CHAPTER 129
Endometrial Biopsy
Endometrial biopsy (EMB) is a safe and cost-effective diagnostic
method of evaluating the endometrium. EMB is an office-based
procedure most commonly used in perimenopausal and postmeno-
pausal women to investigate abnormal uterine bleeding (AUB) and
to rule out endometrial cancer. Endometrial cancer is the most com-
mon invasive gynecologic malignancy, and endometrial hyperplasia
is sometimes a precursor. EMB may be considered in any woman
with risk factors for endometrial hyperplasia or cancer (Box 129.1).
Grand multiparity and use of combined oral contraceptives for 1 or
more years are protective against endometrial cancer.
Although EMB is sensitive enough to diagnose hyperplasia or
cancer, it is less useful for detecting abnormalities such as endome-
trial polyps or the changes of endometrial atrophy. It can also be
difficult to obtain an adequate sample; one study (Elsandabesee,
2005) showed that only 34% of patients had an adequate sample
using the Pipelle. (This is compared with earlier studies showing a
79% to 99% adequacy rate.) However, the false-negative rate for
EMB is 5% to 15% when an adequate sample is obtained. In fact,
when an adequate sample is obtained, the Pipelle method has a high
diagnostic accuracy, with a positive predictive value of 81.7% and a
negative predictive value of 99.1% (Saso, 2011). One predictor of
obtaining an adequate sample is endometrial thickness on transvagi-
nal ultrasound; the likelihood rises to 60% when evaluating women
with an endometrial thickness of at least 5 mm. Although EMB
recently became the preferred initial procedure for evaluating AUB
and had mostly replaced dilation and curettage, it is often combined
with transvaginal ultrasound to measure endometrial thickness. It
can also be combined with sonohysteroscopy. Transvaginal ultra-
sound and sonohysteroscopy may also be combined in lieu of EMB
(see Chapter 130, Hysteroscopy). Because EMB is cost effective, effi-
cient, and readily available in the outpatient setting, it continues to
be an important diagnostic tool.
Anatomy
The EMB involves transcervical sampling of the endometrial lining.
An endocervical curettage of the cervical canal is performed as part
of the EMB.  • Cervical stenosis (see Chapter 136, Cervical Stenosis and Cervi-
Indications
• E  valuation of postmenopausal AUB, regardless of volume (in-
cluding spotting and staining). Transvaginal ultrasound may be
an alternative in appropriately selected women
• Evaluation of abnormal endometrial thickness on transvaginal
ultrasound in postmenopausal women
• Work-up of infertility, especially short luteal phase or anovulation
• Assessment of the effects of hormone therapy
• Investigation of atypical glandular cells of endometrial origin,
atypical glandular cells of any origin if older than 35 years and
risk factors for endometrial cancer, or endometrial cells on Pa-
panicolaou (Pap) smear in women older than 40 years who also
have AUB or risk factors for endometrial cancer
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Beth A. Choby
F ailure to respond to medical treatment of AUB
•
• Surveillance in women previously diagnosed with endometrial
hyperplasia
• AUB in women with risk factors for endometrial cancer (see Box
129.1)
• Women with an intact uterus receiving unopposed estrogen ther-
apy
• Evaluation for endometrial carcinoma or precancerous changes
• Identification of causes of dysfunctional uterine bleeding
• Evaluation of uterine enlargement in conjunction with ultra-
sound
• Screening in hereditary nonpolyposis colon cancer (HNPCC)
syndrome (HNPCC, Lynch syndrome, familial colorectal cancer
syndrome X). The lifetime risk of endometrial cancer in women
with HNPCC ranges between 40% and 60%. Annual or biennial
EMB or transvaginal ultrasound is recommended in women with
HNPCC beginning at 30 to 35 years of age. Recommendations
are based on expert opinion because the effectiveness of gyneco-
logic surveillance is not definitive. Diagnosis of HNPCC requires
histologically confirmed colorectal cancer in three relatives, at
least one of whom must be a first-degree relative. Two successive
generations must be affected and one case has to be diagnosed
before 50 years of age. Screening is appropriate in known carriers
of this autosomal dominant gene or in cases where there is strong
suspicion of HNPCC type syndromes. 
Contraindications
Absolute
P
•  regnancy
• B leeding diathesis/coagulopathy 
Relative
U
•  se of anticoagulant therapy
• Active vaginal, cervical, uterine, or pelvic infection
cal Dilation)
• Morbid obesity
• Significant pelvic relaxation with uterine prolapse 
Equipment
A variety of instruments are available for EMB. The more popular
methods are described for comparison. Equipment common to all
methods is listed here; additional items required with specific aspira-
tors are listed in the aspirator descriptions.
L
•  arge Graves vaginal speculum
• Povidone-iodine solution in nonallergic patients, chlorhexidine
in those allergic to iodine
• Cotton balls
879
880 GYNECOLOGY AND FEMALE REPRODUCTIVE SYSTEM

