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Reduction of blood flow impedance in the uterine arteries of infertile
women with electro-acupuncture
Elisabet Stener-Victorin[1.4], Urban Waldenström[2],
Sven A. Andersson[3] and Matts Wikland[2]
[1]Department of Obstetrics
and Gynaecology [2]Fertility Centre Scandinavia. Department of Obstetrics
and Gynaecology and [3]Department of Physiology University of Gothenburg.
S-413 45 Gothenburg, Sweden
[4]To whom correspondence should be addressed:
Department of Obstetrics and Gynecology. Kvinnokliniken Sahlgrensh
sjukhuset, S-413 45 Golhenburg, Sweden
Source: European Society for
Human Reproduction and Embryology

In order to assess whether electro-acupuncture
(EA) can reduce a high uterine artery blood flow inpedance, 10
infertile but otherwise healthy women with a pulsatility index
(PI) ≥3.0 in the uterine
arteries were treated with EA in a prospective, non-randomized
study. Before inclusion in the study and throughout the entire
study period, the women were down-regulated with a gonadotrophin-releasing
hormone analogue (GnRHa) in order to exclude any fluctuating endogenous
hormone effects on the PI. The baseline PI was measured when the
serum oestradiol was ≤0.1 nmol/l, and thereafter the women were
given EA eight times, twice a week for 4 weeks. The PI was measured
again closely after the eighth EA treatment, and once more 10-14
days after the EA period. Skin temperature on the forehead (STFH)
and in the lumbosacral area (STLS) was measured during the flrst,
fifth and eighth EA treatments. Compared to the mean baseline PI,
the mean PI was significantly reduced both shortly after the eighth
EA treatment (P < 0.0001) and 10-14 days after the EA period
(P < 0.0001). STFH increased significantly during the EA treatments.
It is suggested that both ot these effects are due to a central
inhibition of the sympathetic activity.
Key words: electro acupuncture/pulsatilily index (PI)/trans-vaginal
colour Doppler curve/uterine artery blood flow
INTRODUCTION
Successful in-vitro fertilization (IVF) and embryo transfer demand
optimal endometrial receptivity at the time of implantation.
Blood flow impedance in the uterine arteries, measured as the
pulsatility index (PI) using transvaginal ultrasonography with
pulsed Doppler curves, has been considered valuable in assessing
endometrial receptivity (Goswamy and Steptoe, 1988; Sterzik et
al., 1989; Steer et al., 1992, 1995a,b; Coulam et al., 1995;
Tekay et al., 1995). Steer et al. (1992) found that a PI ≥3.0
at the time of embryo transfer could predict 35% of the failures
to become pregnant. Coulam et al. (1995) did not observe any
significant differences between PI measurements done on the day
of oocyte retrieval compared with PI measurements on the day
of embryo transfer. This would allow prediction of non-receptive
endometria earlier in the cycle.
Previous studies on rats have shown a decreased
blood pressure after electro-acupuncture (EA) with low frequency
(2 Hz) stimulation of muscle afferents (A-d fibres). The decreased
blood pressure was related to reduced sympathetic activity (Yao
et al., 1982; Hoffman and Thoren, 1986; Hoffman et al.. 1987,
1990a,b), and was paralleled by an increase in the ß-endorphin concentration
in the cerebrospinal fluid (CSF), suggesting a causal relationship
to central sympathetic inhibition (Cao et al., 1983; Moriyama 1987;
Reid and Rubin, 1987). The cardiovascular effects of acupuncture
treatment are probably mediated by central opioid activity via
the ß-endorphin system from the hypothalamus.
The aim of this study was to evaluate whether EA can reduce a
high impedance in the uterine arteries. There are several conceivable
mechanisms which may give this effect.
In addition to central sympathetic inhibition via the endorphin
system, vasodilatation may be caused by stimulation of sensory
nerve fibres which inhibit the sympathetic outflow at the spinal
level, or by antidromic nerve impulses which release substance-P
and calcitonin gene-related peptide from peripheral nerve terminals
(Jansen et al., 1989; Andersson, 1993; Andersson and Lundeberg,
1995).
It has been assumed that various disorders in the autonomic nervous
system, such as hormonal disturbances, may be normalized during
auricular acupuncture (Gerhard and Postneck, 1992). It has also
been suggested that the concentrations of central opioids may regulate
the function of the hypothalamic-pituitary-ovarian axis via the
central sympathetic system, and that a hyperactive sympathetic
system in anovulatory patients could be normalized by EA (Chen
and Yin, 1991).

