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Review Article| Volume 38, ISSUE 3, P364-379, March 2019

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Acupuncture performed around the time of embryo transfer: a systematic review and meta-analysis

Published:January 02, 2019DOI:https://doi.org/10.1016/j.rbmo.2018.12.038

      Abstract

      This was a systematic review and meta-analysis to examine the efficacy, effectiveness and safety of acupuncture as an adjunct to embryo transfer compared with controls to improve reproductive outcomes. The primary outcome was clinical pregnancy. Twenty trials and 5130 women were included in the review. The meta-analysis found increased pregnancies (risk ratio [RR] 1.32, 95% confidence interval [CI] 1.07–1.62, 12 trials, 2230 women), live births (RR 1.30, 95% CI 1.00–1.68, 9 trials, 1980 women) and reduced miscarriage (RR 1.43, 95% CI 1.03–1.98, 10 trials, 2042 women) when acupuncture was compared with no adjunctive control. There was significant heterogeneity, but no significant differences between acupuncture and sham controls. Acupuncture may have a significant effect on clinical pregnancy rates, independent of comparator group, when used in women who have had multiple previous IVF cycles, or where there was a low baseline pregnancy rate. The findings suggest acupuncture may be effective when compared with no adjunctive treatment with increased clinical pregnancies, but is not an efficacious treatment when compared with sham controls, although non-specific effects may be active in both acupuncture and sham controls. Future research examining the effects of acupuncture for women with poorer IVF outcomes is warranted.

      Keywords

      Introduction

      Assisted reproductive technology (ART), including IVF, has become widespread for treating infertility [
      • Kupka M.
      • D'Hooghe T.
      • Ferraretti A.
      • de Mouzon J.
      • Goossens V.
      European IVF-Monitoring Consortium (EIM), European Society of Human Reproduction and Embryology (ESHRE)
      Assisted reproductive technology in Europe, 2011: results generated from European registers by ESHRE.
      ]. Today there are over 6 million children that have been conceived through ART (
      • Dyer S.
      • Chambers G.
      • de Mouzon J.
      • Nygren K.
      • Zegers-Hochschild F.
      • Mansour R.
      • Adamson G.
      International Committee for Monitoring Assisted Reproductive Technologies world report: Assisted Reproductive Technology 2008, 2009 and 2010.
      ). Although a well-established treatment, each step of IVF is complex and invasive, and each step carries with it a possibility of failure. IVF is a resource-intensive and costly treatment option for both women and their families, and for public health care expenditure (
      • Chambers G.
      • Sullivan E.
      • Ishihara O.
      • Chapman M.
      • Adamson G.
      The economic impact of assisted reproductive technology: a review of selected developed countries.
      ). Therefore, new therapies that improve reproductive outcomes are highly desirable.
      Women seek information and treatment about complementary health approaches to increase their chances of achieving a pregnancy and live birth (
      • de Lacey S.
      • Smith C.
      • Sanderman E.
      Acupuncture in reproductive medicine: the motivations of infertile women to participate in a randomized controlled trial.
      ,
      • Rayner J.
      • McLachlan H.
      • Forster D.
      • Cramer R.
      Australian women's use of complementary and alternative medicines to enhance fertility: exploring the experiences of women and practitioners.
      ,
      • Rayner J.
      • Willis K.
      • Burgess R.
      Women's use of complementary and alternative medicine for fertility enhancement: a review of the literature.
      ), and also to improve their health, quality of life and to reduce stress whilst undergoing treatment cycles (
      • de Lacey S.
      • Smith C.
      Acupuncture and Infertility treatment: Is there more to the outcome for women than pregnancy?.
      ). Acupuncture has become a frequently used adjunctive treatment prior to and during IVF treatment (
      • Domar A.
      • Conboy L.
      • Denardo-Roney J.
      • Rooney K.
      Lifestyle behaviours in women undergoingin vitro fertilization: prospective study.
      ). In the USA, 30% of a patient cohort engaged in acupuncture prior to IVF treatment and 47% during IVF treatment (
      • Domar A.
      • Conboy L.
      • Denardo-Roney J.
      • Rooney K.
      Lifestyle behaviours in women undergoingin vitro fertilization: prospective study.
      ).
      Acupuncture involves needle insertion and manipulation into specifically chosen acupuncture points located in the subcutaneous tissue. Early trials indicated that a short course of acupuncture administered prior to and immediately following embryo transfer (embryo transfer) may provide benefits in improving reproductive outcomes (
      • Dieterle S.
      • Ying G.
      • Hatzmann W.
      • Neuer A.
      Effect of acupuncture on the outcome ofin vitro fertilization and intracytoplasmic sperm injection: a randomized, prospective, controlled clinical study.
      ,
      • Paulus W.
      • Zhang M.
      • Strehler E.
      • El-Danasouri I.
      • Sterzik K.
      Influence of acupuncture on the pregnancy rate in patients who undergo assisted reproduction therapy.
      ,
      • Smith C.
      • Coyle M.
      • Norman R.
      Influence of acupuncture stimulation on pregnancy rates for women undergoing embryo transfer.
      ). Delivery of this short treatment became common in clinical practice (
      • Bovey M.
      • Lorenc A.
      • Robinson N.
      Extent of acupuncture practice for infertility in the United Kingdom: experiences and perceptions of the practitioners.
      ,
      • Smith C.
      • Armour M.
      • Betts D.
      Treatment of women's reproductive health conditions by Australian and New Zealand acupuncturists.
      ). The number of published randomized clinical trials (RCT) has increased over time, and evidence of the effects from acupuncture compared with controls has become less clear. Systematic reviews have found no statistically significant difference in clinical pregnancy or live birth rates when compared with a control (
      • Cheong Y.
      • Dix S.
      • Hung Yu Ng E.
      • Ledger W.
      • Farquhar C.
      Acupuncture and assisted reproductive technology.
      ,
      • Manheimer E.
      • van der Windt D.
      • Cheng K.
      • Stafford K.
      • Liu J.
      • Tierney J.
      • Bouter L.
      The effects of acupuncture on rates of clinical pregnancy among women undergoingin vitro fertilization: a systematic review and meta-analysis.
      ). This review incorporates new evidence from recently published RCT. The objective of this review was to examine the efficacy, effectiveness and safety of acupuncture as an adjunct to embryo transfer compared with controls or no adjuvant treatment to improve clinical pregnancies live births among women undergoing IVF.

