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FERTILITY AND STERILITY® VOL. 77, NO. 4, APRIL 2002
Copyright ©2002 American Society for Reproductive
Medicine
Published by Elsevier Science Inc.
Influence of acupuncture
on the pregnancy rate in patients who undergo assisted
reproduction therapy
Wolfgang E. Paulus, M.D.,[a] Mingmin Zhang, M.D.,[b]
Erwin Strehler, M.D.,[a]
Imam El-Danasouri, Ph.D.,[a] and Karl Sterzik, M.D.[a]
Christian-Lauritzen-Institut, Ulm, Germany
Received June 5, 2001; revised and accepted October 16,
2001.
Reprint requests: Wolfgang E. Paulus, M.D., Christian-Lauritzen-Institut,
Frauenstr. 51, D-89073, Ulm, Germany (FAX: ++49-731-9665130;
E-mail: paulus@reprotox.de).
[a] Department of Reproductive Medicine, Christian-Lauritzen-Institut.
[b] Department of Traditional Chinese Medicine, Tongji
Hospital, Tongji Medical University, Wuhan, People's Republic
of China.
0015-0282/02/$22.00
PII S0015-0282(01)03273-3
Objective: To evaluate the effect of
acupuncture on the pregnancy rate in assisted reproduction
therapy (ART) by comparing a group of patients receiving
acupuncture treatment shortly before and after embryo
transfer with a control group receiving no acupuncture.
Design: Prospective randomized study.
Setting: Fertility center.
Patient(s): After giving informed consent,
160 patients who were undergoing ART and who had good
quality embryos were divided into the following two groups
through random selection: embryo transfer with acupuncture
(n = 80) and embryo transfer without acupuncture (n =
80).
Intervention(s): Acupuncture was performed
in 80 patients 25 minutes before and after embryo transfer.
In the control group, embryos were transferred without
any supportive therapy.
Main Outcome Measure(s): Clinical pregnancy
was defined as the presence of a fetal sac during an ultrasound
examination 6 weeks after embryo transfer.
Result(s): Clinical pregnancies were
documented in 34 of 80 patients (42.5%) in the acupuncture
group, whereas pregnancy rate was only 26.3% (21 out of
80 patients) in the control group.
Conclusion(s): Acupuncture seems to be
a useful tool for improving pregnancy rate after ART.
(Fertil Steril®2002;77:721- 4. ©2002 by American
Society for Reproductive Medicine.)
Key Words: Acupuncture, assisted reproduction,
embryo transfer, pregnancy rate
Acupuncture is an important element of traditional Chinese
medicine (TCM), which can be traced back for at least
4,000 years. Acupuncture has been shown to alleviate nausea
and vomiting, dental pain, addiction, headache, menstrual
cramps, tennis elbow, fibromyalgia, myofascial pain, osteoarthritis,
carpal tunnel syndrome, and asthma. Both physiologic and
psychological benefits of acupuncture have been scientifically
demonstrated in recent years.
However, so far there have been only a few serious trials
concerning the use of acupuncture in reproductive medicine.
Publications focus primarily on acupuncture therapy for
male infertility (1, 2). Electroacupuncture may reduce
blood flow impedance in the uterine arteries of infertile
women (3). A positive impact of electroacupuncture on
endocrinologic parameters and ovulation in women with
polycystic ovary syndrome has been demonstrated (4). In
addition, auricular acupuncture was successfully used
in the treatment of female infertility (5). In the present
study, we chose acupuncture points that relax the uterus
according to the principles of TCM. Because acupuncture
influences the autonomic nervous system, such treatment
should optimize endometrial receptivity (6). Our main
objective was to evaluate whether acupuncture accompanying
embryo transfer increases clinical pregnancy rate.
Materials
and Methods
This study was a prospective randomized trial at the Christian-Lauritzen-Institut
in Ulm, Germany. It was approved by the ethics committee
of the University of Ulm. A total of 160 healthy women
undergoing treatment with in vitro fertilization (IVF;
n = 101) or intracytoplasmic sperm injection (ICSI; n
= 59) were recruited into the study. The age of the patients
ranged from 21 to 43 (mean age: 32.5 = 4.0 years). The
cause of infertility was the same for both groups (Table
1). Only patients with good embryo quality were included
in the study. Using a computerized randomization method,
patients were assigned into either the acupuncture group
or the control group.