MATERIALS
AND METHODS
Subjects, design and Pl measurements: The
study was approved by the ethics committee of the University of Gothenburg
and was conducted at the Fertility Centre Scandinavia, Gothenburg,
Sweden, a tertiary private IVF unit. All women attending the clinic
for information about the IVF/embryo transfer procedure, had the
PI of their uterine arteries measured by transvaginal ultrasonography
and pulsed Doppler curves (Aloka SSD 680: Berner Medecinteknik, Stockholm,
Sweden). The PI value for each artery was calculated electronically
from a smooth curve fitted to the average waveform over three cardiac
cycles, according to the formula: Pl = (A - B)/mean, where A is the
peak systolic Doppler shift, B is the end diastolic shift frequency
and mean is the mean maximum Doppler shifted frequency over the cardiac
cycle. A reduction in the value of PI is thought to indicate a reduction
in impedance distal to the point of sampling (Steer et al., 1990).
In the routine preparation for their IVF/embryo
transfer treatment, all women were down-regulated with a gonadotrophin-releasing
hormone analogue (GnRHa) (Suprecur: Hoechst. Germany). When their
oestradiol concentration in serum was <0.1 nmol/1, the women were considered
down-regulated and the PI of their uterine arteries was again measured
in those women showing a mean Pl ≥3.0 before down-regulation.
The measurements were done by two of the authors (M.W. and U.W.)
between 08.30 h and 14.30 h. These hours were chosen for practical
reasons, and also to reduce the risk that the PI measurements would
be affected by the circadian rhythm in blood flow, recently reported
by Zaidi et al. (1995). Three measurements were made on the right
and three on the left uterine artery of each patient. Before the
study was conducted, the observers were well trained in PI measurements
with the equipment used. Steer et al. (1995) has shown that in
trained hands, the inter-, and intra-observer variations in vaginal
colour Doppler ultrasound are sufficiently small to provide a basis
for clinically reliable work.
PI measurements were done on all women attending
the unit for an IVF/embryo transfer treatment between November
1992 and February 1993. Of these, all infertile but otherwise
healthy women, with a mean PI ≥3.0 in the uterine arteries
both before and after down-regulation, were invited to be included
in the study.
In all, 10 women accepted after informed consent and they had
a mean age of 32.3 years (range 25-40 years). The infertility diagnoses
were unexplained infertility (n = 6), tubal factor (n = 3) and
polycystic ovarian syndrome (n = 1).
From their inclusion and onwards, the women were kept on the
GnRHa and were given no other pharmacological treatment. Consequently,
their gonadotrophins and ovarian steroids were kept at a constantly
low concentration, both at their inclusion in the study and throughout
the whole study period. Thus, PI changes due to hormonal fluctuations
were avoided.
EA was then given eight times, twice a week for 4 weeks. The
mean PI of the uterine arteries was measured (mean of three PI
on each side) directly after the eighth EA treatment and again
10-14 days after the EA period.
Of the 10 women included, two were later excluded. One of them,
with tubal factor infertility, was excluded because she started
taking medications for her migraine, which could have affected
her PI. The other excluded woman, with unexplained infertility,
stopped her GnRHa treatment because she preferred IVF/embryo transfer
in a natural cycle.
Acupuncture Treatment
The sympathetic outflow may be inhibited at the segmental level
and, for this reason, acupuncture points were selected in somatic
segments according to the innervation of the uterus (Thl2-L2,
S2-S3) (Bonica, 1990).
The needles were inserted i.m. to a depth of
10-20 mm. The aim of the stimulation was to activate group III
muscle-nerve afferents. The needles were twirled to evoke `needle
sensation,' often described as tension, numbness, tingling and
soreness, sometimes radiating from the point of insertion. The
needles were then attached to an electrical stimulator (WQ-6F:
Wilkris & Co. AB, Stockholm,
Sweden) for 30 min. The location of the needles was the same in
all women (Table I).
Table 1. Acupuncture points, their anatomical position and their
innervation