      Materials and methods

      We included RCT that compared acupuncture with sham acupuncture controls or no adjuvant treatment. We considered only RCT where acupuncture was administered during an IVF cycle and included acupuncture treatment administered within 1 day of embryo transfer and with the objective of improving assisting conception and IVF success rates. Trials administered at other stages of the IVF cycle were excluded due to a different treatment rationale. We excluded non-randomized studies, and crossover trials (due to the time-limited intervention). We included women undergoing intracytoplasmic injection (ICSI) or IVF and planning to undergo a fresh or frozen embryo transfer. The intervention included acupuncture involving the needling of meridian points based on the theory of traditional Chinese medicine. We included manual or electro-acupuncture stimulation and excluded dry needling (treatment of myofascial trigger points), transcutaneous electrical nerve stimulation and laser stimulation of acupuncture points.
      The primary outcome was clinical pregnancy, with secondary outcomes including live birth, ongoing pregnancy, miscarriage and adverse events. Trials needed to report on one of the following outcomes to be included: clinical pregnancy (i.e. presence of gestational sac) or a viable pregnancy (evidence of a fetal heartbeat), confirmed by transvaginal ultrasound, ongoing pregnancy (i.e. pregnancy beyond 12 weeks of gestation, as confirmed by fetal heart activity on ultrasound), or live birth.
      The following databases were searched: PubMed, Embase and the Cochrane Register of Controlled Clinical Trials (CENTRAL). We also searched the proceedings of the annual conferences on ART for 2001–2018: American Society for Reproductive Medicine; European Society of Human Reproduction and Embryology; and Pacific Coast Reproductive Society. We also searched for previous systematic reviews on this topic and reviewed their reference lists. We searched using the keywords: acupuncture, acupuncture treatment, acupuncture therapy, electro-acupuncture, auricular acupuncture, acup* and reproductive techniques, assisted reproductive technology, IVF, ICSI, embryo transfer, embryo implantation, egg collection, combined with RCT (Table 1). The search was restricted to English language texts.
      Table 1Database search string and number of records found
      DatabaseSearch stringSearch limitsRecords found
      CENTRAL (Cochrane Register of Controlled Clinical Trials)acupuncture OR “acupuncture treatment” OR “acupuncture therapy” OR electro-acupuncture OR “auricular acupuncture” OR “acup and reproductive techniques” OR “assisted reproductive technology” OR IVF OR ICSI OR “embryo transfer” OR “embryo implantation” OR “egg collection” AND “randomised controlled trial”Title / abstract/ Keywords4187
      PubMed((acupuncture OR “acupuncture treatment” OR “acupuncture therapy” OR electro-acupuncture OR “auricular acupuncture” OR “acup* and reproductive techniques” OR “assisted reproductive technology” OR IVF OR ICSI OR “embryo transfer” OR “embryo implantation” OR “egg collection”)) AND “randomised controlled trial”Title / abstract

      English
      229
      Embase((acupuncture or “acupuncture treatment” or “acupuncture therapy” or electro-acupuncture or “auricular acupuncture” or “acup* and reproductive techniques” or “assisted reproductive technology” or IVF or ICSI or “embryo transfer” or “embryo implantation” or “egg collection”) and “randomised controlled trial”)Abstract

      English
      233
      Total4649
      Conference proceedings and reference trackingnana32
      Grand total4681
      na = not available.
      The titles and abstracts were screened by one author (ZS), and independently verified by a second author (CS). Full text versions of the papers were retrieved by ZS. Any disagreement as to which studies to include were resolved by a third author (MA). For each study two authors (CS, MA, HT, ZS) independently extracted data and independently assessed the methodological quality of the trials using the Cochrane risk of bias tool (
      • Higgins J.
      • Altman D.
      • Gotzsche P.
      • Jüni P.
      • Moher D.
      • Oxman A.
      The Cochrane Collaboration's tool for assessing risk of bias in randomized controlled trials.
      ). Data extraction included details of the study design, intervention and control, characteristics of participants, geographical setting and study outcomes. Authors who had published abstracts were contacted for an update on publication status. When no response was received, relevant data was extracted from a previously published review (
      • Manheimer E.
      • van der Windt D.
      • Cheng K.
      • Stafford K.
      • Liu J.
      • Tierney J.
      • Bouter L.
      The effects of acupuncture on rates of clinical pregnancy among women undergoingin vitro fertilization: a systematic review and meta-analysis.
      ). Two trials (
      • Smith C.
      • Coyle M.
      • Norman R.
      Influence of acupuncture stimulation on pregnancy rates for women undergoing embryo transfer.
      ,
      • Smith C.
      • de Lacey S.
      • Chapman M.
      • Ratcliffe J.
      • Norman R.
      • Johnson N.
      • Fahey P.
      Effect of acupuncture versus sham acupuncture on live births among women undergoingin vitro fertilization: a randomized clinical trial.
      ) undertaken by three authors (CS, RN, NJ) of this review were independently assessed by authors MA, AT and ZS. The quality of the acupuncture delivered during the trial was assessed by two authors using the NICMAN scale (
      • Smith C.
      • Zaslawski C.
      • Cochrane S.
      • Zhu X.
      • Zheng Z.
      • Loyeung B.
      • Fahey P.
      Reliability of the NICMAN Scale: an instrument to assess the quality of acupuncture administered in clinical trials.
      ). The NICMAN scale comprises 11 domains related to study design, rationale of the intervention, specific criteria relating to the acupuncture characteristics including needling stimulation, whether manually or using electro-stimulation, duration and frequency of treatment and practitioner training. Scores were allocated as follows: 2 points for yes, 0 for no, 1 for unclear or partial agreement. The responses to the individual items were summed to create an overall summary score representing the quality of the acupuncture administered. Data were entered into RevMan software (

      The Nordic Cochrane Centre, and The Cochrane Collaboration. (2014). Review Manager 5 (RevMan 5) Version 5.3 [Computer program]. Copenhagen.

      ).

      Data analysis

      Meta-analyses were undertaken using risk ratios (RR) with 95% confidence intervals (CI) reported. The unit of analysis was the participant randomized. In addition, for miscarriage outcomes we also reported as per pregnancy. We included randomized women who commenced an IVF cycle but did not complete treatment due to a cancelled cycle. We excluded data for women who withdrew consent for their data to be used, or for whom data on clinical outcomes was missing. Multiple live births were counted as one live birth event. The sham-controlled and no adjuvant treatment-controlled trials were analysed separately. A random-effects meta-analysis was applied based on the expected heterogeneity within the acupuncture treatment protocols and were conducted using Comprehensive Meta-Analysis software (Version 3). Random-effects meta-analysis was undertaken when there were a minimum of three studies per subgroup. We formally tested heterogeneity by examining the P-value of the I2 statistic. If at least 10 trials were available for a meta-analysis, we assessed for the likelihood of publication bias by constructing funnel plots. Publication bias and meta-regression were carried out using Comprehensive Meta-Analysis software (version 3).

      Subgroup analyses

      We planned a number of subgroup analyses on characteristics that may influence the effects of acupuncture on clinical pregnancy, both participant and intervention related. The relationship between continuous moderators and effect size estimates were explored with meta-regression analyses, with categorical moderators explored through subgroup analysis. Categorical moderators included: fresh or frozen IVF cycle, fresh or frozen embryo transfer, embryo stage at transfer (blastocyst, cleavage or mixed), women's age, number of acupuncture treatments, standardized Paulus protocol or modified treatment protocol, timing of treatments during IVF cycle, type of sham (invasive versus non-invasive), location of sham points (on verum points versus non-acupuncture points) and acupuncture administered on-site at the IVF clinic or off-site. Continuous moderators included acupuncture quality using the NICMAN scale score and previous number of IVF cycles.
      The number of acupuncture treatments were combined into two groups (<3 and >3) to allow for subgroup analysis as meta-regression was not appropriate due to the small range of treatment numbers. Similarly, due to the small age range of women, age was combined into two categories (<38 years and >38 years). We also examined the effect of the control group as a baseline estimate of the pregnancy rate, a clinical characteristic previously found to benefit trials with lower baseline pregnancy rates (
      • Manheimer E.
      • Zhang G.
      • Udoff L.
      • Haramati A.
      • Langenberg P.
      • Berman B.
      • Bouter L.
      Effects of acupuncture on rates of pregnancy and live birth among women undergoingin vitro fertilization: systematic review and meta-analysis.
      ,
      • Manheimer E.
      • van der Windt D.
      • Cheng K.
      • Stafford K.
      • Liu J.
      • Tierney J.
      • Bouter L.
      The effects of acupuncture on rates of clinical pregnancy among women undergoingin vitro fertilization: a systematic review and meta-analysis.
      ). In these two reviews the variable was categorized as higher (32% or greater, the European pregnancy rates per embryo transfer) or lower (
      • Calhaz-Jorge C.
      • De Geyter C.
      • Kupka M.
      • de Mouzon J.
      • Goossens V.
      European IVF-monitoring Consortium, European Society of Human Reproduction and Embryology (ESHRE)
      Assisted reproductive technology in Europe, 2013: results generated from European registers by ESHRE.
      ). Planned comparisons of location of sham points and acupuncture treatment location (on-site versus off-site) could not be included due to fewer than three studies being present in one of the comparison groups. Separate analysis of fresh or frozen trials in the meta-regression was not possible due to an insufficient number of frozen trials to make any meaningful comparisons.

