Acupuncture Before & After Embryo Transfer-a study

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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., 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

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.

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).

(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. In addition, we used small stainless needles (0.2 X 13 mm)

for auricular acupuncture. 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

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.

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

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

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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