1. Gestational Trophoblastic Disease
Current management

2. Background Incidence – U.S. and Europe 1/1500
South East Asia 1/150 (↓ Carotene, animal fat and Vit. A)
Can follow any gestational event – abortion, miscarriage, ectopic, normal pregnancy
Curable in vast majority – chemotherapy 1956
Complete & partial mole
Invasive mole
Placental-site trophoblastic tumour
Choriocarcinoma ( always if follows term pregnancy 1/50,000 )
Latter 3 usually derive from molar pregnancy

3. Complete Mole
Pathology: Generalized hydatidiform swelling and trophoblastic hyperplasia
fetal/embryonic tissue absent
Karyotype: 90% 46XX haploid sperm fertilizes ovum and duplicates
ovum nucleus either absent or inactivated
10% 46XY
Clinical: Vaginal bleeding 95% (prune juice, anaemia)
Enlarged uterus 50%
Theca lutein cysts 50% (often >6cm.- may take 3 months)
Hyperemesis 25%
PET 25% (no reported case of eclampsia)
Hyperthyroidism 5% (if free T4↑ - B-blockade)
Trophoblastic emboli 2%
Diagnosis: U/S usually very sensitive – generalized swelling (snow-storm )

5. Complete Mole

6. Complete Mole Histology

7. Partial Mole Triploid karyotype – extra haploid set paternal
Sometimes fetus present – usually triploid growth restricted / multiple anomalies
Pathology differs from complete: focal hydatidiform swelling
varying size of chorionic villi
marked villous scalloping
focal trophoblastic hyperplasia
identifiable embryonic or fetal tissues
Clinical: Usually as a regular incomplete or missed abortion
Excessive uterine enlargement / PET very rare
No hyperemesis / hyperthyroidism / theca-lutein cysts
Diagnosis: U/S may detect focal cystic spaces of varying diameter
Diagnosis on histology of curettings

8. Partial Mole Histology

9. Management Pre-operative assessment – medical complications / CXR
Evacuation - oxytocin infusion after curettage
heavy bleeding should not deter from cervical dilatation
suction curettage (fundal massage)
uterus usually dramatically reduces in size / bleeding controlled
complete with sharp curettage
Histological evaluation of all tissue
Natural history: Complete - 15% local uterine invasion
4% metastatic disease
High risk - hCG >
(40%) large uterus 30% local invasion
theca lutein cysts > 6cm. 9% metastases
Partial mole - 4% local uterine persistence/no cases choriocarcinoma
Many centres have abandoned follow-up

10. Follow up Weekly -hCG (syncytiotrophoblast) levels until
normal for 3 consecutive weeks
Can take weeks
Then monthly until normal
for 6 months
Contraception: Immediate
Oral / barrier / permanent
No IUCD until hCG normal (perforation)
No  persistent disease on OCP and regression time not influenced

11. GTN Follow-up

12. WHO Prognostic Scoring
Original assessment and scoring system 1984 changed in 2000
Metastatic disease occurs in 4% patients with molar pregnancy
Plateau: 4 values over 3 weeks
Rise:  10% for 3 values over 2 weeks
Clinical examination – especially pelvis, vagina and vulva
U/S to exclude pregnancy
Brain – MRI superior to CT scan
Chest – CXR adequate for counting metastases / CT scan also acceptable
Abdomen – CT scan

13. WHO Prognostic Scoring
Prognostic score
Prognostic factor
Age < >39
Antecedent pregnancy Mole Abortion Term pregnancy
Interval (months)
Pre-treatment -hCG (log) < <4 < >5
Largest tumour
Site of metastases Spleen GI tract Brain
Kidney Liver
Number of metastases >8
Previous Chemo. Failed Single drug or more
Changes: ABO group deleted, Liver mets score upgraded, no medium risk group
Low risk =   single agent chemotherapy
High risk =  7  combination chemotherapy

14. FIGO Staging Stage 1 Tumour confined to uterus
Stage 2 Tumour confined to pelvis
Stage 3 Metastases to lung ( with/without pelvic metastases )
Stage 4 Distant organ metastases ( with/without lung metastases )

15. Chemotherapy
Low-risk If non-metastatic - always curable ( Hysterectomy if chemo fails)
Methotrexate: Many regimes
I.M. Methotrexate 1mg/Kg days 1,3,5,7
I.M./ P.O. Folinic acid 0.1mg/Kg days 2,4,6,8
I.M. Methotrexate 40mg/m² weekly
Actinomycin D: I.V. push 1.25mg/m² every 14 days
Follow-up: -hCG, FBC, LFTs and U/Es, creatinine prior to each cycle
Continue treatment cycle for 1-3 weeks after normal -hCG
Check -hCG monthly for 12 months, then 2 monthly for 12 months
Contraception for 12 months
Complete remission in 85-90% 80% require only one course
Toxicity: Thrombocytopenia 2%, neutropenia 6% and hepatotoxicity 14%

16. High Risk GTN
Invasive mole: invades myometrium / diagnosed at hysterectomy / can metastasize
mets may be choriocarcinoma
Placental site trophoblastic tumour: Locally invasive composed of cytotrophopblast small if any rise in hCG (<3000)
vaginal bleeding usually after amenorrhoea
Large polypoid tumour / insensitive to chemotherapy Curettage sometimes successful / Hysterectomy
Choriocarcinoma: Accounts for majority of metastatic disease
Early vascular invasion and widespread dissemination
Fragile vessels  haemorrhagic complications
80% have lung mets – any respiratory symptom
30% have vaginal mets – highly vascular (avoid biopsy)
10% have liver mets – usually only with extensive tumour elsewhere
10% have brain mets – never isolated ( lung / vagina)
Treatment: EMA-CO chemotherapy +/- surgical resection / radiotherapy
Prognosis: 75% complete response rate Salvage chemo – BEP varying success

17. Pregnancy After GTN
No evidence of increased congenital anomalies after one year contraception
Recent Japanese data – Women who concieved during follow-up period < 1 year
No adverse effect on anomalies nor preterm delivery
Risk of further molar pregnancy: % if one previous molar
33% if two previous molar
3 molar pregnancies – poor live birth rate
Risk of molar pregnancy increases with number of previous spontaneous abortions
Previous term pregnancies reduce risk of GTN

18. Conclusions GTN is rare Ultrasound diagnosis becoming more common
Senior staff should perform ERPC ( suction and sharp curettage)
Follow-up – clinical and serum -hCG measurements in specialized clinics
Chemotherapy curative in vast majority low risk patients