Ultrasound studies of vascular and morphological changes in the

Human Reproduction vol.11 no.2 pp.369-375, 19%
Ultrasound studies of vascular and morphological
changes in the human uterus after a positive self-test for
the urinary luteinizing hormone surge
T.H.Bourne, H.-G.Hagstrbm, S.Granberg,
B Josefsson, M.Hahlin, P.Hellberg, L.Hamberger
and W.P.Collins1'2
Department of Obstetrics and Gynaecology, Sahlgrenska University
Hospital, S 413-45 Goteborg, Sweden and 'Department of
Obstetrics and Gynaecology, King's College School of Medicine
and Dentistry, Denmark Hill, London SE5 8RX, UK
2
To whom correspondence should be addressed
The aim of the study reported here was to establish complementary data for changes in uterine size, echogenicity and
vascularity during the menstrual cycle relative to a positive
self-test for urinary luteinizing hormone (LH) and day 1 of
next menses. Thirteen volunteers (aged 23-32 years) with
apparently regular menstrual cycles were recruited from
the nursing staff. The plan was to examine all women by
transvaginal ultrasonography with colour Doppler imaging
on day 11 of the menstrual cycle. A urinary LH self-test was
to be used daily until a positive result was obtained and the
women were to be re-scanned daily until the dominant follicle
had ruptured. All women were then to be scanned at least
every 48 h (within ± 2 h of the same time of day) until day 6
of the next menstrual cycle. Matched samples of peripheral
blood were taken at the time of each scan for hormone
analysis. The main outcome measures were the times of
follicular rupture, a positive test result for urinary LH and
the start of menses, uterine volume, cavity length, endometrial thickness and grade, pulsatility index (PI), and timeaveraged and peak systolic maximum velocities in uterine
and radial arteries and in subendometrial vessels. Nine
women fulfilled the criteria for an ovulatory cycle, and seven
provided data over the complete study. The principal
changes relative to a positive urinary LH test were (i) a
continued rise in endometrial thickness to days 3 and 4 (this
index then remained relatively constant, but the layered
appearance was lost) and (ii) a gradual decrease in the uterine
arterial PI. There was a significant rise in uterine volume,
cavity length and uterine arterial PI around the time of the
next menses, and a fall in endometrial thickness and blood
velocity in the uterine and radial arteries and subendometrial vessels. The data may have implications for the
assessment of reproductive status and the design of future
studies on disorders of implantation or menstruation.
Key words: colour Doppler imaging/endometrium/LH test/
transvaginal ultrasonography/uterine arteries
Introduction
The uterus undergoes characteristic changes in form, blood
flow and function during menstrual and conceptional cycles.
© European Society for Human Reproduction and Embryology
Transabdominal ultrasonography with B mode imaging is one
of the least invasive methods for monitoring changes in
endometrial thickness, consistency and volume (Sakamoto and
Nakano, 1982; Hackeloer, 1984; Fleischer et al, 1986a,b;
Giorlandino et al, 1987). The use of transvaginal ultrasonography produces clearer images (Timor-Tritsch et aL,
1986; Randall et aL, 1989; Bakos et al, 1993), and the
additional facilities of colour Doppler imaging and pulsed
Doppler spectral analysis provide information on blood flow
in the main uterine arteries (Hata et al, 1988; Scholtes
et al, 1989; Steer et al, 1990; Kupesic and Kurjak, 1993;
Sladkevicius et al, 1993, 1994) and subendometrial vessels
(Sladkevicius, 1993).
There is still a need, however, for a comprehensive, longitudinal study of uterine size, form and blood flow during the
secretory phase of the menstrual cycle in relation to instant,
external reference points of ovarian and uterine function. This
information would be of value in the assessment of reproductive
status and the design of investigations into disorders of
implantation or menstruation. Accordingly, our aim was to
obtain complementary data on ultrasound-derived indices of
uterine physiology in relation to a positive result from a simple
self-test for urinary luteinizing hormone (LH), and day 1 of
next menses. We are reporting data from the same study on
serial changes in the corpus luteum and the concentration of
serum progesterone (Bourne et al., 1996) relative to the same
reference points.
Materials and methods
Transvaginal ultrasonography with attachments for colour Doppler
imaging and pulsed Doppler spectral analysis was used to scan
healthy women in the semi-recumbent position over the peri-ovulatory
period and during the secretory phase of the menstrual cycle.
