1. family and parenting
2. motherhood
3. pregnancy

Radiol Clin N Am 42 (2004) 297 – 314
Sonographic evaluation of first-trimester bleeding
Raj Mohan Paspulati, MD*, Shweta Bhatt, DMRD, DMRE, Sherif Nour, MD
Department of Radiology, University Hospitals of Cleveland, Case Western Reserve University, 11100 Euclid Avenue,
Cleveland, OH 44106, USA
Vaginal bleeding in the first trimester of pregnancy is a common presentation in emergency care
facilities. About 25% of all gestations present with
vaginal spotting or frank bleeding in the first few
weeks of pregnancy; half of these progress into
miscarriage or abortion [1]. The acuity of these
symptoms may vary from occasional spotting to severe hemorrhage, associated with cramping and abdominal pain. The bleeding often is self-limited and
is most likely caused by implantation of the conceptus into the endometrium. The important causes of
first-trimester bleeding are spontaneous abortion, ectopic pregnancy, and gestational trophoblastic disease. The clinical assessment of pregnancy outcome
is unreliable and ultrasound (US) evaluation combined with quantitative beta human chorionic gonadotropin (b-hCG) is an established diagnostic tool in
these patients. This article reviews the role of ultrasonography in the evaluation of patients presenting
with first-trimester bleeding.
Sonographic anatomy
The uterus is a pear-shaped, muscular organ that
varies greatly in size and shape depending on age and
prior pregnancies. The normal postpuberty uterus in
an adult measures approximately 7.5 to 8 cm in
length, 4 to 5 cm in width, and about 2 cm in anteroposterior dimension. The normal cervix is 3.5 to
4 cm in length. The cervix is comprised of internal
* Corresponding author.
E-mail address: [email protected] (R.M. Paspulati).
and external cervical os. The internal os is the
junction of the uterine cavity and the cervical canal
and the external os is the junction of the cervical
canal and the vagina. Transvaginal US (TVUS) of the
normal myometrium reveals three distinct layers.
Arcuate vessels separate the thin outer layer from
the thick middle layer, and both layers are homogeneous with the outer layer more hypoechoic relative
to the middle layer [2]. The inner layer consists of a
thin hypoechoic halo that surrounds the endometrium
and corresponds to the junctional zone seen on MR
imaging. The endometrial thickness measurements
are optimally made on sagittal (long-axis) images of
the uterus; this measurement should be performed
on the thickest portion of the endometrium excluding
the hypoechoic inner myometrium (Fig. 1). The endometrial thickness should be reported as the ‘‘double thickness’’ measurement [3]. If endometrial fluid
is present, its diameter should be omitted; in such
cases the endometrial thickness should be reported
as the sum of the measurements obtained from the
anterior and posterior endometrial walls. An endometrial thickness of 4 to 14 mm is normal in an adult
premenopausal woman. Endometrial thickness and
appearance vary with the phase of the menstrual
cycle [4].
The position of the ovaries is variable but they are
usually found in the posterior fold of the broad
ligament, posterior and distal to the fallopian tubes.
On sonography the ovaries can be localized anterior
to the internal iliac vessels. The postpubertal ovary
measures approximately 3 cm in length, 2 cm in
width, and 1 cm in anteroposterior dimension. The
upper limit for normal ovarian volume is highest in
young adult women measuring approximately 9.8 to
14 mL and declines with increasing age [5]. Normal
0033-8389/04/$ – see front matter D 2004 Elsevier Inc. All rights reserved.
doi:10.1016/j.rcl.2004.01.005
298
R.M. Paspulati et al / Radiol Clin N Am 42 (2004) 297–314
ler US in early pregnancy, the concept of ‘‘as low as
reasonably achievable’’ is important [7] and the
advantages of the Doppler US should outweigh the
potentially harmful effects on the conceptus.
Normal first-trimester sonography
Fig. 1. Sagittal TVUS of the uterus demonstrates a normal
endometrial lining (arrowheads).
fallopian tubes cannot be visualized with current US
imaging equipment
Scanning technique
Ultrasound evaluation of the female pelvis is
conducted with a real-time scanner, preferably using
a sector or curvilinear transducer. The scanner is
adjusted to operate at the highest clinically appropriate frequency, realizing that there is a trade-off
between the resolution and beam penetration.
Transabdominal pelvic US is performed with a
full bladder using transducer frequencies of 3.5 MHz
and above. Adequate distention of the bladder displaces the bowel from the field of view. Transabdominal US gives an initial overview of the uterus,
adnexa, and any intra-abdominal free fluid. TVUS is
performed with the patient’s bladder being empty,
using a transducer frequency of 5 to 7.5 MHz. TVUS
gives detailed information about the uterus and the
adnexa. Higher-frequency transvaginal probes can be
positioned closer to the pelvic organs resulting in
improved spatial resolution and diagnostic accuracy.
Currently available transducers of 10 MHz and above
can identify the finer details of intrauterine gestation
and have greatly contributed to the early diagnosis of
abnormal gestation and to the management of firsttrimester bleeding. Color flow Doppler and pulsed
Doppler may be added to the examination, as indicated by the gray-scale US findings. It is important to
bear in mind that the energy output of Doppler US is
substantially higher than that used for imaging and it
may have potentially harmful effects on the conceptus [6]. Because of this risk, caution has been
expressed over the routine use of Doppler US in
early pregnancy evaluation. While performing Dopp-
Scanning in the first trimester may be performed
either transabdominally or transvaginally. TVUS is
preferred and is the community standard. The firsttrimester milestones are given in Tables 1 and 2.
A gestational sac can be identified with TVUS at
5 weeks of gestational age, when it measures 5 mm.
The yolk sac should always be seen by TVUS when
a gestational sac measures greater than 10 mm and
by transabdominal US when the mean sac diameter
is greater than 20 mm [8,9]. An embryo with cardiac activity should be seen transvaginally when the
gestational sac measures greater than 18 mm, and
transabdominally when the gestational sac measures
2.5 cm. These discriminatory criteria should be used
as guidelines. If the findings of the US examination
are equivocal and the examination is technically
difficult, a follow-up examination should be obtained.
Gestational sac
The blastocyst implants into the endometrium by
approximately 23 days of menstrual age [10]. It measures 0.1 mm and is too small to be visualized on
TVUS. Demonstration of peritrophoblastic flow by
transvaginal color flow Doppler at this focal decidual
thickening has improved the diagnostic sensitivity of
intrauterine pregnancy (IUP) from 90% with TVUS
alone to 99% using transvaginal color flow Doppler [11,12]. The peritrophoblastic flow has a characteristic high-velocity and low-impedance flow caused
by shunting of blood from the spiral arteries into the
intervillous spaces. According to Emerson et al [11],
the peak systolic velocity of peritrophoblastic flow
in a normal IUP ranges from 8 to 30 cm/second, before the visualization of the gestational sac. Yeh et al
Table 1
First-trimester scanning milestones
Parameter
Transabdominal US Transvaginal US
Gestational sac
—
Yolk sac
Always present
if GS > 20 mm
Cardiac activity GS > 2.5 cm
Present at 5 wk
(5 mm)
Always present
when GS > 10 mm
GS > 18 mm
Abbreviations: GS, gestational sac; US, ultrasound.
