Placental Development, Indications for and Methods of Examination
Section 6 -
Phyllis C. Huettner, M.D.
Multiple gestation has always been an unusual and therefore fascinating occurrence. From a
medical point of view, twin and higher order multiple gestations are associated with much higher rates of
mortality and morbidity compared to singleton gestations. Twins account for 12.6% of perinatal mortality
even though they make up only 2.5% of the population. Some forms of morbidity that are more common in
multiple gestation, such as low birth weight, anomalies, malformations and cerebral palsy, can be seen in
any type of gestation, whereas other complications, such as twin-twin transfusion syndrome, occur only in
multiple gestations where vascular anastomoses in the placenta result in shared circulation between the
twins. Despite the increased incidence of twinning with the widespread use of assisted reproductive
technologies and our appreciation of the complications to which they are prone, there are no prospective,
randomized studies that address the important issue of how to optimally follow twin pregnancies for
complications throughout gestation.
Twins make up about 1 in 90 pregnancies but this figure may not be precise because some
gestations thought to be twins in the early first trimester will be singleton gestations by the end of
the second trimester. Assisted reproductive technologies (ART) have resulted in a dramatic increase in
multiple gestations, particularly triplets and higher order multiples. It is estimated that today about
50% of twins are conceived through ART.
About 70% of twins are dizygous (fraternal) resulting from the fertilization of two ova.
About 30% of twins are monozygous (identical) resulting from the fertilization of a single ovum that
splits very early in gestation. The rates of monozygous twinning are constant whereas the rates of
dizygous twinning vary widely among different populations reflecting a genetic tendency to ovulate more
than one ovum.
The complications that twins experience are not related so much to whether they are
monozygous or dizygous, but more specifically to the type of placentation they have. All dizygous twins
exhibit diamniotic dichorionic placentation. Monozygous twins, on the other hand, may exhibit any type
of placentation. About 25% are also diamniotic dichorionic but 75% are monochorionic (MC). The type of
placentation seen in monozygous twins is determined by when in gestation the split occurs. If division
occurs before 4 days post fertilization diamniotic dichorionic (DC) placentation will result. If
division occurs between 4 and 8 days post fertilization diamniotic MC placentation will result. If
division occurs after 8 days post-fertilization monoamniotic placentation, sharing a single sac with no
dividing membranes, results. If division occurs after 13 days post fertilization the twin fetuses will
From a practical point of view, dichorionic placentas can be seen in dizygous or in
monozygous twins but monochorionic placentas only occur in monozygous twins. However, a recent report by
Souter et al and further explained in an accompanying editorial by Redline, illustrate a case of dizygous
twins, male and female, with monochorionic placentation. These twins were conceived through ART. So
while monochorionic placentas are almost always associated with monozygous
twins, very rarely twins conceived through ART could have a monochorionic placenta but be dizygotic if
the developing conceptus fuses or aggregates abnormally very early in development.
Diamniotic DC placentas have two separate sacs separated by dividing membranes that are thick
and opaque. The placental parenchyma may be separate or fused. During examination, it is important to
note the relative proportions of total placental parenchyma associated with each sac. Microscopic
sections of the dividing membranes show fused amnion and chorion. The vessels of the two twin
territories may approach the dividing membranes but they do not cross. With very rare exceptions, no
vascular anastomoses are seen in DC placentation.
In diamniotic MC placentas, the dividing membranes are very thin and translucent.
Microscopically one sees fused amnion with no chorion. The vessels of diamnionitic MC placentas show
anastomoses in 85% to 100% of cases. The anastomoses may involve the surface vessels or deeper vessels
within the parenchyma. Injection studies to demonstrate vascular anastomoses should be performed in all
monochorionic placentas. These studies must be performed on fresh placentas. This is discussed in more
detail under twin-twin transfusion. Prenatal ultrasound is able to correctly diagnose about 91% of MC
twins and 96% of DC twins by measuring the thickness of the dividing membranes. This is most accurately
done in the first trimester. The chorionicity of multiple gestations of higher order should be
determined in the same way. For example the dividing membranes between A and B, B and C and A and C
should be examined in triplets.
