What are the RCOG recommendations for managing a confirmed molar pregnancy in a woman, including evacuation, hCG surveillance, contraception, prophylactic methotrexate for high‑risk features, and treatment of persistent disease?

Management of Molar Pregnancy: RCOG-Aligned Guidelines

Initial Evacuation

Women with confirmed molar pregnancy should undergo suction dilation and curettage (D&C) under ultrasound guidance as the primary treatment method, regardless of uterine size, when fertility preservation is desired. 1, 2

• Suction D&C is the safest evacuation method to ensure complete removal of molar tissue while minimizing the risk of uterine perforation 1, 2
• Medical evacuation (prostaglandins, misoprostol) should not be used for molar pregnancy termination 3
• Uterotonic agents (methylergonovine, prostaglandins) must be administered during and after the procedure to reduce hemorrhage risk 2
• Rho(D) immunoglobulin should be given at evacuation to all Rh-negative patients to prevent alloimmunization 1, 2

Role of Second Curettage

• A second D&C for persistent disease does not reliably prevent the need for chemotherapy and carries significant perforation risk 1, 2
• Re-evacuation should only be attempted after consultation with a gestational trophoblastic disease reference center 1, 2
• The remission rate following repeat curettage is low, making it generally not recommended 3

Post-Evacuation hCG Surveillance

All patients require serial quantitative serum hCG monitoring using the same laboratory and assay throughout the entire follow-up period to detect post-molar gestational trophoblastic neoplasia (GTN). 1, 2

Monitoring Protocol

• Measure serum hCG every 1–2 weeks until three consecutive normal values (<5 mIU/mL) are documented 1, 2
• After normalization within 56 days of evacuation: obtain four additional monthly measurements, then discharge from surveillance 3
• After normalization beyond 56 days: continue monthly measurements for six months total 1, 3
• For partial hydatidiform mole (triploid): weekly measurements until two consecutive undetectable values, then discharge 3
• For complete hydatidiform mole (diploid): extended six-month monthly surveillance after normalization 1, 3

Critical Surveillance Pitfalls

• Always use the same laboratory and assay for serial measurements to avoid inter-assay variability that could mislead clinical decisions 2
• If serum hCG results are inconsistent with clinical findings, repeat with an alternative assay and corroborate with urine hCG to exclude false-positive serum values 2

Contraception During Follow-Up

Reliable contraception is mandatory throughout the entire hCG surveillance period; any method may be used provided there are no contraindications, including combined oral contraceptives. 2

• Contraception prevents confusion between rising hCG from a new pregnancy versus persistent GTN 2
• If pregnancy occurs after completing surveillance, obtain confirming ultrasound to verify normal intrauterine pregnancy and recheck serum hCG at approximately 6 and 10 weeks gestation to ensure no disease recurrence 2

Indications for Chemotherapy (Post-Molar GTN Criteria)

Chemotherapy is indicated when any of the following FIGO/UK criteria are met after molar evacuation: 1

Primary Indications

• Plateaued hCG: Four or more equivalent values over at least 3 weeks (days 1,7,14,21) 1
• Rising hCG: Two consecutive rises of ≥10% over at least 2 weeks (days 1,7,14) 1
• Persistent hCG: Detectable hCG ≥6 months after evacuation (this criterion has been omitted in recent UK guidance as hCG may spontaneously normalize) 1
• Elevated hCG: Serum hCG ≥20,000 IU/L more than 4 weeks after evacuation (associated with increased uterine perforation risk) 1

Additional Indications

• Heavy vaginal bleeding requiring transfusion, even if hCG is falling 1
• Histological evidence of choriocarcinoma on tissue diagnosis 1
• Evidence of metastases to brain, liver, or gastrointestinal tract 1
• Radiological lung opacities >2 cm on chest X-ray (smaller lesions may spontaneously regress) 1

Prophylactic Methotrexate for High-Risk Features

Prophylactic chemotherapy at the time of evacuation is controversial and generally not recommended as standard practice, though it may be considered in specific high-risk scenarios when hCG follow-up is unavailable or unreliable. 2, 4

Evidence Base

• A 2024 randomized study found that single-dose methotrexate (50 mg/m²) as prophylactic chemotherapy did not significantly reduce progression to GTN (18.2% vs 36.3%, p=0.12), did not affect spontaneous remission rates, and did not reduce time to remission 5
• Prophylactic chemotherapy may be useful when hormonal follow-up is either unavailable or unreliable, particularly in resource-limited settings 4

High-Risk Features

• Age >40 years 2
• Pre-evacuation hCG >100,000 mIU/mL 2
• Excessive uterine enlargement for gestational age 2
• Theca-lutein ovarian cysts >6 cm 2

Given the lack of proven benefit and the high cure rate even when GTN develops, routine prophylactic chemotherapy cannot be recommended for high-risk molar pregnancy. 5

