Gestational trophoblastic disease is a group of conditions arising from abnormal proliferation of placental trophoblast after an abnormal fertilization. All forms produce human chorionic gonadotropin (hCG), which serves as a highly sensitive tumor marker for diagnosis, treatment response, and follow-up.

Hydatidiform mole (molar pregnancy) — the benign, premalignant form

Gestational trophoblastic neoplasia (GTN) — the malignant forms: invasive mole (invades myometrium), choriocarcinoma (can follow any pregnancy — molar, normal, miscarriage, or ectopic; spreads through blood, most often to the lungs, then vagina, brain, liver), and the rare placental-site and epithelioid trophoblastic tumors (produce little hCG, treated mainly with surgery). GTN is highly curable with chemotherapy, even when metastatic.

Risk factors — extremes of maternal age (under 20 and especially over 40), previous molar pregnancy (recurrence about 1–2%), prior miscarriage; Asian populations have a higher reported incidence.

Why the classic signs occur

• Very high hCG → hyperemesis, theca lutein ovarian cysts (ovarian stimulation), hyperthyroidism (hCG weakly stimulates the TSH receptor)
• Abnormal placenta → early-onset preeclampsia before 20 weeks (a classic clue)

Most moles are now diagnosed in the first trimester by ultrasound, before classic signs develop.

Subjective

• Vaginal bleeding in the first trimester — the most common sign; may be dark brown ("prune-juice") discharge
• Severe nausea and vomiting; pelvic pressure or pain (enlarged theca lutein cysts)
• Passage of grape-like vesicles

Objective

• Uterus larger than expected for gestational age (complete mole)
• No fetal heart tones (complete mole)
• Hypertension, proteinuria, or headache before 20 weeks (preeclampsia)
• Tachycardia, tremor, heat intolerance (hyperthyroidism)
• Anemia from bleeding

GTN (after a molar pregnancy or any pregnancy) — persistent or irregular bleeding; hemoptysis, cough, dyspnea (lung metastases); purple vaginal nodules (vaginal metastases — bleed heavily if biopsied); headache, seizures, or neurologic deficits (brain metastases).

• Quantitative serum hCG — the most important test for diagnosis and follow-up; often far higher than expected for gestational age in a complete mole
• Transvaginal ultrasound — complete mole shows a heterogeneous, multicystic ("snowstorm") mass with no fetus; enlarged multicystic ovaries (theca lutein cysts)
• Pathology of evacuated tissue confirms the diagnosis (and distinguishes complete from partial)
• Before evacuation: CBC, blood type and Rh, crossmatch, coagulation studies, kidney and liver function, thyroid function, urinalysis (protein), chest x-ray (baseline for lung metastases)
• Diagnosis of post-molar GTN (FIGO) — during hCG monitoring:
  • Plateau: 4 values staying within about ±10% over at least 3 weeks (days 1, 7, 14, 21)
  • Rise: an increase of more than 10% across 3 values over at least 2 weeks (days 1, 7, 14)
  • Histologic diagnosis of choriocarcinoma
• GTN staging and risk: chest imaging, pelvic ultrasound, CT/MRI of brain and abdomen if lung metastases or high risk; FIGO/WHO prognostic score — 0–6 = low risk, 7 or more = high risk

Molar pregnancy

• Suction dilation and curettage (D&C) — the preferred evacuation for women who want future fertility, regardless of uterine size
  • Oxytocin is started after evacuation has begun (to reduce bleeding); inducing contractions or medical abortion before evacuation is avoided because it increases trophoblastic embolization and hemorrhage
  • Have blood available; large uteri carry higher risk of hemorrhage and respiratory distress
• Hysterectomy (with ovaries usually preserved) — for women who do not want future pregnancy; it lowers but does not eliminate GTN risk, so hCG follow-up is still needed
• Rh immune globulin for Rh-negative clients
• Treat complications: antihypertensives, beta blockers for hyperthyroid symptoms, antiemetics, fluid and electrolyte replacement. Theca lutein cysts usually regress as hCG falls

hCG surveillance after evacuation

• Serum hCG every 1–2 weeks until undetectable
• Complete mole: then monthly for 3 months
• Partial mole: one more normal value about 1 month later
• Reliable contraception during surveillance — hormonal contraception (including combined pills) is safe to start right after evacuation; an IUD should not be placed until hCG is normal (risk of uterine perforation if disease persists)
• A new pregnancy would raise hCG and hide recurrent disease — this is why pregnancy is deferred until surveillance is complete

