EARLY PREGNANCY

COMPLICATIONS
I. ABORTION
II. ECTOPIC PREGNANCY
III.GESTATIONAL
THTROPHOBLASTIC DISEASE
I. ABORTION
 Definition
• Abortion—(Latin word: aboiriri)—to miscarry

– Spontaneous or induced termination of pregnancy

before fetal viability
– (National center for health statistics, CDC, WHO)
pregnancy termination before 20 weeks gestation
or with a fetus born weighing <500 grams
– 20 week fetus: 320 g
– 22-23 week fetus: 500 g
 Terms
1. Spontaneous abortion— threatened, inevitable,
incomplete, complete, missed
*Septic abortion—complicated further by infection

2. Recurrent abortion— women with repetitive

spontaneous abortions

3. Induced abortion— surgical or medical

termination of a live fetus that has not reached
viability
 Spontaneous abortion
• Threatened—bloody vaginal discharge or bleeding appears
through a closed cervical os

• Inevitable—gross rupture of membranes with cervical dilation

• Incomplete—bleeding that follows partial or complete

placental separation and dilation of the cervical os. Fetus and
placenta may remain within the uterus.

• Complete—expulsion of the entire pregnancy

• Missed—early pregnancy loss or wastage

FIRST TRIMESTER SPONTANEOUS
ABORTION
Pathogenesis:

Death of fetus
↓
Hemorrhage at decidua basalis
↓
Adjacent tissue necrosis
↓
Uterine contractions
↓
expulsion
 FIRST TRIMESTER SPONTANEOUS
ABORTION

• Factors:
1. Either parent is older than 40 years old – rate
is doubled
2. Fetal Factors
3. Maternal Factors
4. Paternal Factors
 FIRST TRIMESTER SPONTANEOUS
ABORTION

FETAL FACTORS
• Anembryonic (50%)—no identifiable embryonic
elements; blighted ovum

• Embryonic (50%)—developmental abnormality of the

zygote, embryo, fetus or placenta
– 50%: aneuploid: chromosomal anomalies
– 50%: euploid: normal chromosomal complement
 FIRST TRIMESTER SPONTANEOUS
ABORTION
FETAL FACTORS
EUPLOID
• Peaks at 13 weeks
• Increases after maternal age exceeds 35 years

ANEUPLOID
• Occurs at earlier gestational ages: 70% occurred by 8
weeks
• 95%:due to maternal gametogenesis errors
• 5%: paternal errors
 FIRST TRIMESTER SPONTANEOUS
ABORTION
FETAL FACTORS

ANEUPLOID
– Autosomal trisomy: most frequent
• All chromosomes except chromosome 1
• Most frequent: 13, 16, 18, 21, 22
– Monosomy X (45, X): Turner’s syndrome
• Single most frequent specific chromosomal abnormality
– Triploidy:
• hydropic or molar placental degeneration
– Tetraploid
 FIRST TRIMESTER SPONTANEOUS
ABORTION
MATERNAL FACTORS

1. Infections 9. Social and behavioral

2. Medical disorders factors
3. Medications 10. Occupational and
4. Cancer environmental
5. Diabetes mellitus 11. Immunological
6. Thyroid disorder 12. Inherited thrombophilias
7. Surgical procedures 13. Uterine defects
8. Nutrition
 FIRST TRIMESTER SPONTANEOUS
ABORTION

1. Infections

• Viral, bacterial and other infectious agents

• Chlamydia trachomatis
• Polymicrobial infection from periodontal disease
• Mycoplasma and ureaplasma
• HIV
• Bacterial vaginosis for second trimester
miscarriage
 FIRST TRIMESTER SPONTANEOUS
ABORTION

2. Medical disorders
• Diabetes Mellitus: related to degree of periconceptional glycemic and
metabolic control
• Thyroid disease: suspected to cause early pregnancy loss and other adverse
pregnancy outcomes
• Anorexia nervosa/bulimia nervosa: subfertility, preterm delivery and fetal-
growth restriction
• Chronic hypertension: no significant risk but at increased risk for fetal-
growth restriction

3. Cancer
• Radiotherapy - abortifacient
• Chemotherapy - not well defined
 FIRST TRIMESTER SPONTANEOUS
ABORTION

3. Medications
• Oral contraceptives or spermicidal agents and
jellies: not associated with an increased
miscarrieage rate
• NSAIDS or ondansetron: not linked
• IUD: increased risk for abortion (septic)
 FIRST TRIMESTER SPONTANEOUS
ABORTION

4. Surgical procedures:
• Not well studied
• Uncomplicated surgical procedures during
pregnancy: do not increase the risk for abortion
• Major trauma (abdominal): can cause fetal loss

