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CLINICAL STUDY Analgesic effect of acupuncture at Hegu LI 4 on transvaginal oo-cyte retrieval with ultrasonography Jianwei Zhang, Xiaohua Wang, Ruisha Lü aa Jianwei Zhang, Reproduction a

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© 2013 JTCM All rights reserved.

CLINICAL STUDY Analgesic effect of acupuncture at Hegu (LI 4) on transvaginal oo-cyte retrieval with ultrasonography

Jianwei Zhang, Xiaohua Wang, Ruisha Lü

aa

Jianwei Zhang, Reproduction and Heredity Center

Combin-ing Traditional Chinese Medicine with Western Medicine in

Hospital Affiliated to Shandong University of Traditional

Chi-nese Medicine, Jinan 250011, China

Xiaohua Wang, Shandong University of Traditional Chinese

Medicine, Jinan 250011, China

Ruisha Lü, Master Degree Candidate of 2006 Grade in

Shan-dong University of Traditional Chinese Medicine, Jinan

250011, China

Correspondence to: Prof Jianwei Zhang, Integrative

Med-icine Reproductive and Genetic Center, Affiliated Hospital of

Shandong University of Traditional Chinese Medicine, Jinan

250011, China zhangjianwei1970@sina.com

Telephone: +86-13075323626

Accepted: January 31, 2013

Abstract

OBJECTIVE: To observe the analgesic effect of

acu-puncture at Hegu (LI 4) in vitro fertilization-embryo

transfer (IVF-ET) transvaginal oocyte retrieval using

ultrasonography and explore its mechanism

METHODS: Ninety patients undergoing IVF-EF

oo-cyte retrieval were randomly divided into three

groups: an acupuncture group with needles

insert-ed into bilateral Hegu (LI 4) points, a placebo group

given placebo needles, and a control group with

routine oocyte retrieval Each group had an

indo-metacin enema 30 min before the operation We

compared the pain-rated index (PRI), visual analogy

scale (VAS), and present pain intensity (PPI)

immedi-ately after operation and 1 h after operation We

al-so determined the neuropeptide Y (NPY) level of

the follicular fluid

RESULTS: PRI, VAS, and PPI after operation and 1 h

after operation in the acupuncture group were sig-nificantly lower than those in the control group (P< 0.01) No obvious difference (P>0.05) was observed

in PRI, VAS, and PPI after operation and 1 h after op-eration between the placebo group and the con-trol group The NPY level of the follicular fluid in the acupuncture group was significantly higher than that in the control group (P<0.01) No obvious dif-ference (P>0.05) was observed in the NPY level of the follicular fluid between the placebo group and the control group

CONCLUSION: The analgesic effect of acupuncture

at Hegu in transvaginal oocyte retrieval using ultra-sonography may be related to the increase in the NPY level of the follicular fluid

© 2013 JTCM All rights reserved

Key words: Acupuncture; Hegu (LI 4); Analgesics,

non-narcotic; Oocyte retrieval; Neuropeptide Y

INTRODUCTION

Oocyte retrieval is an important step in vitro

fertiliza-tion and embryo transfer (IVF-ET) With the vigorous development of assisted reproductive technology (ART), ultrasonographic transvaginal oocyte retrieval has become a routine operation in reproduction cen-ters In recent years, Traditional Chinese Medicine has been used in assisted reproduction, and the analgesic ef-fect of acupuncture has been clinically reported in transvaginal oocyte retrieval.1 In this study, we ob-served the analgesic effect of acupuncture at Hegu (LI 4) in IVF-EF transvaginal oocyte retrieval using ultraso-nography and explored its mechanism

