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Conjoined Twins in a Trichorionic Quadruplet Pregnancy after Ovulation Induction with Clomiphene Citrate

Fetal Diagn Ther 2008;24:51–54
DOI: 10.1159/000132407
Received: February 19, 2007
Accepted after revision: March 23, 2007
Published online: May 27, 2008
Conjoined Twins in a Trichorionic
Quadruplet Pregnancy after Ovulation
Induction with Clomiphene Citrate
Inanc Mendilcioglu Mehmet Simsek
Department of Obstetrics and Gynecology, Akdeniz University, School of Medicine, Antalya, Turkey
Key Words
Monozygotic twins ⴢ Conjoined twins ⴢ Quadruplet ⴢ
Nuchal translucency ⴢ Prenatal diagnosis ⴢ Clomiphene
citrate ⴢ Ovulation induction
Objective: We report a case of conjoined twins in a trichorionic quadruplet pregnancy after ovulation induction with
clomiphene citrate for anovulation. Methods: The diagnosis
of a trichorionic quadruplet pregnancy was made in routine
ultrasound at 11 weeks’ gestation. Results: Conjoined twinning was thoracopagus and presented with increased nuchal translucency. Selective termination of the conjoined
twins was performed with potassium chloride injection. The
patient delivered 2 healthy infants after an uneventful follow-up. Conclusion: Monozygotic twinning has increased
with widespread usage of ovulation induction agents and
assisted reproductive techniques. Early detection of conjoined twinning and chorionicity is essential for an optimal
obstetric management and outcome.
Copyright © 2008 S. Karger AG, Basel
Conjoined twinning is a unique abnormality and the
estimated frequency is 1 in 50,000 deliveries [1]. Incomplete splitting of a monozygotic embryo is the generally
accepted theory for embryology of conjoined twinning,
© 2008 S. Karger AG, Basel
Fax +41 61 306 12 34
E-Mail karger@karger.ch
Accessible online at:
however, secondary union of two originally separate
monovular embryonic discs has also been proposed as a
fusion theory [2]. Ovulation induction and assisted reproductive techniques are responsible for most multiple
gestations including not only multizygotic pregnancies
but also monozygotic pregnancies [3]. Conjoined twinning has been reported in twin and triplet pregnancies
after IVF and ICSI [4–9]. Conjoined twinning in a quadruplet pregnancy is an extremely rare condition and has
been reported only in 2 cases which were IVF-ICSI pregnancies [10, 11].
We report a case of conjoined twins diagnosed in an
early quadruplet pregnancy which was managed by selective termination.
Case Report
A 22-year-old woman, gravida 1, para 0, was referred at 11
weeks for conjoined twins in a quadruplet pregnancy occurring
after ovulation induction with clomiphene citrate. Her medical
history was unremarkable except for chronic anovulation. Sonographic evaluation revealed conjoined twins in a trichorionic
quadruplet pregnancy (fig. 1). In one gestational sac, 2 fetuses had
a single thorax and abdomen with two heads which was diagnosed as thoracopagus. Increased nuchal translucency was observed in the conjoined twins (fig. 2). The other 2 embryos were
consistent with gestational weeks and had normal nuchal translucency measurements. The family opted to have selective termination of the conjoined twins. Intracardiac injection of potassium
Inanc Mendilcioglu, MD
Department of Obstetrics and Gynecology, Akdeniz University, School of Medicine
Dumlupinar Bulvari
TR–07070 Arapsuyu/Antalya (Turkey)
Tel. +90 242 243 0450, Fax +90 242 227 4490, E-Mail imendilcioglu@hotmail.com
Fig. 1. Longitudinal view of the conjoined twins in a trichorionic
quadruplet pregnancy.
Fig. 3. Selective termination of the conjoined twins with the needle inserted in the heart (arrow).
chloride was performed with a single insertion at 12 weeks’ gestation (fig. 3). The remaining pregnancy follow-up was unremarkable. Two healthy infants were delivered with cesarean section in
a state hospital at 36 weeks’ gestation.