5. Nutrition
• Extremes of nutrition: increased miscarriage risks
• Obesity: subfertility and increased risk of
miscarriage and recurrent abortion
 FIRST TRIMESTER SPONTANEOUS
ABORTION
6. Social and behavioral factors

• Alcohol: regular and heavy use

• Cigarette smoking: intuitive but unproven
• Excessive caffeine consumption: 5 cups of coffee/day (500 mg of
caffeine) ↑ risk of abortion
• Illicit drug use

7. Occupational and environmental factors

• DDT (dichlorodiphenyltrichloroethane): excessive miscarriage
rates
• Occupational exposures: antineoplastic drugs, sterilizing agents
and x-rays
 FIRST TRIMESTER SPONTANEOUS
ABORTION
8. Immunologic factors
– APS (antiphospholipid antibody syndrome)

PATERNAL FACTORS
– Not well studied
– Increasing paternal age: increased risk for abortion
Clinical Classification of abortion
A. THREATENED ABORTION:

– Bloody vaginal discharge or bleeding

appears through a closed cervical os
during the first 20 weeks

– Bleeding then cramping abdominal pain

follows hours to days later
 Clinical Classification of abortion
• THREATENED ABORTION VS ECTOPIC PREGNANCY
– Ascertain intrauterine live fetus
– Serial quantitative βhCG, progesterone levels,
transvaginal sonography
• βhCG: robust uterine pregnancy: ↑ at least 53-66% for 48
hours
• Progesterone levels
– <5 ng/mL: dying pregnancy
– >20 ng/mL: healthy pregnancy
• TVS: locate pregnancy, determine live fetus
 Clinical Classification of abortion
THREATENED ABORTION
• Gestational sac: anechoic fluid collection
– May be seen by 4.5 weeks
– Unembryonic gestation:
• Mean gestational sac >20 mm
• No embryo is seen
– Embryonic death:
• Embryo measuring >10 mm
• Has no cardiac activity
 THREATENED ABORTION
• Management
– Acetaminophen-based analgesia: relieve discomfort
– Bed rest: if uterine evacuation is not indicated
– Pregnancy evacuation: significant anemia and
hypovolemia
– Anti-D immunoglobulin: 2% of Rh D-negative are
alloimmunized
• Treatment: anti Rh(O) immunoglobulin
– 300 µg IM—for all gestational ages
– 50 µg IM for < 12 weeks
– 300 µg for > 13 weeks
 Clinical classification of abortion
B. SEPTIC ABORTION

Bacteria: uterine entry

↓
Colonize dead conception products
↓
Invade myometrial tissue
↓
Parametritis, peritonitis, septicemia, endocarditis

*group A streptococcus(S. pyogenes): severe necrotizing infections

and toxic shock syndrome
 Clinical classification of abortion
• Septic abortion

– Signs and symptoms: may be afebrile, capillary

leakage, hemoconcentration, hypotension,
profound leukocytosis

– Management:
• broad spectrum antibiotics
• Suction curettage: retained placenta fragments
Management of spontaneous abortion

1. Expectant management of spontaneous

incomplete abortion: failure rate 50%
2. Medical therapy with progtaglandin E1
(PGE1): failure rates 5-40%
3. Curettage: quick resolution 95-100%
successful
 Clinical classification of abortion
Classification bleeding BOW Pain Cervical management
dilation
Threatened
+/- + Close Bed rest; Tocolysis; Pain
management
Inevitable
+/- Ruptured
+/- Open Expectant management;
Evacuation after expulsion
Incomplete: partial/
complete placental + Ruptured
+ Open Completion Curettage

separation
Complete:
expulsion of entire +/- +/- Close/
Open
Sonography: minimally
thickened endometrium
products of (<15 mm) without
pregnancy gestational sac.
Missed abortion:
dead products - +/- Close Uterine evacuation

retained for days,

weeks, months
 RECURRENT MISCARRIAGE

 Repetitive early spontaneous pregnancy losses

 Recurrent spontaneous abortion
 Recurrent pregnancy loss
 Habitual abortion
 Three or more consecutive pregnancy losses
at <20 weeks or with a fetal weight of < 500
grams
 RECURRENT MISCARRIAGE
• (American Society for reproductive Medicine)—two or more
failed clinical pregnancies confirmed by either sonographic or
histopathological examination

• Causes:
1. Parental chromosomal abnormalities
2. Antiphospholipid antibody syndrome
3. Uterine abnormalities

• Other causes:
1. Alloimmunity
2. Endocrinopathies
3. Environmental toxins
4. Various infectons
 RECURRENT MISCARRIAGE
1. PARENTAL CHROMOSOMAL ABNORMALITIES

