How
If the endometrium cannot be seen clearly in its entirety, it should be reported as ‘non‐measurable’ and no attempt should be made to measure it. The proportion of cases in which the endometrium cannot be measured may exceed 10%
59
, especially in older patients
60
.
Endometrial thickness should be measured at its maximum point in the sagittal plane and include both endometrial layers (double‐layer endometrial thickness)
1
(Figure 5 ). The calipers should be placed on the two opposite endometrial–myometrial interfaces in an appropriately magnified image, and the endometrium should be measured at the point at which it appears to be thickest, measuring perpendicular to the endometrial midline. The measurement should be reported in millimeters, rounded up to one decimal point.
Example of double‐layer measurement of endometrial thickness on ultrasound (sagittal section). Calipers should be placed on the two opposite endometrial–myometrial interfaces in an appropriately magnified image (with the full length of the endometrial cavity visible and the uterus filling more than half of the screen), and the endometrium measured at the point at which it appears to be thickest, measuring perpendicular to the endometrial midline.
When intracavitary fluid is present, the thickness of both single layers should be measured, and their sum recorded. In the presence of an intracavitary lesion (e.g. polyp), the total endometrial thickness should include the diameter of the lesion in the sagittal plane as well as both underlying anterior and posterior layers of the background endometrium. However, if an intracavitary myoma is clearly identified, the myoma should not be included in the measurement of endometrial thickness. Intracavitary lesions should be measured in three perpendicular diameters in millimeters, rounded up to one decimal point. If an intracavitary lesion is present, the total endometrial thickness is less relevant than the measurement and description of the lesion itself.
The echogenicity of the intracavitary fluid should be specified (e.g. anechoic, low level, hemorrhagic).
An evaluation of endometrial morphology should include assessment of endometrial echogenicity, the endometrial midline and the endometrial–myometrial junction
1
.
The echogenicity of the endometrium is described as hyperechogenic, isoechogenic or hypoechogenic compared with the echogenicity of the myometrium
1
. Endometrial echogenicity should be defined as ‘uniform’ if the endometrium is homogeneous, with symmetrical anterior and posterior sides. A uniform endometrium generally has either a three‐layer pattern (as seen in the proliferative phase of the cycle) or a homogeneous hyperechogenic pattern (as seen in the late secretory phase of the cycle). Endometrial echogenicity is defined as ‘non‐uniform’ if the endometrium appears heterogeneous, asymmetrical or cystic.
The endometrial midline is defined as ‘linear’ if a straight interface within the endometrium is visualized, as ‘non‐linear’ if a waved interface is seen (Figure 6, V ideoclips S1 and S2 ), as ‘irregular’ or as ‘not defined’ in the absence of a distinct interface
1
.
Ultrasonographic examples of a non‐linear endometrial midline, in sagittal section. (a) Without fluid instillation, it can be seen that the endometrial midline is not linear. (b) After fluid instillation, note the irregular and polypoid delineation of the cavity.
The endometrial–myometrial junction is the interface between the basal endometrium and the inner myometrium. It is described as ‘regular’, ‘irregular’, ‘interrupted’ or ‘not defined’
1
. The inner myometrium underlying the endometrium is also called the ‘junctional zone’.
The aim of gynecological ultrasonography in women with abnormal bleeding is to exclude or detect intracavitary lesions such as endometrial polyps, intracavitary fibroids, endometrial hyperplasia, endometrial cancer or retained pregnancy tissue
61
,
62
,
63
.
Although the focus of this Consensus Statement is on the endometrium, when investigating abnormal uterine bleeding an ultrasound examination allows a broader evaluation of adjacent structures, including the myometrium (e.g. adenomyosis, fibroids, myometrial vascularity), ovaries (e.g. corpus luteum, endometrioma, granulosa cell tumor, tubo‐ovarian abscess), Fallopian tubes (e.g. hydrosalpinx, pyosalpinx, hematosalpinx, tubal pregnancy, tubal cancer), bladder (e.g. transitional‐cell carcinoma, endometriosis, lithiasis, cystitis), cervix (e.g. endocervical polyp, cervical carcinoma, cervical involvement of endometrial carcinoma) and rectum (e.g. endometriosis, malignancy) (Figure 7 ).
Diagnostic algorithm for women with abnormal uterine bleeding: stepwise diagnostic approach. An ultrasound examination is performed, first, to search for lesions in the bladder, rectum, ovaries, cervix or myometrium, and second, to evaluate the endometrium, triaging women in whom office sampling is most likely to yield an accurate histological diagnosis, those in whom hysteroscopy is indicated and those who do not need further testing.
