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Acupuncture and assisted reproductive technology

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Background

Acupuncture is commonly undertaken during an assisted reproductive technology (ART) cycle although its role in improving live birth and pregnancy rates is unclear.

Objectives

To determine the effectiveness and safety of acupuncture as an adjunct to ART cycles for male and female subfertility.

Search methods

All reports which described randomised controlled trials of acupuncture in assisted conception were obtained through searches of the Menstrual Disorders and Subfertility Group Specialised Register, CENTRAL, Ovid MEDLINE, EMBASE, CINAHL (Cumulative Index to Nursing & Allied Health Literature), AMED , www.clinicaltrials.gov (all from inception to July 2013), National Research Register, and the Chinese clinical trial database (all to November 2012).

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 that was deemed to contraindicate ART or acupuncture were excluded.

Data collection and analysis

Twenty randomised controlled trials were included in the review and nine were excluded. Study selection, quality assessment and data extraction were performed independently by two review authors. Meta‐analysis was performed using odds ratio (OR) and 95% confidence intervals (CI). The outcome measures were live birth rate, clinical ongoing pregnancy rate, miscarriage rate, and any reported side effects of treatment. The quality of the evidence for the primary outcome (live birth) was rated using GRADE methods.

Main results

This updated meta‐analysis showed no evidence of overall benefit of acupuncture for improving live birth rate (LBR) regardless of whether acupuncture was performed around the time of oocyte retrieval (OR 0.87, 95% CI 0.59 to 1.29, 2 studies, n = 464, I2 = 0%, low quality evidence) or around the day of embryo transfer (ET) (OR 1.22, 95% CI 0.87 to 1.70, 8 studies, n = 2505, I2 = 69%, low quality evidence). There was no evidence that acupuncture had any effect on pregnancy or miscarriage rates, or had significant side effects.

Authors' conclusions

There is no evidence that acupuncture improves live birth or pregnancy rates in assisted conception.

PICO

Population
Intervention
Comparison
Outcome

El uso y la enseñanza del modelo PICO están muy extendidos en el ámbito de la atención sanitaria basada en la evidencia para formular preguntas y estrategias de búsqueda y para caracterizar estudios o metanálisis clínicos. PICO son las siglas en inglés de cuatro posibles componentes de una pregunta de investigación: paciente, población o problema; intervención; comparación; desenlace (outcome).

Para saber más sobre el uso del modelo PICO, puede consultar el Manual Cochrane.

Plain language summary

Acupuncture and assisted conception

Review question: does acupuncture improve the outcomes of assisted reproduction?

Background: one in seven couples suffer from subfertility and many will seek help in the form of assisted reproductive technology (ART). Although the use of acupuncture has gained popularity, the use of this traditional Chinese medical treatment in conjunction with ART treatments is still controversial. This review summarised the evidence from well designed studies and evaluated the effectiveness and safety of acupuncture in assisted conception.

Search date: the evidence is current to July 2013.

Study characteristics: there were 20 randomised controlled studies identified. Six studies compared acupuncture at the time of egg collection (912 women) and 14 studies compared acupuncture in assisted conception (3632 women). The studies were further divided into those which used placebo needles in their control groups versus those that had controls who did not undergo any treatment. All the studies identified involved participants undertaking in vitro fertilization (IVF); there were no studies reporting the effect of acupuncture in ovulation induction or intrauterine insemination.

Funding of included studies: no included studies had external funding.

Key results: there is no evidence of benefit for the use of acupuncture in participants undergoing assisted conception treatment around the time of embryo transfer or at egg collection in terms of improving the live birth rate, ongoing or clinical pregnancy rate. There is also no evidence that acupuncture has any effect on miscarriage rate or had significant side effects.

Quality of the evidence: overall, the results are not similar across the studies. This was due to different study designs including the use of different types of control groups that could have introduced bias. More research is needed before recommendations can be made, including studies in which some controls receive placebo needling and others receive no intervention.

Authors' conclusions

Implications for practice

We found no evidence that acupuncture improves live birth rate, ongoing pregnancy rate or clinical pregnancy rate. We also found no evidence that acupuncture increases the rate of miscarriage.

Implications for research

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 realm 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.The use of 'sham needles' may enhance the quality of the studies performed, though further research into the biological effect of sham acupuncture is needed. Ideally, studies in this area should carefully consider how they determine the necessary treatment points, gather qualitative as well as quantitative data in parallel with a three arm study design, acupuncture, no intervention and placebo needling. They should also provide their centre's pregnancy rates during the time course of the study for comparison. It is with this comprehensive study design that any clinical benefit of acupuncture can be delineated.

Summary of findings

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Summary of findings for the main comparison. Acupuncture around the time of oocyte retrieval versus control (sham, placebo, no acupuncture) for women undergoing ART

Acupuncture around the time of oocyte retrieval versus control (sham, placebo, no acupuncture) for women undergoing assisted reproductive technology (ART)

Population: women undergoing ART
Intervention: Acupuncture around the time of oocyte retrieval versus control (sham, placebo, no acupuncture)

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

No of Participants
(studies)

Quality of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

Control

Acupuncture around the time of oocyte retrieval versus control (sham, placebo, no acupuncture)

Live birth rate

357 per 1000

326 per 1000
(247 to 418)

OR 0.87
(0.59 to 1.29)

464
(2 studies)

⊕⊕⊝⊝
low1,2

No significant difference in live birth rate was found between the two groups

*The basis for the assumed risk is the median control group risk across studies. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: Confidence interval; OR: Odds ratio;

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

1 Neither study clearly reported method of random sequence generation, one did not clearly describe method of allocation concealment
2 Only two studies (n=464), wide confidence intervals.

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Summary of findings 2. Acupuncture on the day of ET versus control for women undergoing ART

Acupuncture on the day of embryo transfer (ET) versus control for women undergoing assisted reproductive technology (ART)

Population: women undergoing ART
Intervention: Acupuncture on the day of ET versus control (sham, placebo, no acupuncture)

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

No of Participants
(studies)

Quality of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

Control

Acupuncture on the day of ET versus control

Live birth rate

281 per 1000

323 per 1000
(254 to 399)

OR 1.22
(0.87 to 1.7)

2505
(8 studies)

⊕⊕⊝⊝
low1,2,3

No significant difference in live birth rate was found between the two groups

*The basis for the assumed risk is the median control group risk across studies. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: Confidence interval; OR: Odds ratio;

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

1 Two studies did not describe method of random sequence generation; six did not clearly describe method of allocation concealment
2 High statistical heterogeneity (I‐squared =69%)
3 Wide confidence intervals

Background

Description of the condition

One in seven to 10 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. The use of acupuncture has increasing gained popularity (Fisher 1994; Klein 2012; Thomas 2001) although its use as an adjuvant treatment to assisted conception is still controversial (El‐Toukhy 2010; Huang 2011; Meldrum 2013).

