no data regarding whether the combined use of any of these measures decreases
blood loss more effectively than individual measures.
Care should be taken to avoid intravascular injection of vasopressin and
resultant cardiovascular collapse. Nonetheless, cardiovascular complications have
been reported following intramyometrial injection. The maximal safe dose of
vasopressin is not well established, but less than 5 units in total is suggested. The
half-life of intramuscular vasopressin is 10 to 20 minutes, with a duration of
action of 2 to 8 hours. Loss of peripheral pulses and nonmeasurable arterial blood
pressure following vasopressin injection have been attributed to cardiovascular
collapse or hypotension. Severe peripheral arterial vasospasm and elevated
proximal blood pressure may occasionally occur with high-dose vasopressin and
should be considered before administering additional vasopressors (121). The use
of vasopressin to decrease blood loss during myomectomy is an off-label use of
this drug.
Cell savers may be considered for use during myomectomy. Use of the cell
saver avoids the risks of infection and transfusion reaction, the oxygen transport
capacity of salvaged red blood cells is equal to or better than stored allogeneic red
cells, and the survival of red blood cells appears to be at least as good as
transfused allogeneic red cells (122). The device suctions blood from the
operative field, mixes it with heparinized saline, and stores the blood in a canister.
If the patient requires blood reinfusion, the stored blood is washed with saline,
filtered, centrifuged to a hematocrit of approximately 50%, and given back to the
patient intravenously. Consequently, the need for preoperative autologous blood
donation or heterologous blood transfusion often can be avoided (123). In a study
of 92 women who had myomectomy for uterine size greater than 16 cm the cell
saver was used for 70 women with a mean volume of reinfused packed red blood
cells of 355 mL (124).
The cost of using a cell saver compared with donation of autologous blood was
not studied for abdominal myomectomy. However, economic models suggest it is
cost effective (124). Most hospitals charge a minimal fee for having the cell saver
available “on-call” and charge an additional fee if it is used. Assuming that most
women who donate autologous blood prior to myomectomy do not require blood
transfusion, availability of the cell saver should spare many women the time and
expense of donating, storing, and processing autologous blood. For a cohort of
women, the cost of using the cell saver should, therefore, be significantly lower
than the cost of autologous blood.
561When heavy bleeding is anticipated or if copious bleeding is encountered,
ligation of both uterine arteries can be performed (125). UAE was used
successfully to control bleeding at the time of, or following, myomectomy (126).
Because the uterine arteries recannulate, future fertility should not be
compromised. These techniques often obviate the need for hysterectomy.
Uterine incisions can be made either vertically or transversely, because fibroids
distort normal vascular architecture, making attempts to avoid the arcuate vessels
impossible (127). Careful planning and placement of uterine incisions can
avoid inadvertent extension of the incision to the uterine cornua or ascending
uterine vessels.
Based on vascular corrosion casting and examination by electron microscopy,
fibroids are completely surrounded by a dense blood supply and no distinct
vascular pedicle exists at the base of the fibroid (Fig. 11-4) (128). Extending the
uterine incisions through the myometrium and entire pseudocapsule until the
fibroid is clearly distinguished identifies a less vascular surgical plane, which is
deeper than commonly recognized.
FIGURE 11-4 Corrosion casting of fibroid vessels.
562Limiting the number of uterine incisions has been suggested in order to reduce
the risk of adhesions to the uterine serosa (129). However, in this manner tunnels
must be created within the myometrium in order to extract distant fibroids,
making hemostasis more difficult within these defects. Hemostasis is important in
order to avoid adhesion formation, and fibrin, leucocytes, and platelets in the
presence of erythrocytes leads to adhesion formation. If tunneling incisions are
avoided and hemostasis secured immediately, the risk of adhesion formation
should be lessened. Therefore, if incisions are made directly over the fibroids and
only those fibroids that are easily accessed are removed, the defects can be
promptly closed and hemostasis can be secured immediately (115). Multiple
uterine incisions may be needed, but adhesion barriers may help limit adhesion
formation (130).
Laparoscopic Myomectomy
Available instruments make laparoscopic myomectomy feasible, although the size
and number of fibroids reasonably removed limits the wide application of this
approach because of the technical difficulty of the procedure and laparoscopic
suturing (131). Although microprocessor-assisted myomectomy (robotic) may
obviate some of these technical problems, the added cost and longer operating
times associated with this approach must be considered (see Chapter 28).
