This document discusses molar pregnancy, which occurs when abnormal placental tissue develops instead of an embryo. It defines molar pregnancy and describes the classification of gestational trophoblastic disease. It also covers the pathogenesis, risk factors, clinical features, diagnosis, and management of complete and partial molar pregnancies. The key aspects are evacuation of the molar tissue followed by monitoring of hCG levels to detect persistent trophoblastic disease.

1. 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

3. WHAT IS MOLAR PREGNANCY?
⚫A molarpregnancy happenswhen tissue that normally
becomes a fetus instead becomes an abnormal growth
in uterus. Even though it isn't an embryo, this growth
triggers symptomsof 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 adistinct tumor marker –β HCG as tumor
arises from gestational rather than maternal tissue.

4. What is the classification of
gestational trophoblastic
disease?

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

6. It is aspectrumof trophoblasticdiseases thatdevelops
malignantsequelae. GTN includes:
Invasive mole
Choriocarcinoma
Placental site trophoblastictumour
Epitheloid trophoblastic tumour
Gestational Trophoblastic Neoplasia (GTN)
=Malignant Gestational Trophoblastic Disease
Disaia &Creasman Clinical Gynecological Oncology 2007
Cunningham et al Williams Obsterics 23rd , 2010

7. MOLAR PREGNANCY ?

8. Aetiology:
⚫Immunological
factors
⚫Racial factors
⚫Dietary factors

9. 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 GroupAB andA
High gamma globin in absence of hepatic disesase

10. WHAT IS THE INCIDENCE?

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

12. WHAT IS THE CHROMOSOMAL
BASIS OF DEVELOPMENT OF
MOLE?

13. Pathogenesis and Cytogenetics of HM
Genetic
Constitution
Diploid 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

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

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

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

17. 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. thisabnormality have been
localised toa singlegene- NALP7.
⚫This is the first causativegenedefect identified in H.
MOLE.

18. -
Describe Complete
Hydatidiform Mole

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

20. What is the pathological features of
complete hydatidiform mole?

21. Complete H. Mole
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%
Microscopically Enlarged, edematous villi and abnormal
trophoblastic proliferation that diffusely involve the
entire villi.
No fetal tissue, RBCs or amnion are produced

22. 1-Trophoblastic proliferation
2-Hydropic Degeneration
Complete hydatidiform mole: Microscopically Enlarged,
edematous villi and abnormal trophoblastic proliferation that
diffusely involve the entire placenta

23. 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"

24. Complete Hydatiform Mole
Uterine wall

25. CLINICAL FEATURES OF COMPLETE
MOLE
Historyof amenorrhoeaof 8-12 weeks
Irregular Vaginal bleeding- commonest (90%).
mayvary from spotting to profuse haemorrhage.
Expulsion of grapes likevesicles per vaginum (50%)
Lowerabdominal pain- a) overstretching of uterus
b) concealed haemorrhage
c) uterinecontraction toexpel out the content
d) infection
e) perforationof the uterus by invasive mole.

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

27. Points to be noted during
examination
GENERAL EXAMINATION:
⚫Patient looks more ill and Pallor isoutof proportionof
bleeding.
⚫PR-tachycardia, RR- tachypnea /dyspnoea
⚫Features of preeclampsia present .usually there is early
onset of preeclampsia.
P/A-
⚫Uterine enlargement> than expected GA.
⚫The uterus is soft and doughydue toabsence of the
amniotic fluid sac.
⚫Fetal parts not felt
⚫FHS cannot be detected.

28. P/S-
⚫Cervical os may beopen orclose.
⚫Vuval orvaginal metastasis mayappearas purple
nodule.
P/V-
⚫Note the uterinesize.
⚫Internal ballotmentcannot beelicited.
⚫Unilateral or bilateral theca luteincystof ovary
palpable in 25-35% of cases.

29. PATHOLOGY OF PARTIAL
H. MOLE

30. 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

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

32. Partial Hydatiform Mole
Vesicles
Maternal side

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

34. Partial H. mole.

35. CLINICAL FEATURES OF PARTIAL
MOLE
History:
⚫Vaginal bleeding
⚫Usuallydiagnosed as missed or incomplete
abortion(91%).
Physical :
⚫A uteruscorrespondsorsmall forgestation age
⚫Excessiveuterinesize noted(4%)
⚫Toxemiaof pregnancy(4%)

36. Diagnosis:
History
Clinical examination
Ultrasound examination
Serum hCG levels
Histopathological examination
Cytogenetic and molecular biological examination
Immunostaining of p57kip2 gene recent
development in diagnosticaccuracy.it is a paternally
imprinted genewhich is maternallyexpressed
.positive in PHM

37. U/S is helpful in making a pre-evacuation diagnosis
but the definitive diagnosis is made by histological
examination.
U/S: Earlydetection reduced from 16 weeks (passageof
vesicles) to 12 wks
βhCG levels > 2 multiplesof the median may beof
value in thediagnosisoften exceeding 105 IU/l.
RCOG Guideline No. 38 ; 2010

38. 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.

