Abortion.

Gestational
trophoblastic disease

Dr. Ciprian Pătru

2020
 • Abortion is the spontaneous or induced termination of pregnancy before fetal
viability.
•Because popular use of the word abortion implies a deliberate pregnancy
termination, some prefer the word miscarriage to refer to spontaneous fetal
loss before viability. Because the widespread use of sonography and serum
measurement of human chorionic gonadotropin levels allows identification of
an extremely early pregnancy, a number of other names have come into
common use. These include, for example, early pregnancy loss or early
pregnancy failure.
•The National Center for Health Statistics, the Centers for Disease Control and
Abortion Prevention (CDC), and the World Health Organization (WHO) define abortion as
pregnancy termination prior to 20 weeks' gestation or a fetus born weighing
less than 500 g. Despite this, definitions vary widely according to state laws.
Miscarriage, Spontaneous Abortion, or Early Pregnancy Failure .More than 80
percent of spontaneous abortions are in the first 12 weeks of pregnancy.
• Hemorrhage into the decidua basalis, followed by necrosis of tissues adjacent
to the bleeding, usually accompanies early miscarriage. In these cases, the
ovum detaches, stimulating uterine contractions that result in its expulsion.
When a gestational sac is opened, fluid is commonly found surrounding a small
macerated fetus, or alternatively no fetus is visible—the so-called blighted
ovum.
•Fetal Factors
Early spontaneous abortions commonly
display a developmental abnormality of the Table Chromosomal Findings in
Abortuses

zygote, embryo, early fetus, or at times the

placenta. Of 1,000 spontaneous abortions,
one-half had a degenerated or absent   Incidence in Percent

embryo, which are the blighted ova

described previously. Normal (euploid)      

In 50 to 60 percent of spontaneously   46, XY and 46, XX 46   51   54  

aborted embryos and early fetuses, Abnormal (aneuploid)      

abnormalities in chromosomal numbers   Autosomal trisomy 31   31   22  

account for most wastage.   Monosomy X (45, X) 10 5 19

  Triploidy 7 6 8

  Tetraploidy 2 4 3

  Structural anomaly 2 4 3

  Double or triple trisomy 2 0.9 0.7

•Aneuploid Abortion
About 95 percent of chromosomal abnormalities are caused by maternal gametogenesis errors, 5 percent are
due to paternal errors.
Autosomal trisomy is the most frequently identified chromosomal anomaly with first-trimester miscarriages.
Although most trisomies result from isolated nondisjunction, balanced structural chromosomal rearrangements
are present in one partner in 2 to 4 percent of couples with recurrent miscarriage (American College of
Obstetricians and Gynecologists, 2001). Autosomal trisomies for all except chromosome number 1 have been
identified in abortuses, and those with autosomes 13, 16, 18, 21, and 22 are most common.
Monosomy X (45, X), is the single most common specific chromosomal abnormality. These cause Turner
syndrome, which usually results in abortion and much less frequently in live-born females. Conversely,
autosomal monosomy is rare and incompatible with life.
•Triploidy is often associated with hydropic placental (molar) degeneration. Incomplete (partial) hydatidiform
moles may be triploid or trisomic for only chromosome 16. Although these fetuses frequently abort early, the
few carried longer are grossly malformed. Advanced maternal and paternal age does not increase the incidence
of triploidy.
•Tetraploid abortuses are rarely live born and are most often aborted early in gestation. Chromosomal structural
abnormalities infrequently cause abortion. Some infants who are live born with a balanced translocation may
appear normal as discussed in Parental Chromosomal Abnormalities.
•Euploid Abortion
Chromosomally normal fetuses tend to abort later in gestation than those with aneuploidy
The incidence of euploid abortions increases dramatically after maternal age exceeds 35 years.
•Maternal Factors
The causes of euploid abortions are poorly understood, although a variety of medical
disorders, environmental conditions, and developmental abnormalities have been
implicated.
•Infections
According to the American College of Obstetricians and Gynecologists, infections are
an uncommon cause of early abortion. Even in their study of insulin-dependent
diabetic women—presumably more susceptible to infection—. A number of specific
infections have been studied. For example, although Brucella abortus and
Campylobacter fetus cause abortion in cattle, they do not do so in humans.
There is also no evidence that either Listeria monocytogenes or Chlamydia trachomatis
stimulate abortions in humans.
Evidence that Toxoplasma gondii causes abortion in humans remains inconclusive.
Early abortions are rarely secondary to chronic wasting diseases such as tuberculosis or
carcinomatosis. Celiac sprue, however, has been reported to cause both male and
female infertility and recurrent abortions.
Endocrine Abnormalities
•Hypothyroidism
Iodine deficiency may be associated with miscarriages. Thyroid
hormone deficiency is common in women, and it is usually caused by an
autoimmune disorder, but any effects of hypothyroidism on early
pregnancy loss have not been adequately studied. Even without
hypothyroidism, thyroid autoantibodies are associated with an increased
incidence of miscarriage.
 
