Molar pregnancy

MOLAR
PREGNANCY
DR. YOGESH PATEL
MBBS, DGO
DIPLOMA IN LAPAROSCOPY (D. MAS)
FELLOWSHIP IN LAPAROSCOPY (F. MAS)
FELLOWSHIP IN INFERTILITY (F. ART)
PG DIPLOMA IN ULTRASONOGRAPHY (D. USG)
EMERGENCY MEDICINE SPECIALIST
FORMER CONSULTANT AIIMS NEW DELHI
MEMBER OF THE WORLD ASSOCIATION OF LAPROSCOPIC SURGEONS

 A molar pregnancy happens when tissue that normally
becomes a fetus instead becomes an abnormal growth
in uterus. Even though it isn't an embryo, this growth
triggers symptoms of pregnancy
DEFINATION:
 A heterogeneous group of interrelated lesions arising from
the trophoblastic epithelium of the placenta ,(tropho
means nutrition, blast means early developmental cells)
characterized by a distinct tumor marker –β HCG as tumor
arises from gestational rather than maternal tissue.
WHAT IS MOLAR PREGNANCY?

What is the classification of
gestational trophoblastic
disease?

It is a spectrum of trophoblastic diseases that includes:
Hydatiform mole (Benign)
Complete mole
Partial mole
Gestational trophoblastic neoplasia (Malignant)
Invasive mole
Choriocarcinoma
Placental site trophoblastic tumour
Epitheloid trophoblastic tumour
Gestational Trophoblastic Disease (GTD)
The last 3 may follow abortion, ectopic or normal pregnancy
FIGO oncology committee; Williams Obsterics
23rd , 2010

It is a spectrum of trophoblastic diseases that develops
malignant sequelae. GTN includes:
Invasive mole
Choriocarcinoma
Placental site trophoblastic tumour
Epitheloid trophoblastic tumour
Gestational Trophoblastic Neoplasia (GTN)
=Malignant Gestational Trophoblastic Disease
Disaia &Creasman Clinical Gynecological Oncology 2007
Cunningham et al Williams Obsterics 23rd , 2010

Aetiology:
Immunological factors
Racial factors
Dietary factors

Risk Factors
Age: extremes of age <15 yr and >40 yr
Reproductive history:
Prior Molar Pregnancy
Previous spontaneous abortion: double the incidence
Second molar: 1% - Third molar : 20%!
Diet: increase incidence in high carbohydrate diet, low protein and Vit. A or
carotene diet (complete mole)
Malnutrition and debilitated condition.
Repetitive H. moles in women with different partners
Maternal Blood Group AB and A
High gamma globin in absence of hepatic disesase

In the United States,
1 in 1,500 -2,000
pregnancies
In Asian countries,
•The rate is 10 times
higher than in Europe and
North America
In Saudi Arabia;,
•1.48 in 1000 live births
(hospital-based study;
Felemban AA, et al; 1969)
1 in 200-300 pregnancies in
south east asia.
1-2 in 1,000 pregnancies in
China and Japan.
Incidence
highest in
philippines i,e
1 in 80

WHAT IS THE CHROMOSOMAL
BASIS OF DEVELOPMENT OF
MOLE?

Pathogenesis and Cytogenetics of HM
Genetic
ConstitutionDiploid Triploid/ teraploid
Patho-genesis
4%
Fertilization
of an empty
ovum by two
sperms
“Diandric
dispermy”
90%
Triploid
fertilization of
a normal
ovum by two
sperms
“Dispermic
triploidy”
96%
Fertilization
of an empty
ovum by one
sperms that
undergoes
duplication
“Diandric
diploidy”
10%
Tetraploid
fertilization of
a normal
ovum by
three sperms
“Dispermic
triploidy”
Karyotype
46XX
69XXX
69YXX
69YYX
46XX
46XY
Complete Partial

Complete Mole, Pathogenesis
Duplication 46XX
Empty ovum
23X
Diandric diploidy
Androgenesis M:F 2:0
Paternal
chromosomes only

Complete Mole, Pathogenesis
46XX
Empty ovum
23X
Dispermic diploidy
Paternal
chromosomes only
23X 23X
23X

Partial Mole, Pathogenesis
69XXY
Normal ovum
23X
Dispermic triploidy M:F 2:1
Paternal extra set
23Y 23X
23Y 23X
23X

Familial biparental hydatidiform
mole
 Familial biparental hydatidiform mole (FBHM) is
inherited in an autosomal recessive pattern .
 Extensive mapping studies had demonstrated a
defective locus at 19q13.4. this abnormality have been
localised to a single gene- NALP7.
 This is the first causative gene defect identified in H.
MOLE.

