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Endometrial sampling procedures

Endometrial sampling procedures
Literature review current through: Jan 2024.
This topic last updated: Jan 25, 2022.

INTRODUCTION — Equipment and techniques for office-based endometrial sampling has generally replaced the need for diagnostic dilation and curettage (D&C) performed in the hospital. These techniques provide a minimally invasive option for diagnosis of endometrial cancer, hyperplasia, and other endometrial pathology.

Techniques for office procedures for endometrial sampling will be reviewed here. An overview of the diagnostic approach to endometrial evaluation for malignant and premalignant disease (including how to choose the method [eg, endometrial biopsy, D&C, transvaginal ultrasound] and advantages/disadvantages of each method), as well as a description of the D&C procedure, are discussed separately. (See "Overview of the evaluation of the endometrium for malignant or premalignant disease" and "Dilation and curettage".)

INDICATIONS AND CONTRAINDICATIONS

Indications — General indications for endometrial sampling are to evaluate for a precancerous or cancerous lesion (table 1) or to assess for a subclinical infection (eg, endometritis). Specific indications are discussed in detail in topics related to the underlying condition.

Contraindications — The only absolute contraindication to endometrial sampling is the presence of a viable and desired pregnancy.

A bleeding diathesis is a relative contraindication since bleeding may be excessive in such patients. In general, endometrial sampling may be performed in patients who are on anticoagulant therapy if coagulation parameters have consistently been within the standard therapeutic range. Laboratory testing should be performed within one month prior to the biopsy. If biopsy is required in a patient with an uncontrolled bleeding diathesis, consultation should be sought from the clinician managing this aspect of the patient's care. These patients may need to have anticoagulation reversed or have other treatments (eg, desmopressin). Patients with an uncontrolled bleeding diathesis should undergo endometrial sampling in an operating room setting with access to blood products and anesthesia. (See "Management of hemorrhage in gynecologic surgery".)

In the presence of acute vaginal, cervical, or pelvic infection, the procedure should be deferred, if possible, until the infection has been treated. This does not apply to clinical situations in which the indication for the biopsy is to evaluate for a subclinical infection.

In rare instances, in which endometrial sampling needs to be performed in a patient with cervical cancer, an obstructing cervical lesion may be a relative contraindication in some patients due to increased risk of bleeding or uterine perforation.

Sampling can be performed with an intrauterine device in place. In our practice, we have done so without complications. In addition, an ongoing clinical trial reports doing so as part of the study design [1]. No studies have evaluated whether performing endometrial sampling with an intrauterine device in place decreases the diagnostic performance.

PREPROCEDURE PREPARATION

Anesthesia — Office sampling procedures can usually be performed without significant pain. Discomfort can be minimized by reassuring the patient, explaining each step before doing it, and avoiding use of mechanical cervical dilators and/or a tenaculum, if possible. Some clinicians recommend an oral nonsteroidal anti-inflammatory drug (NSAID) 30 to 60 minutes prior to the procedure to decrease cramping, and others administer a paracervical block or use an intrauterine instillation of local anesthetic. Intrauterine instillation of a local anesthetic has been found to be more effective than placebo in randomized trials, although one trial found a significant effect only when the anesthetic was combined with an NSAID (5 mL of intrauterine 2% lidocaine and 550 mg of naproxen sodium) [2,3]. Topical 10% lidocaine spray (4 "puffs") significantly reduced pain during the procedure, but there was no difference by 15 minutes afterward [4]. Selective use of these techniques may be useful in some circumstances. (See "Pudendal and paracervical block".)

Cervical preparation and dilation — Cervical preparation or dilation is not required in many patients, particularly premenopausal parous patients. For those in whom it may be difficult to pass the sampling device without cervical dilation, misoprostol (200 to 400 mcg) orally, per vagina, or both may be given the night before the procedure [5]. The vaginal route of administration appears to be more effective than oral. Use of misoprostol for cervical preparation is discussed in detail separately. (See "Overview of hysteroscopy", section on 'Cervical preparation and dilation'.)