R.M. Paspulati et al / Radiol Clin N Am 42 (2004) 297–314
299
Table 2
Land marks of normal first-trimester pregnancy
Gestational age
Embryologic change
Sonographic appearance
23 d
3.5 – 4 wk
Blastocyst implantation
Decidual changes at
implantation site
Trophoblastic tissue
Blastocyst measures 0.1 mm and is too small to visualize
Focal echogenic decidual thickening at implantation site
4 – 4.5 wk
4.5 – 5 wk
5 – 5.5 wk
Exocoelomic cavity of
the blastocyst
Secondary yolk sac
5 – 6 wk
Embryo
5 – 6 wk
Embryonic cardiac
activity
High-velocity and low-impedance trophoblastic flow at the implantation site
on TVCFD
Gestational sac (a sonographic term) is always seen when it measures > 5 mm
and the serum b-hCG is between 1000 and 2000 mIU/mL (IRP)
Yolk sac is seen as a thin-walled cystic structure within the gestational sac and
should always be seen when the GS is > 10 mm; it is the first sign of a true
gestational sac before the visualization of embryo
Seen as a focal echogenic area adjacent to the yolk sac; should always be seen
when the GS is > 18 mm
Embryonic cardiac activity should always be seen when the embryo is > 5 mm;
normal heart rate ranges from 100 – 115 beats/min between 5 – 6 wk of gestation
Abbreviations: CG, human chorionic goradotropin; GS, gestational sac; IRP, international reference preparation; TVCFD,
transvaginal color flow Doppler.
[13] described a focal, eccentric, anechoic area in the
endometrium caused by the embedded blastocyst as
the ‘‘intradecidual sign.’’ They described this sign as
early as 3.5 weeks of menstrual age on transabdominal US and reported a sensitivity rate of 92%, a
specificity rate of 100%, and an accuracy rate of
93%. Laing et al [14] used TVUS to demonstrate this
sign and found that the overall sensitivity, specificity,
and accuracy for the intradecidual sign were only
48%, 66%, and 45%, respectively. With currently
available high-frequency transvaginal probes, a gestational sac as small as 2 to 3 mm can be demonstrated at 4 weeks of gestational age [15 – 17]. On
TVUS, the gestational sac is seen as a well-defined
fluid-filled cavity with a surrounding hyperechoic
rim, embedded eccentrically in the endometrial lining
of the fundus or midbody of the uterus (Fig. 2). The
sonographic term ‘‘gestational sac’’ represents the
exocoelomic cavity of the blastocyst and the surrounding echogenic rim is caused by the developing
chorionic villi and decidual tissue. The echogenic rim
should have a minimum thickness of 2 mm and its
echogenicity should exceed that of myometrium [1].
The double decidual sac sign of intrauterine
gestation was first described in 1982 [18]. The double
decidual sac sign consists of two concentric echogenic rings encasing a central anechoic focus that impress on the endometrial stripe. The inner echogenic
rim represents the decidua capsularis and chorion
laeve, whereas the outer echogenic rim represents
the decidua parietalis; these echogenic rims are separated by a thin rim of fluid in the endometrial cavity
(Fig. 3). This is a useful sign of IUP between 4 and
6 weeks of gestation. The crown-rump length (CRL)
of the embryo is a more accurate indicator of gestational age than the mean gestational sac diameter. The
mean gestational sac diameter should be recorded,
however, when an embryo is not identified.
Because hCG production and gestational sac
growth are related to trophoblastic function, there is
excellent correlation of the serum hCG level, sac size,
and the stage of pregnancy [19]. Kadar et al [20] first
introduced the concept of a discriminatory level of
the b subunit of hCG. The range of the serum b-hCG
level at which an intrauterine gestational sac is
visualized is the discriminatory zone. Although the
discriminatory range of b-hCG varies from one laboratory to another, the widely accepted range is from
Fig. 2. Coronal TVUS of the uterus shows a gestational sac
with hyperechoic margins (arrow) and endometrial cavity
(curved arrow).
300
R.M. Paspulati et al / Radiol Clin N Am 42 (2004) 297–314
Fig. 3. Double decidual sac sign. (A) Coronal TVUS of the uterus reveals an intrauterine gestational sac (straight arrow),
decidua capsularis (curved arrow), decidua parietalis (arrowhead), and effaced endometrial cavity (asterisks). (B) Corresponding
line diagram.
1000 to 2000 mIU/mL international reference preparation (IRP) for TVUS and 2400 to 3600 mIU/mL
(IRP) for transabdominal US [10]. In normal pregnancy serum b-hCG should double or increase by at
least 66% in 48 hours.
Yolk sac
available high-frequency transvaginal transducers,
the embryonic disk is initially seen as a focal echogenic area of 1- to 2-mm thickness adjacent to the
yolk sac between 5 and 6 weeks of gestational age
[26 – 29]. Embryonic cardiac activity should always
be seen when an embryo measures greater than 5 mm.
Occasionally the heartbeat may be seen adjacent to
the yolk sac even before the embryo is clearly visible.
The first structure to be seen within the gestational
sac is the secondary yolk sac, which is a reliable
indicator of a true IUP with a positive predictive
value of 100%. The primary yolk sac is not seen by
US because it shrinks at 4 weeks menstrual age and
gradually disappears with the formation of the secondary yolk sac [21]. The secondary yolk sac is first
seen on TVUS as a thin-walled cystic structure by the
fifth gestational week and is virtually always seen by
5.5 weeks gestational age (Fig. 4) [22]. The yolk sac
is round, measures less than 6 mm, and should be
visualized by TVUS when a gestational sac measures
more than 10 mm [10]. The yolk sac is involved in
nutritive, metabolic, hemopoietic, and secretive functions during early embryonic development and organogenesis [23,24]. Abnormalities in its size and
appearance are predictors of abnormal gestation [25].
Embryo
The embryo should always be visualized by
TVUS when the gestational sac measures greater than
18 mm, and transabdominally when the gestational
sac measures 2.5 cm (Fig. 5). With the currently
Fig. 4. TVUS of the uterus demonstrates a yolk sac (thin
arrow) outside the amniotic membrane (arrowhead), which
has not yet fused with the chorion (curved arrow). Embryo
(thick arrow) is seen within the amniotic sac.
R.M. Paspulati et al / Radiol Clin N Am 42 (2004) 297–314
301
branes before 14 weeks of gestation is considered
normal (see Figs. 4 and 5).
Spontaneous abortion
Spontaneous abortion is defined as pregnancy
terminating before the 20th completed week of gestation. Approximately 80% of spontaneous abortions
occur in the first trimester. The causes of spontaneous
abortions fall into two categories: genetic and environmental (maternal) as listed next:
Fig. 5. TVUS of the uterus shows a normal embryo and
separate amniotic membrane (arrow) in close relation to the
embryo. This should not be mistaken for nuchal translucency.
Levi et al [3] suggested a 4-mm CRL cutoff because
their study demonstrated cardiac activity in all embryos with a CRL of 4 mm [30]. Other studies
demonstrated 5 mm as the discriminatory CRL for
detecting cardiac activity [31,32]. Although visualization of a living embryo does not ensure a viable
pregnancy, the abortion rate decreases for living embryos as the gestational age increases, with a 0.5%
demise rate for living embryos between 6 and 10 mm
[33]. If the length of the embryo is less than 5 mm,
follow-up US should be performed until the expected
CRL exceeds the discriminatory value. Most of the
studies reported a heart rate of 100 to 115 beats per
minute between 5 and 6 weeks [34 – 36]. By 9 weeks
of gestational age, the mean heart rate increases to
about 140 beats per minute. The cardiac activity
should be documented by M-mode.