– 2-4% of recurrent losses

– Balanced reciprocal translocations: 50%
– Robertsonian translocation: 25%
– X chromosome mosaicism (47 XXY or Klinefelter
syndrome): 12%
– Management: IVF followed by preimplantation
genetic diagnosis
 RECURRENT MISCARRIAGE
2. ANATOMICAL FACTORS
– Congenital or acquired uterine anomaly: 15% of
women with three or more consecutive miscarriages
– Uterine synechiae—Asherman syndrome—result
from destruction of larger areas of endometrium
• Hysteroscopic lysis of adhesions
– Uterine leiomyomas
– Congenital genital tract anomalies—from mullerian
duct formation
 RECURRENT MISCARRIAGE
3. UTERINE ABNORMALITIES

Uterine anomaly Proportion of all Pregnancy loss rate

anomalies (%) (%)
Bicornuate 39 40-70
Septate or 14-24 34-88
unicornuate
Didelphys 11 40
Arcuate 7
Hypo- or aplastic 4
 RECURRENT MISCARRIAGE
4. IMMUNOLOGIC FACTORS

– Autoimmune theory
• SLE-were fount to have antiphospholipid antibodies
• Antiphospholipid antibody syndrome (APS)
 RECURRENT MISCARRIAGE
5. ENDOCRINE FACTORS

– Progesterone deficiency caused by luteal-phase

defect and polycystic ovarian syndrome
– Uncontrolled Diabetes
– Overt hypothyroidism and severe iodine deficiency
 MIDTRIMESTER ABORTION
• Extends from the end of the first trimester
until the fetus weighs > 500 g or gestational
age reaches 20 weeks
• Less common
• Incidence decrease thereafter
• First trimester bleeding doubles the incidence
of second-trimester loss
Some Causes of Midtrimester Spontaneous
Pregnancy Losses
• Fetal anomalies • Placental causes
– Chromosomal – Abruption, previa
– Structural – Defective spiral artery
• Uterine defects transformation
– Chorioamnionitis
– Congenital
– Leiomyomas • Maternal disorders
– Incompetent cervix – Autoimmune
– Infections
– Metabolic
 Management
• Similar to first trimester abortions

• Except, later gestational ages

– Oxytocin in concentrated doses is highly effective
for labor induction or augmentation
– Surgical termination by dilatation and evacuation
has fewer complications than labor induction
MIDTRIMESTER ABORTION
 Midtrimester Abortion treatment
1. 20 mg prostaglandin E2, suppository in
posterior vaginal fornix
– Side effects:
• Nausea, vomiting: antiemetic
• fever: antipyretic
• diarrhea: antidiarrehal

2. Misoprostol (Cytotec)
– 600 ug vaginally followed by 400 ug every 4 hours
 Cervical insufficiency
• Aka: incompetent cervix: painless cervical
dilatation in the second trimester
↓
Followed by prolapse and ballooning of
membranes
↓
Expulsion of a immature fetus
 Cervical insufficieny
• Risk factors
– Previous cervical trauma (D and C)
• Conization, cauterization or amputation
– Abnormal cervical development
 Cervical Insufficiency
• Evaluation and treatment
– Cervical secretions tested for gonorrhea and
chlamydia infection
– Cerclage: reinforces cervix by a purse-string suture

• Contraindications:
1. Bleeding
2. Uterine contractions
3. Ruptured membranes
 Cervical insufficiency
• Timing: depends on clinical circumstance
• Elective cerclage: between 12-14 weeks
gestation

• If clinical indication of cerclage is questionable

– Decrease physical activity
– Abstain from intercourse
– Cervical examination every 2 weeks
 Cerclage procedure
• McDonald – simpler procedure
• Shirodkar – more complicated operation

• Transabdominal cerclage:
– Suture placed at uterine isthmus
– Severe cervical anatomical defects or prior
transvaginal cerclage
 Complications of Cerclage
1. membrane rupture
2. Preterm labor
3. Hemorrhage
4. Infection
5. combination
 INDUCED ABORTION
• Medical or surgical termination of pregnancy
before the time of fetal viability

1. Therapeutic
• persistent cardiac decompensation
• Advanced hypertensive vascular disease or diabetes
• Malignancy
2. Elective or voluntary
• patient’s request
 Cervical Preparation
• Hygroscopic dilators
– Devices that draw water from cervical tissues and
expand to gradually dilate the cervix
• Laminaria algae: harvested from the ocean floor
• Dilapan-S: acrylic-based gel
• Cervical ripening medications
1. Misoprostol (cytotec) 400-600 ug: oral, SL,
intravaginal
2. Mifepristone (Mifeprex): progesterone antagonist:
200-600 ug orally
3. Prostaglandin E2 and F2a: second line drugs
•
 Surgical Abortion
• Transvaginal approach
– Dilatation and Curettage
– Dilatation and evacuation
– Dilatation and extraction
– Menstrual aspiration
– Manual vacuum aspiration