A systematic review of randomized controlled trials of laparoscopic versus
open myomectomy included six studies with a total of 576 patients (132).
Laparoscopic myomectomy was associated with longer operating times but
reduced operative blood loss, less postoperative decline in hemoglobin levels,
reduced postoperative pain, more patients fully recuperated at day 15, and fewer
overall complications. Major complications, pregnancy rates, and new appearance
of fibroids were comparable in the two groups.
Case series without controls show the feasibility of laparoscopic surgery in
women with large fibroids. In a series of 144 women with mean fibroid diameter
of 7.8 cm (range, 5 to 18 cm), only 2 women required conversion to laparotomy
(133). In another series of 332 consecutive women undergoing laparoscopic
myomectomy for symptomatic fibroids as large as 15 cm, only 3 women required
conversion to laparotomy (134).
Surgical Technique for Laparoscopic Myomectomy
Port placement should be based on the position and size of the fibroids to be
removed (Fig. 11-5). Laparoscopic suturing may be more ergonomic if there are
two ports on either the patient’s right side for right-handed surgeons or left side
for left-handed surgeons; a 12-mm port about 2 cm medial to the iliac crest for
563suture access, and another 5-mm lateral port near the level of the umbilicus (135).
A left upper quadrant approach may be used for initial access when the uterine
size is near or above the umbilicus (136).
564565566567568569FIGURE 11-5 Laparoscopic myomectomy. A: A 7-cm, posterior intramural fibroid. B:
Transverse incision through myometrium until fibroid reached. C: Traction on fibroid and
countertraction on myometrium to tease fibroid away from myometrium. D: Adherent
attachments to myometrium are cut. E: Minimal use of bipolar electrosurgery to control
larger vessels. F: Three-layer suture closure of myometrium. G: Morcellator used to
remove fibroid from abdominal cavity. H: Pelvis irrigated and suctioned. I: Adhesion
barrier placed over uterine incision.
Vasopressin is injected into the fibroid. An incision is made directly over the
fibroid and carried deeply until definite fibroid tissue and the avascular surgical
plane is noted. Transverse incisions permit more ergonomic suturing. The fibroid
is grasped with a tenaculum for traction and the plane between the myometrium
and fibroid is dissected until the fibroid is free. Bleeding vessels in the
myometrial defect are desiccated sparingly with bipolar electrosurgical paddles,
taking care not to devascularize the myometrium and interfere with wound
healing. Delayed absorbable sutures are placed in one, two, or three layers, as
needed, adhering to accepted surgical technique at laparotomy. Morcellation of
the fibroid with an electromechanical device is accomplished under direct vision.
The pelvis and abdomen are irrigated, the fluid suctioned, and an adhesion barrier
may be placed.
Tissue Morcellation
Morcellation describes a surgical method of dividing tissue into small sections in
order to allow the tissue to be removed from the abdomen or vagina. With
laparoscopic myomectomy, morcellation is usually necessary through the vagina,
a Mini-laparotomy incision or electromechanical morcellation passed through a
laparoscopic port incision. Morcellation allows many women the benefits of
minimally invasive surgery: lower mortality rates, fewer intraoperative and
postoperative complications, less postoperative pain with less need for narcotic
pain medication, shorter hospital stays, and faster return to work and family.
Morcellation should not be performed in the presence of known or suspected
uterine or cervical malignancy. Ultrasound or MRI findings of a large irregular
vascular mass, often with irregular anechoic (cystic) areas reflecting necrosis or
enhancement of uterine masses on MRI with gadolinium imaged in the arterial
phase, should raise suspicion of LMS.
There is no evidence that the type of morcellation, electromechanical or
scalpel, alters survival for women with LMS. Analysis of 16 studies that included
196 women with sarcomas reported no significant difference in 5-year survival
rates between women having electromechanical morcellation, scalpel
570morcellation, or no tissue morcellation (137). Importantly, laparoscopic-aided
morcellation allows the surgeon to inspect the pelvic and abdominal cavities,
remove tissue fragments, and copiously irrigate and suction under visual control.
In contrast, the possibility of retained tissue fragments is greater with vaginal or
mini-laparotomy morcellation procedures because the surgeon cannot visually
inspect the peritoneal cavity.