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MATERIALS AND METHODS

Clinical data

Ninety patients underwent transvaginal IVF-ET

oo-cyte retrieval using ultrasonography at the Center of

Reproduction and Heredity, Affiliated Hospital of

Shandong University of Traditional Chinese Medicine

from April to October 2010 Patients were 25-40 years

old, had no severe disease, and had no prior

acupunc-ture treatment Patients were excluded if they had

aller-gies or were uncooperative The 90 patients were

ran-domly divided with a single-blind method into an

acu-puncture group, a placebo group, and a control group

(n=30) Average age was (31±5) years in the

acupunc-ture group, (32±3) years in the placebo group, and (32±

5) years in the control group The infertility illness

course was (5±3) years in the acupuncture group, (5±3)

years in the placebo group, and (4±3) years in the

con-trol group Body weight was (59±9) kg in the

acupunc-ture group, (58±8) kg in the placebo group, and (60±

10) kg in the control group There were 15 cases of

pri-mary infertility and 15 cases of secondary infertility in

the acupuncture group, 17 cases of primary infertility

and 13 cases of secondary infertility in the placebo

group, and 14 cases of primary infertility and 16 cases

of secondary infertility in the control group There was

no statistical difference in age, infertility course, and

disease history among the three groups (P>0.05) This

study was approved by the ethics committee of the

hos-pital and all the patients signed a participation

agree-ment

Methods

Therapy: thirty minutes before the operation, a 0.1 g

indometacin enema (produced by Shanghai Modern

Pharmaceutical Limited Company with batch number

H31020401, Shanghai, China) was given to the

pa-tients in the three groups Fifteen minutes before the

operation, needles were inserted into bilateral Hegu

(LI 4) points of the patients in the acupuncture group

with the uniform reinforcing-reducing method and

re-mained there until the end of the operation Hegu (LI

4) points of the patients in the placebo group were

tapped with placebo needles (15 mm was cut off from

25 mm filiform needle, the section was ground round

and smooth and the needle was inserted into a slice of

rubber) without pricking the epidermis, making the

pa-tient think that the filiform needle had been inserted

into their skin The rubber slice was fixed with

adhe-sive plaster to fix the needle in place No acupuncture

was given to the patients in the control group

Evaluation of analgesic effect: after the oocyte retrieval

and 1 h after the operation, the patient was asked to

fill out the short-form of McGill pain questionnaire

(SF-MPQ) The pain-rated index (PRI) consists of 11

sensory pain-describing phrases and four affective

pain-describing phrases For all the pain-describing

phrases, 0 means no pain, 1 means mild pain, 2 means

moderate pain, and 3 means severe pain The visual analogy scale (VAS) is a straight line, 100 mm long, with one end showing no pain and the other end show-ing acute pain The length of a section of the line shows the extent of pain The present pain intensity (PPI) is divided into no pain, mild discomfort, discom-fort, pain, moderate pain, and extreme pain expressed

as 0, 1, 2, 3, 4, and 5 respectively

Collection of follicular fluid: at the beginning of the oocyte retrieval, the main follicle was punctured to ex-tract the follicular fluid and avoid the filtration of blood as much as possible The follicular fluid was cen-trifuged for 10 min The supernatant was put in a ster-ile test tube and stored at -20℃ until examination Detection of NPY: enzyme-linked immunosorbent as-say (ELISA) was used to determine neuropeptide Y (NPY) level in the follicular fluid according to the man-ufacturer's instructions (Shanghai Fuzhong Biological Sci-tech Development Limited Company, Shanghai, China)

Statistical analysis

Measurement data are expressed with mean ± standard

deviation ( xˉ ± s ) A t-test was used for differences

be-tween two groups, and the SPSS 16.0 software (Inter-national Business Machines Co., Ltd Beijing, China) package was used to carry out statistical processing

RESULTS

PRI, VAS, and PPI scores of patients in the three groups immediately after oocyte retrieval

As shown in Table 1, the PRI, VAS, and PPI scores of patients in the acupuncture group after operation were significantly lower than those in the control group and

placebo group (P<0.01) No obvious difference (P>

0.05) was observed in the PRI, VAS, and PPI scores af-ter operation between the placebo group and the con-trol group