      Results

      A total of 4681 potential references were identified. After 727 duplicates were removed, the studies were examined by title, abstract and full text for eligibility (Figure 1). Of the 37 studies examined by the full text, 20 trials met the inclusion criteria for this review (
      • Andersen D.
      • Løssl K.
      • Nyboe Andersen A.
      • Fürbringer J.
      • Bach H.
      • Simonsen J.
      • Larsen E.
      Acupuncture on the day of embryo transfer: a randomized controlled trial of 635 patients.
      ,
      • Arnoldi M.
      • Diaferia D.
      • Cprbucci M.
      • Lauretis L.
      The role of acupuncture in patients at unfavourable reproductive prognosis in IVF.
      ,
      • Craig L.
      • Rubin L.
      • Peck J.
      • Anderson M.
      • Marshall L.
      • Soules M.
      Acupuncture performed before and after embryo transfer: a randomized controlled trial.
      ,
      • Dieterle S.
      • Ying G.
      • Hatzmann W.
      • Neuer A.
      Effect of acupuncture on the outcome ofin vitro fertilization and intracytoplasmic sperm injection: a randomized, prospective, controlled clinical study.
      ,
      • Domar A.
      • Meshay I.
      • Kelliher J.
      • Alper M.
      • Douglas Powers R.
      The impact of acupuncture onin vitro fertilization outcome.
      ,
      • Feliciani F.
      • Paesano C.
      • Pellizzaro E.
      • Magli M.
      • Gianaroli L.
      The role of acupuncture in ART: preliminary results of an ongoing prospective randomized study.
      ,
      • Gillerman K.
      • Rehman N.
      • Dilgil M.
      • Homburg R.
      The impact of acupuncture on IVF success rates: a randomized controlled trial.
      ,
      • Madaschi C.
      • Braga D.
      • Figueira Rde C.
      • Iaconelli A.
      • Borges E.
      Effect of acupuncture on assisted reproduction treatment outcomes.
      ,
      • Morin S.
      • Frattatelli J.
      • Franasiak J.
      • Juneau C.
      • Scott R.
      Laser acupuncture before and after embryo transfer Improvesin vitro Fertilization outcomes: a four-armed randomized controlled trial.
      ,
      • Moy I.
      • Milad M.
      • Barnes R.
      • Confino E.
      • Kazer R.
      • Zhang X.
      Randomized controlled trial: effects of acupuncture on pregnancy rates in women undergoingin vitro fertilization.
      ,
      • Omodei U.
      • Piccioni G.
      • Tombesi S.
      • Dordoni D.
      • Fallo L.
      • Ghilardi F.
      Effect of acupuncture on rates of pregnancy among women undergoingin vitro fertilization.
      ,
      • Paulus W.
      • Zhang M.
      • Strehler E.
      • El-Danasouri I.
      • Sterzik K.
      Influence of acupuncture on the pregnancy rate in patients who undergo assisted reproduction therapy.
      ,
      • Paulus W.
      • Zhang M.
      • Strehler E.
      • Seybold B.
      • Sterzik K.
      Placebo-controlled trial of acupuncture effects in assisted reproduction therapy.
      ,
      • Rashidi B.
      • Tehrani E.
      • Hamedani N.
      • Pirzadeh L.
      Effects of acupuncture on the outcome ofin vitro fertilization and intracytoplasmic sperm injection in women with polycystic ovarian syndrome.
      ,
      • Smith C.
      • Coyle M.
      • Norman R.
      Influence of acupuncture stimulation on pregnancy rates for women undergoing embryo transfer.
      ,
      • Smith C.
      • de Lacey S.
      • Chapman M.
      • Ratcliffe J.
      • Norman R.
      • Johnson N.
      • Fahey P.
      Effect of acupuncture versus sham acupuncture on live births among women undergoingin vitro fertilization: a randomized clinical trial.
      ,
      • So E.
      • Ng E.
      • Wong Y.
      • Lau E.
      • Yeung W.
      • Ho P.
      A randomized double blind comparison of real and placebo acupuncture in IVF treatment.
      ,
      • So E.
      • Ng E.
      • Wong Y.
      • Yeung W.
      • Ho P.
      Acupuncture for frozen-thawed embryo transfer cycles: a double-blind randomized controlled trial.
      ,
      • Villahermosa D.
      • Santos L.
      • Nogueira M.
      • Vilarino F.
      • Barbosa C.
      Influence of acupuncture on the outcomes ofin vitro fertilization when embryo implantation has failed: a prospective randomized controlled clinical trial.
      ,
      • Westergaard L.
      • Mao Q.
      • 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, randomized trial.
      ).
      Figure 1
      Figure 1PRISMA flow chart of included studies.
      Seventeen studies were excluded. Seven studies did not meet the criteria of an RCT (
      • Emmons S.
      • Patton P.
      Acupuncture treatment for infertile women undergoing intracytoplasmic sperm injection.
      ,
      • Ke R.
      • Xu M.
      • Kutteh W.
      Comparison of outcomes in women who accepted or rejected acupuncture treatment duringin vitro fertilization and embryo transfer (IVF).
      ,
      • Pastuszek E.
      • Liss J.
      • Kulwikowska P.
      • Wiśniewska J.
      • Łukaszuk .
      Using propensity score matching to evaluate the effect of complementary medicine on clinical and embryologic outcomes of in vitro fertilization.
      ,
      • Porat-Katz A.
      • Eldar-Geva T.
      • Kahane A.
      • Paltiel O.
      Using propensity score matching to evaluate the effect of complementary medicine on clinical and embryologic outcomes ofin vitro fertilization.
      ,
      • Teshima D.
      • Nune s.C.
      • Chedid-grieco S.
      The effect of acupuncture in assisted reproduction techniques.
      ,
      • Wang W.
      • Check J.
      • Liss J.
      • Choe J.
      A matched controlled study to evaluate the efficacy of acupuncture for improving pregnancy rates followingin vitro fertilization-embryo transfer.
      ,
      • Youran D.
      • Bopp B.
      • Colver R.
      • Reuter L.
      • Adaniya G.
      Acupuncture performed before and after embryo transfer improves pregnancy rates.
      ) and in three studies acupuncture was not performed within a day of embryo transfer (
      • Cui W.
      • Li J.
      • Sun W.
      • Wen J.
      Effect of electroacupuncture on oocyte quality and pregnancy for patients with PCOS undergoingin vitro fertilization and embryo transfer.
      ,
      • Stener-Victorin E.
      • Waldenström U.
      • Nilsson L.
      • Wikland M.
      • Janson P.
      A prospective randomized study of electro-acupuncture versus alfentanil as anaesthesia during oocyte aspiration in in-vitro fertilization.
      ,
      • Stener-Victorin E.
      • Waldenström U.
      • Wikland M.
      • Nilsson L.
      • Hägglund L.
      • Lundeberg T.
      Electro-acupuncture as a peroperative analgesic method and its effects on implantation rate and neuropeptide Y concentrations in follicular fluid.
      ). Two studies were not based on traditional or electro-acupuncture (
      • Shuai Z.
      • Lian F
      • L P.
      • Yang W.
      Effect of transcutaneous electrical acupuncture point stimulation on endometrial receptivity in women undergoing frozen-thawed embryo transfer: a single-blind prospective randomized controlled trial.
      ,
      • Zhang R.
      • Feng X.
      • Guan Q.
      • Cui W.
      • Zheng Y.
      • Sun W.
      Increase of success rate for women undergoing embryo transfer by transcutaneous electrical acupoint stimulation: a prospective randomized placebo-controlled study.
      ), one study was a crossover RCT (
      • Quintero R.
      • Centre G.
      A randomized, controlled, double-blind, crossover study evaluating acupuncture as an adjunct to IVF.
      ), two studies were duplicate publications of an included trial (
      • Benson M.
      • Elkind-Hirsch K.
      • Theall A.
      • Fong K.
      • Hogan R.
      • Scott R.
      Impact of acupuncture before and after embryo transfer on the outcome ofin vitro fertilization cycles: A prospective single blind randomized study.
      ,
      • Fratterelli J.
      • Leondires M.
      • Fong K.
      • Theall A.
      • Locatelli S.
      • Scott R.
      Laser acupuncture before and after embryo transfer improves art delivery rates: results of a prospective randomized double-blinded placebo controlled five-armed trial involving 1000 patients.
      ), one study was ongoing at the time of reporting interim results (
      • Udoff L.
      • Zhang G.
      • Patwardhan S.
      • Wei Z.
      • McClamrock H.
      The effect of acupuncture on outcomes in in-vitro fertilization (IVF).
      ) and there was a significant imbalance between the treatment and control groups in one study (
      • Udoff L.
      • McClamrock H.
      • Chen K.
      • Zhang G.
      The effect of acupuncture on pregnancy outcomes in in-vitro fertilization (IVF): a randomized controlled trial.
      ).

