Acupuncture and assisted conception

Transcription

Acupuncture and assisted conception (Review)
Cheong YC, Hung Yu Ng E, Ledger WL
This is a reprint of a Cochrane review, prepared and maintained by The Cochrane Collaboration and published in The Cochrane Library
2009, Issue 1
http://www.thecochranelibrary.com
Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
TABLE OF CONTENTS
HEADER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
ABSTRACT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
PLAIN LANGUAGE SUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
BACKGROUND . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
OBJECTIVES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
METHODS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
RESULTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Figure 1.
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Figure 2.
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DISCUSSION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
AUTHORS’ CONCLUSIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
ACKNOWLEDGEMENTS
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
CHARACTERISTICS OF STUDIES . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
DATA AND ANALYSES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 1.1. Comparison 1 Acupuncture on the day of ET versus no acupuncture, Outcome 1 Live Birth. . . . .
Analysis 1.2. Comparison 1 Acupuncture on the day of ET versus no acupuncture, Outcome 2 Ongoing pregnancy.
Analysis 1.3. Comparison 1 Acupuncture on the day of ET versus no acupuncture, Outcome 3 Clinical pregnancy rate.
Analysis 1.4. Comparison 1 Acupuncture on the day of ET versus no acupuncture, Outcome 4 Miscarriage. . . .
Analysis 2.1. Comparison 2 Repeated acupuncture versus no acupuncture, Outcome 1 Live Birth. . . . . . . .
Analysis 2.2. Comparison 2 Repeated acupuncture versus no acupuncture, Outcome 2 Ongoing pregnancy. . . .
Analysis 2.3. Comparison 2 Repeated acupuncture versus no acupuncture, Outcome 3 Clinical pregnancy rate. . .
Analysis 2.4. Comparison 2 Repeated acupuncture versus no acupuncture, Outcome 4 Miscarriage. . . . . . .
Analysis 3.1. Comparison 3 Acupuncture versus no acupuncture around the time of oocyte retrieval, Outcome 1 Live Birth
Rate. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 3.2. Comparison 3 Acupuncture versus no acupuncture around the time of oocyte retrieval, Outcome 2 Ongoing
Pregnancy Rate. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 3.3. Comparison 3 Acupuncture versus no acupuncture around the time of oocyte retrieval, Outcome 3 Clinical
Pregnancy Rate. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 3.4. Comparison 3 Acupuncture versus no acupuncture around the time of oocyte retrieval, Outcome 4 Miscarriage
rate. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 4.1. Comparison 4 Sensitivity analysis with sham versus no sham: acupuncture during ET and repeated groups,
Outcome 1 Live Birth. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Outcome 2 Ongoing pregnancy. . . . . . . . . . . . . . . . . . . . . . . . . . . .
Outcome 3 Clinical pregnancy. . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Outcome 4 Miscarriage. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
APPENDICES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
WHAT’S NEW . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
HISTORY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
CONTRIBUTIONS OF AUTHORS . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
DECLARATIONS OF INTEREST . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
SOURCES OF SUPPORT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
INDEX TERMS
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1
2
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3
3
5
9
10
17
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31
32
33
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i
[Intervention Review]
Ying C Cheong1 , Ernest Hung Yu Ng2 , William L Ledger3
1 Obstetrics and Gynaecology, University of Southampton, Southampton, UK. 2 Department of Obstetrics and Gynaecology, University
of Hong Kong, Queen Mary Hospital, Hong Kong, Hong Kong. 3 University of Sheffield, Sheffield , UK
Contact address: Ying C Cheong, Obstetrics and Gynaecology, University of Southampton, Level F, Princess Anne Hospital, Coxford
Road, Southampton, SO16 5YA, UK. [email protected]. [email protected].
Editorial group: Cochrane Menstrual Disorders and Subfertility Group.
Publication status and date: Edited (no change to conclusions), published in Issue 1, 2009.
Review content assessed as up-to-date: 12 October 2007.
Citation: Cheong YC, Hung Yu Ng E, Ledger WL. Acupuncture and assisted conception. Cochrane Database of Systematic Reviews
2008, Issue 4. Art. No.: CD006920. DOI: 10.1002/14651858.CD006920.pub2.
ABSTRACT
Background
Acupuncture has recently been studied in assisted reproductive treatment (ART) although its role in reproductive medicine is still
debated.
Objectives
To determine the effectiveness of acupuncture in the outcomes of ART.
Search strategy
All reports which describe randomised controlled trials of acupuncture in assisted conception were obtained through searches of the
Menstrual Disorders and Subfertility Group Specialised Register, CENTRAL, Ovid MEDLINE (1996 to August 2007), EMBASE
(1980 to August 2007), CINAHL (Cumulative Index to Nursing & Allied Health Literature) (1982 to August 2007), AMED, National
Research Register, Clinical Trials register (www.clinicaltrials.gov), and the Chinese database of clinical trials.
Selection criteria
Randomised controlled trials of acupuncture for couples who were undergoing ART comparing acupuncture treatment alone or
acupuncture with concurrent ART versus no treatment, placebo or sham acupuncture plus ART for the treatment of primary and
secondary infertility. Women with medical illness deemed contraindications for ART or acupuncture were excluded.
Data collection and analysis
Sixteen randomised controlled trials were identified that involved acupuncture and assisted conception. Thirteen trials were included
in the review and three were excluded. Quality assessment and data extraction were performed independently by two review authors.
Meta-analysis was performed using odds ratio (OR) for dichotomous outcomes. The outcome measures were live birth rate, clinical
ongoing pregnancy rate, miscarriage rate, and any reported side effects of treatment.
Main results
There is evidence of benefit when acupuncture is performed on the day of embryo transfer (ET) on the live birth rate (OR 1.86, 95%
CI 1.29 to 2.77) but not when it is performed two to three days after ET (OR 1.79, 95% CI 0.93 to 3.44). There is no evidence of
benefit on pregnancy outcomes when acupuncture is performed around the time of oocyte retrieval.
1
Authors’ conclusions
Acupuncture performed on the day of ET shows a beneficial effect on the live birth rate; however, with the present evidence this could
be attributed to placebo effect and the small number of women included in the trials. Acupuncture should not be offered during the
luteal phase in routine clinical practice until further evidence is available from sufficiently powered RCTs.
PLAIN LANGUAGE SUMMARY
The data from this meta-analysis suggests that acupuncture does increase the live birth rate with in vitro fertilisation (IVF) treatment
when performed around the time of embryo transfer. However, this could be attributed to placebo effect and the small number of trials
included in the review. Larger studies are necessary to confirm the results. Acupuncture may have potential harmful effects in early
pregnancy and hence clinicians should be cautious when giving advice regarding the use of acupuncture in early pregnancy.
BACKGROUND
One in seven to ten couples in industrialised countries suffer from
subfertility (Boivin 2007; Schmidt 1995). Many will seek medical help in the form of assisted reproductive technologies (ART),
including controlled ovarian stimulation (COS) with or without
intrauterine insemination (IUI) and in vitro fertilisation (IVF)
treatment. More than 10,000 children in the United Kingdom
are born each year through IVF treatment. Acupuncture is most
commonly used to treat conditions of chronic pain. Its use has
been studied in assisted reproductive treatment, although its role
in reproductive medicine is still debated (Stener-Victorin 2002).
There are few relevant randomised trials that address this issue.
Acupuncture is an integral part of traditional Chinese medicine
(TCM) and can be dated back at least 3000 years. Its use has gained
increasing popularity in the Western world. In Europe, from consumer surveys (Fisher 1994; Thomas 2001) between 7% and 19%
of the population report using acupuncture for various reasons.
A survey of acupuncture that was released by an NIH Consensus
Development Panel indicated that promising data exist for the
use of acupuncture in treating postoperative and chemotherapy
nausea and vomiting and in postoperative dental pain in adults,
although there were inherent problems of study design, sample
size and appropriate controls in the acupuncture literature (NIH
Consensus 1998).
In its original form, acupuncture was based on the principles of
TCM. According to these the workings of the body are controlled
by a vital force called ’Qi’, which circulates between the organs
along channels called meridians. There are 12 main meridians that
correspond to 12 main functions or ’organs’, although the Chinese
definition of organs corresponds only loosely with that of Western
medicine. The Qi must flow smoothly with strength and quality
for health to be maintained. Acupuncture involves the insertion
of fine needles into the skin along the meridians and provides one
means of altering the flow of energy through the body (Vickers
1999). In a typical treatment, between four to 10 points are needled for 10 to 30 minutes. Needles can be stimulated by manual twirling or with a small electric current as electro-acupuncture
(EA). Some acupuncturists attempt to produce a sensation called
’de Qi’, which is a sense of heaviness, soreness or numbness at the
point of needling, and this is regarded as a sign of correctly stimulating the acupuncture point. There has been little study of the
physiological effects of acupuncture on the male or female reproductive tract.
Acupuncture has been shown to alter plasma beta-endorphin levels which in turn can affect the hypothalamic-pituitary-adrenal
(HPA) axis by altering the release of hypothalamic gonadotrophinreleasing hormone (GnRH) and pituitary gonadotrophin secretion (Chen 2004 1997; Stener-Victorin 2000). In animal studies, acupuncture can affect the HPA axis and the release of corticotrophin-releasing factor (CRF) thus affecting stress responses,
2
which have a known impact on reproductive function (StenerVictorin 2001). Acupuncture has also been shown to reduce uterine artery resistance, which may have a positive impact on implantation (Stener-Victorin 1996). In a study comparing analgesia
with EA versus standard alfentanil analgesia during oocyte aspiration, the EA group was found to have a higher take-home baby
rate (28/75) than did the control group (19/74) (Stener-Victorin
1999); although this was not the main objective of the study.
Other non-randomised trials have shown possible positive effects
of acupuncture on pregnancy outcomes (Gehard 1992). One of
the reasons why both patients and healthcare workers are attracted
to acupuncture is that it is regarded as non-invasive and free of
risk if performed by appropriately trained personnel. A prospective study of over 55,000 acupuncture treatments recorded 63 minor adverse events (1%), such as bruising, bleeding at the site of
puncture or dizziness, with no serious adverse events including
pneumothorax, infection or spinal lesions.
OBJECTIVES
To determine the effectiveness of acupuncture alone or acupuncture with concurrent ART treatment for male and female subfertility when compared with various forms of ART or no treatment.
METHODS
Criteria for considering studies for this review
• primary or secondary subfertility;
• undergoing ART;
• any type of acupuncture at any or all time points before,
during, or after ART with the intention to improve the ART
outcome.
Exclusion criteria:
• couples with any medical illness deemed a contraindication
for ART or acupuncture treatment;
• quasi-randomised controlled trials, or crossover randomised
controlled trials that did not provide pre-crossover data
Types of interventions
We included trials that compared acupuncture therapy with
placebo, sham treatment, or no intervention. We included either
traditional acupuncture, in which needles were inserted in classical
meridian points, or contemporary acupuncture in which the needles were inserted in non-meridian or trigger points. The source
of stimulation could be the hand, fine needle, moxibustion with
warming needle, or electrical stimulation, for example. 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 excluded trials
comparing different acupuncture treatments alone.
Specific interventions to be considered:
1. acupuncture + ART versus no treatment/placebo/sham
acupuncture + ART;
2. acupuncture alone versus no treatment/placebo/sham acupuncture + ART.
Types of studies
Types of outcome measures
All prospective, randomised controlled trials comparing acupuncture treatment versus no treatment, placebo or sham acupuncture
acupuncture during controlled ovarian stimulation (COS) with
or without artificial stimulation by husband (+/- AIH), IVF, or
frozen-thawed embryo transfer (FET) treatment. The two types
of sham or placebo acupuncture that are commonly used are:
a) needling an area that is not a recognised acupoint, and b)
needling a point which is believed to be ineffective for the condition. Needling can be performed by using real needling with skin
penetration or using the sham or placebo needle (for example the
Streitberger placebo needle, Asiamed, Pullach, Germany) where
skin penetration does not occur because the tip of the needle is
blunted.
Primary outcomes
1. Live birth rate
2. Ongoing pregnancy rate
3. Clinical pregnancy rate
Secondary outcomes
1. Rates of Ovarian hyperstimulation syndrome (OHSS)
2. Multiple pregnancy
3. Miscarriage
4. Side effects arising from the use of acupuncture
Rates of OHSS, multiple pregnancy, and miscarriage were defined
by rate per woman.