Laparoscopic Radiofrequency Thermal Ablation
Laparoscopic ultrasound–guided radiofrequency ablation of uterine fibroids can
be accomplished via a hand piece coupled to a radiofrequency generator. HealthRelated Quality of Life (HRQL) scores showed improvement at 3 months, which
was maintained at 36 months. Fourteen of 135 (11%) women required another
treatment intervention for fibroid-related symptoms over 3 years of follow-up
(138). Larger studies will be needed to assess the effectiveness of this treatment.
Adhesions Following Myomectomy
Adhesion formation after myomectomy is well documented (139). A Cochrane
review found that Interceed reduced the incidence of adhesion formation, both de
novo and reformation, at laparoscopy and laparotomy (140). Data were
insufficient to support its use to improve pregnancy rates. There was limited
evidence of effectiveness of Seprafilm (Genzyme, Cambridge, MA) in preventing
adhesion formation in a prospective study that randomized 127 women
undergoing abdominal myomectomy to treatment or no treatment with Seprafilm
(130). During second-look laparoscopy, women treated with Seprafilm had
significantly fewer adhesions and lower adhesion severity scores than untreated
women. This study and others found an increased incidence of adhesions with
posterior uterine incisions compared to anterior incisions (141).
Hysteroscopic Myomectomy
[15] Submucous fibroids, sometimes associated with increased menstrual
bleeding or infertility, often can be removed hysteroscopically. Classification
of submucous fibroids is based on the degree of the fibroid within the cavity;
class 0 fibroids are intracavitary; class I have 50% or more of the fibroid within
the cavity; and class II have less than 50% of the fibroid within the cavity (Fig.
11-6) (55). A meta-analysis of the effect of fibroids on fertility found that
submucous fibroids with distortion of the uterine cavity decreased ongoing
pregnancy/live birth rates by 70% (RR 0.32; 95% CI, 0.12–0.850) and resection
increased ongoing pregnancy/live birth rates (RR 1.13; 95% CI, 0.96–1.33) (68).
571FIGURE 11-6 Fibroid classification. (From Munro MG, Critchley HO, Broder MS, et
al; FIGO Working Group on Menstrual Disorders. FIGO classification system [PALMCOEIN] for causes of abnormal uterine bleeding in nongravid women of reproductive age.
Int J Gynaecol Obstet 2011;113:3–13.)
No meta-analysis of the association of submucous fibroids and abnormal
uterine bleeding was performed. However, most studies show a reduction in
bleeding following resection. Using pictorial assessment to estimate menstrual
blood loss prior to and for 41 months following hysteroscopic resection of
submucous fibroids, a significant decrease in bleeding was reported in 42 of 51
(82%) women with submucous pedunculated (type 0), 24 of 28 (86%) with sessile
(type 1), and 15 of 22 (68%) with intramural fibroids (type 2) (143). A study of
285 consecutive women with heavy menstrual bleeding or irregular menstrual
bleeding who had hysteroscopic resection of submucous fibroid(s) found that
572additional surgery was required for 9.5% at 2 years, 10.8% at 5 years, and 26.7%
at 8 years (144).
Surgical Technique for Hysteroscopic Myomectomy
Hysteroscopic resection of a submucous fibroid can be accomplished under
visual control using a telescope and continuous flow of distension fluid
through the uterine cavity. The electrosurgical working element uses monopolar
or bipolar electrodes. Monopolar electrodes require nonconducting distending
solution (sorbitol 5%, sorbitol 3% with mannitol 0.5%, or glycine 1.5%), while
bipolar electrodes can be used with saline.
Cervical dilation is usually required prior to insertion of the hysteroscope.
Cytotec may facilitate easier dilation (145). The cutting loop is passed beyond the
fibroid and cutting activated only when the loop is moving toward the surgeon
and in direct view. Fibroids should be resected down to the level of the
surrounding myometrium and, if fertility is desired, care should be taken to avoid
excessive thermal damage to normal myometrium. Often, the remaining portion
of the fibroid will be expressed into the uterine cavity by uterine contractions,
allowing further resection. Fragments of fibroid are removed from the cavity with
a grasping forceps or by capturing the fragments with the loop and extracting the
telescope. G0 and G1 fibroids as large as 5 cm may be resected hysteroscopically.
G2 fibroids require careful preoperative evaluation with SIS or MRI to gauge
the thickness of normal myometrium between the fibroid and the serosa in order
to assess the potential risk of uterine perforation with the loop electrode. The risk
of perforation increases with deeper myometrial involvement of the fibroid (146).
