The role of 3D ultrasound in the management ofpregnancies of unknown location

In the first trimester, the location of the pregnancy

should be established using ultrasound, as ectopic

pregnancy (EP) is still one of the most common life

threatening complications of early pregnancy.

Some pregnancies cannot be visualized as either

intra- or extra-uterine pregnancies at the time of

the init ial transvaginal scan (TVS). These

pregnancies are classified as pregnancies of

unknown location or "PULs". Some women are

classified with a PUL at the primary TVS because

they are scanned too early in pregnancy's

development and the trophoblast, whether located

intra- or extra-uterine, is too small to be visualized.

Some women's pregnanc ies have fa i led

spontaneously by the time the scan is performed

and therefore will never be seen on TVS. These are

made up of early complete miscarriages and self-

limiting forms of ectopic pregnancy (EP). The

possible outcomes of PULs are: a failed PUL, intra-

uterine pregnancy (IUP), EP and persistent PUL. The

authors propose the use of 3D TVS to aid in the

prediction of PUL outcome, which potentially can

result in reduced follow up without compromising

care.

W H I T E P A P E R

Article # WP201108-ELS

Issue Date 31 Aug, 2011

George Condous MBBS, MRCOG, FRANZCOG, MD and Shannon Reid, MBBSAcute Gynaecology, Early Pregnancy and Advanced Endosurgery Unit, Nepean Centre for Perinatal Care,

Sydney Medical School Nepean, University of Sydney, Nepean Hospital, Penrith, Sydney, Australia

1

Introduction

MethodsAll women in the first trimester of pregnancy presenting

to the Early Pregnancy Unit (EPU) at Nepean Hospital

underwent a TVS. If the woman was classified as

having a PUL, 2 dimensional (D) images and 3D

volumetric acquisitions were obtained of the

endometrial cavity and adnexal regions using a 4-9

MHz transducer and the Accuvix V20 Prestige

ultrasound machine (Samsung Medison Co., Ltd.).

Virtual organ computer-aided analysis (VOCAL) was

used for off-line analysis of these 3D volumes. The

following volumetric indices were evaluated:

symmetry of the endometrial cavity, endometrial

volume (EV), mean gray-scale index (MGSI), volume

of the ovary containing the corpus luteum (if

present), as well as 3D Power Doppler vascular

indices for the corpus luteum including flow index

(FI), vascular index (VI), vascular-flow index (VFI) for

early pregnancies classified as PULs.

The concept of measuring uterine and ovarian

structures with 3D TVS to confirm early IUP

originates from the knowledge of physiological

changes that occur during menstruation and

implantation of the blastocyst. The combined

reaction to oestrogen and progesterone activity in

the second half of the menstrual cycle leads to

the secretory changes within the endometrium.

The total endometrial height is fixed at roughly

its pre-ovulatory extent of 5 - 6 mm, but the

glands and the vessels continue to grow. This

results in progressive tortuosity of the glands

and intensified coiling of the spiral vessels within

the endometrium. Within the glandular cells,

vacuoles are formed. Initially they are located

under the nucleus and subsequently migrate

towards the glands' lumen to be secreted in the

endometrial cavity. Thereafter, in the late secretory

phase, the stroma cells become large and

polyhedral producing a compact sturdy stroma.

The subepithelial capillaries and spiral vessels

become more and more engorged and by day 21 -

22 of the cycle oedema of the endometrial stroma

due to increased capillary permeability, becomes

the predominant morphologic feature.

Implantation of the blastocyst is usual ly

accompanied by proliferation of the maternal

decidua surrounding the blastocyst. Antero-

posterior thickening of the decidua in the region of

implantation has already been described by

transabdominal scanning in intra-uterine gestations

as early as 3½ weeks. Implantation of the

blastocyst in the decidua is usually asymmetrical

with regard to the transverse direction. We

hypothesized that the decidual reaction may be

present in very early IUPs even when the

gestational sac itself is not visible on TVS.

According to this concept it was hypothesized that

this asymmetrical decidual reaction is lacking in

PULs which subsequently develop into an EP.

The introduction of 3D imaging has allowed for

major advancement in the use of TVS to assess

fetal structures, as well as the uterus and ovaries.

By using 3D imaging, the clinician is able to view

the images interactively in three dimensions. In

addition to improved visualisation of these

structures, 3D TVS is also considered to have the

advantages of improved accuracy, reproducibility

and patient acceptability. When examining the

coronal or C-plane using 3D TVS, the outline of

2

the uterus and endometrial cavity can be assessed

simultaneously using the section reconstruction

method of a 3D volume. This is a major advantage

over traditional TVS or trans-abdominal ultrasound,

as the C-plane is difficult to obtain by the 2D

method. When the uterus is analysed in three

perpendicular planes using the 3D function, the

result is a higher sensitivity and specificity when

compared to 2D analysis. One of the weaknesses

of the 3D imaging has been the lack of clarity of

3D images when compared to 2D. The new

technology of High Definition Volume Imaging

(HDVI™) has overcome this weakness, by

improving the contrast and resolution of 3D

images in the C-plane.

The images in Figures 1 and 2 display the

endometrial cavity evaluated in C-plane to assess

symmetry. Three aspects of the C-plane were

inspected to determine whether the endometrial

cavity was symmetrical or asymmetrical. If all of the

following were present, then the endometrial cavity

was deemed to be symmetrical:

If one or all of the above were absent, then the

endometr ia l cav i ty was deemed to be

asymmetrical.

