ACUPUNCTURE IN IVF

Acupuncture and herbal medicine in in vitro fertilisation: a review ofthe evidence for clinical practice

YING CHEONG1, LUCIANO G. NARDO2,3, TONY RUTHERFORD4, & WILLIAM LEDGER5

1Division of Developmental Origins of Adult Diseases, University of Southampton School of Medicine (DOHaD), Level F,

Princess Anne Hospital, Southampton, UK, 2Department of Reproductive Medicine, St. Mary’s Hospital, Manchester, UK,3North West Fertility, IVF Unit, UK, 4Reproductive Medicine Unit, Leeds General Infirmary, Leeds, UK, and 5Academic

Unit of Reproductive and Developmental Medicine, University of Sheffield, Sheffield, UK

AbstractThe objectives of this systematic review were to determine the effectiveness of (a) acupuncture and (b) Chinese herbalmedicine on the treatment of male and female subfertility by assisted reproductive technologies (ART). All reports fromRCTs of acupuncture and/or Chinese herbal medicine in ART were obtained via searches through The CochraneMenstrual Disorders and Sub-fertility Group’s Specialised Register of controlled trials, and other major databases. Theoutcome measures were determined prior to starting the search, and comprised: live birth rate, ongoing pregnancy rate,clinical pregnancy rate, the incidence of ovarian hyperstimulation syndrome and multiple pregnancy, miscarriage rateand adverse effects arising from treatment. Overall, 14 trials (a total of 2670 subjects) were included in the meta-analysis. The results provided no evidence of benefit in the use of acupuncture during assisted conception. Furtherstudies should attempt to explore the potential placebo, as well as treatment, effects of this complimentary therapy.Essential elements for a quality RCT will be the size of the trial, the use of a standardised acupuncture method and ofplacebo needles.

Keywords: Acupuncture, herbal medicne, assisted conception, IVF, pregnancy, RCT

Introduction

One in seven couples in Western countries suffer

from sub-fertility (Schmidt et al., 1995; Boivin et al.,

2007) and many will seek medical help in the form of

assisted reproductive technologies (ART), including

controlled ovarian stimulation with or without

intrauterine insemination (IUI) and in vitro fertilisa-

tion (IVF) treatment. More than 10,000 children are

born each year in the United Kingdom following

IVF. Traditional Chinese medicine (TCM), espe-

cially in the form of acupuncture and herbal

medicine, is widely used to treat many common

conditions and has been explored in ART. However,

its role and efficacy in reproductive medicine is still a

matter of much debate.

In its original form, the use of acupuncture and

Chinese herbal remedies was based on the princi-

ples of TCM, which is a 3000-year old holistic

system. TCM combines medicinal herbs, acupunc-

ture, food therapy, massage and therapeutic ex-

ercise for the treatment and the prevention of

disease. TCM drug treatment typically consists of

complex prescriptions of a combination of several

components. The combination is based on the

Chinese diagnostic patterns (i.e. inspection, listen-

ing, smelling, inquiry and palpation) and follows a

completely different rationale than many conven-

tional treatments. Herbal medicine is the most

important part of TCM. Acupuncture ‘involves the

insertion of fine needles into the skin along the

meridians and provides a means of altering the flow of

energy through the body’ (Vickers & Zollman, 1999).

In a typical treatment, between 4 and 10 points are

needled for 10–30 min. Needles can be stimulated by

manual twirling or with a small electric current

(electro-acupuncture, EA). Some acupuncturists

attempt to produce a sensation called ‘de Qi’ – a

sense of heaviness, soreness or numbness at the point

of needling. This is regarded as a sign of stimulating

the acupuncture point correctly. To date, there have

been few studies on the physiological effects of

Correspondence: Ying Cheong, Division of Developmental Origins of Adult Diseases (DOHaD), Level F, Princess Anne Hospital, Southampton, UK.

E-mail: y.cheong@soton.ac.uk

Human Fertility, March 2010; 13(1): 3–12

ISSN 1464-7273 print/ISSN 1742-8149 online � British Fertility Society

DOI: 10.3109/14647270903438830

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acupuncture in the male and female reproductive

tract.