BOX 129.1  Risk Factors for Endometrial Hyperplasia to the patient the indications for the procedure, the process itself,
and Cancer side effects, and potential complications so that she may provide
informed consent. See the sample patient education handout
Age >50 years and the sample patient consent for EMB available at www.exper
Atypical endometrial hyperplasia tconsult.com.
Chronic anovulation • Nonsteroidal antiinflammatory drugs (NSAIDs) effectively de-
Polycystic ovary syndrome crease uterine cramping during EMB. Patients can be instructed
Diabetes to take 600 to 800 mg of ibuprofen orally 30 to 60 minutes be-
Hypertension fore the procedure unless they are allergic to aspirin or NSAIDs.
Thyroid disease Other NSAIDs have similar efficacy.
Infertility • In extremely anxious patients, premedication with an oral anxio-
Early menarche, menopause after age 55 years lytic such as 10 mg of oral diazepam (Valium) 1 hour before the
Nulliparity EMB is an option. Patients receiving these medications should be
Obesity* counseled to bring a family member to drive them home.
Tamoxifen • In the patient who faints easily, having 0.5 mg atropine available
Unopposed estrogen therapy to give IM may be useful to avoid the vasovagal effects of nausea,
Family history of endometrial cancer bradycardia, and syncope. Some clinicians give 0.5 mg IM upon
Lynch syndrome, hereditary nonpolyposis colorectal cancer, arrival in a patient with this history or at the first signs of vasova-
familial colorectal cancer syndrome X, Cowden syndrome gal. It may be worthwhile to have another 0.5 mg available, just
   in case an additional dose is needed.
*21–50 lb overweight (relative risk three times that of <50 lb over- • The American Heart Association does not recommend antibiot-
weight) ic prophylaxis against bacterial endocarditis before EMB because
the procedure is unlikely to cause bacteremia. No current studies
specifically stratify this risk.

• Ring forceps
• Postmenopausal women can be scheduled for EMB at any time,
• Uterine sound
although significant bleeding episodes are best avoided to opti-
• Single-tooth tenaculum
mize sample size.
• Endocervical curette without basket (e.g., Kevorkian curette, or
• EMB in reproductive-age women is best performed on day 22 or
disposable plastic one)
23 after the first day of the last menstrual period. The presence
Buffered formalin specimen containers with patient identifica-
•
of secretory glands confirms that ovulation has occurred. Avoid
tion labels (two)*
EMB during menses because stromal breakdown can be misinter-
• Endometrial sampler (special equipment requirements by meth-
preted as cell fragmentation and hemorrhage due to malignancy. 
od)
• Disposable flexible plastic endometrial aspirator (e.g., Pipelle,
Pipet Curet, Pipette, Endocell) Procedure
• Scissors or reusable stainless steel curette (Novak or Randall)
The initial steps for EMB are similar for the various methods. These
• 20-mL syringe or
are listed first (steps 1 through 8) and followed by descriptions of
• Disposable endometrial aspirators with syringe suction and
individual endometrial aspirators and specific instructions for their
more rigid curettes (Karman type Cannula-Curette, Uterine
use. Confirm that the patient is not pregnant, if appropriate, before begin-
Explora, Explora II) or
ning the procedure.
• Tis-U-Trap endometrial curette or a Vabra aspirator (dispos-
able) 1. The patient is placed in stirrups in dorsal lithotomy position
• External suction pump or (after the Pap smear is obtained, if indicated), and a bimanual
• Brush sampler (Tao Brush) examination is performed to determine the size and position of
the uterus. The provider wears nonsterile gloves for this portion
Cervical dilators should be kept available (see Chapter 136, Cer-
of the procedure.
vical Stenosis and Cervical Dilation). 
2. Insert a large Graves speculum vaginally. Visualize the cervix,
and remove any mucus or debris.
Precautions 3. Change into sterile gloves.
4. Prepare the cervix and vagina with povidone-iodine–soaked cot-
• T  he previous Pap smear should be reviewed before the procedure.
ton balls using the ring forceps.
If no recent smear report is available and it is indicated, obtain
5. Perform an endocervical curettage in cases where neoplasm is
one before proceeding with the EMB.
suspected (see Chapter 137, Colposcopic Examination). Insert a
• A bimanual examination identifies extreme uterine anteversion
Kevorkian curette without basket or a disposable curette into the
or retroflexion. There is an increased risk of uterine perforation
endocervical canal. Manipulate the curette 360 degrees circumfer-
when sounding the uterus or collecting the EMB if significant
entially around the entire canal, scraping in and out for two full ro-
angulation is present between the cervical neck and uterus.
tations. Warn the patient about cramping. Collect all of the avail-
• The use of small cervical dilators is often necessary in women
able material. Use ring forceps to collect any blood or secretions
found to have cervical stenosis, so they should be available.
draining from the os. Place all the material on lens paper, and then
Methods for managing cervical stenosis are described in Chapter
place it in formalin. (Disposable plastic endocervical curettage
136, Cervical Stenosis and Cervical Dilation. 
equipment is also available, usually made by same manufacturers
who make plastic endometrial curettage equipment.)
Preprocedure Patient Education and Forms 6. If insertion of the curette is difficult, use a single-tooth tenacu-
lum to grasp the cervix at 12 o’clock while having the patient
• O
 btain a thorough history, and review pertinent clinical records
cough (or whichever position gives best exposure without block-
(see encounter form available at www.expertconsult.com). Explain
ing access to the curette, except not the 3 or 9 o’clock positions).
Traction on the tenaculum straightens the cervical neck and al-
* The Tao Brush uses CytoRich Red solution instead of buffered formalin for lows for easier endocervical curettage. Avoid grasping the 3 and
specimen preservation.

