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Ultrasonographic Assessment of Ovarian Endometrioma

Article  in  Journal of Medical Ultrasound · December 2008


DOI: 10.1016/S0929-6441(09)60001-1

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R E V I E W
A R T I C L E

Ultrasonographic Assessment of
Ovarian Endometrioma
Meng-Hsing Wu*, Yueh-Chin Cheng, Fong-Ming Chang

Endometriosis is a common gynecologic disease that affects about 10% of women of


reproductive age. Most women with endometriosis experience pelvic pain, dysmenorrhea,
dyspareunia and infertility, all of which reduce their quality of life. Ultrasound examination
is an easy and noninvasive method in the differential diagnosis of endometriosis, and is
useful in planning surgical intervention of ovarian endometrioma, as well as preoperative
and postoperative medical therapy. With advances in ultrasonography, the application of
higher-frequency scanning probes can evaluate ovarian endometrioma to improve diag-
nostic accuracy. This includes morphologic assessment with two-dimensional ultrasound
and other various ultrasound modalities such as three-dimensional sonography, color
Doppler, and power ultrasound imaging. The aim of this review will focus on the ultra-
sonographic findings of ovarian endometrioma during diagnosis, in differentiating vari-
ous benign and malignant tumors, and their functional role during treatment.

KEY WORDS — endometrioma, ovary, ultrasonography

■ J Med Ultrasound 2008;16(4):241–248 ■

Introduction [1]. Retrograde menstruation with additional fac-


tors, such as aberrant production of steroids from
Endometriosis, which is defined as ectopic pres- ectopic endometriotic lesions, and alteration and/or
ence of endometrial tissue outside the uterus, is a dysfunction of the immune system (especially mac-
common gynecologic disease that affects about rophages) in the peritoneal microenvironment in-
10% of women of reproductive age. Most women creases the susceptibility of endometriosis. Ovarian
with endometriosis experience pelvic pain, dys- endometrioma is considered to be one entity of nu-
menorrhea, dyspareunia and infertility, all of which merous component endometriotic lesions, and its pa-
reduce their quality of life. Although the mechanism thogenesis may be either implantation or metaplasia
responsible for the development of endometriosis theory from histogenesis of ovarian endometrio-
remains unclear, several hypotheses have been pro- mas. Continuum between the flat cells of the ovar-
posed to investigate the etiology of endometriosis ian surface mesothelium and the endometrial-type

Received: September 1, 2008 Accepted: September 9, 2008


Department of Obstetrics and Gynecology, National Cheng Kung University Hospital and College of
Medicine, National Cheng Kung University, Tainan, Taiwan.
*Address correspondence to: Dr. Meng-Hsing Wu, MD, PhD, Department of Obstetrics and Gynecology, College
of Medicine, National Cheng Kung University, Tainan 70428, Taiwan.
E-mail: mhwu68@mail.ncku.edu.tw

©Elsevier & CTSUM. All rights reserved. J Med Ultrasound 2008 • Vol 16 • No 4 241
M.H. Wu, Y.C. Cheng, F.M. Chang

