Pelvic Organ Prolapse (POP)

Definition

Epidemiology

• Loss of vaginal or uterine support is detectable in 43-90% of women on exam; most is asymptomatic
• Stage 1-2 prolapse is so common it is considered part of the normal spectrum in adult women
• Symptomatic POP (bulge symptoms) affects 3-12% of women
• Prolapse rarely becomes symptomatic until the leading edge reaches the hymenal ring
• Most common site: anterior vaginal wall (cystocele), then posterior, then apex
• Apical prolapse is almost always present with significant anterior or posterior prolapse

Types (Compartments)

Pathophysiology

1. Muscle damage - Levator ani injury (most commonly from vaginal delivery) widens the urogenital hiatus. Up to 20% of primiparous women show MRI-visible levator defects.
2. Connective tissue failure - Endopelvic fascia and pelvic ligaments bear the load once levator tone is lost. Altered collagen I:III ratio is consistently found in POP patients. Connective tissue disorders (Ehlers-Danlos, Marfan syndrome) markedly increase risk.
3. Neuropathic injury - Pudendal and levator nerve injury from childbirth contributes; 24-29% of primiparous women show electromyographic evidence of neuropathy post-delivery.

• Level I: Cardinal/uterosacral ligaments - suspends apex to sacrum/sidewall; loss = uterine/vault prolapse
• Level II: Lateral attachments of vagina to arcus tendineus - loss = cystocele/rectocele
• Level III: Perineal body/urogenital diaphragm - loss = perineal descent

Risk Factors

• Vaginal delivery (number and difficulty of deliveries)
• Advancing age (progressive loss of smooth/striated muscle, increased collagen)
• Prior hysterectomy (increases risk of enterocele and vault prolapse)
• Chronic straining / constipation
• Obesity
• Connective tissue disorders
• Prior pelvic trauma or surgery

Clinical Features

• Pelvic pressure/heaviness (worse in afternoon or after activity)
• Need to manually reduce the bulge to void or defecate ("splinting")
• Urinary symptoms: frequency, voiding dysfunction, incomplete emptying
• Note: Stress urinary incontinence (SUI) decreases in prevalence as prolapse advances beyond the hymen (due to urethral kinking - "occult SUI" may unmask after repair)
• Bowel symptoms: constipation, incomplete evacuation (weak correlation with prolapse severity)
• Sexual dysfunction and negative body image

Grading Systems

• Grade 0: Normal
• Grade 1: Descent halfway to hymen
• Grade 2: Descent to hymen
• Grade 3: Descent halfway past hymen
• Grade 4: Maximum prolapse (procidentia)

Treatment

Conservative

• Pelvic floor muscle training (PFMT/Kegel exercises) - first-line for mild-moderate prolapse
• Vaginal pessaries - mechanical support devices; many shapes/sizes; useful across all ages; improved QoL and body image; long-term success with age ≥72, careful fitting, clear instructions
  • Self-care pessary management is effective and preferred by many patients (meta-analysis 2024, PMID 38634900)
  • Concomitant vaginal estrogen helps prevent tissue complications

Surgical

Key Takeaways

• POP is multifactorial - muscle, nerve, and connective tissue injury interact
• Symptoms correlate poorly with anatomic stage until prolapse reaches the hymen
• Asymptomatic stages 1-2 require no treatment
• Pessary is effective and underused; surgery is for symptomatic women who fail or decline conservative management
• Apical support must always be addressed when repairing anterior or posterior prolapse

Gestational Trophoblastic Disease (GTD)

Definition

Classification

GTD
├── Benign / Nonneoplastic
│   ├── Hydatidiform Mole (Complete or Partial)
│   ├── Placental Site Nodule
│   └── Exaggerated Placental Site
│
└── Gestational Trophoblastic Neoplasia (GTN) — malignant
    ├── Invasive Mole
    ├── Choriocarcinoma
    ├── Placental Site Trophoblastic Tumor (PSTT)
    └── Epithelioid Trophoblastic Tumor (ETT)

1. Hydatidiform Mole

Epidemiology

• 1 in 1,000-2,000 pregnancies in the US
• 2:1,000 in Japan (3x higher than Europe/North America)
• Higher risk at extremes of reproductive age (puberty, perimenopause)
• Risk factors: prior molar pregnancy, prior miscarriage