• Laparotomy
– Hysterotomy
– hysterectomy
 Dilatation and Curettage
• Requires dilating the cervix then evacuating
the pregnancy by mechanically scraping out
the contents
• Complications
– Perforation
– Cervical laceration
– Hemorrhage
– Incomplete removal of placental fetus
– Post op infection
 Dilatation and Evacuation
• Large bore vacuum curette is used to remove
the placenta and remaining tissue
 Dilatation and extraction
• Similar to dilatation and evacuation except
that a suction cannula is used to evacuate the
intracranial contents after delivery of the fetal
body through the dilated cervix
 Menstrual aspiration
• Done within 1-3 weeks after a missed
menstrual period with positive serum or urine
pregnancy test result

• Placental tissue appears soft, fluffy and

feathery
 Manual vacuum aspiration
• Used for early pregnancy failure or elective
termination up to 12 weeks.
• A vacuum is created in the syringe attached to
the cannula, which is inserted transcervically
into the uterus
• Vacuum produces up to 60 mmHg suction
 Medical Abortion
• 3 medications for early medical abortion
1. Antiprogestine (Mifepristone)
2. Antimetabolite (Methotrexate)
3. Prostaglandin (Misoprostol)

*Misoprostol is given initially, used alone or given

with methotrexate or mifepristone
 II.ECTOPIC
PREGNANCY
 Objectives:
1. Define ectopic pregnancy
2. Classify ectopic pregnancy
3. Identify the risk factors
4. Determine the clinical manifestations
5. Know the diagnostic modalities used in ectopic
pregnancy
6. Identify treatment options of ectopic pregnancy
7. Differentiate the other types of ectopic
pregnancy
 Definition
• Implantation elsewhere outside endometrial
lining
 Classification

Sites of implantation of 1800 ectopic pregnancies from a 10-year

population-based study. (Data from Callen, 2000; Bouyer, 2003.)
 Risk Factors
• Surgery for tubal pregnancy, fertility
restoration, sterilization
• Fallopian tube anomalies
• Those causing peritubal adhesions
– Prior tubal infection or STD
– Appendicitis
– Endometriosis
• ART
 Clinical Manifestations

• Classic triad:
1. Delayed menstruation
2. Abdominal Pain
3. Vaginal bleeding or spotting
 Clinical Manifestations
• Diaphragmatic irritation may present as pain
in the neck or shoulder
• Symptoms which points to ruptured ectopic:
– Severe lower abdominal and pelvic pain
– Abdominal tenderness
– Cervical motion tenderness
– Hypotension and bradycardia
– Bulging posterior fornix or tender, boggy mass at
one side of uterus
 Multimodality Diagnosis

1. Serum B-HCG
2. Serum progesterone
3. Transvaginal ultrasound
4. Laparoscopy
 Diagnosis
• Laboratory Test
1. B-HCG:
• (+) pregnancy test at 10-20 mIU/ml
• Discriminatory level of B-HCG is ≥1,500 mIU/ml
2. Serum progesterone
• >25ng/ml excludes ectopic pregnancy (Sn= 92.5%)
• <5 ng/ml nonliving uterine pregnancy or ectopic
pregnancy
• 10-25 ng/ml is the usual level in ectopic pregnancy
 Diagnosis
• Sonography
– To assess the location and the presence of a
gestational sac
1. Transvaginal sonography
a. Endometrial findings:
Gestational Sac At 4.5- 5 weeks
Yolk sac At 5-6 weeks
Fetal pole with heartbeat At 5.5- 6 weeks

Ectopic pregnancy: trilaminar endometrial

pattern (Sp: 94%, Sn: 38%)
 Diagnosis
• Sonography
b. Adnexal finding:
• extrauterine yolk sac, embryo, or fetus
• Hyperechoic halo or tubal ring surrounding an anechoic
sac
c. Hemoperitoneum
 Culdocentesis
– Aspirate on the posterior fornix
– If the fluid does not clot, consider ectopic pregnancy
A. Yolk sac and fetal pole
without cardiac activity

B. Empty extrauterine sac

with a hyperechoic ring

C. “Ring of fire”
 Diagnosis
• Laparoscopy
– Direct visualization of the fallopian tubes and
pelvis by laparoscopy
– Gold standard
 Treatment Options
I. Surgical Management
• Laparoscopy is the preferred surgical treatment for ectopic
pregnancy

