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19 2D Ultrasound in Follicle Monitoring for ART
259
include endometrial blood fl ow, endometrial
echo pattern, and endometrial thickness.
The thickened endometrium provides the critical site for embryo attachment. Controversies
exist, however, regarding the clinical signifi cance of observed variations in endometrial
thickness in relation to pregnancy rates (PR)
during IVF. Some studies reported no correlation
between endometrial thickness and PR, while
others suggest a positive correlation between
endometrial thickness and PR, reporting signifi cantly greater endometrial thicknesses occur in
successful IVF cycles compared to unsuccessful
cycles. Possible reasons for this observed discordancy in results may be attributed to different
treatment protocols and/or the different etiologies of infertility. All studies, however, seem to
agree that a “thin” endometrium is detrimental
to the implantation and development of a pregnancy [ 25 ]. Patients with a thin endometrium
present the clinician with a dilemma, therefore,
whether to continue the cycle despite a possibly
reduced chance of pregnancy or to cancel the
cycle and cryopreserve the embryos [ 26 ]. Most
recently a meta- analysis from 2011 found a signifi cant difference in mean endometrial thickness on the day of hCG administration between
IVF patients achieving pregnancy versus those
failing to achieve a pregnancy; a difference of
0.4 mm (95 % CI 0.22–0.58) and an odds ratio
for pregnancy of 1.40 (95 % CI 1.24–1.58) were
reported [ 27 ].
The use of endometrial blood fl ow in predicting endometrial receptivity has also been studied.
Presence of both endometrial and subendometrial blood fl ow correlates with higher implantation and pregnancy rates, and the absence of
endometrial and subendometrial blood fl ow is
associated with a thinner endometrium and is
associated with higher uterine artery resistance
[ 28 , 29 ].
Studies indicate that echogenic patterns of the
endometrium refl ect histologic processes that are
believed to be involved in the establishment of
receptivity as well. This may explain the reported
association between premature hyperechogenic
patterns of the endometrium and poor implantation rates [ 30 ]. Check et al. demonstrated a trend
for higher pregnancy rates in controlled ovarian
stimulation cycles with triple-line isoechogenic
patterns observed in the late follicular phase [ 31 ].
Although there may be a relationship between
endometrial differentiation and pregnancy,
implantation potential is probably more complex
than a few ultrasound measurements can determine. De Geyter concludes that pregnancy rates
of assisted reproductive procedures are infl uenced only marginally by the degree of endometrial proliferation, and treatment should not
be canceled because of inadequate endometrial
thickness [ 26 , 32 ]. At this point there is no con-
sensus to resolve this question.
Monitoring with 2D Versus 3D
Three-dimensional follicular volume measurements have a stronger correlation with the number of mature oocytes retrieved than 2D
measurements. As 3D technology improves, this
parameter may replace 2D measurements in the
optimal timing of hCG before oocyte retrieval
[ 21 ].
Most recently 3D power Doppler angiography
has been introduced for the study of perifollicular
blood fl ow, and this technique enables the study
of all the ovarian and follicular blood vessels. It
can be used to calculate both the vascularization
index (VI) and the fl ow index (FI) from the whole
ovary [ 33 ].
Monitoring with Power Doppler (In Relation to 2D)
Under physiological gonadotropin stimulation,
granulosa cells produce angiogenesis factors
which contribute to the increasing vascularization needed for follicle development, ovulation,
and optimal function of the corpus luteum (CL).
Around the dominant follicle, neovascularization
can be detected by Doppler ultrasound both during spontaneous ovulation and during ovulation
induction. This phenomenon allows measurement of the increased perifollicular blood fl uxes,
and the associated decreased vascular resistance
260
M. Toftager and D.P. Cohen
indexes, around the preovulatory follicle. A rapid
increase in blood fl ow velocity has been reported
to occur at the time of the LH surge in the perifollicular and ovarian stromal blood vessels and has
been associated with a sign of follicle maturity
and approaching ovulation [ 34 , 35 ].
