For the broader O&G Magazine readership, balanced answers to those curly-yet-common questions in obstetrics and gynaecology.

What is endometrial sampling?

Endometrial sampling, also known as endometrial biopsy, is a common medical procedure performed in women with abnormal uterine bleeding (AUB). It involves taking a tissue sample from the endometrium, the lining of the uterus. This sample undergoes a histological evaluation that can show cell changes due to abnormal tissue, variations in hormone levels or infection. First introduced in the 1930s, endometrial sampling originally used a narrow metal cannula with a side opening, serrated edges and syringe attached for suction as the instrument was removed. Today, the most widely used device is the disposable pipelle. It is cost-effective, safe and usually well-tolerated by patients.¹

Indications and contraindications

Indications for pipelle biopsy:

• Failed medical treatment of menorrhagia after three months;
• Significant risk factors such as BMI over 30 and older than 35 years of age;
• Inter-menstrual bleeding for more than three months in a 12-month period;
• Endometrial cells on cervical smears, with abnormal symptoms.

Absolute contraindications for pipelle biopsy:

• Pregnancy;
• Endometritis or acute pelvic inflammatory disease (PID).

Relative contraindications for pipelle biopsy:

• Coagulation disorders or anti-coagulant therapy;
• Synthetic heart valves or heart murmurs/valve disease. Procedure is preceded by a dose of antibiotics two hours beforehand;
• Previous LLETZ (large loop excision of the transformation zone) or cone biopsy. These can stenose the cervical canal and make insertion difficult.

Aetiology of AUB

AUB refers to uterine bleeding that is excessive or occurs outside of normal cyclic menstruation. AUB can be classified in two major categories.

AUB in non-pregnant reproductive-age women

A comprehensive, but flexible, classification system for underlying aetiologies of AUB has been developed by the International Federation of Gynaecology and Obstetrics Menstrual Disorders Committee (FIGO MDC).

The classification system is stratified into nine basic categories arranged according to the acronym PALM-COEIN: polyp; adenomyosis; leiomyoma; malignancy and hyperplasia; coagulopathy; ovulatory dysfunction; endometrial dysfunction; Iatrogenic; and ‘not otherwise classified’.

The FIGO MDC advised that the diagnoses should be classified under three definable headings:

• Systemic disorders of hemostasis (the coagulopathies) (AUB-C);
• Ovulatory disorders (AUB-O) – Generally reflecting dysfunctional relationships in the hypothalamic-pituitary-ovarian axis that typically manifest with symptoms of the irregular onset of uterine bleeding;
• Primary disorders of endometrial origin (AUB-E) – Disturbances principally caused by the molecular and cellular mechanisms responsible for regulation of the volume of blood lost at menstruation. Other infectious endometrial disorders, such as chlamydial endometritis, should be included here.²

Postmenopausal bleeding

All postmenopausal women with unexpected uterine bleeding should be evaluated for endometrial carcinoma since this potentially lethal disease will be the cause of bleeding in 10 per cent of cases.

The differential diagnosis of bleeding in postmenopausal women is less broad than for abnormal bleeding in premenopausal women, since the various causes of anovulation are not relevant. Causes include: atrophy, cancer (endometrial, fallopian tube or ovarian, vaginal), polyps, endometrial hyperplasia, disease in adjacent organs, anticoagulant therapy, or infection. The management of postmenopausal bleeding (PMB) will depend on ultrasound results:

• If the endometrium is less than 5mm, no further treatment is required (except to treat atrophic vaginitis) and follow up is within two months;
• If the endometrium is more than 5mm thick, or the scan reports fluid or cystic spaces within the endometrium regardless of thickness, a pipelle biopsy is performed.

When the pipelle biopsy is done in the community, further management will depend on the histology report, taking the endometrial thickness into consideration as well.

Gynaecology assessment will be required if:

• The sample is inadequate, insufficient or limited;
• Histology is abnormal;
• The sample is normal but the thickness is greater than 8mm: then a gynaecology assessment needs to look for other pathology, such as a polyp.³

Using a pipelle

Generally, a pipelle biopsy follows this process:

• A vaginal exam is performed to assess cervix position, whether the uterus is anteverted or retroverted, and whether it is enlarged;
• A speculum is inserted to expose the cervix. A tenaculum may be required to hold the cervix steady for the biopsy;
• The pipelle is inserted through the external cervical os until the fundus is reached (touching the fundus is best avoided, as it causes discomfort);
• The central piston is withdrawn to create a vacuum, then the device is rotated while moving back and forth/up and down the cavity, three to five times. The sample should be seen in the chamber of the device;
• The sample obtained is placed in a container with formalin, which is labeled and sent to histology;
• The pipelle procedure takes one minute.