1.

2.

3.

the endometrial areas near the left and right

tubal corner mirrored each other,

the height of the tubal horns, i.e. their distance

from the upper margin of the uterine fundus,

was the same, and

the configuration of both sides of the total

endometrium with respect to the median

uterine long axis was the same.

IUPs represent 35 - 38% of the PUL population,

and these early pregnancies tend to demonstrate

an asymmetrical endometrial cavity on 3D TVS.

Figure 1 represents a 3D image in the C-plane of

an asymmetrical endometrial cavity. The triangular

shape of the endometrium is deformed in this

image, and this endometrial asymmetry is present

in the majority of early IUPs.

Published data suggest that, in experienced

sonological hands, 8 - 14% of women with PUL at

the initial TVS will be later diagnosed with an EP.

Figure 2 represents a 3D image in the C-plane of

the endometr ia l cavi ty in a PUL, which

subsequently developed into an EP. The 3D Mirror

View™ function can also be used to assess cavity

shape, with the added ability to view sagittal and

coronal planes simultaneously (Figure 3). In the

case of early EPs, the endometrial cavity almost

always displays a symmetrical shape on 3D TVS.

The absence of a decidual reaction in EPs may

explain why these pregnancies display a

symmetrical shape compared to IUPs.

Failed PULs represent 50 - 53% of PULs, and these

early pregnancies also demonstrate a symmetrical

endometrial cavity on 3D TVS. Less than 2% of

PULs will remain non-visible on serial 2D TVS,

however the serum human chorionic gonadotrophin

(hCG) levels plateau or continue to rise sub-

optimally. These are known as persistent PULs and

may also display a symmetrical endometrial cavity.

The EV, ovarian volume, and 3D power Doppler

indices (FI, VI, VFI) in the ovary can also be

analyzed using 3D TVS. The ability to manipulate

these 3D images at any chosen section in the

volume data set allows for thorough examination

of the structure of interest. During 3D imaging, the

structure's volume can be measured regardless

3

Results

Figure 1 This image represents an asymmetrical endometrial cavity obtained in the coronal plane during 3D TVS.

Figure 2 This image, obtained in the coronal plane during 3D TVS, represents a symmetrical endometrial cavity in a PUL that subsequently developed into an EP.

Figure 3 These images of the uterus were obtained using the 3D Mirror View ™ function, which allows for simultaneous viewing of both sagittal and coronal planes in 3D.

of its shape. The EV, ovarian volume and 3D Power

Doppler indices of the ovary can be manually

calculated with VOCAL analysis in the longitudinal

plane, with 30 degrees rotational steps. Studies

using 3D TVS with VOCAL analysis to measure

endometrial and ovarian volumes have shown this

method to be acceptable in terms of accuracy,

reliability and intra- and inter-observer agreement,

and are deemed better than that of 2D TVS.

The image in Figure 4 represents the EV and the

corresponding histogram for MGSI in a persistent

PUL. The inferior margin of the endometrial

volume tracing performed during off-line VOCAL

analysis is demarcated at the level of the internal

cervical os. A reduction in EV is predictive of early

pregnancy loss (prior to visualisation of the

gestational sac) in women undergoing IVF. PULs,

which develop into IUPs, tend to have a higher

MGSI compared to PULs that are later identified as

EP or failed PULs. The MGSI for PULs can be

derived using the histogram facility during off-line

VOCAL analysis.

3D TVS and VOCAL analysis has been used in

previous studies to measure ovarian volume and

ovarian Power Doppler indices, mainly in

association with assisted reproduction. 3D Power

Doppler a l lows for the quick and easy

visualization of vessels, with regard to the

overlapping of vessels and the association of

surrounding vessels or structures. Substantial

changes in ovarian volume and ovarian Power

Doppler indices during the normal menstrual

cycle have been confirmed using 3D TVS. Figure 5

displays an image of 3D Power Doppler indices

for an ovary with a corpus luteum in early

pregnancy. According to preliminary data, IUPs

appear to have a significantly higher FI in the

ovary containing the corpus luteum, than seen in

EPs.

4

Figure 4 3D endometrial volume having been calculated using VOCAL. Using the histogram feature of VOCAL, the Mean Gray Scale Index (MGSI) can be calculated.

Figure 5 This image represents the ovarian volume, 3D Power Doppler indices, and MGSI for an ovary with a corpus luteum in early pregnancy.

By using 3D imaging and VOCAL off-line analysis

to determine endometrial cavity symmetry, EV,

MGSI, ovarian volume and ovarian Power Doppler

vascular indices, there appears to be usefulness in

the prediction of both location and viability of

PULs. The novel use of 3D volumetric data and

symmetrical analysis of the endometrium, in

combination with biochemical data, may indeed

have prognostic value in the management of PULs

moving forward. Future research in women with

PULs will aim to evaluate the use of 3D imaging

Discussion

with the advanced technology of HDVI™. If proven

to be valid, the use of 3D volumetric data and off-

line VOCAL analysis of the endometrial cavity and

ovary will localise those pregnancies classified to

be PULs and in turn potentially reduce follow up.

5

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3.

4.

5.

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