GESTATIONAL

THROPHOBLASTIC
DISEASE
GYNAECOLOGICAL EMERGENCIES
 DEFINITION

A diverse group
of interrelated
disease in which
the lesions are
characterized by
abnormal
proliferation of
trophoblast of
the placenta
 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
 Complete Mole Partial Mole
Pathogenesis Empty ovum is fertilised by 23X or 23Y haploid Dispermic fertilisation of 2 haploid sperms with oocyte
sperm. (23X) rsulting in triploidy
(the chromosome duplicates if fertilised by a single
sperm)
Fetus is non-viable; severe congenital abnormalities due
No fetus is formed 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
Absence of fetus echogenicity
The ovaries are enlarged and often contain theca Presence of fetus, with IUGR (amniotic fluid and fetal
lutein cysts heart rate may also be present)
Macroscopic Grossly swollen hydropic vesicles (bunch of Presence of some recognisable fetal parts
appearance grapes)
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 14 weeks 8 weeks
hCG
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 pts 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
 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
>100,000mIU/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%)

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,

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-epidem
iology-clinical-features-diagnosis-staging-and-risk-stratification?s
ource=see_link&sectionName=STAGING%20AND%20RISK%20ASSESSMENT&anchor=
H14900645#H14900645
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3279094/
Obstetric and Gynaecology, Blueprints Sixth Edition
Obstetrics Today