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References
1. Ville Y, Cooper M, Revel A, Frydman R,
Nicolaides KH. Development of a training
model for ultrasound-guided invasive
procedures in fetal medicine. Ultrasound
Obstet Gynecol 1995;5:180–183
2. Timor-Tritsch IE, Yeh MN. In vitro training
model for diagnostic and therapeutic fetal
intravascular needle puncture. Am J Obstet
Gynecol 1987;157:858–859
3. Wapner R. Chorionic villous sampling.
In: Santoyala-Forgas J, Lemery D (eds)
Interventional ultrasound in obstetrics,
gynecology and the breast. Blackwell,
Oxford, 1998:45–59
4. Jackson L, Wapner R, Barr-Jackson M.
Chorionic villus sampling (CVS) is not
associated with an increased incidence of
limb reduction defects. Abstract for the
American Society of Human Genetics 43rd
Meeting, New Orleans, LA, October 1993
5. Brambati B, Oldrini A, Lanzani A.
Transabdominal chorionic villus sampling: a
freehand ultrasound guided technique. Am J
Obstet Gynecol 1987;157:134–142
6. MRC Working Party on the Evaluation of
Chorionic Villus Sampling. MRC European
trial of chorionic villus sampling. Lancet
1991;337:726–741
7. Canadian Collaborative CVSAmniocentesis. Clinical trial of chorionic
villous sampling and amniocentesis. Lancet
1991;337:1491–1509
8. Tabor A, Madsen M, Obel EB, Philip J,
Bang J, Noorgard Pedersen B. Randomised
controlled trial of genetic amniocentesis in
4606 low-risk women. Lancet 1986;i:1287
9. Nicolaides KH, Brizet ML, Patel F,
Snijders R. Comparison of chorion villus
sampling and early amniocentesis for
karyotyping in 1,492 singleton pregnancies.
Fetal Diagn Ther 1996;11:9–15
10. Kappel B, Nielsen J, Brogaard Hansen K,
Mikkelsen M, Therkelsen AAJ. Spontaneous
abortion following midtrimester
amniocentesis. Clinical significance of
placental perforation and blood-stained
amniotic fluid. Br J Obstet Gynaecol
1987;94:50
11. Andreasen E, Kristoffersen T. Incidence of
spontaneous abortion after amniocentesis:
influence of placental localisation and past
obstetric and gynecologic history. Am J
Perinatol 1989;6:268
12. Ville Y, Nicolaides KH. Prenatal diagnosis
and therapeutic techniques in twin
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pregnancies. In: Santoyala-Forgas J,
Lemery D (eds) Interventional ultrasound
in obstetrics, gynecology and the breast.
Blackwell, Oxford, 1998: 146–150
13. Daffos F, Capella-Pavlowsky M, Forestier F.
A new procedure for fetal blood sampling
in utero: preliminary results of 53 cases. Am
J Obstet Gynecol 1983;146:985–998
14. Ghidini A, Sepulveda W, Lockwood C,
Romero R. Complications of fetal
blood sampling. Am J Obstet Gynecol
1993;168:1339–1344
15. Perry KG, Hess LW, Roberts WE et al.
Cordocentesis by maternal fetal fellows:
the learning curve. Fetal Diagn Ther
1991;157:858–859
16. Moise KJ. Intrauterine transfusion with
red cells and platelets. West J Med
1993;159:318–324
17. Evans MI, Sacks AJ, Johnson MP, Robichaux
AG, May M, Moghissi KS. Sequential
invasive assessment of fetal renal function
and intrauterine treatment of fetal
obstructive uropathies. Obstet Gynecol
1991;77:54–55
18. Rodeck CH, Nicolaides KH. Ultrasound
guided invasive procedures in obstetrics.