•Diabetes Mellitus
Spontaneous abortion and major congenital malformation rates are both
increased in women with insulin-dependent diabetes. The risk appears
related to the degree of metabolic control in early pregnancy.
Overt diabetes is a cause of recurrent pregnancy loss- studies have reported
a higher incidence of insulin resistance in those with recurrent miscarriage.
Drug Use and Environmental Factors
A variety of different agents have been reported to be associated with an increased
incidence of abortion.
•Tobacco - Smoking has been linked with an increased risk for euploid abortion.
studies suggested that the abortion risk increases in a linear fashion with the number of
cigarettes smoked per day.
•Alcohol - Both spontaneous abortion and fetal anomalies may result from frequent
alcohol use during the first 8 weeks of pregnancy.The risk seems to be related to both
frequency and dose. A low level of alcohol consumption during pregnancy was not
associated with a significant risk for abortion.
•Caffeine –women who consumed at least five cups of coffee per day had a slightly
increased abortion risk, and that above this threshold, the risk correlated linearly.
Moderate caffeine consumption is unlikely to cause spontaneous abortion.
•Radiation - In therapeutic doses given to treat malignancy, radiation is certainly an
abortifacient. Although lower doses are less toxic, the human dose to effect abortion is
not precisely known - exposure to less than 5 rads does not increase the risk for
miscarriage.
•Contraceptives - Oral contraceptives or spermicidal agents used in contraceptive
creams and jellies are not associated with an increased miscarriage rate. When
intrauterine devices fail to prevent pregnancy, however, the risk of abortion, and
specifically septic abortion, increases substantively   
•Environmental Toxins - Accurately assessing the relationship between environmental
exposures and miscarriage poses challenges. There may be difficulties in measuring the
intensity and duration of exposure, and there is little information to conclusively indict
or absolve any specific agent. Nevertheless, it seems prudent to limit exposure of
pregnant women to environmental toxins.
•Immunologic Factors - A number of immune-mediated disorders are associated with
early pregnancy loss. Many tend to be repetitive, and they are considered with
recurrent miscarriage.
•Inherited Thrombophilias - There are a number of genetic disorders of blood
coagulation that may increase the risk of both arterial and venous thrombosis. Some of
the better studied thrombophilias are caused by mutations of the gene for factor V
Leiden, prothrombin, antithrombin, proteins C and S, and methylene tetrahydrofolate
reductase (hyperhomocysteinemia).
•Maternal Surgery
Uncomplicated abdominal or pelvic surgery performed during early
pregnancy does not appear to increase the risk for abortion.
Ovarian tumors are generally removed without interfering with pregnancy.
An important exception involves early removal of the corpus luteum cyst
or the ovary in which the corpus luteum resides. If performed prior to 10
weeks' gestation, supplemental progesterone is indicated. If between 8 and
10 weeks, then only one injection of intramuscular 17-
hydroxyprogesterone caproate, 150 mg, is required immediately after
surgery. If the corpus luteum is excised between 6 and 8 weeks, then two
additional doses should be given 1 and 2 weeks after the first.
•Trauma
Presumably, major abdominal trauma can precipitate abortion, however,
this is unusual in early pregnancy. Any effects of minor trauma on abortion
rates is difficult to ascertain. Minor trauma without pregnancy
complication is often forgotten, whereas minor trauma temporally
associated with miscarriage is more likely to be recalled. In general, trauma
contributes minimally to the incidence of abortion.
Uterine Defects
•Acquired Uterine Defects
Large and multiple uterine leiomyomas are common, and they may cause
miscarriage. In most instances, their location is more important than their size. Uterine
synechiae—known as Asherman syndrome—usually result from destruction of large
areas of endometrium by curettage. A hysterosalpingogram may show characteristic
multiple filling defects, but hysteroscopy is more accurate. With subsequent pregnancy,
the amount of remaining endometrium may be insufficient to support the pregnancy,
and abortion may ensue.
Developmental Uterine Defects
Abnormal müllerian duct formation or fusion defects may develop spontaneously or
may follow in utero exposure to diethylstilbestrol . Although they can cause
midpregnancy loss and other preterm birth and pregnancy complications, it is
controversial whether uterine defects cause early miscarriage.
•Incompetent Cervix
This describes a discrete obstetric entity characterized by painless cervical dilatation
in the second trimester. It can be followed by prolapse and ballooning of membranes
into the vagina, and ultimately expulsion of an immature fetus.
Clinical Classification of Spontaneous Abortion
The clinical aspects of spontaneous abortion can be classified a number of ways. Commonly used
subgroups include threatened, inevitable, incomplete, and missed abortion. If the products of conception and
pelvic organs are infected, septic abortion is diagnosed. Finally, recurrent miscarriage—also termed recurrent
pregnancy loss—describes consecutive early losses with implied similar etiology.
•Threatened Abortion

