GESTATIONAL

THROPHOBLASTIC
DISEASE
GYNAECOLOGICAL EMERGENCIES
 DEFINITION

Gestational Trophoblastic disease

A diverse group of
interrelated disease
in which the lesions
are characterized by
abnormal
proliferation of

Benign (80%) : molar

trophoblast of the

Malignant (20%)
placenta

pregnancies
 EPIDEMIOLOGY
The true incidence is unknown in all countries as the aborted conceptus may be discarded as a simple
abortion;
 Malaysia : 2.8 in 1000
 Indonesia : 11.5 in 1000
 Philippines: 1 in 173
 UK : 1 in 1200 to 1 in 2000
 US : 1 in 1000 to 1 in 2500

 More common in Asian women than in Caucasian (may be attributed to selection bias in hospital
studies).

 Peak incidence is related to age, usually occur in women under 20y/o and over 45y/o.

“Obstetric today second edn, 2013”

RISK FACTORS

Extremes in age (<20, Prior history

of GTD
>35)

Blood group
Nulliparity
 Complete Mole Partial Mole
Pathogenesis Empty ovum is fertilised by 23X or 23Y haploid sperm. Dispermic fertilisation of 2 haploid sperms with oocyte (23X)
(the chromosome duplicates if fertilised by a single sperm) rsulting in triploidy

No fetus is formed
Fetus is non-viable; severe congenital abnormalities due to triploidy

Karyotype 46XX or 46XY 69XXX or 69XXY

(has paternal contribution only) (has maternal and paternal contribution)
US appearance • Snowstorm appearance • Focal cystic changes in placenta with increased echogenicity
• Absence of fetus • Presence of fetus, with IUGR (amniotic fluid and fetal heart rate
• The ovaries are enlarged and often contain theca lutein cysts may also be present)

Macroscopic • Grossly swollen hydropic vesicles (‘bunch of grapes’) • Presence of some recognisable fetal parts
appearance • Absent viable fetus

Microscopic • Diffuse hydropic chorionic villi • Focal hydropic chorionic villi

appearance • Diffuse trophoblastic hyperplasia • Focal trphoblastic hyperplasia (usually confined to
• Absent scalloping of chorionic villi syncytiotrphoblasts)
• Fetal vessels are absent • Scalloping of the villi and trphoblastic inclusion within the villi
• Fetal vessels & frequently, an embryo are present

hCG levels • High (>100,000) • Slightly elevated

Weeks to normal hCG • 14 weeks • 8 weeks

COMPLETE HYDATIDIFORM MOLE

PARTIAL HYDATIDIFORM MOLE

CLINICAL PRESENTATION
History
 Vaginal bleeding in the first trimester – 90%
 Hyperemesis gravidarum- severe nausea and vomiting
 Hyperthyroidism- nervousness, anorexia, tremor; subclinical hyperthyroidism is more
common
 Preeclampsia prior to 20 weeks’ gestation- irritability, dizziness, photophobia
 Abdominal pain- from large theca lutein cyst
 In partial molar pregnancy, the symptoms are much less severe (hCG levels are normal or only
slightly elevated).
 PHYSICAL EXAMINATION
General examination • GCS (hypovolaemic shock from torrential bleeding)
• Conjunctival pallor
• Hyperthyroidism signs
• Signs of preeclampsia before 20 weeks ; high BP
• Respiratory distress due to cardiopulmonary complications such as
trophoblastic emboli phenomenon, and thyroid crisis

Per abdomen • Uterus is larger than date

• Uterus feels ‘doughy’
• Difficult to palpate for fetal parts
• Absence of fetal heart on auscultation

Speculum examination • Expulsion of grape-like molar clusters

• State of the cervix and cervical os

Bimanual examination • Uterus is larger than date

• Adnexal mass or tenderness- large theca lutein cyst
DIFFERENTIAL DIAGNOSES
 Miscarriage – PV bleeding
 Ectopic pregnancy – PV bleeding, abdominal pain
 Hyperemesis gravidarum – excessive nausea, vomiting
 Multiple pregnancy – uterus larger than date, hyperemesis gravidarum
 Elevated hCG- normal pregnancy, ectopic pregnancy, spontaneous abortion.
 Investigation Indication
BLOOD Serum beta- hCG To quantify serum hCG
Extremely high in complete molar pregnancy
For baseline for serial monitoring after D&C done.
Detection of persistent GTD
FBC Patient may be anemic after torrential blood loss
Coagulation profile Coagulopathy such as DIVC is a known complication
GSH/GXM If blood transfusion is indicated
Renal profile Assessment of pt’s electrolyte and hydration status (Renal
derangement due to excessive nausea and vomiting)
Liver function test To exclude metastases
Blood group and Rhesus factor Need to give anti D ig to Rh negative pt
URINE Urine hCG Alternative if serum b-hCG is not available