Amniotic sac
The amniotic sac is formed in the fourth week
of gestation between the ectoderm layer and the adjacent trophoblast. Before 6.5 weeks the amniotic
membrane is so close to the embryo that the amniotic
cavity around the embryo is not easily seen. The diameter of the amniotic cavity is nearly equal to the
CRL. Between 5 and 7 weeks of gestational age the
embryo is located between the amniotic and yolk
sacs. On US, this amniotic sac – embryo – yolk sac
complex appears as two small sacs and is called the
double bleb sign [9]. The embryo and the inner
amnion grow at a faster rate than the outer chorionic
cavity with eventual fusion of the amniotic and
chorionic membranes by 16 weeks of gestation
[37]. Separation of the amniotic and chorionic mem-
Genetic or fetal causes
Trisomy
Polyploidy or aneuploidy
Translocations
Environmental or maternal causes
Uterine
Congenital uterine anomalies
Leiomyoma
Intrauterine adhesions or synechiae (Asherman’s
syndrome)
Endocrine
Progesterone deficiency (luteal phase defect)
Hypothyroidism
Diabetes mellitus (poorly controlled)
Luteinizing hormone hypersecretion
Immunologic
Autoimmunity: antiphospholipid syndrome, systemic lupus erythematosus
Infections
Toxoplasma gondii, Listeria monocytogenes,
Chlamydia trachomatis, Ureaplasma urealyticum, Mycoplasma hominis, herpes simplex,
Treponema pallidum, Borrelia burgdorferi,
Neisseria gonorrhoeae
Genetic abnormalities are the most common cause
of spontaneous abortions accounting for almost 50%
to 60% of cases. Autosomal trisomy is the most
frequently identified chromosomal abnormality resulting in first-trimester abortions. The incidence of
abortions secondary to chromosomal abnormalities
markedly increases after the maternal age of 35 years.
The environmental or maternal causes account for
a small percentage of spontaneous abortions. These include infection; anatomic defects (maternal mullerian
defects); endocrine factors (failure of corpus luteum);
immunologic factors (antiphospholipid antibody syndrome); and maternal systemic disease (diabetes mellitus, hypothyroidism). The algorithmic approach to
first-trimester bleeding is summarized in Fig. 6.
302
R.M. Paspulati et al / Radiol Clin N Am 42 (2004) 297–314
A
First Trimester Ultrasound
Embryo not visualized
MSD > 18MM
MSD < 18MM
YS absent
YS present
MSD < 10MM
MSD > 10MM
ED
ED
F/U re: sac
growth and
embryo
1
B
Embryo visualized
Cardiac activity
present
CRL > 5MM
YS present
YS normal
MSD-CRL
> 5MM
HR N
? F/U
18 wks
1
Cardiac activity
absent
CRL < 5MM
CRL > 5MM
CRL < 5MM
YS absent
YS abnormal
MSD-CRL
< 5MM
HR AbN
F/U
2
F/U
2wks
re: growth
and cardiac
activity
1
ED
F/U
re: growth and
cardiac activity
1
Fig. 6. (A, B) Proposed algorithms for evaluating women with first trimester bleeding. ED, embryonal demise; F/U, follow-up;
HR ABN, heart rate abnormal; HR N, heart rate normal; YS, yolk sac. (From McGahan J, Goldberg B. Diagnostic ultrasound:
a logical approach. Philadelphia: Lippincott, Williams & Wilkins; 1998; p. 142 – 3; with permission.)
The most common morphologic finding in early
spontaneous abortions is an abnormality of development of the zygote, embryo, early fetus, or the
placenta. Spontaneous abortion is clinically classified
into threatened, inevitable, missed, incomplete, and
complete abortions (Table 3).
Ultrasound findings in abortion
The US findings depend on the developmental
stage of the pregnancy at which the patient presents
with symptoms. Familiarity with normal sonographic
landmarks of first-trimester pregnancy is essential
R.M. Paspulati et al / Radiol Clin N Am 42 (2004) 297–314
303
Table 3
Classification of spontaneous abortion
Types
Clinical features
US findings
Threatened abortion
Vaginal bleeding before 20 wk gestation
without cervical dilatation
Incomplete abortion
Vaginal bleeding with partial expulsion
of products of conception before 20 wk
gestation and cervical dilatation
Embryonic demise before 20 wk of
gestation without expulsion of products
of conception; may or may not have
vaginal bleeding
Vaginal bleeding and expulsion of all
products of conception before 20 wk
gestation
Vaginal bleeding before 20 wk gestation
with cervical dilatation
Depending on the stage of pregnancy, US may show an
empty uterus, intrauterine gestational sac with or without
an embryo
Thick, irregular endometrial lining caused by residual
trophoblastic tissue and fluid
Missed abortion
Complete abortion
Inevitable abortion
Embryo without cardiac activity; small size of the embryo
for the gestational age (see Fig. 10)
Empty uterus
Variable depending on the degree of bleeding and expulsion
of the products of conception
Abbreviations: US, ultrasound.
to diagnose a failing pregnancy. TVUS features of
failing pregnancy are summarized in Table 4. The
sonographic findings are to be correlated with serum
b-hCG and menstrual age. In the pre-embryonic stage,
the pregnancy outcome depends on the presence of
the gestational sac and yolk sac and their morphologic features.
and high diastolic component caused by trophoblastic
arterial flow are noted [40].
Intrauterine gestational sac without an embryo
A common and difficult problem arises when the
gestational sac in the uterus lacks an embryo or yolk
sac [41 – 43]. This can be caused by early normal IUP,
Absent intrauterine gestational sac
Failure to demonstrate intrauterine gestational sac
by TVUS may be secondary to early IUP (b-hCG <
1000 mIU/mL) or secondary to ectopic pregnancy.
When the serum b-hCG is more than 1000 mIU/mL
(IRP) and there is no IUP, an ectopic pregnancy
[19,20] must be excluded by careful evaluation of
the adnexa. If there is no identifiable ectopic gestational sac, adnexal mass, or a large amount of adnexal
fluid in the cul-de-sac, follow-up with b-hCG and
TVUS is necessary until a definite diagnosis is made.
When the endometrial lining is thick with echoes in
the endometrial cavity and no intrauterine gestational
sacs, an incomplete abortion with retained products
of conception must be distinguished from decidual
reaction of ectopic gestation. Transvaginal color flow
Doppler of the endometrial contents is useful in differentiating trophoblastic tissue from blood clots and
pseudogestational sac. Sparse flow on color Doppler
with low peak systolic velocities (< 6 cm/second) and
low to absent end diastolic flow suggests decidual reaction of an ectopic pregnancy (Fig. 7) [38,39]. With
early IUP (< 5 weeks) multiple flashes of color with a
peak systolic velocity of greater than 8 cm/second
Table 4
TVUS features of pregnancy failure
Ultrasound findings
Comments
Absence of IUGS with serum
b-hCG above the
discriminatory level
(1000 mIU/mL)
IUGS > 10 mm without
a yolk sac
IUGS of >18 mm without
an embryo
Embryo of 5 mm and above
without cardiac activity
Embryo with bradycardia
(< 100 beats/min)
Ectopic pregnancy
has to be excluded
Subchorionic hematoma
Follow-up with serum
b-hCG and TVUS
Anembryonic pregnancy
Embryonic demise
Poor prognosis and
needs close follow-up
with TVUS
Correlation of pregnancy
outcome with the size
of hematoma is not well
established and needs
TVUS follow-up
Abbreviations: hCG, human chorionic gonadotropin; IUGS,
intrauterine gestational sac; TVUS, transvaginal ultrasound.
304
R.M. Paspulati et al / Radiol Clin N Am 42 (2004) 297–314
Fig. 7. Decidual reaction. (A) Sagittal TVUS shows thick echogenic endometrial lining without a gestational sac (arrowheads).
This sonographic appearance can be seen in molar pregnancy; correlation with beta hCG is very important. (B) Sagittal TVUS
with color Doppler did not demonstrate trophoblastic flow, confirming it to be decidual reaction (arrowheads). Patient’s beta
hCG was 650 IU. On follow-up, the patient was shown to have a normal intrauterine pregnancy.
anembryonic gestation, or a pseudogestational sac of
ectopic pregnancy. Anembryonic gestation is a form
of failed pregnancy defined as a gestational sac in
which the embryo failed to develop (Fig. 8A). A
mean gestational sac diameter greater than 18 mm
(TVUS) without a visualized embryo is unequivocal
evidence of a failed, anembryonic pregnancy [44].
