Predictive values of ultrasound monitoring of the menstrual cycle
Ratko Matijevic and Ozren Grgic
Purpose of review
This review summarizes the current knowledge about
ultrasound scanning values in monitoring the structural and
functional changes of the uterus and ovaries during the
menstrual cycle.
Recent findings
The views that ovulation is more frequently right sided have
been challenged, with recent data suggesting that ovulation
occurs randomly. A ‘follicular wave phenomenon’, providing
a new model for ovarian function during the menstrual cycle,
has been described. Follicular development occurs in a
wave-like fashion and women with two waves have earlier
endometrial development due to earlier increase of the
dominant follicle estrogen production. Myometrial
contractions during menstrual cycle should be considered
in the assessment of endometrial thickness. Uterine–
ovarian arterial blood flow impedance is important in
understanding the normal physiology of the menstrual cycle
and may be of use in assisted conception protocols.
Summary
At present, ultrasound scanning has an important role in
noninvasive assessment of endometrial and ovarian cyclical
changes and may be of particular importance in assisted
conception procedures. Further work is likely to help in
understanding its full diagnostic potential.
Keywords
endometrium, folliculogenesis, menstrual cycle, ovary,
ultrasound
Curr Opin Obstet Gynecol 17:405–410. # 2005 Lippincott Williams & Wilkins.
University Department of Obstetrics and Gynecology, School of Medicine, Zagreb
University, Sveti Duh Hospital, Zagreb, Croatia
Correspondence to Ratko Matijevic MD PhD MRCOG, Sveti Duh Hospital, Sveti
Duh 64, 10000 Zagreb, Croatia
Tel: +385 1 37 123 17; fax: +385 1 37 455 34;
e-mail: ratko.matijevic@zg.t-com.hr
Current Opinion in Obstetrics and Gynecology 2005, 17:405–410
Abbreviations
3D three-dimensional
IVF in-vitro fertilization
# 2005 Lippincott Williams & Wilkins
1040-872X
Introduction
During each menstrual cycle, the structure and possibly
the function of genital organs and ovaries are modulated
by cyclic hormonal changes of the demonstrated hypotha-
lamic–pituitary–ovarian axis. Some of these changes can
be assessed by ultrasound, particularly transvaginal sono-
graphy alone or combined with the three-dimensional
(3D) ultrasound and Doppler technique [1].
It is clear that the transvaginal approach is superior to the
transabdominal method in most of the measured para-
meters except in the monitoring of follicular growth,
when the performance of both approaches does not differ
significantly [2,3].
Transvaginal sonography has a vital role in infertility
protocols through follicular monitoring, endometrial
assessment, guided follicular aspiration and many other
procedures. During the last decade new techniques have
been developed, including color/pulsed Doppler, power
Doppler and 3D ultrasound. All have the potential to be
new diagnostic tools helping us to better understand the
physiologic changes occurring during the menstrual cycle
as well as monitoring responses to therapeutic modalities.
In this review we aim to summarize our present knowl-
edge, with particular emphasis placed on the new devel-
opments made during the last 2 years.
Uterine and endometrial assessment
Endometrial cyclical changes can be assessed by ultra-
sound and correlated with ovarian function and serum
levels of estrogen and progesterone [4,5]. Assessment is
performed through endometrial thickness measurements
and echogenicity analysis of stratum basalis and stratum
functionalis and their relationship to the myometrium [5].
Ultrasound assessment of endometrium
By the end of the luteal phase the progesterone and
estrogen levels decrease, causing the breakdown of the
functional layer. Ultrasound appearance varies depen-
ding on the number of blood clots and endometrial
fragments giving an impression of echogenic debris
(M pattern) [6].
In the follicular phase the increase in endometrial thick-
ness is associated with rising serum estradiol levels. In the
early stages, endometrial thickness measures 1–3 mm
and has a simple hyperechogenic single stripe (A pattern).
