| Home Contact Us Site Map A Acupuncture & Chinese Herbal Medicine Clinics 665 Main St. E. Hamilton ON L8M 1K1 107--2201 Brant St. Burlington ON L7P 3N8 508--2000 credit Valley Rd. Mississauga ON L5M 4N4 Phone: (905) 317-8650 Copy Right @ 2003 A Acupuncture & Chinese Herbal Medicine Clinics, All Right Reserved. |
| A Acupuncture & Chinese Herbal Medicine Clinics |
 |
| |
 |
| |
 |
| |
 |
| |
 |
| |
 |
| |
 |
| |
 |
| |
 |
| |
 |
Upper Level
FERTILITY AND STERILITY® 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 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)
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.
Upper Level