Aims

(a) To determine the effectiveness of acupuncture

alone or acupuncture with concurrent IVF on

the outcome of treating male and female sub-

fertility compared with the various forms of

IVF and with no treatment alone.

(b) To determine the effectiveness of Chinese

herbal medicine alone or with concurrent

IVF on the outcome of treating male and

female subfertility compared with the various

forms of IVF and no treatment alone.

Trial inclusion criteria

Acupuncture

Searches were conducted for all prospective ran-

domised controlled trials (RCTs) which compared

acupuncture treatment versus no treatment, placebo

acupuncture or sham acupuncture during ovarian

stimulation with or without IUI, IVF or frozen-

thawed embryo transfer (FET) treatment. The two

types of sham or placebo acupuncture commonly

used are (a) needling an area that is not a

recognised ‘point’, and (b) needling a point which

is believed to be ineffective for the particular

condition. Needling can be performed by using

real needling with skin penetration or using a sham

or placebo needle (for example, the Streitberger

placebo needle, Asiamed, Pullach, Germany).

Because the tip of the sham needle is blunted,

skin penetration will not occur. We included either

traditional acupuncture, in which needles are

inserted in classical meridian points, or contem-

porary acupuncture, in which the needles are

inserted in non-meridian or trigger points, regard-

less of the source of stimulation (for example,

hand, fine needle, moxibustion, which is a tradi-

tional Chinese treatment using moxa or mugwort

herb on acupuncture points, with warming needle

or electrical stimulation). We excluded studies of

acupuncture treatment without needling, such as

point injection, acupressure, laser acupuncture,

tap-pricking or cupping on pricked superficial

blood vessels. We also excluded trials comparing

different acupuncture treatments alone.

Chinese herbal medicine

Searches were conducted for all prospective RCTs

comparing Chinese medicinal herbs (single or

compound) with no intervention, placebo or stan-

dard medical interventions, such as clomiphene

citrate and GnRH agonists for ovulatory problems,

and immunological treatments for subfertility.

Search strategy

All the reports from RCTs of acupuncture and/or

Chinese herbal medicine in ART were obtained via

searches through The Cochrane Menstrual Dis-

orders and Sub-fertility Group’s Specialised Regis-

ter of controlled trials; the China Academic Journal

Electronic full text Database in China National

Knowledge Infrastructure, Index to Chinese Peri-

odical Literature, the National Research Register,

PsycINFO or the US equivalent Clinical Trials

register (http://www.clinicaltrials.gov). All refer-

ences of the studies included and excluded were

hand-searched for additional relevant reports. The

levels of evidence used are those shown in Table I.

Statistical analysis was performed in accordance

with the guidelines developed by the Menstrual

Disorders and Sub-fertility Group. Where possible,

the outcomes were pooled statistically. For dichot-

omous data (i.e. proportion of participants with a

specific adverse side effect), results were expressed

for each study as an odds ratio with 95%

confidence intervals (95% CI) and combined them

for meta-analysis with Cochrane Review Manager

software (RevMan 5) using Peto-modified Mantel–

Haenszel method. Continuous differences between

groups in the meta-analysis have been shown as a

weighted mean difference and 95% CI. The fixed

effects model was used. The heterogeneity between

the results of different studies was examined by

inspecting the scatter in the data points, the

overlap in their confidence intervals and, more

formally, by checking the results of the chi-squared

tests. Subgroup analysis and sensitivity analysis

were performed when there was significant clinical

or statistical heterogeneity.

Outcome measures

The outcome measures were determined prior to

starting the search, and comprised: live birth rate

(LBR), ongoing pregnancy rate, clinical pregnancy

rate (CPR), the incidence of ovarian hyperstimula-

tion syndrome (OHSS) and multiple pregnancy,

miscarriage rate and adverse effects arising from

treatment.