The complication rate for twins is highly related to the type of placentation and is much
higher for most complications in MC twins. MC twins have a 12.2% fetal loss rate before 24 weeks
gestation compared to just 1.8% for DC twins. The perinatal mortality rate for MC twins is 2.8% and for
DC twins is 1.6%. About 9.2% of MC twins are delivered before 32 weeks compared to 5.6% of DC twins.
Low birth weight (<5th percentile) in both twins complicates 7.5% of MC twin gestations but
only 1.7% of DC gestations. Interestingly there is little difference in the percentage of twin pairs
with discordant growth (about 12%) in DC and MC gestations, emphasizing that not all discordant growth is
due to the TTTS or vascular anastomoses, both of which only occur in MC twins. Monoamniotic twins have
an even higher rate of complications than MC twins with a mortality rate between 28% and 70% due largely
to prematurity and cord accidents in these twins that share an amniotic sac.
Case 7: Twin-Twin Transfusion Syndrome (TTTS)
TTTS is a devastating condition that occurs in about 15% of MC
twins. It is the result of a chronic imbalance of blood flow across the two placental circulations. One
twin, referred to as the donor, supplies the blood for both twins resulting in hypovolemia, oliguria and
oligohydramnios in this twin. The other twin is the recipient of this extra blood flow and experiences
circulatory overload resulting in polyuria, polyhydramnios and eventually hydrops fetalis. Often, but
not always, the twins are discrepant in size.
The pathophysiology of TTTS is complex but always involves vascular anastomoses between the
two circulations. Vascular anastomoses can be artery to artery (A-A), vein to vein (V-V) or artery to
vein (A-V). A-A and V-V anastomoses are usually superficial and bidirectional. More important
physiologically are A-V anastomoses. These are present at the capillary level and therefore are deep in
the parenchyma, not visible on gross examination. These allow blood to flow in only one direction and
therefore can result in a chronic imbalance of the blood flow. One important clue to the presence of A-V
anastomoses is the presence of a superficial artery or vein without a pair on the surface of the other
twin. A recent study has demonstrated, however, that a high percentage of MC twins have deep A-V
anastomoses without an unpaired superficial artery or vein to serve as a clue to its presence.
Anastomoses can be demonstrated by injecting air, milk or water into a vessel in one twin's circulation
and observing whether the material appears in vessels in the other twin's circulation and in which type
of vessels. These injection studies must be performed before fixation of the placenta. A recent study
has reported the use of color-coded gelatin-dye mixtures which have the advantage of remaining in tissue
after sectioning allowing determination of the size of vessels involved in anastomoses. Certain types of
vascular anastomoses may be protective. For example, TTTS is present in 58% of twins without A-A
anastomoses but only 5% of cases with A-A anastomoses. It is thought that these large superficial A-A
anastomoses may help "balance out" the circulation and protect against TTTS.
Other factors besides vascular anastomoses may determine whether TTTS will develop and how
severe it will be. Velamentous cord insertion is more common in twins with TTTS, especially in the donor
twin. It is thought that compression of the intramembranous vessels by amniotic fluid in these cases may
contribute to the circulatory imbalance. Dysfunction in the placenta of one twin, such as extensive
infarction, may increase the resistance in that part of the circulation, and also contribute to vascular
The mortality rate from TTTS, if untreated, is 90%. Both twins are at risk. If only one
twin dies it is usually the donor. The donor twin may be anemic or hypoglycemic while the recipient twin
may develop heart failure, hemolytic jaundice, thrombosis from secondary hemoconcentration or
kernictuerus. In fatal cases, the organs of the donor are usually small, pale, and anemic while those of
the recipient are heavy and congested. There may be acute shifts in blood flow at the time of delivery,
however, that may alter the appearances of the infants and their organs such that the donor may appear
plethoric and the recipient may be pale and anemic. Similarly, death of one twin may resolve the TTTS
but may also decrease the resistance in that portion of the placenta causing the live twin to
exsanguinate into the relaxed territory of the dead twin.