This appearance is also seen in women taking the com-
bined oral contraceptive pill or in women with some form
405
406 Reproductive endocrinology
of hypothalamic ovulatory dysfunction. With the progres-
sion of the follicular phase, the echogenicity of the
endometrium decreases in comparison with the sur-
rounding myometrium. It takes the characteristic appear-
ance of nonuniform echogenicity with a central area of
brightness which finally changes to a triple line pattern in
the late follicular phase (B pattern). The endometrial
thickness increases to 4–8 mm reaching a maximum of
around 12 mm at the time of the estrogen peak during the
periovulatory period [6,7].
Endometrial thickness remains relatively constant
throughout the luteal phase. This period of static growth
is most likely to be maintained by the increasing proges-
terone levels. The endometrium is extremely sensitive to
a fall in progesterone at this stage regardless of the
estrogen levels [8]. The typical triple-line ultrasound
pattern disappears after ovulation. A more homogeneous,
hyperechogenic endometrium is observed as endometrial
glands branch and expand under the influence of pro-
gesterone (D pattern) [9]. If pregnancy occurs, echogeni-
city and thickness are maintained as decidual reaction to
implantation starts to progress. If not, the endometrium
begins to regress in thickness, but not in the echogenicity,
finally ending in breakdown of the functional layer [6].
Endometrial thickness
Measurement of the endometrial thickness, which should
be performed in the sagittal plane, is the distance
between the anterior and posterior stratum basalis layers
[9]. The hypoechoic part around the endometrium repre-
sents the inner layer of the myometrium and must be
excluded from the measurements [4,6]. Recently it was
found that spontaneous uterine contractions occurring in
a normal menstrual cycle can influence the measure-
ments [10] and it was proposed that the endometrial
thickness should be measured before, during, and after
the wave-like contractions, and the mean value should be
used for further calculations [11].
Endometrial changes detectable by ultrasound are also
associated with follicle wave dynamics, and earlier endo-
metrial development during the follicular phase was
found in women with two follicle waves. This was attrib-
uted to earlier increase in the dominant follicle estrogen
production [12

]. Successive waves of ovarian follicular
development during the menstrual cycle have recently
been documented in humans. This is called a follicular
wave phenomenon and it challenges the traditional
thinking of a single cohort of antral follicles growing only
during the follicular phase. The follicular wave phenom-
enon provides a new model for studying follicular devel-
opment during the menstrual cycle in humans. It is
defined as synchronous growth of a group of follicles in
which only the final follicular wave was ovulatory while
all preceding waves were anovulatory. Dominant follicles
were selected for preferential growth at a diameter of
approximately 10 mm [13]. Approximately two-thirds of
women exhibit two follicular waves while the remaining
one-third exhibit three follicular waves during an inter-
ovulatory interval [14].
Three-dimensional ultrasound in endometrial
assessment
Recently, 3D ultrasound was introduced into clinical
practice. This technique found its place in the endome-
trial assessment through endometrial volume measure-
ments. Both methods (2D and 3D) are reliable, but the
full planar method seems to provide slightly better
reproducibility in endometrium volume measurements
[15,16]. Endometrial volume, similar to endometrial
thickness, increases significantly during the follicular
phase, reaching a plateau around the time of ovulation
and remaining relatively stable throughout the luteal
phase [17
]. However, it is not possible to comment on
the superiority or otherwise of 3D ultrasound compared
with the 2D method in endometrial assessment.
Endometrial assessment and assisted conception
It has been accepted that conception is unlikely in cycles
when the endometrium measures less than 13 mm
11 days following ovulation [18]. The presence of a
multilayered endometrium within 1–2 days of embryo
transfer was found to be associated with a high postovu-
latory conception rate [19]. Ultrasound monitoring of
endometrial thickness in the follicular phase of natural
cycles in fertile or subfertile women may also be useful in
predicting pregnancy rate in subsequent stimulated
cycles [20]. Higher endometrial development (triple line
pattern and thickness 9 mm) in natural cycles was
associated with ‘optimal’ development in subsequent
stimulated cycles in 96% of cases, while lower endome-
trial grades (echogenic pattern or thickness < 9 mm) in
natural cycles improved only in 55% of cases following
ovarian stimulation [20]. However, the data remain
inconclusive. In 25 published reports, eight found statis-
tically significant differences in the mean endometrial
thickness of conception and nonconception cycles, but 17
did not [21]. This observation is confirmed in some recent
studies using clomiphene citrate [22
].