1. Salpingostomy
– used to remove a small unruptured pregnancy that is usually < 2
cm in length and located in the distal third of the fallopian tube
– Linear incision at the antimesenteric border
– Left unsutured to heal by secondary intention

2. Salpingotomy
– Same as above but sutured
 Treatment Options
I. Surgical Management

3. Salpingectomy
―Tubal resection may be used for both ruptured and
unruptured ectopic pregnancies
 Treatment Options
II. Medical Management

Criteria for Medical Management:

1. Stable patient
2. B-HCG <1,500
3. <3.5cm
4. Consent
 Treatment Options
Medical Management:
1. Methotrexate
• Folic acid antagonist
• Increases methotrexate drug level:
– Phenytoin
– Tetracycline
– Salicylate
– Sulfonamide
• Impaired renal clearance:
– NSAID
– Probenecid
– Aspirin
– Penicillin
 Treatment Options
2. Leucovorin
• Folinic acid and has activity equivalent to folic acid
 Treatment Options
II. Medical Management
• Predictors of success:
– Initial B-HCG is the single best prognostic indicator
of successful treatment using one dose of
methotrexate
B-HCG level Failure rate
<1000 mIU/mL 1.5%
<2000 mIU/MI 5.6%
<5000 mIU/mL 3.8%
<10,000 mIU/MI 14.3%
 Treatment Options
• Ectopic pregnancy size
Size Success rate
<3.5 93%
>3.5 87-90%

• Fetal cardiac activity: associated with an increased

failure rate
 Treatment Options
– Side effects:
• Liver toxicity (12%)
• Stomatitis (6%)
• Gastroenteritis (1%)
• Myelosuppression
 Treatment Options
Expectant Management
– Tubal pregnancy only
– Low serum B-HCG
– Diameter of ectopic mass is NOT >3.5 cm
– No intraabdominal bleeding or rupture
 Interstitial Pregnancy
• Implant within the proximal tubal segment
that lies within the muscular uterine wall
• Incorrectly called cornual pregnancies
• previous ipsilateral salpingectomy is a specific
risk factor
• Management:
– Cornual resection
– Cornuostomy
 Abdominal Pregnancy

• Implantation in the peritoneal cavity

exclusive of tubal, ovarian, or
intraligamentous implantations.
 Ovarian Pregnancy
• Criteria:
1) the ipsilateral tube is intact and distinct from
the ovary
2) the ectopic pregnancy occupies the ovary
3) the ectopic pregnancy is connected by the
uteroovarian ligament to the uterus
4) Ovarian tissue can be demonstrated
histologically amid the placental tissue
• Management:
– Cystectomy
– Oophorectomy
 Cervical Pregnancy
• Cervical glands noted histologically opposite
the placental attachment site and by part or
all of the placenta found below the entrance
of the uterine vessels or below the peritoneal
reflection on the anterior uterus
• Management:
– Methotrexate
– Hysterectomy
 Cesarean Scar Pregnancy
• Implantation within the myometrium of a
prior cesarean delivery scar
• Management:
– Hysterectomy
– Methotrexate
 References:
• Williams Obstetrics 24th and 25th Edition
THANK YOU FOR
LISTENING! 
III. GESTATIONAL
TROPHOBLASTIC
DISEASE
 GESTATIONAL TROPHOBLASTIC
DISEASE: DEFINITION
• term used to encompass a group of tumors typified by
abnormal trophoblast proliferation

• Human Chorionic Gonadotropin (hCG) – produced by

trophoblasts, thus essential for GTD diagnosis,
management and surveillance

Divided into:
1. Hydatidiform moles : presence of villi
2. Non-molar trophoblastic neoplasms : without villi
 CLASSIFICATION: HYDATIDIFORM
MOLE

• Excessively edematous immature placentas

• Includes:
1. Complete hydatidiform mole
2. Partial hydatidiform mole
3. Invasive mole – malignant due to its marked penetration
into and destruction of the myometrium as well as it’s
ability to metastasize
 CLASSIFICATION:
HYDATIDIFORM MOLE
• Classic histological findings:
1. Villous stromal edema
2. Trophoblast proliferation
 CLASSIFICATION:
NONMOLAR TROPHOBLASTIC NEOPLASMS
• Includes:
1. Choriocarcinoma
2. Placental Site Trophoblastic Tumor
3. Epitheloid Trophoblastic Tumor
 HYDATIDIFORM MOLE