Nargund et al. studied this correlation and
suggested that a perifollicular fl ow >10 cm/s can
enhance selection of oocytes and ultimately
increase pregnancy rates [ 36 ].
High-grade ovarian perifollicular blood perfusion in the early follicular phase during IVF is
associated with both high-grade perifollicular
blood perfusion in the late follicular phase and a
higher clinical pregnancy rate [ 37 ].
Jadaon et al. measured four Doppler indices in
women prior to IVF treatment: peak systolic
velocity (PSV), pulsatility index (PI), resistance
index (RI), and systole/diastole ratio (S/D). They
found a positive correlation between the number
of ≥14 mm follicles on the day of hCG and PSV.
The number of follicles ≥14 mm and retrieved
oocytes had a signifi cant negative correlation
with RI and S/D ratio. As well, the number of
fertilized oocytes had a signifi cant negative correlation with S/D ratio. Absence of a Doppler signal in one or both ovaries was signifi cantly higher
in the women with a poor response (31 %) as
compared to women with a normal response
(16 %) [ 38 ]. PSV of individual follicles among
women undergoing IVF has been shown to correlate with oocyte recovery, fertilization rate,
developmental potential of the oocyte, and the
quality of the preimplantation embryo [ 39 ].
It has been suggested that the Doppler blood
fl ow analysis of the growing follicles could be
used in IVF to select the best oocytes that lead
to embryos with better implantation potential.
However, it is questionable if power Doppler is
an option in busy practices running IVF cycles.
Controlled ovarian hyperstimulation generates
multiple follicles overlapping one another in normal responders, and it may be diffi cult to assign
a specifi c fl ow to an isolated follicle versus the
neighboring one with 2D Doppler. This may imply
that power Doppler is better to use on low responders, women closer to menopause, or women with a
history of multiple failed IVF cycles.
Conclusion
2D ultrasound monitoring of follicular development and maturation during controlled
ovarian stimulation is an integral component
of most clinical practices. It is not always necessary, particularly when using oral agents to
stimulate ovulation, but it is now a standard
of care during any ovulation induction therapy
in advance of an intrauterine insemination or
in vitro fertilization procedure. It provides the
information needed to permit the safe use of
these medications and to avoid the acute risks
of hyperstimulation syndrome and the longerterm sequelae associated with multiple gestation pregnancies. The accuracy and ease of
use of this technical tool was unchallenged; it
only remains to be determined what the positive and negative predictive values of the data
it generates will be. Regardless of the fi nal
outcomes and interpretations of the studies
still underway to fi nd those answers it will
remain a tool, it will not replace the physician’s required judgment of the entire clinical
presentation.
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3D Ultrasound for Follicle Monitoring in ART
Maximilian Murtinger and Nicolas Herbert Zech
2 0
Introduction
There are many factors that infl uence the success
of assisted reproduction technology (ART). These
include medical indications, health status, hormone levels, the stimulation protocol, the preparation of the endometrium for implantation, and
gamete quality. For most of the aforementioned
factors, ultrasound (US) is becoming increasingly
important for use in reproductive medicine. US is
essential for the evaluation of women for infertility factors and subsequent therapy scheduling. It
is also used for the determination of endometrial
thickness (Fig. 20.1 ) and US measurements allow
and facilitate the evaluation of uterine morphology. US can reveal uterine malformations such as
a uterine septum or bicornuate uterus. Moreover,
US can identify pathologic conditions such as
hydrosalpinx, cysts, polyps, and fi broid tumors. It
can also be helpful for the diagnosis of intrauterine adhesions or fi brosis (Asherman’s syndrome)
or just to confi rm that no abnormalities of the
reproductive system are present.
