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Prenatal diagnosis of a complete mole coexisting with a dichorionic twin

pregnancy: Case report

Article  in  Human Reproduction · June 2004

DOI: 10.1093/humrep/deh211 · Source: PubMed

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Human Reproduction Vol.19, No.5 pp. 1231±1234, 2004 DOI: 10.1093/humrep/deh211
Advance Access publication April 7, 2004

Prenatal diagnosis of a complete mole coexisting with a

dichorionic twin pregnancy: Case report

L.Bovicelli1, T.Ghi1,4, G.Pilu1, A.Farina1, L.Savelli1, G.Simonazzi1, E.Calzolari3, A.Ferlini3,

D.Santini2 and B.Valeri2
1
Department of Obstetrics and Gynecology and 2Department of Pathology, Policlinico S.Orsola-Malpighi, University of Bologna and
3
Section of Medical Genetics, Department of Experimental and Diagnostic Medicine, Ospedale S.Anna, University of Ferrara, Italy
4
To whom correspondence should be addressed at: Medicina EtaÁ Prenatale, Clinica Ostetrica e Ginecologica, Policlinico
S.Orsola-Malpighi, Via Massarenti 13, 40100 Bologna, Italy. E-mail: tullioghi@yahoo.com

A complete mole coexisting with dichorionic twins was diagnosed by the combined use of sonography and chorionic
villus sampling at 10 weeks gestation. The pregnancy resulted in the death of one fetus at 31 weeks from presumed

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feto-maternal haemorrage, while the other fetus survived in good condition. A summary of the available literature,
combined with this report, reveals a total of seven pregnancies with twins and a coexistent complete mole. Only two
out of 14 fetuses survived. Maternal complications included one case of pre-eclampsia and one persistent
trophoblastic tumour. Accurate diagnosis of complete mole is possible by genetic analysis of chorionic villi obtained
with standard transabdominal sampling. Twins with a coexistent complete mole will usually undergo miscarriage.
However, fetal survival is possible and the maternal risks seem limited. A concomitance between gestational
trophoblastic disease and the occurrence of feto-maternal haemorrhage is observed.

Key words: complete mole/feto-maternal haemorrhage/multiple pregnancy/prenatal diagnosis/ultrasound

Introduction
The association of a complete mole with two viable twins is a
rare condition that has only been reported in a handful of cases
(Sauerbrei et al., 1980; Ohmichi et al., 1986; Azuma et al.,
1992; van de Geijn et al., 1992; Amr et al., 2000; Rajesh et al.,
2000). All but one of these pregnancies resulted in miscarriage.
We now report one case of a triplet trichorionic pregnancy,
with two viable twins and one complete mole that was
diagnosed by sonography and chorionic villus sampling at 10
weeks gestation and continued until 31 weeks, with survival of
one of the two fetuses
Case report
The patient, a 32 year old primigravida, had undergone IVF
with sperm microinjection of the oocytes, and replacement of
three embryos in the uterus. A previous transvaginal sonogram
performed elsewhere at 7 weeks gestation had demonstrated
three gestational sacs, two with viable embryos and one empty
(Figure 1). A triplet trichorionic pregnancy with early failure of
one sac had been diagnosed at that time. At 9 weeks the patient
was referred to our unit for a scan because of bleeding. Viable
dichorionic twins were con®rmed but the third sac was
considerably changed in appearance and presented a thickened
trophoblast containing a few microcysts that almost completely
obliterated the cavity of the sac (Figure 2). A molar degener-
ation of the third placenta was suspected. At this time, free b-
Human Reproduction vol. 19 no. 5 ã European Society of Human Reproduction and Embryology 2004; all rights reserved
hCG was 80 000 IU/ml. The patient was already scheduled for
chorionic villus sampling and at 11 weeks gestation all three
trophoblasts were sampled with a transabdominal procedure
using a 20G ultrasound-guided needle (Smidt-Jensen et al.,
1993). The viable twins had normal karyotypes, 46,XX and
46,XY. The cells from the abnormal trophoblast were found to
have a 46, XX karyotype. Molecular genotyping and segrega-
tion analysis of both parental and placenta alleles, by using
several VNTR (D7S481, D7S500, D7S2439, D7S523,
D7S640, D14S301, D14S288, D14S286, D14S283, D15S211,
GABRB3, DXS206, DXS1214) as previously described
(Gualandi et al., 2000), allowed us to establish a fully paternal
origin of the genotype of the abnormal trophoblast leading to
molecular con®rmation of complete mole. The couple was
counselled about the maternal and fetal risks derived from the
coexistence of twins and a complete mole. The limited
experience with such cases and the poor outcome derived
from available reports was discussed. Eventually, the couple
decided to continue the pregnancy. In the following weeks and
for the rest of the pregnancy maternal blood pressure and
thyroid function remained well within normal limits. b-hCG
rose to 300 000 IU/ml at 24 weeks and then plateaued. A
negative chest X-ray was obtained at 24 weeks. Serial
sonography documented normal anatomy and growth of the
living twins. The molar placenta decreased in echogenicity
throughout the pregnancy with a typical multicystic appear-
ance since 14 weeks of gestation (Figure 3). Although a
1231
L.Bovicelli et al.