Patients with cervical stenosis not amenable to misoprostol may require that the procedure be performed under general or regional anesthesia, with mechanical cervical dilation or with ultrasound guidance in a surgical suite.

Prophylactic antibiotics — Prophylactic antibiotics are not necessary during endometrial sampling for the prevention of surgical site infection or bacterial endocarditis [6]. (See "Overview of preoperative evaluation and preparation for gynecologic surgery", section on 'Antibiotic prophylaxis'.)

GENERAL PROCEDURE — The basic steps common to all endometrial sampling procedures are as follows:

Place the patient in the dorsal lithotomy position.

Perform a bimanual examination, paying particular attention to the size, shape, and orientation of the uterus.

Insert a speculum and visualize the cervix.

Cleaning the cervix with antiseptic solution (eg, povidone-iodine) is performed by some, but not all, clinicians. Sterile preparation in patients who are allergic to iodine is discussed separately. (See "Overview of preoperative evaluation and preparation for gynecologic surgery", section on 'Vaginal preparation'.)

If anesthesia is to be used, it is administered prior to any other manipulation.

In many patients, an endometrial sampling device can be inserted without grasping the cervix with a tenaculum. Use of a tenaculum increases patient discomfort.

A tenaculum should be used if the uterus is not close to axial in position. In such cases, place a tenaculum (with teeth in a horizontal position) on the anterior cervical lip and retract outwardly to straighten the cervicouterine angle. Straightening the uterine axis may reduce the risk of uterine perforation. If a tenaculum is required and a paracervical block has not been given, we may apply a local anesthetic (eg, 2% benzocaine gel or 20% benzocaine spray) to the intended site before placing the tenaculum. Directing the patient to cough while simultaneously applying the tenaculum may also decrease discomfort. Patients scheduled for sampling may be advised to take an NSAID prior to arriving at the clinic.

Using steady and moderate pressure, slowly insert the sampling device through the cervical os and on to the uterine fundus. Stop when resistance is met.

If the device will not pass through the cervix, attach a tenaculum (if not already in place), and use a series of small (1 to 4 mm) Hegar or similar dilators to gently dilate the canal.

Many devices are marked with centimeters, so the device can be used to measure the uterine depth. Average uterine length is 6 to 8 cm.

Stabilize the sheath with one hand and pull the piston out as far as possible to create suction.

Move the device tip along the endometrial surface using a corkscrew rotation combined with a repeating cephalic-caudal motion while maintaining suction.

Remove the device when the entire cavity has been sampled. Expel the specimen into a formalin container. If there appears to be insufficient tissue for diagnosis, perform a second pass with the device. The same device may be used if it has not been contaminated; it should not have touched the formalin.

Remove the tenaculum, if present. Most bleeding can be controlled with pressure via cotton swabs or a sponge stick. If bleeding persists, use ferric subsulfate solution (Monsel's solution) or silver nitrate sticks to cauterize the site.

When using a suction device, do not let the sheath come outside of the external os or you will lose the negative pressure. If you do, simply expel the contents of the sheath into the formalin container or onto a sterile nonadhesive bandage (eg, Telfa), taking care not to contaminate the device, and reinsert the sheath. Multiple passes are sometimes needed to assure specimen adequacy.

ENDOMETRIAL SUCTION DEVICES — Suction devices for endometrial sampling consist of a plunger within a sheath. When the sheath is inserted into the uterus, the plunger is retracted, creating negative pressure that draws tissue into the sampling device. Most suction sampling devices utilize low pressure. However, some devices use a canister or syringe at the proximal end to create higher pressure, which removes a greater quantity of tissue. Any collected sample should be submitted for pathologic review, even if the clinician feels placement of the device or amount of gross specimen collected was not optimal.

Low-pressure devices — Low-pressure endometrial suction devices (eg, Pipelle, Endocell) are the most popular method for sampling the endometrial lining. They are typically constructed of flexible polypropylene with an outer sheath that is approximately <3 mm in diameter. The device has a 2.4 mm or smaller side port at the distal end, through which the endometrial sample is obtained (picture 1). The flexibility of this type of sampler allows the cannula to conform to the contour of the uterus and minimizes cramping.

