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Clinical Bulletin No. 5 - Endometrial Biopsy

Endometrial Biopsy*

Clinical Bulletin No. 5 -- June 2001

Introduction

Endometrial biopsy (EMB) is a safe, efficient, and cost-effective means of evaluating the uterine endometrium. The procedure is usually associated with minimal discomfort and is easily accomplished in the outpatient setting. Midwives** possess the educational background needed to make the decision of whether a biopsy is necessary; therefore, incorporating this procedure into the expanded scope of midwifery practice serves a useful purpose. This clinical bulletin outlines the indications for and technique of performing an endometrial biopsy.

EMB is used most often in the perimenopausal or postmenopausal woman to evaluate abnormal uterine bleeding (AUB) and to rule out endometrial cancer. It also serves to identify other hormonally induced changes in the uterine lining (1-3). Table 1 lists reasons to perform EMB.

TABLE 1
Indications for Endometrial Biopsy


Assist in identification of causes of abnormal uterine bleeding (AUB)
Evaluate dysfunctional uterine bleeding (DUB)
Rule out endometrial carcinoma and precancerous lesions
Identify causes of postmenopausal bleeding
Evaluate infertility (specifically short luteal phase)
Follow up presence of endometrial cells on Pap smear (especially if they occur within the last
18 days of the cycle or anytime in a postmenopausal woman)
Assess effects of hormone replacement therapy (HRT)*
Assess impact of tamoxifen on endometrium*

*Indication is controversial.

Endometrial cancer is the most common invasive gynecologic cancer. The American Cancer Society estimates that 38300 women in the United States will develop endometrial cancer in 2001. Thus, EMB should be considered in any women demonstrating risk factors for endometrial hyperplasia and cancer (4). See Table 2. Prolonged stimulation to the endometrium with unopposed estrogen directs the decisions; the age of the woman should not influence the decision whether to biopsy (2).

EMB is sufficiently sensitive to allow accurate diagnosis of endometrial hyperplasia and/or cancer. However, EMB may fail to detect other uterine pathology such as polyps and submucous myomas (5-7). In these instances, endometrial sampling may need to be combined with ultrasonography. Increasingly, correlating all EMB results with ultrasonography is considered appropriate. As transvaginal sonography and sonohysterography improve, it has become more common to use these techniques for uterine valuation and confirmation of endometrial thickness, either with or in lieu of biopsy. An atrophic endometrium decreases the likelihood of an adequate sample but is not generally associated with endometrial carcinoma. Whenever EMB (or any other type of blind sampling) fails to yield sufficient tissue for laboratory examination, or when the report does not explain clinical symptoms of disease, the midwife should consider referring the woman for hysteroscopy to identify possibly missed pathology (7-10).

EMB is not without risk, and contraindications to the procedure do exist (11,12). See Table 3. In premenopausal women, all abnormal bleeding requires an evaluation for possible pregnancy before any invasive procedure. Midwives trained in EMB can safely perform the procedure; however, women presenting with contraindications or abnormal uterine anatomy require physician consultation. Clients with a history of heart murmurs or rheumatic fever usually do not need antibiotic prophylaxis; however, if this decision is unclear, medical consultation is appropriate. Clients with prosthetic heart valves require pre-procedure antibiotic prophylaxis, and a cardiologist or primary care physician should be consulted.

Side Effects and Complications

Side effects associated with EMB are usually minimal and include cramping, uterine spasm, and vasovagal reaction. Rare complications include excessive uterine bleeding (especially with undiagnosed coagulapathies), uterine perforation (0.1-1.3% risk), bacteremia, septicemia, and endocarditis (all extremely rare) (13,14). Information and counseling regarding these risks and side effects should be provided to all women considering EMB.

TABLE 2
Risk Factors for Endometrial Hyperplasia and/or Cancer (4)


Risk Factors Etiology

Age > 50 years Peak age for endometrial cancer is 60 years
Prolonged exposure to cycles with decreased Progesterone
Natural menopause after 52
Hyperandrogenic chronic anovluation (Polycystic ovarian disease)
Prolonged exposure to estrogen
Obesity > 50 lbs Peripheral conversion of androstenedione to estrone in adipose tissues leads to a chronic hyperestrongenic state
Infertility, nulliparity Prolonged exposure to estrogen
Unopposed administration of exogenous
estrogen
Prolonged exposure to estrogen
Diabetes May be due to upper body distribution of fat
Tamoxifen use Controversial

Equipment

Researchers have shown that office endometrial sampling is as effective as curettage (15), is less costly and causes significantly less pain than metal curettes (16). However, if the endometrium is atrophied, the Pipelle and other plastic devices may fail to obtain an adequate sample (14).