epithelium of the endometrioma has been histol- power ultrasound imaging, in evaluating ovarian en-
ogically confirmed [2]. dometrioma will improve diagnostic accuracy. The
Conventional two-dimensional (2D) gray-scale aim of this review will be to focus on the ultrasono-
ultrasound is a valuable diagnostic technique in the graphic findings of ovarian endometrioma in the
clinical practice of gynecology. The use of three- diagnosis differentiating different benign and malig-
dimensional (3D) ultrasound can further help in the nant tumors, and in the functional role of power
analysis of morphological anatomy and the mea- Doppler ultrasound during various treatments.
surement of the volume of the internal genital
organs. Three-dimensional sonography with image
reconstruction is less invasive than hysterosalpin- The Findings of Ultrasound in the
gography for the assessment of uterine anatomy, Diagnosis of Ovarian Endometriomas
and it can visualize both the uterine cavity and the
myometrium on a 3D scan. This facilitates the diag- Endometriosis without the presence of endometri-
nosis of uterine anomalies, especially in the dif- omas is almost invisible when viewed by ultrasono-
ferentiation of septate from bicornuate uteri for graphy. When an endometrioma is suspected with
preoperative surgical planning [3]. In the assessment ultrasonography, the most characteristic finding is a
of the ovaries, three perpendicular planes of the cyst with diffuse homogeneous hypoechoic (ground-
ovaries can be rotated to obtain the largest dimen- glass) appearance (Fig. 1). The cyst may be second-
sions, increasing the ability to evaluate the ovary ary to a hemorrhage. Ectopic endometriotic tissue
and follicles, especially in women with polycystic is shed with menstruation and will increase the size
ovary syndrome [4]. The evaluation of stroma and and content of the cyst but will not disappear with
volume determinations can be obtained more accu- each period. It is described as a chocolate cyst. The
rately by 3D images than by traditional 2D ultra- cyst may present in a solitary or multiple form in the
sonography. Three-dimensional power Doppler ovaries (Fig. 2). Endometrioma may contain a fluid-
ultrasound can also reveal blood flow and vascular- fluid level (Fig. 3), which needs to be differentiated
ity in the target organ or the region of interest, and from a hemorrhagic functional cyst with heteroge-
quantify these for further evaluation. Such applica- neous content which shows as fine linear strands
tions have been proved to be beneficial in the field (“fish-net”) (Fig. 4). The ovaries will fix with adjacent
of infertility and reproductive endocrinology [5].
Ultrasound examination is an easy and non-
invasive method in the differential diagnosis of
endometriosis, and is useful in planning surgical
intervention of ovarian endometrioma, as well as
preoperative and postoperative medical therapy. It
is important to differentiate between the various
gynecologic conditions arising from endometriosis
due to the high prevalence of endometriosis with
clinical symptoms. With the advance of ultrasonog-
raphy, the application of higher-frequency scan-
ning probes is providing greater resolution and
improving the ability to evaluate ovarian endo-
Fig. 1. An endometrioma in a 34-year-old woman viewed
metrioma. Morphologic assessment with 2D ultra-
with Doppler ultrasound. This cyst demonstrated diffuse low-
sound is the foundation of the evaluation of ovarian level internal echoes without any normal ovarian tissue on this
endometrioma. The use of various ultrasound mo- transvaginal sonogram. It had poor vascularity around the cyst
dalities, such as 3D sonography, color Doppler, and without any solid or papillary mass.

242 J Med Ultrasound 2008 • Vol 16 • No 4


Ultrasonographic Assessment of Ovarian Endometrioma

Fig. 2. A multiloculated endometrioma in a 28-year-old woman.


The transabdominal sonogram demonstrated a cystic adnexal Fig. 4. Transvaginal sonogram showing a hemorrhagic corpus
mass with hypoechoic content and internal septations. luteal cyst with heterogeneous content and fine linear with fish
net-like strands.

Fig. 3. Transvaginal sonogram showing an endometrioma in a


30-year-old woman. The lesion is shown with low-level echoes Fig. 5. Transvaginal sonogram showing a vascularity pattern of
with fluid-fluid level (arrowheads). an endometrioma. It was presented as a pericystic flow at the
level of the ovarian hilius (arrowhead).

pelvic structures, even demonstrating the ‘kissing is presented as a pericystic flow at the level of the
ovaries’ feature on the ultrasonography. When pres- ovarian hilius (Fig. 5) [7]. However, the use of color
sure is applied to the ovaries with a transvaginal Doppler imaging does not improve the diagnostic
probe, the ovaries are not movable. Endometrioma accuracy of transvaginal ultrasonography alone in
will contain solid-appearing echoic nodulations (sec- the diagnosis of ovarian endometrioma.
ondary to reactive fibrosis) without vascularity on
color Doppler imaging. Using color Doppler ultra-
sound imaging evaluation of vessel distribution, a Ovarian Endometrioma and Infertility
round-shaped homogeneous hypoechoic ‘tissue’ of
low-level echoes without papillary proliferations asso- There is still controversy over whether endometrio-
ciated with ‘poor’ vascularization, or a round-shaped sis is associated with infertility and the outcome of
homogeneous hypoechoic cyst with an echogenic pregnancy. The mechanism of infertility associated
portion without vascular flow detected indicates the with endometriosis may include hormonal, chemical,
likely presence of ovarian endometrioma [6]. The and immunological changes leading to impaired folli-
typical vascular pattern of ovarian endometrioma culogenesis, luteal phase defects, reduced fertilization