The placentas also usually have markedly different pathologic features as well. The placenta
associated with the donor is typically large, bulky and pale with large, edematous villi and increased
nucleated red blood cells. There may be amnion nodosum related to oligohydramnios in this twin. The
placenta associated with the recipient, on the other hand, is typically small, firm and congested.
Treatment options for TTTS are controversial. If the twins are sufficiently mature, delivery
is the best option. Amnioreduction, to balance the volume of amniotic fluid between the twins is
effective in only mild cases and is associated with a 50% mortality in one or both twins and a 16% rate
of severe neurologic abnormalities. Rupture of the dividing membranes has no proven efficacy.
Laser coagulation of the anastomotic vessels of the chorionic plate has proven effective
even in advanced cases and is associated with an overall survival of 71% and only an 8% rate of major
neurologic sequelae. De Paepe et al have recently described their experience with placental findings
after laser ablation. The coagulated vessels show an abrupt interruption in the flow of dye or other
injected materials. In cases laser coagulated less than a month before delivery, there will be vascular
hemorrhage. If more than a month has lapsed since laser coagulation, the absence of anastomoses will be
obvious with an area of increased subchorionic fibrin between the two vascular territories. Organizing
thrombi, hemosiderin and avascular villi were also observed.
Interestingly many major, lethal anomalies are discordant even in MC twins. About 12% of
twins, both DC and MC, will have a greater than 25% difference in fetal weight. Discrepant weight has a
greater mortality rate in MC twins. Causes of discrepant growth include the inequalities in placental
sharing, the quality of implantation in each of the territories and the details of the
angioarchitecture. The type of umbilical cord insertion may also be important. When only one of a pair
of MC twins has a velamentous cord insertion, about half have discordant fetal growth. Discrepant fetal
growth is not a complication in DC twins when only one umbilical cord is velamentously inserted.
Selective termination may be used to treat severe discrepancies in fetal growth, not related
to TTTS in cases of DC twins, but this therapy cannot be applied to MC twins because vascular anastomoses
between the placental circulations puts the remaining fetus at risk.
Acardiac twinning represents a special form of discordant growth. It complicates about 1% of
MC twins. In this condition a second, grossly malformed twin is attached by an umbilical cord to the
placenta. Some of the acardiac twins are amorphous blobs of tissue whereas others show a remarkable
degree of development, lower extremities more so than upper extremities. All of these twins lack a
functioning heart. Usually the cord to the acardiac twin has a single umbilical artery. An A-A
anastomosis in the umbilical cord or in the vessels of the chorionic plate promote blood flow from the
normal twin to the acardiac twin. The blood flows in reverse in the acardiac and returns to the pump
twin by a V-V anastomosis.
There are two main theories of pathogenesis. One is that the reverse flow is caused by
regression of the heart in one twin. The other theory is that acardiac twinning only occurs in those
special cases of MC twins in which the specific A-A and V-V that allow for this reversal of flow are
The acardiac twin is never sufficiently developed to allow for independant survival after
birth. The pump twin is at increased risk of cardiac failure and preterm delivery.
Intrauterine Death of One Twin
As in TTTS when one twin dies, the vascular system of the dead twin loses its resistance and
the live twin may exsanguinate into the relaxed vasculature of the dead twin. This situation is
associated with significant morbidity in the surviving twin that is thought to be related to sudden
hypotension and hypoperfusion of the organs rather than thrombi or embolization into the vessels of the
survivor. It has recently been suggested that the injuries in the survivor are related to the sudden
changes in the placental territory that is now perfused by the live twin.
Placental examination is helpful in documenting and timing an intrauterine death. When one
twin dies weeks earlier than the other, the territory of the dead twin may be much thinner and paler than
that of the live twin. When one twin dies early in gestation, the mummified remnant of the fetus may be
present in the placenta. This is called a fetus papyraceous. Often the compressed gestational sac and
atretic umbilical cord can also be identified. It is particularly important to look for this in cases of
ART, especially when it was known that more than one fetus was present early in gestation.
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