molar pregnancy

Molar pregnancy

Presented ByNirsuba Gurung

Masters in nursing Women health and development

Gestational Trophoblastic disease comprises a spectrum of interrelated conditions originating from the placenta.

Gestational trophoblastic disease is a prolifirative disorder of trophoblastic cells

It can be benign, premalignant or malignant

Classification of gestational Trophoblastic disease

WHO Classification

Malignant neoplasms of various types of trophoblats

Malformations of the chorionic villi that are predisposed to develop trophoblastic malignacies

Benign entities that can be confused with with these other lesions

Choriocarcinoma

Complete

Hydatidiform moles

Placental site nodule

Exaggerated placental site

Epithilioid trophoblastic tumors

Placental site trophoblastic tumor Partial

Invasive

Non-metastatic disease: confined to the uterus

Metastatic A- low risk-good prognosis B – high risk-poor prognosis

Low risk Disease present in less than 4 mooths

duration Initial serum hCG level < 40,000 IU/ml Metastasis limited to lung and vagina No prior chemotherapy No preceding term pregnancy

High risk Long duration of disease Initial serum hCG level > 40,000 IU/ml Brain or liver metastasis Failure of prior chemotherapy Following term pregnancy

Hydatidiform Mole Definition:

In latin"hydatid" means "drop of water”"mole" means "spot”

Pathologically,Hydatidiform moles represents placentas with

abnormally developed chorionic villi (enlarged, edematous and vesicular villi with variable amounts of proliferative trophoblast)

Macroscopic of Hydatidiform mole

Hydropic villi Grapelike vesicles filled clear material

usually 1 to 3cm diameter

proliferation of the

trophoblast

Hydatidiform mole(molar pregnancy)Molar pregnancy is an abnormal form of

pregnancy, wherein a non viable , fertilized egg implants in the uterus, and thereby converts pregnancy process into pathological ones.

It is characterized by presence of hyadatidiform moles.

It is an abnormal condition of the placenta where there are partly degenerative and partly proliferative changes in the young chorionic villi.

These results in the formation of clusters of small cysts of varying size

It is regarded as a begin neoplasia of the chorion with malignant potential

INCIDENCE There is considerable geographical

and environmental influences in incidence.

The incidence is higher in eastern than western countries. Its incidence in India is 1:160 and 1:2000 in UK.

Hydatidiform Mole Incidence:

In the United States, 1in 600 therapeutic abortions 1 in 1,500 pregnancies

Internationally: In Japan & China, 1-2 in 1,000 pregnancies In Indonesia & India, 12 in 1,000 pregnancies

In the United Arab of Emirates, 2 in 1000 deliveries (population-based study; Graham IH,

Fajardo AM; 1988) In Saudi Arabia;

1.48 in 1000 live births (hospital-based study; Felemban AA, et al; 1969)

In the United States, • 1in 600

therapeutic abortions

• 1 in 1,500 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)

Contd……. It is prevalent among teenage and elderly

patient with high parity.

TYPES1. COMPLETE2. PARTIAL

Complete mole A complete mole is caused by a single

sperm combining with an egg which has lost its DNA.

The genotype is typically 46XX due to subsequent mitosis of fertilizing sperm but can also be 46XY.

Partial mole Partial mole occurs when an egg is

fertilized by 2 sperm or by ,sperm which reduplicates itself yielding the genotype of 69 XXY or 92XXXY

Hydatidiform mole Complete mole Partial mole Partial mole

Partial mol ( fetal tissue)Grossly placenta a mixture of normal and hydropic villi

Fetus Severe growth restriction Multiple congenital anomalies

Risk Factors hydatidiform mole Strongest risk factors are Age and a history of prior hydatidiform

mole

Both extremes of reproductive age adolescents twofold risk Older than 40 tenfold risk

History of Prior mole High parity Disturbed maternal immune mechanism

suggested by: Rise in gammaglobulin level in absence of

hepatic disease Increased association with AB blood group

which possess no ABO antibody

An ethnic predisposition Diet (Deficiencies of protein or) (Vitamin A deficiency) Animal fat Smoking Increased paternal age

The risk of another mole Complete mole is 1.5 percent Partial mole is 2.7 percent

Two prior molar pregnancies the risk is 23 percent

Pathogenesis and Cytogenetics of HM

Genetic Constitution

Diploid Triploid/ teraploid

Patho-genesis

4%Fertilization of an empty ovum by two sperms“Diandric dispermy”

90%Triploidfertilization of a normal ovum by two sperms“Dispermic triploidy”

96%Fertilization of an empty ovum by one sperms that undergoes duplication“Diandric diploidy”

10%Tetraploidfertilization of a normal ovum by three sperms“Dispermic triploidy”