Description of the intervention

Acupuncture is an integral part of traditional Chinese medicine (TCM) and can be dated back at least 3000 years. In Europe, from consumer surveys (Fisher 1994; Klein 2012; Thomas 2001) between 7% and 19% of the population report using acupuncture for various reasons, and studies have shown promising results for its efficacy in adult postoperative and chemotherapy induced nausea and vomiting (Garcia 2013; Holmer 2012; NIH Consensus 1998).

In its original form, acupuncture is based on the principles of TCM and involves the insertion of fine needles into the skin along the meridians, providing a 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). There have been few studies of the physiological effects of acupuncture on the male or female reproductive tract, although for many years acupuncture has been widely used as an adjuvant to ART. Opinion about the effectiveness of acupuncture in women undergoing assisted conception varies considerably. Some regard the traditional Chinese treatment as effective (Zheng 2012) whilst others consider acupuncture as primarily a placebo treatment (Meldrum 2013) or even as a treatment that is unscientific and futile (El‐Toukhy 2010). It is, therefore, critical to examine the current evidence available using stringent methodology and analysis to evaluate the effectiveness of acupuncture in couples undertaking ART.

How the intervention might work

The mechanisms of action of acupuncture are largely unknown. Its influence on plasma beta‐endorphin levels via the hypothalamic‐pituitary‐adrenal (HPA) axis (Chen 2004; Stener‐Victorin 2000; Stener‐Victorin 2001), on uterine artery blood flow (Stener‐Victorin 1996) and analgesic actions have been described (Stener‐Victorin 1999).

Why it is important to do this review

Given the controversy surrounding this topic, it is important to perform an up‐to‐date review so that subfertile couples, fertility practitioners and general practitioners are better informed of the benefits or harm of acupuncture in assisted conception.

Objectives

To determine the effectiveness and safety of acupuncture as an adjunct to ART cycles for male and female subfertility.

Methods

Criteria for considering studies for this review

Types of studies

Published and unpublished randomised controlled trials (RCTs) were included in the review. We excluded non‐randomised studies (for example studies with evidence of inadequate sequence generation such as alternate days, patient numbers) as they are associated with a high risk of bias. We did not include crossover trials with no first phase data.

Types of participants

Participants in the trials had to meet all the following criteria to be included in the review.

Inclusion criteria:

  • primary (subfertility in couples who have never conceived) or secondary subfertility (couples who have subfertility after previously having children);

  • women 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:

  • participants 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

RCTs comparing acupuncture treatment of participants (men or women, or both) versus no treatment, placebo or sham acupuncture during controlled ovarian stimulation (COS) with or without artificial stimulation by partner (± artificial insemination by husband (AIH)), IVF, or frozen‐thawed embryo transfer (FET) treatment were considered.

We included studies using 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. 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.

The timing of acupuncture treatment was generally either around the time of oocyte retrieval or around the time of embryo transfer (ET) (a few days before, the day of, and a few days after).

Needling in the control groups could either be with a sham needle (for example Streitberger placebo needle, Asiamed, Pullach, Germany, where skin penetration does not occur because the tip of the needle is blunted) or normal acupuncture needles, needling an area not recommended by TCM practitioners for fertility treatment. The other type of control group had no needling treatment.

Specific interventions to be considered:

  1. acupuncture + ART versus no treatment, placebo, sham acupuncture + ART; i.e. all women received ART;

  2. acupuncture alone versus no treatment, placebo, sham acupuncture + ART;

  3. acupuncture versus acupuncture + ART.

Types of outcome measures

Primary outcomes

1. Live birth rate, defined as delivery of a live fetus after 20 completed weeks gestational age

Secondary outcomes

1. Ongoing pregnancy rate, defined as evidence of a gestational sac with fetal heart motion at greater than 12 weeks (12 to 18 weeks), confirmed with ultrasound

2. Clinical pregnancy rate, defined as evidence of a gestational sac with fetal heart motion measured at seven to eight weeks, confirmed with ultrasound

3. Adverse events including miscarriage, ectopic pregnancy, fetal abnormalities, side effects, ovarian hyperstimulation syndrome (OHSS) and infection

All rates were per woman randomised.

Search methods for identification of studies

Electronic searches

We searched the following electronic databases, trials registers and web sites.

  1. Menstrual Disorders and Subfertility Group (MDSG) Specialised Register (inception to 22.7.13).

  2. Ovid Cochrane Central Register of Controlled Trials (CENTRAL) (inception to 22.7.13).

  3. Ovid MEDLINE® In‐Process & Other Non‐Indexed Citations, Ovid MEDLINE® Daily and Ovid MEDLINE® (inception to22.7.13).

  4. Ovid EMBASE (01.01.10 to 22.7.13). EMBASE was only searched for recent records as the UK Cochrane Centre has handsearched EMBASE to this point and these trials are already in CENTRAL.

  5. Ovid PsycINFO (inception to 22.7.13).

  6. Ovid AMED (inception to 22.7.13).

Other electronic sources of trials included:

  1. Database of Abstracts of Reviews of Effects (DARE) in The Cochrane Library (http://www.cochrane.org/index.htm);

  2. ClinicalTrials.gov (http://clinicaltrials.gov/ct2/home);

  3. World Health Organization International Clinical Trials Registry Platform search portal (http://apps.who.int/trialsearch/);

  4. OpenSigle for Grey literature from Europe (http://opensigle.inist.fr/);

  5. China Academic Journal Electronic full text Database in China National Knowledge Infrastructure;

  6. Index to Chinese Periodical Literature.

There was no language restriction in these searches. The search strings are in the appendices.

Searching other resources

We also handsearched reference lists of articles retrieved by the search and contacted experts in the field to obtain additional data when required. We handsearched relevant journals and conference abstracts that are not covered in the MDSG register, in liaison with the Trials Search Co‐ordinator.

Data collection and analysis

Selection of studies

After an initial screening of titles and abstracts that were retrieved by the search, conducted by YC and SD, the full texts of all potentially eligible studies were retrieved. Two review authors (YC and SD) independently examined these full text articles for compliance with the inclusion criteria and selected studies eligible for inclusion in the review. We corresponded with study investigators to clarify study data and eligibility. Disagreements as to study eligibility were resolved by discussion without requiring referral to a third review author (WL). Study investigators were contacted for further data on methods or results, as required.

The selection process is documented with a PRISMA flow chart in Figure 1.


Study selection PRISMA flow diagram.

Study selection PRISMA flow diagram.

Data extraction and management

Two review authors (YC and SD) independently extracted data and assessed trial quality using forms designed according to Cochrane guidelines. Disagreements as to study eligibility were resolved by discussion without requiring referral to a third review author (WL). Where studies had multiple publications, the main trial report was used as the reference and additional details were derived from secondary papers. We corresponded with study investigators to clarify further data on methods and results.