      Trial characteristics

      Twenty RCT were included. Characteristics of the studies are shown in Table 2. Four studies were undertaken in the USA, three each in Italy and Germany. Two studies were each undertaken in Australia, Brazil, China, and Denmark. Single studies were undertaken in Iran and the UK. Twenty trials reported on clinical pregnancy rates, 13 trials reported on ongoing pregnancy rates, 14 trials reported on live birth rates. Five trials reported on adverse events (
      • Morin S.
      • Frattatelli J.
      • Franasiak J.
      • Juneau C.
      • Scott R.
      Laser acupuncture before and after embryo transfer Improvesin vitro Fertilization outcomes: a four-armed randomized controlled trial.
      ,
      • Moy I.
      • Milad M.
      • Barnes R.
      • Confino E.
      • Kazer R.
      • Zhang X.
      Randomized controlled trial: effects of acupuncture on pregnancy rates in women undergoingin vitro fertilization.
      ,
      • Smith C.
      • de Lacey S.
      • Chapman M.
      • Ratcliffe J.
      • Norman R.
      • Johnson N.
      • Fahey P.
      Effect of acupuncture versus sham acupuncture on live births among women undergoingin vitro fertilization: a randomized clinical trial.
      ,
      • So E.
      • Ng E.
      • Wong Y.
      • Lau E.
      • Yeung W.
      • Ho P.
      A randomized double blind comparison of real and placebo acupuncture in IVF treatment.
      ,
      • So E.
      • Ng E.
      • Wong Y.
      • Yeung W.
      • Ho P.
      Acupuncture for frozen-thawed embryo transfer cycles: a double-blind randomized controlled trial.
      ). Sample sizes ranged from 46 to 848 women, and studies were reported between 2002 and 2018. Fourteen trials recruited women undergoing a fresh cycle, one trial restricted eligibility to women undergoing a frozen cycle and one trial recruited women doing a mixture of fresh or frozen cycles, and four trials did not report this characteristic. Eleven trials undertook a cleavage-day embryo transfer, five trials reported a mixture of cleavage and blastocyst embryo transfer and four trials did not report this characteristic. One trial recruited women with polycystic ovary syndrome (PCOS) only (
      • Rashidi B.
      • Tehrani E.
      • Hamedani N.
      • Pirzadeh L.
      Effects of acupuncture on the outcome ofin vitro fertilization and intracytoplasmic sperm injection in women with polycystic ovarian syndrome.
      ).
      Table 2Characteristics of studies included in this review
      StudyCountryNumberOutcomesAcupunctureControlFresh or frozen cycleStage of embryo development
      AndersenDenmark635Pregnancy, ongoing, live birth30 min pre and post ET
      Modified Paulus protocol.
      Non-invasive sham controlFreshCleavage
      ArnoldiItaly204PregnancyThree sessions: (i) day 5 of ovarian stimulation; (ii) 30 min before ET; (3) immediately after ET
      Modified Paulus protocol.
      No adjunctive treatmentNot reportedCleavage
      CraigUSA113Pregnancy, live birthOff site. First within 1–2 h before ET; second within 1–2 h after ET
      Modified Paulus protocol.
      No adjunctive treatmentFreshBlastocyst and cleavage
      DieterleGermany225Pregnancy, ongoing pregnancy, live birthTwo sessions: first immediately after ET; second 3 days after ET
      Modified Paulus protocol.
      Invasive sham control
      Needles but into areas away from ‘true points’ or points that were not associated with fertility.
      FreshCleavage
      DomarUSA146PregnancyTwo sessions: first 25 min before ET; second immediately after ETLying quietly for 25 minFreshNot reported
      FelicianiItaly46Pregnancy, ongoing pregnancy, live birthThree sessions: first 5–7 days before egg retrieval; second 2 to 3 days before oocyte retrieval; third within 1 h after ET
      Modified Paulus protocol.
      No adjunctive treatmentFreshBlastocyst and cleavage
      GillermanUK157Pregnancy, live birthThree sessions: first between days 6 and 8 of ovarian stimulation; second 25 min before ET; second immediately after ETNo adjunctive treatmentNot reportedNot reported
      VillahermosaBrazil84Clinical pregnancyFive sessions; on 1st and 7th day of ovarian stimulation, day before ovarian induction and the day after transferInvasive sham
      Needles but into areas away from ‘true points’ or points that were not associated with fertility.
      control and no adjunctive treatment
      FreshCleavage
      MadaschiBrazil416Pregnancy, ongoing pregnancy, live birthTwo sessions: first 25 min before ET; second immediately after ETNo adjunctive treatmentNot reportedCleavage
      Morin
      843 women randomized to four-arm study, data extracted on two groups, acupuncture vs no adjunctive control (n = 210).
      USA843Pregnancy, live birthTwo sessions: first 25 min before ET; second immediately after ETNo adjunctive treatmentFresh and frozenBlastocyst and cleavage
      MoyUSA161Pregnancy, live birthTwo sessions: first 25 min before ET; second immediately after ETInvasive sham control
      Needles but into areas away from ‘true points’ or points that were not associated with fertility.
      FreshCleavage
      OmodeiItaly168Pregnancy, ongoing pregnancy, live birthTwo sessions: first 25 min before ET; second immediately after ET
      Modified Paulus protocol.
      No adjunctive treatmentNot reportedNot reported
      PaulusGermany160Pregnancy, ongoing pregnancy, live birthTwo sessions: first 25 min before ET; second immediately after ETNo adjunctive treatmentFreshCleavage
      PaulusGermany200Pregnancy, ongoing pregnancy, live birthTwo sessions: first 25 min before ET; second immediately after ETNon-invasive sham controlFreshNot reported
      RashidiIran62PregnancyFive sessions, day 21 of previous cycle, first day of ovarian stimulation, 2 days before oocyte retrieval, two on the day of ET
      Modified Paulus protocol.
      No adjunctive treatmentFreshCleavage
      SmithAustralia228Pregnancy, ongoing pregnancyThree sessions: first between day 9 of ovarian stimulation; second 25 min before ET; second immediately after ET
      Modified Paulus protocol.
      Non-invasive sham controlFreshBlastocyst and cleavage
      Smith
      39 missing or women withdrew consent for data to be used.
      Australia848Pregnancy, live birthThree sessions: first between days 6 and 8 of ovarian stimulation; second 25 min before ET; second immediately after ET
      Modified Paulus protocol.
      Non-invasive sham controlFreshBlastocyst and cleavage
      SoHong Kong/China370Pregnancy, ongoing pregnancy, live birthTwo sessions: first 25 min before ET; second immediately after ETNon-invasive sham controlFreshCleavage
      SoHong Kong/China226Pregnancy, ongoing pregnancy, live birthOne session immediately after ET
      Modified Paulus protocol.
      Non-invasive sham controlFrozenCleavage
      Westergaard
      27 women withdrew consent or treatment cancelled.
      Denmark300Pregnancy, ongoing pregnancyTwo sessions: first 25 min before ET; second immediately after ET
      Modified Paulus protocol.
      No adjunctive treatmentFreshCleavage
      ET = embryo transfer
      a Modified Paulus protocol.