Commonly used sampling devices include the Pipelle Aspirator, Tis-u-Trap, and Novak curette.

Pipelle Endometrial Aspirator

The Pipelle aspirator is made of a clear, flexible ploypropylene sheath with an inner plunger. The device is well tolerated by patients and is easy to use. No external suction if required; the device is disposable. The Pipelle enables quick sampling of the endometrium (5-15 seconds of operating time), and the entire procedure can be accomplished within 10-15 minutes. A large meta-analysis examining the various devices for endometrial sampling reported the Pipelle to be the most sensitive technique (17).

 

TABLE 3
Contraindications to Endometrial Biopsy


Absolute contraindications
Pregnancy
Relative contraindications
Presence of cervicitis or endometritis
Uterine infection (pelvic inflammatory disease)
Coagulation disorders or on anticoagulant drug therapy
Other blood dyscrasias
Heart murmur or rheumatic heart disease
Febrile client
Cervical stenosis


Novak Curette

The Novak curette has been manufactured for more than 50 years and is made of stainless steel (11). The cannula is rigid and the device is nondisposable. A plastic syringe (10-20 mL) is attached to the noncutting end of the curette, and the histologic sample of endometrium is drawn into the cannula and syringe via negative pressure when the syringe plunger is withdrawn. A disadvantage of the Novak curette is its association with a greater amount of pain than the flexible plastic alternatives (16).

Tis-u-Trap Endometrial Curette and Vabra Aspirator

The Tis-u-Trap is a disposable sampling device and requires external suction via the vabra aspirator. The Tis-u-Trap is filled with formalin. The specimen is collected directly into it and sent to the laboratory for evaluation. The sampling devices (curettes) are made of either plastic or more rigid materials. The requirement of external suction limits portability of the device.

Equipment required for performance of an EMB is listed in Appendix A. Before beginning the procedure check to make certain all necessary equipment has been obtained and is ready for use. Figure 1 displays the equipment used with a Pipelle aspirator.

Procedure

In patients being evaluated for endometrial cancer, timing within the menstrual cycle is not important (11,14).

The optimal time to obtain an endometrial sample for confirmation of ovulation is on day 22-23. Timing of the procedure is critical when evaluating luteal phase defects commonly associated with infertility (11).

FIGURE 1
Equipment used for endometrial biopsy with a Pipelle aspirator. (Photo by Heather East, provided courtesy of the Frontier school of Midwifery and Family Nursing.)

A thorough history must be obtained before performing an EMB, an appropriate gynecologic examination must be performed, and any necessary labs should be ordered. Ideally, the procedure is discussed at a visit that is separate from the day of the biopsy. Before performing the biopsy, the reason for the EMB, possible causes of the problem, side effects, and potential complications should be reviewed with the woman and er informed consent obtained.
If the client is not allergic to aspirin or ibuprofen, she may take 600 to 800 mg of ibuprofen or another nonnarcotic nonsteroidal anti-inflammatory drug about 30 to 60 minutes before the procedure to decrease her discomfort during the EMB. Midwives who perform paracervical blocks may offer it, although they are rarely necessary. If a tenaculum is required, topical benzocaine gel 20% may be applied to the tenaculum site to relieve any discomfort experienced when the cervix is grasped (11).

Before the biopsy, the women is placed in the lithotomy position and bimanual examination is performed to document the size, shape, and position for the uterus. Water rather than lubricating gel should be used so that test results are not artificially altered.

Appendix B outlines the clinical procedure followed in performing an endometrial biopsy. It is important for the sampling device to reach the fundus to obtain an adequate sample for an accurate histologic examination. The functionalis layer, located in the upper two thirds of the endometrium, is the basis of morphologic interpretation. Interpretation from the basalis layer alone may well be inaccurate (14).

The procedure, illustrated in Figure 2, is generally well tolerated when the reason and technique are carefully explained before the biopsy, the midwife uses a gentle approach during the procedure, minimal force is used during the insertion of the sampling device, and additional analgesia is provided if requested. Most women recover quickly after the procedure and may return to work or other daily activities. A pad or tampon should be provided in case spotting continues. Bleeding due to the procedure is usually minimal.

Complications and risks of the procedure can be minimized by taking the following precautions. Use of the softer, more flexible plastic sampling devices will minimize pain and cramping. Vasovagal reaction and cramping are often avoided if the women eats before the procedure (even if the meal is light) and if analgesia is provided either in the form of a nonsteroidal anti-inflammatory drug or paracervical block. Excessive bleeding may be avoided by using a gentle technique, i.e., not forcing the sampling device during insertion.