Assessment of risk of bias in included studies

The included studies were assessed for risk of bias using the Cochrane risk of bias assessment tool (Cochrane Handbook for Systematic Reviews of Interventions Version 5.1) to assess the following domains: random sequence generation; allocation concealment; blinding; incomplete outcome data; selective reporting; and other bias.

Two authors (YC and SD) independently assessed these six domains, with any disagreements resolved by consensus or by discussion with the third author (WL).

As this was a review of surgical studies, where blinding was not possible, absence of blinding was not considered a significant source of bias. Risk of bias assessment is summarised (Figure 2 and Figure 3).


Methodological quality summary: review authors' judgements about each methodological quality item for each included study.

Methodological quality summary: review authors' judgements about each methodological quality item for each included study.


Methodological quality graph: review authors' judgements about each methodological quality item presented as percentages across all included studies.

Methodological quality graph: review authors' judgements about each methodological quality item presented as percentages across all included studies.

We took care to search for within trial selective reporting.

Measures of treatment effect

We performed statistical analysis in accordance with the guidelines and methods developed by The Cochrane Collaboration (Higgins 2011). All data were dichotomous. We expressed results for each study as odds ratio (OR) with 95% confidence interval (CI).

Unit of analysis issues

The unit of analysis was per participant and not per cycle. Multiple live births were counted as one live birth event.

Dealing with missing data

The data was analysed on an intention‐to‐treat basis and we have attempted to obtain missing data from the original trialists. Where these were unobtainable, imputation of individual values was undertaken for the primary outcomes only. Live births were assumed not to have occurred in participants without a reported outcome. For other outcomes, only the available data were analysed.

Assessment of heterogeneity

Heterogeneity was assessed using the I2 statistic, according to the guidelines set out in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). An I2 value greater than 50% indicated substantial heterogeneity.

Assessment of reporting biases

In view of the difficulty in detecting and correcting for publication bias and other reporting bias, we minimised their potential impact by ensuring a comprehensive search for eligible studies and by being aware of duplicated data. In the case where 10 or more studies were present in our analysis, we used a funnel plot to explore the possibility of a small study effect.

Data synthesis

Where possible, we pooled the outcomes and combined them for meta‐analysis. Dichotomous data for primary and secondary outcomes in studies that were sufficiently similar were combined with RevMan software using the Peto‐modified Mantel‐Haenszel method and fixed‐effect and random‐effects models in the following comparisons.

1. Acupuncture around the time of oocyte retrieval versus control (changed for consistency).

2. Acupuncture on the day of ET versus control.

We used a fixed‐effect model and examined heterogeneity between the results of different studies by inspecting the scatter in the data points, the overlap in their CIs, and more formally by checking the results of the Chi2 test and the I2 statistic. An I2 greater than 50% was taken to indicate substantial heterogeneity and in that case a random‐effects analysis was used.

Subgroup analysis and investigation of heterogeneity

The analysis was stratified to examine the separate evidence within the following subgroups:

1) studies with control groups that had sham or needling acupuncture;

2) studies with control groups that had no acupuncture.

Sensitivity analysis

None applicable

Results

Description of studies

See the tables Characteristics of included studies and Characteristics of excluded studies.

Results of the search

In the original review, 16 randomised trials were identified involving acupuncture and assisted conception; 13 met the inclusion criteria and three were excluded. In the updated search, 14 further randomised trials were identified, giving a total of 30. In total, 20 trials were included and nine were excluded; see Figure 1. Five ongoing studies were also identified (ACTRN12611000226909; IRCT201011275181N4; NCT00317317; NCT01449396; NCT01608048).

Included studies

Study design and setting

Twenty randomised controlled trials were included in this review. Four of the trial reports were abstracts (Benson 2006; Craig 2007; Fraterelli 2008; Paulus 2003). All 20 trials had a parallel design (Andersen 2010; Benson 2006; Craig 2007; Dieterle 2006; Domar 2009; Fraterelli 2008; Gejervall 2005; Ho 2009; Humaidan 2004; Madaschi 2010; Moy 2011; Paulus 2002; Paulus 2003; Sator‐K 2006; Smith 2006; So 2009; So 2010; Stener‐Victorin 1999; Stener‐Victorin 2003; Westergaard 2006).

Participants

The studies included a total of 4544 participants. All were women undergoing IVF and intracytoplasmic sperm injection (ICSI). The characteristics of the participants can be found in the table Characteristics of included studies.

Interventions

A summary of the acupuncture points used in the various studies is provided in Table 1.

Open in table viewer
Table 1. Table 1. Summary of acupuncture points used.

Acupuncture points

Craig 2007

Westergaard 2006

Dieterle 2006

Paulus 2002 Paulus 2003 Andersen 2010 ; Domar 2009

Madaschi 2010

Ho 2009

Moy 2011

Smith 2006

So 2009

So 2010

Stener‐Victorin 1999

Stener‐Victorin 2003

Gejervall 2005

Humaidan 2004

Sator‐K 2006

Cv6 (Qi Hai)

Y (before ET)

Y

Cx6 (Neiguan)

Y

Y

Y

DU 20

(bai hui)

Y

GV 20 (Baihui)

Y

Y (around ET and ET + 2)

Y

Y

Y

Y

Y

Y

Y

Y

Y

Liv 2 (Xingjian)

Liv 3 (Taichong)

Y

Y

Y

Y

LI 4 (Hegu)

Y

Y ( ET + 2)

Y (ET + 3)

Y

Y

Y

Y

Y

Y

Y

Y

Y

Y

Y

LI 10 (Shoushanli)

Y

LR 3 (Taichong)

Y

Y

Y

Y

LU 7

(lieque)

Y

SP 6 (Sanyinjiao)

Y

Y ( ET + 2)

Y (ET + 3)

Y

Y

Y

Y

Y

Y

Y

Y

Y

SP 8 (Diji)

Y

Y

Y

Y

Y

Y

Y

Y

SP 10 (Xuehai)

Y

Y

Y

Y

Y

Y

Y

Y

ST28

Y

ST29 (Guilai)

Y

Y (ET and ET + 2)

Y

Y

Y

Y

Y

Y

Y

Y

Y

ST36 (Zushanli)

Y

Y (ET + 3)

Y

Y

Y

Y

Y

Y

Y

Y

Y

PC6 (Neiguan)

Y

Y

Y

Y

Ren 3 (Zhongji)

Y (ET + 2)

RN 4 (Guanyuan)

Y

Y

RN6 (Qihai)

Y

Y

K3 (Tai Xi)

Y (after ET)

K13 (Taxiu)

Y (ET + 3)

K1 11(Henggu)

Y

Y

TE 5 (Weiguan)

Y

EX‐CA 1 (Zigong)

Y

Control groups

No sham or needling:

With sham or needling:

Outcomes

  • 11/20 studies reported on live birth rate

  • 11/20 studies reported on ongoing pregnancy rate

  • 20/20 studies reported on clinical pregnancy rate

  • 2/20 studies reported on multiple pregnancy rates

  • 0/20 studies reported on rates of OHSS

  • 9/20 studies reported on miscarriage rates

  • 4/20 studies reported on side effects arising from use of acupuncture

Further details of the included studies can be found in the table Characteristics of included studies.

