Introduction

The endometrium is sampled when pathology is suspected; this may be when the patient experiences a change in her normal pattern of menstrual bleeding or when bleeding is unexpected, e.g. after the menopause.

When a patient presents with any of these symptoms the GP should undertake a full pelvic examination, including speculum examination of the cervix.

Guidelines advising when to refer urgently state:¹

Risk factors for endometrial cancer

These include:²

• Nulliparity.
• Family history of endometrial or colonic cancer.
• Tamoxifen or unopposed oestrogens.
• Polycystic ovary syndrome.
• Obesity.

Initial investigations

• Transvaginal ultrasound measurement of endometrial thickness has become a routine procedure and an initial investigation in patients with abnormal uterine bleeding.
• There is debate as to whether a cut-off of 5 mm or 4 mm endometrial thickness should be employed. 5 mm has become standard for the postmenopausal patient.³
• If the endometrial thickness is above these values, polyps have been diagnosed or the patient is presenting with recurrent bleeding, endometrial disease has to be excluded by histological assessment.
• It should also be remembered that advanced endometrial cancer has subsequently been diagnosed where the endometrium was measured at ≤5 mm, so high-risk patients should also have sampling.⁴
• Outpatient aspiration curettage has superseded dilatation and curettage, which was previously considered to be the gold standard for obtaining endometrial tissue, and provides the same sensitivity in detecting endometrial disease.⁵
• Hysteroscopy allows visualisation of the uterine cavity and the opportunity for targeted biopsy and removal of endometrial polyps.

Endometrial biopsy

• Performed without prior cervical dilatation.⁶
• Introduced in the 1930s, using narrow metal cannula with side opening with serrated edges and syringe attached for suction as instrument removed.
• As the cannula is rotated during removal, a strip of endometrium is peeled off and sucked into the syringe. This causes significant cramping during removal.
• A more recent alternative is the Vabra® curette requiring vacuum source and also causing significant cramping.
• Recent research has trialled transcervical instillation of 5 mls 2% lidocaine. This significantly reduced pain during endometrial sampling.⁷

Today the most popular device is the disposable Cornier® pipelle.⁸

Pipelle biopsy

• Pipelle endometrial biopsy is a cost-effective and safe procedure that is well-tolerated by patients.
• There is less pain and a lower risk of perforation with the pipelle than with the Novak® curette.⁹
• In addition, the pipelle is more portable than the Novak® curette and the Vabra® aspirator, both of which require external suction.
• The detection rates for endometrial carcinoma using the pipelle device were found by one meta-analysis to be 99.6% in postmenopausal women and 91% in premenopausal women.⁸
• In postmenopausal women, the combined use of pipelle sampling and ultrasound has a high detection rate for endometrial carcinoma.^10,11
• The pipelle is poor at detecting endometrial pathologies such as polyps and submucosal myomas.¹⁰
• Pipelle aspirates provide accurate endometrial sampling in premenopausal patients with abnormal uterine bleeding.¹²
• However, sampling error is greater with the pipelle and the device samples only 4% of the endometrium compared with 42% with the Vabra® aspirator.¹³

Procedure

• Bimanual examination to asses the uterus.
• The cervix is then visualised and cleaned.
• A tenaculum is applied to the anterior lip of the cervix, and is used to provide gentle traction whilst a sound is inserted though the cervical os. This minimises the risk of perforation.
• Dilators may be required if there is difficulty in passing the sound.
• When the position and size of the uterine cavity have been assessed, the pipelle is inserted through the cervical os and advanced until gentle resistance is felt.
• The inner piston of the device is then withdrawn to create suction and the endometrial sample is obtained by moving the pipelle up and down within the uterine cavity by approximately 2-3 cm but not beyond the cervical os.
  
  
• This procedure should be repeated at least four times and the device rotated 360° to ensure adequate coverage of the area.
• The pipelle is then withdrawn from the cervical os and the endometrial sample expelled into a solution of formalin for transport to the laboratory.

Pipelle endometrial sampling can also be combined with hysteroscopy.
Other devices include the Gravlee Jet Washer®, Mi-Mark® spiral sampler, Gynoscann® surface stripper (based on intrauterine contraceptive device (IUCD) insertion principle), the H Pipelle®¹⁴ and the Tao brush®.¹⁵

Contra-indications

These include:

• Pregnancy.
• Acute vaginal or cervical infection.
• Pelvic inflammatory disease.
• Clotting disorders.

