GESTATIONAL AND PLACENTAL

DISORDERS

Ectopic Pregnancy; ZK 3
Hydatidiform Mole, Partial; N99
Choriocarcinoma, Hydatidiform Mole; N 100_101
Diseases of pregnancy and pathologic conditions of the placenta are important causes of fetal intrauterine
or perinatal death, congenital malformations, intrauterine growth retardation, maternal death, and
morbidity for both mother and child.
The placenta is composed of chorionic villi that sprout from the chorion to provide a large contact area
between the fetal and maternal circulations.
In the mature placenta, the maternal blood
enters the intervillous space through
endometrial arteries (spiral arteries) and
circulates around the villi to allow gas and
nutrient exchange. The deoxygenated blood
flows back from the intervillous space to the
decidua and enters the endometrial veins.
Deoxygenated fetal blood enters the placenta
through two umbilical arteries that branch
radially to form chorionic arteries. Chorionic
arteries branch further as they enter the villi.
In the chorionic villi they form an extensive
capillary system, bringing fetal blood in close
proximity to maternal blood. The gas and
nutrient diffusion occurs through the villous
capillary endothelial cells and thinned-out
syncytiotrophoblast and cytotrophoblast.
Under nor­mal circumstances there little or no
mixing between the fetal and maternal blood,
though sufficient free fetal DNA reaches the
maternal circulation to permit prenatal genetic
testing. Blood oxygenated in the placenta
returns to the fetus through the single
umbilical vein.
DISORDERS OF EARLY PREGNANCY
SPONTANEOUS ABORTION
Spontaneous abortion = miscarriage: a pregnancy loss before 20 weeks of gestation.
22% of early pregnancies in otherwise healthy women terminate spontaneously.

The causes of spontaneous abortion:

Fetal: chromosomal anomalies, other subtle genetic defects
Maternal: endocrine factors: luteal-phase defect, poorly controlled diabetes, and other uncorrected
endocrine disorders,
physical defects of the uterus: submucosal leiomyomas, uterine polyps, or uterine or mal-
formations preventing implantation adequate to support fetal development.
systemic disorders affecting maternal vasculature: antiphospholipid antibody syndrome,
coagulopathies, and hypertension,
infections: bacteria (Mycoplasma, Listeria), protozoa (Toxoplasma) as well as viral infections,
Ascending infection is particularly common in second-trimester losses.
In many cases the mechanisms leading to early loss of pregnancy are still unknown.

INCOMPLETE ABORTION:  haevy bleeding (metrorrhagia). Emergency curretage

necessary.
ECTOPIC PREGNANCY
An implantation of the fetus in any site other than a normal
intrauterine location:
- fallopian tubes (∼90%),
- the ovary,
- the abdominal cavity, and
- the intrauterine portion of the fallopian tube (cornual
pregnancy).
It happens in 2% of confirmed pregnancies.
The most important predisposing condition - prior pelvic
inflammatory disease (present in 35% to 50% of patients) 
fallopian tube scarring (chronic follicular salpingitis).
Other factors contributing to salpingeal scarring:
appendicitis, endometriosis, and previous surgery (but in
some cases, however, the fallopian tubes are apparently
normal), intrauterine contraceptive devices (an increase in
the risk of ectopic pregnancy by about 2.5 fold).
Ovarian pregnancy is
presumed to result from the
rare fertilization and trapping
of the ovum within the
follicle just at the time of its
rupture. Abdominal
pregnancies may develop
when the fertilized ovum fails
to enter or drops out of the
fimbriated end of the tube.
Morphology: Tubal pregnancy is the most common cause of hematosalpinx (blood-filled fallopian tube)
and should always be suspected when a tubal hematoma is present. Still less commonly, the tubal
pregnancy is extruded through the fimbriated end into the abdominal cavity (tubal abortion).

Clinical Features of ectopic pregnancy

• severe abdominal pain, about 6 weeks after a previous normal
menstrual period,
• when rupture of the tube leads to pelvic hemorrhage (emergency)
• hemorrhagic shock with signs of an acute abdomen
• Confirmation: Chorionic gonadotropin assays (pregnancy test),
ultrasound studies, and laparoscopy
 PLACENTAL INFECTIONS
(1). Ascending infection through the birth canal, by far the most common
and virtually always bacterial
Produces premature rupture of membranes and preterm delivery.
The amniotic fluid may be cloudy with purulent exudate.

The placenta
contains greenish
opaque membranes.