An important strategy to facilitate ART success
is to increase the number of mature oocytes at the
M. Murtinger , MD
IVF Centers Prof. Zech,
Römerstrasse 2, Bregenz 6900, Austria
e-mail: m.murtinger@ivf.at
N. H. Zech , MD (*)
Department of Obstetrics and Gynecology,
Medical University Graz,
Römerstrasse 2, 6900 Bregenz , Austria
e-mail: n.zech@ivf.at
time of ovum pickup (OPU). Therefore, follicular
maturation and timing of oocyte development and
retrieval must be geared to maximize the mature
oocyte yield, thus providing the best chance of an
in vitro fertilization (IVF) success. US monitoring plays a crucial role in this process, even in the
event of unanticipated diffi culties encountered
during embryo transfer. Following ART and successful implantation, US is necessary to monitor the course of pregnancy: (1) to confi rm fetal
heartbeat, (2) to detect fetal growth restriction,
and (3) to detect fetal abnormalities such as anencephaly, spina bifi da, or cardiac defects.
Regarding the course and outcome, there are
major differences between a natural cycle and a
hormonally induced, controlled ovarian hyperstimulation (COH) with multifollicular growth
with ART. Usually, in a natural menstrual cycle,
an average of 10 follicles compete for dominance;
however, ultimately only one follicle prevails and
only one oocyte becomes mature; the other follicles degenerate. Within COH, the preconditions
and course differ completely from a natural cycle.
Although the stimulation protocols might
vary, IVF is usually based on the administration of gonadotropins, which are glycoprotein
hormones such as follicle-stimulating hormone
(FSH), luteinizing hormone (LH), and chorionic
gonadotropin. Basically, three different protocols of stimulation are used with major or minor
modifi cations (gonadotropin-releasing hormone
(GnRH) agonist (long or short protocol) and
GnRH antagonist protocol). The most commonly
used stimulation protocol is the long protocol; it
L.A. Stadtmauer, I. Tur-Kaspa (eds.), Ultrasound Imaging in Reproductive Medicine,
DOI 10.1007/978-1-4614-9182-8_20, © Springer Science+Business Media New York 2014
263
264
M. Murtinger and N.H. Zech
Fig. 20.1 Measurement of endometrial thickness
was fi rst described almost 30 years ago in 1984
[ 1 ]. Even though several infertility clinics apply
generally the two other protocols, short and
antagonist protocols were designed for distinct
medical indications such as low responders or
patients at high risk for ovarian hyperstimulation
syndrome (OHSS) syndrome [ 2 , 3 ].
Before initiating follicular growth using the
long protocol, the fi rst step after the medical
examination is the downregulation of the pituitary gland by supraphysiological doses of GnRH
agonists. These pharmaceutical peptides (i.e.,
triptorelin, ganirelix, cetrorelix, and buserelin)
prevent a premature LH surge. Indeed, in almost
one-fourth of all cycles, such an LH surge occurs
only when gonadotropins are used [ 4 ]. Provided
the menstrual cycle is regular, the initiation of
GnRH agonists in the long protocol is normally
between days 18 and 22 of the menstrual cycle.
GNRH agonists are usually administered via a
subcutaneous injection. These agonists do not
quickly dissociate from the GnRH receptor and
block the GnRH function by reversibly binding
to the GnRH receptor of the pituitary gland (also
known as competitive inhibition). As a result, the
release of FSH and LH from the pituitary gland is
suppressed.
This physiological state, also called downregulation, is usually confi rmed by two main criteria:
(1) the determination of blood hormone levels
(serum estradiol <200 pmol/l) by a clinical laboratory and (2) transvaginal ultrasound (TVUS) by
a physician. The pituitary downregulation should
be confi rmed by a hypoestrogenic state, and additionally, the endometrial thickness (ETS) should
be <5 mm. Measurement of the ETS diameter performed by 3D TVUS can be a highly predictive
method to determine the state of hypoestrogenism [ 5 ]. It should also be noted that an endome-
trial morphology examination is also necessary to
20 3D Ultrasound for Follicle Monitoring in ART
265
determine whether the embryos can be transferred
in a fresh cycle or it is advisable to cryopreserve
them in order to perform a transfer in a subsequent
cryo-cycle (this will be further discussed later in
this chapter). Examinations of the endometrial
volume and the endometrial morphology are crucial to estimate the implantation success, the risk
of spontaneous abortion, or other risks.