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 129 –––– ENDOMETRIAL BIOPSY 881

9 o’clock positions because of the presence of arteries at these

points. Topical benzocaine gel (20%) or benzocaine spray (Hur-
ricaine) may be applied to the tenaculum site to decrease pain. If
used, the anesthetic needs to be in place several minutes before
it has an effect. A submucosal injection of lidocaine works well A
(see explanation in Chapter 149, Loop Electrosurgical Excision
Procedure for Treating Cervical Intraepithelial Neoplasia). Sampling part at distal end
7. Once a gritty sensation is noted, remove the curette. Collect all
tissue obtained, and place it in formalin. Outer plastic sheath Inner piston rod
8. Proceed with EMB using one of the following techniques. With
all EMB techniques, insert the sterile sampling device through B
the cervical os without touching the vulva or vaginal walls. Do
not touch or contaminate the part of the sampler that is placed
into the uterus. Sterile gloves and speculum are not necessary if a
“no-touch” technique is used. C
Fig. 129.1  (A) Pipelle endometrial sampler. (B) Pipelle sheath and piston.
Plastic Endometrial Aspirators (e.g., Endocell, (C) Opening at the end of the Pipelle. (Courtesy CooperSurgical, Inc., Trum-
Pipelle, Pipet Endometrial Aspirator) bull, CN, with permission.)
Disposable flexible endometrial sampling devices are the most popu-
lar method for EMB (Fig. 129.1A–B). The device is made of a clear,
flexible polypropylene tube with an inner plunger. This functions or if the aspirator fills with blood or other material before four
as a piston and creates negative pressure when retracted quickly. A complete passes have been made, a second insertion may be at-
2.4-mm distal side port allows for tissue sampling. The stiffer-tipped tempted using the same catheter as long as it has not touched
aspirators are more useful when cervical stenosis is present. More the formalin or vaginal sidewalls. The manufacturers often rec-
flexible types may be “stiffened” by placing them in a freezer for 10 ommend that the tip of the catheter be cut off using scissors
to 15 minutes. before the sample is expelled into formalin, although this is
The Pipelle samples 5% to 15% of the endometrial surface. Sev- unnecessary. Additional sampling would then require an addi-
eral types are calibrated and can be used to sound the uterus (6.5 to tional unused aspirator.
10 cm is normal). If the endometrial thickness is adequate, 79% to 15. Remove the speculum from the vagina. 
99% of specimens obtained using the Pipelle are adequate for histo-
pathologic diagnosis.
The procedure for flexible endometrial aspirators follows, contin-
Reusable Stainless Steel Curette (Novak or Randall)
ued from previous steps 1 through 8.
and Disposable Endometrial Aspirators with Syringe
Suction (Cannula Curette, Uterine Explora, Explora II)
9. Sound the uterus using either a calibrated flexible aspirator with
The Novak curette is made of stainless steel and has been avail-
the piston fully inserted or a metal sound (when using an un-
able for more than 50 years (Fig. 129.3A). The cannula is rigid and
calibrated product). Document the depth of the endometrial cav-
is attached to a 10- to 20-mL disposable plastic syringe. When the
ity (usually 6.5 to 10 cm). If the sound cannot be inserted, use
syringe plunger is pulled, the negative pressure generated draws
a tenaculum to grasp the cervix at 12 o’clock while having the
endometrial tissue into the cannula. Both the Novak and Ran-
patient cough (or whichever position gives best exposure with-
dall curettes are reusable after sterilization. A disadvantage of this
out blocking access to the curette, except not the 3 or 9 o’clock
method is that patients complain of greater pain than with flexible
positions, as discussed earlier). Outward traction straightens the
plastic aspirators.
cervical neck and allows the sound to pass through the cervical
Several disposable methods allow easier use of suction by con-
os. If the sound still will not pass, cervical dilation may be neces-
necting a locking syringe to the end of the plastic aspirator. The
sary (see Chapter 136, Cervical Stenosis and Cervical Dilation).
Cannula-Curette, Uterine Explora, and Explora II combine the
10. Introduce the aspirator, with internal piston fully inserted, into
benefits of a rigid cannula with disposability. Both Explora mod-
the endocervix. Pass it through the cervix and into the uterine
els are nylon with a sharp Randall-type cutting edge (see Fig.
cavity. Stop once the fundus is reached or resistance is encoun-
129.3B). The Explora has one distal port, whereas the Explora
tered (Fig. 129.2A).
II has two distal ports on opposing sides of the aspirator. Tissue
11. Stabilize the sheath with one hand while the piston is drawn
is obtained with suction using a scraping and peeling action. In
back with the other hand. Negative pressure builds up in the
women with large endocervical canals, the Cannula Curette may
lumen of the tube (see Fig. 129.2B).
be a better option (Fig. 129.4). It comes in sizes ranging from 3
12. Rotate the sheath 360 degrees between the thumb and index
to 7 mm, whereas the Explora and Explora II are available only
finger. At the same time, withdraw the aspirator going from the
in 3- and 4-mm sizes. When AUB is present, the larger-diameter
fundus to the internal os. Most of the endometrial cavity can be
Cannula Curette is less likely to clog than the smaller curettes.
sampled with a minimum of four complete in-and-out, fundus to
Sensitivity and specificity of these types of endometrial samplers
internal os, circumferential passes. As the aspirator completes a
are similar to those for the flexible plastic endometrial aspirators.
helical arc against the uterine walls, negative pressure within
These type aspirators may be more likely to get tissue in the pre-
the sheath draws the sheared-off endometrial tissue through
menopausal woman or one who is having menstrual bleeding at
the distal port and into the lumen. The aspirator must be kept
the time of the procedure.
within the cervix or suction is lost (see Fig. 129.2C).
After completing previous steps 1 through 8, the procedure for
13. Withdraw the entire device from the uterus, with the piston
the reusable stainless steel curette (Novak or Randall) and dispos-
pulled back the full distance. Avoid contaminating the tip. Do
able endometrial aspirators with syringe suction (Cannula Curette,
not push the piston back into the sheath before removal because
Uterine Explora, Explora II) is as follows:
the tissue sample will be lost.
14. Expel the sample into formalin by advancing the piston into the 9. Apply a tenaculum to the anterior or posterior tip of the cer-
sheath (see Fig. 129.2D to F). If insufficient tissue is o­ btained vix, depending on the direction of flexion of the uterus. Grasp