The clinical diagnosis of threatened abortion is presumed when a bloody vaginal discharge or bleeding
appears through a closed cervical os during the first half of pregnancy. Vaginal spotting or heavier bleeding
develops in 20 to 25 percent of women during early gestation and it may persist for days or weeks.
Approximately half of these pregnancies will abort, although the risk is substantially lower if fetal cardiac
activity can be documented .
•Differential Diagnosis, transvaginal sonography, serial serum quantitative -hCG and
serum progesterone levels, used alone or in combination, can help to ascertain if a
fetus is alive and within the uterus. None of these tests in early gestation are 100-
percent accurate to confirm fetal death, thus subsequent evaluations over a week or
two may be necessary.
•Ectopic pregnancy should always be considered in the differential diagnosis of
threatened abortion.
•Anti-D Immunoglobulin
Treatment of D-negative women with anti-D immunoglobulin is recommended
following miscarriage because up to 5 percent of D-negative women will become
isoimmunized without it.
•Inevitable Abortion
Gross rupture of the membranes, evidenced by leaking amnionic fluid, in the presence of cervical dilatation signals almost certain abortion. Commonly, either
uterine contractions begin promptly, resulting in miscarriage, or infection develops. Rarely, a gush of fluid from the uterus during the first half of pregnancy is without
serious consequence. The fluid may have collected previously between the amnion and chorion. Because of this possibility, if a sudden discharge of fluid in early
pregnancy occurs before pain, fever, or bleeding, then diminished activity with observation is reasonable. If after 48 hours no additional amnionic fluid has escaped
and if there is no bleeding, pain, or fever, a woman may resume her usual activities except for any form of vaginal penetration. If, however, the gush of fluid is
accompanied or followed by bleeding, pain, or fever, then abortion should be considered inevitable, and the uterus emptied.
•Incomplete Abortion
Bleeding ensues when the placenta, in whole or in part, detaches from the uterus. During incomplete abortion, the internal cervical os opens and allows passage of
blood. The fetus and placenta may remain entirely in utero or may partially extrude through the dilated os. Before 10 weeks, the fetus and placenta are commonly
expelled together, but later they are delivered separately. In some women, additional cervical dilatation is necessary before curettage is performed. In many cases,
retained placental tissue simply lies loosely in the cervical canal, allowing easy extraction from an exposed external os with ring forceps. Suction curettage effectively
evacuates the uterus.
In clinically stable women, expectant management can also be a reasonable option Hemorrhage from incomplete abortion of a more advanced pregnancy is
occasionally severe but rarely fatal. Therefore, in women with more advanced pregnancies or with heavy bleeding, evacuation is promptly performed. If there is fever,
appropriate antibiotics are given before curettage.
•Missed Abortion—Early Pregnancy Failure

The term missed abortion is contemporaneously imprecise because it was defined many decades before the advent of immunologic pregnancy tests and sonography
.
Septic Abortion

In the past septic abortion and maternal deaths associated with

criminal abortions were common, but currently are rare. That said,
miscarriage and elective abortion are occasionally complicated by
severe and even fatal infections. Uterine infection is the most
common manifestation of postabortal sepsis, but parametritis,
peritonitis, septicemia, and even endocarditis, occasionally
develop.
Treatment of infection includes prompt administration of
intravenous broad-spectrum antibiotics followed by uterine
evacuation. With severe sepsis syndrome, acute respiratory
distress syndrome or disseminated intravascular coagulopathy
may develop, and supportive care is essential.
 Clinical and Laboratory Criteria for Diagnosis of Antiphospholipid
Antibody Syndrome