In women with abnormal uterine bleeding, endometrial malignancy is unlikely if the total endometrial thickness is considered ‘thin’
64
,
65
, if the endometrium has a uniform three‐layer pattern or if the endometrial midline is regular and linear
4
,
66
,
67
. In women presenting with postmenopausal bleeding, the endometrium is considered ‘thin’ if its thickness is ≤ 4 mm, but the clinician may decide to use a lower threshold (e.g. 3 mm) to increase the sensitivity and negative predictive value (Table 2 ).
Summary estimates of sensitivity, specificity, positive (PPV) and negative (NPV) predictive values and positive (LR+) and negative (LR−) likelihood ratios to detect endometrial cancer at different thresholds of endometrial thickness
Studies from which the summary estimates are derived are given.
Alongside endometrial thickness, endometrial morphology, adequate visualization of the endometrial–myometrial junction and vascularization are also important in differentiating malignant from benign lesions. Endometrial cancer is typically associated with a thickened endometrium (i.e. > 4 mm in postmenopausal women), a heterogeneous endometrium, the presence of irregular cysts, a non‐visible endometrial midline, an irregular, interrupted or ill‐defined endometrial–myometrial junction, multiple vessels of focal or multifocal origin and/or a high color score of 3–4
4
,
68
(Figure 8 ).
Color Doppler ultrasound image and diagram showing features suggestive of endometrial cancer
4
: thickened endometrium (arrows; interquartile range (IQR) = 11–26 mm in women with cancer), heterogeneous endometrium, presence of irregular cysts, non‐visible endometrial midline, irregular, interrupted or ill‐defined endometrial–myometrial junction, multiple vessels of focal or multifocal origin and/or high color score of 3–4. For postmenopausal women, an endometrial thickness > 4 mm is generally used to define thickened endometrium.
Endometrial thickness changes continuously in response to hormonal stimulation. Unlike after menopause, a cut‐off value for endometrial thickness is not useful prior to menopause, and endometrial features other than thickness are more relevant
4
. To investigate abnormal uterine bleeding, ultrasound examination is recommended in the first half of the menstrual cycle, after bleeding has stopped
1
,
4
. In the secretory phase, the endometrium may appear thickened and more echogenic, and physiological endometrial changes may be difficult to distinguish from pathology. In such cases, a repeat ultrasound examination after the cessation of menstrual bleeding may be indicated.
In women with a spontaneous menstrual cycle, information about the day of the cycle and the presence or absence of a dominant follicle or corpus luteum will allow better interpretation of the endometrial features observed at ultrasound. Concordance or discordance between the endometrial appearance, the day of the cycle and the ovarian characteristics should be reported.
Endometrial thickness is affected by the use and type of hormonal contraception (e.g. progestogen‐only pill, monophasic or sequential combined oral contraception). The endometrium of women on continuous hormonal therapy tends to be thin and more hyperechogenic.
In the presence of an IUCD/IUS, owing to shadowing, part of the underlying endometrium is hidden. The endometrium should be recorded as ‘not measurable’. The endometrium alongside the IUCD/IUS is generally visible and relevant sonographic features may be reported. In patients using a copper IUCD, the endometrium displays the usual cyclical hormonal changes, while it stays thin and hyperechogenic in women who have a levonorgestrel IUCD/IUS.
Without HRT, endometrial thickness is expected to be thin (i.e. ≤ 4 mm) after the menopause
4
.
The endometrial thickness in women using HRT is affected by the HRT regimen, composition and dosage and varies according to the time during the pseudocycle at which the measurement is taken
69
. According to the British Menopause Society joint guidelines
70
, the cut‐off for a thickened endometrium is defined as 4 mm for women on continuous combined HRT (ccHRT) and 7 mm for women on sequential HRT (sHRT). However, there is insufficient evidence that endometrial thickness in women using ccHRT differs substantially from that in women using sHRT if the measurement is taken soon after the end of the planned withdrawal bleed. There has been even less research on the effect of current day ‘body‐identical’ HRT regimens on endometrial thickness. In the absence of robust data, clinicians should adopt the same conservative endometrial thickness cut‐off as that used for non‐HRT patients (i.e. 4 mm).
Ultrasonography should be the first‐line examination for women with abnormal uterine bleeding on SERM therapy (e.g. tamoxifen)
71
. Cysts are frequently observed in women treated with tamoxifen. Cysts of various different sizes will typically be present in the subendometrial layer, within the (apparently) thickened endometrium or within glandulocystic polyps
72
. In the absence of abnormal uterine bleeding, there is no indication to perform a routine ultrasound evaluation of the endometrium in women on SERM therapy
71
,
73
(Figure 9 ).
Diagnostic algorithm in patients taking tamoxifen. In those without abnormal uterine bleeding (AUB), ultrasonography is not indicated. In those presenting with AUB, ultrasonography will guide the clinician in triaging patients who do not need further testing (and may be followed up clinically), those in whom office sampling is most likely to yield an accurate histological diagnosis and those in whom hysteroscopy is indicated. *Saline‐contrast sonohysterography or gel‐instillation sonography.