This also is referred to as an ‘‘empty amnion’’ sign
(Fig. 8B) because of its sonographic appearance of a
large well-defined amniotic sac without an embryo
[45]. The growth rate of an anembryonic gestational
sac is slower than that of a normal gestational sac,
which increases by 1.13 mm/day. An abnormal gestational sac can be identified confidently when the
rate of increase of the mean sac diameter is less than
0.6 mm/d on follow-up US [46]. Other minor criteria of an abnormal gestational sac include distorted
sac shape and weakly echogenic or irregular choriodecidual reaction (Fig. 9). The presence of gestational
sac in the lower uterine segment or cervix is usually
seen in patients with abortion in progress (Fig. 10),
but can also be seen secondary to low implantation.
Demonstration of trophoblastic vascular flow on
color Doppler is useful in differentiating low implantation from abortion.
Yolk sac criteria of an abnormal gestation
The absence of a yolk sac when the mean sac
diameter of the gestational sac is more than 10 mm is
Fig. 8. Anembryonic pregnancy. (A) TVUS of uterus shows a large (> 18 mm) gestational sac (arrow) without an embryo. (B) An
‘‘empty amnion sign’’ of anembryonic gestation (arrow).
R.M. Paspulati et al / Radiol Clin N Am 42 (2004) 297–314
305
the viability of the gestation. The most convincing
evidence that a pregnancy has failed is to document
absence of cardiac activity when CRL length is
greater than 5 mm. In a missed abortion, the embryo
may be small for the gestational age with a discrepancy between the mean sac diameter and the CRL
(Fig. 11). Embryonic bradycardia is a poor prognosticator of pregnancy viability and requires follow-up
[58]. Embryonic bradycardia is defined as a heart rate
of less than 100 beats per minute before 6.2 weeks
gestational age and less than 120 beats per minute
between 6.3 and 7 weeks [59].
Fig. 9. Abnormal shape of the gestational sac. A 30-year-old
woman with 5 week’s of amenorrhea presents with vaginal
spotting. A TVUS of the uterus shows an intrauterine gestational sac of abnormal shape and lobulated contour. On follow-up patient had a spontaneous complete abortion.
indicative of an abnormal gestation and is associated
with spontaneous abortion [47 – 49]. A failing or
failed pregnancy is also suggested when the yolk
sac is abnormal in size and shape. Large (> 6 mm)
irregular and calcified yolk sacs have been found to
correlate with early pregnancy failure [50 – 52]. A
large yolk sac is considered to be caused by an
alteration of the metabolic functions of the yolk sac
membrane with accumulation of secretions following
embryonic death [53]. The association of a large yolk
sac with aneuploidy has also been reported [50].
Although abnormal large yolk sac size is reported
to be associated with subsequent pregnancy failure,
another study with yolk sac diameter greater than the
95th percentile for gestational age reported normal
pregnancy outcomes [54]. Because of this controversial issue, any patient with a large yolk sac should
have a follow-up US because there is increased risk
of spontaneous abortion. Apart from size, irregular,
echogenic, calcified, or double yolk sacs (vitelline
duct cyst) also are associated with early pregnancy
failure [55,56].
Intrauterine growth restriction
First-trimester growth restriction is a sign of a
failing pregnancy. Growth restriction is detected by
comparing the mean sac diameter with the CRL or
by serial follow-up of these growth parameters. The
average gestational sac diameters should be at least
5 mm larger than the CRL. A difference in size between mean sac diameter and CRL of less than 5 mm
caries a high risk of subsequent embryonic demise
[60]. When there is sac size and CRL discrepancy, a
follow-up US examination is recommended because
these fetuses have higher incidence of low birth
weight and premature delivery [61,62].
Subchorionic hematoma
Up to 20% of women with a threatened abortion
have a subchorionic hematoma [44]. Perigestational
Gestational sac with an embryo
Although visualization of a living embryo does
not ensure a viable pregnancy, the abortion rate
decreases for living embryos as the gestational age
increases, with a 0.5% demise rate for living embryos
between 6 and 10 mm [29]. Because cardiac activity
may not be demonstrated [57] in early normal embryos (CRL < 4 mm), follow-up US and correlation
with the serum b-hCG level is useful in determining
Fig. 10. Abortion in progress. A TVUS of the uterus shows a
low-lying gestational sac (arrow). Mixed hyperechoic and
hypoechoic contents in the endometrial cavity of the fundus
(arrowheads) represent decidual reaction and hemorrhage.
The patient had a complete spontaneous abortion a few
hours after the scan.
306
R.M. Paspulati et al / Radiol Clin N Am 42 (2004) 297–314
with that in younger women (13.8% versus 7.3%, respectively), and was 2.3 times higher in women who
presented with vaginal bleeding at 8 weeks gestational age or less compared with that in women who
presented with bleeding at more than 8 weeks gestational age (13.7% versus 5.9%, respectively). Some
investigators have calculated the volume of a subchorionic hematoma as a percentage of the gestational sac volume. When the volume of a hematoma
is less than 40% of the gestational sac volume, the
pregnancy outcome is favorable [64,66].
Fig. 11. Missed abortion. A 35-year-old woman with
10 weeks of amenorrhea presents with intermittent vaginal
bleeding. TVUS shows a relatively small-sized embryo (arrow) compared with the gestational sac. No cardiac activity
was demonstrated on pulsed Doppler.
hemorrhage from chorionic frondosum is the most
common source of vaginal bleeding in the first
trimester of pregnancy. Subchorionic hemorrhage is
secondary to abruption of the edge of the chorion
frondosum – decidua basalis complex or may be
caused by marginal sinus rupture [63,64]. Although
the hemorrhage usually abuts or elevates the edge of
the chorion frondosum – decidua basalis complex, the
bulk of the hemorrhage is usually situated between
the decidua capsularis, chorion laeve, and the decidua
vera. Acute hemorrhage may be hyperechoic or
isoechoic relative to the chorion, and it becomes
isoechoic with the chorionic fluid in 1 to 2 weeks
(Fig. 12). Several studies have correlated the pregnancy outcome in these patients with the size of the
subchorionic hematoma, gestational age, and the
maternal age. One of the largest studies [65] showed
that the rate of pregnancy loss increases with hematoma size, advancing maternal age, and earlier gestational age. In this study, the size of the hematoma was
graded according to the percentage of the chorionic
sac circumference elevated by the hematoma. It was
graded as small when it involved less than one third
of the chorionic sac circumference, moderate when it
involved one-third to one-half of the chorionic sac
circumference, and large when two-thirds or greater
of the chorionic sac circumference was involved.
There was little difference in the rates of spontaneous
abortion between pregnancies with small- and moderate-size hematomas (7.7% and 9.2%, respectively),
but the rate doubled with large hematomas (18.8%).
The spontaneous abortion rate was also twice as
high in women 35 years of age or older compared
Retained products of conception
Retained products of conception typically consist
of retained placental tissue. An echogenic mass in the
uterine cavity is the most suggestive US finding. A
heterogeneous mass or collection in the central cavity
may represent a blood clot, or some combination of
retained placenta, necrotic debris, and clot (Fig. 13).
Color Doppler may help to differentiate vascularized
trophoblastic tissue from nonvascularized blood clots.
A normal-appearing endometrial stripe or punctate
echogenic foci not associated with a discrete mass
makes retained products of conception unlikely.
Gestational trophoblastic disease
Gestational trophoblastic disease is a spectrum of
pregnancy-related trophoblastic proliferative abnormalities that can present with first-trimester bleeding.
Fig. 12. Subchorionic hemorrhage. TVUS shows a gestational sac (curved arrow), chorion (straight thick arrow),
and a subchorionic hemorrhage (straight thin arrow).
R.M. Paspulati et al / Radiol Clin N Am 42 (2004) 297–314
307
Fig. 13. Retained products of conception with variable appearance. Sagittal (A) and coronal (B) TVUS in two different patients
with persistent vaginal bleeding after spontaneous abortion show retained products of conception with increased echogenicity
(arrowheads) in (A) and heterogeneous appearance in (B). This appearance is secondary to necrosis and blood clots. (C) Increased
vascularity on color flow Doppler evaluation in a patient with retained products of conception.