Uterine blood flow assessment
Color Doppler assessment of uterine artery blood flow
and its branches has a significant role in monitoring the
menstrual cycle. A uterine artery pulsed Doppler wave-
form in the follicular phase is characterized by high peak
systolic velocity, proto-diastolic notch and low end-dia-
stolic velocity. Impedance to the blood flow is high and
related to high estrogen levels, representing the
increased resistance in distal vascular branches [23,24].
It becomes even higher at the time of ovulation. This
can be related to increasing uterine contractility and
 Ultrasound monitoring of the menstrual cycle Matijevic and Grgic 407
compression of the uterine artery branches in the myo-
metrium because of the sudden drop in serum estrogen.
Compression decreases the diameter of blood vessels
resulting in high resistance, sometimes even completely
disrupting diastolic blood flow. During the luteal phase,
the typical pulsed Doppler profile of the uterine artery is
characterized by high peak systolic velocity but end
diastolic flow increases and the proto-diastolic notch
disappears. Impedance to the blood flow is significantly
lower compared with the follicular phase and it is related
to high progesterone levels [25].
In assisted reproduction cycles, Doppler assessment of
uterine artery blood flow can help to determine a time
interval within the menstrual cycle related to optimal
endometrial status for embryo implantation [26

].
Significantly lower impedance indices were found in
pregnant than in nonpregnant women before embryo
transfer, but there were no significant differences
between the two groups 5–6 days after the transfer.
In the last two decades, there has been an increasing
interest in the blood flow assessment of more distal
branches of the uterine artery, including the arcuate
and radial arteries. The pulsed Doppler pattern and
cyclical changes in these vessels are similar to those in
uterine arteries [24].
The terminal ends of uterine circulation are spiral
arteries. Their importance in blood supply is well docu-
mented in pregnancy and there is increasing interest in
their assessment in in-vitro fertilization (IVF) cycles
[24,25,26

,27–29]. Spiral arteries can be visualized
within the functional zone of the endometrium and
sometimes are named subendometrial vessels. Their
pulsed wave velocity waveform is characterized by lower
velocity and impedance compared with uterine arteries,
and they follow the same cyclical changes with lower
impedance in the luteal compared with the follicular
phase [24]. The uterine artery and its branches can clearly
be identified with the color Doppler technique. How-
ever, this is not always the case with spiral arteries, where
power Doppler was found to be superior as it has better
sensitivity, displaying lower velocities and being angle
independent [28].
With 3D ultrasound the whole of the uterine vascular
network can be examined and this technique may
provide an impression of complete uterine perfusion
[29]. Total examination time may be reduced signifi-
cantly by using the 3D/power Doppler technique.
However, neither the volume nor the thickness of
the endometrium on the day of embryo transfer had
a predictive value for conception during the IVF cycle,
although the patients who become pregnant were
characterized by significantly lower impedance in
subendometrial vessels [29].
A recent publication examining 3D/power Doppler [30
]
demonstrated distinct changes in the vascularity of the
uterus during the normal menstrual cycle. It also supports
Doppler parameters, with a preovulatory peak and a
postovulatory fall in the impedance that reaches a nadir
at the time of implantation. The changes were similar to
those seen in serum estradiol levels during the follicular
phase and serum progesterone during the luteal phase.
A better understanding of endometrial blood flow during
the menstrual cycle is clearly of paramount importance in
terms of both physiological and pathophysiological
changes, possibly allowing the definition of new etiolo-
gies or facilitating assessment of future therapeutic treat-
ments. The myometrium and endometrium have
separate and discrete vascular beds and should therefore
be considered independently.
Ovarian assessment
Ultrasound has an important role in assessment of folli-
cular development in natural and stimulated cycles.
Although the maturity of oocytes can only be indirectly
assessed by the size of the follicle, such information can
be used to make a distinction between physiologic and
insufficient or abnormal cycles.
Human follicular development (follicle stimulation hor-
mone), in its entirety, occurs from a diameter of approxi-
mately 0.03 mm and continues for more than 150 days
until ovulation is achieved. Follicles are assessed at only
advanced stages of development (i.e. 4 mm or more).