Excluded studies

Ten studies were excluded from the review for the following reasons:

  • Quintero 2004 was excluded due to the lack of first phase results in its crossover design;

  • Cui 2011 randomised women with polycystic ovary syndrome (PCOS) undergoing ET to either electro‐acupuncture (n = 34) or the control of no treatment (n = 32). However, the description of the randomisation process showed a high risk of bias with an inadequate randomisation process, based on odd or even numbers;

  • Chen 2004; Chen 2009; Cui 2007; Evans 2005; Feliciani 2011; Li 2009 and Omodei 2010 were excluded because they were apparently not randomised.

  • Chen 2012 reported on supplementary analgesia and improvement of adverse reactions induced by dolantin in oocyte retrieval, which were not outcoems of interest in the review

Characteristics of excluded studies can be found in the table Characteristics of excluded studies.

Risk of bias in included studies

Risk of bias assessment focused on six main domains: random sequence generation, allocation concealment, blinding, incomplete data outcome, selective reporting and other potential bias. Details of the findings can be found in the relevant risk of bias summary figures (Figure 2; Figure 3) and the Characteristics of included studies table.

Allocation

Sequence generation

Eleven trials were at low risk of selection bias related to sequence generation (Andersen 2010; ; Domar 2009; Gejervall 2005; Madaschi 2010; Moy 2011; Paulus 2002; Paulus 2003; Sator‐K 2006; Smith 2006; So 2009; So 2010; ). The other nine trials (Benson 2006; Craig 2007; Dieterle 2006; Fraterelli 2008; Ho 2009; Humaidan 2004; Stener‐Victorin 1999; Stener‐Victorin 2003; Westergaard 2006)were at an unclear risk due to a lack of detail of their methods of sequence generation.

Allocation concealment

Four trials were at low risk of bias for allocations concealment (Humaidan 2004; Moy 2011; So 2009; So 2010). The other sixteen trials (Andersen 2010; Benson 2006; Craig 2007; Dieterle 2006; Domar 2009; Fraterelli 2008; Gejervall 2005; Ho 2009; Madaschi 2010; Paulus 2002; Paulus 2003; Sator‐K 2006; Smith 2006; Stener‐Victorin 1999; Stener‐Victorin 2003; Westergaard 2006) were at unclear risk of bias for allocation concealment.

Blinding

Due to the nature of the studies, double blinding was often not possible. Eleven trials (Benson 2006; Craig 2007; Domar 2009; Gejervall 2005; Ho 2009; Madaschi 2010; Paulus 2002; Sator‐K 2006; Stener‐Victorin 1999; Stener‐Victorin 2003; Westergaard 2006) had no sham acupuncture intervention for the control group and so were at high risk of performance and detection bias. Five trials (Andersen 2010; Humaidan 2004; Paulus 2003; So 2009; So 2010) were low risk of performance and detection bias due to the use of sham acupuncture controls for blinding. Moy 2011 and Dieterle 2006 used an actual needling procedure on acupoints that were not considered to affect fertility and so were also low risk. Smith 2006 used sham acupuncture for the control groups but was deemed at an unclear risk of performance and detection bias as, after the 3rd session, 24 in the treatment group and 10 in the control group had guessed their allocation correctly.

Incomplete outcome data

Fifteen trials were at low risk of attrition bias without significant incomplete outcome data (Andersen 2010; Craig 2007; Dieterle 2006; Gejervall 2005; Humaidan 2004; Madaschi 2010; Moy 2011; Paulus 2002; Paulus 2003; Sator‐K 2006; So 2009; So 2010; Stener‐Victorin 1999; Stener‐Victorin 2003; Westergaard 2006). In three trials the risk was unclear as they did not report on the number of participants who completed the study (Benson 2006; Domar 2009; Fraterelli 2008). Ho 2009 had a high risk of attrition bias as 12 of the 26 control group participants dropped out of the trial. Smith 2006 also had a high risk of attrition bias as 36 women (15%) were withdrawn from the trial after randomisation.

Selective reporting

Three trials (Andersen 2010; So 2009; So 2010) were at low risk of reporting bias as they reported live birth data as prestated outcomes. Seven trials (Dieterle 2006; Humaidan 2004; Madaschi 2010; Paulus 2002; Paulus 2003; Stener‐Victorin 2003; Westergaard 2006) were at unclear risk of reporting bias as they reported live birth data but it was not a prestated outcome. The remaining 10 trials (Benson 2006; Craig 2007; Domar 2009; Fraterelli 2008; Gejervall 2005; Ho 2009; Moy 2011; Sator‐K 2006; Smith 2006; Stener‐Victorin 1999) did not report on live birth rate outcomes and so were also at unclear risk.

Other potential sources of bias

One study (Stener‐Victorin 1999) was rated as at unclear risk of other potential bias, related to co‐intervention in some women. The other studies were rated as at low risk of bias in this domain.

Effects of interventions

See: Summary of findings for the main comparison Acupuncture around the time of oocyte retrieval versus control (sham, placebo, no acupuncture) for women undergoing ART; Summary of findings 2 Acupuncture on the day of ET versus control for women undergoing ART

Overall, 20 studies were included in the meta‐analysis. 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.

Open in table viewer
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

Actions and effects:
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, 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

Actions and effects:
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

Actions and effects:
Releases the exterior for wind‐cold or wind‐heat syndromes.
Strengthens the wei qi, improves immunity.
Regulates the sweat glands, for excessive sweating tonify LI 4 then disperse KD 7 and vice versa.
Any problem on the face ‐ sense organs, mouth, teeth, jaw, toothache, allergies, rhinitis, hay fever, acne, eye problems, etc.
Toothache use both LI 4 & ST 44 ‐ LI for the lower jaw & ST for the upper jaw.
Headache, especially frontal, sinus (yangming area).
Chronic pain.
Influence the circulation of Qi and blood ‐ use the four gates, LI 4 & LV 3 to strongly move the Qi and blood in the body clearing stagnation and alleviating pain.
Promote labor or for retained placenta.

LI 10 (Shoushanli)

Location: 2 cm below LI 11 on the LI 5 to LI 11 line.

Actions and effects:
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 cm below LI 11 on the LI 5 to LI 11 line.

SP 6 (Sanyinjiao)

Location: 3 cm directly above the tip of the medial malleolus on the posterior border of the tibia.


Precautions: no needle in pregnancy

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

Actions and effects:
Tonify Yin and blood, all spleen disorders.
Digestive disorders, sinking or prolapse.
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 cm below SP 9 on line connecting SP 9 and the tip of the medial malleolus.

Point associations:
Xi Cleft point.