Examinations for each woman were performed at the same time each
day ( ± 2 h). A matched sample of peripheral venous blood was taken
at the time of each scan for subsequent hormone analysis. The first
scans were performed on day 11. The women tested their urine each
morning with a commercial urinary LH dipstick from day 11 until a
positive result was obtained (Clear Plan One Step; Unipath Ltd.,
Bedford, UK). The women then underwent daily scans until the
dominant follicle had ruptured, and every other day thereafter. The
time of next menses was recorded and the women were studied until
day 5 or 6 of the next menstrual cycle. Morphological and blood
flow data from each scan were recorded on colour prints. Qualitative
and quantitative data relating to ovarian morphology and blood flow
were entered into a database using a commercial software package
installed on a personal computer. The protocol was approved by the
local Ethics Committee of Sahlgrenska Hospital, GOteborg, Sweden.
369
T.H.Bourne et al
Subjects
Thirteen nurses employed at the hospital (mean age 28 years, range
23-32) volunteered to take part in the study. All had regular menstrual
cycles (length 26-32 days) and had not used any form of hormone
treatment for al least 6 months. Subsequently, four women withdrew
from the study; two because they could not comply with the minimum
number of scans required (at least four), and two because they had
not developed a dominant follicle by day 18 of the menstrual cycle.
Therefore data from nine women were recorded and analysed.
Pelvic ultrasonography
An Aloka SSD 2000 scanner was used for all scans with a transvaginal
probe for B-mode, pulsed and colour Doppler imaging (Aloka Co.
Ltd., Tokyo, Japan). The vaginal probe was equipped with a 5 MHz
transducer for both B-mode and Doppler functions. Methods for
examining uterine morphology, vascularity and blood flow in semirecumbent women have been described previously (Bourne, 1991).
The maximum longitudinal diameter (length) of the uterus (D\) was
measured in cm from the internal os to the fundus, and the largest
diameters in the transverse ( D J and anterior/posterior (O3) planes.
The volume (in ml) was estimated as (D1XD2XD3V2. Cavity length
(cm) was measured from the internal cervical os to the surface of the
endometrium at the fundus. The total maximum endometrial thickness
was measured in the longitudinal plane from one myometrialendometrial interface to the other across the lumen of the cavity.
Endometrial appearance was classified into one of three grades,
namely, grade 1, triple layered, grade 3, uniformly hypcrechogenic
and grade 2, intermediate between grades 1 and 3. Peristaltic activity
was recorded as the number of apparent endometrial movements/10 s.
Colour Doppler imaging was used to identify the uterine artery as
it ascends just lateral to the internal os of the cervix. The left and
right branches of the artery were located at points where the angle
of the ultrasound beam approached zero. A pulsed Doppler range
gate was placed over each vessel in turn to generate flow velocity
waveforms with, the highest peak systolic velocity (PSV). The
dominant uterine artery was defined as the artery on the same side
as the largest follicle or corpus luteum. Indices of blood flow in a
mid-fundal radial artery and in subendometrial vessels were determined after the probe had been positioned to produce waveforms
with the highest PSV. Subendometrial flow was defined arbitrarily as
waveforms emanating from an area *3.0 mm from the apparent basal
layer of the endometrium. It is generally accepted that enough vessels
will be at a low or zero angle to the path of insonation so that
reproducible measurements can be made. Blood flow impedance was
expressed as the pulsatility index (PI) to allow for the possible
absence of diastolic flow. The PI was calculated electronically from
smooth curves fitted to waveforms over three cardiac cycles according
to the formula PI = (S - DVTAMXV, where S is the peak systolic
Doppler shifted frequency, D is the minimum diastolic Doppler
shifted frequency and TAMXV is the rime-averaged maximum
velocity over the cardiac cycle. A reduction in PI is thought to reflect
a decrease in impedance distal to the point of sampling. A previous
one-way analysis of variance of replicate data (3—5 measurements)
taken from the uterine arteries of 10 women gave a coefficient of
variation of 7.6% for PI and 12.0% for PSV (Bourne, 1991). The
TAMXV (cm/s) and the PSV (cm/s) were recorded from the uterine
and radial arteries and from a subendometrial vessel.
Hormone assay
Serum concentrations of oestradiol, luteinizing hormone (LH) and
follicle stimulating hormone (FSH) were measured by direct automated immunoassay using an enzyme label and a fluorescent end
point (IMX; Abbott Scandinavia AB, Stockholm, Sweden). Serum
370
progesterone was measured by a direct competitive binding immunoassay using time-resolved fluorescence to determine the end point
(Delphia; Pharmacia, Uppsala, Sweden).