PRI, VAS, and PPI scores 1 h after oocyte retrieval among the three groups

As shown in Table 2, the PRI, VAS, and PPI scores 1 h after oocyte retrieval in the acupuncture group were sig-nificantly lower than those in the control group and

the placebo group (P<0.01) No obvious difference (P>

0.05) was observed in the PRI, VAS, and PPI scores 1 h after operation between the placebo group and the con-trol group

NPY level in the follicular fluid among the three groups

As shown in Table 3, the NPY level in the follicular

flu-id of the acupuncture group was significantly higher than that in the control group and the placebo group

(P<0.01) No obvious difference (P>0.05) was

ob-served in the NPY level of the follicular fluid between the placebo group and control group

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Transvaginal oocyte retrieval is a microtraumatic

opera-tion under the guidance of ultrasonography with slight

pain and no anesthesia However, it is difficult to take

eggs from some IVF patients with severe adhesion of

the pelvic cavity and high ovary position, thus

increas-ing pain in these patients With improvement in the

various parts of IVF, oocyte retrieval has become

in-creasingly popular Therefore, the search for a safe and

effective analgesic method is necessary in clinical

re-search.2,3

Hegu (LI 4), a source point of the Large Intestine

Channel of Hand-Yangming, promotes the circulation

of Qi, removes stagnancy, clears channels and activates

collaterals It is an important point for regulating Qi

and blood There are many reports on acupuncture at

Hegu (LI 4) enhancing the pain threshold and having

an analgesic and anesthetic effect in clinical opera-tions.4 In oocyte retrieval, the lower limbs of the pa-tient are fixed, the operational area is covered with a sterile sheet, and the upper limbs are exposed to easily choose a point The hypothesis that analgesia with acu-puncture is attributed to the transfer of attention was addressed by setting up a placebo group In reference

to Streitberger5 for placebo needles, a section of a fili-form needle is ground round and smooth and tapped

on the skin surface to make the patient think that the filiform needle has been inserted into skin The real acupuncture procedure is mimicked and patients who have had prior acupuncture are excluded.6The result of this study showed that the PRI, VAS, and PPI scores af-ter operation and 1 h afaf-ter operation in the acupunc-ture group were significantly lower than those in the

control group and the placebo group with (P<0.01) Moreover, no obvious difference (P>0.05) was

ob-served in the PRI, VAS, and PPI scores after operation and 1 h after operation between the placebo group and the control group, indicating that acupuncture at Hegu has a better analgesic effect in transvaginal IVF-ET oo-cyte retrieval

NPY is widely distributed in the central peripheral nerves.7,8 NPY regulates the pain threshold of the cen-tral nervous system on the spinal cord level and above the spinal cord.9-12This study showed the NPY level of the follicular fluid in the acupuncture group was signif-icantly higher than that in the control group and the

placebo group (P<0.01) This indicates that analgesic

Table 1 PRI, VAS and PPI scores after the ovum retrieval (xˉ ± s )

Group

Treatment group

Placebo-contro1 group

Control group

F value

P value

n

30 30 30

-PRI 3.0±1.5 ab 6.8±2.1 c 6.7±2.6 7.898 0.001

VAS 2.3±1.3 ab 3.9±1.1 c 4.0±1.5 15.332 0.000

PPI 1.6±0.7 ab 2.2±0.8 c 2.3±0.9 32.345 0.000 Notes: treatment group was given needles inserted into bilateral Hegu (LI 4) points; placebo group was given placebo needles; control group was given routine oocyte retrieval PRI: pain rating index; VAS: visual analogue scale; PPI: present pain intensity aP<0.01,cP>0.05,

compared with control group; bP<0.01, compared with placebo-contro1 group.

Table 2 PRI, VAS and PPI scores 1 h after the oocyte retrieval (xˉ ± s )

Group

Treatment group

Placebo-contro1 group

Control group

F value

P value

n

30 30 30

-PRI 0.4±0.7 ab 1.3±0.9 c 1.4±0.9 9.194 0.000

VAS 0.2±0.6 ab 1.0±1.0 c 1.1±1.2 6.418 0.003

PPI 0.1±0.3 ab 0.6±0.6 c 0.5±0.5 12.811 0.000 Notes: treatment group was given needles inserted into bilateral Hegu (LI 4) points; placebo group was given placebo needles; control group was given routine oocyte retrieval PRI: pain rating index; VAS: visual analogue scale; PPI: present pain intensity Compared with control group, aP<0.01,cP>0.05; compared with placebo-contro1 group,bP<0.01.

