The role of transvaginal ultrasound in the management of abnormal uterine bleeding
© Springer-Verlag Berlin / Heidelberg 2004
Published: 3 March 2004
Abnormal uterine bleeding is a common symptom. Modern management should be based on a “one-stop” approach to which transvaginal ultrasound is ideally suited as a primary diagnostic tool. In premenopausal women focal pathology, such as fibroids and polyps, as well as extra uterine pathology, can be accurately diagnosed. In postmenopausal women endometrial cancer can be excluded. In the majority of women diagnostic hysteroscopy can thus be avoided, and patients with focal pathology detected with transvaginal ultrasound can be triaged for operative intervention. Outpatient endometrial biopsy should still be used to exclude endometrial pathology. This one-stop ultrasound-based clinical approach provides a rapid, accurate diagnosis, with the minimum of investigations and invasive procedures. In this way multiple outpatient visits and unnecessary inpatient admissions can be avoided.
Abnormal uterine bleeding (AUB) can occur at any stage of a woman’s life. Although the cause is usually benign pathology, it can be a cause of anxiety for the patient and usually warrants investigation to exclude any sinister underlying pathology. Patients who present with AUB make up a significant proportion of the caseload in the gynaecology clinic. Outpatient assessment and investigation has changed the management of many common gynaecological conditions. This change has been driven by the demands of both patients and clinicians to provide rapid, accurate diagnosis, with a minimum of investigations, invasive procedures and in particular hospital visits, which are often expensive and time-consuming.
Transvaginal ultrasonography (TVS) plays an important role in the assessment of women with AUB. Transvaginal probes provide high-resolution images of the pelvic organs, providing reliable and reproducible information . The fact that a full bladder is not required improves patient acceptability.
Patients with AUB are ideally suited to assessment by transvaginal ultrasonography at the time of presentation or assessment in the outpatient setting. A scan should be seen as a part of the overall clinical assessment of the patient and never examined in isolation. There are obvious advantages to the gynaecologist performing the scan as they can weigh up all the available information about the patient and place the scan findings in the correct context. An accurate scan can enable the clinician to avoid surgery in some cases and select the correct surgical approach in others. In women with AUB, TVS can be combined with outpatient endometrial sampling techniques as part of a “one-stop” approach to diagnosis and management . The basic requirements for ultrasonography are a transvaginal probe (5–7.5 MHz), a 3.5-MHz transabdominal transducer and facilities for capturing images, either as a hard copy or digitally. The facility to perform Doppler studies or carry out three-dimensional ultrasonography is not essential. The transducer should be cleansed with a germicidal (e.g. 70% alcohol) cloth or spray effective in preventing cross infection.
This review aims to deal with the role of ultrasonography (in particular TVS) in the assessment of the patient presenting with AUB, in which gynaecological pathology is suspected. Transvaginal ultrasonography as an extension of the clinical examination may not diagnose the cause of all presenting complaints; however, the failure to demonstrate pathology can be highly reassuring and obviate the need for further investigation
Saline infusion sonography
Saline infusion sonography (SIS) is a simple technique involving the instillation of sterile saline into the uterine cavity [4, 5, 6]. A bi-valve speculum is used to visualise the cervix, then a catheter is used to instil the saline through the cervical canal into the uterine cavity. We use a 5-F paediatric nasogastric feeding tube. A number of catheters with or without balloon catheters are commercially available. The balloon helps to reduce backflow of saline and maintain uterine distension; however, in our experience they are rarely needed. The balloon devices tend to more expensive, are not readily available and distension of the balloon at the internal cervical os can cause increased discomfort, and obscure the view in the lower aspect of the cavity. The SIS facilitates the generation of clear images of the endometrial cavity and this obviates the need for hysteroscopy in the majority of women.
Thickened or irregular endometrium
Poor views of the endometrium, e.g. due to axial position of uterus or a large fibroid distorting the cavity.
Preoperative localisation, size and relation to cavity of submucous fibroids/endometrial polyps prior to hysteroscopic surgery.
Transvaginal ultrasonography is a well-tolerated procedure, even when SIS is performed the routine use of analgesia is not required in most cases [7, 8]. In a randomised trial Timmerman et al.  demonstrated that patients preferred TVS with SIS to outpatient hysteroscopy. The SIS should not be performed in the presence of overt pelvic infection. Although the risk of pelvic infection following SIS is very small, in our practice we give prophylactic antibiotics to all potentially fertile women. An important practical requirement is a database system for archiving ultrasound images and producing reports. This enables the operator to produce a report as soon as the scan has been completed and facilitates audit and clinical review.