Definitions
The urinary LH test result was classified (according to the manufacturer's instructions) as positive if the blue line in the larger window
of the dipstick was more intense than the corresponding line in the
smaller window (i.e. the end point was based on the concentration
of LH exceeding a threshold value). The day of follicle rupture was
the day on which ultrasonography showed a marked reduction (>80%)
in the volume of follicular fluid. Day 1 of menses was defined as the
first day of blood loss through the vagina requiring sanitary protection.
A study menstrual cycle was considered to be normal if the
following criteria were fulfilled retrospectively: (i) the length was
between 25 and 33 days, (ii) the time of the positive test for urinary
LH was associated with elevated serum concentrations of LH, (iii)
die interval from the positive urinary LH test to day 1 of next menses
minus 1 was between 8 and 18 days, (iv) there was ultrasound
evidence of follicle rupture and (v) the highest concentration of serum
progesterone was 2»15 nmol/1.
Statistical analysis
The day and time of the positive test result for urinary LH were
recorded and the maximum time to follicle rupture was calculated.
The data for each end point were plotted for each individual and
subsequently pooled for the whole group in 2-day intervals relative
to the day of the positive LH test (for days 1-14), and also to the
first day of the next menses (day —4 to day 4). The distribution of
pooled values for each end point at all time points was assessed. The
data were expressed as the mean and standard deviation. The
Pearson coefficient of linear correlation r was calculated to assess
the relationship between end points for paired values.
Results
Some characteristics of the nine study cycles are summarized
in Table I. Seven women completed the whole study (10-12
scans); and two were studied up to day 6 or 7 of the secretory
phase (four scans). All indices of ovarian function (derived
by ultrasonography and immunoassay) were consistent with
normal ovulatory cycles. Figure 1 is an example of an oblique
transverse colour Doppler image of the uterus 2 days after a
positive urinary LH test The triple-layered appearance of the
endometrium (grade 1) can be seen above blood flow in a
radial artery. Figure 2 shows an example of the uterine
appearance on day 6 after a positive urinary LH test The
endometrium appears uniformly hyperechogenic (grade 3)
above a network of blood vessels. Occasionally the diastolic
component of the derived flow velocity waveforms was not
continuous with the systolic component, but the pattern was
consistent for a given vessel and scan. Seven (78%) of the
endometria were grade 3 by day 4 after a positive urinary LH
test (all nine by day 8). The earliest return of grade 1 was day
2 of next menses; all seven women providing data at this time
were grade 1 by day 6. The number of peristaltic movements
(mean ± SD) was constant up to the day of a positive LH
test plus 4 (2.4 ± 0.3) and then continued at a lower frequency
to day of LH plus 10 (1.6 ± 0.2).
Uterine morphology and vascularity
Table I. Characteristics of the nine menstrua] cycles studied
Variable
Median
Cycle length (days)
Day of positive urinary LH test
Maximum time to follicle rupture (h)1
Secretory phase length (days)*
No. of ultrasound scans
27
12
25
14
11
Mean (SD)
Minimum
Maximum
27(1)
12(1)
35(22)
14(1)
9(3)
27
29
W
11
7
13
4
77
16
12
'From time of positive luteinizing hormone (LH) test
Figure 1. Colour Doppler oblique transverse image of the uterus showing blood flow in a radial artery (day 2 from a positive urinary
LH test).
LOKP
I
2000
3 74
3. 74
:
41/42
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]
07 : 4 9
2CV
PWR :
Figure 2. Colour Doppler oblique transverse image of the uterus showing subendometrial blood flow (day 6 from a positive urinary
LH test).
371
<rt aL
50
PSV
PI
60
6
50
5
40
4
30
3
20
2
10
1
0
0
I
30
Uterine'
40
20
PSV
10
-4,-3 -2,-1
1,2
3,4
5,6
7,8
9,10 11-14
Days relative to positive LH test
-5,-3 -2,-1
1 *
3,4
Days relative to menses
Figure 3. Mean and SE changes in uterine volume relative to
day 1 of a positive urinary LH test and day 1 of next menses.
-4,-3 -2,-1
1,2
3,4
5,8
7,8
B,10 11-14
•6,-S -2,-1 U
Figure 5. Mean and SE changes in the pulsatility index (PI) and
peak systolic velocity (PSV) in the dominant uterine artery relative
to day 1 of a positive urinary LH test and day 1 of next menses.
