Reduction of blood flow impedance in the uterine arteries of infertile women with electro-acupuncture

Abstract

In order to assess whether electro-acupuncture (EA) can reduce a high uterine artery blood flow impedance, 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 PL The baseline PI was measured when the serum oestradiol was ≤0.1 nmol/1, 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 first,
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 of these effects are due to a central inhibition of the sympathetic activity.

Full text

Human Reproduction vol.11 no.6 pp.1314-1317, 1996
Reduction of blood flow impedance in the uterine
arteries of infertile women with electro-acupuncture
Elisabet Stener-Victorin
1
-
4
, Urban Waldenstrdm
2
,
Sven A.Andersson
3
and Matts Wikland
2
'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
^o whom correspondence should be addressed at: Department of
Obstetrics and Gynecology, KvinnokJiniken, Sahlgrenska sjukhuset,
S-413 45 Gothenburg, Sweden
In order to assess whether electro-acupuncture (EA) can
reduce a high uterine artery blood flow impedance, 10
infertile but otherwise healthy women with a pulsatility
index (PI) 5*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-releas-
ing hormone analogue (GnRHa) in order to exclude any
fluctuating endogenous hormone effects on the PL The
baseline PI was measured when the serum oestradiol was
=s0.1 nmol/1, 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 first, 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 of these effects are
due to a central inhibition of the sympathetic activity.
Key words: electro-acupuncture/pulsatility index (PI)/trans-
vaginal colour Doppler curve/uterine artery blood flow
merits 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-8 fibres). The
decreased blood pressure was related to reduced sympathetic
activity (Yao etal, 1982; Hoffman and Thor6n, 1986; Hoffman
et al, 1987, 1990a,b), and was paralleled by an increase in
the P-endorphin concentration in the cerebrospinal fluid (CSF),
suggesting a causal relationship to central sympathetic inhibi-
tion (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 [J-endor-
phin 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 endor-
phin system, vasodilatation may be caused by stimulation of
sensory nerve fibres which inhibit die 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 concentra-
tions of central opioids may regulate the function of the
'hypodialamic^jituitary-ovarian axis via the central sym-
pathetic system, and that a hyperactive sympathetic system in
anovulatory patients could be normalized by EA (Chen and
Yin, 1991).
Introduction
Successful in-vitro fertilization (IVF) and embryo transfer
demand optimal endometrial receptivity at the time of implanta-
tion. Blood flow impedance in die uterine arteries, measured
as die 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*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 measure-
Materials and methods
Subjects, design and PI measurements
Tlie 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 ultrasono-
graphy and pulsed Doppler curves (Aloka SSD 680. Berner Medecin-
teknik, 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: PI =
(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
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Uterine artery Mood flow and electro-acupuncture
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-rcleasing
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 PI &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) (Bon-
ica, 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).
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 03 ms duration. The intensity
was low, giving non-painful paraesthesia.
Mean PI
3.4 -r
Before
first EA
After
eight
EA
10-14 days
after EA
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
Table I.
Points'
BL23
BL28
SP6
BL57
Acupuncture points, their anatomical position and their innervation
Segmental innervation
(afferent muscle)
LI,
2, 3
L4,
5, SI, 2,3
L4,
5, S2, 3
SI,
2
Muscle localization
Erector spinae thoracolumbale
Erector spinae lumbosacrale
Tibialis posterior at the medial
side
Gastrocnemius and m. soleus at
the dorsal side
'All were placed bilaterally.
BL = bladder channel.
SP = spleen channel.
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 thermo-
meter (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 analyse the data.
Results
Blood flow impedance
Compared to the mean baseline PI, the mean PI was signific-
antly 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).
The right and left uterine arteries responded similarly to
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ILStener-Vlctorin et al
H
Individual
1 patients
Before down-
regulation
• Before
first EA
After
eight EA
B 10-14 days
after EA
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.
Table H. The individual mean pulsatility index
EA treatment, 10-14 days after the EA period.
PI value
Before down-regulation
Before EA
After eight EA
10-14 days after eight EA
(PI)
and
i
before down-regulation,
average mean values
Individual patients
A
3.00
3.38
3.24
2.25
B
3.00
3.15
2.07
2.01
C
3.30
3.27
2.37
2.40
before the first
D
3.75
3.04
2.57
2.60
electro-acupuncture (EA)
E
3.90
3.30
2.59
2.40
F
3.25
3.50
2.80
3.84
treatment.
G
3.14
3.10
2.54
2.54
immediately
H
3.33
3.34
3.34
3.20
after the eighth
Mean value
3.34
3.26
2.68
2.65
14 21 30
EA (mln)
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'.
EA. The difference 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.
Discussion
It has been shown in previous studies that a high PI in the
uterine arteries is associated with a decreased pregnancy rate
following rVF-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 conditions.
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 ah, 1982; Hoffman and Thore'n,
1986;
Hoffman et al, 1987, 1990a,b). A decrease in sym-
pathetic activity appears to be generalized. In microneuro-
graphic studies on humans, EA in the upper limbs resulted in
an initial increase and then a decrease in the activity of
sympathetic efferents in the
tibia!
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 acupuncture hand
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Uterine artery blood flow and electro-acupuncture
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 humans 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 Thor6n, 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) sug-
gested that electrical stimulation of muscle afferents innervating
ergoreceptors increases the concentration of pVendorphin in
the CSF. They found support for the hypothesis that the
hypothalamic P-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 significantly
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 significantly increased 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.
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Received on June 27, 1995; accepted on March 20, 1996
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