In a subsequent step, ovarian stimulation is performed by FSH (i.e., Puregon ® , Gonal-F ® ,
Altermon ® , or Bravelle ® ) or combinations of LH
and FSH (i.e., Pergoveris ® , Merional ® , or
Menopur ® ); these are administered by subcutaneous or intramuscular injections. The administration
of such high, ultra-physiological doses of human
FSH triggers the stimulation, growth, and retrieval
of multiple follicles, thus increasing the number of
mature oocytes [ 6 ]. The retrieval of good quality
oocytes increases the likelihood of a high fertilization rate and an adequate number of high-quality
embryos. Before initiating ovarian stimulation, an
US is a prerequisite for planning the IVF therapy in
detail; it can estimate the ovarian reserve, which can
be done most accurately by an antral follicle count.
To date, as previously mentioned, there are
many applications of US for gynecology and
reproductive biology; furthermore, a variety of
US equipment and techniques are available to
perform US scans. However, as a matter of principle, US techniques can be differentiated by 2or 3-dimensional techniques. Very recently, 4D
US has emerged. With 4D US, only 3D data can
be acquired in real-time mode.
Conventional 2D US instruments are based on
cross-sectional scans, where only a single focus
is visualized. In contrast, 3D US is based on a
series of 2D images, received either by manual or
automatic systems; the 3D image is then calculated and generated. In 3D mode, several scans
are assembled into a 3-dimensional structure;
therefore, the limitation of 3D US quality depends
on the quality of the initial 2D imaging. Thus, it
must be kept in mind that when the original 2D
quality is low, there might be a loss of spatial
resolution in the reconstructed 3D image also.
A 3D US examination comprises four steps:
(1) data acquisition, (2) volume calculation, (3)
image animation, and (4) data storage and trans-
fer. In regard to the mode of data acquisition, US
scans can be obtained either freehand, by manual
movement through the region of interest (ROI),
or automatically, by sweeping through the ROI.
It is indisputable that the former modality is more
subjective and is more susceptible to inter- and
intraobserver reliability, while the latter is more
standardized and accurate. However, it should be
noted that 3D US needs post-processing of the
received data. Data can be stored and visualized
in various displays such as multi-planar with
navigation through the planes or surface rendering mode. The 3D US technique allows for an
easy volume calculation of the examined objects,
which is one of its greatest fortitudes in contrast
to 2D imaging; furthermore, the determination of
the mean diameter of the analyzed object can be
determined. Additionally, post-processing software allows the presentation of 3-dimensional
structures of the examined object in the so-called
inversion mode [ 7 ]. According to differences
in density of tissues or structures, there are differences in ultrasound refl ection and scattering,
which is also referred as echogenicity. Normally,
the degree of echogenicity can be visualized by a
gray scale. Minor echogenicity is represented by
black voxels, while regions of high echogenicity
are pictured by white voxels. The gray-scale
voxels of volume data sets can be inverted; this
sometimes allows a better illustration of anechoic
structures such as cysts. Inversion mode can be
used for a better determination of tissue boundaries and effi cient volume calculation. Some software programs also picture the captured objects
in different colors and, therefore, enable a clear
overview. This is needed when many objects are
scanned and counted (i.e., follicles).
One of the major advantages of US is that it is
a noninvasive, painless, and harmless procedure.
In contrast to X-ray, US scans are not hazardous
either to the patients or to the follicles; furthermore, US radiation does not impair the developmental potential of implanted embryos [ 8 , 9 ].