Clinical criteria
  1.    Three or more consecutive spontaneous abortions before 10 weeks
(recurrent pregnancy loss); delivery before 34 weeks; one or more

•Antiphospholipid unexplained fetal deaths of a morphologically normal infant; or severe

preeclampsia or placental insufficiency necessitating delivery before

Antibody Syndrome
34 weeks.
 

  2.    Arterial or vascular thrombosis without an obvious precipitating cause;

small-vessel thrombosis in any tissue or organ, without significant
evidence of vasculitis.

Laboratory criteria
  1.    Moderate to high levels of IgG or IgM anticardiolipin antibodies.
 

  2.    Detection of lupus anticoagulant. These tests must be positive on at

least two occasions at least 6 weeks apart.
IgG=immunoglobuline G, IgM=immunoglobuline M. At least one
critical and laboratory criterion each must be present for diagnosis.
Evaluation of Couples with Recurrent Pregnancy Loss

Etiology Diagnostic Evaluation Abnormal Therapy

Genetic Karyotype partners 3–5% Genetic counseling, donor gametes
Anatomic Hysterosalpingography 15–20% Septum transection, myomectomy, adhesiolysis, metroplasty
Hysteroscopy
Sonohysterography
Magnetic resonance imaging

Endocrinologic Midluteal progesterone 8–12% Progesterone

  Thyroid-stimulating hormone   Levothyroxine
  Prolactin   Dopamine agonists
  Fasting insulin:glucose   Metformin
Immunologic Lupus anticoagulant, antiphospholipid antibodies 15–20% Heparin + aspirin
Microbiologic Cervical cultures 5–10% Antibiotics
Thrombophilia Antithrombin III, protein C or S deficiency; factor V Leiden or prothrombin mutation 8–12% Heparin + aspirin, low-molecular-weight heparin

  Hyperhomocysteinemia   Folic acid

Psychological Interview Varies Support groups, counseling
Questionnaire

Toxic Tobacco, alcohol use 5% Behavior changes

  Exposure to toxins, chemicals   Eliminate exposure
•Induced Abortion
Induced abortion is the medical or surgical termination of pregnancy before the time
of fetal viability
•Classification of Induced Abortion
•Therapeutic Abortion

Some indications for early termination of pregnancy include persistent cardiac

decompensation, advanced hypertensive vascular disease, and invasive carcinoma of
the cervix.
In addition to medical and surgical disorders that may be indications for termination,
there are others. Certainly in cases of rape or incest most consider termination
indicated. Another commonly cited indication is to prevent birth of a fetus with a
significant anatomic or mental deformity. The seriousness of fetal deformities is wide
ranging and frequently defies social, legal, or political classification

•Elective (Voluntary) Abortion

The interruption of pregnancy before viability at the request of the woman, but not
for medical reasons, is usually termed elective or voluntary abortion.
Abortion Techniques