EPIDEMIOLOGY
• GTD are seen worldwide
• the incidence of HM is higher in Asia than in
North America or Europe.
• The incidence of PHM in the United Kingdom,
where all GTD cases are registered in a national
database, is 3/1000 pregnancies, and
• CHM ranges from 1 to 3/1000 pregnancies
 HYDATIDIFORM MOLE

RISK FACTORS
• strongest risk factors are age and a history of prior hydatidiform mole.
• adolescents and women aged 36 to 40 years have a twofold risk, those
older than 40 have an almost tenfold risk.
• reproductive history including HM is another risk factor : increasing the
risk of pregnancies by 5- to 40-fold that of the general population.
• Diet: decreasing consumption of animal fat and beta-carotene (precursor
to vitamin A) and folic acid .
• Genetics: rare autosomal recessive disorder known as familial recurrent
HM has been identified on chromosome 19q
 Complete mole
pathogenesis
• molar pregnancies arise from chromosomally abnormal
fertilizations
• Complete moles most often have a diploid chromosomal
composition usually are 46,XX and result from androgenesis,
meaning both sets of chromosomes are paternal in origin.
• an ovum is fertilized by a haploid sperm, which then duplicates its
own chromosomes after meiosis. The chromosomes of the ovum
are either absent or inactivated.
• Less commonly, the chromosomal pattern may be 46,XY or 46,XX
and due to fertilization by two sperm, that is, dispermic fertilization
or dispermy
• ( enuvleate ovum + normal sperm which replicates itself , rarely 2
sperms , karyotype 46xx most common)
 Pathology

• Placental abnormality
severe hyperplasia of trophoblasts : hydropic(swollen) chorionic villi
hydropic degeneration –grape like vesicles filling uterus
-Absent fetus
- Abnormal proliferation of syncytiotrophoblast – high hcg levels
(>100000)
theca lutein cyst
hyperthyroidism
hyperemesis gravidarum , early pre-eclampsia
 Partial mole
• Pathogenesis: normal ovum fertilized by two sperm
simultaneously
• It usually have a triploid karyotype—69,XXX, 69,XXY( most
common)—or much less commonly, 69,XYY. These are each
composed of two paternal haploid sets of chromosomes
contributed by dispermy and one maternal haploid set.
• Less frequently, a similar haploid egg may be fertilized by an
unreduced diploid 46,XY sperm. These triploid zygotes result
in some embryonic development, however, it ultimately is a
lethal fetal condition. Fetuses that reach advanced ages have
severe growth restriction, multiple congenital anomalies, or
both.
 Pathology
• Placenta abnormality :-
resulting in placenta abnormality
characterized by focal hydropic villi
and trophoblastic hyperplasia primarily of the
cytotrophoblast
• Normal or only slightly elevated hCG level
• Presence of fetus
• Lower malignancy potential
 The histopathologic differences between
CHM
CHM and PHM PHM

1)lack of fetal or embryonic tissues 1) presence of fetal or embryonic

tissues

2) hydropic (edematous) villi 2) less diffuse, focal hydropic swelling of villi;

3) diffuse trophoblastic 3) focal trophoblastic hyperplasia;

hyperplasia

4) marked atypia of trophoblasts at the implantation 4) less pronounced trophoblastic

site atypia at the molar implantation site;

(5) absence of trophoblastic stromal 5) Presence of trophoblastic scalloping and stromal

inclusions inclusions
 Clinical Findings
• Due to early prenatal care and increased use sonography the
clinical presentation of women with a molar pregnancy has
changed remarkably in the present developed world.
• diagnosis of CHM today is 9.6 weeks
• Following a delayed menses, CHM typically presents in the first
trimester as vaginal bleeding, with or without the passage of molar
vesicles and others classic signs of CHM are
a large-for-date uterus, absence of fetal movement,
anemia secondary to occult hemorrhage,
gestational hypertension before 20 weeks’ gestation,
presence of theca lutein cysts, hyperemesis, hyperthyroidism, and
respiratory distress from trophoblastic emboli to the lungs.
• PHM usually presents incidentally following histopathologic
examination of the products of conception from uterine
evacuation of a suspected missed or therapeutic abortion.
• Medical complications such as gestational hypertension,
hyperthyroidism, theca lutein cysts, and respiratory distress
are rare with PHM
• With a low clinical suspicion for PHM underdiagnosis is a risk,
reflecting the importance of a thorough hmhistopathologic
examination of curettage specimens to ensure quality care.
• Less severe symptoms and diagnose later than CHM
• Abdomen is usually smaller than dates
 DIAGNOSIS
• Due to amenorrhea that is followed by irregular bleeding it prompts
always to have pregnancy testing and sonography and Some with
spontaneous passage ofmolar tissue.
• Sonography- mainstay of trophoblastic disease diagnosis but not all
confirmed initially. CHMs are easier to diagnose than PHM, which are
diifcult to differentiate from incomplete or missed abortion.
• A CHM has the appearance on US of an echogenic endometrial mass
accompanying an enlarged uterus, the so-called “snowstorm
appearance” where as PHM has Swiss-cheese appearance of
intrauterine tissue.
• Features suggestive of CHM on US are
(1) absence of fetal or embryonic tissue,
(2) absence of amniotic fluid,
(3) enlarged placenta with multiple cysts,
and (4) ovarian theca lutein
cysts