Search methods for identification of studies
Types of participants
Couples in the trials had to meet all the following criteria to be
included in the review.
Inclusion criteria:
All reports which described randomised controlled trials of
acupuncture in assisted conception were identified using the following search strategy.
3
1) The Menstrual Disorders and Subfertility Group Specialised
Register was searched for any trials with acupuncture in the title, abstract or keyword sections. Keywords CONTAINS “IVF”
or “in vitro fertilization” or “in-vitro fertilisation” or “ICSI”
or“intracytoplasmic sperm injection” or “Embryo” or “in-vitro fertilization” or Title CONTAINS “IVF” or “in vitro fertilization”
or “in-vitro fertilisation” or “ICSI” or“intracytoplasmic sperm injection” or “Embryo” or “in-vitro fertilization”
Trial characteristics
1. Method of randomisation
2. Presence of absence of blinding to treatment allocation
3. Quality of allocation concealment
4. Number of patients randomised, excluded, or lost to follow up
5. Whether an intention-to-treat analysis was done
6. Whether a power calculation was done
7. Duration, timing, and location of the study
AND
Characteristics of the study participants
1. Age and any other recorded characteristics of women in the
study
2. Other inclusion criteria
3. Exclusion criteria
Keywords CONTAINS “acupoint” or “acupressure” or “acupressure-acupuncture therapy” or “Acupuncture” or “electroacupuncture” or “electroacupuncture” or “moxibustion” or Title CONTAINS “acupoint” or “acupressure” or “acupressureacupuncture therapy” or “Acupuncture” or “electro-acupuncture”
or “electroacupuncture” or “moxibustion”. The terms used in
Chinese were “ZHEN JIU”,“BU YUN”,“BU YU”,“FU ZHU
SHENG ZHI”,“FU ZHU SHENG YU”,“ REN GONG SHOU
JING”,“REN GONG SHENG ZHI”,“PAI LUAN”,“NAN
XING BU YUN”,“
NAN XING BU YU”,“ XI BAO JIANG NEI JING ZI ZHU SHE
FA”,“ LUAN MU XI BAO JIANG NEI DAN JING ZI XIAN
WEI ZHU SHE”,“PEI TAI”,“ DIAN ZHEN”,“AI JIU”,“XUE
WEI”,“ XUE WEI AN YA”.
2) The electronic databases CENTRAL, MEDLINE (1996 to August 2007), EMBASE (1980 to August 2007), CINAHL (Cumulative Index to Nursing & Allied Health Literature) (1982 to August 2007), and AMED were searched using Ovid software (see
Appendix 1; Appendix 2; Appendix 3; Appendix 4; Appendix 5).
3) Chinese literature databases were searched for Chinese studies: the China Academic Journal Electronic full text Database in
China National Knowledge Infrastructure and the Index to Chinese Periodical Literature. The key words included acupuncture,
assisted reproduction, ovulation, and male factor. One hundred
and eighty-one papers were found using the relevant key word
search, in Chinese and English, in the Chinese literature.
We
searched
for
trials
in
the National Research Register, PsycINFO, and the Clinical Trials
register (www.clinicaltrials.gov). All the references of the included
and excluded studies were handsearched for additional relevant
studies.
Data collection and analysis
Two review authors (YC and EN) selected trials for inclusion in
the review after employing the search strategy described above.
We analysed included trials for the following quality criteria and
methodological details.
Interventions used
1. Type, site, timing of acupuncture and placebo or sham acupuncture
2. Stimulation protocol for the relevant ART
3. Acupuncture versus no treatment without ART
Outcomes
1. Live birth rate
2. Ongoing pregnancy rate
3. Clinical pregnancy rate
4. Rates of OHSS and multiple pregnancy
5. Miscarriage rate
6. Side effects arising from use of acupuncture
Two review authors (YC and EN) independently extracted data
and assessed trial quality using forms designed according to
Cochrane guidelines. A third review author (WL) resolved any disagreements. Where further information was necessary, we wrote
to the authors of the relevant studies to request further data.
We performed statistical analysis in accordance with the guidelines
and methods developed by the Menstrual Disorders and Subfertility Group. Where possible, we pooled the outcomes. For dichotomous data (for example the proportion of participants with
a specific adverse side effect), we expressed results for each study
as an odds ratio (OR) with 95% confidence intervals (CI) and
combined them for meta-analysis with RevMan software using
the Peto-modified Mantel-Haenszel method. For continuous data,
differences between groups were shown as weighed mean differences (WMD) and 95% CI in the meta-analysis. We used a fixedeffect model and examined heterogeneity between the results of
different studies by inspecting the scatter in the data points, the
overlap in their CI, and more formally by checking the results of
the Chi2 test. Subgroup and sensitivity analyses were performed
when there was significant clinical and statistical heterogeneity,
respectively.
4
RESULTS
Description of studies
See: Characteristics of included studies; Characteristics of excluded
studies.
Sixteen randomised controlled trials were identified that involved
acupuncture and assisted conception. Thirteen trials were included
and three were excluded.
Trials excluded from the review
Quintero 2004 conducted a randomised double-blind but
crossover study using a needle-like device for the sham acupuncture. In that study, only 17 women were recruited and seven
of them completed both arms of the study. The seven women
were crossed over after the first cycle. There was no difference in
pregnancy rates between the two groups but the amount of gonadotrophins used was significantly reduced following acupuncture treatment. The trial had a high attrition rate, women were
crossed over after the first cycle, in addition their was a lack of
allocation concealment, it was therefore excluded. Chen 2004 and
Evans 2005 were excluded because there was inadequate information given about the trial design, allocation concealment, and
pregnancy outcome.
Trials included in the review
Thirteen randomised controlled trials were included in this review. Three of the trial reports were abstracts (Benson 2006; Craig
2007; Paulus 2003). All 13 trials had a parallel design (Benson
2006; Craig 2007; Dieterle 2006; Domar 2006; Gejervall 2005;
Humaidan 2004; Paulus 2002; Paulus 2003; Sator-K 2006; Smith
2006; Stener-Victorin 1999; Stener-Victorin 2003; Westergaard
2006). Three of the studies were performed in fertility clinics
in Germany (Dieterle 2006; Paulus 2002; Paulus 2003), three
were from the United States (Benson 2006; Craig 2007; Domar
2006) and one each from Australia (Smith 2006), Denmark (
Westergaard 2006) and Austria (Sator-K 2006). Four studies were
performed in Sweden (Gejervall 2005; Humaidan 2004; StenerVictorin 1999; Stener-Victorin 2003). Five trials were designed to
examine the fertility outcome of acupuncture performed around
the time of ET (Dieterle 2006; Paulus 2002; Paulus 2003; Smith
2006; Westergaard 2006) whilst the other five trials were designed
with the primary objective of assessing the effect of acupuncture
as an analgesic during oocyte retrieval but had pregnancy rate as
one of the primary outcomes (Gejervall 2005; Humaidan 2004;
Stener-Victorin 1999; Stener-Victorin 2003; Smith 2006).
Participants
Benson 2006 conducted a study randomising women into five
study groups: needle acupuncture (n = 53), laser acupuncture (n =
53), sham laser acupuncture (n = 520), relaxation treatment (n =
50), and no treatment (n = 50). For the purpose of this meta-analysis, only the results from the needle acupuncture and no treatment
groups were used. There were no details on the demographics as
this report was presented as an abstract. Craig 2007 randomised
women into two groups: one with acupuncture treatment (n =
48) and one without (n = 46). There were no details on demographics as this report was presented as an abstract. Domar 2006
randomised women into acupuncture (n = 78) and no treatment
(n = 68) groups. The average age of the two groups of women was
36 years, with similar numbers of previous IVF cycles in the two
groups. In Dieterle 2006 the average age (± SD) of the study group
(n = 116) was 35.1 years (± 3.8) compared to 34.7 years (± 4) for
the placebo group (n = 109). There were no statistical differences
in the body mass index (BMI), causes of subfertility, and number of previous cycles between the study and control groups. In
Gejervall 2005 the average age of the women (± SD) in the control
group (n = 80) was 33.9 years (± 3.7) compared to 33.2 years (±
3.6) in the intervention group; the average number of IVF cycles
performed was 1.56 (± 0.93) compared to 1.48 (± 0.93). The majority of women had male factor or unexplained subfertility. In
Humaidan 2004 the average age (and range) of the study group (n
= 100) was 30.5 years (22 to 39) compared to 31.5 years (23 to 29)
in the control group (n = 100); both groups had a similar BMI (24
kg/m2 ). The main causes of subfertility were unexplained, male
factor, and tubal disease with similar proportions in both groups.
In Paulus 2002 the age of the women (± SD) in the control group
(n = 80) was 32.1 years (± 3.9) compared to 32.8 years (± 4.1) in
the acupuncture group (n = 80). In the control group the average
number of previous cycles was 2.0 (± 2.0) versus 2.1 (± 2.1) in
the treatment group. Most women had tubal disease, followed by
male factor infertility then polycystic ovarian disease. These were
in equal portions in both the study and control groups. Paulus
2003 had 100 women in each of the study and control groups
but did not present any demographic details. In Sator-K 2006 the
mean ages (± SD) of the women undergoing IVF treatment in
the group receiving electro-acupuncture with remifentanil (EA),
acupuncture with remifentanil (A), and remifentanil with placebo
(CO) were 33.3 years (± 1.7), 34.2 years (± 1.1) and 33.9 years
(± 1.9), respectively. There were no differences in the number of
failed cycles or causes of subfertility. In Smith 2006 the average
age of the control group (± SD) was 35.9 years (± 4.7) versus 36.1
years (± 4.8) in the study group; there were no differences in the
number of previous treatment cycles, BMI, duration of subfertility. In Stener-Victorin 1999 the mean ages (range) of the study
and control groups were 33.3 years (25 to 42) and 34.4 years (25
to 46). There was no difference in the two groups in terms of the
cause of subfertility and the number of previous cycles. In StenerVictorin 2003 the mean age (range) in the study group was 32.9
years (22 to 38) and for the control group it was 32.9 years (25 to
38). The causes of infertility and number of IVF attempts did not
differ between the two groups. In Westergaard 2006 the average
ages of the three groups of women were: 37 years (27 to 45) in the
control (n = 87) group, 37 years (24 to 45) in the group who had
acupuncture on the day of ET (n = 95), and 37 years (27 to 45) for
5
those with repeated acupuncture (ET + 2) (n = 91). There was no
difference in the BMI between the three groups and about 67%
of women had one or more attempts of IVF in the three groups.
The main causes of subfertility were described as male factor or
unexplained.
Interventions
Timing of acupuncture
Seven trials were conducted around the time of ET only (
Benson 2006; Craig 2007; Domar 2006; Paulus 2002; Paulus
2003; Smith 2006; Westergaard 2006) and acupuncture was performed during the time of oocyte retrieval in five trials (Gejervall
2005; Humaidan 2004; Sator-K 2006; Stener-Victorin 1999;
Stener-Victorin 2003). However, in two trials (Dieterle 2006;
Westergaard 2006) the intervention was also performed two to
three days after the ET: in Dieterle 2006 acupuncture was applied
30 minutes immediately after ET and again three days later; in
Westergaard 2006 one group had acupuncture 25 minutes before
and 25 minutes after ET whilst the other group had acupuncture
25 minutes before and after ET and one session two days later (ET
+ 2). Five trials (Benson 2006; Craig 2007; Domar 2006; Paulus
2002; Paulus 2003) performed acupuncture 25 minutes before
and 25 minutes after the embryo transfer on the treatment group.
Smith 2006 described all women in the treatment group as receiving three sessions of treatment, the first undertaken on day nine
of stimulation injections, the second before ET, and the third immediately after ET. In the rest of the studies, acupuncture was performed during oocyte retrieval (Gejervall 2005; Humaidan 2004;
Sator-K 2006; Stener-Victorin 1999; Stener-Victorin 2003).
Acupuncture points
A summary of the acupuncture points used in the various studies
is provided in Table 1. Westergaard 2006 used the acupuncture
points: DU 20 (Baihui), ST29, SP8, PC6, LR3 before and immediately after ET, but in the group with the treatment at ET +
2 days they used the acupuncture points: DU20, Ren 3, ST29,
SP10, SP6, ST36, and LI 4. In Dieterle 2006 the treatment group
had acupuncture at the points: Guanyuan (RN4), Qihai (RN6),
Guilai (ST 29), Neiguan (PC6), Xuehai (SP10), and Diji (SP8).