In some cases, repeat resection may be required after a few weeks, as the
remaining portion of the fibroid is expressed into the uterine cavity by uterine
contractions.
Hysteroscopic Tissue Removal systems (HTRs) using intrauterine morcellation
in physiologic saline solution for distension and irrigation, have been developed
for the management of polyps and submucous fibroids. A systematic review of 8
studies included 283 women who underwent intrauterine morcellation of
submucous fibroids (147). A deficit of 2,500 mL of isotonic solution is well
tolerated by healthy women and no significant intra- or postoperative
complications were reported. Complete resection rates were comparable to
resectoscopic surgery. There was no significant difference in postoperative
hemoglobin levels or patient satisfaction between the resection group compared
with HTRs at 3-month follow-up. Uterine Fibroid Symptom-Quality of Life and
Health-Related Quality of Life scores improved significantly 12 months after
myomectomy using HTRs. As is true with resectoscopic surgery, type 0 and 1
submucous fibroids were found to be easier to manage than type 2.
573Procedure-Specific Risks
Cervical dilatation or insertion of the hysteroscope can cause uterine perforation,
as can deep myometrial resection. Often the first sign of perforation is a rapid
increase in the fluid deficit. Careful inspection of the uterine cavity should be
undertaken to look for brisk bleeding or bowel injury. If no injury is apparent, the
procedure should be terminated and the patient should be observed and may be
discharged if stable (148). If a perforation occurs during activation of the
electrode, then laparoscopy should be performed to carefully inspect for bowel or
bladder injury.
Fluid Absorption and Electrolyte Imbalance
Intravascular absorption of distending media is a potentially dangerous
complication that can result in pulmonary edema, hyponatremia, heart
failure, cerebral edema, and death (149). Careful monitoring of the fluid deficit
is important and a fluid deficit of 750 mL during surgery should serve as a
warning sign, with planned termination of the procedure. Many authors suggest
termination of the procedure when the fluid deficit exceeds 1,000 mL,
although other guidelines suggest termination after introduction of 1,500 mL
of a nonelectrolyte solution or 2,500 mL of an electrolyte solution (149).
Electrolytes should be assessed and corrected if necessary and diuretics
considered. Risk factors for fluid overload include resection of fibroids with deep
intramural extension or prolonged operating time. The use of normal saline
combined with bipolar energy reduces the risk of hyponatremia, but a fluid deficit
over 1,500 mL can lead to cardiac overload (150).
Endometrial Ablation for Abnormal Bleeding Associated With Fibroids
In selected women not desiring future childbearing, endometrial ablation with or
without hysteroscopic myomectomy may be efficacious. Pad counts following
ablation with or without fibroid resection found that 48 of 51 (94%) women had
resolution of abnormal bleeding after a mean follow-up of 2 years (range, 1 to 5
years) (151). A study of 62 women followed for an average of 29 months (range,
12 to 60 months) found that 74% of the women had hypomenorrhea or
amenorrhea, and only 12% required a hysterectomy (152).
Hydrothermal ablation was used to treat 22 women with known submucous
fibroids up to 4 cm, with 91% reporting amenorrhea, hypomenorrhea, or
eumenorrhea after a minimum of 12 months’ follow-up (153). In a study of 65
women with menometrorrhagia and type 1 or 2 submucous myomas up to 3 cm,
after treatment with NovaSure endometrial ablation device (Hologic, Bedford,
MA), normal bleeding or amenorrhea was observed in most women at 1 year
574(154).
NEW APPEARANCE OF FIBROIDS
Although new fibroids may sometimes develop following myomectomy, most
women will not require additional treatment. If the first surgery is performed
in the presence of a single fibroid, only 11% of women will need subsequent
surgery (155). If multiple fibroids are removed during the initial surgery, only
26% will need subsequent surgery (mean follow-up 7.6 years). Individual
fibroids, once removed, do not grow back. Fibroids detected after myomectomy,
often referred to as “recurrence,” result either from failure to remove fibroids at
the time of surgery or are newly developed fibroids. Perhaps this circumstance is
best designated “new appearance” of fibroids (156).
Sonography found that 29% of women had persistent fibroids 6 months after
myomectomy (157). In addition, the background formation of new fibroids in the
general population should be considered. A hysterectomy study found fibroids in
77% of specimens from women who did not have a preoperative diagnosis of
fibroids (4).
