Triploidy & Hydatidiform Moles

Question 1

What is incidence of triploidy in pregnancy?

Answer 1

1-3% recognised pregnancies.

99.9% spontaneously abort during 1st trimester, or lost during 2nd trimester as fetal death in utero.

Livebirn triploids extremely poor prognosis (<1mth).

Question 2

Diandry (type 1):

• Double paternal contribution (2 paternal sets, 1 maternal).
• show cystic villi that have trophoblastic hyperplasia (partial hydatidiform mole).
• Most common (60-80%).

How can diandric triploids arise?

Answer 2

• Maj fertilisation of normal egg by 2 sperm (dispermy).
• minority: fertilisation of normal egg by diploid sperm (complete nondisjunction of entire set at spermatogenesis).
• Generally abort between 10-12wk

Question 3

Digyny: (type II):

• Double Maternal contribution (2 sets maternal, 1 paternal).
• Non hydronic villi
• Placenta is non molar & generally smaller.

How can digyny triploids arise?

Answer 3

• Fertilisation of a diploid egg (nondisjunction of entire chromosome set at MI or MII) by a haploid sperm.
• Retention of a polar body in a fertilised egg!
• Fusion of 2 eggs (dieggy) & fertisation by a haploid sperm
• Maj digyny can triploids abort at 10wks!

Question 4

What are clinical features of triploidy?

Answer 4

• face to chest fusion
• development retardation
• Macrocephaly
• neural tube defects
• syndactyly (usually 3 to 4)
• heart/renal defects

Question 5

Phenotype of digynic (maternal)?

Answer 5

• IUGR
• Large head
• small placenta (without cystic formation)
• oligohydramnios
• Holoprosencephaly

Question 6

Phenotype of diandric (paternal)?

Answer 6

• Accounts for >90% partial hydatidiform moles.
• Symmetrical IUGR with structural abnorm (neural tube defects)
• Normal head size
• Large cystic placenta
• High Maternal hCG (80% cases)
• increased risk of pre eclampsia

Question 7

Recurrence risk of moles?

Answer 7

• Mostly sporadic
• Not increased above general population!
• Diandric triploidy with partial mole: 1-1.5% risk
• Digynic triploidy: recurrent in few families!

Question 8

What is most common form of gestational trophoblastic disease?

Answer 8

• Hydatidiform moles!

Question 9

WHO classification of GTD (gestational trophoblastic disease)?

Answer 9

GTD WHO:
- Pre-malignant forms: complete hydatidiform mole or partial hydatidiform mole.

• malignant forms:
  Invasive mole
  Choriocarcinoma
  Placental site trophoblastic tumours.
• 95% malignant GTD can be successfully treated if diagnosed early.
• All GTD tumours produce hCG (aids detection).

Question 10

What is a complete hydatidiform mole?

Answer 10

• Diploid androgenic pregnancy (both sets paternally derived)
• 90% 46,XX, 10% 46,XY
• 75% hydatidiform moles are complete moles!

Question 11

Features of complete hydatidiform mole?

Answer 11

• No fetal development!
• Placenta has swollen villi with marked hypoplasia
• extensive hydrous
• evacuated before 12wks gestation
• clinical symptoms: hypertension, oedema, vaginal bleeding.

Question 12

Causes of Complete Hydatidiform Moles?

Answer 12

• 20% dispermic fertilisation (2 sperm fertilising empty egg; can be Xx or XY)
• 80% monospermic fertilisation (single spermatozoon fertilises empty egg with male pronucleus dividing to form diploid nucleus; can only be XX as XY zygotes lack essential genes on X necessary for development!

Question 13

What are Partial Hydatidiform moles?

Answer 13

• Triploid with additional set of chromosomes being paternal (diandric)
• 69,XXX or 69,XXY or 69,XYY (rare)
• Features: 2 populations of villi- small normal appearing & large hydronic
• Enlarged villi
• irregular villi have scalloped edges
• Trophoblast hypoplasia

-Fetal development occurs: atonal blood vessels, umbilical cord, amino & chorionic plate but malformation of fetal parts evident.

Question 14

How are molar pregnancies diagnosed?

Answer 14

• painless vaginal bleeding in 4th to 5th mth pregnancy.
• Blood tests show high levels of hCG
• Diagnoses suggested by ultrasound, moles resembles bunch of grapes!
• Definitive diagnosis by histopath exam

Question 15

Hydatidiform mole recurrence risks?

Answer 15

• Subsequent preg following complete hydatidiform mole = 1 in 100
• Risk following 2 consecutive complete moles = 1 in 5!
• small increase of second hydatidiform mole following partial = 1 in 600
• recurrence can be either of the same (complete or partial) or of other type…

Question 16

What is familial recurrent Hydatidiform moles (FRHM)?

Answer 16

• Maternal effect autosomal recessive
• V.rare! Women have inherited predisposition to recurrent molar pregnancies (particularly complete moles).
• 75% of these women pregnancies develop as complete hydatidiform mole.
• CHM associated with FRHM are diploid & genetically Biparental!
• Differs from sporadic complete hydatidiform moles (paternal in origin)

Question 17

What are 2 genes assoc with FRHM?

Answer 17

• NLRP7 & KHDC3L (mutations)

Question 18

Risk of invasive mole following complete mole?

Answer 18

• ~15% risk of invasive mole following complete mole
• 0.5% risk following partial mole!
• Presentation of high hCG following previous molar pregnancy, or abnormal bleeding, abdominal pain or swelling.

Question 19

Risk of gestational choriocarcinoma (malignant) following moles?

Answer 19

• 3% following complete mole, 0.1% following partial mole.

- increased levels of hCG!

Question 20

What is treatment for GTDs?

Answer 20

• Suction evacuation recommended for complete or partial molar pregnancies.
• After molar preg, hCG levels should be monitored for period of time (usually weekly).
• monitor for up to 2 yrs after complete, 6mths after partial molar pregnancy.

Question 21

Summary: karyotyping for complete & partial mole?

Answer 21

• complete = 46,XX (46,XY)
• Partial: 69,XXY
• hCG increased in both (but lot higher in complete).
• Convert to Choriocarcimona (2%), partial (rare)
• Fetal parts: complete - NO, partial: yes!
• Risk of complications: complete mole (15-20% malignant trophoblastic disease), partial (<5%, low risk of malignancy).