Actions and effects:
Xi Cleft point ‐ acute and painful menstrual issues due to blood stagnation ‐ clotting, fibroids, dysmenorrhoea.
Male infertility.

SP 10 (Xuehai)

Location: with knee flexed, 2 cm above the superior medial border of the patella on the bulge of the medial portion of quadriceps femoris (vastus medialis).

Actions and effects:
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 cm lateral to the AML level with CV 3.

Actions and effects:
Excess or cold/deficient disorders of the lower warmer ‐ amenorrhoea, irregular menstruation, qi stagnation/masses.
Running Piglet disorder.

ST36 (Zushanli)

Location: 3 cm 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

Actions and effects:
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 cm 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

Actions and effects:
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 cm superior to qugu. Regulates LR, warms KI, irregular menses.

RN 4 (Guanyuan)

Location: 1.5 cm 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 cm 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, dysmenorrhoea, asthma.

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 cm posterior to Wuchu (UB 5), 1.5 cm 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 cm 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.

1. Acupuncture around the time of oocyte retrieval

None of the studies with the intervention performed around the time of oocyte retrieval had controls using sham or needling acupuncture.

1.1 Live birth rate (LBR)

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 (75/229) and the control group (84/235) (OR 0.87, 95% CI 0.59 to 1.29, I2 = 0%) (Analysis 1.1; Figure 4).


Forest plot of comparison: 1 Acupuncture around the time of oocyte retrieval versus control (sham, placebo, no acupuncture), outcome: 1.1 Live Birth Rate.

Forest plot of comparison: 1 Acupuncture around the time of oocyte retrieval versus control (sham, placebo, no acupuncture), outcome: 1.1 Live Birth Rate.

1.2 Ongoing pregnancy rate

Two trials (Humaidan 2004; Stener‐Victorin 2003) reported an ongoing pregnancy rate of 78/229 in the treatment group versus 88/235 in the control group (OR 0.86, 95% CI 0.58 to 1.26, I2 = 0%) (Analysis 1.2).

1.3 Clinical pregnancy rate

In the pooled results of six trials (Gejervall 2005; Ho 2009; Humaidan 2004; Sator‐K 2006; Stener‐Victorin 1999; Stener‐Victorin 2003), there was no evidence of a difference in the clinical pregnancy rate between the treatment group (174/478) and the control group 150/434 (OR 1.12, 95% CI 0.78 to 1.62, P = 0.53, I2 = 34%) (Analysis 1.3).

1.4 Miscarriage rate

The pooled results from four trials (Humaidan 2004; Sator‐K 2006; Stener‐Victorin 1999; Stener‐Victorin 2003) showed no significant difference in miscarriage rates between the treatment group and control: 25/142 versus 29/120 (OR 0.79, 95% CI 0.42 to 1.47, I2 = 17%) (Analysis 1.4; Figure 5).


Forest plot of comparison: 1 Acupuncture around the time of oocyte retrieval versus control (sham, placebo, no acupuncture), outcome: 1.4 Miscarriage rate.

Forest plot of comparison: 1 Acupuncture around the time of oocyte retrieval versus control (sham, placebo, no acupuncture), outcome: 1.4 Miscarriage rate.

1.5 Multiple pregnancy

No trials reported multiple pregnancy.

1.6 Ovarian hyperstimulation syndrome (OHSS)

No trials reported OHSS.

2. Acupuncture on or around the day of embryo transfer

2.1 Live birth rate (LBR)

In women who had acupuncture on the day of and around ET (Andersen 2010; Dieterle 2006; Madaschi 2010; Paulus 2002; Paulus 2003; So 2009; So 2010; Westergaard 2006) (N = 2505), the overall LBR was 389/1302 compared to the controls 338/1203 (OR 1.22, 95% CI 0.87 to 1.70, P = 0.30, I2 = 69%) (Analysis 2.1; Figure 6). This was not statistically significant.


Forest plot of comparison: 2 Acupuncture on and around the day of ET versus control, outcome: 2.1 Live Birth.

Forest plot of comparison: 2 Acupuncture on and around the day of ET versus control, outcome: 2.1 Live Birth.

In studies that had controls without sham acupuncture or needling (Madaschi 2010; Paulus 2002; Westergaard 2006), the LBR in the acupuncture group was significantly higher at 154/474 compared to 90/375 (OR 1.55, 95% CI 1.14 to 2.12, I2 = 0%) in the controls. In the studies that had controls with sham acupuncture (Andersen 2010; Dieterle 2006; Paulus 2003; So 2009; So 2010) the results were 235/828 in the acupuncture group compared to 248/828 (OR 1.03, 95% CI 0.67 to 1.58, P = 0.88, I2 = 72%) in the controls. This was not statistically significant.

2.2 Ongoing pregnancy rate

In the pooled results of 10 trials (Andersen 2010; Craig 2007; Dieterle 2006; Fraterelli 2008; Paulus 2002; Paulus 2003; Smith 2006; So 2009; So 2010; Westergaard 2006) (N = 2807), the overall ongoing pregnancy rate was 460/1451 in the acupuncture group compared to 427/1356 for all controls (OR 1.10, 95% CI 0.80 to 1.52, P = 0.56, I2 = 72%) (Analysis 2.2).

In studies that had controls without sham acupuncture or needling (Craig 2007; Fraterelli 2008; Paulus 2002; Westergaard 2006), the ongoing pregnancy rate in the acupuncture group was 183/514 compared to 143/410 in the controls (OR 1.08, 95% CI 0.57 to 2.07, P = 0.81, I2 = 77%). In the studies that had controls with sham acupuncture (Andersen 2010; Dieterle 2006; Paulus 2003; Smith 2006; So 2009; So 2010) the results were 277/937 in the acupuncture group compared to 284/946 in the controls (OR 1.10, 95% CI 0.74 to 1.65, P = 0.63, I2 = 73%). This was not statistically significant .

2.3 Clinical pregnancy rate

In the pooled results of 14 trials (Andersen 2010; Benson 2006; Craig 2007; Dieterle 2006; Domar 2009; Fraterelli 2008; Madaschi 2010; Moy 2011; Paulus 2002; Paulus 2003; Smith 2006; So 2009; So 2010; Westergaard 2006) (N = 3632) the clinical pregnancy rate was 734/1876 in the acupuncture group compared to 658/1756 for all controls (OR 1.11, 95% CI 0.87 to 1.42, P = 0.39, I2 = 66%). This was not statistically significant (Analysis 2.3).

In studies that had controls without sham acupuncture or needling (Benson 2006; Craig 2007; Domar 2009; Fraterelli 2008; Madaschi 2010; Paulus 2002; Westergaard 2006) the clinical pregnancy rate in the acupuncture group was 365/853 compared to 285/736 (OR 1.21, 95% CI 0.84 to 1.73, P = 0.30, I2 = 62%). In the studies that had controls with sham acupuncture (Andersen 2010; Dieterle 2006; Moy 2011; Paulus 2003; Smith 2006; So 2009; So 2010) the results were 369/1023 compared to 373/1020 (OR 1.04, 95% CI 0.74 to 1.46, P = 0.83, I2 = 68%). This was not statistically significant.