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882 GYNECOLOGY AND FEMALE REPRODUCTIVE SYSTEM

A B

C F
Fig. 129.2  (A) With the piston fully advanced in the sheath, insert the aspirator transcervically into the endometrial cavity. (B) Hold the outer sheath with one
hand while simultaneously pulling back the piston to create negative pressure. (C) Roll the sheath between the fingers while simultaneously moving the sheath
in and out from the fundus to the internal os. Complete a minimum of four passes. (D) Appearance of tissue in the sampler. (E) Expressing the tissue into the
formalin bottle. (F) Sample as it appears in the formalin container.

Fig. 129.3  (A) Close-up of the end of the Novak stainless

steel curette. (B) Uterine Explora and Explora II endometrial B
aspirators. (Courtesy CooperSurgical, Inc., Trumbull, CN.)

the cervix with the tenaculum teeth in the horizontal position.
Grasping the cervix at the 3 or 9 o’clock position with the te-
naculum in the vertical plane decreases the diameter of the ex-
ternal os. Local anesthesia (2 mL of 2% lidocaine solution or
spray) where the tenaculum teeth are applied decreases patient
discomfort (optional).
10. Insert a uterine sound into the cervix while applying gentle
traction to the tenaculum. Halt when the fundus is reached,
and note the insertion measurement in centimeters. Remove
the sound from the patient. If stenosis is present, cervical dila-
tion may be necessary (see Chapter 126, Cervical Stenosis and
Cervical Dilation).
11. Gently insert the curette into the endometrial cavity while ap-
plying traction with the tenaculum. Stop insertion once the cu-
rette is at the depth that was sounded.
12. Before attaching the curette, draw up 1 to 2 cm of air into the
syringe. This will be used to evacuate the curette when the pro-
cedure is completed.
13. Attach a 20-mL syringe to the curette hub. Pull the syringe back to
the 10- to 15-mL mark to create suction. The Explora models rec-
ommend pulling the syringe back to 1 or 2 mL to avoid discomfort.
14. Apply pressure against the uterine sidewalls, and perform four to six
single-strip curettages. Sample from the fundus to the lower uterine
segment, and obtain at least one sample from each quadrant. More
sampling can be done if the patient is tolerating the procedure well.
15. Release the pressure on the syringe, withdraw the curette from
the uterus, and express the sample into the formalin bottle by
pushing the plunger of the syringe toward the curette. Label the
formalin bottle.
16. Remove the speculum from the vagina. 