39. Complete Molar Pregnancy

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

41. In most patients with a partial mole,
the clinical and U/S diagnosis is
Usually missed or incompleteabortion.
Thisemphasizes the need fora
thorough histopathologicevaluationof
all missed or incompleteabortions
How Is Partial H .Mole Diagnosed?
RCOG Guideline No. 38 ; 2010

42. Classically: A thickened, hydropicplacentawith
fetal orembryonic tissue
Multiplesoft markers, including:
Cysticspaces in the placentaand
Transverseto AP dimension a ratio of the
gestationsacof > 1.5, is required forthe reliable
diagnosisof a partial molarpregnancy βhCG ≥
105 U/L
RCOG Guideline No. 38 ; 2010
How Is Partial H .Mole Diagnosed?

43. egnancies

44. Hydatidiform Mole
⚫Diagnosis:
⚫Histopathological
examination:
⚫It should always be doneas faras
possible .

45. There are 2 important basic lines :
1 Evacuationof the mole
2Regular follow-up to detect
persistent trophoblasticdisease
If both basic lines are done
appropriately, mortalityratescan be
reduced to zero.
What Is The Plan of Management?

46. The Management Of
Gestational Trophoblastic
Disease
RCOG Guideline No. 38 ; 2010

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

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

49. ⚫Suction Evacuation is method of choice –
can be done by conventional suction
curretageaswell as by MVA
⚫Two MVA setshould beavailable
⚫Cervical preparation with prostaglandinsor
misoprostol , should be avoided to reduce
the risk of embolisation
RCOG Guideline No. 38 ; 2010
What Is The Best Method Of
Evacuating A Molar Pregnancy?

50. For Partial mole: Itdepends 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 forchemotherapy is 0.1- 0.5%.
RCOG Guideline No. 38 ; 2010
Is That The Same For Partial Mole?

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

52. Suction curettage has been performed
using 10mm canula under U/S guidance :
E
El
l SH
SHE
ER
RBIN
BINY
Y
H
O
S
H
O
S
P
P
Canula

53. Garner UpToDate 2010
Suction Curettage
⚫Supervision of seniorsurgeon
⚫Blood should becross matched and
keptavailable
⚫Maintain two i/v line
⚫Procedure to be carried out in OT
⚫Cervical os to bedilated up to 12mm
sizesuction 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 thecomplitionof procedure.
• The useof oxytocin infusion priorto
completion of evacuation is not
recommended

54. The Molar Content For Histopathological Examination

55. When Anti-D Is Required?
It is required in Partial due to the presenceof
fetal RBCs
⚫In Complete mole because of poor
vascularisation of thechorionicvilli and
absence of the anti-D antigen, anti-D
prophylaxis is not required.
⚫Although ACOG recommend togive Anti-D
in all cases.
RCOG Guideline No. 38 ; 2010

56. Barrier methods – most preffered method.
Oral contraceptive method-Once βhCG level have
normalized: COC pill may be used.( as it mayactsas
growth factorfortrophoblastic tissue)
Lowdose OCP is preffered.
If oral COCwasstarted before thediagnosisof GTD
,COCcan becontinueas its potential to increase
risk of GTN isvery low
IUCD should not be used until β hCG levelsare
normal to reduceuterineperforation.
Permanentsterilisation- prefered in thosecouples
whose family has been completed.
What Is Safe Contraception Following GTD?
RCOG Guideline No. 38 ; 2010

57. 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.
Soper. Obstet Gynecol 108:176, 2006 Garner UpToDate 2010
Cunningham et al,Williams Obstetrics,23rd ,2010

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

59. Second Uterine Evacuation : not required
routinely RCOG Guideline No. 38 ; 2010
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. * *
American College of Obstetricians and Gynecologists, 2004*

60. 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
researcherconsider thisevidence to be lowquality.
⚫When GTN did occurthe time todiagnosed in women
received PC is longer and these women require more
coursesare require tocure GTN.
⚫Unnecessary exposure to toxicadverseeffect.

61. ⚫Prophylactic Chemotherapy:
⚫In one randomized clinical trial, a single course of
methotrexate(0.4mg/ kg/day ) and folinicacid 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 sizegreater than 6 cm
All associated factors like PE, hyperthyroidism,
hyperemesis. Acute respiratorydistress.
Post evacuation uterine haemorrhage/subinvolution
⚫Still thegold standard is careful follow up
of each and every patient and serial
estimation of β HCG.