Although there is no place for endometrial cancer screening in the general population
74
,
75
,
76
, gynecological ultrasonography is often performed in women without abnormal uterine bleeding for other indications, such as when there is suspicion of an ovarian cyst or pelvic pain
5
,
77
.
Although concern regarding endometrial pathology may not have been the indication for the ultrasound scan, it remains a challenge to manage incidental endometrial ultrasound findings in the absence of abnormal uterine bleeding
77
. Many studies have focused on the risk of endometrial cancer in relation to endometrial thickness in the postmenopausal population
78
. However, endometrial thickness should not be the only sonographic feature that is taken into consideration when deciding on further invasive endometrial testing
79
.
In a woman without abnormal uterine bleeding, further testing should be considered in the presence of two or more warning signs observed during ultrasound examination for another indication. Warning signs include: a thickened endometrium (> 4 mm in postmenopausal women); non‐uniform endometrium with an irregular outline; and multiple vessels with or without branching (Figure 10 ). However, this algorithm has yet to be validated in a randomized controlled trial. In the absence of robust evidence, the incidental finding of a thickened endometrium (> 4 mm in postmenopausal women) may prompt a more detailed examination during the scan, first to scrutinize both intrauterine and extrauterine features and second to actively exclude the other two warning signs. If both these steps are reassuring, it can be stated that no immediate further action is required. However, patients should be advised to remain vigilant for any postmenopausal bleeding that may occur subsequently, mandating further evaluation.
Diagnostic algorithm in women without abnormal uterine bleeding (AUB). In women without AUB, sonographic screening for endometrial pathology is not indicated. If an ultrasound scan (US) is performed for another indication, sonographic ‘alarm features’ within the endometrium (ET) are evaluated. These include: (1) a thickened ET > 4 mm in postmenopausal women, (2) non‐uniform endometrium with irregular outline and (3) multiple vessels with or without branching. In a woman without AUB, the incidental finding of two or more of these alarm features indicates that further testing should be considered. *The patient should be asked to return if she experiences further AUB. SCSH, saline contrast sonohysterography.
The presence of pre‐existing intracavitary fluid should be reported
1
, and the examiner should assess whether a possible explanation for the fluid can be found. Although anechoic intracavitary fluid after menopause due to endometrial atrophy is a common feature and does not deserve further investigation, fluid may also be secondary to bleeding due to intracavitary or tubal pathology (e.g. polyp, fibroid, hematometra with a thin endometrium in women taking contraception associated with intermenstrual spotting or cancer)
80
,
81
. The echogenicity of intracavitary blood often has a ground‐glass appearance or may show a sedimentation level
1
.
Endometrial polyps are well‐circumscribed protrusions into the uterine cavity
73
,
74
,
75
. The presence of endometrial polyps can be suspected on grayscale ultrasound by the presence of a ‘bright edge’, seen as a sharp and smooth echogenic line that is generated by the interface between the polyp and the juxtaposed endometrium
1
,
82
(Figure 11 ).
Diagram and ultrasound image showing the ‘bright‐edge’ sign (formed by the interface between the intracavitary lesion and the endometrium), suggestive of focal intracavitary endometrial pathology. Adapted from Leone et al .
1
.
Endometrial cysts are commonly associated with endometrial polyps after menopause, but can also be seen in atrophic or hyperplastic endometria
4
,
5
. The detection of polyps can be improved by dynamic assessment
13
. As with blood clots, targeted gentle pressure from the probe against the uterine corpus, or autonomic uterine peristalsis
28
,
29
,
30
,
31
, can unmask the presence of intracavitary lesions by elongation or sliding (i.e. the ‘sliding (polyp) sign’)
1
. The use of color/power Doppler will typically demonstrate the presence of a dominant vessel originating from the myometrium and reaching into the central part of the endometrium (i.e. the ‘pedicle‐artery’ sign)
1
,
4
,
5
,
26
. The risk of malignancy depends on various clinicodemographic factors
83
. Endometrial cancer within a polyp may be suspected on ultrasonography
3
,
4
,
5
,
84
,
85
if the lesion has an irregular outline, if there are multiple internal vessels with an irregular branching pattern or if the lesion is large (> 18 mm)
3
,
4
,
5
,
85
. The presence of intracavitary fluid (pre‐existing or after fluid instillation) improves visualization of the lesion's outline (Figure 12 ).
Power Doppler and grayscale ultrasound images and diagrams highlighting the differences between premenopausal (a) and postmenopausal (b) focal endometrial pathology on fluid‐instillation sonography. Before menopause, a polyp most often appears hyperechogenic and has a distinct dominant vessel, while after menopause, approximately half of polyps show regular internal cysts and the feeding vessel is often less distinct or even not visible. Adapted from Van den Bosch et al .