(2). Hematogenous (transplacental) infection, frequently elicits a fetal response with “vasculitis” of
umbilical and fetal chorionic plate vessels.
Causes: TORCH (Toxoplasmosis and Others [syphilis, tuberculosis, listeriosis], Rubella, Cytomegalovirus,
Herpes simplex). They give rise to inflammatory infiltrates in the chorionic villi, usually of chronic
inflammatory cells (chronic villitis). Often, the cause of chronic villitis is obscure and may involve
immunological phenomena.
ABNORMALITIES OF PLACENTAL IMPLANTATION
Abnormal placental implantations may have significant consequences for the pregnancy outcome.
Placenta previa is a condition in which the placenta implants in the lower uterine segment or cervix, often
with serious third-trimester bleeding. A complete (total) placenta previa covers the internal cervical os and
thus requires delivery via cesarean section to avert placental rupture and fatal maternal hemorrhage during
vaginal delivery.
PLACENTA ACCRETA: partial or complete absence of the
decidua with adherence of the placental villous tissue
directly to the myometrium and failure of placental
separation in 3rd stage of labor. It is an important cause
of postpartum bleeding, which often may be life-
threatening to the mother. Common predisposing factors
are placenta previa (in up to 60% of cases) and history of
previous cesarean section.
PREECLAMPSIA AND ECLAMPSIA
Preeclampsia is a systemic syndrome characterized by widespread maternal endothelial dysfunction that
presents during pregnancy with
1. hypertension,
2. edema,
3. proteinuria.
It occurs in about 3% to 5% of pregnant women, usually in the last trimester and more commonly in
primiparas. Some developing convulsions = eclampsia.
Other complications stemming from systemic endothelial dysfunction include hypercoagulability, acute renal
failure, and pulmonary edema.
Approximately 10% develop HELLP syndrome (microangiopathic hemolytic anemia, elevated liver enzymes,
and low platelets).
Pathogenesis.
While the exact mechanisms leading to development of preeclampsia not fully understood, it is clear that the
placenta plays a central role in the pathogenesis of the syndrome, since the symptoms disappear rapidly
after delivery of the placenta. The critical abnormalities in preeclampsia are diffuse endothelial dysfunction,
vasoconstriction (leading to hypertension), and increased vascular permeability (resulting in proteinuria and
edema). Recent work has demonstrated that these effects are most likely mediated by placenta-derived
factor(s) released into the maternal circulation. Although the release of these factors and the clinical
syndrome develop late in gestation, the pathogenesis of the disease appears to be closely tied to the
earliest events of pregnancy and placentation.
The precipitating events in the pathogenesis of preeclampsia are
• abnormal trophoblastic implantation
• a failure of physiologic remodeling of the maternal vessels,
spiral arteries .
• Failure to convert the decidual from small-caliber resistance
vessels to large capacity uteroplacental vessels lacking a
smooth muscle coat.
• the development of placental ischemia.

Preeclampsia is also associated with a hypercoagulable state that

may lead to the formation of thrombi in arterioles and capillaries
throughout the body, but particularly in the liver, kidneys, brain,
and pituitary.

The physiologic alterations in the uterine spiral arteries and the

failure of their remodeling in preeclampsia.
Morphology
The placenta reveals various microscopic changes, most of which reflect malperfusion,
ischemia, and vascular injury. These include
(1) infarcts, which are larger and more numerous that those that may be seen in normal
full-term placentas,
(2) (2) exaggerated ischemic changes in the chorionic villi and trophoblast, consisting of
increased syncytial knots,
(3) (3) frequent retroplacental hematomas due to bleeding and instability of
uteroplacental vessels, and
(4) (4) abnormal decidual vessels, which may show thrombi, lack of normal physiologic 3
conversion, fibrinoid necrosis, or intraintimal lipid deposition (acute atherosis).

Changes involve: Liver (focal hemorrhages and necrosis), kidneys (renal cortical necrosis),
brain (microscopic foci of hemorrhage along with small-vessel thromboses), the heart and
the anterior pituitary.
Clinical Features.
Preeclampsia most commonly
• starts after 34 weeks of gestation but begins earlier in women with hydatidiform mole or preexisting
kidney disease, hypertension, or coagulopathies.
• hypertension and edema, with proteinuria.
• Headaches and visual disturbances are serious events = severe preeclampsia, often requiring delivery.
Eclampsia is heralded by central nervous system involvement, including convulsions and eventual
coma.
For term pregnancies, delivery is the treatment of choice regardless of disease severity.
In preterm pregnancies,
• the mild disease can be managed expectantly by closely monitoring the mother and fetus.
• severe preeclampsia with maternal end-organ dysfunction, fetal compromise, or the HELLP syndrome
are indications for delivery regardless of gestational age.
Antihypertensive therapy does not affect the disease course or improve outcomes.
Proteinuria and hypertension usually disappear within 1 to 2 weeks after delivery except when they
predate the pregnancy.
Although in most instances preeclampsia has no lasting sequelae, recent studies indicate that about 20% of
affected women develop hypertension and microalbuminuria within 7 years of a pregnancy complicated
by preeclampsia. There is also a twofold increase in the long-term risk of vascular diseases of the heart
and the brain.
HYDATIDIFORM MOLE

Characterized histologically by
• cystic swelling of the chorionic villi and
• variable trophoblastic proliferation.
The most important reason for the correct recognition of moles is that they are
associated with an increased risk of persistent trophoblastic disease (invasive
mole) or choriocarcinoma.