Complications

These include:

• Prolonged bleeding.
• Infection.
• Uterine perforation and post-procedure pain.
• Bacteraemia can occur after endometrial sampling (antibiotic prophylaxis must be given to patients at risk of endocarditis.¹⁶)

Dilatation and curettage

This has been the traditional technique for obtaining samples of endometrium for pathological examination. However, 'blind' dilatation and curettage (D&C) has been shown to miss significant amounts of pathology, including:

• Endometrial polyps
• Intrauterine mucous fibroids
• Small areas of endometritis
• Hyperplasia or cancer
• Lost IUCDs

• Uterine perforation. This is rarely serious, with healing usually rapid and complete.
• It is more common in postmenopausal or postpartum women.
• False passage in the cervix or cervical damage producing cervical incompetence from a large dilator.
• Infrequently, postoperative infection or intrauterine adhesions.

Hysteroscopy is the gold standard but not always readily available.

Endomyometrial resection biopsy

• 3-5 mm deep biopsy obtained with hystero-resectoscope loop.
• This is used to identify adenomyosis or to investigate deep lesions of the endometrium.
• It permanently removes a narrow strip of basal endometrium with underlying myometrium.
• This usually heals well.

Document references

1. Referral for suspected cancer, NICE Clinical Guideline (2005)
2. Oehler MK, Rees MC; Menorrhagia: an update.; Acta Obstet Gynecol Scand. 2003 May;82(5):405-22. [abstract]
3. Nutis M, Garcia KM, Nuwayhid B, et al; Use of ultrasonographic cut point for diagnosing endometrial pathology in postmenopausal women with multiple risk factors for endometrial cancer. J Reprod Med. 2008 Oct;53(10):755-9. [abstract]
4. Dimitraki M, Tsikouras P, Bouchlariotou S, et al; Clinical evaluation of women with PMB. Is it always necessary an endometrial Arch Gynecol Obstet. 2011 Feb;283(2):261-6. Epub 2010 Aug 4. [abstract]
5. Oehler MK, MacKenzie I, Kehoe S, et al; Assessment of abnormal bleeding in menopausal women: an update.; J Br Menopause Soc. 2003 Sep;9(3):117-20, 121. [abstract]
6. Seamark CJ; Endometrial sampling in general practice.; Br J Gen Pract. 1998 Sep;48(434):1597-8. [abstract]
7. Hui SK, Lee L, Ong C, et al; Intrauterine lignocaine as an anaesthetic during endometrial sampling: a randomised double-blind controlled trial.; BJOG. 2006 Jan;113(1):53-7. [abstract]
8. Dijkhuizen FP, Mol BW, Brolmann HA, et al; The accuracy of endometrial sampling in the diagnosis of patients with endometrial carcinoma and hyperplasia: a meta-analysis.; Cancer. 2000 Oct 15;89(8):1765-72. [abstract]
9. Hill GA, Herbert CM 3rd, Parker RA, et al; Comparison of late luteal phase endometrial biopsies using the Novak curette or PIPELLE endometrial suction curette. Obstet Gynecol. 1989 Mar;73(3 Pt 1):443-5. [abstract]
10. Van den Bosch T, Vandendael A, Van Schoubroeck D, et al; Combining vaginal ultrasonography and office endometrial sampling in the diagnosis of endometrial disease in postmenopausal women. Obstet Gynecol. 1995 Mar;85(3):349-52. [abstract]
11. Stovall TG, Photopulos GJ, Poston WM, et al; Pipelle endometrial sampling in patients with known endometrial carcinoma. Obstet Gynecol. 1991 Jun;77(6):954-6. [abstract]
12. Goldchmit R, Katz Z, Blickstein I, et al; The accuracy of endometrial Pipelle sampling with and without sonographic measurement of endometrial thickness. Obstet Gynecol. 1993 Nov;82(5):727-30. [abstract]
13. Rodriguez GC, Yaqub N, King ME; A comparison of the Pipelle device and the Vabra aspirator as measured by endometrial denudation in hysterectomy specimens: the Pipelle device samples significantly less of the endometrial surface than the Vabra aspirator. Am J Obstet Gynecol. 1993 Jan;168(1 Pt 1):55-9. [abstract]
14. Madari S, Al-Shabibi N, Papalampros P, et al; A randomised trial comparing the H Pipelle with the standard Pipelle for endometrial sampling at 'no-touch' (vaginoscopic) hysteroscopy. BJOG. 2009 Jan;116(1):32-7. [abstract]
15. Williams AR, Brechin S, Porter AJ, et al; Factors affecting adequacy of Pipelle and Tao Brush endometrial sampling. BJOG. 2008 Jul;115(8):1028-36. [abstract]
16. Livengood CH 3rd, Land MR, Addison WA; Endometrial biopsy, bacteremia, and endocarditis risk. Obstet Gynecol. 1985 May;65(5):678-81. [abstract]

Internet and further reading

• Menorrhagia, Clinical Knowledge Summaries (2007)
• National Cancer Institute. Endometrial Cancer: screening

Acknowledgements