Four needles were located bilaterally at the thoracolumbar and
lumbosacral levels of the erector spinae, and were stimulated with
high frequency (100 Hz) pulses of 0.5 ms duration. The intensity
was low, giving non-painful paraesthesia.
Four needles were located bilaterally in the calf muscles, and
were stimulated with low frequency (2 Hz) pulses of 0.5 ms duration.
The intensity was sufficient to cause local muscle contractions.
Skin temperature: The skin temperature
was measured with a digital infrared thermometer (Microscanner
D-series: Exergen, Watertown, MA, USA) between the applied acupuncture
needles in the lumbosacral region (25 mm from each needle), skin
temperature lumbosacral (STLS), and on the forehead, skin temperature
forehead (STFH). The measurements were made during the first, fifth
and eighth EA treatments. The first measurements were made after
10 min rest, and just before the EA, these being considered as
`baseline.' Thereafter, further measurements of STLS and STFH were
done every seventh minute during the EA and immediately after the
EA. The room temperature was constant during the three EA treatments.
Statistics: Analysis of variance
(ANOVA: Newman-Keul's range test) was used to analyze the data.

RESULTS
Blood flow impedance: Compared to the mean
baseline PI, the mean PI was significantly reduced both soon after
the eighth EA treatment (P < 0.0001) and 10-14 days after the
EA period (P < 0.0001) (Figure 1), at which time six women had
a mean PI <2.6
(Table II and Figure 2).

Figure 1. The mean pulsatility index (PI) (n = 8) for all women before
the first electro-acupuncture (EA) treatment, immediately after the
eighth EA treatment and 10-14 days after the EA period.
*** = significant changes (P < 0.0001) compared to the mean PI before the
first EA treatment.

Figure 2. The individual mean pulsatility index (PI) before down-regulation,
before the first electro-acupuncture (EA) treatment, immediately
after the eighth EA treatment and 10-14 days after the EA period.

The right and left uterine arteries responded
similarly to EA. The diffcrence in mean PI between the two arteries
was ≤0.3
(not significant), both before down-regulation, during down-regulation
and throughout the whole study period. There was no significant
difference in the mean PI for patients with different causes of
infertility.
Skin temperature: The pooled results from all skin
temperature measurements are presented in Figure 3. Compared with
the starting point, mean STFH increased significantly after 21
min of EA (P = 0.02), and directly after the EA treatments (P =
0.002). STLS did not change significantly.

Figure 3. Pooled mean values (n = 8) of skin temperature on forehead
(STFH) and skin temperature in the lumbosacral area (STLS) during
the first, fifth and eighth electro-acupuncture (EA) treatments.
* = significant changes (P = 0.02) after 21 min and ** = significant
changes (P = 0.002) immediately after EA compared to the time just
before needles were inserted. 0 = `baseline'.

