Endometrial Evaluation in Peri-menopausal Abnormal Uterine Bleeding

Endometrial Evaluation in Peri-menopausal Abnormal Uterine Bleeding

Abnormal uterine bleeding (AUB): An Overview

Abnormal uterine bleeding (AUB) is one of the most common presenting complaints encountered in a Gynecologist’s office. AUB is defined as ‘bleeding that is excessive or occurs outside of normal cyclic menstruation’. It is one of the most common health problems encountered by women. It affects about 20% women of reproductive age, and accounts for almost two thirds of all hysterectomies. Because of its broad range of differential diagnosis, the diagnosis of AUB can be quite challenging; despite a detailed history, various blood tests, and a thorough pelvic examination often involving transvaginal ultrasonography (TVS), the cause of the bleeding is established in only 50-60% of the cases.

AUB in  Peri-menopause : What makes it so challenging !

The major challenge to address is to allay the worries about possible uterine cancer while treating a lady for AUB in peri-menopause and post-menopause. A visual and the histological assessment of the endometrium; therefore remains the cornerstone in the gynecologic practice. Besides systemic, iatrogenic or hormonal age-related causes, an endometrial pathology (polyps, submucous myomas, endometrial hyperplasia, and endometrial carcinoma) should always be suspected, and evaluation appears to be mandatory. Infectious endometritis can also be a cause for irregular bleeding and even endometrial atrophy may, at times, manifest as abnormal bleeding. 

The consequences of abnormal uterine bleeding on an individual’s overall health determine the degree to which intervention may be required. Diagnostic evaluations and treatment modalities have been evolving over time. The onus in AUB management is to exclude complex endometrial hyperplasia and endometrial cancer. Diagnosis and treatment of endometrial pathology can nowadays benefit from well-established techniques, ranging from clinical examination to TVS, saline infusion sonohysterography (SIS), hysterosalpingography, hysteroscopy (HYS), and endometrial biopsy.

The American College of Obstetricians and Gynecologists (ACOG) in it’s Practice Bulletin “Management of Abnormal Uterine Bleeding Associated With Ovulatory Dysfunction” (July 2013) recommends, 

“All women older than 45 years who present with suspected anovulatory uterine bleeding should be evaluated with endometrial biopsy (after pregnancy has been excluded).”


Evaluation of  Endometrium


Evaluation of the endometrium as a cause of AUB is mainly three in modes;

• Imaging of patterns endometrium by transvaginal ultrasound, Saline infusion sonohysterography (SIS) and to some extent a magnetic resonance imaging (MRI)

• Visual assessment by Hysteroscopy (HYS),  and

• Cellular assessment by microscopic evaluation of endometrial samples


Hysteroscopy and visually directed endometrial biopsy

Hysteroscopic evaluation for abnormal uterine bleeding is an option providing direct visualization of cavitary pathology and facilitating directed biopsy. Hysteroscopy may be performed in an office setting with or without minor anesthesia or in the operating room with regional or general anesthesia. Directed biopsies under direct vision provide the main benefit over “blind” dilation and uterine curettage. A hysteroscopic evaluation of the endometrial cavity and visually directed biopsy for histopathological evaluation is considered the gold standard for assessing the endometrium and detecting or ruling out endometrial cancer in gynecologic practice. 

The risks of hysteroscopy include perforation of the uterus, infection, cervical lacerations, creation of false passages, and fluid overload.

ACOG  in it’s Practice Bulletin “Management of Abnormal Uterine Bleeding Associated With Ovulatory Dysfunction” (July 2013) recommends, 

“Hysteroscopy permits full visualization of the endometrial cavity and endocervix and is extremely helpful in diagnosing focal lesions that may be missed with endometrial sampling. Performing hysteroscopy in the office is quick and less expensive than performing it in an operating room setting. Rapid visual inspection permits targeted biopsy and accurate diagnosis of atrophy, endometrial hyperplasia, polyps, leiomyomas, and endometrial cancer. The likelihood of endometrial cancer diagnosis after a negative hysteroscopy result is 0.4–0.5%.”


Transvaginal sonography 

Transvaginal sonography allows detailed assessment of anatomical abnormalities of the uterus and endometrium. In addition, pathologies of the myometrium, cervix, tubes, and ovaries may be assessed. This investigative modality may assist in the diagnosis of endometrial polyps, adenomyosis, leiomyomas, uterine anomalies, and generalized endometrial thickening associated with hyperplasia and malignancy.

Transvaginal ultrasonography is generally not recommended in the virginal patient, and transabdominal imaging is less sensitive and of limited value in the evaluation of the endometrium, but can be used to evaluate other structural abnormalities. 


Saline infusion sonohysterography (SIS)

SIS, an office-based imaging procedure, involves the introduction of 5 to 15 mL of saline into the uterine cavity during transvaginal sonography and improves the diagnosis of intrauterine pathology. Especially in cases of uterine polyps and fibroids, SIS allows for greater discrimination of location and relationship to the uterine cavity. As a result, SIS can also obviate the need for MRI in the diagnosis and management of uterine anomalies. 