Portable magnetic resonance tomography (MRT)
instruments are now available; however, the
advantage of US over other imaging techniques
such as MRT is that US equipment is less expensive and easier to operate. Examination with MRT
266
M. Murtinger and N.H. Zech
is more time-consuming than US; furthermore,
it requires contrast agents. Moreover, regarding
imaging and velocity, 3D Doppler sonography
is the only established imaging method for ART
that can display liquid fl ow such as blood circulation; this is accomplished by calculating the frequency shift within the analyzed sample volume.
Due to these various options, Doppler sonography is applicable to a broad fi eld of diagnostic
applications.
Interestingly, the principle of 3D US is not
a new innovation; the technique itself has been
in existence for almost three decades [ 10 ]. This
fact might be quite astonishing; however, it must
be kept in mind that in the past its application
was limited because of the restricted calculation and memory capacity of computer systems
at that time. With the tremendous acceleration
of technical advancements in this fi eld, instruments also became available at an affordable
price for medical applications. Fast computers
now enable 3D ultrasound picture construction,
and the Digital Imaging and Communications in
Medicine (DICOM) specifi cation has facilitated
the full integration of ultrasound into the picture
archiving and communication system (PACS).
Use of 3D Ultrasound of the Female Reproductive System Before and During IVF in Regard to Endometrial Receptivity
On occasion, ultrasound can help determine factors involved in female infertility. Threedimensional TVUS allows evaluation of the
pelvic organs, and it is useful for the detection of
pelvic pathologies such as myomata, polyps, or
cysts, which can have detrimental effects on a
patient’s health, fertility, and pregnancy outcome.
US aids in the identifi cation of malformations of
the uterus such as unicornuate uterus, bicornuate
uterus, or uterine septae. Patients with these malformations require intense pregnancy surveillance
because pregnancy loss, premature birth, and
other complications are more common [ 11 – 14 ].
Furthermore, approximately about one- fourth of
patients with recurrent pregnancy loss may have
uterine anomalies [ 15 ]. The use of 3D ultrasound
techniques is superior to other modalities for the
detection of uterine malformations. The correct
diagnosis of malformations is crucial for deciding
whether to correct them i.e., by hysteroscopy or to
refrain from surgical intervention.
Although 3D US can confi rm the status of a
woman’s reproductive system, the medical literature contains only a handful of studies in this
regard. A prospective study encompassing 284
women demonstrated the reliability of 3D US for
the detection of Müllerian anomalies [ 16 ]. The
accuracy was verifi ed by endoscopy, and the
authors noted that the scan could be performed in
a brief period of time. Their fi ndings confi rmed
previous studies by other investigators [ 17 , 18 ].
Furthermore, the high intra- and interobserver
reliability for 3D sonography has been reported
[ 15 ]. In view of this, it must be kept in mind that
2D US of the pelvic organs cannot achieve this
degree of accuracy. Rosendahl et al. demonstrated this feature by comparing the true ovarian
volume and the volume determined by 2D US;
they reported a discrepancy of approximately
30 % [ 19 ].
Ultrasound not only allows the imaging of the
major organs but also the detection of small histological abnormalities. For example, a recent study
evaluated 275 consecutive women undergoing an
IVF cycle in which TVUS was applied; it showed
that the clinical and ongoing pregnancy rates
drastically decreased when women had adenomyosis [ 20 ]. The authors pointed out that the diag-
nosis of adenomyosis could be promptly made
with high-resolution transvaginal ultrasound. The
fi nding that adenomyosis can impair pregnancy is
also supported by a former retrospective study of
748 IVF patients who underwent a TVUS to identify possible pelvic pathology before starting IVF
therapy with the GnRH antagonist protocol. The
investigators found that the clinical pregnancy rate
was reduced by 50 % in patients with adenomyosis, compared to women without the condition
[ 21 ]. Nevertheless, these authors correctly stated
that “there is no consensus regarding the impact
of adenomyosis on implantation potential.” This
fi nding is quite remarkable because the worldwide
IVF success rates are still unsatisfactorily low and
20 3D Ultrasound for Follicle Monitoring in ART
267
assisted reproduction facilities are still facing the
challenge of pregnancy rate improvement. This
situation might be explained by the fact that US
advancements, especially the 3D techniques, have
only recently appeared; thus, IVF pregnancy rates
may increase in the near future.
