Gestational Trophoblastic Disease

SWARAJ HOSPITAL & RESEARCH INSTITUTE

BOLANGIR, ODISHA  •  OBSTETRICS & GYNAECOLOGY CLINICAL PATHWAY SERIES

Clinician Reference Infographic

Gestational Trophoblastic Disease — Molar Pregnancy to GTN

Gestational trophoblastic disease ranges from a benign hydatidiform mole to a highly curable cancer (gestational trophoblastic neoplasia). The pathway is simple but unforgiving: recognise it, evacuate it safely, follow hCG to normal, and treat promptly if hCG plateaus or rises.

🎯 AT A GLANCE — THE SPECTRUM OF GTD

Gestational trophoblastic disease (GTD) is a group of conditions arising from abnormal proliferation of placental trophoblast, all of which make hCG

Benign (premalignant): complete hydatidiform mole and partial hydatidiform mole

Gestational trophoblastic neoplasia (GTN): invasive mole, choriocarcinoma, placental site trophoblastic tumour (PSTT) and epithelioid trophoblastic tumour (ETT)

Commoner in Asia than in Western countries (roughly 1 in 500 pregnancies against 1 in 1000 or fewer); risk factors are maternal age under 15 or over 35, a previous molar pregnancy, and prior miscarriage

GTN is among the most curable cancers — with timely diagnosis and chemotherapy, cure rates exceed 90–95%, and fertility is usually preserved. The key is reliable hCG follow-up.

🔬 COMPLETE VERSUS PARTIAL MOLE

Complete Mole

46,XX (rarely 46,XY), entirely paternal in origin — no maternal DNA

No fetus or embryonic tissue; diffuse swelling of all villi

hCG usually very high (often above 100,000 IU/L)

p57 negative on immunostaining

15–20% go on to need chemotherapy for GTN

Partial Mole

Triploid (69,XXY or 69,XXX): two paternal and one maternal set

Abnormal fetal or embryonic parts, with focal villous swelling

hCG often only modestly raised

p57 positive (maternal gene present)

1–5% develop GTN — much lower, but not zero

🩺 HOW IT PRESENTS — AND WHAT THE SCAN SHOWS

Vaginal bleeding in early pregnancy (the commonest symptom) — sometimes passage of grape-like vesicles

Uterus larger than dates, hyperemesis, and bilateral theca-lutein ovarian cysts from very high hCG

Systemic effects: early-onset pre-eclampsia (before 20 weeks), hyperthyroidism (hCG acts on the TSH receptor), anaemia

Ultrasound: complete mole shows a heterogeneous mass with many small cystic spaces — the “snowstorm” or “cluster of grapes” pattern and no fetus; partial mole shows a thickened cystic placenta with an abnormal or growth-restricted fetus

Many moles are now found on routine early scans, before classic features appear. Any miscarriage tissue should be sent for histology — a molar pregnancy can look like a simple missed miscarriage. See our Miscarriage guide.

🚨 STABILISE FIRST — COMPLICATIONS TO LOOK FOR BEFORE EVACUATION

Hyperthyroidism or thyroid storm: tachycardia, tremor, fever — give a beta-blocker, and treat before anaesthesia

Severe pre-eclampsia or eclampsia in the first half of pregnancy, with blood-pressure control and magnesium sulphate

Heavy bleeding, anaemia, or coagulopathy — cross-match blood before evacuation

Acute respiratory distress from trophoblastic embolisation or high-output failure — can follow evacuation of a large mole

📋 WORK-UP ON DIAGNOSIS

1

Quantitative serum hCG — the baseline for all follow-up

2

Blood group and Rh type, full blood count, clotting screen, and liver and renal function

3

Thyroid function (TSH, free T4) if clinical or biochemical features of hyperthyroidism

4

Chest X-ray for baseline lung metastases; further imaging only if GTN or symptoms

🛠️ TREATMENT OF A MOLAR PREGNANCY

Suction evacuation under ultrasound guidance is the treatment of choice, whatever the uterine size — even in women who want future fertility

Start oxytocin at or just after evacuation, once the cervix is dilated and the uterus is being emptied, to limit bleeding

Avoid medical evacuation with prostaglandins or misoprostol and avoid hysterotomy — these raise the risk of bleeding and persistent disease

Hysterectomy can be offered if she has completed her family or has uncontrollable bleeding, though it does not remove the risk of GTN

Rh-negative women: give anti-D immunoglobulin after evacuation

Send all evacuated tissue for histology (and p57 staining if needed)

📈 FOLLOW-UP AFTER EVACUATION — hCG SURVEILLANCE

Weekly hCGStarting after evacuation, until 3 consecutive normal results (ACOG-style protocol) — local protocols vary

Monthly hCGFor about 3–6 months after normalisation in complete mole; for partial mole, a shorter course is usually enough

RegisterEnrol in the national or hospital trophoblastic disease registry where available — it supports long-term follow-up and early treatment

Contraception is essential until hCG surveillance is complete — a new pregnancy would confound hCG interpretation

Combined oral contraceptives are acceptable; avoid an IUCD until hCG has normalised (perforation risk with an invasive mole)

Follow serum hCG, not urine tests alone. A plateau or rise in hCG is the signal for GTN, and every missed follow-up visit delays treatment.