In a typical procedure, 5 to 15 percent of the endometrial surface area is sampled [7]. Failure to obtain tissue occurs in approximately 0 to 8 percent of low-pressure endometrial suction device procedures [8-12].

One approach to improving the tissue adequacy rate is by using a technique that combines a corkscrew twisting motion and uterine curettage. When using this method, the device is inserted to the fundus and then withdrawn to the lower uterine segment, alternating between a corkscrew twisting motion and the motion usually used to curette the endometrium during a dilation and curettage (D&C). Data are limited on the relative efficacy of the combined approach. In a retrospective review with uniform pathology evaluation, use of a corkscrew twisting motion and uterine curettage yielded adequate tissue in 95 percent of cases, which was higher than the 77 percent success rate with a corkscrew technique alone [13]. (See "Dilation and curettage", section on 'Procedure'.)

Higher pressure devices — Higher pressure devices (eg, Vabra aspirator, Karman cannula) are used less frequently than low-pressure devices because they are generally perceived as being less comfortable for the patient. They are also less flexible and typically require use of a tenaculum, cervical dilation, and/or paracervical block [14].

An advantage of the Vabra and Karman systems is that they yield a large tissue sample, comparable to D&C. These devices are particularly useful in patients with moderate bleeding since, in our experience, they can circumvent the intrauterine clots and reach the endometrial surface more reliably than low-pressure devices.

Vabra – The Vabra aspirator is available as a 4 mm disposable plastic or a 2 or 3 mm stainless steel device (picture 1) [15]. Suction is initiated via an external vacuum pump, which can be noisy. The tissue sample is retrieved from a tissue trap and placed in formalin.

Karman – The Karman cannula comes in diameters of 4 to 6 mm and is made of flexible plastic with two ports at the distal end [16]. Suction is provided by a reusable syringe connected to the disposable cannula. An external vacuum pump can also be used.

ENDOMETRIAL BRUSH — The endometrial brush (eg, Tao Brush) is a disposable device with a brush at the distal end, similar to the brush commonly used for endocervical sampling.

Several observational studies have compared endometrial sampling results from the endometrial brush with those of an endometrial suction sampling device [17-23]. In a larger study, 526 pre- and postmenopausal patients were evaluated using both the Tao Brush and the Pipelle [22]. In the postmenopausal patients, endometrial sampling with the brush resulted in a significantly higher proportion of adequate endometrial samples compared with the suction device, whether the techniques were performed with (83 versus 50 percent) or without (61 versus 36 percent) the assistance of hysteroscopy. In premenopausal patients, no differences were found between the two techniques in regard to adequacy of sampling.

Another approach is to use the brush and suction device sequentially during the same visit. In one study of 101 patients, combined use had a sensitivity and specificity of 100 percent for diagnosis of endometrial hyperplasia or cancer [17].

SIDE EFFECTS AND COMPLICATIONS — The most common side effect of endometrial sampling is cramping, which subsides rapidly after the procedure is completed. Cramping tends to be more severe with the higher pressure suction devices than low-pressure devices because the former is more rigid, the suction is greater, and larger samples are removed. Many patients will experience light vaginal bleeding or spotting for several days following the procedure.

Vasovagal reactions are not uncommon during endometrial sampling. Such reactions can generally be prevented by allowing the patient to eat and drink before the procedure and by minimizing pain through use of analgesics and, if necessary, local anesthesia. The risk of uterine perforation is approximately 1 to 2 per 1000 procedures [13,17,24].

Rare complications include excessive uterine bleeding (especially with undiagnosed coagulopathies), uterine perforation (risk, 0.1 to 1.3 percent), pelvic infection, and bacteremia (including sepsis and endocarditis).

Uterine perforation during office endometrial biopsy is rare and is difficult to detect. Most cases are likely to be asymptomatic, or the patient may have atypical pain during the procedure. Theoretically, leakage of clear peritoneal-type fluid from the vagina may indicate a possible perforation; however, this is a nonspecific finding. If perforation is suspected, additional measures should be taken for evaluation and management. In our practice, if we have a small, but low suspicion of a perforation, we counsel the patient to call with worsening abdominal pain or fever. Uterine perforation is discussed in detail separately. (See "Uterine perforation during gynecologic procedures".)