Classification of gestational trophoblastic disease is
as follows:
Hydatidiform mole
Complete mole
Partial mole
Gestational trophoblastic tumors
Choriocarcinoma
Invasive mole
Placental site trophoblastic tumor
Hydatidiform mole (molar pregnancy)
Molar pregnancy is a noninvasive process characterized by varying degrees of trophoblastic prolif-
eration and edema of villous stroma. Its incidence is
1 in every 1000 to 2000 pregnancies [67] and is
estimated to be as high as 1 in 41 in patients with
miscarriages [68]. Hydatidiform mole constitutes
80% of the cases of gestational trophoblastic disease
with relatively high frequency of molar pregnancy at
the beginning and end of the childbearing period.
Mole recurrence is seen in about 1% to 2% of cases
[69]. The absence or presence of fetus or embryonic
elements is used to classify a molar pregnancy into
complete or partial moles. Complete molar pregnancies are most often 46 XX, with the chromosomes
completely of paternal origin and are referred to as
‘‘androgenesis.’’ The karyotype in partial mole is usually triploid (69 XXY) or even tetraploid (92 XXXY)
with one maternal and two paternal haploid compo-
308
R.M. Paspulati et al / Radiol Clin N Am 42 (2004) 297–314
nents. The fetus in partial mole is usually nonviable
and exhibits features of triploidy, which include
multiple congenital anomalies and growth restriction
[70]. Histologically, the molar tissue has prominent
villi with central acellular space corresponding to the
macroscopic appearance of vesicles. In partial mole
these changes are focal and less advanced.
The clinical presentation of molar pregnancy,
listed below, has changed appreciably over the last
decades because of early diagnosis with TVUS and
quantitative b-hCG estimation.
Uterine bleeding, which may vary from spotting
to profuse hemorrhage
Uterine enlargement out of proportion to the
duration of pregnancy in 50% of cases
Absence of fetal parts or fetal heart sounds
despite an enlarged uterus
Pregnancy-induced hypertension before
24 weeks gestation
Hyperemesis
Thyrotoxicosis, which is usually subclinical
History of passage of grape-like vesicles trans-
vaginally
Uterine bleeding is the most common presentation
and it may vary from spotting to profuse bleeding.
Occasionally patients may pass grape-like vesicles
transvaginally. Clinically the uterine fundal height is
more than is expected for the gestational period. Di-
agnosis is made by markedly elevated serum b-hCG
levels expected for the stage of gestation and by the
characteristic sonographic appearance.
Sonographic features of molar pregnancy
Molar changes can be detected from 8 weeks of
pregnancy by US. The uterine cavity is filled with
multiple sonolucent areas of varying size and shape.
This has been described as a ‘‘snow storm’’ appearance with low-frequency transabdominal scanning.
With high-frequency transvaginal transducers, numerous discrete, anechoic (cystic) spaces are visualized corresponding to the hydropic villi (Fig. 14).
These cystic spaces range from 1 to 30 mm in size
and increase in size with gestational age. Large sonolucent areas or maternal lakes resulting from the stasis
of maternal blood are seen between the vesicles. In
partial mole, an intrauterine embryo is noted along
with molar changes [71,72]. Because the trophoblastic changes develop at a slower rate in partial mole,
it may present as enlarged placenta without macroscopic vesicular changes [73]. Women with a high
b-hCG level for the gestational age without sonographic molar changes should have follow-up US to
exclude partial mole. In missed abortion, impaired
trophoblastic vascularity leads to hydropic degeneration of villi and can resemble a partial hydatidiform
mole on US. The serum b-hCG is not elevated, however, and may be normal or at a lower level than for
Fig. 14. Complete hydatidiform mole. (A) Transabdominal sonogram of the uterus shows a complex mass with multiple welldefined anechoic cystic areas (arrows) corresponding to the vesicles of hydatidiform mole. There was no associated embryo.
(B) Corresponding T1-weighted postgadolinium image of the uterus demonstrates intrauterine complex mass (arrowheads) with
multiple well-defined hypointense lesions that are not enhancing and represent vesicles of hydatidiform mole (arrow).
R.M. Paspulati et al / Radiol Clin N Am 42 (2004) 297–314
the expected gestational age. Rarely, a viable fetus
may be associated with complete molar pregnancy
[74] and is caused by the coexistence of a true mole
and a normal fetus in dizygotic twin gestation. Demonstration of the typical trophoblastic flow is useful
in differentiating the trophoblastic tissue of molar
pregnancy from intrauterine blood clots in a patient
with abortion. Theca-leutin ovarian cysts are seen in
up to 25% to 60% of cases because of hyperstimulation of the ovaries by chorionic gonadotrophin
secreted by the trophoblastic tissue [75]. In this condition, the ovaries are enlarged with multiple cysts
having a soap bubble or spoke-wheel appearance.
Treatment of hydatidiform mole consists of immediate evacuation of the mole and subsequent follow-up with serial measurement of serum b-hCG for
detection of persistent trophoblastic proliferation
or malignant change. TVUS is useful in monitoring patients following evacuation and chemotherapy
[76 – 79]. If the b-hCG levels plateau or continue to
rise, persistent trophoblastic tissue is diagnosed. Following evacuation of a hydatidiform mole, 18% to
29% with complete hydatidiform mole and 1% to
11% with partial mole develop a persistent trophoblastic tumor [80 – 83]. TVUS reveals nodules of
residual echogenic trophoblastic tissue and central
hypoechoic blood spaces. Doppler interrogation
reveals typical low-resistance and high-peak systolic
velocity vascular flow of trophoblastic tissue.
Gestational trophoblastic tumors
Gestational trophoblastic tumor refers to choriocarcinoma, invasive mole, and placental site trophoblastic tumor. It may follow a normal or a molar
pregnancy, abortion, or ectopic pregnancy. Diagnosis
is made primarily by persistent elevation of the serum
b-hCG. Fifty percent of these tumors arise following
hydatidiform mole, 25% following abortion, and 25%
following normal or ectopic pregnancy [84].
Choriocarcinoma
Choriocarcinoma is a malignant form of trophoblastic tumor that invades uterine myometrium and
blood vessels resulting in distant metastasis. The absence of villous pattern is characteristic of choriocarcinoma, in contrast to hydatidiform mole and
invasive mole. The most common sites of metastases
are the lungs (over 75%) and the vagina (50%). Other
sites of metastases include the vulva, liver, kidneys,
brain, ovaries, and bowel [85]. The US appearance
is indistinguishable from a complete mole, except
in cases with myometrial and parametrial extension.
TVUS reveals a heterogeneous intrauterine mass with
309
or without myometrial invasion. Doppler interrogation reveals typical trophoblastic flow and differentiates trophoblastic tissue from areas of hemorrhage
and necrosis. Ovarian theca-leutin cysts are identified
in more than a third of such cases. Cross-sectional
imaging with CT and MR imaging is more accurate in
demonstrating invasion of the myometrium and parametrium. Radiologic evaluation for distant metastases
is mandatory in all cases of choriocarcinoma.
Invasive mole
This is defined as excessive trophoblastic overgrowth with invasion of the myometrium and occasional extension to the peritoneum or adjacent
parametrium. Unlike choriocarcinoma there are no
distant metastases. Invasive mole presents clinically
as heavy vaginal bleeding after the evacuation of the
molar pregnancy with persistent elevation of serum
b-hCG. On TVUS it appears as focal areas of increased echogenicity within the myometrium [86].
Doppler color flow mapping of this area can evaluate
the extent of this lesion and its subsequent response
to chemotherapy (Fig. 15) [87 – 89].