Surgical techniques
  Cervical dilatation followed by uterine evacuation
     Curettage
     Vacuum aspiration (suction curettage)
     Dilatation and evacuation (D&E)
     Dilatation and extraction (D&X)
  Menstrual aspiration
  Laparotomy
     Hysterotomy
     Hysterectomy
Medical techniques
  Intravenous oxytocin
  Intra-amnionic hyperosmotic fluid
     20% saline
     30% urea
  Prostaglandins E2, F2?, E1, and analogues
     Intra-amnionic injection
     Extraovular injection
     Vaginal insertion
     Parenteral injection
     Oral ingestion
  Antiprogesterones (RU 486 [mifepristone] and epostane)
  Methotrexate (intramuscular and oral)
  Various combinations of the above
•Surgical Abortion
Early surgical pregnancy termination requires first dilating the cervix and
then evacuating the pregnancy by mechanically scraping out the contents
(sharp curettage), by suctioning out the contents (suction curettage), or
both
Vacuum aspiration, the most common form of suction curettage, requires a
rigid cannula attached to an electric-powered vacuum source. Alternatively,
manual vacuum aspiration uses a similar cannula that attaches to a
handheld syringe for its vacuum source
The likelihood of complications increases after the first trimester. These
include uterine perforation, cervical laceration, hemorrhage, incomplete
removal of the fetus and placenta, and infection. Small and large bowel
injuries may also occur
Accordingly, sharp or suction curettage should be performed before 14 to
15 weeks. In the absence of maternal systemic disease, abortion procedures
do not require hospitalization. When abortion is performed outside a
hospital setting, capabilities for cardiopulmonary resuscitation and for
immediate transfer to a hospital must be available.
•Prostaglandins
Various prostaglandin preparations may be used instead of hygroscopic
dilators to aid subsequent dilation. These may be taken orally or placed
into the posterior vaginal fornix.
Manual Vacuum Aspiration
This office-based procedure is used for surgical treatment of early
pregnancy failures as well as elective termination up to 12 weeks'
gestation. A vacuum is created in the syringe and attached to the cannula,
which is inserted transcervically into the uterus. The vacuum is created and
produces up to 60 mm Hg suction. Although complications are similar to
other surgical methods, they are not increased. With pregnancies less than
8 weeks, no cervical preparation is required. After this time, some
recommend either osmotic dilators placed the day before or misoprostol
given 2 to 4 hours before the procedure. A paracervical block with or
without intravenous sedation, or conscious sedation is used for anesthesia
Regimens for Medical Termination of Early Pregnancy

Mifepristone/misoprostol
a
Mifepristone, 100–600 mg orally followed by:
b
Misoprostol, 200–600 g orally or 800 g vaginally in 6–72 hours

Methotrexate/misoprostol
c
Methotrexate, 50 mg/m2 intramuscularly or orally followed by:
d
Misoprostol, 800 g vaginally in 3–7 days; repeat if needed 1 week after methotrexate initially given

Misoprostol alone
800 g vaginally, repeated for up to three doses
 Gestational
Trophoblastic Disease
The term gestational trophoblastic disease refers to pregnancy-related trophoblastic proliferative abnormalities. In the past, classification of
these abnormalities was confusing because it was defined by histological criteria as well as by clinical findings. As experience accrued, it
became evident that a histological diagnosis was not necessary to provide effective treatment. Thus, a system has been adopted based
principally on clinical findings and serial measurement of serum human chorionic gonadotropin (hCG) levels. In 1983, the World Health
Organization Scientific Group on Gestational Trophoblastic Diseases published recommendations for the definition, classification, and staging
of trophoblastic disease. This classification was recently updated by the International Federation of Gynecology and Obstetrics (FIGO
Oncology Committee, 2002). Gestational trophoblastic disease is divided into two groups, hydatidiform mole and postmolar gestational
trophoblastic neoplasia (Table). The latter is termed malignant gestational trophoblastic disease by the American College of Obstetricians and
Gynecologists (2004).
Table. Criteria for Diagnosis of Gestational Trophoblastic Disease

Hydatidiform Mole 
  Complete
  Partial
Gestational Trophoblastic Neoplasia–Postmolar GTN 
1. Plateau of serum hCG level (±10%) for four measurements during a period of 3 weeks or longer—days 1, 7, 14, 21.
2. Rise of serum hCG > 10% during three weekly consecutive measurements or longer, during a period of 2 weeks or more—days 1, 7, 14.
3. The serum hCG level remains detectable for 6 months or more.
4. Histological criteria for choriocarcinoma.
 Hydatidiform Mole (Molar Pregnancy)
Molar pregnancy is characterized histologically by abnormalities of the chorionic villi that consist of trophoblastic proliferation and edema of villous
stroma. Moles usually occupy the uterine cavity, however, occasionally they develop in the oviduct and even the ovary .The absence or presence of a fetus
or embryonic elements has been used to describe them as complete and partial moles