Diagnosis in the past was made in most patients in the fourth or fifth month
of pregnancy (vaginal bleeding, prune juice-like discharge may occur).

Currently, hydatidiform moles are being diagnosed at earlier gestational ages

due to routine ultrasound (US)

Molar pregnancy can develop at any age (the risk is higher at the far ends
of reproductive life: in teens and between the ages of 40 and 50 years).
Morphology. The classic gross appearance is of a delicate, friable mass of thin-walled, translucent, cystic,
grapelike structures consisting of swollen edematous (hydropic) villi. Fetal parts are frequently seen in
partial moles. On histologic examination complete moles show abnormalities that involve all or most of
the villous tissue. The most impressive abnormality is, however, an extensive trophoblast proliferation that
involves the entire circumference of the villi, in addition to “extravillous” islands of trophoblast
proliferation. The implantation site often displays atypia and an exuberant proliferation of implantation
trophoblast. In contrast, partial moles demonstrate villous enlargement and architectural disturbances in
only a proportion of villi.
Histologic distinction of complete mole from partial molar gestations is important. In equivocal cases
immunostaining for p57, a cell cycle inhibitor, may aid the diagnosis. The p57KIP2 gene is maternally
transcribed but paternally imprinted, and shows expression in maternal decidual tissue as well as
cytotrophoblast and stromal cells of the villi, when maternal genetic material is present in the conceptus.
In contrast, since both the X chromosomes in complete moles are derived from the father, there is no
expression of p57 protein in the cytotrophoblast or stromal cells of the villi in complete moles.
Clinical Features
Most women with partial and early complete moles present with spontaneous pregnancy loss or
undergo curettage because of abnormalities in ultrasound showing diffuse villous enlargement
(“snowstorm” or “cluster of grapes” or multiple intrauterine echoes ). In complete moles quantitative
analysis of human chorionic gonadotropin (HCG) shows levels of hormone greatly exceeding those
produced during a normal pregnancy of similar gestational age (β-hCG usually > 100,000 mIU/mL).

The vast majority of moles are removed by thorough curettage. Monitoring serum concentrations of
HCG is necessary to determine the early development of persistent trophoblastic disease or
carcinoma (10%), Therefore, serum HCG levels are usually followed until they fall to and remain at
zero for 6 months to a year.
INVASIVE MOLE
A mole that penetrates or even perforates the uterine wall. There is invasion of the myometrium by
hydropic chorionic villi, accompanied by proliferation of both cytotrophoblast and syncytiotrophoblast

The tumor is manifested clinically by vaginal bleeding and irregular uterine enlargement. It is always
associated with a persistently elevated serum HCG and varying degrees of luteinization of the ovaries.
The tumor responds well to chemotherapy but may result in uterine rupture and necessitate
hysterectomy.
Ectopic Pregnancy; ZK 3 Decidua
HYDATIDIFORM MOLE, PARTIAL; N99
Decidua