Table
1
Descriptive data on acupuncture and control group (mean
± SD or total number).
| |
Control
group |
Acupuncture
group |
Statistics |
| |
(n
= 80) |
(n
= 80) |
Statistics |
| Age
of patients (years) |
32.1
± 3.9 |
32.8
± 4.1 |
NS |
| No.
of previous cycles |
2.0
± 2.0 |
2.1
± 2.1 |
NS |
| No.
of transferred embryos |
2.1
± 0.5 |
2.2
± 0.5 |
NS |
| IVF
(n) |
54
|
47
|
NS |
| ICSI
(n) |
26 |
33 |
NS |
| No.
of cycles with male factor infertility |
46 |
47 |
NS |
| No.
of cycles with tubal disease |
21 |
22 |
NS |
| No.
of cycles with polycystic ovaries |
2 |
2 |
NS |
| No.
of cycles with unknown cause of infertility |
11 |
9 |
NS |
| Endometrial
thickness (mm) |
9.9
± 2.7 |
9.1
± 2.4 |
NS |
| Plasma
estradiol on day of embryo transfer (pg/mL) |
1001
-± 635 |
971
± 832 |
NS |
| Pulsatility
index of uterine arteries (PI) before embryo transfer |
2.00
± 0.56 |
2.02
± 0,45 |
NS |
| Pulsatility
index of uterine arteries (PI) after embryo transfer |
2.19
± 0.52 |
2.22
± 0,44 |
NS |
| Pregnant |
21/80
(26.3%) |
34/80
(42.5%) |
P=.03 |
NS = not significant (P>.05).
Paulus. Acupuncture in ART. Fertil Steril 2002.
Ovarian stimulation, oocyte retrieval, and in vitro culture
were performed as previously described (7). Transvaginal
ultrasound-guided needle aspiration of follicular fluid
was performed 36 to 38 hours after hCG administration.
Immediately after follicle puncture, the oocytes were
retrieved, assessed, and fertilized in vitro. Sperm preparation
and culture conditions did not differ for either group.
In cases of severe male subfertility, ICSI was preferred,
as described in the literature (8). Forty-eight hours
after the IVF or ICSI procedure, embryos were evaluated
according to their appearance as type 1 or 2 (good), type
3 or 4 (poor), as described in literature (9).
Just before and after embryo transfer, all patients underwent
ultrasound scans of the uterus using a 7-MHz transvaginal
probe (LOGIQ 400 Pro, GE Medical Systems Ultra-sound Europe,
Solingen, Germany). Pulsed Doppler curves of both uterine
arteries were measured by one observer. The pulsatility
index (PI) for each artery was calculated electronically
from a smooth curve fitted to the average waveform over
three cardiac cycles.
A maximum of three embryos, in accordance with German
law, were transferred into the uterine cavity on day 2
or 3 after oocyte retrieval. For embryo replacement, the
patient was placed in a dorsal lithotomy position, with
an empty bladder. The cervix was exposed with a bivalved
speculum, then washed with culture media prior to embryo
transfer. Labotect Embryo Transfer Catheter Set (Labotect
GmbH, Go¨ ttingen, Germany) was used for atraumatic
replacement owing to the curved guiding cannula with a
ball end, allowing the set to be used reliably even with
difficult anatomic conditions. The metallic reinforced
inner catheter shaft al lowed safe passage through the
cervical canal. When the catheter tip lay close to the
fundus, the medium containing the embryos was expelled
and the catheter withdrawn gently. After this procedure,
the patient was placed at bed rest for 25 minutes. All
oocyte retrievals and embryo transfers were performed
by one examiner using the same method. The examiner was
not aware of the patient's treatment group (control or
acupuncture).
At the time of the embryo transfer, blood samples (10
mL) were obtained from the cubital vein. Plasma estrogen
was determined by an immunometric method using the IMMULITE
2000 Immunoassay System (DPC Diagnostic Product Corporation,
Los Angeles, CA).
Luteal phase support was given by transvaginal progesterone
administration (Utrogest®, 200 mg, three times per
day; Kade, Berlin, Germany). Progesterone administration
was initiated on the day after oocyte retrieval and was
continued until the serum ß-hCG measurement 14 to
16 days after transfer and, in cases of pregnancy, until
gestation week 8.