IMAGING Abdominal/Transvaginal ultrasound • Features are as discussed

Chest X ray • Considered if sign of metastases
Ct scan • Lungs are a primary site of metastases for malignant
trophoblastic tumors

INVASIVE Suction and curettage, send for HPE Features are as discussed
Important to differentiate partial mole from a simple
miscarriage
MANAGEMENT
-Patient’s resuscitation
and stabilization
-If patient has PE, antihypertensives
may be used to decrease the risk of
maternal stroke
-If patient has hyperthyroidism, use of
-Pre-operative B-blockers can avoid precipitation of
thyroid storm by anaesthesia and
investigation surgery.

Definitive treatment: Dilation and suction curettage,

send sample for HPE
For partial molar pregnancies (or twin pregnancies
when there is a normal pregnancy with a molar
pregnancy,) and the size of the fetal parts deters the use
of suction curettage, then medical evacuation can be
used.
Total abdominal hysterectomy is a reasonable option
for patients who do not wish to preserve their fertility.

After removal of uterine contents,

administer IV oxytocin to stimulate

Follow up
uterine contraction and minimize
blood loss, in the case of significant
hemorrhage
RhoGAM should be given to all Rh-
negative women
  Molar pregnancy-associated hyperthyroidism will resolve with treatment of the gestational
trophoblastic disease (GTD). Some patients will require antithyroid therapy until GTD
treatment is complete.
 Theca lutein cysts usually regress slowly over two to four months following evacuation with
declining hCG levels.
  Preeclampsia associated with complete molar pregnancy resolves promptly after molar
evacuation and usually does not require medical management
FOLLOW UP
  to confirm successful treatment, and to identify women with persistent or malignant GTD who
may require adjuvant chemotherapy or surgery at an early stage.
 The risk of persistent or recurrent GTD is greatest in the first 12 months after evacuation, with
most cases presenting within 6 months.
 Follow-up parameter:
 Serial hCG level

 Duration of f/up:
 If hCG has reverted to normal within 56 days of the pregnancy event then follow up will be for 6 months
from the date of uterine evacuation.
 If hCG has not reverted to normal within 56 days of the pregnancy event then follow-up will be for 6
months from normalisation of the hCG level.
 Malaysia: 2 years follow-up is recommended

 Pregnancy is not advisable during follow up

b-HCG regression curve
PERSISTENT GTD/ GESTATIONAL
TROPHOBLASTIC NEOPLASIA
 GTN comprises specific histologic entities, including:
 Invasive mole
 Choriocarcinoma
 Placental site trophoblastic tumor (PSTT)
 Epithelioid trophoblastic tumor (ETT)

 GTN may develop after a molar pregnancy, a non-molar pregnancy or a live birth (GTN that occurs after a molar pregnancy is most commonly
persistent/invasive GTD, and GTN that occurs after a nonmolar pregnancy is most commonly choriocarcinoma.)
 Following evacuation of a complete or partial molar pregnancy, if hCG levels rise or remain elevated over several weeks, the patient is
classified as having GTN.
 The diagnosis of postmolar GTN is based upon the following International Federation of Gynecology and Obstetrics (FIGO)
criteria:
 hCG levels plateau (remain within ±10 percent of the previous result) across four measurements over a three-week period (eg, days 1, 7, 14, and 21)

 hCG level increases >10 percent across three values over a two-week duration (eg, measurements on days 1, 7, and 14, increase is >10 percent from

day 1 to day 14)

 Persistence of detectable serum hCG for more than six months after molar evacuation
 Among women with molar pregnancy, the risk factors for developing GTN include:
 (1) complete mole with signs of trophoblastic proliferation (uterine size greater than gestational age,
serum human chorionic gonadotropin [hCG] levels >100,000 mIU/mL); 
 (2) ovarian theca lutein cysts >6 cm in diameter; and
 (3) age >35 to 40 years.

 Common sites of metastases:

 Lungs (80%)
 Vagina (30%)
 Pelvis (20%)
 Brain (10%)
 Liver (10%)
 MANAGEMENT

• Women with scores ≤ 6 are at low risk and are treated with single-agent intramuscular methotrexate alternating
daily with folinic acid for 1 week followed by 6 rest days.

• Women with scores ≥ 7 are at high risk and are treated with intravenous multi-agent chemotherapy, which
includes combinations of methotrexate, dactinomycin, etoposide, cyclophosphamide and vincristine.