• Features suggestive of PHM on US are

(1) presence of fetal or embryonic tissue,
(2) presence of amniotic fluid,
(3) abnormal placenta with multiple cysts or increased echogenicity of
chorionic villi,
(4) increased transverse diameter of gestational sac, and
(5) absence of theca lutein cysts
 Serum β-HCG Measurements

• Increase in CHM (> 100,000 U/L ) relatively normal in PHM

• high values can lead to erroneous false-negative urine pregnancy
test results because of oversaturation of the test assay by
excessive β-hCG hormone
Pathological Diagnosis

• Surveillance for subsequent neoplasia following molar pregnancy

is crucial. Thus, moles must be histologically distinguished from
other types of pregnancy failure that have hydropic placental
degeneration, which can mimic molar villous changes.
• Before 10 weeks villi may not be enlarged and may not be
edematous and avascular. Such situations, other techniques are used
to differentiate. One takes advantage of the differing ploidy to
distinguish partial (triploid) moles from diploid entities. Complete
moles and nonmolar pregnancies with hydropic placental
degeneration are both diploid.
• histological immunostaining to identify the p57KIP2 nuclear protein
• As a result, the combined use of ploidy analysis and p57KIP2
immunostaining can be used to differentiate:
(1) a complete mole (diploid/p57KIP2-negative),
(2) a partial mole(triploid/p57KIP2-positive), and spontaneous abortion
with hydropic placental degeneration (diploid/p57KIP2-positive)
 TREATMENT
• Maternal deaths from molar pregnancies are
rare because of early diagnosis, timely
evacuation, and vigilant postevacuation
surveillance for GTN.
• Preoperative evaluation attempts to identify
known potential complications such as
preeclampsia, hyperthyroidism, anemia,
electrolyte depletions from hyperemesis, and
metastatic disease
 Termination of Molar Pregnancy
• Suction Dilation and Curettage: preferred method of uterine evacuation
of HM under general anesthetic.
• Cervix is serially dilated and then a large suction curette is advanced just
past the endocervix into the endometrial canal. After activating the
suction device, a solution of crystalloid and oxytocin (20 U/L) is infused
to increase uterine tone; this is continued postoperatively to reduce
bleeding.
• Hysterectomy : diagnosed with HM preoperatively for whom continued
fertility is not an issue, hysterectomy with preservation of the adnexa is
a treatment option
• decreases local (myometrial) persistence, but it does not eliminate the
risk of distant metastases.
• 40 years with HM = risk 53% and 60% in women older than 50 to have
GTN
Postevacuation Surveillance

• Close biochemical surveillance for persistent gestational neoplasia

should follow hydatidiform mole evacuation. reliable contraception
is imperative to avoid confusion caused by rising β- hCG levels from a
new pregnancy.
• Most recommend either combination hormonal contraception or
injectable medroxyprogesterone acetate
• Intrauterine devices are not used until β-hCG levels are undetectable
because of the risk of uterine perforation if there is an invasive mole.
• Finally, barrier and other methods are not recommended because
of their relatively high failure rates
• serial measurements of serum β-hCG to detect persistent or
renewed trophoblastic proliferation and to ensure a timely
diagnosis of postmolar malignant GTN
• Within 48 hours of evacuation, a baseline β-hCG level should be
obtained and repeated weekly until the level returns to normal
(<5 mIU/mL).
• Most cases of postmolar GTN will occur within 6 months of
evacuation, so monthly β-hCG monitoring is recommended
following normalization for an additional 6 to12 months.
• risk factors for developing trophoblastic neoplasia following
molar evacuation : chm 15 to 20 %, PHM = 1 to 5 % along with
older age, β-hCG levels > 100,000 mIU/mL, uterine size that is
large-forgestational age, theca-lutein cysts > 6 cm, and slow
decline in β-hCG levels
GESTATIONAL TROPHOBLASTIC NEOPLASIA