J Med Ultrasound 2008 • Vol 16 • No 4 243


M.H. Wu, Y.C. Cheng, F.M. Chang

and abnormal embryogenesis [8]. The gold standard There were significantly decreased intra-ovarian
for the diagnosis of endometriosis is laparoscopic stromal blood flow parameters, including vascular-
examination. Surgical removal of endometriomas ization index (VI), flow index (FI) and vascularization
and/or in vitro fertilization (IVF) is indicated for flow index (VFI), in the patients with endometrio-
women who desire pregnancy. Surgery may lead sis who did not have any evident difference in total
to a decreased ovarian reserve, but it does not impair ovarian volume on the day of human chorionic go-
fertility outcomes of IVF in women previously oper- nadotropin. There was also significantly decreased
ated for ovarian endometriomas [9]. Conversely, uterine artery velocimetry (RI and PI) values as deter-
direct controlled ovarian hyperstimulation and IVF mined by Doppler analysis between two groups.
treatment is suggested in women with asymptom- Therefore, a deficient intra-ovarian vascularity poten-
atic ovarian endometriomas, because removal of tially may be an initial marker of a reduced ovarian
endometriomas before IVF does not improve fertil- reserve before the increase of serum follicle stimu-
ity outcome [9]. Lower peak estrogen levels, higher lating hormone (FSH) levels in early follicular phase,
gonadotropin injection doses, lower oocyte yield, and and an important predictor of ovarian response.
a higher cancellation rate of IVF cycles are demon- The above results all demonstrated that women
strated in women with advanced-stage endometri- who underwent previous conservative surgery for
osis who have undergone previous surgery compared endometriomas showed signs of a diminished ovar-
with tubal-factor infertility subjects, but no differ- ian reserve. Ovarian damage during surgery may lead
ences in fertilization, cleavage, implantation, preg- to decreased intra-ovarian vascularity in the endo-
nancy, miscarriage, and delivery rates are found metriosis group. It was interesting that there were
between two groups [10]. However, the IVF outcome no significant differences in stromal blood flow pa-
is significantly affected in women who previously rameters of 3D power Doppler ultrasound between
underwent bilateral endometriomas cystectomy the endometriomatous ovaries post-endometrioma
[11]. It still needs higher doses of gonadotrophins surgery and the contralateral control ovaries in the
during controlled ovarian hyperstimulation and same individuals, which may be compatible with
has a higher withdrawal rate for poor response, but decreased ovarian reserves in both ovaries of the
the follicular number of follicles, oocytes retrieved, patients with previous endometriomas after surgery
embryos obtained, clinical pregnancy rate and de- in our study [12]. Therefore, 3D power Doppler can
livery rate per cycle are all significantly lower than be used to demonstrate the dynamic vascularity of
in women without surgery [11]. In our previous the IVF process and may provide a prognostic tool
study, lower body mass index, higher LH levels in for IVF outcomes in patients with endometriomas.
baseline day 2 data, lower oocyte retrieval numbers It is possible that restricted blood supply to the
and lower pregnancy rates were found in women ovarian stroma in endometrioma after conservative
with endometriosis [12]. Nearly half of our cases surgery might be associated with impaired embryo
had large endometriomas and bilateral involve- quality. Leptin is considered an angiogenic factor
ment [12]. The clinical pregnancy rate per started and may serve as a sensitive marker of IVF outcomes.
cycle in our endometrioma cases was slightly higher The angiogenic effect of leptin is equivalent to that
than women operated on for bilateral ovarian endo- of vascular endothelial growth factor (VEGF), but
metriomas [11]. Although fertilization rates were the angiogenic response is evident earlier compared
similar, our results suggested that embryo quality with VEGF [13]. It means leptin plays a possible role
and uterine receptivity may still affect women with in conditions where new blood vessel growth is cru-
large and/or bilateral endometriomas [12]. cial, such as a decreased ovarian reserve in patients
We used 3D power Doppler ultrasonography to with endometriosis after surgery. Elevated levels of
investigate the differences of ultrasound findings serum leptin are associated with poor ovarian re-
between cases with endometriosis and control [12]. sponse, as well as decreased follicle maturation,