In addition, the treatment group received a Chinese drug placed
in the ear which stimulates ear point 55 (Shenmen), ear point 58
(Zhigong), ear point 22 (Neifenmi), and ear point 33 (Pizhixia).
At ET + 3 days, the treatment groups received acupuncture at
the points: Hegu (LI14), Sanyinjiao (SP6), Zusanli (ST36), Taixu
(K13), and Taichong (LR3). Domar 2006, Paulus 2002 and Paulus
2003 used the acupuncture points: Cx6 (Neiguan), Sp8 (Diji),
Liv3 (Taichong), Gv20(Baihui), and S29 (Guilai) before ET in
the treatment group; and: S36 (Zusanli), Sp6 (Sanyinjiao), Sp10
(Xuehai), and Li4 (Hegu) after ET. In the study by Smith 2006
the exact points were based on Paulus 2002 except for two modifications: an initial acupuncture treatment was administered before
ET and two acupuncture points were excluded: liver 2 and governing vessel 20. However, Smith 2006 was the only study which
administered acupuncture point selection based on TCM diagnosis (a structured interview was used to determine the infertility
diagnosis based on a TCM perspective). Stener-Victorin 2003 and
Stener-Victorin 1999 used the points: ST36, GV20, ST29, TE5,
and LI4. Gejervall 2005 described the stimulation of the points:
KI 11, ST 29, LI 10, LI 4, ST 36, and GV 20. Sator-K 2006 used
auricular acupuncture points: 29, 55, and 57. The points L1 4,
GV 20 and SP6 were used by Humaidan 2004.
Table 1. Table 1. Summary of acupuncture points used.
Study
Craig
2007
Cv6
Y (before
ET)
Westergaard
2006
Cx6
Y
(Neiguan)
GV 20 Y
(Baihui)
Y (around
ET and
ET + 2)
Dieterle
2006
Paulus
2002
Paulus
2003;
Domar
2006
Smith
2006
Y
Y
Y
Y
StenerVictorin
1999
StenerVictorin
2003
Gejervall
2005
Humaidan
2004
Sator-K
2006
Y
Y
Y
Y
Y
6
(Continued)
Liv 2 (
Xingjian)
Liv 3 ( Y
Taichong)
Y
Y
LI
4 Y
(Hegu)
Y ( ET + Y (ET + Y
2)
3)
Y
Y
Y
LI
10 (Shoushanli)
Y
Y
Y
Y
Y
LR 3 (
Taichong)
Y
SP
Y
6 (Sanyinjiao)
Y ( ET + Y (ET + Y
2)
3)
Y
SP
(Diji)
Y
8 Y
Y
Y
Y
Y
Y
Y
Y
(ET Y
and ET +
2)
Y
Y
Y
Y
Y
Y (ET + Y
3)
Y
Y
Y
Y
SP
10 Y
(Xuehai)
ST29
(Guilai)
Y
Y
ST36 ( Y
Zushanli)
PC6
(Neiguan)
Y
Ren
3
(Zhongji)
Y (ET +
2)
Y
RN
4 (Guanyuan)
Y
RN6 (Qihai)
Y
7
k3
(Continued)
Y (after
ET)
K13
(Taxiu)
Y (ET +
3)
K1 11( Y
Henggu)
Y
TE
5
(Weiguan)
Control groups
All the studies used a different control intervention, extending
from no intervention to the use of sham acupuncture points. The
control groups in five studies (Benson 2006; Craig 2007; Domar
2006; Paulus 2002; Westergaard 2006) had their ET without
supportive therapy. Smith 2006 and Paulus 2003 used the sham
acupuncture needles (Asiamed, Pullach, Germany) described by
Streitberger (Streitberger 1998) for their control group; Smith
2006 needled close to but not on the real acupuncture points, while
Paulus 2003 used the same acupoints and scheme as for the study
group. Dieterle 2006 used placebo acupuncture points (control
ear points: earpoint 17, 14, 8, and 53; control acupuncture points:
San Jiao (SJ9), SJ12 (Xiaoluo), gallbladder GB31 (Fengshi), GB
32 (Zhongdu), and GB34 (Yang ling qua)). In the Gejevall 2005
study the control group received a sedative pre-medication consisting of 0.5 mg of oral flunitrazepam and 1 g of rectal paracetamol
prior to a paracervical block (PCB). In the operating theatre, 0.5
mg of alfentanil was administered intravenously before oocyte retrieval was begun. Controls in two studies (Stener-Victorin 1999;
Stener-Victorin 2003) had alfentanil and PCB. Controls in the
Sator-K 2006 study received standard analgesia with remifentanil.
In the control group in Humaidan 2004, patients were pre-medicated with benzodiazepine 10 mg orally (Stesolid; Dumex-Alpharma A/S, Copenhagen, Denmark) one hour before the ovum
pick up (OPU). Immediately before the application of the PCB,
0.25 mg of alfentanil was given intravenously The alfentanil bolus
was repeated (1 ± 3 times) during the OPU, up to a maximum
dose of 1 mg.
Acupuncturists
Y
The acupuncturists in Westergaard’s study (Westergaard 2006)
were nurses who were trained by two professional acupuncturists. ’Well-trained examiners’ performed the procedures in Paulus
2002 and Paulus 2003; while in Smith 2006 the procedures were
performed by two acupuncturists, one being the acupuncturist
researcher. Dieterle 2006 stated that all the acupuncture procedures were performed by the same practitioner. None of these trials stated the exact experience of the acupuncturists. Acupuncture
in the Gejevall 2005 study was performed by four midwives who
had been trained in the IVF unit. Two experienced nurses performed the acupuncture treatment in the Stener-Victorin 2003
study while Stener-Victorin 1999 and Sator-K 2006 did not mention who performed the acupuncture treatment. Acupuncture
in Humaidan 2004 was administered by ’well trained nurses’.
We have no details on the qualifications and experience of the
acupuncturists in the Benson 2006 study. Craig 2007 stated that
acupuncture was performed by “one or two acupuncturists at an
offsite location”.
Assisted conception protocols
Three studies (Dieterle 2006; Gejervall 2005; Westergaard 2006)
used standard, long protocol GnRH down regulation and the
follicle stimulating hormone (FSH) or human menopausal gonadotrophin (hMG). Nine studies (Benson 2006; Craig 2007;
Domar 2006; Humaidan 2004; Paulus 2002; Paulus 2003; SatorK 2006; Smith 2006; Stener-Victorin 2003) did not provide a
breakdown of the protocols used. All 13 trials stated that there was
no difference in the demographics or causes of subfertility between
the study and control groups. Stener-Victorin 1999 and StenerVictorin 2003 did not specify the type of stimulation protocols
used.
8
Risk of bias in included studies
See Figure 1; Figure 2
Figure 1. Methodological quality summary: review authors’ judgements about each methodological quality
item for each included study.
9
Figure 2. Methodological quality graph: review authors’ judgements about each methodological quality
item presented as percentages across all included studies.
Randomistation and allocation and concealment Figure 2
All 13 trials (Benson 2006; Craig 2007; Dieterle 2006; Domar
2006; Gejervall 2005; Humaidan 2004; Paulus 2002; Paulus
2003; Sator-K 2006; Smith 2006; Stener-Victorin 1999; StenerVictorin 2003; Westergaard 2006) were rated A for allocation concealment as the randomisation was centralised and clear.
Blinding
Due to the nature of the studies, double blinding was often not
possible. Double blinding was possible in Smith 2006 and Paulus
2003 as they used sham acupuncture needles, although Smith
2006 needled close to but not on the real acupuncture points
while Paulus 2003 used the same acupoints and scheme as the
study group. Dieterle 2006 used an actual needling procedure
on acupoints that were not considered to affect fertility. These
three trials were, therefore, single blinded. Eleven studies (Benson
2006; Craig 2007; Domar 2006; Gejervall 2005; Humaidan 2004;
Sator-K 2006; Smith 2006; Stener-Victorin 1999; Stener-Victorin
2003; Paulus 2002; Westergaard 2006) had no intervention for
the control group and hence these were not blinded trials.
Intention-to-treat analysis and follow up
Four trials (Humaidan 2004; Sator-K 2006; Smith 2006; StenerVictorin 2003) stated that they used an intention-to-treat analysis.
None of the other trials performed an intention-to-treat analysis.
Baseline similarity of comparison groups
We were able to ascertain that all but two trials (Benson 2006;
Craig 2007) had comparable baseline characteristics (age, parity,
causes of subfertility) between the study and control groups; these
two trials were published as abstracts. We were unable to obtain
details of the characteristics of the two trials from the authors.
Effects of interventions
Overall, 13 studies were included in the meta-analysis. The studies
included a total of 2209 participants. However, the studies were
of three types: firstly, those in which acupuncture was given on
the day of ET only (Benson 2006; Domar 2006; Paulus 2002;
Paulus 2003; Smith 2006; Westergaard 2006); secondly, those with
acupuncture on the day of ET and then two to three days after
ET (repeated acupuncture) (Dieterle 2006; Westergaard 2006);
and thirdly, those who had acupuncture around the time of oocyte
retrieval (Stener-Victorin 1999; Stener-Victorin 2003; Humaidan
2004; Sator-K 2006; Gejervall 2005). We obtained live birth data
from seven studies (Benson 2006; Domar 2006; Dieterle 2006;
Humaidan 2004; Paulus 2002; Paulus 2003; Stener-Victorin
2003). The most commonly used acupuncture points were: GV
20, LI 4, SP6, and ST 29 (Table 1). A summary of the intended
treatment with the various acupuncture points is given in Table 2.
10
Table 2. Table 2. Summary of the treatment intended for the respective acupuncture points
Acupuncture points
Intended treatment
Cx6 (Neiguan)
Location: 2 cun above the transverse crease of the wrist, between the tendons of muscle palmaris longus and
muscle flexor radialis.
Indications
Cardiac pain, palpitation, stuffy chest, pain in the hypochondriac region, stomach ache, nausea, vomiting,
hiccups, mental disorders, epilepsy, insomnia, febrile diseases, irritability, malaria, contracture and pain in
elbow and arm.
Traditional action
Opens the chest, regulates heart Qi and blood, regulates and clears the Triple Burner, calms the mind, regulates
the terminal Yin, harmonizes the stomach.
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.
Liv 2 (Xingjian)
Location: on the dorsum of the foot between the 1st and 2nd toes, proximal to the margin of the web at the
junction of the red and white skin.
Point associations:
Ying Spring point
Fire point
Actions and effects:
Generally, clears LV Fire - extreme irritability, red face, eyes, tongue.
Clears heat from the lower Jiao - burning urination.
Useful for “true heat, false cold” - lack of Qi flow to the extremities (cold hands or feet).
Liv 3 (Taichong)
Location: on the dorsum of the foot in a depression distal to the junctions of the 1st and 2nd metatarsal
bones.
Point associations:
Shu Stream point
Earth point
Yuan source point
Generally, resolves stagnation and tonifies Yin - balancing for all LV pathologies.
LV Qi Stagnation, LV Yang Rising - headaches, dizziness, canker sores.
Eye issues - blurred vision, red, swollen, painful eyes.
11
(Continued)
Menstrual issues from deficient blood, Yin, Qi, LV Qi stagnation - dysmenorrhea, amenorrhoea, PMS, breast
tenderness.
Genital issues - pain and swelling, hernia, impotence, seminal emission.
Stagnation in the middle warmer - subcostal tension, chest or flank pain, swellings in the axillary region.
Digestive issues from LV attacking ST/SP - nausea, vomiting, constipation, diarrhoea with undigested food.
Calming point - anger, irritability, insomnia, anxiety.
With LI 4, four gates treatment - powerfully effects the flow of Qi and blood in the body.
Location: On the dorsum of the foot in a depression distal to the junctions of the 1st and 2nd metatarsal
bones.
Point associations:
Shu Stream point
Earth point
Yuan source point
Generally, resolves stagnation and tonifies Yin - balancing for all LV pathologies.
LV Qi Stagnation / LV Yang Rising - headaches, dizziness, canker sores.
Eye issues - blurred vision, red, swollen, painful eyes.