Placental site trophoblastic tumor
This is a very rare trophoblastic tumor, which arises
from the placental implantation site following either a
normal term pregnancy or abortion. These patients
present with either abnormal bleeding or amenorrhea
and might be presumed to be pregnant. Moreover, the
b-hCG levels are not as high as in other forms of
gestational trophoblastic disease [90,91]. They may
invade the myometrium and in 15% to 20% cases
behave in a malignant fashion with distant metastases.
US features are indistinguishable from those of other
gestational trophoblastic tumors [92,93].
Arteriovenous malformation of the uterus
It is important to consider arteriovenous malformations in the differential diagnosis of first-trimester
bleeding because of their sonographic resemblance
to retained products of conception and gestational
trophoblastic disease. Vascular malformations of the
uterus are rare and potentially life-threatening lesions. They can be congenital or acquired following
uterine trauma (surgery or curettage); use of intrauterine contraceptive devices; endometrial or cervical carcinoma; and previous treatment of gestational
trophoblastic tumors [94]. Congenital arteriovenous
malformations have multiple arteriovenous communications and may extend through the myometrium
into the parametrium. Acquired lesions are arterio-
310
R.M. Paspulati et al / Radiol Clin N Am 42 (2004) 297–314
Fig. 15. Invasive mole. (A) TVUS showing molar tissue invading the myometrial wall (arrowheads) of the fundus and
endometrial cavity (arrow). (B) Color flow Doppler evaluation shows vascularity of the invaded myometrium. Endometrial
cavity is shown by arrow. (C) Corresponding T2-weighted, sagittal image of the uterus demonstrates hyperintense myometrium
(arrow) representing invasive molar tissue. Uninvolved endometrial lining is shown (arrowheads).
venous fistulas between a single artery and a vein.
Vascular malformations persist following treatment
in 10% to 15% of patients with gestational trophoblastic tumors. Gray-scale US shows multiple anechoic
spaces with mosaic pattern of color signals within the
cystic spaces on color Doppler US. Spectral analysis
of the vessels shows high-velocity blood flow with a
low resistive index [95,96], indistinguishable from a
gestational trophoblastic disease (Fig. 16). These
vessels can be distinguished from gestational trophoblastic disease because the serum b-hCG is normal.
Uterine arteriovenous malformations are one of the
common causes of spontaneous abortions. Contrastenhanced CT, MR imaging, and angiography are other
imaging modalities used to diagnose uterine arteriovenous malformations. The diagnosis of uterine arteriovenous malformations as the cause of vaginal
bleeding is crucial because treatment is entirely different from that for retained products of conception or
gestational trophoblastic disease, which can mimic
arteriovenous malformations. The treatment of arteriovenous malformations is by embolization if the
R.M. Paspulati et al / Radiol Clin N Am 42 (2004) 297–314
311
Fig. 16. Uterine arteriovenous malformation in a 35-year-old woman with history of spontaneous abortion presenting with
vaginal bleeding. She was referred to exclude retained products of conception. (A) TVUS shows complex endometrial mass
(arrowheads) with anechoic spaces (arrow). (B) Corresponding color flow Doppler demonstrates the mosaic pattern of flow
within the mass (arrowheads). Arrow points to endometrial cavity. Pulsed Doppler (C) shows arterialized venous flow,
diagnostic of arteriovenous malformation.
patient desires fertility and by hysterectomy if fertility
is not an issue.
Summary
Vaginal bleeding is a leading cause of presentation
for emergency care during the first trimester of the
pregnancy. Clinical assessment of the pregnancy
outcome at this stage is less reliable. US examination
is crucial in establishing IUP and early pregnancy
failure and to exclude other causes of bleeding, such
as ectopic pregnancy and molar pregnancy. Diagnosis
of a normal IUP at this stage not only assists the
physician in an expectant management, but also gives
a psychologic boost to the patient. With recent advances in US technology and the availability of highfrequency transvaginal transducers, reliable diagnosis
of early pregnancy failure can be made even before
the embryo is visible.
Acknowledgment
The authors thank Bonnie Hami, MA, Department
of Radiology, University Hospitals of Cleveland,
Ohio, for her editorial assistance in the preparation of
this article.
References
[1] Nyberg DA, Laing FC, Filly RA. Threatened abortion:
sonographic distribution of normal and abnormal gestation sacs. Radiology 1986;158:397 – 400.
312
R.M. Paspulati et al / Radiol Clin N Am 42 (2004) 297–314
[2] Laing FC, Brown DL, DiSalvo DN. Gynecologic ultrasound. Radiol Clin North Am 2001;39:523 – 40.
[3] Goldstein RB, Bree RL, Benson CB, Benacerraf BR,
Bloss JD, Carlos R, et al. Evaluation of the woman
with postmenopausal bleeding: Society of Radiologists
in Ultrasound-Sponsored Consensus Conference statement. J Ultrasound Med 2001;20:1025 – 36.
[4] Forrest TS, Elyaderani MK, Mulenberg MI, et al. Cyclic endometrial changes: US assessment with histologic correlation. Radiology 1988;167:233 – 7.
[5] Tamarkin S, Dogra V. Benign and malignant adnexal
lesions. In: Dogra V, Rubens D, editors. Ultrasound secrets. Philadelphia: Hanley & Belfus; 2004. p. 97 – 104.
[6] Kremkeu FW. Performance and safety. In: Kremkau
FW, editor. Diagnostic ultrasound: principles and instruments. 4th edition. Philadelphia: WB Saunders;
1993. p. 286.
[7] Implementation of the principle of as low as reasonably
achievable (ALARA) for medical and dental personnel.
NRCP report 107. Bethesda, MD: National Council
on Radiation Protection and Measurements; 1990.
[8] Nyberg DA, Hill LM. Normal early intrauterine pregnancy: sonographic development and HCG correlation.
In: Patterson AS, editor. Transvaginal ultrasound. St.
Louis: Mosby; 1992. p. 64 – 85.
[9] Yeh HC, Rabinowitz JG. Amniotic sac development:
ultrasound features of early pregnancy: The bouble
bleb sign. Radiology 1988;166:97 – 103.
[10] Moore KL. Formation of the bilaminar embryo: the
second week. In: Keith L, editor. The developing human: clinically oriented embryology. 5th edition. Philadelphia: WB Saunders; 1988. p. 38.
[11] Emerson DS, Cartier MS, Altieri LA, et al. Diagnostic
efficacy of endovaginal color flow imaging in an ectopic pregnancy scanning program. Radiology 1992;
183:413 – 20.
[12] Dillon EH, Feyock AL, Taylor KJ. Pseudogestational
sacs: Doppler US differentiation from normal or abnormal intrauterine pregnancies. Radiology 1990;176:
359 – 64.
[13] Yeh HC, Goodman JD, Carr L, Rabinowitz JG. Intradecidual sign: a US criterion of early intrauterine pregnancy. Radiology 1986;161:463 – 7.
[14] Laing FC, Brown DL, Price JF, et al. Intradecidual
sign: Is it effective in diagnosis of an early intrauterine
pregnancy? Radiology 1997;204:655 – 60.
[15] Trimor-Tritsch IE, Farine D, Rosen MG. A close look at
early embryonic development with the high frequency
transvaginal transducer. Am J Obstet Gynecol 1988;
159:676 – 81.
[16] Rosavic IK, Torjusen GO, Gibbons WE. Conceptual
age and ultrasound measurements of gestational sac
and crown-rump length in vitro fertilization pregnancies. Fertil Steril 1988;49:1012 – 7.
[17] de crespigny LC, Cooper D, Mckenna M. Early detection of intrauterine pregnancy with ultrasound. J Ultrasound Med 1988;7:7 – 10.
[18] Bradley WG, Fiske CE, Filly RA. The double sac sign
[19]
[20]
[21]
[22]
[23]
[24]
[25]
[26]
[27]
[28]
[29]
[30]
[31]
[32]
[33]
[34]
[35]
of early intrauterine pregnancy: use in exclusion of
ectopic pregnancy. Radiology 1982;143:223 – 6.