2.4 Miscarriage rate

Six trials evaluated the possible impact of acupuncture on miscarriage (Dieterle 2006; Madaschi 2010; Smith 2006; So 2009; So 2010; Westergaard 2006). The miscarriage rate was 71/340 in the acupuncture group compared to 57/276 in the overall controls (OR 1.10, 95% CI 0.73 to 1.67, I2 = 0%) (Analysis 2.4; Figure 7). There was no significant difference found between the two groups in the subgroup analysis.


Forest plot of comparison: 2 Acupuncture on and around the day of ET versus control, outcome: 2.4 Miscarriage.

Forest plot of comparison: 2 Acupuncture on and around the day of ET versus control, outcome: 2.4 Miscarriage.

2.5 Multiple gestations

Two trials reported on multiple pregnancy rates (Andersen 2010; Moy 2011); both had control groups which used sham acupuncture. There was no significant difference detected between the acupuncture (30/400) and control groups (25/395) (OR 1.32, 95% CI 0.74 to 2.35, I2 = 0%) (Analysis 2.5).

2. 6 Ovarian hyperstimulation syndrome (OHSS)

None of the 14 trials reported ovarian hyperstimulation.

2.7 Any side effects

So 2009 and So 2010 did not report any statistically significant difference between side effects in the 'real' and 'placebo' acupuncture groups; side effects included nausea, dizziness, fainting, tiredness, headache, chest pain and puncture site itching. However, Moy 2011 suggest a difference between the two groups in the main categories of the McGill pain score. Women in the true arm reported greater affective perception of being tired and fearful as well as more achiness.

Assessment of heterogeneity

Heterogeneity was generally absent or low when studies of acupuncture around the time of oocyte retrieval were pooled

However when analyses of studies of acupuncture on or around the day of embryo transfer were pooled there was high heterogeneity (I‐squared >50%) for several outcomes, and we considered clinical and methodological differences between the studies that might account for this. The increased heterogeneity may be a result of the large variation in the definition of controls and acupuncture points used in the included studies (see below).

Discussion

Summary of main results

This updated review reports no evidence of overall benefit of acupuncture in improving live birth rate (LBR) when acupuncture was performed around the time of oocyte retrieval or on and around the day of ET.

The subgroup analysis showed that in studies with controls without sham or needling, women who had acupuncture on and around the day of ET had a higher LBR than the controls (OR 1.55, 95% CI 1.14 to 2.12); however this evidence of benefit was not present in studies where the control group had sham acupuncture (acupuncture compared to sham controls (OR 0.93, 95% CI 0.75 to 1.15). The difference in findings between the two subgroups could possibly be due to study quality: only two RCTs, both in the sham acupuncture group, reported satisfactory methods of allocation concealment.

There was no evidence that acupuncture had an effect on miscarriage rates or other treatment side effects.

Most authors in the field assume that acupuncture has little detrimental effect. Our review reports no evidence of effect on the miscarriage rate between acupuncture groups and all controls, regardless of the timing of the intervention. 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.

Overall completeness and applicability of evidence

It is generally accepted that acupuncture is relatively painless and has few side effects, although recent studies have shown that serious adverse events can occur (He et al, 2012). 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 variable. The variety of controls used for the RCTs included in this review ranged across no intervention, placebo needling, and sham acupuncture needles. Although sham needles are regarded as an acceptable control, true patient blinding has been shown to be a challenge (Tan 2011). It is possible that acupuncture needling could elicit a placebo or true biological effect over a wide area of the body not specific to 'points'. It has been suggested that a placebo effect may positively influence reproductive outcomes through mechanisms related to stress relief (Domar 2011; Meissner 2007), although postulating the biological impact of placebo is very much outside the context of this review.

Studies included in this review also had a large variation in pregnancy rates, but most studies did not report their centre's normal pregnancy rate for comparison.

Although all 20 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 this is the case. 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 practicing 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.

At the time of writing this review, the authors knew of four further studies in the area that are ongoing (ACTRN12611000226909; IRCT201011275181N4; NCT00317317; NCT01449396).

Quality of the evidence

The overall quality of evidence for live birth outcomes was rated as low, using GRADE methods (seesummary of findings Table for the main comparison and summary of findings Table 2). The quality of individual studies was generally low, with over 75% failing to describe an adequate method of allocation concealment (see Figure 2 and Figure 3).

Potential biases in the review process

We made every effort to identify all potentially eligible studies, and sought additional data from study authors as necessary. However, it is possible that there are unpublished studies that were not retrieved.

Agreements and disagreements with other studies or reviews

Several meta‐analyses have been published in the last six years in this area (Anderson 2007; Cheong 2010; El‐Toukhy 2010; Manheimer 2008; Zheng 2012). Depending on the data included and when the reviews were published, researchers have reached different conclusions about the beneficial effects on acupuncture on women undergoing IVF. Such discrepancies will continue to exist unless agreed standard scientific principles and research methodologies are incorporated into future studies (MacPherson 2010).

Study selection PRISMA flow diagram.
Figuras y tablas -
Figure 1

Study selection PRISMA flow diagram.

Methodological quality summary: review authors' judgements about each methodological quality item for each included study.
Figuras y tablas -
Figure 2

Methodological quality summary: review authors' judgements about each methodological quality item for each included study.

Methodological quality graph: review authors' judgements about each methodological quality item presented as percentages across all included studies.
Figuras y tablas -
Figure 3

Methodological quality graph: review authors' judgements about each methodological quality item presented as percentages across all included studies.

Forest plot of comparison: 1 Acupuncture around the time of oocyte retrieval versus control (sham, placebo, no acupuncture), outcome: 1.1 Live Birth Rate.
Figuras y tablas -
Figure 4

Forest plot of comparison: 1 Acupuncture around the time of oocyte retrieval versus control (sham, placebo, no acupuncture), outcome: 1.1 Live Birth Rate.

Forest plot of comparison: 1 Acupuncture around the time of oocyte retrieval versus control (sham, placebo, no acupuncture), outcome: 1.4 Miscarriage rate.
Figuras y tablas -
Figure 5

Forest plot of comparison: 1 Acupuncture around the time of oocyte retrieval versus control (sham, placebo, no acupuncture), outcome: 1.4 Miscarriage rate.

Forest plot of comparison: 2 Acupuncture on and around the day of ET versus control, outcome: 2.1 Live Birth.
Figuras y tablas -
Figure 6

Forest plot of comparison: 2 Acupuncture on and around the day of ET versus control, outcome: 2.1 Live Birth.