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 129 –––– ENDOMETRIAL BIOPSY 883

Fig. 129.4  Cannula curette endometrial aspirator. (Courtesy CooperSur-

gical, Inc., Trumbull, CN.)
Fig. 129.5  Tis-U-Trap plastic disposable aspirator, including flat and
cone-shaped collection chamber, sound, and endometrial curettes. (Courtesy
CooperSurgical, Inc., Trumbull, CN.)
Tis-U-Trap, Vabra Aspirator, and Karman Cannula
The sterile and disposable Tis-U-Trap is a clear plastic tissue collec-
tion chamber (Fig. 129.5). It comes with a funnel, two sealing caps,
a resealable bag, and either a flat or cone-shaped tissue trap. The
Tis-U-Trap is used with one of several types of endometrial curettes.
The trap is attached to an external suction source such as a pump or
wall suction. Endometrial tissue is aspirated directly into the collec-
tion chamber, eliminating the need to transfer the tissue sample into
another container. The design of the collection chamber permits
easy visualization of the tissue collected and simplifies routine tissue
handling for pathology.
The Vabra aspirator uses a 4-mm disposable curette or 2- to
3-mm stainless steel curette with an external vacuum pump. The
vacuum pump is noisy, and this method is less commonly used than A
those listed previously. Tissue collected is gathered from a trap and
placed in formalin.
The Karman cannula is made of flexible plastic and comes in
diameters of 4 to 6 mm. It can be attached to a reusable syringe or
external vacuum pump.
These devices are usually less comfortable for the patient due
to the larger diameter and often require use of a tenaculum, dila-
tion, and a paracervical block. However, they yield large amounts
of tissue, similar to that of a dilation and curettage (D&C). They
are particularly useful in women with moderate menstrual bleeding;
they often allow the clinician to circumvent the clots and obtain
tissue.
After completing previous steps 1 through 8, follow these steps
for using the Tis-U-Trap, Vabra aspirator or Karman cannula-curette:
9. Apply a tenaculum to the anterior or posterior lip of the cervix.
10. Using a metal sound, carefully measure the depth of the endo- B
metrial cavity. Measurements usually range between 6.5 and 10
cm. If stenosis is present, cervical dilation may be necessary (see Fig. 129.6  (A) Initiate suction by covering the hole on the curette. (B)
Remove the curette from the trap and cap the outlet. Pour formalin into the
Chapter 126, Cervical Stenosis and Cervical Dilation).
trap to cover all tissue and then seal.
11. Attach the device to the external suction pump (or large syringe
for Karman cannula-curette).
12. Insert the curette through the cervical os, and gently advance
until the fundus is reached. The depth should coincide with the Tao Brush
uterine sound measurement. The Tao brush sampler consists of a tube with a distal brush (Fig.
13. Activate the pump to 55 cm H2O. 129.7A). The brush is covered by a 26-cm, 9.0-Fr vinyl sheath. By
14. Initiate suction by covering the suction hole with a finger (Fig. keeping the brush covered during insertion, the sheath allows for
129.6A). sampling of endometrial cells only, without contamination from the
15. Carefully curette the entire endometrium using a circumferen- vagina or cervix, because the brush is uncovered only once when
tial in-and-out movement. Keep the curette within the uterine it is in the uterine cavity. The brush obtains an adequate sampling
cavity. The tissue passes through the curette and into the trap, from the entire endometrium. It is supplied in a sterile package and
where it collects on the grid. intended for one-time use only. The Tao brush may be used alone or
16. When sufficient tissue accumulates in the trap, halt suction and before or after use of a plastic aspirator. In one study (Del Priore) of
then remove the curette from the uterus. 101 women, the combination of the brush with a plastic aspirator
17. Turn the suction pump off, and disconnect the curette from the had a sensitivity and specificity of 100% for diagnosis of endometrial
trap. hyperplasia or cancer. The manufacturer also suggests it can be used
18. Add formalin to the trap, and ensure that all tissue is exposed. Cap at the time of a routine Pap smear.
and label the trap for submission to pathology (see Fig. 129.6B). After following previous steps 1 through 8, the Tao brush proce-
19. Remove the speculum from the vagina.  dure is as follows:

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884 GYNECOLOGY AND FEMALE REPRODUCTIVE SYSTEM
A the uterus, or when the cervix is stenotic. If the uterine sound
B vical curettage, pain after the procedure is usually minimal. Pain
Fig. 129.7  Tao brush. (A) Endometrial sampler with sheath. (B) Brush in-
serted in the endometrial cavity with sheath retracted to allow for sampling.
(Courtesy Cook Women’s Health, Spencer, IN.)
9. Sound the uterus (up to 10 cm is normal). If stenosis is present,
cervical dilation may be necessary (see Chapter 126, Cervical
Stenosis and Cervical Dilation).
10. Insert the Tao brush with the outer sheath covering the brush.
Gently advance it until the fundus is reached, based on the ini-
tial sounding depth.
11. Slide back the outer sheath to expose the plastic bristles and
rotate 360 degrees once clockwise and then once counterclock-
wise against the uterine walls (see Fig. 129.7B).
12. Slide the sheath back in to cover the brush, and then remove
the Tao brush and speculum.
13. Place the brush into the supplied CytoRich Brush Cytology Pre-
servative. Rotate the brush in the preservative. Pull the sheath
back and forth 10 times to dislodge the endometrial tissue.
­CytoRich Brush Cytology Preservative allows the pathologist to
prepare a “thin-layer” sample (liquid-based cytology).  cramping lasting longer than 48 hours, or bleeding heavier than a
Sample Operative Report
See the sample encounter form available at www.expertconsult.com. 
Common Errors
• Inability to develop suction with a Pipelle or Novak/Ran-
dall-type endometrial aspirator. If the endocervical canal is
large, change to a larger-diameter cannula and reattempt as-
piration.
• Loss of suction during the biopsy. If the distal port of the Pipelle
or syringe suction aspirator is pulled too far outside the endocer-
vix, suction is lost as air is pulled in. To avoid this error, con-
centrate on keeping the aspirator within the uterine cavity and
endocervix until the sample is obtained.
• Use of a small-diameter cannula in the setting of significant uter-
ine bleeding. Large clots clog the cannula and make obtaining
an adequate sample (rather than just blood) challenging. Switch
to a larger-diameter cannula or Karman cannula-curette, Tis-U-
Trap or Vabra aspirator, and reattempt aspiration.  used (Box 129.2).
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Complications
• U  terine perforation occurs in 0.1% to 1.3% of EMBs. Perforation
most often occurs with the use of rigid devices, while sounding
passes more than 12 cm in a uterus that does seem that large
on palpation, perforation is suspected. Stop the procedure, and
withdraw all instruments. Observe the patient closely for bleed-
ing. No other intervention is indicated unless symptoms develop.
Patients may be discharged home with close follow-up if bleeding
is minimal and vital signs are stable after 30 minutes of obser-
vation. Precautions regarding infection and bleeding should be
discussed before release. Repeat biopsy can be attempted in 6 to
8 weeks.
• Excessive uterine bleeding is possible, especially in patients with
undiagnosed coagulation disorders or perforation.
• Missed pathology is possible because only a small area of the en-
dometrium is sampled. Although the sensitivity of EMB is esti-
mated to be high as 96%, it may miss up to 18% of focal lesions.
Fibroids and polyps will also not be identified.
• A vasovagal response occurs in an estimated 10% of patients af-
ter EMB. As previously discussed, use of IM atropine may help to
minimize the risk of this complication.
• Although most women experience cramping during the endocer-
lasting longer than 24 hours should be reported to the provider.
• Bacteremia, septicemia, and endocarditis have been reported af-
ter EMB, although they are exceedingly rare. The patient should
report any fever or foul discharge. 
Postprocedure Management
• P  atients should remain semirecumbent for 10 minutes after the
EMB has been taken. Assess for vasovagal reaction.
• Painful uterine cramps (if present) usually subside rapidly or are
relieved with NSAIDs.
• Patients with minimal cramping and bleeding may be discharged
home.
• Although a follow-up visit is usually not necessary, it may be
needed to discuss pathology findings. If AUB persists, further
evaluation with a repeat EMB, D&C, hysteroscopy, or pelvic ul-
trasound is indicated. 
Postprocedure Patient Education
Bleeding and cramping usually resolve within 24 to 48 hours. Fever,
normal period should be reported. NSAIDs can be used for pain or
cramping. Sexual relations may be resumed after bleeding has stopped. 
Interpretation of Results
1. When submitting an EMB, conveying adequate clinical history
to the pathologist is essential. The patient’s age, clinical indica-
tion for biopsy, menopausal status, and date/length of last men-
strual period in premenopausal women are important. Exogenous
hormones, hormonal contraceptives, and drugs such as tamox-
ifen can alter the morphology of the endometrium and cause
false-positive or false-negative results (Fig. 129.8).
2. Biopsy interpretation is based on the status of the functionalis
layer located in the upper two thirds of the endometrium. The
basalis layer usually shows minimal change. Atrophic, denuded,
or scarred endometrium may not yield sufficient tissue for diag-
nosis. Inadequate samples are possible in biopsies immediately
after menses, with hypoestrogenism, with prolonged bleeding, or
with intrauterine adhesions/synechiae. Menopausal status has a
greater effect on specimen adequacy than the type of instrument
 129 –––– ENDOMETRIAL BIOPSY 885