FIGURE 2
Position of the biopsy instrument during endometrial biopsy. (Courtesy of Bristol-Myers, reproduced by permission.)

Perforation risk is decreased by ruling out pregnancy, performing a pelvic exam before the procedure to determine uterine position, and ensuring that the uterus is well involuted if the client is postpartum (8 weeks is suggested).

Postprocedure Care

The women should remain in a semirecumbent position for a few moments after the procedure while the midwife or the assistant assesses for vasovagal response. During this time, any cramping incurred with the procedure normally subsides. If no heavy bleeding is observed and the client is not light-headed, she can be discharged. Persistent pain can be managed with NSAIDS. The woman should be told she may resume sexual relations in 2-3 days or after bleeding has stopped. Post-procedure instructions include telling the woman to report any fever, cramping after 48 hours, or bleeding heavier than a normal period that occurs within 24 to 48 hours of the biopsy.

Findings and Follow-up

Discuss all findings with the client and explain any necessary treatment and follow-up. Generally, results are reported as inadequate, benign, cystic or adenomatous hyperplasia, atypical adenomatous hyperplasia or carcinoma.

Benign results are noted if secretory or proliferative tissue is retrieved in the sample. If the biopsy was done to evaluate AUB and the results are benign, treatment consists of prescribing oral contraceptives or cycling the woman with Provera or other progestational agent.

If the results indicate cystic or adenomatous hyperplasia and the client desires a pregnancy, consultation or referral to a physician may be necessary because ovulation induction is often suggested. If pregnancy is not desired or the woman is menopausal, treatment can be provided by cycling with either oral contraceptives or using Provera 10 mg beginning day 14 and continuing for 10 to 12 days (4, 18). A follow-up biopsy may need to be done at 6 months. If at that time the hyperplasia persists, physician consultation or referral is necessary.

All clients with atypical adenomatous hyperplasia or cancer need to be referred to a gynecologic oncologist (18).

Incorporation of the Procedure into Practice

Midwives are expected to follow the Guidelines for the Incorporation of New Procedures into Nurse-Midwifery/Midwifery Practice whenever a procedure is added to clinical practice that reflects an expanded scope. It is recommended that endometrial biopsies be done with an experienced practitioner before performing the procedure alone. The circumstances of training, the number of observed biopsies, and the experienced practitioner who provided observation must be documented. Finally, practice guidelines on when and how this procedure may be used are essential.

REFERENCES

  1. Berek JS, Adashi EY, Hillard PA, editors. Novak’s gynecology. 12th ed. Baltimore: Williams & Wilkins, 1996.
  2. Speroff L., Glass R, Kase N. Anovlation and the Polycystic ovary. In: Speroff L, Glass R, Kase N, editors. Clinical gynecologic endocrinology and infertility. 6th ed. Baltimore: Lippincott Williams 7 Wilkins, 1999.
  3. Scoggin J, Morgan G. Practice guidelines or obstetrics and gynecology, Philadelphia: Lippincott, 1997
  4. Lurain JR. Uterine cancer. In: Berek JS, Adashi EY, Hillard PA, editors. Novak’s gynecology. 12th ed. Baltimore: Williams & Wilkins, 1966.
  5. Ash S, Farrell S, Flowerdew G. Endometrial biopsy in DUG. J Reprod Med 1966; 41:892-6.
  6. Dubinsky T, Abu-Gazzeh Y, Stroehlein K. Role fo transvaginal sonography and endometrial biopsy in evaluation of dysfunctional uterine bleeding in premenopausal women. J Clin Ultrasound 1998;26;180-1.
  7. Van den Bosch T, Vandandael A, Van Schourbroeck D, Wranz P, Lombard C. Combining vaginal ultrasonography and office endometrial sampling in the diagnosis of endometrial disease in postmenopausal women. Obstet. Gynecol 1995;85:349-52.
  8. Bakour SH, Khan KS, Gupta JK. Controlled analysis of factors associated with insufficient sample on outpatient endometrial biopsy. Br J Obstet Gynecol 2000;107:1312-4.
  9. Gull B, Carlsson S, Karlsson B, Ylostalo P, Milsom I, Granberg S. Transvaginal ultrasonography of the endometrium in women with post-menopausal bleeding: is it always necessary to perform an endometrial biopsy. Am J Obstet. Gynecol 2000;182_509-15.
  10. O’Connell LP, Fries MH, Meringue E, Brahm W. Triage of abnormal postmenopausal bleeding: ac comparison of endometrial biopsy and trans-vaginal sonoysterography versus fractional curettage with hysterography. Am J Obstet Gynecol 1998; 178-956-61.
  11. Apgar BS, Newkick GR. Endometrial biopsy. Primary Care 1997; 24:303-26.
  12. Nesse RE. Menometrorrhagia and causes of abnormal premenopausal vaginal bleeding. IN: Speroff L, Glass R, Kase N, editors. Clinical gynecologic endocrinology and infertility. 6th ed. Baltimore: Lippincott Williams & Wilkins, 1999.
  13. Apgar B. Endometrial biopsy. In: Pfenninger J, Fowler G, editors. Procedures for primary care physicians. Ist ed. Baltimore: Mosby, 1994.
  14. Apgar BS. Dysmenorrhea and dysfunctional uterine bleeding. Primary Care 1997;24:161-78.
  15. Grimes D. Diagnostic dilation and curettage: a reappraisal. Am J Obstet Gynecol 1982;142:1-6.
  16. Nichols D, McGoldrick K. Minor and ambulatory surgery. In: Nichols D, Sweeney P, editors. Ambulatory gynecology. 2nd ed. Philadelphia: Lippincott, 1995.
  17. Dijkhuizen FP, Mol BW, Brolmann HA, Heintz Ap. The accuracy endometrial sampling in the diagnosis of patients wit endometrial carcinoma and hyperplasia: a meta-analysis. Cancer 2000;89:1765-72.
  18. Bayer SR, DeCherney AH. Clinical manifestations and treatment of dysfunctional uterine bleeding. JAM 1993;269:1823-8.