SIS can determine the presence or absence of intracavitary lesions and depth of myometrial involvement with leiomyomas, and it more accurately evaluates the endometrium compared with transvaginal ultrasonography alone. One study demonstrated that endometrial thickness alone should not be used to exclude benign endometrial pathology in premenopausal women because this would miss one out of six intracavitary lesions. The study authors advocate the use of saline infusion sonohysterography or hysteroscopy to further evaluate the endometrium in premenopausal women with abnormal bleeding and normal endometrial thickness.

ACOG  in it’s Practice Bulletin “Management of Abnormal Uterine Bleeding Associated With Ovulatory Dysfunction” (July 2013) recommends, 

“Saline infusion sonohysterography coupled with endometrial biopsy is a good predictor of the type of surgical or medical intervention that can be offered. That is, when the results of Saline infusion sonohysterography and endometrial biopsy are both negative, the likelihood of identifying endometrial pathology is low, and conservative options can be offered. This streamlined approach facilitates patient care and minimizes unnecessary surgical intervention. Hysteroscopic surgery is recommended for focal intracavitary or endocervical lesions.”


MRI

MRI is rarely used to assess the endometrium in patients who have menorrhagia. It may be helpful to map the exact location of fibroids in planning surgery and prior to therapeutic embolization for fibroids. It may also be useful in assessing the endometrium when transvaginal ultrasound or instrumentation of the uterus (i.e., congenital anomalies) cannot be performed.


QUESTIONS


What is the role of “Dilatation and Curettage” (D and C) for the assessment of the endometrium?

A literature review (2013) for the evaluation of endometrium with the goals of finding an accurate reason causing the AUB and to rule out endometrial cancer or a potential for the cancer in future, mentioned the following;

“A blind D and C  used to be a gold standard procedure for all women with AUB in 40 + age group! However, a classic article questioned the efficacy and highlighted the limitations of this procedure. In 10-25% of patients, D and C alone may miss an existing endometrial pathology. It is associated with uterine perforation in 0.6-1.3% of cases, infection 0.3-0.5% and unexpected hemorrhage in 0.4% of cases. D and C, the former gold standard, and Vabra® are now recognized as other blind sampling techniques which often sample less than half of the endometrium and should no longer be performed, with limited exception. Hysteroscopically-directed sampling detects a higher percentage of abnormalities when compared directly with D and C as a diagnostic procedure.”

According to The Society of Obstetricians and Gynaecologists of Canada (SOGC) clinical practice guideline “Abnormal Uterine Bleeding in Pre-Menopausal Women” (May 2013);

“Dilatation and Curettage is no longer the standard of care for the initial assessment of the endometrium. It is a blind procedure, with sampling errors and risks of complications similar to hysteroscopy.”


Can “office endometrial biopsy” be offered to patients with Abnormal uterine bleeding associated with ovulatory dysfunction (AUB-O) ?

A literature review (2013) for the evaluation of endometrium with the goals of finding an accurate reason causing the AUB and to rule out endometrial cancer or a potential for the cancer in future, mentioned the following;

“Hysteroscopy and directed biopsy is the ‘gold standard’ approach for most accurate evaluation of endometrium to rule out focal endometrial Ca. Blind endometrial biopsies should no longer be performed as the sole diagnostic strategy in perimenopausal as well as in postmenopausal women with AUB.”

According to the American College of Obstetricians and Gynecologists (ACOG) Practice Bulletin “Management of Abnormal uterine bleeding associated with ovulatory dysfunction” (July 2013);

  • Office endometrial biopsy for the diagnosis of endometrial hyperplasia or cancer is preferred over dilation and curettage because it is less invasive, safer, and less expensive.  The biopsy also may provide information about the hormonal status of the endometrium.
  • However, the sensitivity of office endometrial biopsy is influenced by:
    • Type of lesion that is present (focal or diffuse)
    • Pathologic diagnosis (intracavitary leiomyoma or polyp)
    • Size of the lesion
    • Presence of uterine malformation
    • Volume of pathology
    • Surface area of the endometrial cavity, and 
    • Number of lesions
  • A meta-analysis noted that the sensitivity of endometrial biopsy was 68% in studies that used hysterectomy and 78% in studies that used dilation and curettage as the reference. Additionally, the meta- analysis concluded that there was a 0–54% rate of sampling failure.
  • An important limitation of office endometrial biopsy is that it samples an average of 4% of the endometrium with a reported range of 0–12%. The failure of office endometrial biopsy in postmenopausal women is particularly concerning. In postmenopausal women in whom the result of the office endometrial sampling was determined to be insufficient, 20% had uterine pathology after a secondary investigation, and 3% of the patients had malignant disease.
  • A classic study in 1995 demonstrated that endometrial cancer may be focal but that the Pipelle had a reported 83% sensitivity in detecting endometrial cancer. A retrospective study of 375 patients found that office-based endometrial biopsy had a low sensitivity for detecting polyps and leiomyomas, only 0.10 compared with 0.33 for diagnosing hyperplasia. Lesions that are focal or encompass a small surface area may be missed with office endometrial biopsy.