Clin Obstet Gynecol 1983;10:515–540
19. Yamamoto M, El Murr L, Robyr l, Leleu F,
Takahashi Y, Ville Y. Incidence and impact
of perioperative complications in 175
fetoscopy-guided laser coagulations of
chorionic plate anastomoses in fetofetal
transfusion syndrome before 26 weeks
of gestation. Am J Obstet Gynecol
2005;193:1110–1116
20. Firth H. Chorion villus sampling and limb
deficiency – cause or coincidence? Prenat
Diagn 1997;17:1313–1330
21. Gonce A, Borrel A, Fortuny A et al.
First-trimester screening for trisomy 21
in twin pregnancy: does the addition of
biochemistry make an improvement? Prenat
Diagn 2005;25:1156–1161
22. Stewart KS, Johnson MP, Quintero RA,
Evans MI. Congenital abnormalities in
twins: selective termination. Cur Opin
Obstet Gynecol 1997;9:136–139
23. Westgren M, Selbing A, Stangenberg M.
Fetal intracardiac transfusions in patients
with rhesus isoimmuniation. BMJ
1988;296:885–886
24. Evans MI, Ciorca D, Britt DW, Fletcher JC.
Update on selective reduction. Prenat Diagn
2005;25:807–813
Invasive procedures in obstetrics
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Multiple pregnancies
Kurt Hecher Werner Diehl
ABSTRACT
Detection of the number of fetuses, chorionicity and amnionicity should be
achieved during the first-trimester scan. Invasive diagnostic techniques such as
chorion villous sampling and amniocentesis may be used to obtain karyotypes of
all fetuses and this should be discussed individually with the couple, taking into
account the risk to benefit ratio, i.e. the procedure-related risk of a miscarriage and
the individual risk for chromosomal abnormalities.
Fetal growth impairment in dichorionic twins will more often reflect
uteroplacental insufficiency as compared to singleton pregnancies and fetal
surveillance including Doppler ultrasound should be intensified. In monochorionic
twins, one should be aware of the risk for the development of twin–twin transfusion
syndrome, and amniotic fluid volumes and their relation to bladder filling of both
twins should be monitored from the early stages of gestation onwards.
Monoamniotic twins, occurring in 5% of monochorionic gestations, show the highest
risk for structural anomalities and poor outcome. The assessment of monoamniotic
pregnancies implies close fetal monitoring and detection of cord implications.
Conjoined twins represent the most severe form of splitting disorders in
monozygotic twins. They occur in 1% of monochorionic pregnancies, and their
outcome depends mainly on the site of conjoining and the organs involved.
KEYWORDS
Amnionicity, chorionicity, early risk assessment, fetal surveillance, multiple
pregnancy, zygocity.
INTRODUCTION
Perinatal mortality and morbidity rates are increased three to seven times in twin
pregnancies,8 as compared to singleton gestations. Although twin pregnancies
247
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account only for 2.5% of the population, they are responsible for up to 12.6% of
the overall perinatal mortality rate.28 Additionally, assisted reproduction techniques have led to an increase in the incidence of twinning with almost 50% of
the twins resulting from infertility treatment.22 The application of such techniques has also contributed to an increase in the incidence of multiple pregnancies of a higher grade (e.g. triplets, quadruplets). The fact that this population
also shows a higher number with women at an advanced age, with an increased
age-related risk for chromosomal abnormalities and for impairment of the
uteroplacental perfusion, also contributes to the high risk in this collective.
Approximately two-thirds of twin pregnancies are dizygotic and therefore
dichorionic and diamniotic. One-third is monozygotic; of these, one-third is dichorionic (splitting occurring at less than 4 days after conception) and the other twothirds are monochorionic and diamniotic (splitting occurring from days 4 to 8
after conception). A later splitting (9–13 days) leads to the occurrence of monoamniotic twins, and a division beyond the 14th day to conjoined twins.
It is known that mortality and morbidity rates are higher in monochorionic
16,17,32
twins.