Forest plot of comparison: 2 Acupuncture on and around the day of ET versus control, outcome: 2.4 Miscarriage.
Figuras y tablas -
Figure 7

Forest plot of comparison: 2 Acupuncture on and around the day of ET versus control, outcome: 2.4 Miscarriage.

Comparison 1 Acupuncture around the time of oocyte retrieval versus control (sham, placebo, no acupuncture), Outcome 1 Live Birth Rate.
Figuras y tablas -
Analysis 1.1

Comparison 1 Acupuncture around the time of oocyte retrieval versus control (sham, placebo, no acupuncture), Outcome 1 Live Birth Rate.

Comparison 1 Acupuncture around the time of oocyte retrieval versus control (sham, placebo, no acupuncture), Outcome 2 Ongoing Pregnancy Rate.
Figuras y tablas -
Analysis 1.2

Comparison 1 Acupuncture around the time of oocyte retrieval versus control (sham, placebo, no acupuncture), Outcome 2 Ongoing Pregnancy Rate.

Comparison 1 Acupuncture around the time of oocyte retrieval versus control (sham, placebo, no acupuncture), Outcome 3 Clinical Pregnancy Rate.
Figuras y tablas -
Analysis 1.3

Comparison 1 Acupuncture around the time of oocyte retrieval versus control (sham, placebo, no acupuncture), Outcome 3 Clinical Pregnancy Rate.

Comparison 1 Acupuncture around the time of oocyte retrieval versus control (sham, placebo, no acupuncture), Outcome 4 Miscarriage rate.
Figuras y tablas -
Analysis 1.4

Comparison 1 Acupuncture around the time of oocyte retrieval versus control (sham, placebo, no acupuncture), Outcome 4 Miscarriage rate.

Comparison 2 Acupuncture on and around the day of ET versus control, Outcome 1 Live Birth.
Figuras y tablas -
Analysis 2.1

Comparison 2 Acupuncture on and around the day of ET versus control, Outcome 1 Live Birth.

Comparison 2 Acupuncture on and around the day of ET versus control, Outcome 2 Ongoing pregnancy.
Figuras y tablas -
Analysis 2.2

Comparison 2 Acupuncture on and around the day of ET versus control, Outcome 2 Ongoing pregnancy.

Comparison 2 Acupuncture on and around the day of ET versus control, Outcome 3 Clinical pregnancy.
Figuras y tablas -
Analysis 2.3

Comparison 2 Acupuncture on and around the day of ET versus control, Outcome 3 Clinical pregnancy.

Comparison 2 Acupuncture on and around the day of ET versus control, Outcome 4 Miscarriage.
Figuras y tablas -
Analysis 2.4

Comparison 2 Acupuncture on and around the day of ET versus control, Outcome 4 Miscarriage.

Comparison 2 Acupuncture on and around the day of ET versus control, Outcome 5 Multiple gestation.
Figuras y tablas -
Analysis 2.5

Comparison 2 Acupuncture on and around the day of ET versus control, Outcome 5 Multiple gestation.

Summary of findings for the main comparison. Acupuncture around the time of oocyte retrieval versus control (sham, placebo, no acupuncture) for women undergoing ART

Acupuncture around the time of oocyte retrieval versus control (sham, placebo, no acupuncture) for women undergoing assisted reproductive technology (ART)

Population: women undergoing ART
Intervention: Acupuncture around the time of oocyte retrieval versus control (sham, placebo, no acupuncture)

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

No of Participants
(studies)

Quality of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

Control

Acupuncture around the time of oocyte retrieval versus control (sham, placebo, no acupuncture)

Live birth rate

357 per 1000

326 per 1000
(247 to 418)

OR 0.87
(0.59 to 1.29)

464
(2 studies)

⊕⊕⊝⊝
low1,2

No significant difference in live birth rate was found between the two groups

*The basis for the assumed risk is the median control group risk across studies. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: Confidence interval; OR: Odds ratio;

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

1 Neither study clearly reported method of random sequence generation, one did not clearly describe method of allocation concealment
2 Only two studies (n=464), wide confidence intervals.

Figuras y tablas -
Summary of findings for the main comparison. Acupuncture around the time of oocyte retrieval versus control (sham, placebo, no acupuncture) for women undergoing ART
Summary of findings 2. Acupuncture on the day of ET versus control for women undergoing ART

Acupuncture on the day of embryo transfer (ET) versus control for women undergoing assisted reproductive technology (ART)

Population: women undergoing ART
Intervention: Acupuncture on the day of ET versus control (sham, placebo, no acupuncture)

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

No of Participants
(studies)

Quality of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

Control

Acupuncture on the day of ET versus control

Live birth rate

281 per 1000

323 per 1000
(254 to 399)

OR 1.22
(0.87 to 1.7)

2505
(8 studies)

⊕⊕⊝⊝
low1,2,3

No significant difference in live birth rate was found between the two groups

*The basis for the assumed risk is the median control group risk across studies. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: Confidence interval; OR: Odds ratio;

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

1 Two studies did not describe method of random sequence generation; six did not clearly describe method of allocation concealment
2 High statistical heterogeneity (I‐squared =69%)
3 Wide confidence intervals

Figuras y tablas -
Summary of findings 2. Acupuncture on the day of ET versus control for women undergoing ART
Table 1. Table 1. Summary of acupuncture points used.

Acupuncture points

Craig 2007

Westergaard 2006

Dieterle 2006

Paulus 2002 Paulus 2003 Andersen 2010 ; Domar 2009

Madaschi 2010

Ho 2009

Moy 2011

Smith 2006

So 2009

So 2010

Stener‐Victorin 1999

Stener‐Victorin 2003

Gejervall 2005

Humaidan 2004

Sator‐K 2006

Cv6 (Qi Hai)

Y (before ET)

Y

Cx6 (Neiguan)

Y

Y

Y

DU 20

(bai hui)

Y

GV 20 (Baihui)

Y

Y (around ET and ET + 2)

Y

Y

Y

Y

Y

Y

Y

Y

Y

Liv 2 (Xingjian)

Liv 3 (Taichong)

Y

Y

Y

Y

LI 4 (Hegu)

Y

Y ( ET + 2)

Y (ET + 3)

Y

Y

Y

Y

Y

Y

Y

Y

Y

Y

Y

LI 10 (Shoushanli)

Y

LR 3 (Taichong)

Y

Y

Y

Y

LU 7

(lieque)

Y

SP 6 (Sanyinjiao)

Y

Y ( ET + 2)

Y (ET + 3)

Y

Y

Y

Y

Y

Y

Y

Y

Y

SP 8 (Diji)

Y

Y

Y

Y

Y

Y

Y

Y

SP 10 (Xuehai)

Y

Y

Y

Y

Y

Y

Y

Y

ST28

Y

ST29 (Guilai)

Y

Y (ET and ET + 2)

Y

Y

Y

Y

Y

Y

Y

Y

Y

ST36 (Zushanli)

Y

Y (ET + 3)