      b Needles but into areas away from ‘true points’ or points that were not associated with fertility.
      c 843 women randomized to four-arm study, data extracted on two groups, acupuncture vs no adjunctive control (n = 210).
      d 39 missing or women withdrew consent for data to be used.
      e 27 women withdrew consent or treatment cancelled.
      Twelve trials used a no adjunctive treatment control (
      • Arnoldi M.
      • Diaferia D.
      • Cprbucci M.
      • Lauretis L.
      The role of acupuncture in patients at unfavourable reproductive prognosis in IVF.
      ,
      • Craig L.
      • Rubin L.
      • Peck J.
      • Anderson M.
      • Marshall L.
      • Soules M.
      Acupuncture performed before and after embryo transfer: a randomized controlled trial.
      ,
      • Domar A.
      • Meshay I.
      • Kelliher J.
      • Alper M.
      • Douglas Powers R.
      The impact of acupuncture onin vitro fertilization outcome.
      ,
      • Feliciani F.
      • Paesano C.
      • Pellizzaro E.
      • Magli M.
      • Gianaroli L.
      The role of acupuncture in ART: preliminary results of an ongoing prospective randomized study.
      ,
      • Gillerman K.
      • Rehman N.
      • Dilgil M.
      • Homburg R.
      The impact of acupuncture on IVF success rates: a randomized controlled trial.
      ,
      • Madaschi C.
      • Braga D.
      • Figueira Rde C.
      • Iaconelli A.
      • Borges E.
      Effect of acupuncture on assisted reproduction treatment outcomes.
      ,
      • Morin S.
      • Frattatelli J.
      • Franasiak J.
      • Juneau C.
      • Scott R.
      Laser acupuncture before and after embryo transfer Improvesin vitro Fertilization outcomes: a four-armed randomized controlled trial.
      ,
      • Omodei U.
      • Piccioni G.
      • Tombesi S.
      • Dordoni D.
      • Fallo L.
      • Ghilardi F.
      Effect of acupuncture on rates of pregnancy among women undergoingin vitro fertilization.
      ,
      • Paulus W.
      • Zhang M.
      • Strehler E.
      • El-Danasouri I.
      • Sterzik K.
      Influence of acupuncture on the pregnancy rate in patients who undergo assisted reproduction therapy.
      ,
      • Rashidi B.
      • Tehrani E.
      • Hamedani N.
      • Pirzadeh L.
      Effects of acupuncture on the outcome ofin vitro fertilization and intracytoplasmic sperm injection in women with polycystic ovarian syndrome.
      ,
      • Villahermosa D.
      • Santos L.
      • Nogueira M.
      • Vilarino F.
      • Barbosa C.
      Influence of acupuncture on the outcomes ofin vitro fertilization when embryo implantation has failed: a prospective randomized controlled clinical trial.
      ,
      • Westergaard L.
      • Mao Q.
      • 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, randomized trial.
      ). One trial included three arms: acupuncture, a sham and no adjunctive control (
      • Villahermosa D.
      • Santos L.
      • Nogueira M.
      • Vilarino F.
      • Barbosa C.
      Influence of acupuncture on the outcomes ofin vitro fertilization when embryo implantation has failed: a prospective randomized controlled clinical trial.
      ). A sham control was used in nine trials (
      • Andersen D.
      • Løssl K.
      • Nyboe Andersen A.
      • Fürbringer J.
      • Bach H.
      • Simonsen J.
      • Larsen E.
      Acupuncture on the day of embryo transfer: a randomized controlled trial of 635 patients.
      ,
      • Dieterle S.
      • Ying G.
      • Hatzmann W.
      • Neuer A.
      Effect of acupuncture on the outcome ofin vitro fertilization and intracytoplasmic sperm injection: a randomized, prospective, controlled clinical study.
      ,
      • Moy I.
      • Milad M.
      • Barnes R.
      • Confino E.
      • Kazer R.
      • Zhang X.
      Randomized controlled trial: effects of acupuncture on pregnancy rates in women undergoingin vitro fertilization.
      ,
      • Paulus W.
      • Zhang M.
      • Strehler E.
      • Seybold B.
      • Sterzik K.
      Placebo-controlled trial of acupuncture effects in assisted reproduction therapy.
      ,
      • Smith C.
      • Coyle M.
      • Norman R.
      Influence of acupuncture stimulation on pregnancy rates for women undergoing embryo transfer.
      ,
      • Smith C.
      • de Lacey S.
      • Chapman M.
      • Ratcliffe J.
      • Norman R.
      • Johnson N.
      • Fahey P.
      Effect of acupuncture versus sham acupuncture on live births among women undergoingin vitro fertilization: a randomized clinical trial.
      ,
      • So E.
      • Ng E.
      • Wong Y.
      • Lau E.
      • Yeung W.
      • Ho P.
      A randomized double blind comparison of real and placebo acupuncture in IVF treatment.
      ,
      • So E.
      • Ng E.
      • Wong Y.
      • Yeung W.
      • Ho P.
      Acupuncture for frozen-thawed embryo transfer cycles: a double-blind randomized controlled trial.
      ,
      • Villahermosa D.
      • Santos L.
      • Nogueira M.
      • Vilarino F.
      • Barbosa C.
      Influence of acupuncture on the outcomes ofin vitro fertilization when embryo implantation has failed: a prospective randomized controlled clinical trial.
      ). Three sham control trials inserted needles but into areas away from verum points or at verum points not associated with fertility (Table 3). Six sham controls used non-invasive (non-penetrating) sham needles. Two trials placed these sham needles on sham points, and four trials placed the sham device on verum points. Twelve trials administered two treatments immediately before and after embryo transfer, five trials administered two treatments on the day of embryo transfer, and either additional treatment during the time of ovarian stimulation (four studies) and/or in the luteal phase (three studies). Seven trials administered the standardized Paulus acupuncture protocol (
      • Paulus W.
      • Zhang M.
      • Strehler E.
      • El-Danasouri I.
      • Sterzik K.
      Influence of acupuncture on the pregnancy rate in patients who undergo assisted reproduction therapy.
      ).
      Table 3Characteristics of acupuncture and sham control interventions
      StudyNICMAN score (0–23)Number of treatmentsNumber of stimulation phase treatmentsPre- and post-ET intervention onlyOn-site ET treatmentPaulus protocol or modified protocolPost-ET treatmentInvasive sham controlSham points
      Andersen1720YesYesModifiedNoNoNo
      Arnold1231NoYesModifiedNonana
      Craig2120YesNoModifiedNonana
      Dieterle1320NoYesModifiedYesYesNon-fertility points
      Domar1320YesYesPaulusNonana
      Feliciani1232NoYesModifiedNonana
      Gillerman22991NoYesModifiedNonana
      Madashi1920YesYesPaulusNonana
      Morin1620YesYesPaulusNonana
      Moy1620YesYesPaulusNoYesNo
      Paulus1520YesYesPaulusNonana
      Paulus1520YesYesPaulusNoNoNo
      Omoedi620YesYesModifiedNonana
      Rashidi1552NoYesModifiedNonana
      So2020YesYesPaulusNoNoNo
      So201NoYesModifiedYesNoNo
      Smith2231NoYesModifiedNoNoYes
      Smith2331NoYesModifiedNoNoYes
      Villahermosa1542NoYesModifiedNoYesNo
      Westergaarde1620YesYesModifiedYesnana
      ET = embryo transfer; na = not applicable.