Karyotype46XX

69XXX69YXX69YYX

46XX46XY

Complete Partial

Complete Mole, Pathogenesis

Duplication 46XX

Empty ovum

23X

Diandric diploidyAndrogenesis

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

Paternal extra set

23Y 23X23Y 23X23X

Hydatidiform Mole

Alterations in gene expression profiles

Up-regulation and down-regulation of proteins committed to cell growth control

e.g. Up-regulation of growth factor and cytokine mediated pathways, and antiapoptosis genes

Trophoblastic hyperplasia

e.g. Down-regulation of insulin growth factor binding proteins and tumor necrosis factor receptor

Pathogenesis Principally a disease of the chorion Death of the ovum ir failure of the embryo

to grow is essential to develop complete H. mole

The secretion from the hyperplastic cells and transferred substances from the maternal blood accumulates in the stroma of the villi which are deviod of blood vessels

This results in distension of the villi to form small vesicles

The distension may also be due to edema and liquification of the stroma

Vesicle fluid is interstitial fluid and is almost similar to ascitic or edema fluid but rich in hCG

Naked eye appearance The mass filling the uterus is made of

multiple chains and clusters of cysts of varying sizes

No trace of embryo or the amniotic sac Hemorrhage, if occurs, takes place in the

decidual space

Microscopic appearance Marked prolifiration of syncitial and

cytotrophoblastic epithelium Marked thining of the sromal tissue due to

hydropoc degeneration Absence of blood vessels

FEATURES COMPLETE MOLE PARTIAL MOLE

karyotype 46XX, paternal Triploid or quadriploid

Embryo/fetus absent Present

Villious edema All villi Some villi

Trophoblastic proliferation

Diffuse, circumferential Focal, slight

Uterine size More than the date Less than the date

Beta hCG High(>50000) Slight elevation

Behaviour 2% choriocarcinoma Rare

Clinical features Amenorrhea 8-12 weeks with following

manifestation Vaginal bleeding Varying degree of abdominal pain Constitutional symptoms

Patient become sick without any apparent reason Vomiting of pregnancy becomes excessive Breathlessness Thyrotoxic symptoms

Expulsion of grape like vesicles per vaginum

History of quickening absent

Clinical Presentation:Complete mole:

Vaginal bleeding

Severe anemia

Passage of hydropic villi

Signs Features suggestive of early pregnancy Pallor Features of pre-eclampsia Per abdomen

Uterus –more than gestational period (70%) Uterus feels firm elastic(doughy ) Fetal parts not palpable Absence of fetal movement and FHS

Vaginal examination Internal ballotement cannot be elicited Unilaternal or bilaternal enlargement of

ovary (25-50%) Finding of vesicles in the vaginal discharge Open cervical os

Classical symptom of a complete mole Abnormal vaginal bleeding Lower abdominal pain Hyperemesis gravidarum Features of early onset of pre-eclampsia Uterus > dates No fetal parts and FHS

Classical symptoms contd….

Expulsion of vesicular tissues Theca lutein cyst of ovaries Hyperthyriodism Serum hCG >1,00,000 IU/ml USG –snow strom appearance

Hydatidiform Mole Diagnosis:

History Clinical examination Ultrasound examination Serum hCG levels Histopathological examination Cytogenetic and molecular biological

examination


Ultrasonography:* The diagnosis of molar pregnancy is nearly always

made by ultrasonography

Complete mole• The classical finding is a

“snow storm" pattern• Theca lutein cysts are frequent

findings on ultrasound

The snow storm appearance of complete hydatidiform mole

Theca lutein cysts, a frequent finding on ultrasound


Ultrasonography:

Partial mole

Abnormal gestational sac The classic vesicular

sonographic findings of a complete mole are usually not seen

Focal sonographic cystic changes and/or hydropic changes in the placenta are significantly associated with the diagnosis of a partial molar pregnancy


Ultrasonography: However, based on ultrasound, correct diagnosis

can be suspected in only: • 84% of patients with complete mole and • 30% of patients with partial mole (Lindholm and Flam, 1999)

The accuracy of ultrasonogrophy is gestational age dependentIn comlete mole:• 100% of cases cane be diagnosed at a gestational age of

13 weeks or more• 50% of cases cane be diagnosed in earlier pregnancies(Lazarus et al, 1999)


Serum hCG levels: Serum hCG levels of greater than 92 000 IU/l

associated with absent fetal heart beat indicate a diagnosis of complete hydatidiform moles (Romero et al, 1985)

Serum hCG level decreases quickly if the patient has an abortion, but it does not in molar pregnancy


Histopathological examination: It should always be done as far as possible and

samples should be kept for DNA analysis for a final diagnosis when histology can not differentiate molar pregnancy from abortion