Results

Acupuncture

Overall, 14 trials (a total of 2670 subjects) were

included in the meta-analysis. The reports were of

three types: (a) those in which acupuncture was

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undertaken around the time of oocyte retrieval

(Stener-Victorin et al., 1999, 2003; Humaidan &

Stener-Victorin, 2004; Gejervall et al., 2005;

Sator-Katzenschlager et al., 2006); (b) those in

which acupuncture was done on the day of

Embryo Transfer only (Paulus et al., 2002,

2003; Benson et al., 2006; Smith et al., 2006;

Westergaard et al., 2006; Craig et al., 2007;

Domar et al., 2008; So et al., 2009) and (c) those

in which acupuncture was performed on the

Table I. Grading of evidence.

Hierarchy of evidence

1a Systematic review and meta-analysis of randomised controlled trials (RCTs).

1b At least one randomised controlled trial.

2a At least one well-designed controlled study without randomisation.

2b At least one other type of well-designed quasi-experimental study.

3 Well designed non experimental descriptive studies, such as comparative studies, correlation studies or case studies.

4 Expert committee reports or opinions and/or clinical experience of respected authorities.

Grade strength of evidence

A Requires at least one RCT as part of a body of literature of overall good quality and consistency addressing the specific

recommendations. (Evidence levels 1a, 1b)

B Requires the availability of well controlled clinical studies but no randomised clinical trials on the topics of recommendation. (Evidence

levels 2a, 2b, 3)

C Requires evidence obtained from expert committee reports of opinions and/or clinical experiences of respected authorities. Indicates an

absence of directly applicable clinical studies of good quality. (Evidence level 4)

GPP Good practice point.

Table II. Description of location of the four most commonly used acupuncture points.

Acupuncture points Intended treatment

GV 20 (Baihui) Location: on the midline of the head, 7 cun directly above the posterior hairline, approximately on the midpoint

of the line connecting the apexes of the two auricles.

Indications: Headache, vertigo, tinnitus, nasal obstruction, aphasia by apoplexy, coma, mental disorders,

prolapse of the rectum and the uterus.

Traditional action: Clears the mind, lifts the spirits, tonifies yang, strengthens the ascending function of the spleen,

eliminates interior wind, promotes resuscitation.

Location: in the middle of the 2nd metacarpal bone on the radial side.

Precautions: no moxa, no needle in pregnancy.

Point associations: Yuan source point, entry point, command point for face, nose, mouth and jaw

LI 4 (Hegu) Actions and effects:

Releases the exterior for wind-cold or wind-heat syndromes

Strengthens the wei qi, improves immunity.

Regulates the sweat glands, for excessive sweating tonify LI 4 then disperse KD 7 and vice versa

Any problem on the face - sense organs, mouth, teeth, jaw, toothache, allergies, rhinitis, hay fever, acne,

eye problems, etc.

Toothache use both LI 4 & ST 44 - LI for the lower jaw & ST for the upper jaw

Headache, especially frontal, sinus (yangming area)

Chronic pain

Influence the circulation of Qi and blood - use the four gates, LI 4 & LV 3 to strongly move the Qi and blood

in the body clearing stagnation and alleviating pain.

Promote labor or for retained placenta

SP 6 (Sanyinjiao) Location: 3 cun directly above the tip of the medial malleolus on the posterior border of the tibia

Precautions: no needle in pregnancy

Point associations:

Intersection point of the SP, LV and KD (3 leg yin meridians)

Actions and effects:

Tonify Yin and blood, all spleen disorders.

Digestive disorders, sinking or prolapse.

Gynaecological issues, male sexual issues, difficult labour (expel foetus)

Bleeding disorders, cool blood in hot skin diseases

Insomnia and other anxiety-related emotions

Location: 2 cun lateral to the AML level with CV 3

ST29 (Guilai) Actions and effects:

Excess or cold/deficient disorders of the lower warmer - amenorrhoea, irregular menstruation, qi stagnation/masses

Running Piglet disorder

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day of ET and then 2–3 days after ET (repeated

acupuncture) (Dieterle et al., 2006; Westergaard

et al., 2006). Data relating to LBR were

obtained from six trials (Paulus et al., 2002,

2003; Stener-Victorin et al., 2003; Humaidan &

Stener-Victorin, 2004; Benson et al., 2006;

Dieterle et al., 2006; Domar et al., 2008).