Incomplete follow-up, insufficient length of follow-up, the use of either
transabdominal or transvaginal sonography (with different sensitivity), detection
of very small clinically insignificant fibroids, or use of calculations other than
life-table analysis confound many studies of new fibroid appearance (158).
Clinical Follow-Up
Self-reported diagnosis based on symptom questionnaires has reasonably good
correlation with sonographic or pathologic confirmation of significant fibroids
and may be the most appropriate method of gauging clinical evidence of new
appearance (18). One study of 622 patients aged 22 to 44 at the time of surgery
and followed over 14 years found the cumulative new appearance rate based on
clinical examination and confirmed by ultrasound was 27% (Fig. 11-7) (159). An
excellent review of life-table analysis studies found a cumulative risk of clinically
significant new appearance of 10% 5 years after abdominal myomectomy (160).
575FIGURE 11-7 Overall 10-year new appearance after initial myomectomy. (From
Candiani G, Fedele L, Parazzini F, et al. Risk of recurrence after myomectomy. Br J
Obstet Gynecol 1991;98:385–389.)
Sonographic Follow-Up
[16] Routine ultrasound follow-up is sensitive but detects many clinically
insignificant fibroids. One hundred forty-five women, with mean age 38
(ranging from 21 to 52), were followed after abdominal myomectomy with
clinical evaluation every 12 months and TVS at 24 and 60 months (sooner, with
clinical suspicion of new fibroids) (157). No lower size limit was used for the
sonographic diagnosis of fibroids and, thus, the cumulative probability of new
appearance was 51% at 5 years. A study of 40 women who had a normal
sonogram 2 weeks following abdominal myomectomy found that the cumulative
risk of sonographically detected new fibroids larger than 2 cm was 15% over 3
years (161).
Need for Subsequent Surgery
Meaningful information for a woman considering treatment for her fibroids is the
approximate risk of developing symptoms that would require yet additional
treatment. A study of 125 women followed by symptoms and clinical examination
after a first abdominal myomectomy found that a second surgery was required
during the follow-up period (average 7.6 years) for 11% of women who had one
fibroid removed initially and for 26% of women who had multiple fibroids
removed (155). Crude rates of hysterectomy after myomectomy vary from 4% to
16% over 5 years (162,163).
576Prognostic Factors Related to New Appearance of Fibroids
Age
Given that the incidence of fibroids increases with increasing age, 4 per 1,000
woman-years for 25 to 29 year olds and 22 per 1,000 for 40 to 44 year olds, new
fibroids would be expected to form as age increases, even following
myomectomy (13).
Subsequent Childbearing
The 10-year clinical new appearance rate for women who subsequently gave birth
was 16%, but for those women who did not the rate was 28% (159).
Number of Fibroids Initially Removed
After at least 5 years of follow-up, 27% of women who initially had a single
fibroid removed had clinically detected new fibroids and 59% of women with
multiple fibroids initially removed had new fibroids (151).
Gonadotropin-Releasing Hormone Agonists
Preoperative treatment with GnRH-a decreases fibroid volume and may make
smaller fibroids harder to identify during surgery. A randomized study found that
3 months following abdominal myomectomy, 5 (63%) of 8 women in the GnRH
group had fibroids less than 1.5 cm detected sonographically, while only 2 of 16
(13%) untreated women had small fibroids detected (157).
Laparoscopic Myomectomy
New appearance of fibroids is not more common following laparoscopic
myomectomy when compared with abdominal myomectomy. Eighty-one
women randomized to either laparoscopic or abdominal myomectomy were
followed with TVS every 6 months for at least 40 months (164). Fibroids larger
than 1 cm were detected in 27% of women following laparoscopic myomectomy
compared to 23% in the abdominal myomectomy group, and no woman in either
group required any further intervention.
UTERINE ARTERY EMBOLIZATION
[17] Uterine artery embolization (UAE) is an effective treatment for selected
women with uterine fibroids. The effects of UAE on early ovarian failure,
fertility, and pregnancy are unclear. Therefore, many interventional
radiologists advise against the procedure for women considering future fertility.
Appropriate candidates for UAE include women who have sufficiently
577bothersome symptoms to warrant hysterectomy or myomectomy. Although
extremely rare, complications of UAE may necessitate life-saving hysterectomy,
and women who would not accept hysterectomy, even for life-threatening
complications, should not undergo UAE. Contraindications to treatment of
fibroids with UAE include women with active genital infection, genital tract
malignancy, diminished immune status, severe vascular disease limiting access to
the uterine arteries, contrast allergy, or impaired renal function (165). UAE
outcomes are well studied and documented.