Each patient in the experimental group received an acupuncture
treatment 25 minutes before and after embryo transfer.
Sterile disposable stainless steel needles (0.25 X 25
mm) were inserted in acupuncture point locations. Needle
reaction (soreness, numbness, or distention around the
point = Deqi sensation) occurred during the initial insertion.
After 10 minutes, the needles were rotated in order to
maintain Deqi sensation. The needles were left in position
for 25 minutes and then removed. The depth of needle insertion
was about 10 to 20 mm, depending on the region of the
body undergoing treatment. Before embryo transfer, we
used the following locations: Cx6 (Neiguan), Sp8 (Diji),
Liv3 (Taichong), Gv20 (Baihui), and S29 (Guilai).
After embryo transfer, the needles were inserted at the
following points: S36 (Zusanli), Sp6 (Sanyinjiao), Sp10
(Xuehai), and Li4 (Hegu).
In addition, we used small stainless needles (0.2 X 13
mm) for auricular acupuncture at the following points,
without rotation: ear point 55 (Shenmen), ear point 58
(Zhigong), ear point 22 (Neifenmi), and ear point 34 (Naodian).
Two needles were inserted in the right ear, the other
two needles in the left ear. The four needles remained
in the ears for 25 minutes. The side of the auricular
acupuncture was changed after embryo transfer. The patients
in the control group also remained lying still for 25
minutes after embryo transfer. All treatments were performed
by the same well-trained examiner, in the same way.
The primary point of the study was to determine whether
acupuncture improves the clinical pregnancy rate after
IVF or ICSI treatment. Student's t-test was used as a
corrective against any possible imbalance between the
two groups regarding the following variables: age of patient,
number of previous cycles, number of transferred embryos,
endometrial thickness, plasma estradiol on day of transfer,
method of treatment (IVF or ICSI), and blood flow impedance
in the uterine arteries (pulsatility index). Chi-square
test was used to compare the two groups. All statistical
analyses were carried out using the software package Statgraphics
(Manugistics, Inc., Rockville, MD).
Results
A total of 160 patients was recruited for the study. Patients
who failed to conceive during the first treatment cycle
were not reentered into the study. According to the randomization,
80 patients were treated with acupuncture, and 80 patients
underwent the usual therapy without acupuncture.
As Table 1 shows, there were no statistically significant
differences between the two groups with respect to the
following covariants: age of patient, number of previous
cycles, number of transferred embryos, endometrial thickness,
plasma estradiol on day of transfer, or method of treatment
(IVF or ICSI). Clinical indications for ART were the same
for patients of both groups. The blood flow impedance
in the uterine arteries (pulsatility index) did not differ
between the groups before and after embryo transfer.
The analysis shows that the pregnancy rate for the acupuncture
group is considerably higher than for the control group
(42.5% vs 26.3%; P=.03).
Discussion
The acupuncture points used in this study were chosen
according to the principles of TCM (10): Stimulation of
Taiying meridians (spleen) and Yangming meridians (stomach,
colon) would result in better blood perfusion and more
energy in the uterus. Stimulation of the body points Cx6,
Liv3, and Gv20, as well as stimulation of the ear points
34 and 55, would sedate the patient. Ear point 58 would
influence the uterus, whereas ear point 22 would stabilize
the endocrine system.
The anesthesia-like effects of acupuncture have been studied
extensively. Acupuncture needles stimulate muscle afferents
innervating ergoreceptors, which leads to increased ß-endorphin
concentration in the cerebrospinal fluid (11). The hypothalamic
ß-endorphinergic system has inhibitory effects on
the vasomotor center, thereby reducing sympathetic activity.
This central mechanism, which involves the hypothalamic
and brainstem systems, controls many major organ systems
in the body (12). In addition to central sympathetic inhibition
by the endorphin system, acupuncture stimulation of the
sensory nerve fibers may inhibit the sympathetic outflow
at the spinal level. By changing the concentration of
central opioids, acupuncture may also regulate the function
of the hypothalamic-pituitary-ovarian axis via the central
sympathetic system (13).
Kim et al. (14) suggested that Li4 acupuncture treatment
could be useful in inhibiting the uterus motility. In
their rat experiments, treatment on the Li4 acupoint suppressed
the expression of COX-2 enzyme in the endometrium and
myometrium of pregnant and nonpregnant uteri.