12
?
10
I
6
M
Days relative to menses
Days relative to positive LH test
k
PSV
I
I •
TAMXV
-4,-3 -1,-1
1,1
3,4
S4
7,B »,10 11-14
Days relative to positive LH test
-4,-3 -2r1 1A
3,4
W
Days relative to menses
Figure 4. Mean and SE changes in endometrial thickness relative
to day 1 of a positive urinary LH test and day 1 of next menses.
Uterine morphology
The changes in uterine volume (mean ± SE) relative to day
1 of a positive test for urinary LH and to day 1 of next menses
are shown in Figure 3. The volume (mean ± SD) on days -2
and -1 (50.1 ± 14.4 ml) relative to days 1 and 2 of menses
(37.7 ± 15.1 ml) was significantly higher (P < 0.05, Student's
paired /-test). The length of the cavity (mean ± SD) on days
- 2 and -1 (4.01 ± 0.50 cm) relative to days 1 and 2 of menses
(3.28 ± 0.48 cm) was also significantly higher (P < 0.5,
Student's Mest). The mean change in endometrial thickness is
shown in Figure 4. The values (mean ± SE) increased until
days 3 and 4 after a positive test for urinary LH, and started
to decrease on days —2 and - 1 relative to day 1 of next menses.
Uterine arterial blood flow
Mean changes in the PI and PSV in the dominant uterine
artery relative to day 1 of a positive test for urinary LH and
to day 1 of next menses are shown in Figure 5. There was a
tendency for the PI to decrease from the time of the LH test
to days 11-14. In contrast, the mean PSV tended to fall until
days 7 and 8 and then increased. The PI tended to increase
and the PSV to reduce on day - 2 to +2 of menses. There was
no overall significant difference in PI or PSV between the
dominant and non-dominant uterine arteries, but the trends
372
-4,-3 -2,-1
1,2
3yt
tfi
7,1
»,10 11-14
Days relative to positive LH test
-5,-3 -2,-1
1 *
S,4
Days relative to mens
Figure 6. Mean and SE changes in blood velocity in
subendometrial vessels relative to day 1 of a positive urinary LH
test and day 1 of next menses. TAMXV = time-averaged
maximum velocity; PSV = peak systolic velocity.
were more apparent for mean values derived from the dominant
artery (data not shown).
Subendometrial blood flow
Mean changes in the TAMXV and PSV in subendometrial
vessels relative to day 1 of a positive test for urinary LH and
to day 1 of next menses are shown in Figure 6. There was an
initial decrease in both indices of blood velocity on days 3 or
4 after the positive LH test with a subsequent rise. The value
for both indices tended to fall over days - 2 to +4 of menses.
There was no apparent change in PI during the secretory phase
of the cycle (data not shown).
Comparison of blood flow indices
Values for the PI (mean ± SD) in the dominant uterine and
radial arteries and in subendometrial vessels in relation to the
time of a positive test for urinary LH are shown in Table II.
The values were significantly lower in the radial compared
with the dominant uterine artery. The values tended to be
lowest in the subendometrial vessels. The mean percentage
Uterine morphology and vascnlarity
Table IL Mean changes (±SD) in the minimum pulsatility index (PI) in various uterine vessels in relation to the time of a positive self-test for urinary
luteinizing hormone (LH)
Blood vessel
Dominant uterine artery
Radial artery
Subendome trial
Days from positive urinary LH test
1 and 2
3 and 4
5 and 6
7 and 8
9 and 10
11-14
3.3(1.4)
1.4(0.4)
1.1 (0.3)
3.2 (1 6)
2.2(1.6)
1.2(0.7)
2.6 (0.6)
1.9 (1.3)
0.9 (03)
2.2 (0.4)
1.4 (0.2)
0.8 (0.2)
2.3 (0.4)
1.1 (03)
1.0(0.4)
1.9 (0.4)
1.3 (0.2)
0.8 (0.2)
Table m . Mean changes (±SD) irl time-averaged maximum velocity (TAMXV) in various uterine vessels in relation to the time of a positive self-test for
urinary luteinizing hormone (LH)
Blood vessel
Dominant uterine artery
Radial artery
Subendome trial
Days from positive urinary LH test
1 and 2
3 and 4
5 and 6
7 and 8
9 and 10
11-14
12.4 (4.0)
4.4 (2.3)
3.5 (0.9)
13.0 (5.0)
3.7(2.9)
2.4(1.3)
14.6 (8.3)
4.9 (2.3)
2.9 (1.3)
13.2 (4.4)
3.7 (0.8)
3.5 (0.8)
13.0 (3.8)
4.5 (1.8)
3.0(1.8)
19.4 (3.5)
4.8(1.3)
3.9(1.6)
TaWe IV. Mean changes (±SD) in peak systolic velocity (PSV) in various uterine vessels in i•elation to the time of a positive self-test for urinary LH
Blood vessel
Dominant uterine artery