• Treatment is continued, in all cases, until the hCG level has returned to normal and then for a further 6
consecutive weeks.
 Complete remission is documented in about 75% of patients treated with multi-agent
chemotherapy
 If brain metastases is detected, local radiation therapy is indicated.
 Hysterectomy can be performed in those patients in whom the tumor is resistant to treatment.
 COUNSELING
 Future pregnancy does not increase the risk of obstetric complications

 Normal reproductive function can be anticipated

 Avoid subsequent pregnancy for 6 months after b-hCG returns to normal

 Women with molar pregnancy must be advised to use reliable contraception during the entire interval of hCG
monitoring.
 Risk of recurrent molar :
 After one molar pregnancy (1 to 1.9 percent)
 After two molar pregnancies (15 to 17.5 percent)

 Early ultrasound confirmation of pregnancy is advised as soon as the pregnancy is missed

 B-HCG is done 6 weeks postpartum of any future pregnancy

 Regular menstruation occurs after completion of chemotherapy for GTN within 2-6 months. Further pregnancy is
advised after 12 months of completion of chemotherapy
PERSISTENT/INVASIVE MOLES
 Following D&C, about 15% will have persistent local disease (mostly invasive/persistent), and
4 % will have metastatic disease (mostly choriocarcinoma)
 Invasive moles are characterized by the penetration of large, swollen villi and thropoblast into
the myometrium.
 In rare cases, persistent/invasive GTD can cause uterine rupture, hemoperitoneum, and severe
anemia. Despite this, invasive moles rarely metastasise and capable of spontaneous regression.
 Treatment:
 Nonmets: single agent chemo
 Mets: low risk (single agent), high risk (multiagent chemo)
 Follow up: serial hCG
CHORIOCARCINOMA
 Malignant necrotizing tumor
 50% had preceding complete molar pregnancy, 25% develop disease after normal-term
pregnancy, and 25% after miscarriage,abortion, or ectopic pregnancy.
 Histology: sheets of anaplastic cytotrophoblast and syncytiotrophoblast in the absence of
chorionic villi.
 It invades the uterine wall and uterine vasculature, causing destruction of uterine tissue,
necrosis, and potentially severe hemorrhage.
 Often metastases, usually to the lungs,vagina,pelvis,brain,liver,intestines,kidneys.
 History: late postpartum bleeding, irregular uterine bleeding, symptoms of metastases.
 PE: signs of metastatic disease: uterine enlargement, vaginal masses, bilateral theca lutein cyst,
neurologic signs from CNS involvement.
 Pelvic ultrasound: uterine mass with hemorrhage and necrosis. On Doppler analysis, these
tumors are highly vascular.
 Treatment: same as invasive/persistent
PLACENTAL SITE
TROPHOBLASTIC TUMOR
(PSTT)
 Extremely rare tumor that arise from the placental implantation site.
 Intermediate cytotrophoblast from the placental sites infiltrate the myometrium and invade the
blood vessels.
 Histology: absence of villi and proliferation of intermediate throphoblasts and excessive
production of human placental lactogen (hPL).
 Clinical presentation: irregular vaginal bleeding, enlarged uterus.
 Diagnostic evaluation: chronic low level of hCG because these tumors lack proliferation of
syncytiotrophoblast, serum hPL, pelvic u/s revealed uterine mass with less hemorrhage than in
choriocarcinoma.
 Treatment: not sensitive to chemotherapy. Hysterectomy + multiagent chemotherapy for 1
week post op to prevent recurrent disease.
PROGNOSIS
 Prognosis for molar pregnancy is excellent, with 95%-100% cure rates after suction curettage.
 Persistent disease develop in 15% to 25% of patients with complete moles and in 4% of
patients with partial moles.
 The risk of developing recurrent GTD is approximately 1%-2% after one molar pregnancy, but
as high as 16% to 28% after two molar pregnancies.
 In choriocarcinoma, the cure rate for good prognosis disease (nonmets) is 95% to 100%, and
the cure rate for poor prognosis (mets) disease is 50-70%.

Obstetrics and Gynaecology, Sixth edn, Blueprints.

THANK YOU
REFERENCES
 https://www.rcog.org.uk/globalassets/documents/guidelines/gtg_38.pdf
 https://www.uptodate.com/contents/hydatidiform-mole-management
 https://
www.uptodate.com/contents/gestational-trophoblastic-neoplasia-epidemiology-clinical-feature
s-diagnosis-staging-and-risk-stratification?source=see_link&sectionName=STAGING%20AN
D%20RISK%20ASSESSMENT&anchor=H14900645#H14900645
 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3279094/
 Obstetric and Gynaecology, Blueprints Sixth Edition
 Obstetrics Today