-
Describe Complete
Hydatidiform Mole

Feature Partial mole Complete mole
Karyotype
Most commonly
69, XXX or - XXY
Most commonly
46, XX or -,XY
Pathology
Fetus Often present Absent
Amnion, fetal RBC Usually present Absent
Villous edema Variable, focal Diffuse
Trophoblastic proliferation Focal, slight-moderate Diffuse, slight-severe
Clinical presentation
Diagnosis Missed abortion Molar gestation
Uterine size Small for dates 50% large for dates
Theca lutein cysts Rare 25-30%
Medical complications Rare 10-25%
Postmolar GTN 1-5% 15-20%
Disaia &Creasman Clinical Gynecological Oncology 2007
Cunningham et al Williams Obsterics 23rd , 2010

What is the pathological features of
complete hydatidiform mole?

Complete H. Mole
Microscopically Enlarged, edematous villi and abnormal
trophoblastic proliferation that diffusely involve the
entire villi.
No fetal tissue, RBCs or amnion are produced
Macroscopically, these microscopic changes transform the
chorionic villi into clusters of vesicles with variable
dimensions “ like bunch of grapes“.
No fetal or embryonic tissue are produced
Uterine enlargement in excess of gestational age .
Theca-lutein cyst associated in 30%

1-Trophoblastic proliferation
2-Hydropic Degeneration
Complete hydatidiform mole: Microscopically Enlarged,
edematous villi and abnormal trophoblastic proliferation that
diffusely involve the entire placenta

Complete hydatidiform mole: Macroscopically, these
microscopic changes transform the chorionic villi into clusters of
vesicles with variable dimensions the name hydatidiform mole
stems from this "bunch of grapes"

Complete Hydatiform Mole
Uterine wall

CLINICAL FEATURES OF COMPLETE
MOLE
History of amenorrhoea of 8-12 weeks
Irregular Vaginal bleeding- commonest (90%).
may vary from spotting to profuse haemorrhage.
Expulsion of grapes like vesicles per vaginum (50%)
Lower abdominal pain- a) overstretching of uterus
b) concealed haemorrhage
c) uterine contraction to expel out the content
d) infection
e) perforation of the uterus by invasive mole.

Hydatidiform Mole
Usually, in
association
with,
Theca lutein cysts (25-50%)
Very early onset Preeclampsia
( 26%)
Markedly elevated hCG 100,000
mIU/mL
Breathlessness or acute respiratory
distress(2%)
Hyperemesis gravidarum (25%)
Hyperthyroidism (1-7%)
Excessive uterine enlargement
(50%)

Points to be noted during
examination
GENERAL EXAMINATION:
 Patient looks more ill and Pallor is out of proportion of
bleeding.
 PR-tachycardia, RR- tachypnea /dyspnoea
 Features of pre eclampsia present .usually there is early
onset of pre eclampsia.
P/A-
 Uterine enlargement> than expected GA.
 The uterus is soft and doughy due to absence of the
amniotic fluid sac.
 Fetal parts not felt
 FHS cannot be detected.

P/S-
 Cervical os may be open or close.
 Vuval or vaginal metastasis may appear as purple
nodule.
P/V-
 Note the uterine size.
 Internal ballotment cannot be elicited.
 Unilateral or bilateral theca lutein cyst of ovary
palpable in 25-35% of cases.

Partial H. Mole
Microscopically: The enlarged, edematous villi and
abnormal trophoblastic proliferation are slight and
focal and did not involve the entire villi.
There is a scalloping of chorionic villi with undulating
border.
Fetal or embryonic or fetal RBCs
Macroscopically: The molar pattern did not involve
the entire placenta.
Uterine enlargement in excess of gestational age is
uncommon.
Theca-lutein cysts are rare
Fetal or embryonic tissue or amnion

Scalloping of chorionic villi
Partial Hydatidiform Mole
Trophoblastic proliferation are slight and focal

Partial Hydatiform Mole
Vesicles
Maternal side

Fetal hand demonstrating syndactyly. The fetus had a triploid
karyotype, and the chorionic tissues were a partial mole

CLINICAL FEATURES OF PARTIAL
MOLE
History:
 Vaginal bleeding
 Usually diagnosed as missed or incomplete
abortion(91%).
Physical :
 A uterus corresponds or small for gestation age
 Excessive uterine size noted(4%)
 Toxemia of pregnancy(4%)