Menstrual issues from deficient blood, Yin, Qi a/or LV Qi stagnation - dysmenorrhea, amenorrhoea, PMS,
breast tenderness.
Genital issues - pain and swelling, hernia, impotence, seminal emission.
Stagnation in the middle warmer - subcostal tension, chest/flank pain, swellings in the axillary region.
Digestive issues from LV attacking ST/SP - nausea, vomiting, constipation, diarrhoea with undigested food.
Calming point - anger, irritability, insomnia, anxiety.
With LI 4, four gates treatment - powerfully effects the flow of Qi and blood in the body.
LI 4 (Hegu)
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
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.
12
LI 10 (Shoushanli)
(Continued)
Location: 2 cun below LI 11 on the LI 5 to LI 11 line.
The following relationships exist between the ST and the LI and can be used to treat ST, LI and SI organ
problems.
SI: LI 8 & ST 39.
LI: LI 9 & ST 37.
ST: LI 10 & ST 36.
Shoulder, elbow and wrist pain issues, general aches in these areas.
Less dispersive and more tonifying than other LI points.
Epigastric and abdominal pain, ulcers, vomiting.
Location: 2 cun below LI 11 on the LI 5 to LI 11 line.
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)
Tonify Yin and blood, all spleen disorders.
Digestive disorders, sinking or prolapse.
Gynecological issues, male sexual issues, difficult labor (expel fetus).
Bleeding disorders, cool blood in hot skin diseases.
Insomnia and other anxiety related emotions.
SP 8 (Diji)
Location: 3 cun below SP 9 on line connecting SP 9 and the tip of the medial malleolus.
Point associations:
Xi Cleft point.
Xi Cleft point - acute and painful menstrual issues due to blood stagnation - clotting, fibroids, dysmenorrhea.
Male infertility.
SP 10 (Xuehai)
Location: with knee flexed, 2 cun above the superior medial border of the patella on the bulge of the medial
portion of quadriceps femoris (vastus medialis).
Any gynaecological issues originating from blood, heat, stasis and/or deficiency - irregular menstruation,
cramping, PMS.
Skin problems from damp-heat or hot blood.
ST29 (Guilai)
Location: 2 cun lateral to the AML level with CV 3.
Excess or cold/deficient disorders of the lower warmer - amenorrhoea, irregular menstruation, qi stagnation/
masses.
13
(Continued)
Running Piglet disorder.
ST36 (Zushanli)
Location: 3 cun below ST 35, one finger width lateral from the anterior border of the tibia.
Point associations:
He Sea point
Lower Lower He Sea point of the ST
Earth point
Sea of Water and Grain point
Command point of the abdomen
Tonify deficient Qi or blood.
Tonify Wei Qi.
All issues involving the stomach or the spleen.
Clear disorders along the course of the channel - breast problems, lower leg pain.
Earth as the mother of Metal - will support lung function in cases of asthma, wheezing, dyspnoea.
Psychological/Emotional disorders - PMS, depression, nervousness.
PC6 (Neiguan)
Location: 2 cun above the wrist crease between the tendons of palmaris longus and flexor carpi radialis.
Point associations:
Luo Connecting point
Yin Wei Master point coupled with SP 4
Similar to PC 3 but more for chronic heart symptoms from Qi stagnation.
Opens and relaxes the chest, chest tightness, asthma, angina, palpitations.
Insomnia, other spirit disorders of an excess or deficient nature, mania, nervousness, stress, poor memory.
Nausea, seasickness, motion sickness, vomiting, epigastric pain.
Carpal tunnel syndrome.
Ren 3 (Zhongji)
Location (zhongji): 1 cun superior to qugu. Regulates LR, warms KI, irregular menses.
RN 4 (Guanyuan)
Location: 1.5 cun lateral to the Du meridian, at the level of the lower border of the spinous process of the
5th lumbar vertebra.
Indications
Low back pain, abdominal distension, diarrhoea, enuresis, sciatica, frequent urination.
Traditional action
Strengthens the lower back, removes obstructions from the channel.
RN6 (Qihai)
Location: 1.5 cun lateral to the Du meridian, at the level of the lower border of the spinous process of the
third lumbar vertebra.
Indications
Low back pain, irregular menstruation, dysmenorrhea, asthma.
14
(Continued)
Traditional action
Strengthens lower back, removes obstructions fro mchannel, regulates Qi and blood.
KI 3 (Taixi)
Location: in the depression between the medial malleolus and tendo calcaneus, at the level with the tip of the
medial malleolus.
Indications
Sore throat, toothache, deafness, tinnitus, dizziness, spitting of blood, asthma, thirst, irregular menstruation,
insomnia, nocturnal emission, impotence, frequency of micturition, pain in the lower back.
Traditional action
Tonifies the kidneys, benefits essence, strengthens the lower back and knees, regulates the uterus.
KI 11 (Henggu)
Location: 1.5 cun posterior to Wuchu (UB 5), 1.5 cun lateral to the Du meridian.
Indications
Headache, blurring of vision, nasal obstruction.
Traditional action
Clears heat and eliminates vexation, brightens the eyes and opens the portals.
TE 5 (Weiguan)
Location: 1.5 cun lateral to the lower border of the spinous process of the eighth thoracic vertebra.
Indications
Diabetes, vomiting, abdominal pain, pain in the chest and hypochorondriac region.
Traditional action
Relieves stagnation of blood.
Acupuncture on the day of ET
1.32 to 2.53; P = 0.0003) favouring the acupuncture treatment
group.
Live birth rate (LBR)
Clinical pregnancy rate
In the pooled results of three trials (Paulus 2002; Paulus 2003;
Westergaard 2006) (N = 542), the LBR was 35% (95/275) in the
acupuncture group and 22% (59/267) in the control group (OR
1.86, 95% confidence interval 1.27 to 2.73).
In the pooled results of six trials (Benson 2006; Domar 2006;
Paulus 2002; Paulus 2003; Smith 2006; Westergaard 2006) (N
= 1022) the clinical pregnancy rate of the acupuncture treatment
group was 39% (201/518) compared to 30% (150/504) in the
control group (OR 1.50, 95% CI 1.15 to 1.95; P = 0.002) favouring the acupuncture treatment group.
Ongoing pregnancy rate
In the pooled results of four trials (Paulus 2002; Paulus 2003;
Smith 2006; Westergaard 2006) (N = 769), the ongoing pregnancy
rate of the acupuncture treatment group was 32% (126/384) compared to 21% (81/385) in the control group (OR 1.83, 95% CI
Miscarriage rate
Only two trials (N = 409) evaluated the possible impact of
acupuncture on miscarriage (Smith 2006; Westergaard 2006).
15
There was no evidence of a difference between the acupuncture
treatment group (4%, 9/204) and the control group (5%, 10/205)
(OR 0.88, 95% CI 0.35 to 2.22; P = 0.78).
Acupuncture around the time of oocyte retrieval
Side effects
None of the 10 trials described ovarian hyperstimulation. Smith
2006 was the only trial that reported on the experience of the patients. They reported no difference in the SF-36 scores between
the study and control groups. The most frequently reported outcome in that trial was relaxation and women in the control group
were more likely to report relaxation with acupuncture.
Repeated acupuncture after ET
Two studies (Humaidan 2004; Stener-Victorin 2003) reported on
the LBR. There was no evidence of a difference in the LBR between
the treatment group (33%, 75/229) and the control group (36%,
84/235) (OR 0.87, 95% CI 0.59 to 1.29).
The two trials reported an ongoing pregnancy rate of 34%
(78/229) in the treatment group versus 37% (88/235) in the control group (OR 0.86, 95%CI 0.58 to 1.26).
From the pooled results of two trials (Dieterle 2006; Westergaard
2006) (N = 403) there was no statistical difference in the LBR
between acupuncture and the control when acupuncture was performed at the time of ET and then again two to three days later.
The LBR was 28% (57/207) in the acupuncture group compared
to 17% (34/196) in the control group (OR 1.79, 95% CI 0.93 to
3.44; P = 0.08).
In the pooled results of five trials, the clinical pregnancy rate of
the treatment group was 37% (165/448) while that of the control
group was 35% (146/420) (OR 1.14, 95% CI 0.76 to 1.72).
Miscarriage rate
2006) (N = 403) there was no statistical difference in the ongoing
pregnancy rate between the acupuncture and the control groups
when acupuncture was performed around ET and then again two
to three days later. The ongoing pregnancy rate of the acupuncture
treatment group was 28% (57/207) compared to 16% (32/196)
for the control group (OR 1.79, 95% CI 0.93 to 3.44; P = 0.08).
The pooled results from four trials (Humaidan 2004; Sator-K
2006; Stener-Victorin 1999; Stener-Victorin 2003) showed that
the miscarriage rate of the treatment group was 13% (9/71) versus
16% (12/68) in the control group (OR 0.81, 95% CI 0.46 to
1.46).
Sensitivity Analysis: acupuncture versus sham
controls
2006) (N = 403) the clinical pregnancy rate 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 to 3.51; P = 0.0006).
Live birth rate
The LBR was higher in the acupuncture group (OR 1.91, 95%
CI 1.22 to 3.00; OR 2.17, 95% CI 1.32 to 3.54) both with and
without a sham acupuncture control, respectively (Dieterle 2006;
Paulus 2003).
Miscarriage rate
Two trials (n = 403) evaluated the impact of repeated acupuncture
on miscarriage (Dieterle 2006; Westergaard 2006). There was no
statistical differences in the miscarriage rate between acupuncture
and the controls when acupuncture was performed around ET
and then again two to three days later. The miscarriage rate in the
acupuncture group was 14% (30/207) compared to 9% (18/196)
in the control group (OR 1.68, 95% CI 0.90 to 3.12; P = 0.10).
The OR for ongoing pregnancy rate in studies with a sham
acupuncture control (Dieterle 2006; Paulus 2003; Smith 2006)
was 1.79 (95% CI 1.24 to 2.58), which favoured the acupuncture
group. With no sham acupuncture, there was no evidence of a
benefit (OR 1.66, 95% CI 0.35 to 7.92).
16
The OR for the clinical pregnancy rate in studies with a sham
acupuncture control group (Benson 2006; Craig 2007; Domar
2006; Smith 2006; Westergaard 2006) was 1.71 (95% CI 1.11 to
2.65), favouring the acupuncture group. In studies with no sham
acupuncture control there was no evidence of a benefit (OR 1.18,
95% CI 0.64 to 2.18).
Significant statistical heterogeneity was noted in several outcomes
and the random-effects model was used.
DISCUSSION
This meta-analysis shows that acupuncture around the time of
embryo transfer (ET) achieves a higher live birth rate (LBR) of
35% compared to 22% without active acupuncture. There is no
evidence of benefit for having acupuncture around the time of
oocyte retrieval or for repeating acupuncture two to three days after
ET. These results should be interpreted with caution as the trials
included in the meta-analysis had significant clinical heterogeneity
as discussed below.
Acupuncture clearly has the advantages of being relatively painless
and causing few side effects. However, before routine treatment
can be accepted into mainstream medicine, acupuncture needs
to have proven efficacy. In other words, acupuncture has to be
demonstrably more effective than placebo. However, the use of
an appropriate placebo in this context is relatively difficult and a
variety of controls were used for the RCTs included in this review,
ranging from no intervention to using sham acupuncture needles
(Dieterle 2006; Smith 2006). Sham needles are regarded as the
gold standard placebo although their use has been criticised because they could possibly induce an ’acupressure effect’. Furthermore, placement of a needle in any position elicits a biological
response that complicates the interpretation of studies involving
sham needle acupuncture. Placebo acupoint application, whether
with real or sham needling, can mean needling on acupoints that
are unrelated to fertility or on points next to but not on the real
acupuncture points. As yet there is no consensus on what constitutes a good placebo in trials examining the effects of acupuncture.
Furthermore, the placebo effect of sham or placebo acupuncture
can be large, which may well be the results of the attention given
and time spent with the patient. This is especially so around the
time of ET when women were relaxed and the sham acupuncture
generated better results than with the actual acupuncture.
Acupuncture is a complex intervention that can have different effects on patients with similar complaints. The number and length
of treatments needed, and the specific points used, may vary among
individuals and during the course of treatment. Although all 13
trials in this review examined the use of acupuncture for improving
the pregnancy rate with IVF, different acupuncture points were selected to achieve the same objective and it is unclear why. In Western medicine, where the standardisation of methodology is of key
importance in medical research, the absence of complete concordance of the acupuncture points in these studies is an unfamiliar
concept. There is no consensus amongst practising acupuncturists
as to what constitutes a reasonable variation of the acupuncture
treatment protocol. There is also no consensus as to how much
experience or training an acupuncturist needs to provide effective
acupuncture treatment, although courses are available that provide
a license to practice the art.