The most commonly used acupuncture points

appeared to be GV 20, LI 4, SP6 and ST 29

(Table II).

Acupuncture versus Control (all categories) (Figure 1)

Live birth rate. In the pooled results from seven

trials (Stener-Victorin et al., 1999; Paulus et al.,

2002, 2003; Humaidan & Stener-Victorin, 2004;

Dieterle et al., 2006; Westergaard et al., 2006; So

et al., 2009) (a total of 1601 subjects), the LBR was

32% (258/805) in the acupuncture group and 29%

(229/796) in the control group (odds ratio 1.31, 95%

CI 0.88–1.95).

Clinical pregnancy rate. In the pooled results from

14 trials (n¼ 2670) (Stener-Victorin et al., 1999,

2003; Paulus et al., 2002, 2003; Humaidan &

Stener-Victorin, 2004; Gejervall et al., 2005;

Benson et al., 2006; Dieterle et al., 2006; Sator-

Katzenschlager et al., 2006; Smith et al., 2006;

Westergaard et al., 2006; Craig et al., 2007;

Domar et al., 2008; So et al., 2009), the CPR

Figure 1. Outcomes of acupuncture versus control (all categories): (a) Live birth. (b) Clinical pregnancy. (c) Miscarriage.

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was 38% (531/1406) in the acupuncture group and

35% (440/1264) in the control group (odds ratio

1.21, 95% CI 0.9–1.63).

Miscarriage. In the pooled results from three

trials (Dieterle et al., 2006; Smith et al., 2006;

Westergaard et al., 2006; So et al., 2009) (a total

of 908 subjects), the miscarriage rate was 13% (65/

492) in the acupuncture group and 12% (54/416) in

the control group (odds ratio 1.21, 95% CI 0.8–

1.83).

Acupuncture around the time of oocyte retrieval

(Figure 2)

Live birth rate. Only two trials reported on LBR

(Stener-Victorin et al., 2003; Humaidan & Stener-

Victorin, 2004) (a total of 464 subjects). There was no

difference in the LBR between the patients who had

acupuncture (75/229, 33%) and the control group (84/

235, 36%) (odds ratio 0.87, 95% CI 0.59–1.29).

Clinical pregnancy rate. In the pooled results from

five trials (Stener-Victorin et al., 1999, 2003; Humai-

dan & Stener-Victorin, 2004; Gejervall et al., 2005;

Sator-Katzenschlager et al., 2006) (a total of 868

subjects), the CPR in the treatment group was 37%

(165/448) and in the control group was 35% (146/

420) (odds ratio 1.08, 95% CI 0.82–1.44).

Miscarriage rate. The pooled results from four trials

(Stener-Victorin et al., 1999, 2003; Humaidan &

Stener-Victorin, 2004; Sator-Katzenschlager et al.,

2006) (a total of 378 subjects) showed no difference

in the miscarriage rate between the treatment group

and controls (9/71, 13% and 12/68, 16%; odds ratio

0.81, 95% CI 0.46–1.46).

Acupuncture on the day of ET (Figure 3)

Live birth rate. In the pooled results from four trials

(Paulus et al., 2002, 2003; Westergaard et al., 2006;

So et al., 2009) (n¼ 912 subjects), the LBR was 33%

(151/460) in the acupuncture group and 29% (130/

452) in the control group (odds ratio 1.43, 95% CI

0.77–2.65). There was no statistical difference in

LBR in the acupuncture compared to the control

group.

Figure 2. Outcomes of acupuncture during oocyte retrieval versus control: (a) Live birth. (b) Clinical pregnancy. (c)

Miscarriage.

Acupuncture and herbal medicine 7

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Clinical pregnancy rate. In the pooled results of

seven trials (Paulus et al., 2002, 2003; Benson et al.,

2006; Smith et al., 2006; Westergaard et al., 2006;

Domar et al., 2008; So et al., 2009) (n¼ 1486

subjects), the CPR was 39% (294/751) in the

acupuncture treatment group and 37% (273/735)

in the controls (odds ratio 1.14, 95% CI 0.76–1.69).