Fig. 2. Transverse (a) and sagittal (b) views of increased nuchal
translucency in the conjoined twins.
Fetal Diagn Ther 2008;24:51–54
This is the first report of conjoined twinning in a quadruplet pregnancy following ovulation induction without any IVF-ICSI procedure. Two cases were reported as
conjoined twinning in a quadruplet pregnancy. The first
case occurred after transfer of cryopreserved ICSI embryos [10]. The latter was the result of a transfer of fresh
embryos after ICSI with laser-assisted zona hatching [11].
Both cases were thoracopagus and managed with selective embryo reduction. Conjoined twinning in triplets after the IVF-ICSI procedure has been reported in 6 cases
of which 2 cases were following assisted hatching [4–9].
After extensive usage of ovulation induction and assisted reproductive techniques, monozygotic twinning
has increased to become 2–8 times more common than
among the general population [3, 12, 13]. ICSI and IVF
are usually the cause of that increase in monozygotic
twinning. In vitro cultures have been questioned for the
increased incidence of monozygotic twinning [14]. Another hypothesis was about zonal manipulation. It was
suggested that zonal manipulation leads to structural
changes in the zona pellucida which trigger monozygosity [15]. Ovulation induction with gonadotrophins and
clomiphene citrate without IVF-ICSI has been reported
as a cause in a few reports [3, 13, 16]. In a recent study it
has been shown that clomiphene citrate is associated with
higher monozygotic twinning compared with other ovulatory drugs. Furthermore, monozygotic twinning was
higher in the ovulation induction group than the assisted
reproduction group [16]. However, a major problem in
those studies is to diagnose the monozygosity correctly.
As one third of monozygotic pregnancies are dichorionic,
the diagnosis of these pregnancies is a great challenge. In
the ART group a certain diagnosis of monozygosity in a
dichorionic pregnancy can be done when the number of
embryos in ultrasound exceeds the number of embryos
transferred. However, a monozygotic dichorionic pregnancy can occur without such a condition in multiple
pregnancies, which leads to underestimation of the true
incidence of monozygotic dichorionic pregnancy. In that
study, in a non-ART group, zygosity and chorionicity determinations have been done with a prospective survey.
Among all monozygotic twins, the frequency of monochorionic placentas in all induced cases (ART and nonART) was higher than in spontaneous cases (80 vs. 64%
respectively) [16]. It can be assumed that the frequency of
conjoined twinning is increasing as a result of increasing
monozygosity in the ovulation induction group.
Increased nuchal translucency is associated with chromosomal abnormalities, fetal cardiovascular and pulmonary defects, skeletal dysplasias, congenital infections,
and metabolic and hematologic abnormalities [17]. Increased nuchal translucency has been demonstrated in
thoracopagus conjoined twins in several reports [18, 19].
Hemodynamic disturbances due to cardiac insufficiency
are the most likely cause of increased nuchal translucency. With the advent of ultrasound technology, detection
of conjoined twinning can be done very early in pregnancy, even for rare forms [20, 21]. However, scanning for
nuchal translucency measurement between 11 and 14
weeks of gestation allows clinicians a more accurate diagnosis of conjoined twinning and also gives a chance for
major anomaly detection in embryos. Therefore, management of the abnormality can be done more precisely.
Early ultrasound in multiple pregnancy gives accurate
information regarding chorionicity which is essential for
further management options. Selective termination of
the conjoined twins in triplets or quadruplets is the preferred option to manage the pregnancy in di- and trichorionic pregnancies [10, 11, 18]. Conjoined twins in monochorionic triplets has been managed in several ways such
as endoscopic laser occlusion of the single umbilical cord,
termination of pregnancy and expectant management
[18, 22–24].
In conclusion, higher monozygotic pregnancies are
expected after ovulation induction cycles, conjoined
twinning is therefore presumably on the increase. Scanning for nuchal translucency measurement is crucial for
early diagnosis of many abnormalities as well as the confirmation of conjoined twinning and accurate definition
of chorionicity which allows the obstetrician the most appropriate management options.
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