Fibroid and uterine volume decreased significantly and consistently following
UAE and reports from the EMMY trial confirmed that fibroid and uterine volume
reductions persisted up to 5 years after UAE (61). However, 28% of women
underwent subsequent hysterectomy. Other studies, with length of follow-up
ranging from 6 to 60 months, reported the need for subsequent treatment:
hysterectomy in 17.5%, myomectomy in 8.8%, repeat embolization in 6.3%, IUD
placement in 8%, medical therapy in 6.7%, and endometrial ablation in 1.2%.
Decline in bleeding and/or pain were reported in most RCTs. Major procedurerelated complication rates ranged from 1.2% to 6.9%.
A Cochrane review found no difference between UAE and myomectomy or
hysterectomy in the risk of major complications, but UAE was associated with a
higher rate of minor complications (166). UAE had an increased likelihood of
requiring surgical intervention within 2 to 5 years of the initial procedure. One
small study found that myomectomy was associated with better fertility outcomes
than UAE. Patient satisfaction rates at up to 5 years following UAE versus
myomectomy or hysterectomy found no difference between the interventions.
The American College of Obstetricians and Gynecologists recommends
that women considering UAE have a thorough evaluation with a gynecologist
to help facilitate collaboration with the interventional radiologist and that
responsibility of caring for the patient be clear (168).
Uterine Artery Embolization Technique
Percutaneous cannulation of the femoral artery is performed by a properly trained
and experienced interventional radiologist (Fig. 11-8) (169). Embolization of the
uterine artery and its branches is accomplished by injecting gelatin sponges,
polyvinyl alcohol particles (PVA), or tris-acryl gelatin microspheres via the
catheter until occlusion, or slow flow, is documented. Total radiation exposure
(approximately 15 cGy) is comparable to one or two computed tomography scans
or barium enemas (170).
578579580FIGURE 11-8 A–C: UAE techniques. A: A catheter is threaded to the uterine arteries and
embolic material injected to block off blood flow to the uterus. B: Contrast dye shows the
vessels supplying the fibroid prior to UAE. C: Following UAE, embolic material blocks
blood flow to the fibroid.
Tissue hypoxia secondary to UAE causes postprocedural pain that usually
requires pain management in the hospital for 1 day. NSAID medications are
usually taken for 1 to 2 weeks, and many women return to normal activity within
1 to 3 weeks. Approximately 5% to 10% of women have pain for longer than 2
weeks (170). Ten percent of women require readmission to the hospital for
postembolization syndrome, characterized by diffuse abdominal pain, nausea,
vomiting, low-grade fever, malaise, anorexia, and leukocytosis. Treatment with
intravenous fluids, NSAID medications, and pain management usually leads to
resolution of symptoms within 2 to 3 days (170). Persistent fever should be
managed with antibiotics. Failure to respond to antibiotics may indicate
sepsis, which needs to be aggressively managed with hysterectomy.
Uterine Artery Embolization Outcomes
The largest prospective study reported to date includes 555 women aged 18 to 59
(mean, 43), 80% of whom had heavy bleeding, 75% had pelvic pain, 73% had
urinary frequency or urgency, and 40% of women had required time off work due
to fibroid-related symptoms (171). Telephone interviews 3 months after UAE
found that heavy menstrual bleeding improved in 83% of women, dysmenorrhea
improved in 77%, and urinary frequency in 86%. Mean fibroid volume reduction
of the dominant fibroid was 33% at 3 months, but improvement in heavy
menstrual bleeding was not related to preprocedural uterine volume (even >1,000
cm3) or to the degree of volume reduction obtained. Of note, two women (0.4%)
had continued uterine growth and worsening pain and were found to have
sarcomas. The hysterectomy rate caused by complications was 1.5%. Within the
follow-up period, 3% of women under 40, but 41% of women over 50, had
amenorrhea.
A prospective, randomized trial comparing hysterectomy and UAE in 177
women with symptomatic fibroids found that major complications were rare.
Hospital stay was significantly shorter for UAE (2 vs. 5 days), but UAE was
associated with more readmissions (9 vs. 0) for pain and/or fever in the 6-week
postoperative period. Significant complications included one woman who
required resection of a submucous fibroid, one who had sepsis in the UAE group,
and one woman who had a vesicovaginal fistula following hysterectomy.
