Key Facts

Molar pregnancy is the most common form of gestational trophoblastic disease (GTD), characterised by abnormal proliferation of trophoblastic tissue. Prompt diagnosis, evacuation, and βhCG surveillance are essential to detect and treat malignant transformation.

Epidemiology

• UK incidence: approximately 1 in 714 live births
• Complete moles more common than partial moles
• Risk factors: extremes of reproductive age (<16, >45), previous molar pregnancy (1-2% recurrence), Asian ethnicity
• GTN develops in 15-20% of complete moles and 0.5-5% of partial moles

Aetiology

• Complete mole: fertilisation of an empty ovum by a single sperm that duplicates (90% 46XX) or two sperm (10% 46XY); entirely paternal DNA
• Partial mole: fertilisation of a normal ovum by two sperm, resulting in triploid (69 chromosomes); both maternal and paternal DNA present

Pathophysiology

• Abnormal fertilisation leads to excessive trophoblastic proliferation
• Complete mole: diffuse villous oedema with trophoblastic hyperplasia, no embryonic tissue
• Partial mole: focal villous oedema, some normal villi, may contain fetal tissue
• Trophoblastic tissue invades the myometrium and may metastasise (lungs most common)
• βhCG is produced in excess and serves as a tumour marker

Typical Presentation

• Vaginal bleeding in the first trimester (most common symptom, 84%)
• Uterus large for dates (in complete mole)
• Passage of grape-like vesicles (pathognomonic but rare now due to earlier detection)
• Markedly elevated βhCG (often >100,000 IU/L in complete mole)

Associated Features

• Hyperemesis gravidarum (due to very high βhCG)
• Early-onset pre-eclampsia (before 20 weeks - suspect molar pregnancy)
• Hyperthyroidism (βhCG structurally similar to TSH, cross-reacts with TSH receptor)
• Theca lutein cysts (bilateral ovarian enlargement from high βhCG)

Red Flags

• Pre-eclampsia before 20 weeks gestation
• Uterus significantly larger than expected for dates
• Hyperthyroidism symptoms in early pregnancy
• Respiratory symptoms (pulmonary metastases)

Bedside

• Urine pregnancy test (strongly positive)
• Blood pressure (pre-eclampsia before 20 weeks)
• Thyroid examination

Bloods

• Serum βhCG: markedly elevated (often >100,000 IU/L in complete mole)
• TFTs (hyperthyroidism screening)
• FBC (anaemia)
• Group and save
• Coagulation screen
• U&Es, LFTs

Imaging

• Transvaginal ultrasound: snowstorm appearance (complete mole); mixed echogenic mass with cystic spaces (partial mole); may see theca lutein cysts
• CXR: baseline for comparison if GTN develops (pulmonary metastases)

Special Tests

• Histological examination of all products of conception: essential to confirm diagnosis and classify mole type
• Immunohistochemistry: p57 (absent in complete mole, present in partial mole)
• Genotyping/flow cytometry to confirm ploidy

Non-pharmacological

• Register with UK GTD centre (Charing Cross Hospital London or Weston Park Hospital Sheffield)
• Provide written information and support from GTD patient support organisations
• Reliable contraception until βhCG follow-up complete (barrier methods or hormonal; avoid IUCD until βhCG normal)

Pharmacological

• Anti-D immunoglobulin for RhD-negative women
• If hyperthyroid: beta-blockers (propranolol 40mg TDS) for symptom control
• Do not use oxytocic agents before evacuation (risk of trophoblastic embolism)

Surgical/Interventional

• Suction evacuation under ultrasound guidance: treatment of choice for both complete and partial moles
• Avoid medical evacuation (misoprostol) as it may increase risk of GTN and incomplete evacuation
• Second evacuation may be needed if retained products

Referral Criteria

• All confirmed molar pregnancies must be registered with a UK GTD centre
• βhCG follow-up: weekly until normal, then monthly for 6 months from evacuation (complete mole) or from normalisation (if βhCG normalises within 56 days of evacuation for partial mole)
• If βhCG plateaus or rises: refer urgently for GTN assessment and staging

• Complete mole: 80-85% resolve after evacuation; 15-20% develop GTN
• Partial mole: 95-99.5% resolve after evacuation; 0.5-5% develop GTN
• GTN is highly curable with chemotherapy (cure rate >98%)
• Recurrence risk of molar pregnancy: 1-2% after one mole; 15-20% after two moles
• Future fertility: normal pregnancy outcomes expected after complete βhCG follow-up
• Advised to wait until βhCG surveillance is complete before conceiving again

Complete vs Partial Mole Comparison

βhCG Follow-up Protocol (UK GTD Centres)