Most authors in the field assume that acupuncture has little detrimental effect. Out meta-analysis showed evidence of benefit in
terms of a higher live birth rate in women undergoing acupuncture immediately around the time of ET compared to controls.
However, there was no evidence of benefit on the live birth rate in
the pooled results for women who had additional acupuncture two
to three days after ET. This data does not prove that acupuncture
is free of harm in early pregnancy and one should apply caution
when giving advice to women about undergoing acupuncture in
early pregnancy.
Therefore, the question of whether acupuncture increases pregnancy rates with IVF remains unanswered. The data from this
meta-analysis suggests that acupuncture may potentially increase
the live birth rate of IVF treatment; however, this could be attributed to a placebo effect. Acupuncture may also have harmful
effects in early pregnancy.
Future research into the value of acupuncture in improving the
pregnancy rate of women undergoing IVF treatment should incorporate basic scientific principles and methodologies. Within
the realms of RCTs, studies in this area should focus on the use
of standardised acupuncture methods so that reasonable comparisons can be made; live birth rate should be used as the primary
outcome; and the use of ’placebo needles’ can enhance the quality
of the studies performed. Once these methodological questions
are resolved, the preliminary data presented in this meta-analysis
are sufficiently encouraging to support a large multicentre trial.
AUTHORS’ CONCLUSIONS
Implications for practice
Acupuncture may improve IVF pregnancy rates, and the perception that acupuncture is harmless may encourage patients and clinics to offer this as an adjunct to IVF treatment. The evidence from
17
current literature suggests that acupuncture should be offered only
at the time of ET, and not at the time of putative implantation.
The use of acupuncture in the luteal phase of the cycle should not
be encouraged in routine clinical practice until further evidence
is available from properly powered RCTs concerning the possible
associations between luteal phase acupuncture and miscarriage.
Implications for research
Future research into the value of acupuncture in improving the
pregnancy rate of women undergoing IVF treatment needs to focus
on basic scientific principles and methodologies. Basic research
should also be targeted at elucidating the mechanisms of action
of acupuncture in this respect. Certainly, within the realms of
RCTs, studies in this area should focus on the use of standardised
acupuncture methods so that reasonable comparisons can be made
using live birth rate as the primary outcome and ’sham needles’ to
enhance the quality of the studies performed.
ACKNOWLEDGEMENTS
We thank the Cochrane Menstrual Disorders and Subfertility
Group for providing us with the search strategy and for proof reading the review.
REFERENCES
References to studies included in this review
Benson 2006 {published data only}
Benson MR, Elkind-Hirsch KE, Theall A, Fong K, Hogan RB,
Scott RT. Impact of acupuncture before and after embryo transfer
on the outcome of in vitro fertilization cycles: A prospective single
blind randomized study. Fertility and Sterility 2006;86 Suppl(3):
135.
Craig 2007 {published data only (unpublished sought but not used)}
Craig LB, Criniti AR, Hansen KR, Marshall LA, Soules MR.
Acupuncture lowers pregnancy rates when performed before and
after embryo transfer. Fertility and Sterility 2007;88 Suppl1:40.
Dieterle 2006 {published data only}
Dieterle S, Ying G, Hatzmann W, Neuer A. Effect of acupuncture
on the outcome of in vitro fertilisation and intracytoplasmic sperm
injection: a randomised, prospective, controlled clinical study.
Fertility and Sterility 2006;85:1347–51.
Domar 2006 {published data only}
Domar AD. Acupuncture and infertility: we need to stick to good
science. Fertility and Sterility 2006;85:1359–61.
Gejervall 2005 {published data only}
Gejervall A, Stener-Victorin E, Moller A, Janson PO, Werner C,
Bergh C. Electro-acupuncture versus conventional analgesia: a
comparison of pain levels during oocyte aspiration and patients’
experiences of well-being after surgery. Human Reproduction 2005;
20:728–35.
Humaidan 2004 {published data only}
Humaidan P, Stener-Victorin E. Pain relief during oocyte retrieval
with a new short duration electro-acupuncture technique - an
alternative to conventional analgesic methods. Human Reproduction
2004;19:1367–72.
Paulus 2002 {published data only}
Paulus WE, Zhang M, Strehler E, El-Danasouri I, Sterzik K.
Influence of acupuncture on the pregnancy rate in patients who
undergo assisted reproductive technology. Fertility and Sterility
2002;77:721–44.
Paulus 2003 {published data only}
Paulus WE, Zhang M, Strehler E, Seybold B, Sterzik K. Placebocontrolled trial acupuncture effects in assisted reproductive therapy.
Human Reproduction 2003; Vol. 18 Suppl:18.
Sator-K 2006 {published data only}
Sator-Katzenschlager SM, Wölfler MM, Kozek-Langenecker SA,
Sator K, Sator PG, Li B, et al.Auricular electro-acupuncture as an
additional perioperative analgesic method during oocyte aspiration
in IVF treatment. Human Reproduction 2006;21:2114–20.
Smith 2006 {published data only}
Smith C, Coyle M, Norman R. Influence of acupuncture
stimulation on pregnancy rates for women undergoing embryo
18
transfer. Fertility and Sterility 2006;85:1352–8.
Stener-Victorin 1999 {published data only}
Stener-Victorin E, Waldenstrom U, Andersson SA, Wikland M,
Janson PO. A prospective randomised study of electro-acupuncture
versus alfentanil as anaesthesia during oocyte aspiration in in-vitro
fertilisation. Human Reproduction 1999;14:2480–4.
Stener-Victorin 2003 {published data only}
Stener-Victorin E, Waldenstrom U, Wikland M, Nilsson L,
Hagglund L, Lundeberg T. Electro-acupuncture as a preoperative
analgesic method and its effects on implantation rate and
neuropeptide Y concentrations in follicular fluid. Human
Reproduction 2003;18:1454–60.
Westergaard 2006 {published data only}
Westergaard LG, Mao QH, Krogslund M, Sandrini S, Lenz S,
Grinsted J. Acupuncture on the day of embryo transfer significantly
improves the reproductive outcome in infertile women: a
prospective, randomised trial. Fertility and Sterility 2006;85:
1341–6.
References to studies excluded from this review
Chen 2004 {published data only}
Chen D, Shi XL, Cai MX. Clinical observation on treatment of
functional anovulation by acupunctural prick. Zhongguo Zhong Xi
Yi Jie He Za Zhi Zhongxiyi Jiehe Zazhi 2004;27(8):735–7.
Evans 2005 {published data only}
Evans J. A pilot study to explore the effects of acupuncture in
women with unexplained infertility. South Bro Tak R&D
Consortium 2005.
Quintero 2004 {published data only}
Quintero R. A randomised controlled, double-blind, cross-over
study evaluating acupuncture as an adjuct to IVF. Fertility and
Sterility 2004;81 Suppl 3:11.
Additional references
Boivin 2007
Boivin J, Bunting L, Collins JA, Nygren KG. International
estimates of infertility prevalence and treatment-seeking: potential
need and demand for infertility medical care. Human Reproduction
2007;22:1506–12.
Fisher 1994
Fisher P, Ward A. Complementary medicine in Europe. BMJ 1994;
309:107–11.
Gehard 1992
Gehard I, Postneek F. Auricular acupuncture in the treatment of
female infertility. Gynecological Endocrinology 1992;6:171–81.
NIH Consensus 1998
NIH Concensus Development Panel of Acupuncture.
Acupuncture. JAMA 1998;280:1518–24.
Schmidt 1995
Schmidt L, Munster K, Helm P. Infertility and the seeking of
infertility treatment in a representative population. British Journal
of Obstetrics and Gynaecology 1995;102:978–84.
Stener-Victorin 1996
Stener-Victorin E, Waldenstrom U, Andersson SA, Wikland M.
Reduction of blood flow impedence in the uterine arteries of
infertile women with electro-acupuncture. Human Reproduction
1996;11:1314–7.
Stener-Victorin E, Lundeberg T, Waldenstrom U, Tagnfors U,
Lundeberg T, Lindstedt G, Janson P. Effects of electro-acupuncture
on anovulation in women with polycystic ovary syndrome. Acta
Obstetricia et Gynecologica Scandinavica 2000;79:180–8.
Stener-Victorin E, Lundeberg T, Waldenstrom U, BileviciuteLindstedt I, Janson P. Effects of acupuncture on corticotropin
releasing factor (CRF) in rats with experimentally induced
polycystic ovaries. Neuropeptides 2001;6:1–5.
Elisabet Stener-Victorin. Alternative treatments in reproductive
medicine: much ado about nothing. Human Reproduction 2002;
17:1942–6.
Thomas 2001
Thomas KJ, Nicholl JP, Coleman P. Use and expenditure on
complimentary medicine in England: a population based survey.
Complementary Therapies in Medicine 2001;9:2–11.
Vickers 1999
Vickers A, Zollman C. ABC of complementary medicine:
Acupuncture. BMJ 1999;319:973–6.
∗
Indicates the major publication for the study
19
CHARACTERISTICS OF STUDIES
Characteristics of included studies [ordered by study ID]
Benson 2006
Methods
Randomised controlled trial of fertility patients in US
Participants
Patients (n=258) who had been scheduled for ET were randomised into needle acupuncture (n=53), laser acupuncture (n=53), sham laser acupuncture (n=52) and no treatment
(n=50)
Interventions
No treatment, needle acupuncture, sham laser acupuncture
Outcomes
Notes
Abstract only
Risk of bias
Item
Authors’ judgement
Description
Adequate sequence generation?
Unclear
Abstract only
Allocation concealment?
Unclear
No reply from authors
Blinding?
All outcomes
No
No sham needle group used
Incomplete outcome data addressed?
All outcomes
No
Emailed authors for LBR but no reply
Free of selective reporting?
Yes
Free of other bias?
Yes
Craig 2007
Methods
Multicentre prospective RCT
Participants
107 patients undergoing IVF
Interventions
Acupuncture versus no acupuncture
Outcomes
Ongoing and clinical pregnancy rate
Notes
20
Craig 2007
(Continued)
Risk of bias
Item
Description
Unclear
Abstract only
Unclear
No reply from authors
Blinding?
All outcomes
No
No sham acupuncture control used
All outcomes
No
Emailed authors for LBR and sequence generation but
no reply
Yes
Free of other bias?
Yes
Dieterle 2006
Methods
Randomised controlled trial, fertility patients in clinic in Germany
Participants
225 patients randomised: 116 to treatment (30 min after ET and 3 days later) and 109
placebo. Treatment included placing Chinese herbs in patients’ ears. No loss to follow
up. Placebo treatment at sites that will not affect fertility, but physicians performing ET
blinded
Interventions
Treatment included acupuncture + chinese herbs in ears versus acupuncture but at sites
that do not affect fertility
Outcomes
Live birth rate, clinical pregnancy rates and ongoing clinical pregnancy rates
Notes
Placebo group did not have drugs placed in ears
Risk of bias
Item
Yes
Yes
Adequate: randomised by sealed randomisation envelopes
Blinding?
All outcomes
Yes
Use of placebo treatment in control group
Description
21
Dieterle 2006
(Continued)
All outcomes
Yes
Yes
Free of other bias?
Yes
Domar 2006
Methods
Randomised controlled trial, fertility patients in the US
Participants
150 patients recruited: 81 had needle acupuncture and 69 had no treatment
Interventions
Traditional needling techniques versus no treatment
Outcomes
Notes
Risk of bias
Item
Description
Yes
Computer-generated randomisation numbers
Yes
Sealed randomisation envelopes; curtains
drawn so that none of physicians or nurses
could see which group patients were randomised to
Blinding?
All outcomes
Yes
Only clinicians blinded; control group did
not have sham acupuncture so participants
not blinded
All outcomes
Yes
Yes
Free of other bias?
Yes
22
Gejervall 2005
Methods
The study was an open, prospective, randomised single-centre trial performed at the IVF
unit of Reproductive Medicine at Sahlgrenska University Hospital in Goteborg.