Figure 1. Ultrasound scan at 7 weeks of gestation: an empty sac

(arrow) is noted beside a living fetus.

Figure 3. Ultrasound scan at 30 weeks of gestation: cystic

appearance of molar placenta (arrow) is noted.

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Figure 2. Ultrasound scan at 9 weeks of gestation: the empty sac is
now shrunken and appears almost completely ®lled by a thickened
placental ring (arrow).
Figure 4. After delivery, the morphologically normal placenta
(white arrow) of the dead twin in close proximity to a completely
molar placenta (black arrow)
quantitative analysis of the molar placenta was not possible, the
qualitative impression was that the placental disk grew
similarly to the normal placentas.
Fetal surveillance with weekly biophysical pro®les was
initiated at 29 weeks gestation. At 31 weeks + 4 days the
patient reported a reduction in fetal movements. A biophysical
pro®le was immediately performed. The twins were of normal
size and amniotic ¯uid volume, but the male fetus had no
movements, absent tone and absent end diastolic velocities in
the Doppler waveforms of the umbilical artery.
Cardiotocography demonstrated a non-reactive tracing, with
no heart rate accelerations and a severe reduction in variability.
The female fetus demonstrated normal movements, tone, Figure 5. Pictures from complete hydatiform mole: (a) macroscopic
umbilical artery Doppler and had a reactive non-stress test. appearance with all villi showing vesicular changes; (b)
photomicrograph of sectioned tissue: the distended villi give rise to
An emergency Caesarean section was performed. A female
formation of cisterns and atypically proliferating trophoblast is
infant with an Apgar score of 8 and 9 and a stillborn male infant noted.
weighing respectively 1700 and 1640 g were delivered with
their own placentas. A third placenta with a macroscopic molar
appearance was removed (Figure 4). The female infant was
admitted to intensive care unit due to prematurity but had an on maternal blood. Furthermore, at 72 h after delivery a large
uneventful neonatal course and was eventually discharged in amount of free DNA of fetal origin was retrieved in maternal
good condition. Pathology con®rmed the presence of a plasma by quantitative PCR as described in the literature
complete mole (Figure 5). Examination of the dead fetus and (Bianchi et al., 1997).
his placenta was compatible with acute exsanguination as a At 6 months of age, the female twin is thriving well and is
cause of death. The skin of the fetus was extremely pale, and following normal developmental milestones. Maternal serum
petechial lesions were present on the lung surface and gastric b-hCG completely disappeared after 4 months.
mucosa. The placenta of the dead twin, which was close to the
molar placenta, also appeared pale and hypovascular (Figure 6).
An acute feto-maternal haemorrhage affecting the male twin Discussion
was suspected. The hypothesis of an acute materno-fetal The case described here is unique for several reasons. The
transfusion was suppported by a positive Kleihauer±Betke test molecular diagnosis of complete mole with determination of
1232