4
.
In women presenting with a focal endometrial lesion and abnormal uterine bleeding, hysteroscopic removal is recommended. For the more common clinical scenario of an incidentally identified endometrial polyp in asymptomatic premenopausal or postmenopausal patients, additional sonographic features can help to guide management. The presence of multiple vessels with or without an irregular branching pattern, as well as the observation of an irregular endometrial echogenicity or outline of the intracavitary lesion, should prompt in‐depth discussion on the need for histological diagnosis of the lesion (Figures 13 and 14 ). In the absence of such warning signs, the following management approaches may be considered: (1) expectant management with no immediate intervention; (2) interval reassessment to evaluate for spontaneous resolution at a later date; (3) sonohysterography to confirm that the lesion is solitary and well‐circumscribed prior to making a management decision.
Power Doppler ultrasound image and diagrams showing multiple vessels with an irregular branching pattern, within an extended (upper diagram) or localized (lower diagram) intracavitary lesion with an irregular outline. Adapted from Van den Bosch et al .
4
.
Diagnostic/management algorithm for focal endometrial lesions. The sonographic detection of a focal endometrial lesion (e.g. polyp) in a woman with abnormal uterine bleeding (AUB) warrants operative hysteroscopy with complete removal of the lesion. In the absence of AUB, a stepwise diagnostic approach is proposed. Hysteroscopy is indicated if multiple intralesional vessels, or an irregular lesion outline, are seen on ultrasound imaging. In the absence of abnormal sonographic features as well as of risk factors for endometrial malignancy, the patient may decide, after appropriate counseling, to undergo expectant management or hysteroscopy.
(Socio)demographic characteristics
86
, clinical and sonographic findings
87
and the patient's preference should be taken into account when considering further management.
When focal lesions are found at sonohysterography, they should be removed using hysteroscopy, while when the endometrium is globally thickened blind sampling techniques may be adequate
88
.
If endometrial malignancy is suspected based on the sonographic features (Figures 7 , 9 and 10 ), office endometrial sampling is indicated
89
and should be processed with priority. Pipelle sampling has good accuracy to detect endometrial (pre)malignancy
89
,
90
and is a cost‐effective first diagnostic step
91
. Ultrasound guidance should be considered to optimize sampling adequacy if access to the uterine cavity is difficult. If the sample is inadequate or inconclusive or shows only benign findings, hysteroscopy is recommended.
During endometrial sampling, the tissue yield should be assessed and compared with the sonographic features. If there is minimal tissue yield in a woman with a thickened endometrium at ultrasound scan, a lesion has most probably been missed, and the results of the histology will most probably not be representative
92
,
93
,
94
,
95
. In these cases, hysteroscopy with targeted biopsy is suggested as a diagnostic alternative (Figure 7 )
96
. Office hysteroscopy is a cost‐effective alternative to immediate operative hysteroscopy
97
.
J. Preisler , Departamento de Ginecología y Obstetricia, Facultad de Medicina, Clínica Alemana‐Universidad del Desarrollo, Santiago, Chile; Departamento de Ginecología y Obstetricia, Hospital Clínico Universidad de Chile, Santiago, Chile
O. Rotenberg , Department of Obstetrics & Gynecology and Women's Health, Albert Einstein College of Medicine/Montefiore Medical Center, Bronx, NY, USA
H. Marret , Department of Obstetrics, Gynecology and Reproductive Medicine, University Hospital of Tours, Tours, France
G. Condous , Acute Gynaecology, Early Pregnancy, and Advanced Endosurgery Unit, Nepean Hospital, Kingswood, NSW, Australia
J. L. Alcázar , Department of Obstetrics and Gynecology, Clinica Universidad de Navarra, School of Medicine, Pamplona, Spain
D. Fischerová , Department of Obstetrics and Gynecology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic
U. Metzger , Département d'Échographie en Gynécologie et Obstétrique, Centre d'Échographie de l'Odéon, Paris, France
C. Van Pachterbeke , Department of Obstetrics and Gynecology, Brugmann University Hospital, Brussels, Belgium
D. Franchi , Preventive Gynecology Unit, Division of Gynecology, European Institute of Oncology IRCCS, Milan, Italy
M. Nisolle , Department of Obstetrics and Gynecology, Hospital de La Citadelle, University of Liege, Liege, Belgium
J. Huirne , Department of Gynecology and Obstetrics, Research Institute ‘Reproduction and Development’, Amsterdam UMC, Location VUmc, Amsterdam, The Netherlands
C. Fotopoulou , Gynaecological Oncology, Department of Surgery and Cancer, Imperial College London, London, UK
S. Goldstein , Department of Obstetrics and Gynecology, New York University, New York City, NY, USA