62. Post-evacuation Surveillance
Why?
Todeterminewhen pregnancy
can beallowed
Todetect persistent trophoblastic
disease (i.e. GTN)

63. A baseline serum β -hCG level is obtained within 48
hoursafterevacuation.
Levelsare monitored everyweek till a normal value is
achieved. Level usually becomes normal by 8-10
weeks.
Monitor HCG every month forfurther 6 months from
the date of evacuation if HCG has to return to normal
within 56 daysafterpregnancyevent.
>56 daysof the pregnancyevent :Follow up is 6 months
from normalization of the hCG level.
These levelsshould progressively fall toan undetectable
level (<5 mu/ml).
RCOG Guideline No. 38 ; 2010
The Post-evacuation Surveillance. How?

64. 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

65. Hydatidiform Mole
⚫Complications associated with molar pregnacy:
⚫ Theca-luteincysts
⚫ Pre eclampsia,
⚫ hyperthyroidism,
⚫ Respiratorydistress
⚫ Hyperemesis
⚫ Uterineperforation ,
⚫ Excessive haemorrhage,
⚫ Respiratory distress syndrome.
⚫ Development of persistent mole.

66. Theca lutein cyst (>5-6cm)
(25-35%)
pain or
pressure
torsion, ruptureor
bleeding
post molar
GTD
Requireaspiration require
opherectomy
The mean time fortheca luteal cysts toregress isapproximately 8 weeks

67. RESPIRATORY DISTRESS SYNDROME
(rare event)
Pathophysiology:
⚫embolisation of trophoblastic tissue , pulmonary
metastasis
⚫ Risk factors :
⚫uterinesize > 14-16 weeks
⚫ high HCG level
⚫Contributing factors- anaemia, thyrotoxicosis
It should resolvewithin 24 to 48 hoursafter molarevacuation

68. Hyperthyroidism:
⚫Prevalence:
⚫ Clinical hyperthyroidism is seen in less than 10% of
patientswith molarpregnancies
⚫ Management:
⚫ Beta-blockers should be administered prior to
molarevacuation to prevent thyroid storm that
may be induced byanesthesiaand surgery.

69. When can women whose last pregnancy was a
complete or partial hydatidiform molar
pregnancy try to conceive in the future ?
⚫Womenshould beadvised not toconceiveuntil
their follow-up is complete.
⚫Womenwho undergochemotherapyareadvised
not toconceive for 1 yearaftercompletionof
treatment.
⚫Patientwith metastatic GTN – 2 years

70. Pregnancy after Hydatidiform Mole:
⚫Risk of another molarpregnancy:
(1–2% incidence)
⚫Current recommendations for
managementof subsequent pregnancies:
⚫P/V in first trimesterand ultrasound toconfirm
normal gestational developmentand dates
⚫Examination of the placentaorproductsof
conception histologicallyat the timeof delivery
orevacuation .
⚫An hCG level should be obtained 6 weeks
and 10 weeks post evacuation or delivery
to confirm normalization.

71. A hydatidiform mole and a co-existent
fetus:
⚫Prevalence: Rare (0.005%-0.01% pregnancies)
⚫ Diagnosis:
⚫ Ultrasound
⚫ In diagnosticdoubt , invasive testing for karyotyping to
be done.
⚫ Examinationof 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 forpostmolargestational trophoblastic
disease.

72. 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 dilutionsof the serum

73. Prognosis:
⚫Post-molar gestational trophoblastic disease:
⚫ Risk:
⚫ Following complete mole: 20%
⚫ Following partial mole: 5%
⚫ Type:
⚫ 70% to 90% are persistentor invasive moles
⚫ 10% to 30% are choriocarcinomas.
Recurrence-
Risk of recurrencwith prior molar pregnancy is
1-4%

74. 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.

75. Criteria for diagnosis of gestational
trophoblastic neoplasia or post molar GTD
⚫ Plateau of serum β-hcg level (+/-10%) forfour measurements
during a period of 3 weeksor longer– days 1,7,14,21.
⚫ Riseof serum β-hcg > 10% during threeweeklyconsecutive
measurementor longer, during a period of 2 weeksor more –
days 1,7,14.
⚫ The serum β -hcg level remainsdetectable for 6 monthsor more
after moleevacuation.
⚫ Histological criteria forchoriocarcinoma.

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

77. 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 tootherdistantsites.

78. Indication for therapy
Indication for therapyafterevacuation-
⚫An abnormal hcg regression pattern (10% or> rise in hcg
level or plateauing hcg or 3 stablesvalueover 2 weeks)
⚫An hcg rebound.
⚫Histological diagnosis of choriocarcinoma or placental site
trophoblastic tumour.
⚫The presenceof metastases.
⚫High hcg levels(.20,000miu/ml more than 4 weeks
postevacuation)
⚫Persistentlyelevated hcg levels 6 months post evacuation.

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

80. THANK YOU ! ! !