Figure 6. A comparison between the two morphologically normal placentas is shown: fresh (a), after ®xation (b) and after section (c); the
placenta of dead twin (arrow) on the right side appears pale compared to the placenta of the living twin.
paternal origin of the chromosomes on placental tissue
obtained after miscarriage or delivery has been reported
previously (Sauerbrei et al., 1980; Ohmichi et al., 1986;
Azuma et al., 1992; van de Geijn et al., 1992; Amr et al., 2000;
Rajesh et al., 2000). However, to our knowledge this is the ®rst
time that the diagnosis has been made antenatally in an ongoing
pregnancy by the use of chorionic villus sampling.
The ability to diagnose a molar placenta in an ongoing
pregnancy is clinically relevant. The ultrasound demonstration
of a multicystic placenta coexisting with one or more viable
fetuses is frequently a diagnostic dilemma. Differentiation
between a complete mole, a partial mole and placental
mesenchymal dysplasia may be dif®cult; the prognostic
implications of these entities are quite different (Jauniaux,
1999), although obstetric management is similar as close feto-
maternal surveillance is required. Excessive placental growth
is associated with an increased risk of pre-eclampsia, vaginal
bleeding, thyroid disorders, premature delivery, etc. In
particular, partial mole is lethal for the fetus and carries a
small risk of a persistent trophoblastic tumour to the mother.
Placental mesenchymal dysplasia is in general a benign entity,
although an association with fetal Beckwith±Wiedemann
syndrome has been reported. A complete mole coexisting
with one normal fetus carries signi®cant risks to both mother
and fetus and requires close surveillance. The fetal loss rate is
~60%, while severe maternal complications (pre-eclampsia,
pulmonary embolism) occur in 10% of cases. The risk of
tumour persistence is in the range of 20%, and does not seem to
be in¯uenced by the duration of the pregnancy (Sebire et al.,
2002).
In our opinion, it is unlikely that ®ne needle biopsy would
increase signi®cantly the risk of spreading the tumour,
particularly when one considers that molar pregnancies are
commonly evacuated by dilatation and curettage, a procedure
probably much more invasive than chorionic villus sampling.
In a situation in which the nature of a multicystic placenta
coexistent with a fetus is uncertain, we do believe that the
clinical importance of a speci®c diagnosis outweighs by far the
theoretical risks of the invasive procedure.
In our case, thanks to chorionic villus sampling, the cause of
placental abnormality was available early. Other conditions
Complete mole with a dichorionic twin pregnancy
which may cause placental overgrowth (see above) were
excluded and couple could decide how to manage the
pregnancy after being fully informed about the case and its
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prognostic implications.
Usually, complete mole appears sonographically as a
multicystic placenta in the late ®rst trimester. To the best of
our knowledge, this is the ®rst paper to report the appearance of
a complete mole at 7 weeks gestation. At this time, the
sonographic ®ndings were aspeci®c and were compatible with
a blighted ovum. In early pregnancy, a sonographic aspect
suggestive of early missed abortion had been previously
reported (Sebire et al., 2001).
The coexistence of a complete mole with a twin pregnancy
has been reported previously in six cases (Sauerbrei et al.,
1980; Ohmichi et al., 1986; Azuma et al., 1992; van de Geijn
et al., 1992; Amr et al., 2000; Rajesh et al., 2000) (see Table I).
In ®ve pregnancies, miscarriage or labour occurred before 25
weeks. In the two remaining pregnancies, including the present
case, delivery occurred prematurely and only one fetus from
each survived. Maternal complications included one case of
pre-eclampsia and one case of persistent trophoblastic tumour.
We speculate that the fetal death in our case was the
consequence of a severe feto-maternal haemorrhage. The
clinical data, the pathological examination and the presence of
a large number of fetal blood cells and fetal DNA in the
maternal circulation soon after delivery are all compatible with
this hypothesis. Feto-maternal haemorrhage has been previ-
ously reported in association with gestational trophoblastic
disease (Theunissen et al., 1992; Lee and Ho, 1999; Suh, 1999;
Takai et al., 2000; Lam et al., 2002). The pathophysiological
mechanism that favours haemorrhage from the fetal to the
maternal circulation in the presence of a coexistent abnormal
placenta remains obscure. It is of note that in our case the
placenta of the dead fetus was in close proximity to the molar
placenta.
In conclusion, our case and a summary of the literature
suggest the following: at 7 weeks gestation a complete mole
may appear sonographically as a blighted ovum; accurate
prenatal diagnosis of complete mole may be achieved by
genetic analysis of chorionic villus sampling; although most
twins with a coexistent complete mole will undergo miscar-
1233
L.Bovicelli et al.
Table I. Previous cases of complete mole coexisting with two living fetuses: summary of feto-maternal outcome
Author (year) Outcome of twins (week of delivery)
Sauerbrei et al. (1980) Miscarriage (22 weeks)
Azuma et al. (1992) Miscarriage (19 weeks)
Van de Geijn et al. (1992) Miscarriage (25 weeks)
Amr et al. (2000) 1 survivor, 1 perinatal death (30 weeks)
Ohmichi et al. (1986) Miscarriage (17 weeks)
Rajesh et al. (2000) Labour at 24 weeks; early neonatal death of both
Present case 1 survivor, 1 perinatal death (31 weeks)
riage, there is a slight chance of intact fetal survival (two of 14
fetuses thus far reported), and the maternal risks of continuing
the pregnancy seem limited; there appears to be an association
between trophoblastic disease coexisting with living fetuses
and feto-maternal haemorrhage. The available experience is
too limited to establish the optimal obstetric management in
these cases. Serial ultrasound examinations and close clinical
and laboratory surveillance of the mother are certainly
indicated. We also suggest fetal monitoring in the third
trimester and delivery as soon as fetal maturity is achieved.
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1234
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Maternal complications
Vaginal bleeding; pre-eclampsia
Vaginal bleeding
Vaginal bleeding
None
Persistent trophoblastic tumour
Vaginal bleeding
None
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Submitted on August 11, 2003; resubmitted on December 15, 2003;
accepted on February 11, 2004