Complete vs. Partial Mole

Clinical Features

• First-trimester bleeding (most common presentation)
• Uterus large for dates
• Theca lutein cysts (adnexal masses from hCG stimulation)
• Hyperemesis
• Early-onset preeclampsia (before 20 weeks - a red flag)
• Hyperthyroidism (hCG has TSH-like activity)
• Complete moles: diagnosed on USS as anechoic spaces with no fetal parts ("snowstorm")
• Partial moles: enlarged placenta with cystic lesions + fetal parts may be seen

hCG

• Key marker: elevated disproportionately high; serial hCG levels guide diagnosis and post-evacuation surveillance
• Phantom hCG: false-positive from heterophilic antibodies - exclude by urine hCG (these antibodies are NOT excreted in urine) or serial dilution

2. Gestational Trophoblastic Neoplasia (GTN)

Types

• Follows ~20% of complete mole evacuations
• Penetrates myometrium; may cause heavy bleeding
• Metastasizes (most often to lung) in ~15%
• Risk increased with: treatment delay >4 months, very large uterus, age >39, prior GTD

• Most often follows complete mole, but can arise after any pregnancy (normal term, ectopic, abortion)
• Highly malignant; distant metastases are common (lung most frequent, then vagina, brain, liver)
• Highly chemosensitive - essentially curable

• Rare; arise from intermediate trophoblasts
• Relatively chemoresistant compared to choriocarcinoma
• Treatment of choice: hysterectomy (for nonmetastatic disease)
• hCG levels may be only mildly elevated; human placental lactogen (hPL) is a useful marker for PSTT

Metastatic Sites (in order of frequency)

3. Staging (FIGO)

4. WHO Prognostic Scoring System

• Total score <7 = Low risk
• Total score ≥7 = High risk (requires combination chemotherapy)

5. Management

Step 1: Evacuation of Mole

• Surgical uterine evacuation (suction curettage) under anesthesia, with ultrasound guidance
• Uterotonics after evacuation begins
• Medication-only evacuation is discouraged (25% incomplete evacuation, risk of hemorrhage, trophoblastic embolism)
• If hyperthyroidism present: multidisciplinary management pre-operatively to prevent thyroid storm

Step 2: hCG Surveillance Post-Evacuation

• Weekly hCG until normal, then monthly
• Contraception during surveillance (oral contraceptives are safe)
• GTN is diagnosed if:
  • hCG plateau over 3 weeks
  • hCG rise over 2 weeks
  • Persistently elevated hCG at 6 months
  • Histologic diagnosis of choriocarcinoma

Step 3: Treatment of GTN

• Single-agent options:
  • Methotrexate (MTX): 5-day regimen, 8-day regimen, or weekly pulse; MTX with folinic acid (MTX-FA) achieves 87-90% remission with minimal toxicity
  • Actinomycin-D (ActD): 5-day or pulsatile biweekly; a GOG phase III trial showed 73% remission vs. 58% for weekly MTX pulse (ActD statistically superior in that comparison)
  • All low-risk patients ultimately achieve remission even with cross-over between agents

• Primary combination chemotherapy required
• Standard regimen: EMA-CO (Etoposide, Methotrexate, Actinomycin-D, Cyclophosphamide, Vincristine)
• Surgery to control complications (hemorrhage, resistant sites)
• Brain metastases: whole-brain radiation (3,000 cGy) ± craniotomy
• Liver metastases: resection or embolization

• Switch to second-line combination chemotherapy
• EP-EMA, BEP, or platinum-based salvage regimens

PSTT/ETT

• Hysterectomy is primary treatment (not single-agent chemo)
• Combination chemo for metastatic disease, but less responsive

6. Prognosis

• Low-risk GTN: near 100% cure rate
• High-risk/metastatic GTN: cure rates 90-95% with modern combination chemotherapy (98-100% in UK registry programs)
• After remission, future fertility is preserved - subsequent pregnancies are normal in outcome

Key Takeaways

• Any woman with abnormal bleeding or hCG elevation after any pregnancy event should be evaluated for GTD
• hCG is the cornerstone of diagnosis, monitoring, and follow-up
• Partial moles rarely become malignant; complete moles carry ~20% risk of GTN
• PSTT/ETT are relatively chemo-resistant - hysterectomy is the treatment of choice
• Stage IV and WHO score ≥7 = high risk - start combination chemo (EMA-CO)
• GTD is one of the few solid tumors curable even with widespread metastases