Participants
There were 160 women randomised in the study: 80 to the EA (electro-acupuncture)
group and 80 to the CA (conventional acupuncture) group
Interventions
The study compared EA and a PCB (EA group) with conventional analgesia (intravenous
alfentanil) and a PCB (CA group)
Outcomes
Wellbeing was evaluated with the State Trait Anxiety Inventory (STAI). Pain and subjective expectations and experiences were recorded on a visual analogue scale (VAS).
Time and drug consumption were recorded. Pregnancy rate was recorded as secondary
outcome
Notes
Study designed to assess effectiveness of acupuncture as an analgesic
Risk of bias
Item
Description
Yes
Computerised randomisation
Yes
Adequate, concealed using envelopes
Blinding?
All outcomes
Yes
All outcomes
Yes
Yes
Free of other bias?
Yes
Humaidan 2004
Methods
Patients were randomised prospectively using sealed, unlabelled envelopes
Participants
Fertility Clinic, Skive Hospital, Denmark
The CONSORT guidelines for reporting of randomised trials were followed (Moher et
al, 2001). All patients included in the IVF programme were informed about the study
~3 days to 1 week before the ovum pick up (OPU). No exclusion criteria were used
Interventions
The 2 groups had pain relief with either EA in combination with a paracervical block
(PCB) (n=100) or conventional medical analgesia (CMA) in combination with a PCB
(n=100)
23
Humaidan 2004
(Continued)
Outcomes
VAS scale
Notes
Risk of bias
Item
Description
Yes
Computer-generated randomisation
Yes
Adequate: randomisation using sealed unlabelled envelopes containing a study number
Blinding?
All outcomes
Yes
All outcomes
Yes
Yes
Free of other bias?
Yes
Paulus 2002
Methods
Randomised controlled trial in fertility clinic in Germany
Participants
160 patients randomised: 80 to treatment and 80 to control; auricular acupuncture also
performed on the treatment group
Interventions
Acupuncture 25 min before and after ET for treatment group
Outcomes
Clinical pregnancy rates
Notes
Same authors as Paulus 2003 but different group of patients
Risk of bias
Item
Description
Unclear
Abstract only, no reply
Unclear
As above
24
Paulus 2002
(Continued)
Blinding?
All outcomes
No
All outcomes
Yes
Yes
Free of other bias?
Yes
No sham group
Paulus 2003
Methods
Prospective, randomised placebo-controlled trial
Participants
In the control group (n=100) a placebo needle set was used without penetrating the skin,
but at the same acupoints and after the same scheme
Interventions
Patients were divided into two groups by random selection: embryo transfer with verum
acupuncture (n=100) and embryo transfer with placebo needling (n=100)
Outcomes
Notes
Only included women with good embryos
Risk of bias
Item
Description
Yes
Computerised randomisation
Yes
Adequate
Blinding?
All outcomes
Yes
Sham group used
All outcomes
Yes
Yes
Free of other bias?
Yes
25
Sator-K 2006
Methods
Randomised controlled trial in fertility clinic in Austria
Participants
Patients were randomised in proportions of 1:1:1 to treatment with EA group (n=32),
the auricular acupuncture group without electrical stimulation (n=32) or the control
group without needles and electrical stimulation (n=30)
Interventions
EA, or EA with electrical stimulation or control
Outcomes
Pain intensity and subjective well being were assessed using a visual analogue scale Nausea
and tiredness were also assessed using a visual rating scale
Analgesic drug requirements during the entire study period
Notes
Risk of bias
Item
Description
Yes
Randomisation was performed by one doctor on the day of the last ultrasound examination before oocyte retrieval
Yes
A computer-generated randomisation list
was used for allocation. The randomisation
was continued until at least 30 patients had
been allocated to each group
Blinding?
All outcomes
Yes
Each P-Stim™ was programmed by an independent technician for electrical stimulation or no stimulation before the study.
To ensure blinding of the investigator, each
P-Stim™ was packed in a non-transparent case in which the respective permanent needles or adhesive tapes were also included. The packages were numbered consecutively, according to the randomisation
list. Patients and investigators were blinded
to the randomisation
All outcomes
Yes
Yes
Free of other bias?
Yes
26
Smith 2006
Methods
Randomised controlled trial in fertility clinic in Australia
Participants
228 randomised, 36 excluded: 110 in treatment group and 118 in control group. Sham
group: acupuncture sham needle was used close to but not on the treatment point
Interventions
All women had 3 sessions: day 9 of stimulation, immediately before ET, and immediately
after ET
Outcomes
Notes
After 3rd session, 24 in treatment group and 10 in control group guessed their allocation
group correctly
Risk of bias
Item
Description
Yes
Randomisation in balanced blocks of random size prepared by researcher not involved in the trial
Yes
Adequate, as above
Blinding?
All outcomes
Yes
Use of sham acupuncture
All outcomes
Yes
No live birth data available, confirmed by
author via email
Yes
Free of other bias?
Yes
Methods
Prospective, randomised controlled trial
Participants
150 women undergoing IVF and ET were randomised to receive either EA plus PCB or
alfentanil plus PCB
Interventions
Acupuncture was performed at least 30 min before oocyte aspiration and PCB was placed
at the start of the procedure and terminated directly after oocyte aspiration
Outcomes
VAS, level of stress, implantation and pregnancy rates
Notes
Aim of study was to evaluate the anaesthetic effect during oocyte aspiration of a paracervical block in combination with either electro-acupuncture or IV alfentanil
27
(Continued)
Risk of bias
Item
Description
Yes
Computer randomisation
Yes
Adequate, randomisation in sealed unlabelled envelopes
Blinding?
All outcomes
No
No sham group
All outcomes
Yes
Yes
Free of other bias?
Yes
Methods
The study was a prospective, randomised, controlled multicentre trial comparing EA
and PCB (EA group) with alfentanil and PCB (alfentanil group) performed in 5 IVF
units in Sweden
Participants
Women were given EA and a PCB of lidocaine hydrochloride during oocyte aspiration.
Those women randomised to the alfentanil group were given alfentanil and a PCB during
oocyte aspiration
Interventions
The acupuncture stimulation began at least 30 min before oocyte aspiration
Outcomes
VAS were used for pain assessment. Other variables recorded included abdominal pain,
pain during placement of PCB, time of discomfort, adequacy of analgesia, stress level,
nausea. IVF outcomes were pregnancy rate (number of pregnancies per embryo transfer)
, implantation rate (number of gestational sacs per number of transferred oocytes) and
on-going pregnancies (number of pregnancies per embryo transfer after the 16th week
of gestation)
Notes
Stopped after interim analysis as results show no difference between two groups. Study
designed to assess effectiveness of acupuncture as an analgesic
Risk of bias
Item
Description
Yes
Randomisation using sealed unlabelled envelopes concealed from patients and physi-
28
(Continued)
cians until treatment
Yes
Blinding?
All outcomes
No
All outcomes
Yes
Yes
Free of other bias?
Yes
Adequate
Westergaard 2006
Methods
Randomised controlled trial with patients from private clinic in Denmark
Participants
273 included: 87 allocated to no acupuncture and 95 to acupuncture on ET day only;
91 acupuncture on ET and ET+2 days; 27 excluded
Interventions
Acupuncture was performed on patients undergoing ET on the day of ET, ET+2 and
not on controls
Outcomes
Clinical pregnancy rate on ultrasound
Notes
No sham placebo, thus patients and practitioners not blinded
Risk of bias
Item
Description
No
Randomisation via sealed opaque envelope
on the day of oocyte retrieval but envelopes
then placed in cardboard box from which
patients selected one
Yes
Randomsiation procedure handled by
nurse not involved in study
Blinding?
All outcomes
No
All outcomes
Yes
Yes
29
Westergaard 2006
Free of other bias?
(Continued)
Yes
Characteristics of excluded studies [ordered by study ID]
Chen 2004
No reply to written and electronic request; study design, allocation concealment and outcomes unclear.
Evans 2005
Lack details on pregnancy outcome, study design, allocation concealment and type of randomisation; no reply to
written or electronic letters
Quintero 2004
Lacks details on allocation concealment and randomisation, no reply to requests for details; crossover design
30
DATA AND ANALYSES
Comparison 1. Acupuncture on the day of ET versus no acupuncture
Outcome or subgroup title
1 Live Birth
2 Ongoing pregnancy
3 Clinical pregnancy rate
4 Miscarriage
No. of
studies
No. of
participants
3
5
7
2
542
863
1116
409
Statistical method
Odds Ratio (M-H, Fixed, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Effect size
1.86 [1.27, 2.73]
1.38 [0.78, 2.44]
1.26 [0.85, 1.88]
0.88 [0.35, 2.22]
Comparison 2. Repeated acupuncture versus no acupuncture
1 Live Birth
2 Ongoing pregnancy
3 Clinical pregnancy rate
4 Miscarriage
No. of
studies
No. of
participants
2
2
2
2
403
403
403
403
Statistical method
Effect size
1.79 [0.93, 3.44]
1.79 [0.93, 3.44]
2.23 [1.41, 3.51]
1.68 [0.90, 3.12]
Comparison 3. Acupuncture versus no acupuncture around the time of oocyte retrieval
No. of
studies
No. of
participants
1 Live Birth Rate
2 Ongoing Pregnancy Rate
3 Clinical Pregnancy Rate
4 Miscarriage rate
2
2
5
4
464
464
868
378
Statistical method
Effect size
0.87 [0.59, 1.29]
0.86 [0.58, 1.26]
1.14 [0.76, 1.72]
0.81 [0.46, 1.46]
Comparison 4. Sensitivity analysis with sham versus no sham: acupuncture during ET and repeated groups
No. of
studies
No. of
participants
1 Live Birth
1.1 Sham acupuncture
1.2 No sham acpuncture
2 Ongoing pregnancy
4
2
2
6
3
767
425
342
1080
644
Statistical method
Effect size
2.02 [1.45, 2.82]
1.91 [1.22, 3.00]
2.17 [1.32, 3.54]
1.77 [0.91, 3.42]
1.79 [1.24, 2.58]
31
2.2 No sham acupuncture
3 Clinical pregnancy
3.1 Sham acupuncture control
4 Miscarriage
3
8
3
5
3
2
1
436
1341
652
689
634
452
182
1.66 [0.35, 7.92]
1.39 [0.94, 2.06]
1.71 [1.11, 2.65]
1.18 [0.64, 2.18]
1.14 [0.63, 2.05]
1.15 [0.59, 2.24]
1.11 [0.33, 3.76]
Analysis 1.1. Comparison 1 Acupuncture on the day of ET versus no acupuncture, Outcome 1 Live Birth.
Review:
Comparison: 1 Acupuncture on the day of ET versus no acupuncture
Outcome: 1 Live Birth
Study or subgroup
Favours Control
Control
Odds Ratio
n/N
n/N
M-H,Fixed,95% CI
Paulus 2002
26/80
14/80
24.2 %
2.27 [ 1.08, 4.77 ]
Paulus 2003
35/100
26/100
43.2 %
1.53 [ 0.84, 2.81 ]
34/95
19/87
32.6 %
1.99 [ 1.03, 3.86 ]
275
267
100.0 %
1.86 [ 1.27, 2.73 ]
Westergaard 2006
Total (95% CI)
Weight
Odds Ratio
M-H,Fixed,95% CI
Total events: 95 (Favours Control), 59 (Control)
Heterogeneity: Chi2 = 0.71, df = 2 (P = 0.70); I2 =0.0%
Test for overall effect: Z = 3.19 (P = 0.0014)
0.05
0.2
Favours Control
1
5
20
Favours Acupuncture
32
Analysis 1.2. Comparison 1 Acupuncture on the day of ET versus no acupuncture, Outcome 2 Ongoing
pregnancy.
Review:
Outcome: 2 Ongoing pregnancy
Study or subgroup
Acupuncture
Control
n/N
n/N
Craig 2007
21/48
32/46
17.5 %
0.34 [ 0.15, 0.79 ]
Paulus 2002
26/80
14/80
19.2 %
2.27 [ 1.08, 4.77 ]
Paulus 2003
35/100
26/100
21.5 %
1.53 [ 0.84, 2.81 ]
Smith 2006
31/109
22/118
21.2 %
1.73 [ 0.93, 3.23 ]
34/95
19/87
20.6 %
1.99 [ 1.03, 3.86 ]
432
431
100.0 %
1.38 [ 0.78, 2.44 ]
Westergaard 2006
Total (95% CI)
Odds Ratio
Weight
M-H,Random,95% CI
Odds Ratio
M-H,Random,95% CI
Total events: 147 (Acupuncture), 113 (Control)
Heterogeneity: Tau2 = 0.30; Chi2 = 13.86, df = 4 (P = 0.01); I2 =71%
0.1 0.2
0.5
Favours Control
1
2
5
10
Favours Acupuncture
33
Analysis 1.3. Comparison 1 Acupuncture on the day of ET versus no acupuncture, Outcome 3 Clinical
pregnancy rate.