      Methodological quality of the trials

      The risk of bias assessment is presented in Figure 2. The most frequent risk of bias was from inadequate blinding of study participants, with eight of the 20 studies at a low risk of bias. Overall the risk of any selection bias at randomization appears low.
      The NICMAN scores (out of 23) ranged from 6 (
      • Omodei U.
      • Piccioni G.
      • Tombesi S.
      • Dordoni D.
      • Fallo L.
      • Ghilardi F.
      Effect of acupuncture on rates of pregnancy among women undergoingin vitro fertilization.
      ) to 23 (
      • Smith C.
      • de Lacey S.
      • Chapman M.
      • Ratcliffe J.
      • Norman R.
      • Johnson N.
      • Fahey P.
      Effect of acupuncture versus sham acupuncture on live births among women undergoingin vitro fertilization: a randomized clinical trial.
      ) (Table 2). The majority of trials scored 16. Only one trial (
      • Smith C.
      • de Lacey S.
      • Chapman M.
      • Ratcliffe J.
      • Norman R.
      • Johnson N.
      • Fahey P.
      Effect of acupuncture versus sham acupuncture on live births among women undergoingin vitro fertilization: a randomized clinical trial.
      ) scored full points on each of the domains (Figure 3). Overall the general methodological domains related to participants, interventions, comparison group, outcomes and study design all scored high. The domains related to acupuncture were mixed. Both justification for point selection and the number of treatments used were adequate in the majority of trials. The lowest-scoring domains related to the reporting of practitioner experience, acupuncture point location and the use of differential diagnosis.

      Effect of the interventions

      There was no statistical difference between acupuncture and sham control for clinical pregnancy, ongoing pregnancy, live birth and miscarriage (Figures 4 to 7). There was evidence of statistically significant increased pregnancies when acupuncture was compared with no adjunctive treatment (RR 1.32, 95% CI 1.07–1.62, 12 trials, 2230 women). This positive effect was seen with ongoing pregnancies (RR 1.42, 95% CI 1.17–1.73, 6 trials, 1144 women), live births (RR 1.30, 95% 1.00–1.68, 9 trials, 1980 women) and reduced miscarriage (RR 1.43, 95% CI 1.03–1.98, 10 trials, 2042 women). The benefit for miscarriage was not significant when expressed as per pregnancy (RR 1.08, 95% CI 0.79–1.46). However, there was substantial heterogeneity for clinical pregnancy (I2 = 61%) and live birth (I2 = 63%) outcomes. The funnel plot for the outcome of clinical pregnancy suggests some asymmetry (Figure 8). Applying the Begg and Mazumdar test for publication bias (one-tailed), no evidence of publication bias was found in the sham control group (P= 0.038) (
      • Begg C.
      • Mazumdar M.
      Operating characteristics of a rank correlation test for publication bias.
      ). The subsequent Duval and Tweedie's trim and fill analysis (
      • Duval S.
      • Tweedie R.
      Trim and fill: A simple funnel-plot-based method of testing and adjusting for publication bias in meta-analysis.
      ) for sham controls showed no significant change in the primary outcome of clinical pregnancy when adjusting for potential effects of publication bias (RR 1.04, 95% CI 0.86–1.28).
      Figure 4
      Figure 4Effect of acupuncture versus control on clinical pregnancy.
      Figure 5
      Figure 5Effect of acupuncture versus control on ongoing pregnancy.
      Figure 6
      Figure 6Effect of acupuncture versus control on live birth.
      Figure 7
      Figure 7Effect of acupuncture versus control on miscarriage.
      Six trials reported on adverse effects. Trials reported nausea, dizziness, tiredness, drowsiness, headache, chest pain, pain/itching at needle site, feeling relaxed, calm and energized. There was a significant increase in pain/itching at the needle site from acupuncture compared with the non-invasive sham control (RR 1.51, 95% CI 1.24–2.00, 3 trials, 1204 women) (Figure 9). One trial found increased bruising for the acupuncture group compared with the non-invasive sham control (RR 3.82, 95% CI 1.28–11.39, 608 women) (
      • Smith C.
      • de Lacey S.
      • Chapman M.
      • Ratcliffe J.
      • Norman R.
      • Johnson N.
      • Fahey P.
      Effect of acupuncture versus sham acupuncture on live births among women undergoingin vitro fertilization: a randomized clinical trial.
      ), and one trial found increased relaxation in the non-invasive sham control (RR 0.76, 95% CI 0.61–0.95, 228 women). One study found women receiving acupuncture reported their sessions to be more tiring (P< 0.05), and that they felt more fearful (P< 0.001) and experienced greater achiness (P< .018) (
      • Moy I.
      • Milad M.
      • Barnes R.
      • Confino E.
      • Kazer R.
      • Zhang X.
      Randomized controlled trial: effects of acupuncture on pregnancy rates in women undergoingin vitro fertilization.
      ). No side effects were reported by women in one trial (
      • Morin S.
      • Frattatelli J.
      • Franasiak J.
      • Juneau C.
      • Scott R.
      Laser acupuncture before and after embryo transfer Improvesin vitro Fertilization outcomes: a four-armed randomized controlled trial.
      ).
      Figure 9
      Figure 9Effect of acupuncture versus control on side effects/adverse effects.