Diagnosis:
History
Clinical examination
Ultrasound examination
Serum hCG levels
Histopathological examination
Cytogenetic and molecular biological examination
Immunostaining of p57kip2 gene recent
development in diagnostic accuracy.it is a paternally
imprinted gene which is maternally expressed
.positive in PHM

U/S is helpful in making a pre-evacuation diagnosis
but the definitive diagnosis is made by histological
examination.
U/S: Early detection reduced from 16 weeks (passage of
vesicles) to 12 wks
βhCG levels > 2 multiples of the median may be of
value in the diagnosis often exceeding 105 IU/l.
RCOG Guideline No. 38 ; 2010

Guideline to hCG Levels During Pregnancy
hCG levels in weeks from LMP (gestational age)* :
3 weeks LMP: 5 – 50 mIU/ml
4 weeks LMP: 5 – 426 mIU/ml
5 weeks LMP: 18 – 7,340 mIU/ml
6 weeks LMP: 1,080 – 56,500 mIU/ml
7 – 8 weeks LMP: 7, 650 – 229,000 mIU/ml
9 – 12 weeks LMP: 25,700 – 288,000 mIU/ml
13 – 16 weeks LMP: 13,300 – 254,000 mIU/ml
17 – 24 weeks LMP: 4,060 – 165,400 mIU/ml
25 – 40 weeks LMP: 3,640 – 117,000 mIU/ml
Non-pregnant females: <5.0 mIU/ml
Postmenopausal females: <9.5 mIU/ml
* These numbers are just a GUIDELINE– every woman’s level of
hCG can rise differently. It is not necessarily the level that
matters but rather the change in the level.

Complete hydatidiform mole. The classic "snowstorm"
appearance is created by the multiple placental vesicles.

In most patients with a partial mole,
the clinical and U/S diagnosis is
Usually missed or incomplete abortion.
This emphasizes the need for a
thorough histopathologic evaluation of
all missed or incomplete abortions
How Is Partial H .Mole Diagnosed?

Classically: A thickened, hydropic placenta with
fetal or embryonic tissue
Multiple soft markers, including:
Cystic spaces in the placenta and
Transverse to AP dimension a ratio of the
gestation sac of > 1.5, is required for the reliable
diagnosis of a partial molar pregnancy βhCG ≥
105 U/L
How Is Partial H .Mole Diagnosed?

Hydatidiform Mole
Diagnosis:
Histopathological examination:
 It should always be done as far as
possible .

There are 2 important basic lines :
1-Evacuation of the mole
2-Regular follow-up to detect
persistent trophoblastic disease
If both basic lines are done
appropriately, mortality rates can be
reduced to zero.
What Is The Plan of Management?

The Management Of
Gestational Trophoblastic
Disease

Management:
Investigations:
Laboratory:
 Pre-evacuation hCG
 Complete blood count
 Electrolytes, BUN, creatinine
 Liver function tests
 Thyroid function tests
 HIV
Imaging:
 Pelvic ultrasound
 Chest x-ray

Management:
The patient should be stabilized hemodynamically 
Medical care:
Correction of:
i. Anemia
ii. Dehydration
iii. Hyperthyroidism
iv. Hypertension
Surgical care

 Suction Evacuation is method of choice –
can be done by conventional suction
curretage as well as by MVA
 Two MVA set should be available
 Cervical preparation with prostaglandins or
misoprostol , should be avoided to reduce
the risk of embolisation
What Is The Best Method Of
Evacuating A Molar Pregnancy?

For Partial mole: It depends on the fetal parts
Small fetal parts :Suction curettage
Large fetal parts: Medical (oxytocics)
In partial mole the oxytocics is safe ,as the hazard to
embolise and disseminate trophoblastic tissue is
very low
Also, the needing for chemotherapy is 0.1- 0.5%.
Is That The Same For Partial Mole?

Canula up to a maximum of 12 mm, is usually
sufficient to evacuate all complete molar
pregnancies

Suction curettage has been performed
using 10mm canula under U/S guidance :
El SHERBINY HOSPEl SHERBINY HOSP
Canula

Garner UpToDate 2010
Suction Curettage Supervision of senior surgeon
 Blood should be cross matched and
kept available
 Maintain two i/v line
 Procedure to be carried out in OT
 Cervical os to be dilated up to 12mm
size suction cannula.
 Deep insertion of suction cannula
avoided
 Gentle curettage is performed after
evacuation is complete and tissue
sent for histopathology.
 Intraop USG , if available help to
ensure the complition of procedure.
• The use of oxytocin infusion prior to
completion of evacuation is not
recommended

The Molar Content For Histopathological Examination

When Anti-D Is Required?
It is required in Partial due to the presence of
fetal RBCs
 In Complete mole because of poor
vascularisation of the chorionic villi and
absence of the anti-D antigen, anti-D
prophylaxis is not required.
 Although ACOG recommend to give Anti-D
in all cases.