Radial artery
Subendometrial
Days from positive urinary LH test
1 and 2
3 and 4
5 and 6
7 and 8
9 and 10
11-14
39.4 (8.0)
8.2 (3.6)
4.8 (1.4)
37.7 (6.1)
7.8 (3.9)
3.8(1.5)
36.6(11.4)
8.7 (2.9)
5.7(1.8)
34.6 (8.6)
7.3 (1.5)
5.7 (2.5)
37.9 (8.8)
7.8 (2.6)
5.8 (3.4)
45.0 (9.9)
9.0 (2.2)
6.8 (2.2)
reduction from the dominant uterine arterial to subendometrial
vessels ranged from 56.5 to 66.7. Values for the TAMXV
(mean ± SD) in the same selection of uterine vessels in
relation to the time of a positive test for urinary LH are shown
in Table HI. The values were significantly lower in the radial
compared with the dominant uterine artery. There was a trend
for the values to be lower in subendometrial vessels. The
mean percentage reduction from dominant uterine arterial to
subendometrial vessel ranged from 71.2 to 81.6. Values for
the PSV (mean ± SD) in the same selection of uterine vessels
in relation to the time of a positive test for urinary LH are
shown in Table IV. The values were significantly lower in
radial (compared with the dominant uterine arteries) and
subendometrial vessels (compared with the radial arteries).
The mean percentage reduction from dominant uterine arterial
to subendometrial vessel ranged from 83.5 to 89.9. There was
a good correlation between the TAMXV and the PSV in the
dominant uterine arteries (r = 0.80), the radial arteries (r =
0.85) and the subendometrial vessels (r = 0.73). There was
no correlation between any index of uterine blood flow and
the concentration of serum progesterone or oestradiol.
Discussion
To the best of our knowledge this is the first study to relate
physiological changes in uterine morphology and blood flow
to the time of a practical self-test for urinary LH. We have
already reported data from the same study on changes in the
serum concentration of LH, FSH, progesterone and oestradiol,
and in ultrasound indices of corpus luteum structure and blood
flow (Bourne et aL, 1996). There have been previous reports
on the use of transvaginal ultrasonography to determine uterine
size and echogenicity, and the additional use of colour Doppler
imaging to derive indices of blood velocity and impedance to
flow, which are relatively independent of the continuity of
blood flow throughout the cardiac cycle. The data from these
studies have either been related to the peak plasma or urinary
LH concentration as determined retrospectively by laboratory
techniques (Randelle/aL, 1989; Steeretal., 1990; Bakos e7 a/.,
1993), the time of follicle rupture according to ultrasonography
(Sladkevicius et aL, 1993), or the time of menstruation
(Sladkevicius et aL, 1994). One study focused on the periovulatory period (Sladkevicius et aL, 1993), while others
obtained longitudinal data for one or more indices of uterine
morphology (Randall et aL, 1989; Bakos et aL, 1993) or blood
flow (Steer et aL, 1990) at defined times, or regular intervals,
throughout the menstrual cycle.
We sampled at least every 48 h throughout the secretory
phase and the next menstruation. Our results showed that
endometrial thickness remained relatively constant after days
3 and 4 from the positive test for urinary LH. The triple-layered
appearance of the endometrium, however, had disappeared by
day 4 from the positive LH test in seven of the nine women,
and from all endometria by day 8. These data are consistent
with those reported by Bakos et al. (1993). In addition, the
number of endometrial movements was higher up to day 4
from the time of the positive test for urinary LH. These
findings may be relevant to ovum and sperm transport in the
373
TJLBourne et aL
female reproductive tract, and to the appearance of an embryo
in the uterus of a conception cycle. It is also of interest that
there appears to be a physiological increase in the size of the
uterus (i.e. volume and cavity length) before menstruation.
Both of these indices and endometrial thickness decreased
during days - 2 and - 1 relative to day 1 of the next menses.
The endometria of all seven women had returned to grade 1
by day 6 of the menstrual cycle. This finding may have some
implications for the onset of the next period of potential fertility.