      Subgroup analysis

      In studies where more than three treatments were performed, the clinical pregnancy rate significantly improved (N = 8 / n = 1595, RR 1.50, 95% CI 1.18–1.90, P=0.001) while in studies where fewer than three treatments were performed, clinical pregnancy rate did not improve (N = 13 / n= 3535, RR 1.09, 95% CI 0.93–1.29, P> 0.05) (Table 4). Studies that used a modified Paulus treatment protocol significantly improved clinical pregnancy rate (N= 14 / n= 3254, RR 1.34, 95% CI 1.07–1.67, P= 0.009), while those using the standard Paulus protocol did not (N= 7 / n= 1876, RR 1.05, 95% CI 0.88–1.24, P> 0.05). The timing of the treatment delivery was a significant factor in clinical pregnancy rate. Studies that delivered treatments post the day of embryo transfer showed no benefit to clinical pregnancy rates (N= 3 / n= 743, RR 1.36, 95% CI 0.76–2.45, P> 0.05) while those that did not deliver any treatments post the day of embryo transfer did (N= 18 / n= 4387, RR 1.17, 95% CI 1.007–1.36, P= 0.04). The baseline pregnancy rate was a significant modifier of the outcome. Studies where the baseline pregnancy rate was below 32% had a significantly greater chance of clinical pregnancy, regardless of the control group (N= 11 / n= 2394, RR 1.60, 95% CI 1.36–1.88, P< 0.001) compared with those studies with a baseline pregnancy rate of 32% or greater (N= 10 / n= 2736, RR 0.95, 95% CI 0.84–1.07, P> 0.05). The type of sham used, type of cycle (fresh, frozen or mixed), maternal age or stage of embryo transfer were not significant modifiers of clinical pregnancy rate.
      Table 4Subgroup analysis on clinical pregnancy rate
      Meta-analysisHeterogeneity
      ComparisonsRisk ratio95% CIP-valueI2P-value
      Number of acupuncture treatments (<3 or >3)211.211.061.380.00665.9>0.001
      Fresh cycle vs frozen cycle161.110.941.310.2264.1>0.001
      Embryo stage at transfer141.160.951.410.1569.2>0.001
      Women's age at time of transfer (<38 or >38)171.150.971.370.10267.8>0.001
      Type of sham (invasive vs non-invasive)91.010.861.190.9165.40.003
      Type of protocol (Paulus vs modified)211.151.01.320.04165.9>0.001
      Timing of treatment (post day of ET vs no further treatment)211.181.021.360.02465.9>0.001
      Baseline pregnancy rate in control group (under 32% or 32% and over)211.141.041.260.00765.9>0.001
      The meta-regression analysis found that a higher NICMAN score was related to less chance of showing a difference between active and comparator groups for clinical pregnancy rate (N = 21 / n = 5130, B = –0.042, SE = 0.0213, Z = –1.98, P = 0.047). The type of comparison group was expected to be a major factor as studies with higher NICMAN scores were more likely to use sham controls. The addition of the type of comparator as a factor in the meta-regression meant the NICMAN score no longer had a significant association with clinical pregnancy rate (N = 21 / n = 5130, B = –0.031, SE = 0.0251, Z = –1.25, P> 0.05). The number of previous IVF cycles was associated with a greater clinical pregnancy rate, with studies having a greater proportion of women undergoing their second or greater IVF cycle having a significant association with clinical pregnancy rate (N= 6 / n= 2498, B = 0.0150, SE = 0.007, Z = 2.19, P = 0.029).