There was no evidence of benefit for the use of

acupuncture treatment in terms of CPR compared to

the controls.

Miscarriage rate. Only three trials (Smith et al.,

2006; Westergaard et al., 2006; So et al., 2009)

(n¼ 592) evaluated the possible impact of acupunc-

ture on the day of embryo transfer on miscarriage.

There was no difference between the acupuncture

treatment group (22%: 64/285) and the control

group (18% (55/307), odds ratio 1.38, 95% CI 0.90–

2.11).

Repeated acupuncture after ET (Figure 4)

Live birth rate. The pooled results of three studies

(Dieterle et al., 2006; Westergaard et al., 2006; So

et al., 2009) (n¼ 403) indicated that there was no

statistical difference in the LBR between the acu-

puncture treatment and the control groups when

acupuncture was performed at the time of ET and

repeated 2–3 days later. The LBR was 28% (57/207)

in the acupuncture group compared to 17% (34/196)

in the control group (OR 1.83, 95% CI 1.00–3.85;

P¼ 0.05).

Clinical pregnancy rate. From the pooled results of

two trials (Dieterle et al., 2006; Westergaard et al.,

2006) (n¼ 403), the CPR of the acupuncture

treatment group was 35% (72/207) compared to

19% (38/196) for the control group (OR 2.23, 95%

CI 1.41–3.51; P¼ 0.0006).

Figure 3. Outcomes of acupuncture on the day of ET versus control: (a) Live birth. (b) Clinical pregnancy. (c)

Miscarriage.

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Miscarriage rate. Two trials (n¼ 403) evaluated the

impact of repeated acupuncture on miscarriage

(Dieterle et al., 2006; Westergaard et al., 2006).

There was no statistical difference in the miscarriage

rate between acupuncture and the controls when

acupuncture was performed around ET and repeated

2–3 days later. The miscarriage rate in the acupunc-

ture group was 14% (30/207) compared to 9% (18/

196) in the control group (OR 1.68, 95% CI 0.90–

3.12; P¼ 0.10).

Side effects

None of the 14 trials reported on the occurrence of

OHSS. Smith et al. (2006) were the only ones to

report on patients’ experiences. The authors found

no difference in the quality of life (SF-36 scores)

between the study and control groups. The most

frequently reported outcome in that particular trial

was relaxation; subjects in the control group (who

did not received acupuncture) reported being more

relaxed compared to the study group.

Sensitivity analysis (Figure 5): acupuncture versus sham

controls around the time of ET

Live birth rate. There was no evidence of benefit

of acupuncture treatment in the sham group

(Paulus et al., 2003; Dieterle et al., 2006; So

et al., 2009) (Odds Ratio 1.12, 95% CI 0.83–

1.52). However, the group having acupuncture had

a favourable LBR, in the pooled results where non-

sham controls were used (Paulus et al., 2002;

Westergaard et al., 2006) (odds ratio 2.17, 95% CI

1.32–3.54).

Clinical pregnancy rate. The odds ratio for CPR in

studies with a sham acupuncture control group

(Paulus et al., 2002; Benson et al., 2006;

Westergaard et al., 2006; Craig et al., 2007; Domar

et al., 2008; So et al., 2009) was 1.33 (95% CI 0.72–

2.45) whilst that in studies with no sham acupunc-

ture control was 1.18 (95% CI 0.64–2.18) (Paulus

et al., 2002; Benson et al., 2006; Westergaard et al.,

2006; Craig et al., 2007; Domar et al., 2008). There

was no evidence of benefit for the use of acupuncture

versus control in terms of CPR.

Chinese herbal medicine

Meta-analytical pooling was not feasible as there

were no RCTs on the use of Chinese herbal

medicine in ART.

