Gestational trophoblastic disease (GTD) is a group of rare tumors that develop in the uterus during or after pregnancy, primarily from trophoblastic tissue. Most types of GTD, including molar pregnancies, are noncancerous and highly treatable. Symptoms may include excessive uterine enlargement, vaginal bleeding, and nausea. Treatment options are available, and in the majority of cases, GTD can be cured.

1. Gestational
Gestational
Trophoblastic Disease
Trophoblastic Disease
Current management
Current management

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

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

5. Complete Mole
Complete Mole

6. Complete Mole Histology
Complete Mole Histology

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

8. Partial Mole Histology
Partial Mole Histology

9. Management
Management
Pre-operative assessment – medical complications / CXR
Pre-operative assessment – medical complications / CXR
Evacuation -
Evacuation - oxytocin infusion after curettage
oxytocin infusion after curettage
heavy bleeding should not deter from cervical dilatation
heavy bleeding should not deter from cervical dilatation
suction curettage (fundal massage)
suction curettage (fundal massage)
uterus usually dramatically reduces in size / bleeding controlled
uterus usually dramatically reduces in size / bleeding controlled
complete with sharp curettage
complete with sharp curettage
Histological evaluation of all tissue
Histological evaluation of all tissue
Natural history:
Natural history: Complete - 15% local uterine invasion
Complete - 15% local uterine invasion
4% metastatic disease
4% metastatic disease
High risk - hCG > 100000
High risk - hCG > 100000
(40%)
(40%) large uterus
large uterus 30% local invasion
30% local invasion
theca lutein cysts > 6cm.
theca lutein cysts > 6cm. 9% metastases
9% metastases
Partial mole -
Partial mole - 4% local uterine persistence/no cases choriocarcinoma
4% local uterine persistence/no cases choriocarcinoma
Many centres have abandoned follow-up
Many centres have abandoned follow-up

10. Follow up
Follow up
Weekly
Weekly 
-hCG (syncytiotrophoblast)
-hCG (syncytiotrophoblast)
levels
levels until
until
normal for 3 consecutive weeks
normal for 3 consecutive weeks
Can take 12-14 weeks
Can take 12-14 weeks
Then monthly until normal
Then monthly until normal
for 6 months
for 6 months
Contraception:
Contraception: Immediate
Immediate
Oral / barrier / permanent
Oral / barrier / permanent
No IUCD until hCG normal (perforation)
No IUCD until hCG normal (perforation)
No
No 
 persistent disease on OCP and
persistent disease on OCP and
regression time not influenced
regression time not influenced

11. GTN Follow-up
GTN Follow-up

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

13. WHO Prognostic Scoring
WHO Prognostic Scoring
Prognostic score
Prognostic score
Prognostic factor
Prognostic factor 0
0 1
1 2
2 4
4
Age
Age <39
<39 >39
>39
Antecedent pregnancy
Antecedent pregnancy Mole
Mole Abortion
Abortion Term pregnancy
Term pregnancy
Interval (months)
Interval (months) 4
4 4-6
4-6 7-12
7-12
Pre-treatment
Pre-treatment 
-hCG (log)
-hCG (log) <3
<3 <4
<4 <5
<5 >5
>5
Largest tumour
Largest tumour 3-4
3-4 5
5
Site of metastases
Site of metastases Spleen GI tract
Spleen GI tract Brain
Brain
Kidney
Kidney Liver
Liver
Number of metastases
Number of metastases 1-4
1-4 5-8
5-8 >8
>8
Previous Chemo. Failed
Previous Chemo. Failed Single drug 2 or more
Single drug 2 or more
Changes:
Changes: ABO group deleted, Liver mets score upgraded, no medium risk group
ABO group deleted, Liver mets score upgraded, no medium risk group
Low risk =
Low risk = 
 6
6 
 single agent chemotherapy
single agent chemotherapy
High risk =
High risk = 
 7
7 
 combination chemotherapy
combination chemotherapy

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

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

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

17. Pregnancy After GTN
Pregnancy After GTN
No evidence of increased congenital anomalies after one year contraception
No evidence of increased congenital anomalies after one year contraception
Recent Japanese data –
Recent Japanese data – Women who concieved during follow-up period < 1
Women who concieved during follow-up period < 1
year
year
No adverse effect on anomalies nor preterm
No adverse effect on anomalies nor preterm
delivery
delivery
Risk of further molar pregnancy:
Risk of further molar pregnancy: 0.5-2.5% if one previous molar
0.5-2.5% if one previous molar
33% if two previous molar
33% if two previous molar
3 molar pregnancies – poor live birth rate
3 molar pregnancies – poor live birth rate
Risk of molar pregnancy increases with number of previous spontaneous abortions
Risk of molar pregnancy increases with number of previous spontaneous abortions
Previous term pregnancies reduce risk of GTN
Previous term pregnancies reduce risk of GTN

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