DISCUSSION
It has been shown in previous studies that a high PI in the uterine
arteries is associated with a decreased pregnancy rate following
IVF-embryo transfer (Goswamy et al., 1988; Sterzik et al., 1989;
Steer et al., 1992, 1995a.b; Coulam et al., 1995). The results
reported by Tekay et al. (1995) support the hypothesis postulated
by Steer et al. (1992) that uterine receptivity is improved when
the PI value is between 2.0 and 2.99 on the day of embryo transfer.
When a high PI is found before embryo transfer in a stimulated
cycle, treatment options are few. Goswamy et al. (1988) successfully
tried pre-treatment with exogenous oestrogens in the next cycle,
but their results have not been verified by others. It has been
proposed that the embryos should be frozen, thawed and transferred
in an unstimulated cycle (Goswamy et al., 1988; Steer et al., 1992,
1994), but there is little support for the hypothesis that the
PI would be lower under these contitions.
In experiments on spontaneously hypertensive rats, EA at low
frequency (2-3 Hz) induced a long-lasting, significant fall in
blood pressure which was associated with decreased activity in
sympathetic fibres (Yao et al., 1982; Hoffman and Thoren, 1986;
Hoffman et al., 1987, 1990a,b). A decrease in sympathetic activity
appears to be generalized. In microneurographic studies on humans,
EA in the upper limbs resulted in an initial increase and then
a decrease in activity of sympathetic efferents in the tibial nerve,
with a parallel increase in the temperature of the skin (Moriyama,
1987). Kaada (1982) reported that transcutaneous stimulation of
acupuncture points in the hand increased the skin temperature,
giving pain relief in limbs suffering from Reynaud's phenomenon.
Kaada (1982) also found that electrical stimulation of accupuncture
hand points in patients with ischaemic conditions of the lower
limbs, increased the skin temperature in the lower limbs and possibly
enhanced the healing of long-standing ulcers. It has been noted
in both animals and humms that EA has greater effects on pathological
conditions, e.g. hypertension or hypotension, whereas normal blood
pressure is only slightly changed (Yao et al., 1982: Hoffman and
Thoren, 1986: Hoffman et al., 1987, 1990a,b).
The mechanisms of sympathetic inhibition following
EA are poorly understood. Based on animal experiments, Hoffmann
and Thoren (1986) and Hoffman et al. (1987, 1990a,b) suggested
that electrical slimulation of muscle efferents innervating ergoreceptors
increases the eoncentration of ß-endorphin in the CSF. They found support for the hypothesis
that the hypothalamic ß-endorphinergic system has inhibitory
effects on the vasomotor centre, and thereby a central inhibition
of sympathetic activity. It has been suggested that this central
mechanism, involving hypothalamic and brain stem systems, is important
in changing the descending control of many different organ systems,
including the vasomotor system (Andersson. 1993; Andersson and
Lundeberg, 1995).
In this study, the PI of the uterine arteries was signifieantly
decreased soon after the eighth EA treatment and remained significantly
decreased 10-14 days after the EA period. These findings suggest
that a series of EA treatments increases the uterine artery blood
flow. Another effect observed in this study was the signifieantly
inereased STFH during the EA treatments.
The most likely cause of these effects is a decreased tonic activity
in the sympathetic vasoconstrictor fibres to the uterus and an
involvement of the central mechanisms with general inhibition of
the sympathetic outflow, in accordance with previously observed
EA effects (Kaada. 1982; Yao et al., 1982; Cao et al., 1983: Hoffman
and Thoren, 1986; Hoffman et al., 1987, 1990a,b; Moriyama, 1987;
Reid and Rubin, 1987; Jansen et al., 1989).
In conclusion. the present study showed a decrease of the PI
in the uterine arteries following EA treatment. Randomized studies
on a greater number of patients are needed to verify these results
and to exclude non-specific effects.