Discussion

This meta-analysis shows that there is no evidence of

benefit from having acupuncture around the time of

Figure 4. Outcomes of repeated acupuncture versus control: (a) Live birth. (b) Clinical pregnancy. (c) Miscarriage.

Acupuncture and herbal medicine 9

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Figure 5. Sensitivity analysis – outcomes of acupuncture on the day of ET versus control: (a) Live birth. (b) Clinical pregnancy.

(c) Miscarriage.

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assisted conception. This finding results from the

inclusion of the most recent trials and is contrary to

many previous studies. There is however, a sub-

stantial amount of clinical heterogeneity in all these

studies, in particular in the use of sham acupuncture

as a control versus no sham, the timing of the

acupuncture treatment during the course of the

assisted conception and the lack of controls for the

placebo effect. Evidence to recommend the use of

herbal medicine during IVF treatment is currently

lacking.

Acupuncture clearly has the advantages of being

painless and having no serious adverse effects.

Nevertheless, before routine treatment can be

accepted into mainstream medicine, it needs to have

proven efficacy. Acupuncture has to be demonstrably

more effective than placebo, which in this context is

relatively difficult to show. In the RCTs included in

this meta-analysis, a variety of placebos were used in

the control groups, ranging from no intervention to

the use of Sham acupuncture needles (Dieterle et al.,

2006; Smith et al., 2006). Sham needles are regarded

as the gold standard placebo although they have been

criticised as possibly inducing an ‘acupressure

effect’. The placement of a needle in any position

elicits a biological response that complicates the

interpretation of studies involving Sham needle

acupuncture. Furthermore, placebo acupoints,

whether with real or Sham needling, can mean

needling on acupoints that are unrelated to fertility,

or on points that are next to, but not on the real,

acupuncture points. There is as yet no national or

international professional group consensus regarding

what constitutes a good placebo in trials examining

the effects of acupuncture. The placebo effect in any

of these combinations of sham or placebo acupunc-

ture can be quite strong and it may well be that the

time and attention given to the patient, especially

around the time of ET, induces relaxation and

generates better outcomes.

Acupuncture is a complex intervention that has

different effects on different patients with similar

medical conditions. The number and length of

treatments needed and the specific points used

may vary among individuals and during the course

of treatment. Although all the trials included in

this review examined the effect of acupuncture in

improving the outcome of IVF, it is unclear why

different acupuncture points were selected to

achieve the same objective. In Western medicine,

where standardisation of methodology is of key

importance in medical research, the absence of

complete concordance of the acupuncture points in

these studies, which were all designed to improve

IVF pregnancy outcome, is an unfamiliar concept.

There is no consensus amongst practicing acu-

puncturists as to what constitutes reasonable

variation of an acupuncture treatment ‘protocol’.

There is also no consensus as to how much

experience and training an acupuncturist requires

in order to provide an effective acupuncture

treatment.

With regards to the safety of acupuncture and the

likelihood of miscarriage, these data provide a degree

of reassurance to both patients and practitioners

though a robust evidence base is lacking and the

current meta-analysis has not examined studies

where acupuncture has been performed in early

pregnancy.

In conclusion, the results of this meta-analysis

suggest that there is no evidence of benefit in the use

of acupuncture during assisted conception. Further

studies should attempt to explore the potential

placebo as well as treatment effects of this compli-

mentary therapy. Essential elements for a quality

RCT will be the size of the trial, the use of a

standardised acupuncture method and of placebo

needles.

References

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R.B., & Scott, R.T. (2006). Impact of acupuncture before and

after embryo transfer on the outcome of in vitro fertilization

cycles: a prospective single blind randomized study. Fertility &

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Recommendation and guidance for practice

There is no evidence of benefit for the use of

acupuncture in IVF treatment. A

Further research is required to optimise and

standardise the acupuncture technique em-

ployed. GPP

There is currently no evidence to recommend

the use of Chinese herbal medicine in IVF

treatment.

Acupuncture and herbal medicine 11

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Werner, C., & Bergh, C. (2005). Electro-acupuncture versus

conventional analgesia: a comparison of pain levels during

oocyte aspiration and patients’ experiences of well-being after

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