Group

Treatment group

Placebo-contro1 group

Control group

F value

P value

n

30 30 30

-NPY (pmol/L) 9±11 ab 2±5 c 2±3 10.494 0.000 Table 3 NPY concentrations in FF (xˉ ± s )

Notes: treatment group was given needles inserted into bilateral

Hegu (LI 4) points; placebo group was given placebo needles;

control group was given routine oocyte retrieval NPY:

neurop-eptide Y; FF: follicular fluid Compared with control group, aP<

0.01, cP>0.05; compared with placebo-contro1 group,bP<0.01.

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acupuncture at Hegu (LI 4) in oocyte retrieval may be

related to an increase in NPY of the follicular fluid

The formation of the follicular fluid is closely related

to the circulation of body fluid However, detecting

NPY in the follicular fluid is only a preliminary trial to

probe the mechanism of analgesic acupuncture at

Hegu (LI 4) It is still necessary to explore the

mecha-nism of regulating pain threshold with acupuncture at

Hegu (LI 4) through the neuroendocrine network in

oocyte retrieval

REFERENCES

1 Sun W, Ji CY, Zhang M Observation on analgesic effect

during and after oocyte retrieval by two kinds of analgesic

methods in assisted reproductive technology Zhong Guo

Fu You Bao Jian 2011; 26(1): 96-97.

2 Liu GW, Shi YS, Xu JS, Chen SL, Chen Y Intravenous

propofol combined with fentanyl for anesthesia during

ul-trasound-guided transvaginal oocyte retrieval Di Yi Jun Yi

Da Xue Xue Bao 2004; 24(11): 1304-1305.

3 Wang YP, Xing JQ, Yu M, et al Observation on analgesic

effect of ear acupuncture during ovum pick-up for in vitro

fertilization-embryo transfer Shanghai Zhen Jiu Za Zhi

2011; 30(1): 33-34.

4 Wang XH, Wu XL, Jin PL, et al Observation on

analge-sia effect of electroacupuncture during gynecologic outpa-tient operation Zhong Guo Zhen Jiu 2012; 32(10): 909-910.

5 Streitberger K, Kleinhenz J Introducing a placebo needle

into acupuncture research The Lancet 1998; 352(9125): 364-365.

6 Wang Y, Liu ZS Thinking on control methods in

acu-puncture trials Zhong Guo Xun Zheng Yi Xue Za Zhi 2011; 11(11): 1335-1338.

7 Gibbs JL, Flores CM, Hargreaves KM Attenuation of

capsaicin-evoked mechanical alodynia by peripheral neuro-peptide Y Y1 receptors Pain 2006; 124(1-2): 167-174.

8 Balasubramaniam A Clinical potentials of neuropeptide

Y family of hormones Am J Sura 2002; 183(4): 430-434.

9 Wang JZ, Lundeberg T, Yu LC Anti-nociceptive effects of

neuropeptide Y in periaqueductal grey in rats with inflam-mation Brain Res 2001; 893(1-2): 264-267.

10 Wang JZ Microinjection of neuropeptide Y into

periaque-ductal grey produces anti-nociception in rats with mono-neuropathy Sheng Li Xue Bao 2004; 56(1): 79-82.

11 Li Y, Li JJ, Yu LC Anti-nociceptive effect of neuropeptide

Y in the nucleus accumbens of rats: an involvement of opi-oid receptors in the effect Brain Researchc 2002; 940 (1-2): 69-78.

12 Zhang Y, Lundeberg T, Yu LC Incolcement of

neuropep-tide Y and Y1 receptor in antinociception in nucleus raphe magnus of rats Regul Pept 2000; 95(1-3): 109-113.

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