Ultrasound in obstetrics and gynaecology
Conditions unique to them, such as twin–twin transfusion syndrome
(TTTS), reverse twin arterial perfusion sequence and monoamniotic pregnancies, are responsible for an increased risk of adverse perinatal outcome. Therefore,
early assessment of chorionicity and amnionicity plays an important role in the
risk stratification of multiple pregnancies and has practical consequences for the
management of those pregnancies. Due to the high-risk nature of multiple pregnancies fetal surveillance should be undertaken in appropriate intervals.
248
FIRST-TRIMESTER ULTRASOUND
PREGNANCY DATING
The crown–rump length (CRL) of the fetuses is the most important ultrasound
parameter for dating of the pregnancy and, if necessary, to correct the gestational
age in cases with a non-reliable menstrual history. The onset of early growth
retardation in one of the fetuses may indicate a higher risk for chromosomal
abnormalities.
Normally, the CRLs correlate between co-twins, although some degree of vari-
ability has been observed in multifetal pregnancies.
19,34
Measurement of the CRL
can easily be done at the time of the first-trimester scan (11–14 weeks of gestation). Later in pregnancy, correction of gestational age should be avoided, since
growth curves in multiple pregnancies differ from those in singleton pregnancies
beyond the second trimester.
NUMBER OF FETUSES
The currently widespread availability of transvaginal ultrasound enables early
detection of multiple pregnancies and their localization. Additionally, it allows
precise assessment of chorionicity and amnionicity. The diagnosis of twins with
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the observation of two embryos may be confusing for the parents, if there is
subsequent disappearance of one of them during further examinations (vanishing twin phenomenon). The spontaneous incidence of this phenomenon in multiple pregnancies has been reported to be between 21%21 and 50% in triplets23
and occurs most frequently during the first 7 weeks of pregnancy and never
beyond 14 weeks. Some authors consider monochorionic twinning as a risk factor for neurological abnormalities in the surviving twin after disappearance of
one embryo, since this form of placentation may predispose to vascular events
in early fetal life.6 After 10 weeks of gestation a reliable identification of the
number of fetuses and their chorionicity may be expected even with transabdominal ultrasound (Fig. 13.1).
Multiple pregnancies
Fig. 13.1 Assessment of chorionicity. (A) Transverse view of the uterus at 12 weeks of
gestation, showing two separate amniotic cavities with two placentae (dichorionicity)
and two fetuses. (B) Intertwin membranes in trichorionic triplets at 20 weeks of gestation
showing the lambda signs at the placental base. (C) The confluence of the intertwin
membranes in a trichorionic triplets pregnancy at 12 weeks of gestation. (D) Pentachorionic
quintuplets pregnancy at 10 weeks of gestation.
249
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CHORIONICITY AND AMNIONICITY
For reasons of risk stratification in multiple pregnancies, one of the most important goals of early ultrasound in this population is the determination of chorionicity and amnionicity.
separate gestational sacs indicates dichorionicity. From 10–14 weeks onwards, a
thick septum and a triangular tissue projection at the placental base of the separating membrane (lambda sign) predict dichorionicity27 (see Fig. 13.1; Fig. 13.2).
This is due to four layers of the intertwin membrane: amniotic and chorionic
layers of fetus 1 and chorionic and amniotic layers of fetus 2. Monochorionic
twins show a very thin intertwin membrane (only two amniotic layers) and no
lambda sign, since there are no chorionic layers between the two amniotic layers of the membrane (see Fig. 13.2). Misdiagnosis of monoamniotic twins due
to visualization of a single gestational sac may occur, if identification of the thin
separating membrane is difficult. Later during pregnancy, identification of fetal
Ultrasound in obstetrics and gynaecology
35–37
Early in gestation (6–9 weeks), the presence of two
250
Fig. 13.2 The lambda sign. (A,C) The lambda sign (arrows) at the placental base of the
intertwin membrane in dichorionic pregnancies at 15 weeks (A) and 10 weeks (C) of gestation.
(B,D) Absence of the lambda sign (arrows) in monochorionic diamniotic twin pregnancies at
16 weeks (B) and 20 weeks (D) of gestation. Note the thin intertwin membrane (M) and the
common anterior placenta (PL).