There are a small number of risks: spotting or bleeding after the procedure (for less than one hour); crampy period-like discomfort (which is usually short-lived); and an extremely small risk of infection or uterine perforation.^{4 5}

Pathway of care incorporated by GPs

Counties Manukau District Health Board (DHB) in Auckland, New Zealand, has a funded pathway for the management of AUB. The model of care incorporates a credentialing module for GPs to diagnose and provide non-surgical treatment and management for women of reproductive age presenting in primary care with symptoms of AUB. Postmenopausal bleeding is excluded from this funding package. The intent is that as many GPs as possible will be credentialed, so a patient can be treated and managed by her ‘regular’ GP without requiring referral to secondary care.

Training and oversight to maintain quality of care is provided by the secondary care clinical lead for gynaecology, in partnership with primary care. GPs are encouraged to manage women completely, however, assistance is readily available for further management or interpretation of results from a gynaecology senior medical officer, by writing an electronic referral to a virtual or actual clinic.⁶

Funding regulation

The credentialed GP will potentially perform an endometrial pipelle biopsy and refer the patient for a transvaginal ultrasound through a local radiology provider for the convenience of the patient. The DHB pays for the ultrasound and the pipelle biopsy. On receipt of the results, the GP will explain the diagnosis to the patient and, where appropriate, provide non-surgical treatment under protocol.

The preferred option for non-surgical treatment of AUB under this pathway is the insertion of a Mirena, a levonorgestrel-releasing intrauterine system. The Mirena is a subsidised item through the Pharmac Pharmaceutical Schedule if certain criteria are met. The initial criteria are:

• A clinical diagnosis of heavy menstrual bleeding;
• A failed response to, or intolerance to, other appropriate pharmaceutical therapies as per the Heavy Menstrual Bleeding Guidelines;
• Serum ferritin levels below 16µ/l (within the last 12 months) or haemoglobin levels below 120g/L.

If the woman would clinically benefit from a Mirena, but does not fulfil the above criteria, a Mirena can be sourced from the DHB on application by referral.^{7 8}

Statistical outcomes

An audit of the program from January to November 2017 found that 78 patients had received care under this pathway. This care was administered by 21 different GPs. The women were completely managed in primary care in 52 per cent of cases. There has been an increase in Mirenas inserted in primary care, with seven inserted in the 11-month time period.

The audit showed that results of the pipelle biopsies and ultrasounds had been managed appropriately, with 100 per cent of patients who needed referral to secondary care having been referred. Although 48 per cent of patients still needed referral to secondary care, they were triaged more appropriately, as their initial investigations had been completed. Despite the numbers being relatively small, this project does have some impact on the work load in secondary care.⁹

The increased use of Ferinject within primary care to treat anaemia associated with AUB completes the package of care for women with menorrhagia.

Why should GPs do pipelle biopsies?

Endometrial sampling offers a number of advantages. Endometrial cancers can be diagnosed in a more timely manner. Patients can be triaged more appropriately if they do need a referral. The burden is reduced on hospitals by avoiding a referral to secondary care (in over 50 per cent of cases, women can be managed in primary care, avoiding a secondary care referral).

1. Payne J. Endometrial sampling. Available from:https://patient.info/doctor/endometrial-sampling).
2. Uptodate. Approach to abnormal uterine bleeding in non-pregnant reproductive-age women. Available from:www.uptodate.com/contents/approach-to-abnormal-uterine-bleeding-in-nonpregnant-reproductive-age-women.
3. Uptodate. Postmenopausal uterine bleeding. Available from: www.uptodate.com/contents/postmenopausal-uterine-bleeding.
4. Wikipedia. Endometrial biopsy. Available from: https://en.wikipedia.org/wiki/Endometrial_biopsy.
5. AUT. The endometrial sampling procedure. Available from: www.fmhs.auckland.ac.nz/en/som/about/our-departments/obstetrics-and-gynaecology/our-research/pip-studies/
   about.html.
6. Counties Manukau Health and Primary Care Partners. Management of Pathway of Care for Menorrhagia. August/2015. Access at:https://poac.rocketspark.co.nz/site_files/359/upload_files/INFORMATIONPACKAGEMENORRHAGIAPATHWAYMAY2015.pdf?dl=1.
7. Counties Manukau Health and Primary Care Partners. Management of Pathway of Care for Menorrhagia. August/2015. Access at:https://poac.rocketspark.co.nz/site_files/359/upload_files/INFORMATIONPACKAGEMENORRHAGIAPATHWAYMAY2015.pdf?dl=1.
8. Pharmac subsidy for Mirena. Available from:www.pharmac.govt.nz/news/notification-2013-11-15-levonorgestrel-ius/.
9. MQSG Annual report 2018. Abnormal uterine bleeding.