 

APPENDIX A
EQUIPMENT REQUIRED TO PERFORM ENDOMETRIAL BIOPSY


Informed consent (documentation)
Vaginal speculum (various sizes; Graves preferred if client can tolerate)
Ring forceps
Antiseptic solution
Cotton balls or large cotton swabs
Scissors
Fromalin sample container with labels
Sampling device
Tenaculum*
Benzocaine gel, 20%*
Vaginal retraction device*


*Optional

 

APPENDIX B
PROCEDURE FOR ENDOMETRIAL BIOPSY USING THE PIPELLE SYSTEM


  1. Insert vaginal speculum and visualize cervix.
  2. Cleanse cervix with antiseptic solution.
  3. If the cervix is not in midposition, a tenaculum may be needed to align the uterus and enable the sample to reach the fundus.
  4. IF a tenaculum is required, apply 20% benzocaine gel to tenaculum site.
  5. Gently introduce the sampling device (piston fully inserted to distal end of sheath) through the cervical os, endocervical canal, internal os, and lower uterine segment. Proceed slowly and stop at any time resistence is met. Once the lower uterine segment is reached, continue up to the uterine fundus. The fundus of the uterus must be reached for accurate sampling.
  6. Document the depth of the uterus.
  7. Stabilize the sheath with one hand and draw the piston completely back by using one continuous motion (creating a negative pressure with the lumen).
  8. Roll the sheath or turn it in one direction between the thumb and forefinger AND at the same time, move the sheath in and out of the fundus and internal os three or four times. (Note: DO NOT bring the sheath outside of the external os or you will lose the negative pressure).
  9. Withdraw the device when the lumen is as full of tissue as possible.
  10. Cut the top of the distal tip with the scissors and discard. Expel the specimen into the formalin bottle by pushing the piston into the sheath thereby discharging the specimen. Label the bottle.
  11. If a tenaculum was used, gently remove it at this time.
  12. Remove any excess blood from the cervix and vagina.
  13. Remove the speculum from the vagina.
  14. Allow the women to recover on the examination table.



CLINICAL BULLETIN DISCLAIMER

*This Clinical Bulletin was developed under the direction of the Division of Standards and Practice of the American College of Nurse-Midwives as an educational aid to members of the college. The Clinical Bulletin is not intended to define a standard of care, to dictate an exclusive course of management, or to substitute for individual professional judgment. It represents recognized methods and techniques of clinical practice that midwives may consider incorporating into t heir practices. The needs of an individual patient or the resources and limitations of an institution or type of practice may appropriately lead to variations in clinical care. The DOSP thanks Kerri Durnell Schuilling, CNM, and Cyndy Perkins, CNM, for developing this Clinical Bulletin.

**Midwifery as used throughout this document refers to the education and practice of certified nurse-midwives (CNMs) and certified midwives (CMs) who have been certified by the American College of Nurse-Midwives (ACNM) or ACNM Certification Council, Inc. (ACC).

   
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