Early Ovarian Failure
581The risk of premature ovarian failure following UAE needs further study.
Transient amenorrhea was reported in as many as 15% of women. Ovarian arterial
perfusion as measured by Doppler sonography immediately following UAE
shows that 35% of women had decreased ovarian perfusion and 54% had
complete loss of perfusion (173). However, basal follicle-stimulating hormone
(FSH) and anti-müllerian hormone (AMH) levels indicated decreased ovarian
reserve in all women in one study (174).
Kim et al. reported a significant decrease of AMH and antral follicle counts
(AFC) at 3 and 12 months after UAE (175). A significant recovery of AMH at the
12-month measurement was seen, but only in patients <40 years of age. These
results suggest that ovaries may be damaged following UAE, but they may
recover in younger women. A study comparing women who underwent UAE with
women having laparoscopic myomectomies found significantly lower AMH
levels and AFC in the UAE group (176). Although normal FSH, estradiol, ovarian
volume, and AFC were documented in most women following UAE, these tests
cannot predict earlier onset of menopause (177). Younger women, whose ovaries
contain a large number of follicles, are likely to maintain a normal FSH despite
destruction of a significant number of follicles, but it is not clear if future fertility
will be impaired. Loss of follicles might cause menopause at an age earlier than
would otherwise be expected. Long-term follow-up of women having UAE will
be necessary to answer this important question.
Fertility and Pregnancy Following Uterine Artery Embolization
Because of the possibility of decreased ovarian function, and the potential for
increased pregnancy complications, women who wish to conceive should not
be treated with UAE (178). Although the risk appears to be low for women
younger than 40 years old, premature ovarian failure would be devastating in this
setting. Potential fertility following UAE is uncertain. A prospective trial of
women with intramural fibroids larger than 4 cm, randomly selected for either
UAE or myomectomy, reported more pregnancies and fewer spontaneous
abortions after surgery than after UAE (176). Obstetrical and perinatal results
were similar.
Two hundred twenty-seven completed pregnancies after UAE were compared
with pregnancies in untreated women matched for age and fibroid location
(controls) (179). Miscarriage rates (35% vs. 17%) and postpartum hemorrhage
rates (14% vs. 3%) were higher in UAE pregnancies compared with controls.
Rates of preterm delivery, IUGR, and malpresentation were similar in UAE
pregnancies and in control pregnancies with fibroids. One small randomized
study compared fertility outcomes of UAE with laparoscopic myomectomy (176).
Twenty-six patients after UAE and 40 after myomectomy tried to conceive, with a
582pregnancy rate of 50% vs. 78% (p <0.05) and miscarriage rate of 53% vs. 19% (p
<0.05) for UAE and myomectomy, respectively. A Cochrane database review
stated that UAE may be associated with less favorable fertility outcomes than
myomectomy, but the data is low quality and should be regarded with extreme
caution (166).
Another study reported eight term and six preterm deliveries, but two women
had placenta previa and one woman had a membranous placenta. It is not clear
whether this high incidence of abnormalities is related to an effect of UAE on the
endometrium or a placental problem inherent to women with uterine fibroids. As
a result, some authors recommend early-pregnancy sonography to look for
placenta accreta (180). Uterine wall defects, necrosis, and fistula have been
reported following UAE, and the integrity of the uterine wall during pregnancy
and childbirth remains unknown (181).
Uterine Artery Occlusion
Alternative methods of uterine artery occlusion include laparoscopic uterine
artery occlusion. Fifty-eight patients were randomized to UAE or laparoscopic
uterine artery occlusion (182). After a median follow-up of 48 months, clinical
failures and symptom recurrence occurred in 14 women after laparoscopy (48%)
and in five women after UAE (17%). Laparoscopic occlusion requires general
anesthesia, is invasive, and requires a skilled laparoscopic surgeon.
Magnetic Resonance–Guided Focused Ultrasound
Ultrasound energy can be focused to create sufficient heat at a specific point so
that protein is denatured and cell death occurs. Concurrent MRI allows precise
targeting of tissue and monitoring of therapy by assessing the temperature of
treated tissue (183). The advantages of this procedure are a very low morbidity
and a very rapid recovery, with return to normal activity in one day. The
procedure is not recommended for women wishing future fertility (183). Initial
studies had treatment limited by the U.S. Food and Drug Administration to
approximately 10% of fibroid volume, and while a 15% reduction in fibroid size
was reported 6 months following treatment, only an additional 4% reduction was
noted at 24 months (184). More recent studies with larger treatment areas reported
better results; 6 months after treatment, the average volume reduction was 31%
(+/−28%) (185).