They grow in minor and major waves of development,
while smaller follicles appear to grow and regress in a
random fashion during the interovulatory interval. The
growth dynamics of follicles up to 4 mm in diameter are
not known. The dominant follicle can usually be
detected at day 10 of the menstrual cycle. It starts to
differ from other follicles and increases in size 2–3 mm
per day. This growth continues and at the time of
ovulation has a mean diameter ranging from 17 to
27 mm [1,31].
The oocyte itself, which is less than 0.1 mm in diameter
in its inactive phase, is surrounded by a cluster of gran-
ulosa cells (cumulus oophurus) which measure approxi-
mately 1 mm and occasionally can be seen in the mature
follicle.
Three-dimensional ultrasound in ovarian assessment
The use of 3D ultrasound imaging will probably allow
more precise characterization of follicles and the corpus
luteum. 3D ultrasound imaging enables more accurate
measurement of follicular volume, but the benefits of
measuring this parameter are still unclear. One possible
benefit is in the measurement of ovarian volume as
smaller ovaries are associated with poor response to
408 Reproductive endocrinology
stimulation [32]. Ovarian volume may be used as a
potential predictor of ovarian hyperstimulation syndrome
in IVF cycles [33]. In combined assessment of ovarian
antral follicle number, ovarian volume, stromal area and
ovarian stromal blood flow, the total number of antral
follicles achieved the best predictive values for favorable
IVF outcome [34].
Ovulation
The day of ovulation is designated either as the day of
maximum follicular growth, or as the day of follicle
rupture [35]. The changes in ultrasound appearance
during ovulation are as follows.
(1) Disappearance or sudden decrease in follicle size has
a sensitivity of more than 80% of predicting ovulation
[36]. However, in some cycles (11%), one out of two
or three dominant follicles collapses during the pre-
ovulatory phase, preceding the effective ovulation of
another follicle [3].
(2) Appearance of ultrasonic echoes in the follicle can
represent the preovulatory sign of the presence of the
cumulus oophorus or a postovulatory sign of follicular
transition to the corpus luteum [37]. The latter is a
more frequent and reliable sign of ovulation [3].
(3) Irregularity of the follicular walls describes transition
from follicle to corpus luteum and can be noted in
67% of cycles on the first day of follicle rupture. The
sensitivity for ovulation is significantly higher com-
pared with the appearance of ultrasonic echoes [3].
(4) Free fluid in the cul-de-sac. It is not uncommon that
1–3 ml of free fluid can be seen prior to ovulation.
Although this is relatively rare and present in only
11% of women, in the luteal phase the amount of fluid
increases to 4–5 ml and even up to 8 ml [38]. Such
fluid can easily be seen after ovulation and it is
present in approximately 77% of women [3]. Unfor-
tunately, none of these indices is constant or specific
[3].
After ovulation, the ruptured follicle is filled with blood
and forms the corpus hemmoragicum, then the corpus
luteum is visualized as a structure containing thick hyper-
echogenic walls enclosing the hypoechoic center [1,6].
Ovarian blood flow
Angiogenesis, vessel maturation and vessel regression
seem to play a critical role in the selection of the domi-
nant follicle, ovulation and corpus luteum formation and
function [39]. These processes can be assessed indirectly
by color and power Doppler [23,40].
Documentation of an ovarian stromal vascular network
may provide useful information as it is related to sub-
sequent ovarian responsiveness in IVF treatment. In a
natural cycle, before formation of the dominant follicle,
blood flow in intraovarian arterioles is characterized by
low velocity and high resistance. During follicular
growth, intraovarian blood flow is continuously increasing
according to the increase in peak systolic velocity [41]. A
marked increase in the blood flow on the base of the
follicle and a decrease in blood flow to the apex can be
noted by color/power Doppler and it has been speculated
that such changes may be essential for the release of a
mature oocyte [42]. The intrafollicular blood flow velo-
city increases approximately 29 h before ovulation and
continues for at least 72 h after the formation of the
corpus hemorraghicum. This may be a consequence of
the penetration of blood vessels into the granulosa cell
layer. Pulsed Doppler analysis of blood flow shows low to
moderate vascular resistance in perifollicular capillaries
(resistance index 0.42–0.48) [24].