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gender may also be helpful in the assessment of chorionicity, although overall
two-thirds of twins are of the same sex: one-third consists of all monochorionic
twins and the other one of 50% of all dichorionic twins. Discordant sex indicates
dichorionicity.
Regarding amnionicity, the lack of an intertwin membrane, despite careful scanning of the whole amniotic cavity, leads to the diagnosis of monoamniotic twinning.25 The presence of a unique yolk sac also indicates
monoamnionicity.
7
NUCHAL TRANSLUCENCY
Between 10 and 14 weeks of gestation, it is possible to assess the woman's individual risk for chromosomal abnormalities combining the measurement of the
nuchal translucency (NT) and maternal age.29 However, in multiple pregnancies,
this risk calculation has to take into account several aspects.
the risk for a chromosomal abnormality is calculated individually for each twin
in the same fashion as for singleton fetuses. However, the risk that at least one
fetus of this pregnancy is affected is the summation of the two individual risks,
which is twice as high as in a singleton pregnancy if the individual risks are almost
the same. Squaring the singleton risk derives from the risk that both fetuses are
affected. In monozygotic twins, the risk for a chromosomal abnormality is the
same as that of a singleton pregnancy, but in cases of an abnormal karyotype both
fetuses are affected. A higher false-positive rate for risk calculations of chromosomal defects in monochorionic twins can be explained due to an early manifestation of a twin–twin transfusion syndrome (TTTS), where an increased NT in
at least one fetus has been shown as a marker for prediction of TTTS.26 Increased
NT in the recipient fetus as a consequence of hypervolaemia is considered as an
early sign for TTTS and the risk for the development of the syndrome is increased
almost fourfold.
The nature of the estimation of a likelihood, the options of invasive diagnostic
procedures for the assessment of the fetal karyotype and the possible consequences
of an abnormal result have to be explained in detail during the counselling. The
knowledge of chorionicity is paramount for risk estimation, the decision regarding
the technique of invasive testing and its consequences.
38,39
In dizygotic twins,
Multiple pregnancies
INVASIVE DIAGNOSTIC PROCEDURES
Chorionic villous sampling (CVS) can be done as early as 10–12 weeks of gestation and has then a risk for a procedure-related pregnancy loss of about 1%. In
another 1% of cases the results may be unclear, for instance due to the presence
of mosaicism in the chorionic tissue. However, studies have established comparable risks to those of second-trimester amniocentesis, if performed by experienced
operators.
In dichorionic twins these risks may increase, if double sampling has to be performed to assure obtaining a result for both fetuses. Thus, sampling has optimally
20
251
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to be performed below the umbilical cord insertions of the respective twins.
The possibility of cross-contamination of the sample, when single puncture is
performed, is about 0.6%. Maternal contamination is another problem of CVS,
as well as sampling the same fetus twice, but these problems occur in less than
1% of procedures, as reported in recent studies.
1,31
The advantage of this procedure, which can be performed earlier than amniocentesis, is that in case of a chromosomal defect of one of the fetuses, an earlier selective fetocide with a lower
procedure-related risk for fetal loss (5% versus 16% at 15 weeks or later) may be
performed.
9
If the individual risk for chromosomal abnormalities, calculated by maternal
age and NT, in at least one of the fetuses is greater than 1 in 50, it may be preferable to perform a CVS for fetal karyotyping. For pregnancies with a lower combined risk calculation, an amniocentesis after 15 weeks of gestation may be more
appropriate.
24
Also, with amniocentesis in dichorionic twins, obtaining a result for both fetuses
has to be guaranteed. This can be achieved by either puncturing each amniotic sac
separately with two needle insertions or with only one uterine needle insertion
Ultrasound in obstetrics and gynaecology
by crossing the intertwin membrane and sampling amniotic fluid separately from
each sac under ultrasound guidance. In structurally normal monochorionic twins,
single sampling may be sufficient, since monozygotic fetuses can be expected to
be genetically identical.