The changes in PI in the dominant uterine artery were
similar to those observed by Steer et al. (1990) for the mean
values of both arteries and included the presence of a small
peak on days 3 and 4 from the positive urinary LH test This
finding is reassuring in view of the different reference point
for the data analysis that was used and the smaller number of
women in our current study. The changes in PI at certain times
appeared to be more pronounced in the dominant uterine artery,
so these data were shown. Nevertheless, there was no significant
difference in values over the whole of the secretory and
menstrual phases. We took measurements at approximately the
same time of day for each woman because a circadian rhythm
has been found in uterine artery blood flow during the follicular
phase of the menstrual cycle (Zaidi et al, 1995). The results
from a previous study have shown that the PI at the mid-luteal
phase tends to be higher in infertile women (Steer et al,
1994). There was a correlation between values for the PSV
and theTAMXV. Both indices tended to rise towards the end
of the secretory phase and may reflect impending menstruation.
The values for PI, PSV and TAMXV tended to remain
constant in the subendometrial vessels throughout the secretory
phase. This finding suggests that a good blood supply is
required if a potential menstrual cycle is to turn into a
conception cycle after coitus during the fertile period. The
results of studies to compare ultrasound indices of uterine
function in menstrual cycles with those of conception cycles
after in-vitro fertilization (TVF) and embryo transfer have
shown that conception only occurs if the endometrial thickness
is above a lower limit of ~5—6 mm (Abdalla et aL, 1994;
Coulam et al., 1994; Noyes et al, 1995) and the mean uterine
arterial PI is below an upper limit of ~3.3 (Steer et al, 1992).
There does not, however, appear to be a significant difference
between endometrial thickness or the resistance index (RI) on
the day of embryo transfer between conception and nonconception cycles after IVF and embryo transfer (Bassil et al,
1995). Similarly, the number of peristaltic movements does
not seem to have any predictive value for pregnancy (Narayan
and Goswamy, 1994). A good correlation has been reported
between ultrasound-derived indices and histological aspects of
normal and abnormal endometrial form (Fleischer et al,
1986c), and between uterine artery PI and immunohistochemical markers of endometrial receptivity in down-regulated
infertile patients receiving exogenous oestradiol and progesterone (Steer et al., 1995). There is, however, a need for
comparative studies of the value of various indices of uterine
structure, blood flow and function for predicting pregnancy in
subfertile women with irregular menstrual cycles. The data of
Dickey et aL (1994) suggest that assessments of uterine blood
374
flow in subfertile women should also include the effect
of posture.
Our data extend previous findings by indicating that the
optimal time for uterine receptivity to an embryo, or for an
ultrasound scan, might be selected on the basis of serial selftesting with a dipstick for urinary LH. Our results also show
that the marked variation in blood flow seen in the uterine
arteries is dampened by the distal uterine vasculature, leading
to a relatively constant blood supply to the presumed target
tissue, i.e. the endometrium. It is of interest that we found that
the PSV and TAMXV were the most sensitive markers of
physiological function for small vessels, such as those adjacent
to the endometrium, whereas an index of impedance seemed
more appropriate for large vessels such as the uterine artery.
This finding is consistent with our studies of the corpus
luteum (Bourne et al., 1995) and ovarian masses (unpublished
observation). Nevertheless, the TAMXV does reach a
maximum at the most likely time of implantation and thus
may reflect an important feature of the reproductive process.
There is also a profound change in vascularity in relation to
the end of the secretory phase and the onset of menstruation.
Impedance to flow increases markedly in the uterine arteries
and there is a marked decrease in PSV in the subendometrial
vessels. Hence, disorders of menstruation may be in part a
function of vascular spasm, leading to relative tissue ischaemia
and pain. The use of vasoactive drugs (e.g. nitric oxide donors)
would be of interest, and transvaginal colour Doppler imaging
(TVCDI) could be used to monitor their effects in vivo.
Acknowledgements
We thank the Swedish Medical Research Council for financial support
for the project (grant no. B95-17x-11237-01A) and for the Fellowship to T.H.B. (grant no. 2873). We are also grateful to Berner
Medicinteknic, Sweden and Aloka Co. Ltd., Tokyo, Japan for the use
of their ultrasound equipment, and to Unipath, Lund, Sweden for
supplying the self-tests for urinary LH (Clear Plan One Step).
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Received on August 10, 1995; accepted on November 2, 1995
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