Nyberg DA, Filly RA, Duarte DL, et al. Abnormal
pregnancy: early diagnosis by US and serum chorionic gonadotropin levels. Radiology 1986;158:393 – 6.
Kadar N, Devore G, Romero R. Discriminatory hCG
zone: its use in the sonographic evaluation for ectopic
pregnancy. Obstet Gynecol 1981;58:156.
Moore KL. Formation of bilaminar embryo. In: Wonsiewicz M, editor. The developing embryo. 4th edition.
Philadelphia: WB Saunders; 1988. p. 38 – 49.
Levi CS, Lyons EA, Lindsay DJ. Early diagnosis of
non viable pregnancy with transvaginal US. Radiology
1988;167:383 – 5.
Moore KL. The placenta and fetal membrane. In:
Moore KL, editor. The developing human embryo:
clinically oriented embryology. 4th edition. Philadelphia: WB Saunders; 1988. p. 121.
Gitlin D, Pericelli A. Synthesis of serum albumin, prealbumin, alpha 1-antitrypsin and transferin by the human yolk sac. Nature 1970;228:995.
Jauniaux E, Jurkovic D, Henreity Y, et al. Development
of the secondary human yolk sac: correlation of sonographic and anatomical features. Hum Reprod 1991;6:
1160 – 6.
Yeh HC, Rabinowitz JG. Letter. J Ultrasound Med
1995;14:97 – 9.
Goldstein SR, Wolfson R. Transvaginal ultrasonographic measurement of early embryonic size as a
means of assessing gestational age. J Ultrasound Med
1994;13:27 – 31.
Daya S. Accuracy of gestational age estimation by
means of the fetal crown-rump length measurement.
Am J Obstet Gynecol 1993;168:903 – 8.
Wisser J, Dirschedl P, Krone S. Estimation of gestational age by transvaginal sonographic measurement of
the greatest embryonic length in dated human embryos.
Ultrasound Obstet Gynecol 1994;4:457 – 62.
Levi CS, Lyons EA, Zheng XH, et al. Transvaginal US:
demonstration of cardiac activity in embryos of less
than 5.0 mm in crown rump length. Radiology 1990;
176:71 – 4.
Brown DL, Emerson DS, Fleker RF, et al. Diagnosis of
early embryonic demise by transvaginal sonography.
J Ultrasound Med 1990;9:631 – 6.
Pennell RG, Needleman L, Pajak T, et al. Prospective
comparison of vaginal and abdominal sonography in
normal early pregnancy. J Ultrasound Med 1991;10:
63 – 7.
Goldstein SR. Embryonic death in early pregnancy: a
new look at the first trimester. Obstet Gynecol 1994;
84:294 – 7.
Hertzberg BS, Mahony BS, Bowie JD. First trimester
fetal cardiac activity: sonographic documentation of a
progressive early rise in heart rate. J Ultrasound Med
1988;7:573 – 5.
Achiron R, Tadmor O, Machiac S. Heart rate as a
predictor of first-trimester spontaneous abortion after
R.M. Paspulati et al / Radiol Clin N Am 42 (2004) 297–314
[36]
[37]
[38]
[39]
[40]
[41]
[42]
[43]
[44]
[45]
[46]
[47]
[48]
[49]
[50]
[51]
[52]
ultrasound proven viability. Obstet Gynecol 1991;78:
330 – 3.
May DA, Sturtevant NV. Embryonal heart rate as a
predictor of pregnancy out come: a prospective analysis. J Ultrasound 1991;10:591 – 3.
Fleischer AC, James AE, Dawes WJ, Paige M, Robinson HP. Sonographic depiction of pregnancy during
embryonic development. In: Sanders RC, James AE,
editors. The principles and practice of ultrasonography
in obstetrics and gynaecology. 3rd edition. Norwalk
(CT): Appleton-Century- Crofts; 1985. p. 61 – 74.
Jaffe R, Dorgan A, Abramowicz JS. Color Doppler
imaging of the uteroplacental circulation in the first
trimester: value in predicting pregnancy failure or complication. AJR Am J Roentgenol 1995;164:1255 – 8.
Emerson DS, Cartier MS, Altieri LA, et al. Diagnostic
efficacy of transvaginal color Doppler flow imaging in
an ectopic pregnancy program. Radiology 1992;183:
413 – 20.
Parvey HR, Dubinsky TJ, Johnston DA, Maklad NF.
The chorionic rim and low-impedance intrauterine arterial flow in the diagnosis of early intrauterine pregnancy: evaluation of efficacy. AJR Am J Roentgenol
1996;167:1479 – 85.
Robinson HP. The diagnosis of early pregnancy failure
by sonar. Br J Obstet Gynaecol 1975;82:849 – 57.
Donald I, Mosley P, Barnett E. The diagnosis of the
blighted ovum by sonar. Br J Obstet Gynaecol 1972;
79:304 – 10.
Jouppila P, Hesva T. Study of blighted ovum by ultrasonic and histopathology methods. Obstet Gynecol
1980;55:574 – 8.
Nyberg DA, Laing FC. Threatened abortion and abnormal first trimester intrauterine pregnancy. In: Patterson
AS, editor. Transvaginal ultrasound. St Louis: Mosby;
1992. p. 85 – 103.
McKenna KM, Feldstein VA, Goldstein RB, Filly RA.
The ‘‘empty amnion’’: a sign of early pregnancy failure. J Ultrasound Med 1995;14:117 – 21.
Bromley B, Harlow BL, et al. Small sac size in the first
trimester: a predictor of poor fetal out come. Radiology
1991;178:375 – 7.
Levi CS, Lyons EA, Lindsay DJ. Early diagnosis of
non viable pregnancy with endovaginal US. Radiology
1988;167:383.
Crooij MJ, Westhuis J, Schoemaker J, et al. Ultrasonographic measurement of the yolk sac. Br J Obstet
Gynecol 1982;89:931 – 4.
Green JJ, Hobbins JC. Abdominal ultrasound examination of the first-trimester fetus. Am J Obstet Gynecol
1988;159:165 – 75.
Lindsay DJ, Lovett IS, Lyons EA, et al. Yolk sac diameter and shape at endovaginal US: predictors of
pregnancy outcome in the first trimester. Radiology
1992;183:115 – 8.
Stampone C, Nicotra M, Muttinelli C, et al. Transvaginal sonography of the yolk sac in normal and abnormal pregnancy. J Clin Ultrasound 1996;24:3 – 9.
Dugoff L, Persutte WH, Schultz L, Hobbins JC. Prog-
[53]
[54]
[55]
[56]
[57]
[58]
[59]
[60]
[61]
[62]
[63]
[64]
[65]
[66]
[67]
[68]
[69]
313
nostic significance of the large yolk sac. Am J Obstet
Gynaecol 1998;178:S165.
Ferrazi E, Brambati B, Lauzani A, et al. The yolk sac
in early pregnancy failure. Am J Obstet Gynaecol
1988;158:137.
Stampone C, Nicotra M, Muttinelli C, Cosmi EV.
Transvaginal sonography of the yolk sac in normal
and abnormal pregnancy. J Clin Ultrasound 1996;24:
3 – 9.
Harris RD, Vincent LM, Askin FB. Yolk sac calcification: a sonographic finding associated with intrauterine
embryonic demise in the first trimester. Radiology
1988;166:109 – 10.
Barzilai M, Lyons EA, Levi CS, Lindsay DJ. Vitelline
duct cyst or double yolk sac. J Ultrasound Med 1989;8:
523 – 6.
Brown DL, Emerson DS, Felker RE, et al. Diagnosis
of early embryonic demise by endovaginal sonography. J Ultrasound Med 1990;9:631 – 6.
Benson CB, Doubilet PM. Slow embryonic heart rate
in early first trimester: indicator of poor pregnancy out
come. Radiology 1994;192:343 – 4.
