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Assisted
Reproduction Therapy (IVF)
Erectile
Dysfunction
Inducing
Ovulation with Electro-Acupuncture for PCOS
Infertility
Study
Low
Sperm Quality
Male
Sterility
Menopause
Sperm
Density
FERTILITY AND
STERILITYÆ VOL. 77, NO. 4, APRIL 2002
Copyright ©2002 American Society for Reproductive Medicine
Published by Elsevier Science Inc., Printed on acid-free paper in
U.S.A.
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 SterilÆ2002;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 (UtrogestÆ, 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 þ-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 þ-endorphin
concentration in the cerebrospinal fluid (11). The hypothalamic þ-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.
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