Table3: Pathological features of complete and partial hydatidiform mole

Complete Mole Partial MoleMacro-scopically

A mass of large, edematous villi that are diffusely distributed, typically described as resembling a cluster of grapes

The placental tissue is less bulkyA few enlarged villi with a focal distributionA fetus may be identified grossly that often has multiple congenital anomalies including syndactyly of the fingers & toes

The grape like vesicles in gross appearance

Table3: Pathological features of complete and partial hydatidiform mole

Complete Mole Partial MoleMicro-scopically

Enlarged edematous villi which show a central acellular fluid-filled space referred to as a “central cistern” Abnormal trophoblastic proliferation that is circumferential in contrast to normal villi in which trophoblastic proliferation is at one end of the villusAbsence of fetal tissue

Two distinct populations of villi. One with large, edematous villi with central cisterns. The other contains small villi that show some degree of stromal fibrosisAbnormal circumferential trophoblastic proliferationFetal tissue, RBSs

DIFFERENTIAL DIAGNOSIS1. THREATENED ABORTION2. FIBROID OR OVARIAN TUMOR WITH

PREGNANCY.3. MULTIPLE PREGNANCY4. MISTAKEN DATE5. ACUTE HYDRAMINOS

Complications associated with molar pregnacy: Those related to the increased trophoblastic

tissue volume: Theca-lutein cysts Pregnancy-induced hypertension, hyperthyroidism, Respiratory distress Hyperemesis

Those related to its management: Uterine perforation

Hydatidiform Mole, complications Theca-lutein cysts:

Prevalence: Clinically evident theca lutein cysts (usually >5–6 cm) are

detected in about 25-35% of women with molar pregnancies Association:

They usually correlate with marked elevation of serum hCG levels above 100,000 IU/l

Complications: Pain or pressure that may require percutaneous aspirations. Torsion, rupture, or bleeding are rare complications that can

require oophorectomy Bilateral theca letein cysts increase the risk of post-molar GTD

Course: The mean time for theca luteal cysts to regress is approximately

8 weeks

Hydatidiform Mole, complications Respiratory distress syndrome:

Prevalence: Rare

Pathophysiology: Embolization of trophoblastic tissue Transient impairment of left ventricular function

during induction of anesthesia for suction D&C of molar pregnancy

coexisting conditions such as anemia, hyperthyroidism, hypertension from preeclampsia

Risk factors: Uterine size larger than 14 to 16 weeks’ High levels of hCG

Hydatidiform Mole, complications

Respiratory distress syndrome: Presentation:

Tachypnia and tachycardia following evacuation Bilateral pulmonary infiltrates on chest x-ray

Management: Central venous monitoring Ventilatory support

Course: It should resolve within 24 to 48 hours after molar

evacuation

Hydatidiform Mole, complications

Hyperthyroidism: Prevalence:

Clinical hyperthyroidism is seen in less than 10% of patients with molar pregnancies

A small number of patients may have elevated thyroid function tests without clinical evidence of disease

Management: Beta-blockers should be administered prior to

molar evacuation to prevent thyroid storm that may be induced by anesthesia and surgery.

A hydatidiform mole and a co-existent fetus: Prevalence:

Rare (1 in 22,000–100,000) partial moles and twin gestations with co-existent fetuses

and molar gestations Diagnosis:

Usually, by ultrasound Few, after examination of the placenta following delivery

Complications: Increased risk of medical complications Increased risk for postmolar gestational trophoblastic

disease Management:

No clear guidelines for management

Risk Factors for post-molar gestational trophoblastic disease: Advanced maternal age Factors that reflect the volume of trophoblastic tissue:Clinical

factors that are associated with high hCG levels (>100,000 mIU/mL) uterus large for date, bilateral theca lutein cysts, Respiratory distress syndrome after molar evacuation, eclampsia, hyperthyroidism, Uterine subinvolution with post evacuation hemorrhage.

(With any one of these factors or a combination of many, the risk of post-molar GTD has ranges from 25% to 100%)

Hydatidiform Mole Risk Factors for post-molar gestational trophoblastic disease:

The presence of “invasive trophoblast antigen (ITA)” which has 100% sensitivity and specificity for invasive trophoblastic tumors(Cole et la, 2003)

*There is no correlation between the degree of anaplasia and the risk of post-molar GTD

COMPLICATIONS

IMMEDIATE1. Hemorrhage and shock2. Sepsis3. Perforation of uterus4. Pre-eclampsia 5. Acute pulmonary insufficiency6. Coagulation failure

LATE Development of choriocarcinoma (2 to 20%)

Risk factors of malignant change: Patient’s age>40 or <20 Parity >3 Serum hCG> 100000 mIU/mL Uterine size> 20 wk Previous history of molar pregnancy Thece leutin cysts: large(>6cm diameter)