Stener-Victorin et al. (3) reduced high uterine artery
blood flow impedance by a series of eight electroacupuncture
treatments, twice a week for 4 weeks. They suggest that
a decreased tonic activity in the sympathetic vasoconstrictor
fibers to the uterus and an involvement of central mechanisms
with general inhibition of the sympathetic outflow may
be responsible for this effect. In our study, we could
not see any differences in the pulsatility index between
the acupuncture and control group before or after embryo
transfer. This may be due to a different acupuncture protocol
and the selected sample of patients with high blood flow
impedance of the uterine arteries (PI = 3.0) in the Stener-Victorin
et al. study.
As we could not observe any significant differences in
covariants between the acupuncture and control groups,
the results demonstrate that acupuncture therapy improves
pregnancy rate.
Further research is needed to demonstrate precisely how
acupuncture causes physiologic changes in the uterus and
the reproductive system. To rule out the possibility that
acupuncture produces only psychological or psychosomatic
effects, we plan to use a placebo needle set as a control
in a future study.
References
1. Siterman S, Eltes F, Wolfson V, Lederman H, Bartoov
B. Does acupuncture treatment affect sperm density in
males with very low sperm count? A pilot study. Andrologia
2000;32:31-9.
2. Bartoov B, Eltes F, Reichart M, Langzam J, Lederman
H, Zabludovsky N. Quantitative ultramorphological analysis
of human sperm: fifteen years of experience in the diagnosis
and management of male factor infertility. Arch Androl
1999;43:13-25.
3. Stener-Victorin E, Waldenstrom U, Andersson SA, Wikland
M. Reduction of blood flow impedance in the uterine arteries
of infertile women with electro-acupuncture. Hum Reprod
1996;11:1314 -7.
4. Stener-Victorin E, Waldenstrom U, Tagnfors U, Lundeberg
T, Lindst-edt G, Janson PO. Effects of electro-acupuncture
on anovulation in women with polycystic ovary syndrome.
Acta Obstet Gynecol Scand 2000;79:180 -8.
5. Gerhard I, Postneek F. Auricular acupuncture in the
treatment of female infertility. Gynecol Endocrinol 1992;6:171-81.
6. Stener-Victorin E, Lundeberg T, Waldenstrom U, Manni
L, Aloe L, Gunnarsson S, Janson PO: Effects of electro-acupuncture
on nerve growth factor and ovarian morphology in rats
with experimentally induced polycystic ovaries. Biol Reprod
2000;63:1497-503.
7. Strehler E, Abt M, El-Danasouri I, De Santo M, Sterzik
K. Impact of recombinant follicle-stimulating hormone
and human menopausal gonadotropins on in vitro fertilization
outcome. Fertil Steril 2001;75: 332-6.
8. Palermo GD, Schlegel PN, Colombero LT, Zaninovic N,
Moy F, Rosenwaks Z. Aggressive sperm immobilization prior
to intracytoplasmic sperm injection with immature spermatozoa
improves fertilization and pregnancy rates. Hum Reprod
1996;11:1023-9.
9. Plachot M, Mandelbaum J: Oocyte maturation, fertilization
and embryonic growth in vitro. Br Med Bull 1990;46:675-94.
10. Maciocia G. Obstetrics and gynecology in Chinese medicine.
New York: Churchill Livingstone, 1998.
11. Hoffmann P, Terenius L, Thoren P. Cerebrospinal fluid
immunoreactive beta-endorphin concentration is increased
by voluntary exercise in the spontaneously hypertensive
rat. Regul Pept 1990;28:233-9.
12. Andersson SA, Lundeberg T. Acupuncture-from empiricism
to science: functional background to acupuncture effects
in pain and disease. Med Hypotheses 1995;45:271-81.
13. Chen BY, Yu J. Relationship between blood radioimmunoreactive
beta-endorphin and hand skin temperature during the electro-acupuncture
induction of ovulation. Acupunct Electrother Res 1991;16:1-5.
14. Kim J, Shin KH, Na CS. Effect of acupuncture treatment
on uterine motility and cyclooxygenase-2 expression in
pregnant rats. Gynecol Obstet Invest 2000;50:225-30.
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