Decidua

Trophoblastic
invagination
GESTATIONAL CHORIOCARCINOMA
A malignant neoplasm of trophoblastic cells derived from a previously normal or abnormal pregnancy,
which can even include extrauterine ectopic pregnancy. Choriocarcinoma is rapidly invasive and
metastasizes widely, but once identified responds well to chemotherapy.
Incidence
1 in 20,000 to 30,000 pregnancies in the US. Much more common in some African countries;
In PNG?
50% arise in hydatidiform moles, 25% in previous abortions, approximately 22% in normal
pregnancies (intraplacental choriocarcinoma), with the remainder occuring in ectopic pregnancies.
Very rarely, a nongestational choriocarcinoma may develop from germ cells in the ovaries or the
mediastinum.
Morphology. Classically a soft, fleshy, yellow-white tumor with a marked tendency to form large pale areas
of ischemic necrosis, foci of cystic softening, and extensive hemorrhage. Histologically, it does not produce
chorionic villi and consists entirely of a mixed proliferation of syncytiotrophoblasts and cytotrophoblasts.
Mitoses are abundant and sometimes abnormal. The tumor invades the underlying myometrium,
frequently penetrates blood vessels and lymphatics, and in some cases extends out onto the uterine serosa
and into adjacent structures. Due to rapid growth it is subject to hemorrhage, ischemic necrosis, and
secondary inflammation. In fatal cases metastases are found in the lungs, brain, bone marrow, liver, and
other organs. On occasion, metastatic choriocarcinoma is discovered without a detectable primary in the
uterus (or ovary), presumably because the primary has undergone complete necrosis.
Clinical Features
Widespread metastases are characteristic. Frequent sites of involvement
are the lungs (50%) and vagina (30% to 40%), followed in descending
order of frequency by the brain, liver, and kidney.
The treatment of gestational choriocarcinoma (and other trophoblastic neoplasms) depends on the type
and stage of the tumor and includes evacuation of the contents of the uterus, surgery, and
chemotherapy. The results of chemotherapy for gestational choriocarcinoma are spectacular and result
in nearly 100% remission and a high rate of cures. Many of the cured patients have had normal
subsequent pregnancies and deliveries.
By contrast, nongestational choriocarcinomas are much more resistant to therapy. The difference is
believed to be due to the expression of paternal antigens in gestational choriocarcinomas that can evoke
an immune response from the mother.
Ectopic Pregnancy; ZK 3
Hydatidiform Mole, Partial; N99
CHORIOCARCINOMA, Hydatidiform Mole; N 100_101

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PRESENTING SYMPTOMS IN OBSTETRICS

Bleeding—during pregnancy
Treat as any symptom. In addition, you should build a clear picture of how much blood is being lost, and
when and how it is affecting the current pregnancy.
After establishing an exact timeline and other details about the symptom, ask about the following:
• Exact nature of the bleeding (fresh or old)
• Amount of blood lost
• Number of sanitary pads or tampons used daily
• Presence of clots (and, if present, size of those clots)
• Presence of pieces of tissue in the blood
• Presence of mucoid discharge
• Fetal movement
• Associated symptoms, such as abdominal pain (associated with placental abruption; placenta previa is
painless).
• Possible trigger factors—recent intercourse, injuries
• Any history of cervical abnormalities and the result of the last smear
Some causes of vaginal bleeding in early pregnancy
Ectopic pregnancy
• Symptoms: light bleeding, abdominal pain, fainting if pain and blood loss is severe
• Signs: closed cervix, uterus slightly larger and softer than normal, tender adnexal mass, cervical motion
tenderness
Threatened miscarriage
• Symptoms: light bleeding; sometimes cramping, lower abdominal pain
• Signs: closed cervix, uterus corresponds to dates; sometimes uterus is softer than normal
Complete miscarriage
• Symptoms: light bleeding; sometimes light cramping, lower abdominal pain and history of expulsion of
products of conception
• Signs: uterus smaller than dates and softer than normal; closed cervix
Incomplete miscarriage
• Symptoms: heavy bleeding; sometimes cramping lower abdominal pain, partial expulsion of products of
conception
• Signs: uterus smaller than dates and cervix dilated
Molar pregnancy
• Symptoms: heavy bleeding, partial expulsion of products of conception that resemble grapes; sometimes
nausea and vomiting, cramping lower abdominal pain, history of ovarian cysts
• Signs: dilated cervix, uterus larger than dates and softer than normal
Information adapted from World Health Organization, Department of Reproductive Health Research (2007). Vaginal bleeding in early
pregnancy. In Managing Complications in Pregnancy and Childbirth: A Guide for Midwives and Doctors. Geneva: WHO.
Some causes of bleeding in second and third trimesters (>24 weeks) – i.e. antepartum hemorrhage
(APH).
Placenta previa
The placenta is positioned over the lower pole of the uterus, obscuring the cervix. Bleeding is usually
after 28 weeks and often precipitated by intercourse. Findings may include a relaxed uterus, fetal
presentation not in the pelvis, and normal fetal condition.
Placental abruption
This is detachment of a normally located placenta from the uterus before the fetus is delivered. Bleeding
can occur at any stage of the pregnancy. Possible findings include a tense, tender uterus, ↓ or absent
fetal movements, fetal distress, or absent fetal heart sounds.
Bleeding—after pregnancy (i.e. postpartum hemorrhage, or PPH).
• Primary PPH:>500 mL blood loss within 24 hours following delivery
• Secondary PPH:any excess bleeding between 24 hours and 6 weeks post-delivery (no amount of blood is
specified in the definition.)
Take a full history as for bleeding during pregnancy. Ask also about symptoms of infection, an important
cause of secondary PPH.
Some causes of postpartum hemorrhage
Primary
• Uterine atony (most frequent cause)
• Genital tract trauma
• Coagulation disorders
• Retained placenta
• Uterine inversion
• Uterine rupture
Secondary
• Retained products of conception
• Endometritis
• Infection
Risk factors for postpartum hemorrhage include placental abnormalities, polyhydramnios, prolonged labor,
very rapid labor, multiple gestation, previous PPH or APH, preeclampsia, coagulation abnormalities, genital
tract lacerations, and small maternal stature.
Abdominal pain
A full pain history should be taken, including site, radiation, character, severity, mode and rate of onset,
duration, frequency, exacerbating factors, relieving factors, and associated symptoms.
Take a full obstetric history and systems review. Ask especially about a past history of preeclampsia, preterm
labor, peptic ulcer disease, gallstones, appendectomy, and cholecystectomy.
Remember that the pain may be unrelated to pregnancy, so keep an open mind!
Causes of abdominal pain in pregnancy include the following:
• Obstetric: preterm or term labor, placental abruption, ligament pain, symphysis pubis
dysfunction,preeclampsia or HELLP (Hemolysis, Elevated Liver enzyme levels, Low Platelet count) syndrome,
acute fatty liver of pregnancy
• Gynecological: ovarian cyst rupture, torsion, hemorrhage, uterine fibroid degeneration
• Gastrointestinal: constipation, appendicitis, gallstones, cholecystitis, pancreatitis, peptic ulceration
• Genitourinary: cystitis, pyelonephritis, renal stones, renal colic