Consider patient factors

• Age
• Clinical indication for biopsy
• Date from last menstrual period
• Menopausal status
• Hormone use
Endometrial biopsy results

Proliferative Complex hypertrophy Complex hyperplasia Dysplasia

or secretory without atypia with atypia or CIS
endometrium
or simple
hyperplasia

Plans to Pregnancy not Consider D&C or Discuss

become wanted hysteroscopy hysterectomy
Hormonal pregnant immediately
treatment or
watchful
waiting
Induce Progestins for Same pathology Higher-grade
ovulation 3 months lesion

Pregnancy test Repeat EMB or Encourage Consult

D&C 1 month pregnancy (soon)
after progestins if desired; possible
Repeat EMB or stopped hysterectomy
perform D&C
after 3–6 months

Resolved or Progression
no worse
A
• Age
• Clinical indication for biopsy
• Menopausal status
• Hormone use
• Medication use (tamoxifen)
Endometrial biopsy results

Insufficient sample Simple hyperplasia Complex hyperplasia Complex hyperplasia

• Biopsy after menses without atypia with atypia
• Atrophic or scarred uterus
• Denuded endometrium
• Hypoestrogenic state
• Prolonged uterine bleeding
No treatment Progestin 20 mg twice daily Consider
necessary for 3–6 months hysterectomy

Repeat EMB Repeat EMB

Resolution Continued
hyperplasia

Regular
follow-up

Fig. 129.8  Management options after

endometrial biopsy in premenopausal (A)
Repeat progesterone Hysteroscopy and postmenopausal (B) women. CIS,
with follow-up EMB if patient preference Carcinoma in situ; D&C, dilation and cu-
B rettage; EMB, endometrial biopsy.