Barrier methods – most preffered method.
Oral contraceptive method-Once βhCG level have
normalized: COC pill may be used.( as it may acts as
growth factor for trophoblastic tissue)
Low dose OCP is preffered.
If oral COC was started before the diagnosis of GTD
,COC can be continue as its potential to increase
risk of GTN is very low
IUCD should not be used until β hCG levels are
normal to reduce uterine perforation.
Permanent sterilisation- prefered in those couples
whose family has been completed.
What Is Safe Contraception Following GTD?

Hysterectomy may be preferred to suction
curettage at age ≥ 40 years with no desire for
further pregnancies especially with other risk
factors for GTN as :
 Large theca lutein cysts( >6 cm)
 Significant uterine enlargement
 Pretreatment βhCG ≥ 105 U/L.
Although hysterectomy does not eliminate
possibility of GTN, it markedly reduces its
likelihood. Post hyst. GTN is observed in 3-5%
of cases.
Garner UpToDate 2010Soper. Obstet Gynecol 108:176, 2006
Cunningham et al,Williams Obstetrics,23rd ,2010

Theca-lutein cyst associated with a complete H. mole in >30%

Prophylactic Chemotherapy: The long-term
prognosis for women with a H. mole is not
improved with prophylactic chemotherapy. Because
toxicity—including death—may be significant, it is
not recommended routinely *
It may be useful in the high-risk cases when
follow-up are unavailable or unreliable. * *
Second Uterine Evacuation : not required
routinely RCOG Guideline No. 38 ; 2010
American College of Obstetricians and Gynecologists, 2004*

Prophylactic chemotherapy after
molar pregnancy
 The controversial practice of prophylactic
chemotherapy in GTN in women with H.mole is not
recommended ( According to recent cochrane data
based review 2012).
 Overall PC reduces the risk of GTN however
researcher consider this evidence to be low quality.
 When GTN did occur the time to diagnosed in women
received PC is longer and these women require more
courses are require to cure GTN.
 Unnecessary exposure to toxic adverse effect.

Prophylactic Chemotherapy:
 In one randomized clinical trial, a single course of
methotrexate(0.4mg/ kg/day ) and folinic acid reduced
the incidence of postmolar trophoblastic disease from
47.4% to 14.3% in patients with high-risk moles:
Age >40 yrs
previous history of molar pregnancy
βhCG levels greater than 100,000 mIU/mL,
Uterine size greater than gestational age,
Ovarian size greater than 6 cm
All associated factors like PE, hyperthyroidism,
hyperemesis. Acute respiratory distress.
Post evacuation uterine haemorrhage/subinvolution
 Still the gold standard is careful follow up
of each and every patient and serial
estimation of β HCG.

Post-evacuation Surveillance
Why?
To determine when pregnancy
can be allowed
To detect persistent trophoblastic
disease (i.e. GTN)

A baseline serum β -hCG level is obtained within 48
hours after evacuation.
Levels are monitored every week till a normal value is
achieved. Level usually becomes normal by 8-10
weeks.
Monitor HCG every month for further 6 months from
the date of evacuation if HCG has to return to normal
within 56 days after pregnancy event.
>56 days of the pregnancy event :Follow up is 6 months
from normalization of the hCG level.
These levels should progressively fall to an undetectable
level (<5 mu/ml).
The Post-evacuation Surveillance. How?

In resource poor setting – UPT and USG.
Monthly USG 1 month after evacuation.
UPT should be perfomed once monthly starting from 3rd to
4th month untill 1 year after evacuation.
The normal time for βhCG to normalise is 99 days in
complete moles and 59 days in partial mole.
Pelvic examination:
 Duration: while hCG is elevated to monitor the
involution of pelvic structures and to aid in the
identification of vaginal metastasis

Hydatidiform Mole
 Complications associated with molar pregnacy:
 Theca-lutein cysts
 Pre eclampsia,
 hyperthyroidism,
 Respiratory distress
 Hyperemesis
 Uterine perforation ,
 Excessive haemorrhage,
 Respiratory distress syndrome.
 Development of persistent mole.