Features of Partial and Complete Hydatidiform Moles

Feature Partial Mole Complete Mole

Karyotype Usually 69,XXX or 69,XXY 46,XX or 46,XY
Pathology
  Embryo-fetus Often present Absent
  Amnion, fetal red blood cells Often present Absent
  Villous edema Variable, focal Diffuse
  Trophoblastic Variable, focal, slight to moderate Variable, slight to 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 Frequent
  Gestational trophoblastic neoplasia <5–10% 20%
 Complete Hydatidiform Mole
In complete hydatiform mole, the chorionic villi transform into a mass of clear vesicles .The vesicles vary in size from barely visible to a few centimeters and often hang in clusters from thin pedicles. The histological structure
typically shows:
Hydropic degeneration and swelling of the villous stroma.
Absence of blood vessels in the swollen villi.
Proliferation of the trophoblastic epithelium to a varying degree
Absence of fetus and amnion.
The chromosomal composition in 85 percent of complete molar pregnancies is 46,XX, with both chromosomes being of paternal origin . This phenomenon is termed androgenesis. Typically, the ovum has been fertilized by a haploid
sperm, which then duplicates its own chromosomes after meiosis. The chromosomes of the ovum are either absent or inactivated. Occasionally, the chromosomal pattern in a complete mole may be 46,XY due to dispermic fertilization.

Chromosomal Composition of Hydatidiform Moles

Chromosomes Complete (n = 151) No. (%) Partial (n = 49) No. (%)

Haploid 1 (0.7) —
Diploid 128 (85) 1 (2)
Triploid 3 (2) 42 (86)
Tetraploid — 2 (4)
Unknown 19 (13) 4 (8)
Partial Hydatidiform Mole

When the hydatidiform changes are focal and less advanced, and some
element of fetal tissue is seen, the term partial hydatidiform mole is used.
There is slowly progressive swelling within the stroma of characteristically
avascular chorionic villi, whereas other vascular villi with a functioning
fetal–placental circulation are spared.
Abnormal growth is also common, 82 percent of fetuses had symmetrical
growth restriction.A twin gestation of a complete mole and a normal fetus
and placenta is sometimes misdiagnosed as a diploid partial mole .
It is important to distinguish between the two, because twin pregnancies
consisting of a normal fetus and a complete mole have a substantively
increased risk of developing subsequent gestational trophoblastic
neoplasia. Generally, gestational trophoblastic neoplasia follows 20 percent
of complete moles, whereas it develops in only 0.5 percent of women after
a partial mole.
Incidence and Risk Factors

Hydatidiform mole develops in approximately 1 in 1000 pregnancies in the United States and Europe.
The role of gravidity, estrogen status, oral contraceptives, and dietary factors in the risk of gestational trophoblastic disease is unclear.
1.Age - the incidence of molar pregnancy highest in women aged 15 years or younger, and those aged 45 years or older.
2.Previous Mole - women with molar pregnancies are at increased risk of developing either a complete or a partial mole in a future pregnancy.
3.Clinical Course - the clinical presentation of molar pregnancy has changed appreciably during the past 20 years. The availability of ultrasonography and quantitative measurement of serum hCG levels now allows earlier diagnosis. Symptoms are more likely to be dramatic
with a complete mole than with a partial mole.
4.Bleeding - uterine bleeding is almost universal, and may vary from spotting to profuse hemorrhage. It may begin just before abortion or, more often, these women may bleed intermittently for weeks and even months. At times there may be considerable hemorrhage concealed
within the uterus. Iron-deficiency anemia is common, and a dilutional effect from appreciable pregnancy-induced hypervolemia is present in some women with larger moles.
5.Uterine Size - the growing uterus often enlarges more rapidly than usual, exceeding in about half of cases that expected from
the gestational age. The uterus may be difficult to identify precisely by palpation because of its soft consistency. At times,
ovarian theca-lutein cysts are difficult to distinguish from the enlarged uterus.
6.Fetal Activity - even though the uterus is enlarged sufficiently to extend well above the symphysis, typically no fetal heart
motion is detected. Infrequently, there may be extensive but incomplete molar degeneration in the placenta accompanied by a
living fetus.
7.Gestational Hypertension - because hypertension caused by pregnancy is rarely seen before 24 weeks, preeclampsia that
develops before this gestational age may be from hydatidiform mole or extensive molar degeneration.
8.Hyperemesis - significant nausea and vomiting may develop. Of interest, none of the 24 complete moles were associated with
preeclampsia, hyperemesis, or clinical hyperthyroidism.
9.Thyrotoxicosis - plasma thyroxine levels in women with molar pregnancy are often elevated, but clinically apparent
hyperthyroidism is unusual., hyperthyroidism is identified in about 2 percent. In these cases, serum free thyroxine is elevated as
the consequence of the thyrotropin-like effect of hCG.