Review:
Outcome: 3 Clinical pregnancy rate
Study or subgroup
Acupuncture
Control
n/N
n/N
Benson 2006
29/53
22/50
12.7 %
1.54 [ 0.71, 3.35 ]
Craig 2007
21/48
32/46
11.6 %
0.34 [ 0.15, 0.79 ]
Domar 2006
24/81
22/69
14.0 %
0.90 [ 0.45, 1.80 ]
Paulus 2002
34/80
21/80
14.5 %
2.08 [ 1.07, 4.04 ]
Paulus 2003
43/100
37/100
16.3 %
1.28 [ 0.73, 2.26 ]
Smith 2006
34/109
27/118
15.9 %
1.53 [ 0.85, 2.76 ]
37/95
21/87
15.0 %
2.00 [ 1.06, 3.81 ]
566
550
100.0 %
1.26 [ 0.85, 1.88 ]
Westergaard 2006
Total (95% CI)
Odds Ratio
Weight
M-H,Random,95% CI
Odds Ratio
M-H,Random,95% CI
0.1 0.2
0.5
1
Favours Control
2
5
10
Favours Acupuncture
Analysis 1.4. Comparison 1 Acupuncture on the day of ET versus no acupuncture, Outcome 4 Miscarriage.
Review:
Outcome: 4 Miscarriage
Study or subgroup
Smith 2006
Westergaard 2006
Total (95% CI)
Acupuncture
Control
Odds Ratio
n/N
n/N
M-H,Fixed,95% CI
Weight
Odds Ratio
3/109
5/118
48.8 %
0.64 [ 0.15, 2.74 ]
6/95
5/87
51.2 %
1.11 [ 0.33, 3.76 ]
204
205
100.0 %
0.88 [ 0.35, 2.22 ]
M-H,Fixed,95% CI
0.1 0.2
0.5
Favours Control
1
2
5
10
Favours Acpuncture
34
Analysis 2.1. Comparison 2 Repeated acupuncture versus no acupuncture, Outcome 1 Live Birth.
Review:
Comparison: 2 Repeated acupuncture versus no acupuncture
Study or subgroup
Acupuncture
Control
n/N
n/N
33/116
15/109
50.5 %
2.49 [ 1.26, 4.91 ]
24/91
19/87
49.5 %
1.28 [ 0.64, 2.56 ]
207
196
100.0 %
1.79 [ 0.93, 3.44 ]
Dieterle 2006
Westergaard 2006
Total (95% CI)
Odds Ratio
Weight
M-H,Random,95% CI
Odds Ratio
M-H,Random,95% CI
0.1 0.2
0.5
1
Favours Control
2
5
10
Favours Acupuncture
Analysis 2.2. Comparison 2 Repeated acupuncture versus no acupuncture, Outcome 2 Ongoing pregnancy.
Review:
Study or subgroup
Dieterle 2006
Westergaard 2006
Total (95% CI)
Acpuncture
Control
n/N
n/N
Odds Ratio
Weight
33/116
15/109
50.5 %
2.49 [ 1.26, 4.91 ]
24/91
19/87
49.5 %
1.28 [ 0.64, 2.56 ]
207
196
100.0 %
1.79 [ 0.93, 3.44 ]
M-H,Random,95% CI
Odds Ratio
M-H,Random,95% CI
Total events: 57 (Acpuncture), 34 (Control)
0.1 0.2
0.5
Favours Control
1
2
5
10
Favours Acupuncture
35
Analysis 2.3. Comparison 2 Repeated acupuncture versus no acupuncture, Outcome 3 Clinical pregnancy
rate.
Review:
Outcome: 3 Clinical pregnancy rate
Study or subgroup
Dieterle 2006
Westergaard 2006
Total (95% CI)
Acupuncture
Control
Odds Ratio
n/N
n/N
M-H,Fixed,95% CI
Weight
Odds Ratio
39/116
17/109
46.0 %
2.74 [ 1.44, 5.22 ]
33/91
21/87
54.0 %
1.79 [ 0.93, 3.43 ]
207
196
100.0 %
2.23 [ 1.41, 3.51 ]
M-H,Fixed,95% CI
0.1 0.2
0.5
1
Favours Control
2
5
10
Favours Acupuncture
Analysis 2.4. Comparison 2 Repeated acupuncture versus no acupuncture, Outcome 4 Miscarriage.
Review:
Study or subgroup
Dieterle 2006
Westergaard 2006
Total (95% CI)
Acpuncture
Control
Odds Ratio
n/N
n/N
M-H,Fixed,95% CI
Weight
Odds Ratio
18/116
13/109
71.8 %
1.36 [ 0.63, 2.92 ]
12/91
5/87
28.2 %
2.49 [ 0.84, 7.40 ]
207
196
100.0 %
1.68 [ 0.90, 3.12 ]
M-H,Fixed,95% CI
Total events: 30 (Acpuncture), 18 (Control)
0.1 0.2
0.5
Favours Control
1
2
5
10
Favours Acupuncture
36
Analysis 3.1. Comparison 3 Acupuncture versus no acupuncture around the time of oocyte retrieval,
Outcome 1 Live Birth Rate.
Review:
Comparison: 3 Acupuncture versus no acupuncture around the time of oocyte retrieval
Outcome: 1 Live Birth Rate
Study or subgroup
Acupuncture
Control
Odds Ratio
n/N
n/N
M-H,Fixed,95% CI
38/88
41/90
42.4 %
0.91 [ 0.50, 1.64 ]
37/141
43/145
57.6 %
0.84 [ 0.50, 1.42 ]
229
235
100.0 %
0.87 [ 0.59, 1.29 ]
Humaidan 2004
Total (95% CI)
Weight
Odds Ratio
M-H,Fixed,95% CI
0.1 0.2
0.5
1
Favours Control
2
5
10
Favours Acupuncture
Outcome 2 Ongoing Pregnancy Rate.
Review:
Outcome: 2 Ongoing Pregnancy Rate
Study or subgroup
Humaidan 2004
Acupuncture
Control
Odds Ratio
n/N
n/N
M-H,Fixed,95% CI
41/88
45/90
43.2 %
0.87 [ 0.48, 1.57 ]
37/141
43/145
56.8 %
0.84 [ 0.50, 1.42 ]
229
235
100.0 %
0.86 [ 0.58, 1.26 ]
Total (95% CI)
Weight
Odds Ratio
M-H,Fixed,95% CI
0.1 0.2
0.5
Favours Control
1
2
5
10
Favours Acupuncture
37
Outcome 3 Clinical Pregnancy Rate.
Review:
Outcome: 3 Clinical Pregnancy Rate
Study or subgroup
Acupuncture
Control
n/N
n/N
Gejervall 2005
23/80
26/80
19.8 %
0.84 [ 0.43, 1.64 ]
Humaidan 2004
41/88
45/90
22.7 %
0.87 [ 0.48, 1.57 ]
Sator-K 2006
30/64
7/30
12.4 %
2.90 [ 1.09, 7.71 ]
28/75
19/75
19.0 %
1.76 [ 0.87, 3.54 ]
43/141
49/145
26.2 %
0.86 [ 0.52, 1.41 ]
448
420
100.0 %
1.14 [ 0.76, 1.72 ]
Total (95% CI)
Odds Ratio
Weight
M-H,Random,95% CI
Odds Ratio
M-H,Random,95% CI
0.1 0.2
0.5
1
Favours Control
2
5
10
Favours Acupuncture
Outcome 4 Miscarriage rate.
Review:
Outcome: 4 Miscarriage rate
Study or subgroup
Acupuncture
Control
Odds Ratio
n/N
n/N
M-H,Fixed,95% CI
15/88
16/90
51.8 %
0.95 [ 0.44, 2.06 ]
Sator-K 2006
1/32
1/29
4.0 %
0.90 [ 0.05, 15.13 ]
3/28
6/19
25.2 %
0.26 [ 0.06, 1.21 ]
6/43
6/49
19.0 %
1.16 [ 0.35, 3.91 ]
191
187
100.0 %
0.81 [ 0.46, 1.46 ]
Humaidan 2004
Total (95% CI)
Weight
Odds Ratio
M-H,Fixed,95% CI
0.1 0.2
0.5
Favours Control
1
2
5
10
Favours acupuncture
38
Analysis 4.1. Comparison 4 Sensitivity analysis with sham versus no sham: acupuncture during ET and
repeated groups, Outcome 1 Live Birth.
Review:
Comparison: 4 Sensitivity analysis with sham versus no sham: acupuncture during ET and repeated groups
Study or subgroup
Acupuncture
Control
Odds Ratio
n/N
n/N
M-H,Fixed,95% CI
Weight
Odds Ratio
Dieterle 2006
33/116
15/109
22.2 %
2.49 [ 1.26, 4.91 ]
Paulus 2003
35/100
26/100
33.8 %
1.53 [ 0.84, 2.81 ]
216
209
56.0 %
1.91 [ 1.22, 3.00 ]
M-H,Fixed,95% CI
1 Sham acupuncture
Subtotal (95% CI)
Heterogeneity: Chi2 = 1.10, df = 1 (P = 0.30); I2 =9%
2 No sham acpuncture
Paulus 2002
26/80
14/80
18.9 %
2.27 [ 1.08, 4.77 ]
Westergaard 2006
35/95
19/87
25.1 %
2.09 [ 1.08, 4.03 ]
Subtotal (95% CI)
175
167
44.0 %
2.17 [ 1.32, 3.54 ]
376
100.0 %
2.02 [ 1.45, 2.82 ]
Total (95% CI)
391
0.01
0.1
Favours Control
1
10
100
Favours Acupuncture
39
repeated groups, Outcome 2 Ongoing pregnancy.
Review:
Study or subgroup
Acupcunture
Control
n/N
n/N
Odds Ratio
Weight
Dieterle 2006
33/116
15/109
16.8 %
2.49 [ 1.26, 4.91 ]
Paulus 2003
35/100
26/100
17.4 %
1.53 [ 0.84, 2.81 ]
Smith 2006
31/109
22/110
17.3 %
1.59 [ 0.85, 2.97 ]
325
319
51.5 %
1.79 [ 1.24, 2.58 ]
M-H,Random,95% CI
Odds Ratio
M-H,Random,95% CI
1 Sham acupuncture
Subtotal (95% CI)
Total events: 99 (Acupcunture), 63 (Control)
Heterogeneity: Tau2 = 0.0; Chi2 = 1.30, df = 2 (P = 0.52); I2 =0.0%
2 No sham acupuncture
Craig 2007
21/48
32/46
15.3 %
0.34 [ 0.15, 0.79 ]
Paulus 2002
26/80
14/80
16.2 %
2.27 [ 1.08, 4.77 ]
Westergaard 2006
58/95
19/87
17.0 %
5.61 [ 2.91, 10.80 ]
Subtotal (95% CI)
223
213
48.5 %
1.66 [ 0.35, 7.92 ]
100.0 %
1.77 [ 0.91, 3.42 ]
Heterogeneity: Tau2 = 1.76; Chi2 = 26.39, df = 2 (P<0.00001); I2 =92%
Total (95% CI)
548
532
0.01
0.1
Favours Control
1
10
100
Favours Acupuncture
40
repeated groups, Outcome 3 Clinical pregnancy.