252
GROWTH DISCREPANCY AND FETAL MONITORING
The longitudinal assessment of fetal growth in both twins gives valuable information about their intrauterine well-being. In dichorionic twins biometry should be
performed at monthly intervals,28 keeping in mind the higher risk for intrauterine
growth retardation, as compared to singleton pregnancies. Beyond the 20th week
of gestation even normal twin fetuses may show smaller biometric measurements
than singletons and, therefore, specially adapted growth curves should be used.15
If the growth curve of one of the fetuses shows the tendency to approach the
5th percentile for gestational age, control intervals should be shortened to every
second week. In small-for-gestational age fetuses, the benefits of Doppler ultrasound should be used. Serial ultrasound examinations from the second trimester
onwards, including Doppler velocimetry if necessary, represent the most reasonable antenatal assessment of twin pregnancies.
However, in monochorionic twins, due to the existence of placental vascular
anastomoses which continuously allow interfetal blood flow, ultrasound examinations should be performed at shorter intervals, every 2–3 weeks. Attention
should be drawn to the amounts of amniotic fluid in each amniotic cavity and
the bladder filling of each fetus. An early TTTS can be recognized following these
criteria. The development of growth restriction of one fetus may result as a consequence of TTTS, but also as a consequence of placental insufficiency.16 Doppler
assessment of the fetal circulation may help to distinguish between these two
conditions.
33
11
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MALFORMATIONS AND FETAL DEMISE
In general, the risk for malformations in twin pregnancies is elevated. It is increased
in monochorionic twins and in monoamniotic twins it is reported to be as high as
4,25,40
38%,
the process of splitting itself.
presence of a chromosomal abnormality in one of the fetuses, is about 10%.
Spontaneous intrauterine death of one twin usually does not affect the co-twin,
because there are no vascular anastomoses in dichorionic placentae. However, the
situation is completely different in monochorionic twins. After a single intrauterine death there is a high risk for damage of the co-twin, due to the presence of placental vascular anastomoses.3 As a consequence of an acute loss of blood towards
the dying fetus or immediately after its death, a hypotensive and anaemic episode
may occur in the co-twin and subsequently lead to its death or to neurological
damage (in 20–30%). This has also to be taken into account if one of the fetuses
of a monochorionic twin pregnancy shows structural anomalies and selective termination is considered. More recently, invasive techniques have been developed
to occlude completely the umbilical vessels by laser or bipolar coagulation of the
umbilical cord, to avoid acute haemodynamic imbalance in the co-twin.
where the inherent mechanism for the malformation may be related to
The risk for fetal loss in dichorionic twins after selective fetocide, due to the
10
Multiple pregnancies
TWIN–TWIN TRANSFUSION SYNDROME
In 10–15% of monochorionic pregnancies, severe midtrimester TTTS develops,
which is associated with a mortality rate of 80–90% if left untreated.
underlying cause for the development of the syndrome is the presence of vascular
anastomoses in all monochorionic placentae. As a consequence of the different
types of anastomoses (arteriovenous, arterioarterial and venovenous) and the blood
flow direction in the arteriovenous anastomoses, a net imbalance in intertwin
blood flow may ensue. The recipient fetus becomes hypervolaemic and polyuric,
leading to polyhydramnios, and may develop congestive heart failure due to cardiac overload. The donor fetus becomes hypovolaemic and anuric, leading to severe
oligo- and anhydramnios. Premature rupture of membranes, owing to the extreme
polyhydramnios, miscarriage and extremely premature delivery, as well as intrauterine death, are the main complications contributing to the high perinatal mortality.