244 J Med Ultrasound 2008 • Vol 16 • No 4


Ultrasonographic Assessment of Ovarian Endometrioma

embryo quality and pregnancy outcomes [12,14]. 1.0 or less [16]. The conventional 2D sonography
In our previous study, follicular fluid leptin (14.38 ± seems to be sufficient as a primary screening modal-
1.74 ng/ml) was higher than serum samples (5.36 ± ity when a malignant tumor is suspected. However,
1.37 ng/ml) examined on ovum pick up day in they found that transvaginal color Doppler ultra-
normal control, which is compatible with the data sound is an effective method for detecting ovarian
from Anifandis et al [14], but there were no signif- cysts in asymptomatic postmenopausal women. In
icant differences in follicular fluid or serum leptin our previous study, 3D power Doppler sonography
concentrations between the patients with endo- has proved that the flow intensity of the ovarian
metriosis and the control group [12]. The value of stroma, including VI, FI and VFI, decreased in the
follicular fluid leptin demonstrated a negative cor- order of the aging process: premenopause, peri-
relation with ovarian stromal FI in the control group, menopause, then postmenopause [17]. There were
but there was an absence of this effect in the endo- a significant increase in ovarian stromal flow indices
metriosis group in our study [12]. Reduced blood in postmenopausal women receiving continuous-
flow (such as decreased FI in our study) through combined hormone replacement therapy, but not in
the ovarian stroma may lead to a follicular hypoxia the control group [18]. Introducing 3D ultrasonog-
followed by the secretion of several angiogenic raphy with power Doppler facilities as a secondary
factors, such as leptin, in ovarian follicles. The re- screening test for ovarian cancer in asymptomatic
duced ovarian response may then be found through peri- and postmenopausal women will further im-
negative feedback of leptin to the ovaries. Loss of prove the accuracy of ovarian cancer screening stud-
the negative correlation between follicular fluid ies. Kurjak et al detected malignant tumors early and
leptin and intra-ovarian FI in the endometriosis group accurately using 3D ultrasonography and power
may represent deficient angiogenic responses in Doppler imaging, in multiloculated, complex or
ovarian cortices after surgery. solid ovarian mass, or persistently cystic mass > 5 cm
in diameter, in which the echo architecture and/or
blood flow pattern was not highly suggestive of
Postmenopausal Endometrioma a benign histology according to 2D morphologic
and Doppler ultrasonic criteria of the ovarian ma-
Endometriosis is uncommon in postmenopausal lignancy and related cut-off scores [19]. Up until
women, because it depends on estrogenic stimula- this point there has been little discussion in the dif-
tion for its continued growth during reproductive ferential diagnosis of ovarian endometrioma with
ages. In asymptomatic postmenopausal women, the malignancy in postmenopausal women using 3D
risk of malignancy of simple adnexal cysts is low ultrasonography.
(0.6%). Almost half of these women, whose meno-
pause tended to occur more recently and they ten-
ded to be younger, resolve spontaneously during close Accuracy of Ultrasonography in the
ultrasound follow-up and avoid unnecessary surgical Differential Diagnosis of Suspected
intervention for physiological cysts [15]. However, Adnexal Tumors
many cysts still persist and/or remain unchanged.
Color Doppler ultrasound is usually recommended Sometimes, the clinical features and biological be-
for screening for ovarian cancer. Vuento et al sug- havior of ovarian cancer might be closely related to
gested that the evaluation criteria for abnormal endometrioma and/or endometriosis. About 0.7% of
ovarian findings in asymptomatic postmenopausal ovarian endometriosis cases demonstrate malignant
women were an ovarian volume of 8 cm3 or greater, transformation [20]. In contrast, the frequency of
nonuniform echogenicity, and/or a pulsatility index endometriosis that occurred in benign, borderline
(PI) of the ovarian artery or tumor vessel, if present, of malignant, and malignant ovarian tumors is 9.7%,