• includes invasive mole, choriocarcinoma, placental site

trophoblastic tumor, and epithelioid trophoblastic
tumor
• tumors almost always develop with or follow some form
of recognized pregnancy. Half follow hydatidiform mole,
a fourth follow miscarriage or tubal pregnancy, and
another fourth develop after a preterm or term
pregnancy
• diagnosed solely by persistently elevated serum β-hCG
levels because tissue is frequently not available for
pathological study
 Clinical Findings
• characterized clinically by their aggressive invasion
into the myometrium and propensity to
metastasize.
• most common finding is irregular bleeding
associated with uterine subinvolution.
• Myometrial perforation from trophoblastic growth
may cause intraperitoneal hemorrhage. In some
women, lower genital tract metastases are evident,
whereas in others there are only distant metastases
with no trace of a uterine tumor.
Diagnosis, Staging, and Prognostic Scoring

• persistent bleeding after any type of pregnancy should prompt

measurement of serum β-hCG levels and consideration for
diagnostic curettage and uterine sized assessed along with
Uterine size is assessed along with careful examination for
lower genital tract metastases.
• search for local disease and metastases includes tests of liver
and renal function, transvaginal sonography, chest CT scan or
radiograph, and brain and abdominopelvic CT scan or MR
imaging.
• Less commonly, positron-emission tomographic (PET) scanning
and cerebrospinal fluid β-hCG level determination are used to
identify metastases
 Histological Classification
• Invasive Mole: previously known as chorioadenoma
destruens, most common trophoblastic neoplasms
that follow hydatidiform moles
• Almost all arise from partial or complete moles
• characterized by extensive tissue invasion by
trophoblast i.e syncytiotrophoblast or
cytotrophoblast hyperplasia and the presence of villi.
• extending into the myometrium constitutes invasion,
and hence the name. Most of these tumors, as in HM,
are diploid; anaplastic tumors are the exception.
 Gestational Choriocarcinoma
• the most common type of trophoblastic neoplasm to follow a
term pregnancy or a miscarriage, and only a third of cases
follow a molar gestation.
• It is composed of cells reminiscent of early cytotrophoblast and
syncytiotrophoblast, however, it contains no villi.
• invades both myometrium and blood vessels to create
hemorrhage and necrosis.
• The most common sites are the lungs and vagina, but tumor
may be metastatic to the vulva, kidneys, liver, ovaries, brain,
and bowel.
• They are commonly accompanied by ovarian theca-lutein cysts.
 Placental Site Trophoblastic Tumor
(PSST)
• uncommon tumor arises from implantation
site-intermediate trophoblast.
• β-hCG levels modestly elevated, but produce
variant forms of hCG, and identification of a
high proportion of free β-hCG (> 30 percent) is
considered diagnostic.
• Treatment by hysterectomy because these
locally invasive tumors are usually resistant to
chemotherapy
 Epithelioid Trophoblastic Tumor
• rare tumor develops from chorionic-type
intermediate trophoblast.
• grows in a nodular fashion.
• Primary treatment hysterectomy because this
tumor is relatively resistant to chemotherapy.
• a fourth of women with this neoplasm will
have metastatic disease, and they are given
combination chemotherapy
 Treatment
• Low-Risk Gestational Trophoblastic Neoplasia and
High-Risk Gestational Trophoblastic Neoplasia
• best managed by oncologists.
• Chemotherapy : primary treatment, and repeat
evacuation is not recommended by most because of
risks for uterine perforation, bleeding, infection, or
intrauterine adhesion formation.
• specific cases hysterectomy may be primary or
adjuvant treatment
Combination chemotherapy is given for high-risk disease, and reported cure rates approximate 90 percent. EMA-CO,
which includes etoposide, methotrexate, actinomycin D, cyclophosphamide, and oncovin (vincristine
 SURVEILLANCE FOLLOWING GESTATIONAL
TROPHOBLASTIC NEOPLASIA
• After β-hCG remission is achieved for three weekly cycles,
patients with high-risk GTN require repeat testing every 2
weeks for 3 weeks and then monthly for 1 year.
• Stage IV patients are encouraged to maintain monthly testing
for 24 months. The risk of relapse beyond the first year is less
than 1%. In patients who relapse, sustained remissions are
achieved in more than 50%, suggesting value to prolonged β-
hCG monitoring every 6 months, extending as long as 5 years
• During this time, effective contraception is crucial to avoid any
teratogenic effects of chemotherapy to the fetus as well as to
mitigate confusion from rising β-hCG levels caused by
superimposed pregnancy.
 RECURRENCE

• 3% for stage I disease, 8% for stage II, 4% for

stage III, and 9% for stage IV

PREGNANCY FOLLOWING GESTATIONAL

TROPHOBLASTIC NEOPLASIA
• patients can expect normal reproductive
outcomes.