POSTPROCEDURE CARE — The patients should remain in a semirecumbent position for several minutes after the procedure to reduce the chance of a vasovagal episode. Patients may then leave the office if they are not lightheaded and there is no heavy bleeding. Cramping can be managed with nonsteroidal anti-inflammatory drugs, although persistent cramping is unusual.

The patient should call to report any fever, cramping continuing for 48 hours or more, increasing pain, foul-smelling vaginal discharge, or bleeding heavier than a normal period. Patients may resume their usual activities, including coitus, as soon as they are ready.

INVESTIGATIONAL APPROACHES — New techniques may replace direct sampling of the endometrium. These include peripheral blood sampling for circulating tumor cells or cell-free DNA and uterine lavage with molecular testing of the sample [25-27]. However, the clinical utility of these techniques has not been validated.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Uterine cancer".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

Beyond the Basics topics (see "Patient education: Heavy periods (The Basics)" and "Patient education: Abnormal uterine bleeding (Beyond the Basics)" and "Patient education: Heavy or prolonged menstrual bleeding (menorrhagia) (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

Office endometrial sampling procedures have largely replaced dilation and curettage for diagnosis of endometrial neoplasia. Indications for endometrial sampling are to evaluate for a precancerous or cancerous lesion or to assess for a subclinical infection (eg, endometritis). The major contraindication to endometrial sampling is pregnancy, whereas acute cervical or uterine infection and bleeding diathesis are relative contraindications. (See 'Indications' above and 'Contraindications' above.)

Endometrial sampling using a disposable low-pressure suction device is a popular technique because discomfort is minimal. Higher pressure devices are useful when a larger sample is desired. (See 'Endometrial suction devices' above.)

For postmenopausal patients, observational data suggest that endometrial sampling with a brush is more likely to yield an adequate sample than sampling with low-pressure suction device. Combined use of these two devices increased the diagnostic performance. (See 'Low-pressure devices' above and 'Endometrial brush' above.)

The most common procedural side effects are cramping and vasovagal reactions; uterine perforation is the most serious potential complication. (See 'Side effects and complications' above.)