10.Embolization - variable amounts of trophoblastic cells with or without villous stroma escape from the uterus into the venous
outflow at the time of molar evacuation . The volume may be such as to produce signs and symptoms of acute pulmonary
embolism or edema. Embolization with a large amount of trophoblastic tissue is probably uncommon, although fatalities have
been described . This tissue, though, can subsequently invade the pulmonary parenchyma to establish metastases.
Diagnostic Features

Spontaneous expulsion is most likely around 16 weeks and is rarely delayed beyond 28
weeks. The greatest diagnostic accuracy is obtained from the characteristic
ultrasonographic appearance of hydatidiform mole. Occasionally, other structures may
have an appearance similar to that of a mole, including uterine myoma and multifetal
pregnancy.
The clinical and diagnostic features of a complete hydatidiform mole are:
1. Continuous or intermittent brown or bloody discharge evident by about 12 weeks
and usually not profuse.
2. Uterine enlargement out of proportion to the duration of pregnancy in about half
of the cases.
3. Absence of fetal parts and fetal heart motion.
4. Characteristic ultrasonographic appearance.
5. Serum hCG level higher than expected for the stage of gestation.
6. Preeclampsia–eclampsia developing before 24 weeks.
7. Hyperemesis gravidarum.
•Prognosis
Current mortality from molar pregnancies has been practically reduced to zero by
prompt diagnosis and appropriate therapy. Earlier evacuation, however, has not
reduced the 20 percent risk for gestational trophoblastic neoplasia.
•Treatment
As a result of greater awareness, and certainly of better technology for diagnosis,
moles now are terminated more often when they are small. There is time for adequate
evaluation of the woman who may be anemic, hypertensive, or hypovolemic.
Hydatidiform mole treatment consists of two phases. The first is immediate evacuation
of the mole, and the second is subsequent evaluation for persistent trophoblastic
proliferation or malignant change. Unless there is other evidence of extrauterine
disease, computed tomography or magnetic resonance imaging to evaluate the liver or
brain is not performed routinely.The rare circumstance of twinning with a complete
hydatidiform mole plus a fetus and placenta presents an unusual therapeutic dilemma,
especially in the absence of karyotypic aberrations or gross fetal anomalies.
•Prophylactic Chemotherapy
The role of prophylactic chemotherapy for women with a hydatidiform mole is
controversial. Such therapy does not improve the long-term prognosis. Moreover, the
toxicity from prophylactic chemotherapy may be significant, including death.
Chemoprophylaxis may be considered in women with high-risk complete moles,
particularly if serum hCG testing is unavailable or follow-up is impossible.
•Vacuum Aspiration
Suction evacuation is the treatment of choice for hydatidiform mole, regardless of
uterine size. For large moles, compatible blood should be available and an intravenous
system established for its rapid infusion, if needed. Cervical dilating agents may be
necessary. The cervix may be further dilated under anesthesia to a diameter sufficient
to allow insertion of a 10- to 12-mm plastic suction curet. After most of the molar
tissue has been removed by aspiration, oxytocin is given. After the myometrium has
contracted, thorough but gentle curettage with a large sharp curet usually is performed.
Intraoperative ultrasonographic examination may help document that the uterine cavity
has been emptied.
•Oxytocin, Prostaglandins, and Hysterotomy
In the United States, labor induction rarely is used for evacuation of hydatidiform
moles. In fact, there are many who feel that medical termination and hysterotomy have
no role in its management
•Hysterectomy
If no further pregnancies are desired, then hysterectomy may be preferred to suction
curettage. Hysterectomy is a logical procedure in women aged 40 and older, because at
least one third develop gestational trophoblastic neoplasia. Although hysterectomy
does not eliminate recurrent disease, it appreciably reduces its likelihood.
Close and consistent follow-up for these women is imperative with the following aims:
1. Prevent pregnancy for a minimum of 6 months using hormonal contraception.
2. Monitor serum hCG levels every 2 weeks. Serial measurement of serum hCG is
important to detect trophoblastic neoplasia, and even small amounts of
trophoblastic tissue can be detected by the assay. These levels should
progressively fall to an undetectable level
3. Chemotherapy is not indicated as long as these serum levels continue to regress. A
rise or persistent plateau in the level demands evaluation for gestational
trophoblastic neoplasia and usually treatment. An increase signifies trophoblastic
proliferation that is most likely malignant unless the woman is again pregnant.
4. Once the hCG level falls to a normal level, test the patient monthly for 6 months;
then follow-up is discontinued and pregnancy allowed.
Estrogen–progestin contraceptives or depot-medroxyprogesterone usually are used to
prevent a subsequent pregnancy during the period of surveillance.
Gestational Trophoblastic Neoplasia