The diagnostic ultrasound criteria for TTTS are the observation of a single
monochorionic placenta, the presence of polyhydramnios in the amniotic cavity
of the recipient fetus, who shows also a distended bladder (Fig. 13.3), and severe
oligo- or anhydramnios in the amniotic cavity of the donor fetus, who shows only
a weak or no bladder filling at all. Due to the absence of amniotic fluid in the
donor's amniotic sac, the intertwin membrane may not be visible as it is adherent
to the fetus who is pressed against the uterine wall or the placenta (stuck twin)
(Fig. 13.4). The absence of a visible intertwin membrane may lead to the misdi-
agnosis of monoamniotic twins. TTTS may develop in the early second trimester
(at 16 or 17 weeks of gestation) and within a short period of time (1 or 2 weeks).
41–43
The
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Fig. 13.3 Twin–twin transfusion syndrome. Note the distended (polyuric) bladder of the
recipient twin and the massive polyhydramnios (gestational age 21+5 weeks; deepest vertical
pool was 14 cm).
Ultrasound in obstetrics and gynaecology
254
Fig. 13.4 Twin–twin transfusion syndrome. The ‘stuck twin’ phenomenon: due to
anhydramnios the donor twin (circle) is stuck to the uterine wall.
Doppler assessment of blood flow in the umbilical arteries and the ductus
venosus of both twins provides valuable information about the fetal cardiovascular condition. In the recipient fetus, signs of congestive heart failure, such as
abnormal ductus venosus flow, tricuspid and mitral regurgitation, fetal hydrops
(ascites, pleural effusions, skin oedema), reduce the probability of survival.
In the donor fetus, an increased placental resistance with absent or reversed end diastolic flow in the umbilical artery is associated with a lower survival rate.
33
As fetal viability is not yet achieved during the second trimester of pregnancy,
delivery is not a realistic option for the management of these cases. There are
two options for therapy: serial amniodrainages and percutaneous fetoscopic laser
coagulation of the placental vascular anastomoses. The latter offers a causal therapeutic approach and an overall survival rate of 68% and 81% of pregnancies with
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at least one survivor can be achieved.18 During laser surgery a mean of 5–6 anastomoses can be identified and coagulated. In all cases arteriovenous anastomoses
from donor to recipient are present, with the majority of cases also showing anastomoses shunting in the opposite direction, and arterioarterial anastomoses are
present in about one-third of pregnancies with TTTS.
12
After laser therapy, follow-up scans are performed at weekly intervals first and
then every second week, as normally done for fetal surveillance in monochorionic
twins, drawing attention to the amounts of amniotic fluid, bladder fillings, growth
patterns and Doppler flow velocity waveforms of both fetuses.
TWIN REVERSED ARTERIAL PERFUSION
The prevalence of twin reversed arterial perfusion (TRAP) or acardiac twins is
about 1 in 35,000 pregnancies. The presence of an arterioarterial and a venovenous anastomosis between both cord insertions in monochorionic twins may
lead to a reversed perfusion of one fetus, if one pulse wave predominates over the
other early in gestation. In the reversely perfused fetus there is no cardiac development at all or only a rudimentary heart tube can be detected. The development
of the upper part of the body is also severely impaired and most of the acardiac
fetuses also show acrania and severe hydrops.
This condition represents a high risk for heart failure and intrauterine demise or
preterm delivery of the pumping twin. The typical ultrasound appearance of the
acardiac twin is a hydropic mass without a heartbeat or only with a rudimentary pulsatile cardiac structure. Colour Doppler sonography reveals the reversed perfusion
via the single umbilical artery (Fig. 13.5). These ultrasound features are unique to this
disorder and may be detected in the first trimester of pregnancy. Treatment strategies
range from vessel obliteration by intracardiac application of alcohol to fetoscopic ligation and bipolar or laser coagulation of the umbilical cord of the acardiac twin.
Multiple pregnancies
Fig. 13.5 Twin reversed arterial perfusion (TRAP sequence). (A) The hydropic acardiac
twin with multiple malformations at 20 weeks of gestation. (B) Colour Doppler depicts the
reversed arterial perfusion (blue) to the acardiac twin and the returning blood flow via the
umbilical vein (red) to the pumping twin.
255