Review:
Outcome: 3 Clinical pregnancy
Study or subgroup
Acupuncture
Control
n/N
n/N
Odds Ratio
Weight
Dieterle 2006
39/116
17/109
12.9 %
2.74 [ 1.44, 5.22 ]
Paulus 2003
43/100
37/100
14.1 %
1.28 [ 0.73, 2.26 ]
Smith 2006
34/109
27/118
13.7 %
1.53 [ 0.85, 2.76 ]
325
327
40.7 %
1.71 [ 1.11, 2.65 ]
M-H,Random,95% CI
Odds Ratio
M-H,Random,95% CI
1 Sham acupuncture control
Subtotal (95% CI)
Benson 2006
29/53
22/50
11.2 %
1.54 [ 0.71, 3.35 ]
Craig 2007
21/48
32/46
10.3 %
0.34 [ 0.15, 0.79 ]
Domar 2006
24/81
22/69
12.2 %
0.90 [ 0.45, 1.80 ]
Paulus 2002
34/80
21/80
12.6 %
2.08 [ 1.07, 4.04 ]
Westergaard 2006
37/95
21/87
13.0 %
2.00 [ 1.06, 3.81 ]
Subtotal (95% CI)
357
332
59.3 %
1.18 [ 0.64, 2.18 ]
100.0 %
1.39 [ 0.94, 2.06 ]
Total (95% CI)
682
659
0.01
0.1
Favours Control
1
10
100
Favours Acupuncture
41
repeated groups, Outcome 4 Miscarriage.
Review:
Study or subgroup
Acupuncture
Control
Odds Ratio
n/N
n/N
M-H,Fixed,95% CI
Weight
Odds Ratio
18/116
13/109
54.2 %
1.36 [ 0.63, 2.92 ]
3/109
5/118
22.4 %
0.64 [ 0.15, 2.74 ]
225
227
76.6 %
1.15 [ 0.59, 2.24 ]
M-H,Fixed,95% CI
1 Sham acupuncture
Dieterle 2006
Smith 2006
Subtotal (95% CI)
Westergaard 2006
6/95
5/87
23.4 %
1.11 [ 0.33, 3.76 ]
Subtotal (95% CI)
95
87
23.4 %
1.11 [ 0.33, 3.76 ]
320
314
100.0 %
1.14 [ 0.63, 2.05 ]
Heterogeneity: not applicable
Total (95% CI)
0.01
0.1
Favours Control
1
10
100
Favours Acupuncture
APPENDICES
Appendix 1. CENTRAL
1 exp Reproduction/
2 exp fertility promoting agent/
3 exp infertility therapy/
4 (In vitro adj5 fertili$).tw.
5 ivf.tw.
6 icsi.tw.
7 (intracytoplas$ adj5 sperm).tw.
8 subfertili$.tw.
9 infertili$.tw.
10 (sperm$ adj5 inject$).tw.
11 suzi.tw.
12 (subzon$ adj5 sperm$).tw.
42
13 (zona adj5 dissect$).tw.
14 pzd.tw
15 (ovar$ adj5 hyperstim$).tw.
16 ohss.tw.
17 (oocyt$ adj5 retriev$).tw.
18 (oocyt$ adj5 picku$).tw.
19 (sperm$ adj5 prepar$).tw.
20 (acrosom$ adj5 sperm$).tw.
21 (sperm$ adj5 stimul$).tw.
22 (sperm adj5 pentox$).tw.
23 (sperm$ adj5 caff$).tw.
24 (sperm$ adj5 kalli$).tw.
25 (sperm$ adj5 swim$).tw.
26 (sperm$ adj5 percol$).tw.
27 (sperm$ adj5 cryopreserv$).tw.
28 (sperm$ adj5 antibod$).tw.
29 (embry$ adj5 biops$).tw.
30 (cocult$ adj5 embry$).tw.
31 (cocult$ adj5 trophobl$).tw.
32 (luteal phase adj5 support).tw.
33 (froz$ adj5 embry$).tw.
34 (antisper$ adj5 antibod$).tw.
35 (artific$ adj5 inseminat$).tw.
36 (cervi$ adj5 inseminat$).tw.
37 (fallopian tub$ adj5 perfu$).tw.
38 (luteal adj5 defect$).tw.
39 (luteal adj5 dysfunction$).tw.
40 (ovulat$ adj5 induct$).tw.
41 (intraut$ adj5 inseminat$).tw.
42 (tub$ adj5 preg$).tw.
43 (ectop$ adj5 preg$).tw.
44 inseminat$.tw.
45 varioc$.tw. (1)
46 Ovary Hyperstimulation/
47 or/1-46
48 acupuncture/
49 ELECTROACUPUNCTURE/
50 acupunctur$.tw.
51 (electroacupunctur$ or electro-acupunctur$).tw.
52 acupoint$.tw.
53 meridian$.tw.
54 ((meridian or non-meridian or trigger) adj10 point$).tw.
55 exp moxibustion/
56 (moxibustion or moxabustion or moxa$).tw.
57 or/48-56
58 47 and 57
59 from 58 keep 1-85
43
Appendix 2. MEDLINE
MEDLINE(R) <1950 to August week 4 2007>
1 randomised controlled trial.pt.
2 controlled clinical trial.pt.
3 Randomized Controlled Trials/
4 Random allocation/
5 Double-blind method/
6 Single-blind method/
7 or/1-6
8 clinical trial.pt.
9 exp clinical trials/
10 (clin$ adj25 trial$).ti,ab,sh. \
11 ((singl$ or doubl$ or tripl$ or trebl$) adj25 (blind$ or mask$)).ti,ab,sh.
12 Placebos/
13 placebo$.ti,ab,sh.
14 random$.ti,ab,sh.
15 Research design/
16 or/8-15
17 animal/ not (human/ and animal/)
18 7 or 16
19 18 not 17
20 exp reproduction techniques/
21 exp fertility agents/
22 (in vitro adj5 fertili$).tw.
23 ivf.tw.
24 icsi.tw.
25 (intracytoplas$ adj5 sperm$).tw.
26 subfertil$.tw.
28 suzi.tw.
31 pzd.tw.
33 ohss.tw.
35 (oocyt$ adj5 pickup).tw.
36 (sperm$ adj5 prepa$).tw.
39 (sperm$ adj5 pentox$).tw.
42 (sperm$ adj5 swimup$).tw.
43 (sperm adj5 percol$).tw.
49 (frozen adj5 embry$).tw.
50 (antisperm$ adj5 antibod$).tw.
44
54 (fallopian tub$ adj5 perfus$).tw.
56 (luteal adj5 dysfunct$).tw.
57 (ovulat$ adj5 induc$).tw.
61 inseminat$.tw.
62 varicoc$.tw.
63 fertility/
64 fertilization/
65 insemination/
66 ovum implantation/
67 Ovarian Hyperstimulation Syndrome/
68 (embry$ adj5 transf$).tw.
69 or/20-68
70 69 and 19
71 acupuncture/
72 exp acupuncture therapy/
73 electroacupuncture/
74 meridians/
75 acupuncture points/ (
76 acupunctur$.tw.
78 acupoint$.tw.
80 exp Moxibustion/
81 (moxabustion or moxibustion or moxa$).tw.
82 or/71-81
83 70 and 82
Appendix 3. EMBASE
EMBASE <1980 to August week 4 2007>
1 Controlled study/ or Randomized Controlled Trial/
2 Double blind procedure/
3 Single Blind Procedure/
4 Crossover procedure/
5 Drug comparison/
6 Placebo/
7 Random$.tw.
8 latin square.tw.
9 crossover.tw.
10 cross-over.tw.
11 placebo$.tw.
12 ((doubl$ or singl$ or tripl$ or trebl$) adj5 (blind$ or mask$)).tw.
13 (comparativ$ adj5 trial$).tw.
14 (clinical adj5 trial$).tw.
45
15 or/7-14
17 exp Reproduction/
18 exp fertility promoting agent/
19 exp infertility therapy/
20 (In vitro adj5 fertili$).tw.
21 ivf.tw.
22 icsi.tw.
23 (intracytoplas$ adj5 sperm).tw.
24 subfertili$.tw.
25 infertili$.tw.
27 suzi.tw.
30 pzd.tw.
32 ohss.tw.
34 (oocyt$ adj5 picku$).tw.
35 (sperm$ adj5 prepar$).tw.
38 (sperm adj5 pentox$).tw.
41 (sperm$ adj5 swim$).tw.
42 (sperm$ adj5 percol$).tw.
49 (froz$ adj5 embry$).tw.
50 (antisper$ adj5 antibod$).tw.
53 (fallopian tub$ adj5 perfu$).tw.
55 (luteal adj5 dysfunction$).tw.
56 (ovulat$ adj5 induct$).tw.
60 inseminat$.tw.
61 varioc$.tw.
62 Ovary Hyperstimulation/
63 or/17-62
64 15 not 16
65 63 and 64
66 acupuncture/
67 ELECTROACUPUNCTURE/
46
68 acupunctur$.tw.
70 acupoint$.tw.
71 meridian$.tw.
73 exp moxibustion/
75 or/66-74
76 65 and 75
Appendix 4. AMED
1 (IVF or ICSI or IUI).tw.
2 “embryo transfer”.tw.
3 (“in vitro fertilisation” or “in vitro fertilization”).tw.
4 (“intrauterine insemination” or “intracytoplasmic sperm injection”).tw.
5 exp Infertility female/
6 exp acupuncture therapy/
7 acupuncture.tw.
8 exp Moxibustion/
10 or/6-9
11 or/1-5
12 10 and 11
Appendix 5. CINHAL
1 Controlled study/ or randomised controlled trial/
2 (drug$ adj5 compar$).ti,ab,hw,tn,mf.
3 placebo/
4 random$.ti,ab,hw,tn,mf.
5 latin square.ti,ab,hw,tn,mf.
6 crossover.ti,ab,hw,tn,mf.
7 cross-over.ti,ab,hw,tn,mf.
8 placebo$.ti,ab,hw,tn,mf.
9 ((doubl$ or singl$ or tripl$ or trebl$) adj5 (blind$ or mask$)).ti,ab,hw,tn,mf.
10 (comparative adj5 trial$).ti,ab,hw,tn,mf.
11 (clinical adj5 trial$).ti,ab,hw,tn,mf.
12 or/1-11
14 12 not 13
15 exp reproduction techniques/
16 exp fertility agents/
17 (in vitro adj5 fertili$).tw.
18 ivf.tw.
19 icsi.tw.
20 (intracytoplas$ adj5 sperm$).tw.
21 subfertil$.tw.
23 suzi.tw.
47
25 (zona adj5 sperm$).tw.
27 pzd.tw.
29 ohss.tw.
31 (oocyt$ adj5 pickup).tw.
32 (sperm$ adj5 prepa$).tw.
35 (sperm$ adj5 pentox$).tw.
36 (sperm$ adj caff$).tw.
38 (sperm$ adj5 swimup$).tw.
39 (sperm adj5 percol$).tw.
45 (frozen adj5 embry$).tw.
46 (antisperm$ adj5 antibod$).tw.
50 (fallopian tub$ adj5 perfus$).tw.
52 (luteal adj5 dysfunct$).tw.
53 (ovulat$ adj5 induc$).tw.
57 inseminat$.tw.
58 varicoc$.tw.
59 fertility/
60 fertilization/
61 insemination/
62 ovum implantation/
63 Ovarian Hyperstimulation Syndrome/
64 (embry$ adj5 transf$).tw.
65 or/15-64
66 65 and 14
67 acupuncture/ or electroacupuncture/ or meridians/ or acupuncture points/
68 acupunctur$.tw.
70 acupoint$.tw.
72 exp MOXIBUSTION/
73 (moxibustion or moxabustion or moxa).tw.
74 or/67-73
75 66 and 74
76 from 75 keep 1-8
48
WHAT’S NEW
Last assessed as up-to-date: 12 October 2007.
13 June 2008
Amended
Converted to new review format.
HISTORY
Protocol first published: Issue 1, 2008
Review first published: Issue 4, 2008
13 October 2007
New citation required and conclusions have changed
Substantive amendment
CONTRIBUTIONS OF AUTHORS
Ying Cheong wrote the protocol and developed the selection criteria. Ernest Ng contributed by performing the search of the Chinese
database. Will Ledger acted as a moderator for the meta-analysis.
DECLARATIONS OF INTEREST
None known
SOURCES OF SUPPORT
Internal sources
• None, Not specified.
External sources
• Cochrane Menstrual and Subfertility Group, New Zealand.
Support of search strategy, advice, refereeing and proof reading
49
INDEX TERMS
Medical Subject Headings (MeSH)
∗ Acupuncture
Therapy; ∗ Reproductive Techniques, Assisted; Embryo Transfer; Live Birth; Randomized Controlled Trials as Topic;
Time Factors
MeSH check words
Female; Humans
50

Acupuncture and assisted conception

Transcription

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