Labor pain
This is usually intermittent and regular in frequency and associated with tightening of the abdominal wall.
Minor symptoms of pregnancy
These so-called minor symptoms of pregnancy are often experienced by many women as normal, physiological changes
occur. This is not to say that they should be ignored, as they may point to pathology.
• Nausea and vomiting: severity varies greatly and is more common in multiple pregnancies and molar pregnancies.
Persistence of vomiting may suggest pathology such as infections, gastritis, biliary tract disease, or hepatitis.
• Frequent urination: an expected finding in pregnancy, it does not exclude the possibility of urinary tract infection.
• Heartburn/gastroesophageal reflux: Heartburn is a frequent complaint during pregnancy due partially to compression of
the stomach by the gravid uterus.
• Constipation: often secondary to ↑ progesterone. It improves with gestation.
• Shortness of breath: due to dilatation of the bronchial tree secondary to ↑ progesterone. Peaks at 20–24 weeks. The
growing uterus also has an impact. Other possible causes (such as PE) need to be considered.
• Fatigue: very common in early pregnancy, peaking at the end of the first trimester. Fatigue in late pregnancy may be due
to anemia.
• Insomnia: due to anxiety, hormonal changes, and physical discomfort
• Pruritus: generalized itching in the third trimester may resolve after delivery. Biliary problems should be excluded.
• Hemorrhoids: may resolve after delivery
• Varicose veins: especially at the feet and ankles
• Vaginal discharge: exclude infection and spontaneous rupture of the membranes.
• Pelvic pain: stretching of pelvic structures can cause ligament pain that resolves in the second half of the pregnancy.
Symphysis-pubis dysfunction causes pain on abduction and rotation at the hips and on mobilization.
• Backache: often first develops during the fifth to seventh months of pregnancy
• Peripheral paresthesias: fluid retention can lead to compression of peripheral nerves, such as carpal tunnel syndrome.
Other nerves can be affected, e.g., lateral cutaneous nerve of the thigh.
Hypertension
Hypertension is a common and important problem in pregnancy. You should be alert to the possible symptoms
that can result from it, such as headache, blurred vision, vomiting, and epigastric pain after 24 weeks,
convulsions, or loss of consciousness.

Pregnancy-induced hypertension
• Two readings of diastolic blood pressure 90–110, systolic BP >140, 4 hours apart after 20 weeks gestation; no
proteinuria

Mild proteinuric pregnancy-induced hypertension/preeclampsia

• Two readings of diastolic blood pressure 90–110, systolic BP >140, 4 hours apart after 20 weeks gestation,
and proteinuria 1–2+

Severe proteinuric pregnancy-induced hypertension/preeclampsia

• Diastolic blood pressure 110 or greater after 20 weeks’ gestation and proteinuria 3+.
• Other symptoms may include hyperreflexia, headache, clouding of vision, oligura, abdominal pain,
pulmonary edema. There may be evidence of HELLP syndrome.

Eclampsia
• Convulsions associated with raised blood pressure and/or proteinuria beyond 20 weeks gestation. The
patient may be unconscious.