The normal endometrial pattern
The “one-stop” ultrasound-based clinic
The average age of the menopause in the UK is 51 years, and women still menstruating after the age of 55 years should be investigated. About 5% of women attending gynaecological clinics present with postmenopausal bleeding (PMB). The majority of women with PMB will have a benign cause for their bleeding, the commonest being genital tract atrophy; however, 10% will have a primary or secondary malignancy. The commonest malignancy is endometrial cancer of which 80% present with PMB. The risk of endometrial cancer in women with PMB increases with age from about 1% at the age of 50 years to 25% at the age of 80 years. The TVS is the first-line investigation of choice in the assessment of PMB. There is good evidence in the literature to show that irrespective of hormone use, an endometrial thickness measurement of 4 mm or less is associated with endometrial atrophy [10, 12, 13, 23, 24]. Irrespective of hormone replacement therapy (HRT) use, using a >4-mm cutoff value to define an abnormal endometrium, 96% of women with endometrial cancer and 92% of women with endometrial disease (hyperplasia, polyps and fibroids) will have an abnormal result, with a false-positive rate of 39 and 19%, respectively .
Irregular bleeding on hormone replacement therapy
Up to 10% of women on HRT report unscheduled vaginal bleeding. There are a variety of hormone replacement preparations available on the market. It is essential to know what type of preparation the patient is on prior to assessing the endometrium, as this may affect the endometrial appearance. For a 4-mm endometrial thickness cutoff, the number of women with false-positive results is higher among women using HRT (23%) compared with non-users (8%) . The higher false-positive results seen in HRT users are related to the day of the cycle when the scan is performed. For patients taking sequential HRT the timing of an ultrasound scan suggested for optimal results is between 5 and 10 days from the end of the progestogen phase [30, 31]. In contrast, TVS can be performed at any time in women receiving continuous HRT. Omodei et al. have shown that the ET does not differ between women taking sequential compared with those on continuous combined HRT (3.6 vs 3.2 mm), if the measurement is taken on the fifth to tenth day following the last progestogen tablet . A woman with a 1% risk of cancer, which is the risk associated with vaginal bleeding in a postmenopausal woman using combined HRT, will have a 0.1% risk of cancer following a negative (≤4 mm) ultrasound examination result.
Tamoxifen and the endometrium
Tamoxifen is used as adjuvant therapy in women diagnosed with breast cancer and more recently its effectiveness as a chemo-prevention agent has been established . Tamoxifen use is associated with an increased risk of developing endometrial cancer (2 of 1000 tamoxifen treated women). The ultrasound appearance of the endometrium in women taking tamoxifen may be difficult to interpret. It may appear as thickened cystic endometrium, and using SIS, 50% of such cases have been shown to harbour large endometrial polyps . The remaining cases have sub-endometrial cystic changes with thin atrophic endometrium. For women who have abnormal bleeding on tamoxifen the ultrasound data are unclear and it is advisable to seek histological confirmation that the cavity is normal.
The TVS has also been proposed as a non-invasive means of screening for endometrial cancer in tamoxifen-treated women. Kedar et al. evaluated 111 asymptomatic at risk women randomly assigned to tamoxifen or placebo in a pilot chemo-prevention study . The TVS was performed after a median time of 2 years and the mean endometrial thickness in the tamoxifen-treated group was nearly twice that of the placebo group. Although no cancers were detected in this study, 10 women had endometrial hyperplasia in the tamoxifen group. They concluded that an endometrial thickness >8 mm had a 100% positive predictive value at detecting endometrial pathology. Other authors have published conflicting data questioning the efficacy of TVS as a surveillance method [35, 36, 37]. Timmerman et al. compared the ability of TVS with SIS to office hysteroscopy, in detecting endometrial pathology in women on adjuvant tamoxifen therapy . In this randomised crossover study there was no difference in the sensitivity and specificity of TVS/SIS and hysteroscopy; however, two endometrial cancers were detected by ultrasound alone. The TVS/SIS was more acceptable to the patients.
Pre-treatment screening has also been suggested. Berliere et al screened 264 women with breast cancer and found that 17% (46 of 264) of asymptomatic postmenopausal had a thickened endometrial lining prior to tamoxifen therapy . Hysteroscopy confirmed submucous myoma (n=7), benign polyps (n=34), simple hyperplasia (n=3), atypical hyperplasia (n=1) and endometrial cancer (n=1). Of the patients who subsequently developed pre-malignant or malignant conditions on tamoxifen therapy, 80% had had an endometrial lesion at pre-treatment assessment. This suggests that pre-treatment assessment might identify women at risk of developing endometrial cancer.
The small increase in risk of endometrial cancer is outweighed by the benefits tamoxifen provides for women who have suffered from or who are at risk of breast cancer. Pre-treatment assessment prior to tamoxifen therapy appears encouraging; however, its cost-effectiveness needs to be assessed prospectively as the majority of the pre-malignant and malignant endometrial lesions present with symptoms and the treatment of early-stage endometrial cancer is quite successful. Only a large randomised trial with reduction in the mortality rate form endometrial cancer as the end point could prove that endometrial cancer monitoring in patients with breast cancer who are treated with tamoxifen is useful.