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886 GYNECOLOGY AND FEMALE REPRODUCTIVE SYSTEM

BOX 129.2  Findings on Endometrial Biopsy Sampling BOX 129.3  International Society of Gynecological
­Pathologists Classification for Endometrial Hyperplasia
Insufficient Tissue
Follow-up depends on clinical situation; may need to repeat Endometrial Hyperplasia
or use other diagnostic techniques  Simple
Normal Complex 
Proliferative endometrium Endometrial Hyperplasia With Atypia
Secretory endometrium Simple
Atrophic endometrium  Complex
Pregnancy Related
Retained products of conception
Decidua (consider an ectopic or missed abortion)  5. Hyperplasia with cytologic atypia is best managed with a hys-
Infectious Etiology terectomy because of the risk of progression to adenocarcinoma.
Endometritis, treat as indicated  Approximately 10% of women with postmenopausal bleeding
have endometrial cancer.
Abnormal 6. Histology determines management. Severity of endometrial hy-
Rarely, endometrial polyp perplasia and the probability of cancer cannot be determined by
Simple (cystic) hyperplasia the amount of bleeding, at what point during the menstrual cy-
• Risk for progression to cancer extremely small; little cle the bleeding occurs, the gross appearance of the sample, or
need for follow-up unless symptoms present. the tissue volume obtained by biopsy. Histopathology must be
Complex (adenomatous) hyperplasia determined. Transvaginal endometrial thickness measurement is
• Low but some risk for progression to cancer never a substitute for histologic tissue assessment in symptomatic
• Treat with progestational agents and follow up with tis- women. 
sue sampling in 6 months
Atypical hyperplasia (simple and complex)
• Significant risk for progression to cancer Patient Education Guides
• Consider hysterectomy because of significant risk of See the patient education and consent forms available at www.exp
progression to invasion and need for long-term follow-up ertconsult.com. 
to detect progression. If childbearing is not complete,
treat with progestational agents and follow with frequent
biopsies. Referral and consultation should be strongly CPT/Billing Codes
considered.
Adenocarcinoma 57505 Endocervical curettage not done as part of dilation and
• Referral indicated for appropriate work-up and treatment curettage
If the endocervical curettage is positive for dysplasia, a coni- 57800 Dilatation of cervical canal, instrumental
zation is indicated. If symptoms persist in spite of treatment, 58100 Endometrial sampling (biopsy) with or without endocer-
regardless of biopsy results, further evaluation is indicated. vical sampling, without cervical dilation, any method
59200 Insertion of cervical dilator (e.g., laminaria)
3. The classification of endometrial hyperplasia is made according to  
guidelines from either the International Society of Gynecological ICD-10-CM Diagnostic Codes
Pathologists or the World Health Organization (Box 129.3). Endo-
metrial hyperplasia covers a spectrum of alterations in the stroma
and glands of the endometrium. Changes range from hyperplasia C54.9 Ca uterus
to atypical hyperplasia to carcinoma. Both hyperplasia and atypical D26.9 Benign neoplasm of uterus
hyperplasia are further categorized as either simple or complex: D07.0 Ca in situ, endometrium
D39.8 Neoplasm of uncertain behavior, uterus
• Simple hyperplasia describes an increased glandular-to- N84.0 Polyp of endometrium
stromal ratio without evidence of glandular crowding or cellu- N85.2 Hypertrophy of uterus; bulky or enlarged uterus
lar atypia. Cystic hyperplasia is an older term that is no longer N85.00 Endometrial hyperplasia unspecified
used. There is no clinical significance to this finding, and no N85.01 Endometrial hyperplasia without atypia
treatment is needed. N85.02 Endometrial hyperplasia with atypia
• In complex hyperplasia, infolding and budding of the glands R87.619 Atypical glandular cells
is noted. Glands are crowded in comparison with simple hy- N94.89 Pain associated with female genital organs
perplasia, but no atypia is noted. The older term adenomatous (requires a fourth digit and must be as specific as
hyperplasia is no longer in use. possible)
• In atypical hyperplasia, cytologic atypia is divided into simple N94.9 Unspecified symptoms associated with female
or complex categories depending on the glandular architecture. genital organs
Large nuclei of varying shape and size, increased nuclear-to-cyto- N92.3 Ovulation bleeding (regular intermenstrual bleed-
plasm ratio, and prominent nucleoli are commonly described. ing)
4. Endometrial hyperplasia without cytologic atypia is usually man- N93.9 Metrorrhagia (bleeding unrelated to menstrual
aged with progestins; 10 to 20 mg medroxyprogesterone acetate cycle; irregular intermenstrual bleeding)
given daily is prescribed for 3 to 6 months. EMB is repeated after N93.8 Dysfunctional uterine bleeding
therapy, and complete reversal of lesions is often noted. If hy- N93.9 Unspecified uterine bleeding
perplasia without atypia is again confirmed, a repeat course of N92.4 Premenopausal menorrhagia
progestin with follow-up EMB or hysteroscopy can be performed. N95.0 Postmenopausal bleeding
Some patients may opt for a hysterectomy at this point. Z79.890 Postmenopausal HRT

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 129 –––– ENDOMETRIAL BIOPSY 887

Z85.40 Personal history of cancer of female genital organ, RECOMMENDED READING

unspecified American College of Obstetricians and Gynecologists. 2009 American
Z85.41 Personal history of cancer of cervix, uteri College of Obstetricians and Gynecologists. Antibiotic prophylaxis
for gynecologic procedures. Practice Bulletin no. 104. Obstet Gynecol.
  2009;113:1180–1189.
Suppliers American College of Obstetricians and Gynecologists. The role of transvagi-
nal ultrasonography in the evaluation of postmenopausal bleeding. Com-
(See contact information available at www.expertconsult.com.) mittee Opinion no. 426. Obstet Gynecol. 2009;113:462–464.
Apgar BS, Kaufman AJ, Bettcher C, Parker-Featherstone E. Gynecologic
Plastic endometrial aspirator (often also make plastic endocervical procedures: colposcopy, treatment of cervical intraepithelial neoplasia,
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Endocell endometrial sampler, Wallach Surgical Braun MM, Overbreek-Wager AE, Grumbo JR. Diagnosis and management
Endocervical curette with Vac-Loc syringe, Pipelle de Cornier, of endometrial cancer. Am Fam Physician. 2016;93(6):468–474.
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Syringe, Explora Models I and II; Milex CooperSurgical, Inc. 2005;25(1):32–34.
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Milex CooperSurgical, Inc. McCluggage W. My approach to the interpretation of endometrial biopsies
Vabra aspirator and curettings. J Clin Pathol. 2006;59:801–812.
Renkonen-Sinisalo L, Butzow R, Leminen A, et al. Surveillance for endome-
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The editors recognize the contributions of Barbara S. Apgar, MD, Smith R, Cokkinides V, Eyre HJ. American Cancer Society Guidelines for
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Online Resources Tanriverdi H, Barut A, Gün B, Kaya E. Is Pipelle biopsy really adequate for
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National Cancer Institute
For practitioners: Endometrial Cancer Treatment (PDQ)–Health Profes-
sional Version: https://www.cancer.gov/types/uterine/hp/endometrial-tre
atment-pdq
For patients: Uterine cancer: www.cancer.gov/types/uterine

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