With the formation of the corpus luteum, the impedance of
the blood flow drops as a reflection of the vascular arcade
that develops within its wall. The velocities increase up to
40 cm/s, representing a fully functional corpus luteum.
The resistance index remains constant 4–5 days after
ovulation and then rises to approximately 0.50 þ 0.04
[24]. Angiogenesis starts about 24 h after the luteinizing
hormone surge and is critical for the formation of a nor-
mally functioning corpus luteum implantation [43].
One group attempted to assess possible differences. Data
suggest that differences exist in the ovarian blood flow in
ovulatory and anovulatory menstrual cycles [44]. In
women with polycystic ovaries, measurable impedance
indices of ovarian stromal vessels are lower in anovulatory
cycles and they are lower compared with normal healthy
controls [44]. Similarly, color/power Doppler can be used
to assess the corpus luteum – a vascular network can be
displayed as a bright colored ring surrounding it and can
be seen throughout the entire lifetime of the corpus
luteum. It is possible to detect three phases of the corpus
luteum cycle depending on the vascularization, organiza-
tion and systemic vascularization. These phases are char-
acterized by a low resistance index with power Doppler,
maturation of the arteriogenesis characterization with a
low to moderate resistance index and lutheolisis or regres-
sion characterized by a moderate resistance index [23,45].
A decreased blood vessel density and an increased resis-
tance to blood flow, as indicated by the pulsatility index,
was established during the course of corpus luteum
development. An inverse correlation between pulsatility
index and volume density of blood vessels was found,
with a high degree of agreement between ultrasono-
graphic and anatomic measurements of the surgically
removed corpus luteum [46

].
3D/power Doppler imaging appears to be a valuable new
technique to evaluate ovarian blood flow characteristics
 Ultrasound monitoring of the menstrual cycle Matijevic and Grgic 409
of ovulating women. This technique may include volume
measurements, total vascularization assessment and
blood flow, and mean grayness during the late follicular
phase of normally ovulating women. It has been found
that the dominant ovary is larger than the nondominant
ovary, with a lower mean grayness and higher perifolli-
cular vascularization in the dominant ovary [47].
Inadequate vascularization of the corpus luteum has been
implicated as a possible cause of luteal phase deficiency
and higher rate of early spontaneous miscarriage [48].
The difference in impedance measurements of the ves-
sels surrounding the corpus luteum is less marked com-
pared with the changes in blood velocity [41]. Studies
have demonstrated that ovulation tends to occur more
frequently in the right ovary and that alternation is closely
related to hormonal factors and differences in the blood
network of the right and left ovaries [49]. Right-side
ovulation has been reported to favor pregnancy more
in subfertile and fertile women [49,50]. This was chal-
lenged recently by Ojha et al. [51]. It was presumed that
the corpus luteum negatively affects the growth of neigh-
boring follicles during the luteal phase of the menstrual
cycle, with the most pronounced effect expressed in the
mid and late-luteal phases [52]. A recent study concluded
that the side of ovulation does not influence the pulsed
Doppler blood flow to the ovarian stroma or follicular or
uterine arteries. Since ovarian stromal Doppler has been
shown to reflect ovarian reserve, follicular Doppler the
oocyte quality, and uterine Doppler the endometrial
receptivity, the results do not support the hypothesis
that a difference exists in the conception rates between
right and left-side ovulation [51].
Conclusion
Currently, ultrasound scanning has an important role in
noninvasive assessment of endometrial and ovarian cycli-
cal changes during the menstrual cycle. Some of these
changes may be of particular importance in assisted
conception procedures. Ultrasound alone or in combina-
tion with some other diagnostic modalities such as color
Doppler, power Doppler, 3D ultrasound and recently
magnetic resonance allow us to gain a better understand-
ing of the menstrual cycle physiology and may permit the
definition of new etiologies or facilitate assessment of
future therapeutic modalities [53
]. However, further
work is likely to help us understand the full diagnostic
potential of these techniques.
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of special interest


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