Menorrhagia is a common symptom in pre- and perimenopausal women. The role of TVS in these patients is to exclude focal or global pathology. In the absence of pathology, and with a normal endometrial biopsy the patient is diagnosed with dysfunctional uterine bleeding. The common pathologies found in women with menorrhagia are fibroids, polyps and adenomyosis.
Timmerman et al.  described the use of colour Doppler as an alternative to SIS and hysteroscopy as a second stage test after TVS. Patients with a clearly visible pedicle artery reaching the central part of the endometrium were regarded as test positive. In this series the pedicle artery sign had a sensitivity of 76.4%, specificity of 95.3% and a positive and negative predict value of 81.3 and 93.8%, respectively. The high negative predictive value of colour Doppler may negate the need for SIS or hysteroscopy in selected patients. In another recent study  blood flow impedance (resistive index, pulsatility index) failed to predict histological type in a cohort of symptomatic and asymptomatic women with endometrial polyps. This study suggests that the objective assessment of blood flow impedance within an endometrial polyp or its size can replace surgical removal and pathologic evaluation to predict histological type; however, the natural history of endometrial polyps is still unclear, and the question as to whether all endometrial polyps should be removed is valid. In a recent study De Waay et al. , over a 2.5-year period, noted that small endometrial polyps frequently regressed, whereas larger polyps were more likely to persist and were associated with the development of abnormal bleeding. It is clear that further prospective studies are needed to assess the natural history of polyps to help develop appropriate treatment strategies. For the moment, the detection of such focal pathology is an intrinsic part of the evaluation of women with abnormal bleeding.
Adenomyosis is a common gynaecological disorder that affects women of reproductive age. Patients are often multiparous and present with menorrhagia and secondary dysmenorrhoea. Adenomyosis is characterised by the presence of endometrial glands and stroma with smooth muscle hyperplasia, which usually affects the inner third of the myometrium, and rarely affects the cervix. Until recently, the diagnosis was rarely made prior to hysterectomy; however, the improved image quality obtained by TVS has led to a significant improvement in diagnostic accuracy. Adenomyosis may be nodular with circumscribed aggregates or diffuse with foci scattered throughout the myometrium. The ultrasound appearance is varied and includes hypoechoeic areas, heterogeneous myometrial echotexture, asymmetric uterine enlargement and subendometrial cysts. In the literature the sensitivity and specificity of the ultrasound diagnosis of adenomyosis is 53–89% and 75–96%, respectively [51, 52, 53, 54, 55]. This suggests that the diagnosis is operator dependent, and that different histological criteria and sampling techniques were used in these studies.
In women with AUB, TVS affords assessment of the adnexa. Ovarian and tubal pathology can be accurately characterised in experienced hands. Jones and Bourne  found adnexal pathology in 13% of patients attending an abnormal uterine bleeding one-stop clinic. The discovery of adnexal pathology may have an immediate impact on management; otherwise, any incidental findings can be surgically treated electively or followed up conservatively.
The AUB is frequently a cause for concern in both pre- and postmenopausal women. Although the majority of the pathology is benign, serious underlying pathology, such as endometrial cancer, should be excluded. Investigations should be outpatient based, with the use of ultrasonography, outpatient hysteroscopy and endometrial biopsy devices. The TVS should be the primary diagnostic tool in the one-stop clinical setting, as when combined with SIS it compares favourably with hysteroscopy. Transvaginal ultrasonography is the least invasive investigative technique available for the investigation of AUB and provides additional information about adnexal pathology. It is well tolerated by patients and provides accurate reproducible images of the pelvic viscera. Experience in the use of TVS is necessary and knowledge of the stage of the menstrual cycle in premenopausal women is essential for accurate interpretation of the findings. The SIS should be used when the endometrial cavity is not seen clearly. This outpatient TVS-based one-stop approach allows patients to be triaged, thus facilitating rapid diagnosis and immediate decisions regarding management. Postmenopausal women can be reassured that in the presence of a thin endometrium they are extremely unlikely to have any sinister endometrial pathology. In premenopausal women, having excluded focal pathology, patients can be treated for dysfunctional uterine bleeding, with medical therapy, progesterone releasing intrauterine devices, endometrial ablation or hysterectomy. Those patients with focal endometrial pathology can be selected for operative hysteroscopy as a day case procedure following a single visit to the hospital. Diagnostic hysteroscopy should be reserved for cases where SIS has been unsuccessful at elucidating the endometrial cavity, and in experienced hands this should be a rare occurrence. With the advances in ultrasound technology and improved training in ultrasonography, in the near future the use of a small portable transvaginal ultrasound machine by a gynaecologist in the outpatient setting will become an intrinsic part of the gynaecological examination of women with AUB.
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