J Med Ultrasound 2008 • Vol 16 • No 4 245


M.H. Wu, Y.C. Cheng, F.M. Chang

12.5%, and 11.4%, respectively [21]. The most


frequent ovarian cancer closely related with endo-
metriosis is endometrioid adenocarcinoma. It is im-
portant in clinical practice that surgeons should be
aware of the possibility of ovarian cancer employing
careful preoperative evaluation when laparotomy or
laparoscopic surgery is arranged in ovarian endome-
trioma cases.
Ultrasound examination is a useful tool for pre-
operative differential diagnosis of adnexal lesions.
The gray-scale ultrasound parameters for predicting
malignancy include the size of the largest solid
Fig. 6. The complex ovarian mass with an irregular wall in a case
component, wall irregularity and lesion size, with a
of clear cell adenocarcinoma in a patient who had a serial follow-
sensitivity of 100% and a false positive rate of 10% up for suspected ovarian endometrioma. The central localization
[22]. The presence of normal ovarian tissue adjacent of vessels in intracystic solid tissue are observed by Doppler
to the ovarian cyst (the ‘ovarian crescent sign’) on sonogram on the last visit before operation (arrowhead).
an ultrasound scan is also a useful morphological
feature to exclude the possibility of an invasive of the tumor scan (with sensitivity 93% vs. 78%,
ovarian malignancy in the preoperative evaluation and a false positive rate 16% vs. 27%) [22].
[23]. Ovarian cancer is diagnosed with a sensitivity Furthermore, borderline malignant tumors in-
of 96% and a specificity of 76% when no normal crease the diagnostic difficulties with only 47% being
ovarian tissue is demonstrated by ultrasound. Several correctly classified as malignant [26]. About 8% of
parameters are used in the evaluation of adnexal pelvic masses are difficult to correctly classify on the
masses by transvaginal color Doppler sonography, basis of ultrasound findings. Papillary projections,
including a number of vessels detected in each ten or more locules existing in a cyst without solid
tumor, tumor vessel location (central vs. peripheral), components, low-level echogenicity of cyst fluid, and
peak systolic velocity, lowest resistance index, mean moderate vascularization as assessed subjectively at
resistance index, lowest pulsatility index and mean color Doppler examination are independent ultra-
pulsatility index [24]. Most parameters demonstrate sound variables associated with unclassified mass.
an overlap between benign and malignant tumors The diagnostic findings of ultrasound in borderline
with a high false-positive rate. The parameters which ovarian tumors are highly specific using the tumor
best differentiate malignant cancers from benign pattern recognition method [27]. The morphologic
tumors are the lowest resistance index with a cut- features viewed through ultrasonography are a
off value of 0.45 (sensitivity 100%; false-positive rate unilocular cyst with a positive ovarian crescent sign
11.4%) and central tumor vessel location (sensitivity and extensive papillary projections arising from the
90%; false-positive rate 11.4%). Using 3D ultra- inner wall, or a cyst with a well defined multilocular
sonography, the central localization of vessels in an nodules. However, typical ultrasound features are
adnexal mass can be easily observed (Fig. 6). In only present in two thirds of cases, the others being
addition, the mean gray index and the flow index misdiagnosed as benign lesions. The most frequent
are potentially important parameters in differential diagnostic ultrasound feature of borderline ovarian
diagnosis [25]. The use of 3D power Doppler ultra- tumors is the presence of papillae, defined as a small
sound can help to discriminate between benign and number of solid tissue projections into the cyst cavity
malignant ovarian tumors. VI in a 5 cm3 ovarian tu- from the cyst wall measuring 1–15 mm in height
mor improves diagnostic performance in the 3D flow and 1–10 mm in both width (base) and length
index, and is superior to that of the color content (base) [28]. Intracystic solid tissue measuring more

246 J Med Ultrasound 2008 • Vol 16 • No 4


Ultrasonographic Assessment of Ovarian Endometrioma

than 15 mm in height or 10 mm in width or length malignant adnexal masses, and is also superior to
would favor invasive malignant masses. serum CA-125 [33].

Serum CA-125 for Ovarian Conclusion


Endometrioma
Ultrasound examination is an easy and noninvasive
CA-125 levels are often used in differentiating tool in the evaluation of ovarian endometriomas. It is
ovarian endometriomas from adenxal masses. The useful in the analysis of morphologic anatomy and
levels are significantly higher in patients with endo- conventional 2D sonography seems to be sufficient
metriotic masses, and increase with the stages of as a primary screening test for ovarian endometrio-
endometriosis [29]. Recently, a multiple-marker mas, even when a malignant tumor is suspected.
screening test for endometriosis involving a four- Color Doppler and 3D power sonography will pro-
marker panel consisting of CA-125, macrophage vide substantial assistance in detecting the functional
chemotactic protein-1, leptin, and macrophage role of ovarian endometriomas, and in discriminat-
migration inhibitory factor, could diagnose 48% of ing ovarian endometriomas from malignant adnexal
subjects as to the presence of endometriosis with masses in preoperative differential diagnosis.
93% accuracy, which may be useful in the workup
of patients with suspected endometriosis [30].
Using a cut-off at ≥ 35 U/mL, elevated CA-125 lev- Acknowledgments
els demonstrates 79.3% sensitivity, 84.6% specificity,
79.3% positive predictive value, and 84.6% nega- The authors are grateful for the financial support provided
tive predictive value in the diagnosis of ovarian by grants from the National Science Council, R.O.C. and
endometrioma in patients scheduled for surgery National Cheng Kung University Hospital.
[7]. In our department’s previous study in women
undergoing surgery for endometriosis [29], CA-125
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