Staging and Treatment of Persistent GTN

Initial Staging Workup

When post-molar GTN is diagnosed, perform the following investigations: 1, 6

• Pelvic Doppler ultrasound (first-line imaging): Confirms absence of new pregnancy, measures uterine size/volume, evaluates pelvic spread, and assesses vascularity via pulsatility index (an independent prognostic factor for methotrexate resistance) 1, 6
• Chest X-ray (mandatory second test): Lungs are the most common metastatic site 1, 6
• If chest X-ray shows lesions >1 cm: Proceed immediately to MRI brain and CT chest/abdomen to exclude brain or liver metastases, which substantially alter treatment strategy 1, 6
• If chest X-ray is normal: No further imaging required; CT chest detection of micrometastases (~40% of cases) does not influence outcome or management in low-risk disease 1, 6

Risk Stratification (FIGO Scoring)

Use the FIGO 2000 prognostic scoring system to determine treatment intensity; this system predicts resistance to single-agent chemotherapy. 1

• FIGO score 0–6 (low-risk): Single-agent chemotherapy 1
• FIGO score ≥7 (high-risk): Multi-agent combination chemotherapy 1
• The FIGO scoring system is not valid for placental site trophoblastic tumor (PSTT) or epithelioid trophoblastic tumor (ETT) 1

Treatment Regimens

Low-Risk Disease (FIGO Score 0–6)

Methotrexate with folinic acid (MTX/FA) is the preferred first-line regimen in most European centers because it is less toxic than methotrexate alone or single-agent actinomycin D, and all patients can expect cure even if first-line therapy fails. 1

• Alternative: Single-agent actinomycin D 1
• Continue chemotherapy for 6 weeks of maintenance treatment after hCG normalization 1
• A randomized trial comparing MTX/FA and actinomycin D regimens is currently underway 1

High-Risk Disease (FIGO Score ≥7)

Multi-agent chemotherapy with EMA/CO (etoposide, methotrexate, actinomycin D, cyclophosphamide, vincristine) is the standard regimen because it is highly effective, simple to administer, and relatively non-toxic. 1

• Maintenance therapy should continue for 6 weeks after hCG normalization, extended to 8 weeks in patients with poor prognostic features such as liver ± brain metastases 1
• For ultrahigh-risk patients, early deaths can be reduced by induction with low-dose etoposide and cisplatin (EP) before EMA/CO 1
• Such patients may benefit from substitution of EMA/CO with EP/EMA 1

Salvage Therapy for Treatment Failures

• High-risk failures can frequently be salvaged with further chemotherapy; most centers use either EP/EMA or TE/TP 1
• Surgery alone can effectively salvage some patients with isolated foci of chemoresistant disease 1
• Residual lung or uterine masses following chemotherapy are not predictive of recurrence and do not require surgical excision 1

Special Considerations

Placental Site Trophoblastic Tumor (PSTT) and Epithelioid Trophoblastic Tumor (ETT)

• Stage I disease presenting within 4 years of last pregnancy: Hysterectomy with pelvic lymph node sampling 1, 3
• Metastatic disease: Multi-agent chemotherapy (e.g., EP/EMA) 1, 3
• Presenting beyond 4 years: May benefit from multi-agent and subsequent high-dose chemotherapy 1
• Lifelong hCG monitoring is recommended for PSTT/ETT 3

Twin Pregnancy with Coexisting Molar Pregnancy

• In genetically verified twin pregnancy with a hydatidiform mole and living fetus, the pregnancy can continue with close monitoring if the patient accepts the risks 3
• Regular ultrasound scans and serial hCG measurements are mandatory 3
• Obstetric complications (preterm birth, hemorrhage, preeclampsia) must be anticipated and managed 3

Recurrent or Familial Molar Pregnancy

• Patients with recurrent hydatidiform mole and/or familial hydatidiform mole should be referred for genetic workup and counseling 3
• Women with hereditary disposition due to NLRP7 mutation should be informed about the possibility of pregnancy via egg donation 3

Long-Term Follow-Up and Reproductive Outcomes

• After successful chemotherapy treatment, approximately 83% of women achieve subsequent pregnancy with no evident increase in congenital malformation rates 2
• The risk of recurrent molar pregnancy in subsequent conceptions is approximately 1% 2
• In all future pregnancies, offer early ultrasound scan (e.g., gestational week 8) and measure serum hCG approximately 8 weeks after termination of any future pregnancy 3
• Long-term monitoring after chemotherapy: hCG measurements for one year (monthly or bimonthly for first 3 months, then every 2–3 months) to detect the ~3% recurrence risk 3

Centralization of Care

Management of GTN is optimized by centralization of care, pathology review, and hCG monitoring at specialized trophoblastic disease reference centers. 1

• Centralized care improves outcomes through standardized protocols, expert pathology review, and coordinated surveillance 1
• All treatment decisions for persistent GTN should involve consultation with a GTD reference center 1, 2