⚠️ WHEN IS IT GTN? — FIGO DIAGNOSTIC CRITERIA

Plateau: hCG within 10% across 4 measurements over 3 weeks (days 1, 7, 14, 21)

Rise: hCG up by more than 10% across 3 weekly measurements over 2 weeks

Persistence: detectable hCG more than 6 months after evacuation

Histological choriocarcinoma, or metastases found on imaging (lung, vagina, brain, liver)

Once GTN is diagnosed: chest CT (or X-ray), pelvic ultrasound with Doppler or MRI; add brain MRI/CT and abdominal imaging if lung metastases or high-risk disease. Biopsy of metastatic lesions is dangerous — avoid.

🗂️ STAGING AND RISK SCORING (FIGO / WHO)

Anatomical Stage

I: disease confined to the uterus

II: spread to adnexa or vagina (genital structures)

III: lung metastases, with or without genital involvement

IV: other metastatic sites — brain, liver, kidney, GI tract

Risk Group (Score)

0–6: low risk

≥ 7: high risk

Score is written after the stage, e.g. stage III:5

Higher scores mean greater chance of resistance to single-agent therapy

Prognostic factor	0	1	2	4
Age (years)	< 40	≥ 40	—	—
Antecedent pregnancy	Mole	Abortion	Term	—
Interval from index pregnancy (months)	< 4	4 – < 7	7 – 12	> 12
Pre-treatment hCG (IU/L)	< 10³	10³ – < 10⁴	10⁴ – 10⁵	> 10⁵
Largest tumour size, incl. uterus	< 3 cm	3 – < 5 cm	≥ 5 cm	—
Site of metastases	Lung	Spleen, kidney	GI tract	Brain, liver
Number of metastases	0	1 – 4	5 – 8	> 8
Previous failed chemotherapy	—	—	Single drug	≥ 2 drugs

💊 TREATMENT OF GTN

Low Risk (score 0–6)

Single-agent chemotherapy: methotrexate (weekly IM, or the 8-day methotrexate–folinic acid regimen) or pulsed actinomycin D

Continue for 2–3 cycles after hCG first normalises (consolidation)

If resistant: switch to actinomycin D or move to multi-agent therapy

Score 5–6 has more resistance to methotrexate — consider an upfront alternative

High Risk (score ≥ 7)

EMA-CO multi-agent regimen: etoposide, methotrexate, actinomycin D, cyclophosphamide, vincristine

Continue until hCG is normal, then 2–3 further cycles

Brain metastases need higher-dose methotrexate with intrathecal therapy ± radiotherapy

Refer to a specialist trophoblastic centre

PSTT and ETT are rare and relatively chemo-resistant, with low hCG — hysterectomy is the primary treatment for non-metastatic disease; multi-agent therapy is used if metastatic

Hysterectomy is also considered in chemo-resistant disease or uncontrolled haemorrhage once childbearing is complete

Doses and schedules follow the oncology protocol and body-surface area; with cure rates this high, treatment belongs in an experienced centre.

🌱 AFTER TREATMENT — PROGNOSIS & FUTURE PREGNANCY

Cure rates: close to 100% for low-risk disease and about 90% or more for high-risk disease

hCG monthly for 12 months after normalisation in GTN; avoid pregnancy for 12 months after chemotherapy ends

Recurrence risk of a mole in a future pregnancy is about 1–2% — raise awareness, and offer an early ultrasound in every later pregnancy

hCG 6–8 weeks after the end of any later pregnancy, and send the placenta for histology

Fertility is usually preserved; most women go on to have healthy babies

Memory Aid

MOLE

The four steps that protect a woman with a molar pregnancy.

M

Make the diagnosis — scan, hCG, histology, and p57 where needed

O

Optimise before evacuation — treat thyroid disease, pre-eclampsia, anaemia, and cross-match blood

L

Lift out the mole with suction evacuation — avoid prostaglandins and hysterotomy

E

Ensure follow-up — weekly hCG to normal, reliable contraception, and a registry

Remember: hCG is the tumour marker. A woman who is followed reliably with hCG can be cured of GTN almost every time — a missed follow-up is the real danger.

Swaraj Hospital & Research Institute · Department of Obstetrics & Gynaecology, Bolangir, Odisha

Clinician-facing summary based on FIGO 2018, ACOG, RCOG and ESMO guidance; follow-up intervals, chemotherapy regimens and doses vary by protocol — manage GTN with a specialist oncology team.