Bleeding in Early Pregnancy

   

3-Gestational Trophoblastic Disease

Originate from placental tissues

Rare human tumors curable even when metastatic

4 entities :

• Complete hydatidiform mole

• Partial hydatidiform mole

• Placental site trophoblastic tumors

• Choriocarcinoma

Pathology

· Complete mole

• Product of an abnormal conception lacking identifiable embryonic or fetal tissue.

• Chorionic villi with generalized hydropic swelling.

• Diffuse trophoblastic hyperplasia.

• Implantation-site trophoblast with diffuse and marked atypia.

Karyotype :

• 90% : 46 XX

• 10% : 46 XY

• Entirely of paternal origin

• Mitochondrial DNA of maternal origin

· Partial mole

• Presence of identifiable embryonic or fetal tissues.

• Variation in size of chorionic villi, focal swelling, cavitations and trophoblastic hyperplasia.

• Implantation-site trophoblast with focal, mild atypia.

If presence of a fetus :

• Growth retardation and multiple congenital malformations.

• Karyotype : 90-93% triploid

• One extra haploid set of paternal origin

· Choriocarcinoma

• Dimorphic population of cytotophoblast and syncitiotrophoblast without formed chorionic villi plus evidence of myometrial invasion.

• Hemorragic nodules and often extensive necrosis.

• Highly metastatic potential.

• Origin : any type of gestation

Hydatidiform mole	45%
Normal term pregnancy	25%
Spontaneous abortion	25%
Ectopic pregnancy	5%

Karyotype : variable

· Placental site trophoblastic tumor

• Intermediate trophoblastic cell lineage

• Recognition difficult : differentiation from cytotrophoblast in continuous series of stage.

Unpredictable behavior :

• 90% benign

• 10% metastatic , killing

Origin : 95% after a term pregnancy
extremely resistant to chemotherapy
Karyotype : variable

EPIDEMIOLOGY AND RISK FACTORS·

Hydatidiform mole

1/1000 pregnancies	USA and most regions of the world
2/1000 pregnancies	Japan
Japanese in Hawaii	incidence> non-Japanese< in Japan
Maternal age	> 35 year old : 2x for> 35 yo ; 7,5x for> 40 yo
	< 20 year old
Previous hydatidiform mole	10x
Diet	¯ risk with diets rich in carotene and adequate amounts of fat intake

· Choriocarcinoma

Epidemiology not well understood

USA	1/24000 pregnancies and 1/19920 live births
ASIA	1/6000 to 1/8000 pregnancies
Age over 40 yo	­ risk 8x
Most important risk factor	history of previous hydatidiform mole (29 to 83% cases)

CLINICAL PRESENTATION

• Vaginal bleeding

• Uterine size palpably larger than gestational age

• Theca lutein ovarian cysts

• Preeclampsia

• Hyperemesis

• Spontaneous incomplete abortion (partial mole)

• Hyperthyroidism (rare)

• Respiratory insufficiency (rare)

METASTATIC DISEASE

• 4% after complete molar pregnancy.

• More commonly after nonmolar pregnancy.

• Often associated with choriocarcinoma, highly vascular and prone to severe haemorrage either spontaneously or during biopsy.

Most common metastatic sites

· Lungs	80%
· Vagina	30%
· Pelvis	20%
· Liver	10%
· Brain	10%

 

 

 

 

DIAGNOSIS

• Ultrasound

  • multiple small sonolucencies (3 to 5 mm diameter) = hydropic villae, without embryo (complete mole) .

  • " Snow storm pattern ".

• b HCG higher than gestational age.

• In placental site trophoblastic tumors : ­ HPL , not b HCG.

TREATMENT

· Hydatidiform mole (non metastatic)

D&C or hysterectomy if no desire of fertility.

Follow up :

• weekly ß HCG ® 3 normal values

• then 1x/month for 6 months

• Return to normal values within 9 to 11 weeks

WHO Prognostic Index Score to determine the resistance to chemotherapy

	Score
	0	1	2	4
Prognostic Factors
Age	= 39	= 39	-	-
Previous pregnancy	Mole	Abortion	Term	-
Interval (months	< 4	4-6	7-12	> 12
ß hCG (mIU/ml)	< 10 3	10 3-10 4	10 4-10 5	> 10 5
ABO groups	-	O or A	B or AB	-
Largest tumor, including uterine(cm)	-	3-5	> 5	-
Site of metastases	Lungs, pelvis, vagina	Spleen, Kidney	GI tract, Liver	Brain
Number of Metastases	-	1-3	4-8	> 8
Prior Chemotherapy	-	-	Single	Multiple

• Low risk : 0-4

• Intermediate risk : 5-7

• High risk : > 8

Persistent Gestational Trophoblastic Tumor

18-29% of complete moles (USA).

Diagnosis : if plateau of ß hCG for 3 consecutive weeks or if ­ ß hCG.

Histology may be different (Choriocarcinoma or placental site trophoblastic tumor).

Criteria of severity

• ß hCG > 100 000 mUI/ml at diagnosis

• ovarian thecomas> 6cm

• preeclampsia, hyperthyroidism, tumor embolism

Risk of persistent trophoblastic disease then 40-50%

Risk diminishes to 10-15% with chemoprophylaxis (Methotrexate or Dactinomycin)

Staging : if pelvic examination and Chest X-Ray(or Chest CT-scan)in order,very low risk of finding metastases elsewhere.

CHEMOTHERAPY

According to WHO prognostic Index Score

• Score= 7 :low to intermediate risk, so monochemotherapy

• Score= 7 :high risk and therefore polychemotherapy.

Monochemotherapy

Methotrexate (MTX) ® 90% CR.

If failure with MTX, with further ttt® 100% CR.

Polychemotherapy

5 drugs : etoposide,MTX,dactinomycin,cyclophophamide (EMA-CO).

83% CR versus 30-45% CR with monochemotherapy in " high risk " situations.

FOLLOW-UP

· b hCG weekly during treatment until 3 normal levels (3 weeks)
· b hCG every 2 weeks for the next 2-3 months.
· b hCG every 1 month for 6 months then every 2 months

*follow-up after one year

*Efficient contraception during treatment and follow-up. Wait a minimum of one year before starting pregnancy

Pregnancy experience, after GTD

· Fertility:

• 68 % live births after complete mole

• 74 % live births after partial mole

• 68 % term live births after persistent GTT.

· Even with chemotherapy

· Risk subsequent molar pregnancy:

• 1% (after one mole)

• 15% to 28% after 2 molar pregnancies

• risk persistent GTT­3x in patients with repeat mole

· Rate of stillbirth higher after persistent GTT than general population (odd ratio 2, 9)

· Infertility rate same as in general population (4%)

 

Enter your search terms Submit search form

Important Disclaimer

The content displayed by the physician writers & editors of arabicobgyn.net. is designed to be educational. Under no circumstance should it replace the expert care and advice of a qualified physician. Arabicobgyn.net does not give medical advice or care to its viewers. Rapid advances in medicine may cause information contained here to become outdated, invalid or subject to debate. Accuracy cannot be guaranteed. Arabicobgyn.net physicians, writers, editors and management assume no responsibility for how information presented is used by the public.
 

 

 

--> Main Page