Also called malignant gestational trophoblastic disease,

this term refers to invasive mole, choriocarcinoma, and
placental site trophoblastic tumor. Any of these may follow
molar pregnancy or normal pregnancy, or develop after
abortive outcomes, including ectopic pregnancy.
•Etiology
Gestational trophoblastic neoplasia almost always
develops with or follows some form of pregnancy.
Approximately half of cases follow a hydatidiform mole,
25 percent follow an abortion, and 25 percent develop after
an apparently normal pregnancy.
•Invasive Mole
The distinguishing features of invasive mole are excessive trophoblastic
overgrowth and extensive penetration by the trophoblastic cells, including
whole villi. These structures penetrate into the depths of the myometrium,
sometimes to involve the peritoneum, adjacent parametrium, or vaginal
vault. Such moles are locally invasive, but generally lack the pronounced
tendency to widespread metastasis typical of choriocarcinoma.
•Placental Site Trophoblastic Tumor
Rarely, trophoblastic neoplasia arises from the placental implantation
site following a normal term pregnancy, spontaneous or induced abortion,
ectopic pregnancy, or molar pregnancy. The tumor is characterized
histologically by predominantly cytotrophoblastic cells, and
immunohistochemical staining reveals many prolactin-producing cells and
few gonadotropin-producing ones.Thus, serum hCG levels may be normal
to elevated. Bleeding is the main presenting symptom.
•Clinical Course
The most common finding is irregular bleeding associated with uterine subinvolution.
The bleeding may be continuous or intermittent, with sudden and sometimes massive
hemorrhage. Uterine perforation caused by invasive trophoblastic growth may cause
intraperitoneal hemorrhage.In some cases, the woman presents with a metastatic lesion
of the vagina or vulva. Occasionally, it has been impossible to locate choriocarcinoma
in the uterus or pelvis because the original lesion has disappeared, leaving only distant
metastases. If untreated, choriocarcinoma is invariably fatal.
•Diagnosis
Recognition of the possibility of gestational trophoblastic neoplasia is the most
important factor in diagnosis.
Any case of unusual bleeding after term pregnancy or abortion should be investigated
by curettage, and especially with measurements of serum hCG. Solitary or multiple
nodules seen in the chest radiograph are suggestive of choriocarcinoma.Persistent or
rising hCG levels in the absence of pregnancy also are indicative of gestational
trophoblastic neoplasia. Anatomical staging before treatment includes pelvic
examination, chest radiograph, and computed tomography (CT) scanning of the
abdomen and pelvis. CT scanning of the chest and head is recommended only if the
chest radiograph is abnormal.
•Treatment
Single-agent chemotherapy is given for nonmetastatic or low-risk metastatic neoplasia.
Methotrexate and other agents effective against malignant tumors, especially actinomycin D, are usually curative.
Several regimens have been used with success. Methotrexate has been used with good results when given orally, by
intravenous infusions, or by intramuscular injections.
Single-dose actinomycin D is also highly effective in women with nonmetastatic disease .
•Prognosis
The recent overall cure rate for gestational trophoblastic
neoplasia of all severities is about 90 percent.
Women with nonmetastatic tumors or low-risk gestational
trophoblastic neoplasia are cured virtually 100 percent of
the time if single-agent chemotherapy is started as soon as
persistent disease is identified.
Women with low-risk metastatic gestational trophoblastic
neoplasia who are treated aggressively with single- or
multiagent chemotherapy do almost as well as those with
nonmetastatic disease.
Women with high-risk metastatic neoplasia have
appreciable mortality rates that depend on which factors
placed them at high risk .
•Pregnancy after Gestational Trophoblastic Disease

Follow-up surveillance is minimally 6 months for molar

pregnancy, 1 year for gestational trophoblastic neoplasia, and up
to 2 years for cases with metastases other than to the lung.
There is no difficulty with fertility or normal pregnancy outcome
following successfully treated gestational trophoblastic disease .
Women who have been given chemotherapy do not have an
increased risk for anomalous fetuses in subsequent pregnancies.
The primary concern is that women who had gestational
trophoblastic disease are at increased risk for developing it again
in a subsequent pregnancy.