The endometrium is the innermost glandular
layer of the uterus and the location for embryo
implantation. Morphology and thickness (volume) of the endometrium can be visualized by
US. This technique is widely used because pathological alternations of the endometrium can drastically impair female fertility. Endometrial polyps
might affect embryo implantation (depending on
their size, position, and number). Therefore,
detection of these polyps is relevant for IVF success. Either subsequent removal by polypectomy
or the application of IVF cryo-cycles is the
method of choice. Nevertheless, to date only limited data is available, and only a few studies have
demonstrated the superiority of 3D techniques in
the diagnosis of endometrial polyps compared to
2D US [ 22 ]. A study of 103 patients with post-
menopausal bleeding revealed the advantages of
3D techniques for the diagnosis of endometrial
pathologies [ 23 ]. Therefore, the application of
3D US allows a conceivably better discrimination between benign and malignant endometrial
pathologies with less false-positive results; furthermore, endometrial volume calculation with
3D US was found to be superior to 2D US for the
measurement of endometrial thickness. The
advantage of 3D US to discriminate between different uterine anomalies was also demonstrated
by two other studies [ 17 , 18 ].
In addition to correctly diagnosing endometrial pathology, a second crucial point is that follicular maturation needs to be synchronized with
endometrial receptivity in order to achieve and
sustain a pregnancy. Endometrial morphology,
thickness, and perfusion are subjected to hormonal alterations, which are refl ected by a shift
in morphology and function. Beginning in the
1990s, the relationship between serum estradiol
levels and endometrial thickness during downregulation has been demonstrated by multiple
studies; however, the fi rst study of the new 3D
US that imaged the endometrium was published
by Yaman et al. [ 5 ]. They fi rst examined endo-
metrial volume by 3D ultrasound in the case of
pituitary downregulation. They found that 3D
measurements of the endometrial volume were
highly accurate; however, the authors reported
no additional benefi ts of the endometrial volume measurement. The endometrial receptivity
for embryo implantation is characterized by certain morphological and biochemical alternations
and is also called the “window of implantation.”
These alternations include an increase in the proliferation and thickness of the endometrium.
According to the application of high, supraphysiological hormone dosages during stimulation, it is sometimes diffi cult to simultaneously
achieve both perfect development of multiple
follicles and optimal endometrium buildup.
Therefore, characteristics of the human endometrium, including thickness (volume), morphology, endometrial blood fl ow, and vascularization,
can be readily and noninvasively monitored by
US monitoring. Nevertheless, a direct correlation
between endometrium buildup and implantation
rates as well as pregnancy rates is still to be confi rmed. Although endometrial patterns have been
reported to correlate with endometrial stages for
the past 15 years [ 24 ], large discrepancies have
been reported in regard to correlations between
the foregoing and endometrial thickness necessary for successful implantation. Some studies
have reported correlations between endometrial
thickness, endometrial morphology, and pregnancy outcome; however, others do not address
those factors [ 25 , 26 ].
Currently, there is still no consensus regarding
the endometrial thickness and endometrial volume necessary for successful implantation.
However, most physicians agree that a certain
degree of buildup is crucial. Several studies have
suggested that pregnancy rates dramatically
decrease when the endometrial thickness is
<5–7 mm or the endometrial volume is <2.5 or
1 ml, respectively [ 5 , 27 – 30 ].
In a 2001 study, it was reported that implantation is unlikely when the endometrial thickness
is <5 mm [ 31 ]. Other investigators report no cor-
relation of endometrial thickness and patterns
to implantation rates [ 32 ]. The reason for these
268
M. Murtinger and N.H. Zech
discrepancies might be based on the application
of different stimulation protocols, the various
sonographic instruments and techniques (primarily 2D US) employed, and especially on the different patient subgroups analyzed. Therefore, the
outcome cannot be directly compared. It must be
noted, however, that there are application limitations of 2D US for this procedure. Measuring
the endometrial volume by this technique yields
limited accuracy and requires signifi cant time.