An evidence-based review found cohort studies involving 1,594 patients with
short-term follow-up (<1 year) (186). Twenty-six major complications (1.6%)
were reported. MRgHIFU resulted in statistically and clinically significant
reductions in fibroid-related symptoms. For women failing medical therapy and
583seeking alternatives to hysterectomy for symptomatic uterine fibroids, the author
concluded that MRgHIFU provides a safe and effective, noninvasive, uterinepreserving treatment with a rapid recovery. Disadvantages of MRgHIFU include
restricted eligibility, lengthy procedure time, and availability of an MR device.
A nonrandomized comparative study of 166 patients with uterine fibroids who
underwent MRgHIFU (n = 99) and laparoscopic myomectomy (n = 67) reported
the laparoscopic myomectomy group showed substantial symptom improvement
in 52 patients and partial symptom improvement in 13 (187). In the MRgHIFU
group, 6 months after treatment, 62 patients showed complete symptom relief and
36 patients showed partial relief. MRgHIFU requires no general anesthesia or
blood loss and leads to quick postoperative recovery. This study had no
description of patient or fibroid characteristics and both patient and physician
selection bias were likely. The lack of high-quality comparative evidence between
MRgHIFU and other, more established uterine-preserving treatments, limits
informed decision making among treatment options.
MANAGEMENT SUMMARY
A woman’s individual circumstance, including fibroid-related symptoms and
their effect on the quality of life, desire (or not) to preserve fertility, and her
wishes regarding treatment options should be considered when discussing
possible treatments. Multiple treatment options usually exist and the following
points should be considered.
For an asymptomatic woman diagnosed with fibroids who desires fertility
in the near future, evaluation of the uterine cavity with SIS, hysteroscopy, or
MRI provides useful information regarding the presence of submucous
fibroids and their potential impact on fertility. If the cavity is not deformed,
fibroids need not be treated and conception may be attempted. If the cavity is
deformed, myomectomy (hysteroscopic or abdominal) can be considered. An
experienced laparoscopic surgeon may offer laparoscopic myomectomy, with a
multilayered myometrial closure.
For an asymptomatic woman who does not desire future fertility,
observation (watchful waiting) should be considered. A periodic review of the
patient’s symptoms and a pelvic examination to evaluate the uterine size should
be accomplished. In the presence of very large fibroids, renal ultrasound or
computed tomography urogram can be considered to rule out significant
hydronephrosis.
For a symptomatic woman who desires future fertility and her primary
symptom is abnormal bleeding, baseline hemoglobin measurement should be
considered because accommodation to anemia can occur. If indicated, further
584evaluation of the endometrium with endometrial biopsy can be performed.
Evaluation of the uterine cavity with SIS, hysteroscopy, or MRI can help
determine the appropriate treatment options.
If the cavity is deformed, myomectomy (hysteroscopic or abdominal)
should be considered. An experienced laparoscopic surgeon may offer
laparoscopic myomectomy. If the symptoms of pain or pressure (bulk symptoms)
are present, and if the uterine cavity is not deformed, myomectomy (abdominal or
laparoscopic) can be considered.
For a symptomatic woman who does not desire future fertility, observation
(watchful waiting) can be considered if no treatment is desired at that time.
A symptomatic perimenopausal woman may desire observation until she
enters menopause, when symptoms often diminish. Baseline hemoglobin
measurements should be obtained and if a significant anemia exists, treatment
should be considered. If irregular menstrual bleeding is present, evaluation of the
endometrium with sonography or endometrial biopsy should be considered. If the
endometrium is normal, a levonorgestrel-IUS or endometrial ablation may be
appropriate treatment. Myomectomy (hysteroscopic, abdominal, or laparoscopic),
hysterectomy (vaginal, laparoscopic, or abdominal), or UAE can be considered.
For a woman with primarily fibroid-related pain or pressure symptoms
(bulk symptoms), myomectomy, hysterectomy, and UAE or focused
ultrasound (limited by size and number of fibroids) may be considered.
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