GTN treatment

• Low risk (score 0–6): single-agent methotrexate (with or without folinic acid/leucovorin) or dactinomycin; continue for cycles beyond the first normal hCG
• High risk (score 7 or more): multi-agent chemotherapy (e.g., EMA-CO: etoposide, methotrexate, dactinomycin, cyclophosphamide, vincristine); radiation or surgery for selected metastases
• After chemotherapy: hCG monthly for 12 months; avoid pregnancy for 12 months after completing chemotherapy

Drug safety

Follow standard hazardous-drug handling and extravasation procedures.

Listed in priority order.

1. Hemorrhage — monitor vital signs, bleeding, and hemoglobin before and after evacuation; large-bore IV, blood available; give oxytocics as ordered after evacuation begins; report tachycardia and hypotension
2. Respiratory distress during or after evacuation (trophoblastic embolization, fluid overload, preeclampsia, thyroid storm) — assess oxygen saturation and breath sounds; oxygen, upright position, notify the provider immediately; sudden chest pain and dyspnea also require evaluation for pulmonary embolism
3. Uterine perforation or intra-abdominal bleeding — sudden severe abdominal pain, pallor, tachycardia, falling blood pressure after evacuation → emergency
4. Monitor for preeclampsia and hyperthyroidism — blood pressure, proteinuria, headache, visual changes; heart rate, temperature (thyroid storm)
5. Infection prevention — temperature, discharge; no tampons or douching; perineal pads to monitor bleeding
6. Rh immune globulin within 72 hours for Rh-negative clients
7. Chemotherapy care — CBC, liver and kidney function before doses; mucositis care (soft toothbrush, saline rinses, cool bland foods); neutropenia precautions
8. Emotional support — the loss of a pregnancy combined with a cancer-related diagnosis; grief, anxiety about fertility; explain that most future pregnancies are normal

• hCG follow-up is essential — keep every blood test appointment until the provider confirms surveillance is complete; rising or plateauing values need treatment
• Use reliable contraception throughout surveillance (and 12 months after chemotherapy); hormonal methods are safe; delay IUD placement until hCG is normal
• Periods may be absent or irregular until hCG normalizes — menstruation usually resumes afterward
• Report: heavy bleeding, foul discharge, fever, severe abdominal pain, cough or coughing blood, shortness of breath, headache or seizures
• Methotrexate: no alcohol, no NSAIDs or folic acid supplements unless the oncology team approves; use sunscreen and avoid sun exposure; report mouth sores, fever, bruising, cough, or yellowing of skin; for oral ulcers eat soft, cool, nonirritating foods
• Future pregnancies: most are normal; request an early ultrasound in the next pregnancy and an hCG test about 6 weeks after any future pregnancy ends (to detect choriocarcinoma); pathology of the placenta is advised
• Avoid alcohol during methotrexate therapy; stopping smoking supports recovery

• Complete mole: 46,XX, paternal only, no fetal tissue, very high hCG, uterus large for dates, higher GTN risk
• Partial mole: triploid, fetal tissue present, lower GTN risk
• Classic signs: first-trimester bleeding ("prune juice"), hyperemesis, preeclampsia before 20 weeks, hyperthyroidism, theca lutein cysts, absent fetal heart tones
• Serum hCG is the key test and tumor marker
• Treatment: suction D&C; oxytocin after evacuation begins; Rh immune globulin if Rh-negative
• Follow-up: hCG every 1–2 weeks until undetectable, then monthly × 3 (complete)
• Contraception during surveillance; hormonal methods safe; no IUD until hCG normal
• GTN: hCG plateau or rise → methotrexate or dactinomycin; very curable
• Choriocarcinoma spreads first to the lungs → chest x-ray; do not biopsy vaginal nodules
• Methotrexate: no alcohol, NSAIDs, or folic acid; sun protection; mucositis and liver toxicity
• Avoid pregnancy 12 months after chemotherapy