Even for endometrial thickness, there is currently no general consensus of a cutoff value
[ 30 ]. However, some authors have proposed a
minimum of 5–8 mm. Despite this situation,
there might be a higher consensus to recommend
embryo cryopreservation in cases of thin and
non-trilaminar endometrium because the likelihood of implantation is low with this fi nding.
One study directly compared 2D and 3D US
applications in US scans of the endometrium [ 30 ];
in addition, several studies have reported the
advantages of 3D US in analyzing the endometrium. The major advantage of 3D US over 2D US
is that it is a simple method of measuring the endometrial volume. The morphology of the endometrium can be readily determined when it appears as
trilaminar (with a central echogenic line, inner
hypoechoic regions, and hyperechogenic outer
walls) or non-trilaminar (as a homogenous layer).
Additionally the advantage of 3D US for calculation of the endometrial volume is its low deviation
of inter- and intraobserver reliability [ 33 , 34 ].
However, these parameters might not in themselves be adequate for the prediction of successful
implantation [ 35 , 36 ]; thus, other factors that can
infl uence the success rate have to be considered.
US Monitoring of Polycystic Ovary Syndrome (PCOS) Patients
Polycystic ovary syndrome (PCOS) is one of the
most common endocrine disorders impairing female
fertility; it has been reported to occur in about 20 %
of the general female population and in up to 50 %
of women undergoing IVF therapy [ 37 – 39 ].
A number of symptoms have been associated
with PCOS that are subject to controversy; how-
ever, four defi ned criteria have broad acceptance
as symptomatic of the disease: (1) chronic irregular ovulation or anovulation (therefore oligomenorrhea, might be an early clinical symptom for
PCOS), (2) hyperandrogenism diagnosed clinically (expressed by alopecia, hirsutism, and/or
acne) or by laboratory fi ndings (serum testosterone >1.4 nmol/l), and (3) the exclusion of other
endocrine disorders. The fourth criterion can only
be defi ned by ultrasound examination. Polycystic
ovaries are defi ned as those which contain ten or
more cysts with a maximum diameter of 10 mm
arranged either peripherally around a dense core
of stroma and/or scattered throughout an increased
amount of stroma [ 40 ]. Moreover, PCOS patients
are more likely to have larger ovarian volumes
(>10 cm 3 ) and ovarian stroma with increased
volume and increased numbers of antral follicles
(12 or more follicles, according to the Rotterdam
criteria) [ 41 ]. Therefore, US scans play a crucial
role in diagnosing this disease. The new automated 3D US techniques facilitate the exclusion
of a false-positive PCOS diagnosis and refl ect
pathophysiological changes in these patients in
a more accurate manner. An early detection of
PCOS is highly recommended for women undergoing IVF treatment, due to the elevated risk for
OHSS. Unfortunately, because 3D ultrasound is a
relatively new imaging modality, the Rotterdam
criteria only take 2D US sonography into account.
At present, only a few studies have evaluated
the use of 3D US for PCOS patients [ 42 ]; further-
more, to date, only one study has addressed automated 3D US (SONO-AVC) [ 43 ]. In a
retrospective cohort study, Allemand et al. analyzed 29 normoandrogenic, ovulatory women
with tubal or male factor infertility and 10 PCOS
women with chronic anovulation and clinical or
biochemical hyperandrogenism [ 42 ]. Mean folli-
cle number/ovary (FNPO) as well as the maximal
number of follicles in a single sonographic plane
(FSSP) was determined by 3D TVUS; simultaneously, the ovarian volume was determined by 2D
TVUS. Interestingly, the authors postulated a
considerably higher threshold of antral follicles
(20 or more) for PCOS patients, which is a considerably higher threshold than that of the
Rotterdam criteria. The authors explained this