Doubilet PM, Benson CB. Embryonic heart rate in the
early first trimester: What rate is normal? J Ultrasound
Med 1995;14:431 – 4.
Bromley B, Harlow BL, Laboda LA, et al. Small sac
size in the first trimester: a predictor of poor fetal out
come. Radiology 1991;178:375 – 7.
Dickey RP, Gasser RF. Ultrasound evidence for variability in the size and development of normal human
embryos before the tenth post insemination week after
assisted reproductive technologies. Hum Reprod 1993;
8:331 – 7.
Smith GS, Smith MF, McNay MB, Flemming JEE.
First trimester growth and the risk of low birth weight.
N Engl J Med 1998;339:1817 – 22.
Nyberg DA, Cyr DR, Mack LA, et al. Sonographic
spectrum of placental abruption. AJR Am J Roentgenol 1987;148:161.
Sauerbrei EE, Pham DH. Placental abruption and sub
chorionic haemorrhage in the first half of pregnancy:
US appearance and clinical out come. Radiology 1986;
160:109 – 12.
Bennett GL, Bromley B, Lieberman E, Benacerraf BR.
Subchorionic hemorrhage in first trimester pregnancies: prediction of pregnancy outcome with sonography. Radiology 1996;200:803 – 6.
Stabile I, Campbell S, Grudzinskas JG. Threatened
miscarriage and intrauterine hematomas: sonographic
and biochemical studies. J Ultrasound Med 1989;
8:289.
Contran RS, Kumar V, Robbins SL. Female genital
tract. In: Contran RS, Kumar V, Robbins SL, editors.
Robbins pathologic basis of disease. 4th edition. Philadelphia: WB Saunders; 1989. p. 1174 – 8.
Jeffers MD, O’Dwyer P, Curran B, et al. Partial hydatidiform mole: a common but under diagnosed condition. Int J Gynecol Pathol 1993;12:315.
Miller DS, Ballon SC, Teng NNH. Gestational tropho-
314
[70]
[71]
[72]
[73]
[74]
[75]
[76]
[77]
[78]
[79]
[80]
[81]
[82]
[83]
R.M. Paspulati et al / Radiol Clin N Am 42 (2004) 297–314
blastic diseases. In: Broody SA, Veland K, editors. Endocrine disorders in pregnancy. Norwalk (CT): Appleton & Lange; 1989. p. 451.
Lawler SD, Fisher RA, Dent J. A prospective genetic
study of complete and partial hydatidiform moles. Am
J Obstet Gynecol 1991;164:1270 – 7.
Szulman AE, Surti U. The syndromes of hydatidiform
mole: I. Cytogenetic and morphologic correlations.
Am J Obstet Gynecol 1978;131:665.
Szulman AE, Surti U. The syndromes of hydatidiform
mole: II. Morphologic evolution of the complete and
partial mole. Am J Obstet Gynecol 1978;132:22.
Fine C, Bundy AL, Berkowitz RS, et al. Sonographic
diagnosis of partial hydatidiform mole. Obstet Gynecol
1989;73:414.
Steller MA, Genest DR, Bernstein MR, et al. Natural
history of twin pregnancy with complete hydatidiform mole and coexisting fetus. Obstet Gynecol 1994;
83:35.
Green CL, Angtuaco TL, Shah HR, Parmley TH. Gestational trophoblastic disease: a spectrum of radiologic
diagnosis. Radiographics 1996;16:1371 – 84.
Tepper R, Shulman A, Altaras M, et al. The role of
color Doppler flow in the management of nonmetatstatic gestational trophoblastic disease. Gynecol Obstet
Invest 1994;38:14.
Mayman R, Schneider D, Schulman A, et al. Serial
color Doppler flow of uterine vasculature combined
with serum beta-hCG measurements for improved
monitoring of patients with gestational trophoblastic
disease. Gynecol Obstet Invest 1996;42:201.
Zanetta G, Lissoni A, Colombo M, et al. Detection of
abnormal intrauterine vascularization by color Doppler
imaging: a possible additional aid for the follow up of
patients with gestational trophoblastic tumors. Ultrasound Obstet Gynecol 1996;7:32.
Long MG, Boultbee JE, Begent RH, et al. Preliminary
Doppler studies on the uterine artery and myometrium
in trophoblastic tumors requiring chemotherapy. Br J
Obstet Gynaecol 1990;97:686.
Jauniaux E, Gulbis B, Hyett J, et al. Biochemical analysis of mesenchymal fluid in early pregnancy. Am J Obstet Gynecol 1998;178:765.
Berkowitz RS, Goldstein DP. Chorionic tumors. N Engl
J Med 1996;335:1740.
Bagshave KD, Lawler SD, Paradinas FJ, et al. Gestational trophoblastic tumors following initial diagnosis
of partial hydatidiform mole. Lancet 1990;335:1074.
Chen RJ, Huang SC, Chow SN, et al. Persistent gesta-
[84]
[85]
[86]
[87]
[88]
[89]
[90]
[91]
[92]
[93]
[94]
[95]
[96]
tional trophoblastic tumour with partial hydatidiform
mole as the antecedent pregnancy. Br J Obstet Gynaecol
1994;101:330.
Cunningham FG, MacDonald PC, Grant NF, Leveno
KJ, Gilstrap LC. Diseases and abnormalities of
the placenta. In: Licht J, editor. Williams obstetrics.
19th edition. Norwalk (CT): Appleton & Lange; 1993.
p. 748 – 59.
Fine C, Bundy AL, Berkowitz RS, et al. Sonographic
diagnosis of partial hydatidiform mole. Obstet Gynecol
1989;73:414.
Aoki S, Hata T, Hata K, et al. Doppler color flow
mapping of an invasive mole. Gynecol Obstet Invest
1989;27:52.
Desai RK, Desberg AL. Diagnosis of gestational trophoblastic disease: value of endovaginal color flow Doppler sonography. AJR Am J Roentgenol 1991;157:787.
Chau MT, Chan FY, Pun TC, et al. Perforation of the
uterus by an invasive mole using color Doppler ultrasound: case report. Ultrasound Obstet Gynecol 1993;
3:51.
Bagshawe KD. Choriocarcinoma: a model for tumour
markers. Acta Oncol 1992;31:99 – 106.
Mazur MT, Kurman RJ. Gestational trophoblastic disease and related lesions. In: Kurman RJ, editor. Blaustein’s pathology of the female genital tract. New York:
Springer Verlag; 1994. p. 1049 – 92.
Caspi B, Elchalal U, Dgani R, Ben-Hur H, Rozenman
D, Nissim F. Invasive mole and placental site trophoblastic tumor: two entities of gestational trophoblastic
disease with a common ultrasonographic appearance.
J Ultrasound Med 1991;10:517 – 9.
Abulafia O, Sherer DM, Fultz PJ, Sternberg LB, Angel C. Unusual endovaginal ultrasonography and
magnetic resonance imaging of placental site trophoblastic tumor. Am J Obstet Gynecol 1993;170:750 – 2.
Newlands ES, Barghawe KD, Begent HJ, Rustin GJS,
Holden L, Dent J. Developments in chemotherapy for
medium and high risk patients with gestational trophoblastic tumors. Br J Obstet Gynaecol 1986;93:63 – 9.
Abu Musa A, Hata T, Hata K, Kitao M. Pelvic arteriovenous malformation diagnosed by color flow Doppler
imaging. AJR Am J Roentgenol 1989;152:1311 – 2.
Sugiyama T. Diagnosis of uterine arterivenous malformation by color and pulsed Doppler ultrasonography.
Ultrasound Obstet Gynecol 1996;8:359 – 60.
Pelage JP, Soyer P, Repiquet D, et al. Secondary post
partum hemorrhage: treatment with selective arterial
embolization. Radiology 1999;212:385 – 9.