The role of detailed history taking and a thorough general and pelvic examination cannot be overemphasized. A clinician must always rule out pregnancy in any women of reproductive age group before proceeding further. History should elicit the duration and severity of symptoms, any associated vaginal discharge, and postcoital bleeding. History of any chronic medical condition like hypertension or diabetes should be taken along with history of any drug intake (e.g., tamoxifen in breast cancer patients, hormone therapy in postmenopausal females). Family history of cancer such as in cases of hereditary non-polyposis colorectal cancer should be sought as such women are at risk of developing endometrial cancer (lifetime risk being 60 %). Initial basic investigation must include a complete blood count to assess degree of anemia, and after confirming that bleeding is from uterus, one must proceed in a systematic fashion to ascertain the exact cause of abnormal uterine bleeding.

Anovulatory bleeding is characterized by abnormal duration, frequency, or volume of bleeding over baseline occurring at irregular intervals and often interspersed with periods of amenorrhea. All reproductive age and perimenopausal females with suspected recurrent anovulatory cycles must undergo evaluation for anovulation which includes endometrial sampling.

Histopathologic evaluation of the endometrium can efficiently exclude endometrial hyperplasia or malignancy but is not required for all patients of AUB. The treating clinician must select women based on a combination of factors which when present increase the risk of endometrial hyperplasia or endometrial carcinoma. Several reports and guidelines use age, personal, and genetic risk factors along with TVS screening for endometrial echo complex thickness to determine which patients should undergo endometrial sampling [5, 7, 8]. Although age over 35 years is nowadays considered as the lower limit for biopsy in women with abnormal bleeding but regardless of age, persistent AUB that is unexplained or not adequately treated requires endometrial sampling, if possible, in association with hysteroscopic evaluation of the endometrial cavity [2, 3]. Several techniques can be used to perform endometrial sampling, but most importantly, one must ensure to obtain an adequate sample before declaring that a woman is at low risk of malignant neoplasm [9].

Office endometrial aspiration is a relatively inexpensive, convenient, and safe procedure which is now preferred over a blind endometrial curettage. It is performed using a small flexible suction cannula (Pipelle device) which suctions the shedded endometrial cells especially the malignant ones which are relatively more fragile, and hence, even a focal malignant lesion is likely to be picked up. In premenopausal women, endometrial biopsy (EB) using Pipelle is 82.3 % sensitive for detecting endometrial hyperplasia with atypia and 91 % sensitive for detecting endometrial carcinoma, while the specificity is 98 % for both. In postmenopausal women the sensitivity is as high as 99.6 %, thus making it the best device for endometrial sampling, and inadequate sampling has been reported only in 10–12 % of cases [10]. Inadequate samples must be re-evaluated with TVS and hysteroscopy to avoid missing an endometrial cancer and must not be construed as negative for malignancy.

ACOG recommends that women with postmenopausal bleeding must be assessed to exclude malignancy with either endometrial biopsy or TVS; the initial assessment does not require performance of both the tests. If on TVS, endometrial thickness (ET) is ≤4 mm, EB is not required, but endometrial thickness of >4 mm or inability to adequately visualize the endometrium must trigger alternative evaluation including office hysteroscopy or EB [11].

To evaluate the structural abnormalities of the uterine cavity, TVS has been utilized as the first-line screening tool in evaluating AUB. The benefits of TVS lie in its effectiveness in assessing the complete pelvis, its ease of application, patient acceptability, and immediate results. On TVS, endometrial thickness is measured as the maximum anteroposterior thickness of the endometrial echo on a long axis view of the uterus. If TVS shows ET of less than 5 mm, the probability of the woman having endometrial cancer is 1.7 % and it is 0.8 % when the cut-off is taken as 4 mm. In perimenopausal and postmenopausal women with AUB, endometrial sampling is generally considered unnecessary when the endometrial thickness is less than 4 mm since the risk of endometrial hyperplasia or cancer is extremely low. Endometrial biopsy is indicated when the clinical history is suggestive of long-term estrogen exposure even when the ET is normal on ultrasound (5–12 mm), and biopsy must be considered when ET is greater than 12 mm even when the clinical suspicion of disease is low [12]. Transvaginal ultrasound detects intracavitary abnormalities like uterine tumors, polyps, and endometrial and myometrial abnormalities with a sensitivity of 60–92 % and a specificity of 62–93 % in perimenopausal women [13, 14]. Since TVS is not 100 % sensitive for diagnosing endometrial polyps and other small lesions, examination with other imaging techniques like saline infusion sonohysterography (SIS) or hysteroscopy should be considered [15]. Another limitation of ultrasound is that it cannot always reliably distinguish between benign proliferation, hyperplasia, polyps, and cancer, and in 5–10 % of women with postmenopausal bleeding, the endometrium cannot be identified on USG, these women need further evaluation with more sensitive techniques [16].

It is usually considered that benign lesions have high resistance vessels (mostly single feeding artery) and malignant lesions have low resistance vessels (mostly multiple feeding vessels with broad base); based on this principle, Doppler studies may be considered useful in differentiating between the two, but studies have shown that Doppler does not improve the detection of premalignant and malignant lesions of the endometrium [17].

Saline infusion sonohysterography (SIS) or sonohysteroscopy is the technique of contrast enhancement of transvaginal scan which further increases the sensitivity and negative predictive value of sonographic evaluation. The procedure involves instillation of 5–10 ml of saline in the uterine cavity using 5–8 F Foley’s catheter followed by TVS. Once the cavity is distended by anechoic saline, lesions like endometrial polyps, submucous fibroid, and lesions distorting endometrial contour are better identified. In a study by Mathew et al., SIS has been shown to have a better sensitivity in evaluating endometrial cavity as compared to TVS alone (91.4 % vs. 72.4 %). Negative predictive value of SIS was found to be 94.1 % as compared to 74 % for TVS [18]. The combination of sonohysterography and endometrial biopsy offers a high sensitivity and negative predictive value for detection of endometrial and uterine pathologies, especially in women with focal endometrial lesions [19]. Although it is feasible to conclude that SIS can be used as an effective screening tool prior to hysteroscopy in evaluating women with abnormal uterine bleeding, increased cost and limited availability as compared to TVS must also be considered. Further studies have also compared the role of 3-D sonohysterography and hysteroscopy in detecting intrauterine lesions and concluded that 3-D sonohysterography is comparable to hysteroscopy for investigating intrauterine lesions in perimenopausal and postmenopausal females with AUB [20].