What are the guidelines for performing an endometrial biopsy in a female patient, likely of reproductive age or postmenopausal, with symptoms of abnormal uterine bleeding and potential comorbidities such as diabetes, hypertension, or bleeding disorders?

Endometrial Biopsy: Indications and Technique

Primary Indications for Endometrial Biopsy

Endometrial biopsy is indicated for postmenopausal bleeding with endometrial thickness ≥4-5mm on transvaginal ultrasound, and for premenopausal women ≥35 years with abnormal uterine bleeding, or younger women with risk factors for endometrial cancer. 1, 2

Postmenopausal Women

• Perform endometrial biopsy when endometrial thickness is ≥5mm on transvaginal ultrasound (TVUS), as thickness ≤4mm has nearly 100% negative predictive value for cancer 2
• Abnormal uterine bleeding occurs in 90% of endometrial cancer cases in postmenopausal women, making tissue diagnosis essential 1
• Always pursue further evaluation with fractional D&C or hysteroscopy if initial biopsy is negative but bleeding persists, given the 10% false-negative rate of office endometrial biopsy 1, 2

Premenopausal Women

• Women ≥35 years with abnormal uterine bleeding should undergo endometrial biopsy to exclude endometrial cancer and hyperplasia 3
• Women <35 years require biopsy if they have risk factors: polycystic ovary syndrome, chronic anovulation, unopposed estrogen exposure, tamoxifen therapy, nulliparity, diabetes mellitus, hypertension, or obesity 1, 3
• All women ≥35 years with atypical glandular cells on Pap smear require endometrial biopsy, and women <35 years with AGC need biopsy if they have risk factors or abnormal bleeding 1

High-Risk Populations Requiring Surveillance

• Women with Lynch syndrome require endometrial biopsy every 1-2 years starting at age 30-35, due to their 30-60% lifetime risk of endometrial cancer 1
• Women on tamoxifen therapy who develop any vaginal spotting or bleeding require immediate endometrial biopsy, as tamoxifen increases endometrial cancer risk to 2.20 per 1000 women-years versus 0.71 for placebo 1

Diagnostic Algorithm

Step 1: Initial Assessment with Transvaginal Ultrasound

• TVUS is the first-line test for all women with abnormal uterine bleeding to measure endometrial thickness and identify structural abnormalities 1, 2
• Perform TVUS during early proliferative phase (days 4-6) when endometrium is thinnest for optimal assessment 1
• If TVUS cannot adequately visualize the endometrium due to body habitus, fibroids, or adenomyosis, proceed directly to endometrial sampling 1

Step 2: Saline Infusion Sonohysterography (If Needed)

• Consider saline infusion sonohysterography when focal lesions (polyps, submucous fibroids) are suspected, with sensitivity of 96-100% and negative predictive value of 94-100% 1

Step 3: Office Endometrial Biopsy

• Use Pipelle or Vabra devices, which have extremely high sensitivity (99.6% and 97.1% respectively) for detecting endometrial carcinoma 1
• The procedure is safe, efficient, and well-tolerated with cramping as the most common adverse effect 4

Step 4: Escalation for Persistent Symptoms or Inadequate Sampling

• If office biopsy is negative, non-diagnostic, or inadequate but symptoms persist, perform fractional D&C under anesthesia 1, 2
• Hysteroscopy with directed biopsy is the gold standard and should be the final step in the diagnostic pathway, particularly for visualizing and sampling focal lesions like polyps 1, 5
• Blind endometrial biopsies should no longer be performed as the sole diagnostic strategy in perimenopausal and postmenopausal women 5

Technique for Office Endometrial Biopsy

Pre-Procedure Pain Management

• Administer oral NSAIDs before the procedure to reduce pain 4
• Apply topical lidocaine to the cervix before starting 4
• Apply tenaculum only if required by cervical mobility or uterocervical angulation, as it increases pain and lengthens procedure time 4

Biopsy Procedure

• Insert the endometrial biopsy catheter through the cervix into the uterine cavity 4
• Draw out the catheter's piston to create suction 4
• Perform tissue sampling by rolling the catheter while moving it in and out of the uterine cavity 4

Contraindications

• Pregnancy is the only absolute contraindication to endometrial biopsy 4

Critical Pitfalls to Avoid

• Never accept a negative or inadequate endometrial biopsy as reassuring in a symptomatic postmenopausal woman, especially those on tamoxifen—the 10% false-negative rate mandates escalation to D&C or hysteroscopy 1
• Do not rely on Pap smear for evaluating postmenopausal bleeding, as it screens for cervical cancer and does not reliably detect endometrial pathology 2
• Do not proceed to hysterectomy without tissue diagnosis, as this exposes patients to unnecessary surgical risk if pathology is benign 1
• Inadequate samples are more common in postmenopausal women due to endometrial atrophy, requiring lower threshold for proceeding to D&C 6
• In premenopausal women with fibroids or adenomyosis presenting with abnormal bleeding, still rule out endometrial cancer and uterine sarcoma before attributing symptoms to benign structural causes 2