  1. Levonorgestrel-Releasing Intrauterine System in Treating Patients With Complex Atypical Hyperplasia or Grade I Endometrial Cancer. http://clinicaltrials.gov/show/NCT00788671 (Accessed on February 26, 2021).
  2. Dogan E, Celiloglu M, Sarihan E, Demir A. Anesthetic effect of intrauterine lidocaine plus naproxen sodium in endometrial biopsy. Obstet Gynecol 2004; 103:347.
  3. Trolice MP, Fishburne C Jr, McGrady S. Anesthetic efficacy of intrauterine lidocaine for endometrial biopsy: a randomized double-masked trial. Obstet Gynecol 2000; 95:345.
  4. Luangtangvarodom W, Pongrojpaw D, Chanthasenanont A, et al. The Efficacy of Lidocaine Spray in Pain Relief during Outpatient-Based Endometrial Sampling: A Randomized Placebo-Controlled Trial. Pain Res Treat 2018; 2018:1238627.
  5. Güney M, Oral B, Mungan T. Intrauterine lidocaine plus buccal misoprostol in the endometrial biopsy. Int J Gynaecol Obstet 2007; 97:125.
  6. ACOG Practice Bulletin No. 195: Prevention of Infection After Gynecologic Procedures. Obstet Gynecol 2018; 131:e172. Reaffirmed 2022.
  7. APGO educational series on women's health issues. Clinical management of abnormal uterine bleeding. Association of Professors of Gynecology and Obstetrics, 2006.
  8. Gordon SJ, Westgate J. The incidence and management of failed Pipelle sampling in a general outpatient clinic. Aust N Z J Obstet Gynaecol 1999; 39:115.
  9. Wagaarachchi PT, Sirisena J. Efficiency of Pipelle device in sampling endometrium. Acta Obstet Gynecol Scand 2000; 79:793.
  10. Elsandabesee D, Greenwood P. The performance of Pipelle endometrial sampling in a dedicated postmenopausal bleeding clinic. J Obstet Gynaecol 2005; 25:32.
  11. Polena V, Mergui JL, Zerat L, Sananes S. The role of Pipelle Mark II sampling in endometrial disease diagnosis. Eur J Obstet Gynecol Reprod Biol 2007; 134:233.
  12. Moberger B, Nilsson S, Palmstierna S, et al. A multicenter study comparing two endometrial sampling devices--Medscand Endorette and Pipelle de Cornier. Acta Obstet Gynecol Scand 1998; 77:764.
  13. Sierecki AR, Gudipudi DK, Montemarano N, Del Priore G. Comparison of endometrial aspiration biopsy techniques: specimen adequacy. J Reprod Med 2008; 53:760.
  14. Kaunitz AM, Masciello A, Ostrowski M, Rovira EZ. Comparison of endometrial biopsy with the endometrial Pipelle and Vabra aspirator. J Reprod Med 1988; 33:427.
  15. Einerth Y. Vacuum curettage by the Vabrar method. A simple procedure for endometrial diagnosis. Acta Obstet Gynecol Scand 1982; 61:373.
  16. Suarez RA, Grimes DA, Majmudar B, Benigno BB. Diagnostic endometrial aspiration with the Karman cannula. J Reprod Med 1983; 28:41.
  17. Del Priore G, Williams R, Harbatkin CB, et al. Endometrial brush biopsy for the diagnosis of endometrial cancer. J Reprod Med 2001; 46:439.
  18. Critchley HO, Warner P, Lee AJ, et al. Evaluation of abnormal uterine bleeding: comparison of three outpatient procedures within cohorts defined by age and menopausal status. Health Technol Assess 2004; 8:iii.
  19. Yang GC, Wan LS, Del Priore G. Factors influencing the detection of uterine cancer by suction curettage and endometrial brushing. J Reprod Med 2002; 47:1005.
  20. Yang GC, Wan LS. Endometrial biopsy using the Tao Brush method. A study of 50 women in a general gynecologic practice. J Reprod Med 2000; 45:109.
  21. Maksem JA. Performance characteristics of the Indiana University Medical Center endometrial sampler (Tao Brush) in an outpatient office setting, first year's outcomes: recognizing histological patterns in cytology preparations of endometrial brushings. Diagn Cytopathol 2000; 22:186.
  22. Williams AR, Brechin S, Porter AJ, et al. Factors affecting adequacy of Pipelle and Tao Brush endometrial sampling. BJOG 2008; 115:1028.
  23. Hirai Y, Sakamoto K, Fujiwara H, et al. Liquid-based endometrial cytology using SurePath™ is not inferior to suction endometrial tissue biopsy for detecting endometrial malignancies: Midterm report of a multicentre study advocated by Japan Association of Obstetricians and Gynecologists. Cytopathology 2019; 30:223.
  24. Cooper JM, Erickson ML. Endometrial sampling techniques in the diagnosis of abnormal uterine bleeding. Obstet Gynecol Clin North Am 2000; 27:235.
  25. Muinelo-Romay L, Casas-Arozamena C, Abal M. Liquid Biopsy in Endometrial Cancer: New Opportunities for Personalized Oncology. Int J Mol Sci 2018; 19.
  26. Nair N, Camacho-Vanegas O, Rykunov D, et al. Genomic Analysis of Uterine Lavage Fluid Detects Early Endometrial Cancers and Reveals a Prevalent Landscape of Driver Mutations in Women without Histopathologic Evidence of Cancer: A Prospective Cross-Sectional Study. PLoS Med 2016; 13:e1002206.
  27. Bats AS, Blons H, Narjoz C, et al. Microsatellite instability analysis in uterine cavity washings to detect endometrial cancer in Lynch syndrome. Anticancer Res 2014; 34:3211.
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