Y

Y

Y

Y

Y

Y

Y

Y

Y

PC6 (Neiguan)

Y

Y

Y

Y

Ren 3 (Zhongji)

Y (ET + 2)

RN 4 (Guanyuan)

Y

Y

RN6 (Qihai)

Y

Y

K3 (Tai Xi)

Y (after ET)

K13 (Taxiu)

Y (ET + 3)

K1 11(Henggu)

Y

Y

TE 5 (Weiguan)

Y

EX‐CA 1 (Zigong)

Y

Figuras y tablas -
Table 1. Table 1. Summary of acupuncture points used.
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

Actions and effects:
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, 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

Actions and effects:
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

Actions and effects:
Releases the exterior for wind‐cold or wind‐heat syndromes.
Strengthens the wei qi, improves immunity.
Regulates the sweat glands, for excessive sweating tonify LI 4 then disperse KD 7 and vice versa.
Any problem on the face ‐ sense organs, mouth, teeth, jaw, toothache, allergies, rhinitis, hay fever, acne, eye problems, etc.
Toothache use both LI 4 & ST 44 ‐ LI for the lower jaw & ST for the upper jaw.
Headache, especially frontal, sinus (yangming area).
Chronic pain.
Influence the circulation of Qi and blood ‐ use the four gates, LI 4 & LV 3 to strongly move the Qi and blood in the body clearing stagnation and alleviating pain.
Promote labor or for retained placenta.

LI 10 (Shoushanli)

Location: 2 cm below LI 11 on the LI 5 to LI 11 line.

Actions and effects:
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 cm below LI 11 on the LI 5 to LI 11 line.

SP 6 (Sanyinjiao)

Location: 3 cm directly above the tip of the medial malleolus on the posterior border of the tibia.


Precautions: no needle in pregnancy

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

Actions and effects:
Tonify Yin and blood, all spleen disorders.
Digestive disorders, sinking or prolapse.
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 cm below SP 9 on line connecting SP 9 and the tip of the medial malleolus.

Point associations:
Xi Cleft point.


Actions and effects:
Xi Cleft point ‐ acute and painful menstrual issues due to blood stagnation ‐ clotting, fibroids, dysmenorrhoea.
Male infertility.

SP 10 (Xuehai)

Location: with knee flexed, 2 cm above the superior medial border of the patella on the bulge of the medial portion of quadriceps femoris (vastus medialis).

Actions and effects:
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 cm lateral to the AML level with CV 3.

Actions and effects:
Excess or cold/deficient disorders of the lower warmer ‐ amenorrhoea, irregular menstruation, qi stagnation/masses.
Running Piglet disorder.

ST36 (Zushanli)

Location: 3 cm 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

Actions and effects:
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 cm 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

Actions and effects:
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 cm superior to qugu. Regulates LR, warms KI, irregular menses.

RN 4 (Guanyuan)

Location: 1.5 cm 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 cm 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, dysmenorrhoea, asthma.

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 cm posterior to Wuchu (UB 5), 1.5 cm 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 cm 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.

Figuras y tablas -
Table 2. Table 2. Summary of the treatment intended for the respective acupuncture points
Comparison 1. Acupuncture around the time of oocyte retrieval versus control (sham, placebo, no acupuncture)

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Live Birth Rate Show forest plot

2

464

Odds Ratio (M‐H, Fixed, 95% CI)

0.87 [0.59, 1.29]

1.1 Acupuncture versus Control

2

464

Odds Ratio (M‐H, Fixed, 95% CI)

0.87 [0.59, 1.29]

2 Ongoing Pregnancy Rate Show forest plot

2

464

Odds Ratio (M‐H, Fixed, 95% CI)

0.86 [0.58, 1.26]

2.1 Acupuncture versus Control

2

464

Odds Ratio (M‐H, Fixed, 95% CI)

0.86 [0.58, 1.26]

3 Clinical Pregnancy Rate Show forest plot

6

912

Odds Ratio (M‐H, Random, 95% CI)

1.12 [0.78, 1.62]

3.1 Acupuncture versus Control

6

912

Odds Ratio (M‐H, Random, 95% CI)

1.12 [0.78, 1.62]

4 Miscarriage rate Show forest plot

4

262

Odds Ratio (M‐H, Fixed, 95% CI)

0.79 [0.42, 1.47]

4.1 Acupuncture versus Control

4

262

Odds Ratio (M‐H, Fixed, 95% CI)

0.79 [0.42, 1.47]

Figuras y tablas -
Comparison 1. Acupuncture around the time of oocyte retrieval versus control (sham, placebo, no acupuncture)
Comparison 2. Acupuncture on and around the day of ET versus control

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Live Birth Show forest plot

8

2505

Odds Ratio (M‐H, Random, 95% CI)

1.22 [0.87, 1.70]

1.1 Acupuncture versus Control (no sham/needling)

3

849

Odds Ratio (M‐H, Random, 95% CI)

1.55 [1.14, 2.12]

1.2 Acupuncture versus Control (sham/needling)

5

1656

Odds Ratio (M‐H, Random, 95% CI)

1.03 [0.67, 1.58]

2 Ongoing pregnancy Show forest plot

10

2807

Odds Ratio (M‐H, Random, 95% CI)

1.10 [0.80, 1.52]

2.1 Acupuncture versus Control (no sham/needling)

4

924

Odds Ratio (M‐H, Random, 95% CI)

1.08 [0.57, 2.07]

2.2 Acupuncture versus Control (sham/needling)

6

1883

Odds Ratio (M‐H, Random, 95% CI)

1.10 [0.74, 1.65]

3 Clinical pregnancy Show forest plot

14

3632

Odds Ratio (M‐H, Random, 95% CI)

1.11 [0.87, 1.42]

3.1 Acupuncture versus Control (no sham/needling)

7

1589

Odds Ratio (M‐H, Random, 95% CI)

1.21 [0.84, 1.73]

3.2 Acupuncture versus Control (sham/needling)

7

2043

Odds Ratio (M‐H, Random, 95% CI)

1.04 [0.74, 1.46]

4 Miscarriage Show forest plot

6

616

Odds Ratio (M‐H, Fixed, 95% CI)

1.10 [0.73, 1.67]

4.1 Acupuncture versus Control (no sham/needling)

2

245

Odds Ratio (M‐H, Fixed, 95% CI)

1.20 [0.57, 2.49]

4.2 Acupuncture versus Control (sham/needling)

4

371

Odds Ratio (M‐H, Fixed, 95% CI)

1.06 [0.64, 1.76]

5 Multiple gestation Show forest plot

2

795

Odds Ratio (M‐H, Fixed, 95% CI)

1.32 [0.74, 2.35]

5.1 Acupuncture versus Control (sham/needling)

2

795

Odds Ratio (M‐H, Fixed, 95% CI)

1.32 [0.74, 2.35]

Figuras y tablas -
Comparison 2. Acupuncture on and around the day of ET versus control