References
1. Andersson, S.A. (1993) The functional
background in acupuncture effects. Scand J. Rehab, Med. Suppl.,
29. 31-60.2. Andersson,
S.A. and Lundeberg. T. (1995) Acupuncture - from empiricism to
science: functional background to acupuncture effects in pain
and disease. Med. Hypoth., 45, 271-281.
3. Bonica, J. (1990) The Management
of Pain, vol. 1, 2nd edn, revised. Lea & Febiger, Philadelphia,
London, 156 pp.
4. Cao, :X.D., Xu. S.F. and Lu. W.X. (1983) Inhibition
of sympathetic nervous system by acupuncture. Acupuncturc Electro-Ther.
Res. Int. J., 8, 25-35.
5. Chen, B.Y. and Jin. Y. (1991) Relationship
between blood radioimmunoreactive beta-endorphin and hand skin
temperature during the electro-acupuncture induction of ovulation.
Acupuncture Electro-Ther. Res. Int. J., 16, 1-5.
6.
Coulam, C.B., Stem.
IJ.. Soenksen D.M., Britten, S. and Bustillo, M. (1995) Companson
of pulsatility indices on the day of oocyte retrieval and embryo
transfer. Hum. Reprod., 10, 82-84.
7.
Goswamy, R.K. and Steptoe, P.C.
(1988) Doppler ultrasound studies of the uterine atery in spontaneous
ovarian cycles. Hum. Reprod., 3, 721-726.
8.
Goswamy, R.K., Williams,
G. and Steptoe, P.C. (1988) Decreased uterine pertusion - cause
of infentlity. Hum. Reprod., 3, 955-959.
9.
Gerhard, I. and Posteck,
F. (1992) Auricular acupuncture in the treatment of female infertility.
Gynecol, Endocinol., 6, 171-181.
10.
Hoffmann, P. and Thoren, P. (1986)
Long-lasting cardiovascular depression induced by acupuncture-like
stimulation of the sciatic nerve in unanaesthetized rats. Effects
of arousal and type of hypertension. Acta Physiol., Scand., 127,
119-112.
11.
Hoffman, P., Friberge, P., Ely, D. and Thoren, P. (1987)
Effect of spontaneous running on blood pressure, heart rate and
cardiac dimension in developing and established spontaneous hypertension
in rats. Acta Physiol., Scand., 129, 535-542.
12.
Hoffman, P., Skarphedinsson,
J.O., Delle, M. and Thoren, P. (1990a) Electrical stimulation of
the gastrocnemius muscle in spontaneously hypertensive rat increases
the pain threshold: role of different serotonergic receptors. Acta
Physiol., Scand., 138, 125-131.
13.
Hoffman, P., Terenius, L. and Thoren,
P. (1990b) Cerebrospinal fluid immunoreactive beta-endorphin concentration
is increased by long-lasting voluntary exercise in the spontaneously
hypertensive rat. Regul. Pept., 28, 233-239.
14.
Jansen, G., Lundeberg,
T., Kjartansson, J. and Samuelsson, U.E. (1989) Acupuncture and
sensory neuropeptides increase cutaneous blood flow in rats. Neurosci.
Lett., 97, 305-309.
15.
Kaada, B. (1982) Vosodilatation induced by transcutaneous
nerve stimulation in peripheral ischemia (Raynaud's phenomenon
and diabetic polyneuropathy), Eur. Heart J., 3, 303-314.
16. Moriyama,
T. (1987) Microneurographic analysis of the effects of acupuncture
stimulation on sympathetic muscle nerve activity in humans: excitation
followed by inhibition. Nippon Seirigaku Zasshi., 49, 711-721.
17.
Reid,
J.L. and Rubin, P.C. (1987) Peptides and central neural regulation
of circulation. Physiol. Rev., 67, 725-749.
18.
Steer, C.V., Campbell,
S., Pampiglione. J.S. et al. (1990) Transvaginal colour flow imaging
of uterine arteries during the ovarian and menstrual cycles. Hum.
Reprod., 5, 391-395.
19.
Steer. C.V., Campbell, S., Tan, S.L. et al.
(1992) The use of transvaginal colour flow imaging after in vitro
fertilization to identify optimum uterine conditions before embryo
transfer. Fertil. Steril., 57, 372-376.
20.
Steer, C.V., Tan. S.L.,
Mason, B.A. and Campbell, S. (1994) Midluteal-phase vaginal color
Doppler assessment of uterine artery impedance in a subfertile
population. Fertil. Steril., 61, 53-58.
21.
Steer, C.V., Williams, J.,
Zaidi, J., Campbell, S. and Tan, S.L. (1995a) Intra-observer, interobserver,
interultrasound transducer and intercycle variation in colour Doppler
assessment of uterine artery impedance. Hum. Reprod., 10, 479-481.
22.
Steer,
C.V., Tan, S.L., Mason, B.A. and Campbell, S. (1995b) Vaginal color
Doppler assessment of uterine artery impedance correlates with
immunohistochemical markers of endometrial receptivity required
for the implantation of an embryo. Fertil., Steril., 61, 101-108.
23.
Sterzik,
K., Hütter, W., Grab, D. et al.
(1989) Doppler sonographic findings and their correlation with
implantation in an in vitro fertilizalion program. Fertil. Steril.,
52, 825-828.
24.
Tekay, A., Martikainen, H. and Jouppila, P. (1995)
Blood flow changes in uterine and ovorian vasculature, and predictive
value of transvaginal pulsed colour Doppler ultrasonography in
an in-vitro fertilization programme. Hum. Reprod., 10, 688-693.
25.
Yao.
T., Andersson, S. and Thoren, P. (1982) Long-lasting cardiovascular
depressor response following sciatic stimulation in SHR. Evidence
for the involvement of central endorphin and serotonin systems.
Brain Res., 244, 295-303.
26.
Zaidi, J., Jurkovic. D., Campbell, S.
et al. (1995) Description of circadian rhythm in artery blood flow
during the peri-ovulatory period. Hum. Reprod., 10, 1642-l646.
Received on June 27. 1995; accepted on March 20, 1996
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