MANAGEMENT The principle of the management:1. Suction evacuation of the uterus2. Supportive therapy3. Counselling for regular follow up

The patient are grouped into two: Group A:the mole is in the process of

expulsion Group B:the uterus remains inert

Management Complete history and physical examination

Investigations

Medical and surgical care

1

3

2

History and physcal examination: Should aim to rule out the classic symptoms and

signs that would lead to a diagnosis of: severe anemia dehydration preeclampsia thyrotoxicosis

The patient should be stabilized hemodynamically

Management: Investigations:

Laboratory: Pre-evacuation hCG Complete blood count Electrolytes, BUN, creatinine Liver function tests Thyroid function tests

Imaging: Pelvic ultrasound Chest x-ray

Hydatidiform Mole Management:

Medical care: Correction of:

Anemia Dehydration Hyperthyroidism hypertension

Management:Surgical Suction curettage (with oxytocin or prostaglandin infusion)

Hysterectomy

• The method of choice

• Increased risk of medical complications

• Associated with a markedly decreased rate of malignant sequelae (3.5%) when compared with suction evacuation.

Hysterectomy Hysterectomy: is indicated in: a)Patient with over 35, b)Patient complete her family

irrespective of age, c)Uncontrolled hemorrhage or

perforation during surgical evacuation,

Counselling Counselling for follow up: Routine follow up is mandatory for all cases

for at least 1 year.Intervals: initially the check up must be made at an

interval of 1 week till the serum hCG levels become negative.This usually happen by 4-8 weeks.

once negative within 56 days,the patient is followed up at every 1 month intervals for 6 months.

Women undergone chemotherapy should be followed up for 1 year after hCG has been normal.

Methods employed in each visit: a)enquire about each symptoms b)abdomino vaginal examination c)investigations:hCG,chest x-ray

PROPHYLACTIC CHEMOTHERAPY If the hCG levels fails to normal by

the stipulated time(10-12) weeks or relevation at 4-8 weeks.

Post evacuation hemorrhage. Where follow up facilities are not

adequate. Evidence of metastasis irrespective of

the level of hCG.

Prophylactic Chemotherapy: In one randomized clinical trial, a single

course of methotrexate and folinic acid reduced the incidence of postmolar trophoblastic disease from 47.4% to 14.3% (P <.05) in patients with high-risk moles:hCG levels greater than 100,000

mIU/mL,uterine size greater than gestational age, ovarian size greater than 6 cm),

However, the incidence was not reduced in patients with low-risk moles

On the other hand, the use or prophylactic chemotherapy increases the risk of drug resistance

Because of the excellent primary cure rates among women with post-molar GTD, and mortality achieved by monitoring patients with serial hCG determinations and instituting chemotherapy only in patients with postmolar gestational trophoblastic disease outweighs the potential risk and small benefit of routine prophylactic chemotherapy.

Pregnancy after Hydatidiform Mole: Risk of another molar pregnancy:

Increased by 10-fold (1–2% incidence) Current recommendations for management of

subsequent pregnancies: an early ultrasound to confirm normal gestational

development and dates A chest x-ray to screen for occult metastasis

masked by the hCG rise of pregnancy Examination of the placenta or products of

conception histologically at the time of delivery or evacuation for evidence of occult trophoblastic disease

An hCG level should be obtained 6 weeks post evacuation or delivery to confirm normalization.

CONTRACEPTIVE ADVICE

The patient is advised not to be pregnant for at least 1 year.

Use of contraception IUD is contraindicated. OCP:after hCG value have been

normal. Barrier method.

Hydatidiform Mole 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

Diagnosis: A rising, plateauing, or persistent elevation of human chorionic

gonadotropin after evacuation of a hydatidiform mole or an ectopic or term pregnancy

PROGNOSIS More than 80% of H. moles are benign. The

outcome after treatment is usually excellent. Highly effective means of contraception are recommended to avoid pregnancy for at least 6 to 12 months.

About 15 to 20% of cases may develop into persistent GTD.

In 2 to 10% of cases it may change into choriocarcinoma.

Over 90% of women with malignant, non spreading cancer are able to survive and retain their ability to conceive and bear children.

In those with metastatic cancer, remission remains at 75 to 85%, although their childbearing ability is usually lost.

NURSING DIAGNOSISAcute pain related to uterine contraction.Risk for fluid volume deficit related to

execessive vascular loss.Ineffective uteroplacental tissue perfusion

related to abnormal trophoblastic proliferation.Risk for maternal injury related to blood

loss,abnormal blood profile,impaired immune system.

Fear related to fetal loss and outcome of pregnancy.

molar pregnancy

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