Theca lutein cyst (>5-6cm)
(25-35%)
pain or torsion, rupture or post molar
pressure bleeding GTD
Require aspiration require
opherectomy
The mean time for theca luteal cysts to regress is approximately 8 weeks

RESPIRATORY DISTRESS SYNDROME
(rare event)
Pathophysiology:
 embolisation of trophoblastic tissue , pulmonary
metastasis
 Risk factors :
 uterine size > 14-16 weeks
 high HCG level
 Contributing factors- anaemia, thyrotoxicosis
It should resolve within 24 to 48 hours after molar evacuation

Hyperthyroidism:
 Prevalence:
 Clinical hyperthyroidism is seen in less than 10% of
patients with molar pregnancies
 Management:
 Beta-blockers should be administered prior to
molar evacuation to prevent thyroid storm that
may be induced by anesthesia and surgery.

When can women whose last pregnancy was a
complete or partial hydatidiform molar
pregnancy try to conceive in the future ?
 Women should be advised not to conceive until
their follow-up is complete.
 Women who undergo chemotherapy are advised
not to conceive for 1 year after completion of
treatment.
 Patient with metastatic GTN – 2 years

Pregnancy after Hydatidiform Mole:
 Risk of another molar pregnancy:
(1–2% incidence)
 Current recommendations for
management of subsequent pregnancies:
 P/V in first trimester and ultrasound to confirm
normal gestational development and dates
 Examination of the placenta or products of
conception histologically at the time of delivery
or evacuation .
 An hCG level should be obtained 6 weeks
and 10 weeks post evacuation or delivery
to confirm normalization.

A hydatidiform mole and a co-existent
fetus:
 Prevalence: Rare (0.005%-0.01% pregnancies)
 Diagnosis:
 Ultrasound
 In diagnostic doubt , invasive testing for karyotyping to
be done.
 Examination of the placenta following delivery.
Outcome of such pregnancies is poor live birth of 25%,
increased risk of early fetal loss(40%), preterm
labour(36%) ,pre eclampsia.
 Complications: Increased risk of medical complications
 Increased risk for postmolar gestational trophoblastic
disease.

False-positive hCG values, also known
as “phantom hCG”
Cause: the presence of non-specific
heterophil antibodies in the patients’ sera.
 Should be suspected if hCG values plateau
at relatively low levels and do not respond
to therapeutic maneuvers
 Evaluation of patients with :
• Urinary hCG
• Serial dilutions of the serum

Prognosis:
 Post-molar gestational trophoblastic disease:
 Risk:
 Following complete mole: 20%
 Following partial mole: 5%
 Type:
 70% to 90% are persistent or invasive moles
 10% to 30% are choriocarcinomas.
Recurrence-
Risk of recurrenc with prior molar pregnancy is
1-4%

PERSISTENT GESTATIONAL TROPHOBLASTIC
DISEASE
 It is defined as persistence of trophoblastic activity as
evidnced by clinical ,imaging, pathological and
hormonal study following initial treatment.
 It may be followingtreatment of hydatiform mole,
invasive mole, choriocarcinoma or placental site
trophoblastic tumour.
INVASIVE MOLE-
In which the trophoblastic tissue invade the
myometrium.

Criteria for diagnosis of gestational
trophoblastic neoplasia or post molar GTD
 Plateau of serum β-hcg level (+/-10%) for four measurements
during a period of 3 weeks or longer – days 1,7,14,21.
 Rise of serum β-hcg > 10% during three weekly consecutive
measurement or longer, during a period of 2 weeks or more –
days 1,7,14.
 The serum β -hcg level remains detectable for 6 months or more
after mole evacuation.
 Histological criteria for choriocarcinoma.

Low risk (score 0-6) and high risk(score ≥7)

Staging
International staging of WHO may be summarized as
follows:
Ⅰ: lesion localized in uterus, no metastasis;
Ⅱ: lesion extends beyond uterus, but still confined to
internal genitalias;
Ⅲ: pulmonary lesion
Ⅳ: metastasis to other distant sites.

Indication for therapy
Indication for therapy after evacuation-
 An abnormal hcg regression pattern (10% or> rise in hcg
level or plateauing hcg or 3 stables value over 2 weeks)
 An hcg rebound.
 Histological diagnosis of choriocarcinoma or placental site
trophoblastic tumour.
 The presence of metastases.
 High hcg levels(.20,000miu/ml more than 4 weeks
postevacuation)
 Persistently elevated hcg levels 6 months post evacuation.

Hydatiform mole
Evacuation
Serial hcg level resolution
GTN
FIGO scoring
Low risk(≤6) high risk(>6)
Single agent (MTX) combination(MAC/EMACO)
chemotherapy chemotherapy
Serial hcg level resolution(life –long
follow up)
Relapse /resistant disease
Second –line chemotherapy ±surgical debulking

Molar pregnancy

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