      Discussion

      The search strategy identified 20 trials and 5130 women for inclusion in this review. A benefit from trials of acupuncture when administered within 1 day of embryo transfer increased clinical pregnancy, ongoing pregnancy and live births when compared with no adjunctive treatment. This was a clinically significant 30% increased chance of an improved reproductive outcome, however there was substantial heterogeneity. There was no evidence of an effect when acupuncture was compared with a sham control. There was evidence of fewer miscarriages when acupuncture was compared with no adjunctive treatment, but not when expressed as per pregnancy. Acupuncture-related side effects were reported in a small number of trials and are similar to those reported in trials in the general population (
      • Witt C.
      • Pach D.
      • Brinkhaus B.
      • Wruck K.
      • Tag B.
      • Mank S.
      Safety of acupuncture: results of a prospective observational study with 229,230 patients and introduction of a medical information and consent form.
      ), and during pregnancy (
      • Park J.
      • Sohn Y.
      • White A.
      • Lee H.
      The safety of acupuncture during pregnancy: a systematic review.
      ). Factors were explored that may influence the effect of acupuncture on reproductive outcomes using post hoc subgroup analysis. Three or more treatments and the use of a modified treatment protocol were significant effect modifiers on clinical pregnancy. The timing of treatment was also a significant modifier, with treatments post the day of embryo transfer showing no benefit on clinical pregnancy. Acupuncture appears to have a significant effect on clinical pregnancy rate, independent of comparator group, when used in women who have had multiple previous IVF cycles, or where there was a low baseline pregnancy rate.
      These findings differ from the other systematic reviews published in 2013 and 2014, which found no difference in clinical outcome when pooling data from all trials of acupuncture around the time of embryo transfer (
      • Cheong Y.
      • Dix S.
      • Hung Yu Ng E.
      • Ledger W.
      • Farquhar C.
      Acupuncture and assisted reproductive technology.
      ,
      • Manheimer E.
      • van der Windt D.
      • Cheng K.
      • Stafford K.
      • Liu J.
      • Tierney J.
      • Bouter L.
      The effects of acupuncture on rates of clinical pregnancy among women undergoingin vitro fertilization: a systematic review and meta-analysis.
      ). The 2014 review, however, found a benefit from acupuncture when performed during ovarian stimulation plus on the day of transfer, and when performed after embryo transfer and during the implantation phase (
      • Shen C.
      • Wu M.
      • Shu D.
      • Zhao X.
      • Gao Y.
      The role of acupuncture inin vitro fertilization: a systematic review and meta-analysis.
      ). The most recent systematic review found an improved pregnancy outcome from acupuncture when all trials were pooled, however there was substantial heterogeneity. Previous subgroup analyses have found higher pregnancy rates from acupuncture trials administered during ovarian stimulation (
      • Qian Y.
      • Xia X.
      • Ochin H.
      • Huang C.
      • Gao C.
      • Gao L.
      • Meng Y.
      Therapeutic effect of acupuncture on the outcomes ofin vitro fertilization: a systematic review and meta-analysis.
      ), and an increased number of treatment sessions performed prior to and including the day of embryo transfer (
      • Hullender Rubin L.
      • Opsahl M.
      • Wiemer K.
      • Mist S.
      • Caughey A.
      Impact of whole systems traditional Chinese medicine onin vitro fertilization outcomes.
      ,
      • Magarelli P.
      • Crdennda D.
      • Cohen M.
      Changes in serum cortisol and prolaction associated with acupuncture during controlled ovarian hyperstimulation in women undergoingin vitro fertilization-embryo transfer treatments.
      ). The finding that acupuncture has a stronger effect on clinical pregnancy rates where there was a low baseline pregnancy rate has been reported in earlier systematic reviews (
      • Manheimer E.
      • Zhang G.
      • Udoff L.
      • Haramati A.
      • Langenberg P.
      • Berman B.
      • Bouter L.
      Effects of acupuncture on rates of pregnancy and live birth among women undergoingin vitro fertilization: systematic review and meta-analysis.
      ,
      • Manheimer E.
      • van der Windt D.
      • Cheng K.
      • Stafford K.
      • Liu J.
      • Tierney J.
      • Bouter L.
      The effects of acupuncture on rates of clinical pregnancy among women undergoingin vitro fertilization: a systematic review and meta-analysis.
      ). The reasons for this finding are proposed to relate to differing country-specific regulations regarding the number of embryos transferred, differences in the inclusion criteria between trials, including the characteristics of women who may have a poor prognosis of IVF success (
      • Manheimer E.
      • van der Windt D.
      • Cheng K.
      • Stafford K.
      • Liu J.
      • Tierney J.
      • Bouter L.
      The effects of acupuncture on rates of clinical pregnancy among women undergoingin vitro fertilization: a systematic review and meta-analysis.
      ).
      To date, techniques intended to ensure optimal embryos for transfer (most notably preimplantation genetic screening [PGS], designed to select chromosomally normal embryos) and to ensure optimal endometrial receptivity (such as the endometrial receptivity array, ERA) have not featured within RCT assessing the effectiveness of acupuncture for boosting the success of IVF. Future trials should specify to what extent these interventions have been used within the population under study and future meta-analyses may benefit from the use of sensitivity analyses where these interventions have (or have not) been used in included RCT.
      Sham controls are used to control for acupuncture needling components such as acupuncture point location, needle insertion and stimulation, and the number of needles. The review found no effect when acupuncture was compared with a sham control. These findings may be partially explained by data from a meta-analysis that suggests that these devices may not be inert (
      • Zhang C.
      • Tan H.
      • Zhang G.
      • Zhang A.
      • Xu e.C.
      • Xie Y.
      Placebo devices as effective control methods in acupuncture clinical trials: a systematic review.
      ), and that some activity may arise when applied, including sensory and psycho-social cues. The overall effects from acupuncture are described as needling, specific non-needling components (palpation, education, self-care and diagnosis), and non-specific components including time, attention, credibility and expectation (
      • Langevin H.
      • Wayne P.
      • MacPherson H.
      • Schyner R.
      • Milley R.
      • Napdow V.
      • Hammerschlag R.
      Paradoxes in acupuncture research: strategies for moving forward.
      ). IVF is a stressful experience (
      • Lemmens G.
      • Vervaeke M.
      • Enzlin P.
      • Bakelants E.
      • Vanderschueren D.
      • D'Hooghe T.
      • Demyttenaere K.
      Coping with infertility: A body–mind group intervention program for infertile couples.
      ) and the effects of acupuncture on psycho-social outcomes have been examined and found to have some benefits (
      • de Lacey S.
      • Smith C.
      • Paterson C.
      Building resilience: A preliminary exploration of women's perceptions of the use of acupuncture as an adjunct toIn vitro Fertilization.
      ,
      • Domar A.
      • Meshay I.
      • Kelliher J.
      • Alper M.
      • Douglas Powers R.
      The impact of acupuncture onin vitro fertilization outcome.
      ). In an RCT of acupuncture performed on the day of embryo transfer, no difference in reproductive outcomes was found for both acupuncture and sham acupuncture groups, however reduced anxiety levels were reported in both acupuncture and sham acupuncture groups (
      • So E.
      • Ng E.
      • Wong Y.
      • Yeung W.
      • Ho P.
      Acupuncture for frozen-thawed embryo transfer cycles: a double-blind randomized controlled trial.
      ). The characteristic non-needling components and non-specific effects may therefore explain why acupuncture treatments, whether verum or sham acupuncture, exert a significant anxiolytic effect during IVF (
      • Cummings M.
      Acupuncture and IVF.
      ). The beneficial effects found when acupuncture was compared with no adjunctive treatment may be explained by previous studies suggesting an improved uterine blood flow (
      • Stener-Victorin E.
      • Waldenström U.
      • Andersson S.
      • Wikland M.
      Reduction of blood flow impedance in the uterine arteries of infertile women with electro-acupuncture.
      ), modulation of endogenous opioid beta-endorphin (
      • Chang R.
      • Chung P.
      • Rosenwaks Z.
      Role of acupuncture in the treatment of female infertility.
      ) and various cytokines (
      • Zijlstra F.
      • van den Berg-de Lange I.
      • Huygen F.
      • Klein J.
      Anti-inflammatory actions of acupuncture.
      ).
      A limitation of this review is the significant heterogeneity found across studies. Although a random-effects model was applied, these differences remained. A further limitation was that non-English language databases were not searched and so studies may have been missed. A number of early studies remain as published abstracts. This impacted on the scoring of studies using the NICMAN scale and a quality assessment. However, we followed up with primary authors, and authors of the
      • Manheimer E.
      • van der Windt D.
      • Cheng K.
      • Stafford K.
      • Liu J.
      • Tierney J.
      • Bouter L.
      The effects of acupuncture on rates of clinical pregnancy among women undergoingin vitro fertilization: a systematic review and meta-analysis.
      review to clarify details and outcomes of this study. This enabled us to ensure we did not double count participants arising from the same trial in our review, unlike one published review (
      • Shen C.
      • Wu M.
      • Shu D.
      • Zhao X.
      • Gao Y.
      The role of acupuncture inin vitro fertilization: a systematic review and meta-analysis.
      ).
      With increased use of acupuncture by women undertaking IVF it is important that women remain informed, with up-to-date evidence about the risks and benefits from acupuncture when used as an adjunct to IVF. Women should understand that acupuncture has not been shown to be superior to a sham control, however there are potentially significant benefits when compared with no adjunctive treatment, and that acupuncture remains a low-risk intervention (
      • Witt C.
      • Pach D.
      • Brinkhaus B.
      • Wruck K.
      • Tag B.
      • Mank S.
      Safety of acupuncture: results of a prospective observational study with 229,230 patients and introduction of a medical information and consent form.
      ).
      Evidence suggests acupuncture may be effective when compared with no adjunctive treatment, with increased clinical pregnancies and live births, but is not an efficacious treatment when compared with sham controls. Future research should focus on different dosing acupuncture regimens, and exploration of the components of acupuncture that are contributing to improved reproductive outcomes. Increased understanding of these components may have broader application to the care and treatment modalities provided to women undergoing IVF. Further exploration of the effects of acupuncture for women with poorer IVF outcomes is warranted.

      Acknowledgements

      The authors would like to thank Dr Eric Manheimer, the primary author of a previous systematic review, for sharing information on studies requiring follow-up with authors. We also thank Dr Joseph Firth for his assistance with the meta-regression.

      References

        • Andersen D.
        • Løssl K.
        • Nyboe Andersen A.
        • Fürbringer J.
        • Bach H.
        • Simonsen J.
        • Larsen E.
        Acupuncture on the day of embryo transfer: a randomized controlled trial of 635 patients.
        Reprod. Biomed. Online. 2010; 21: 366-372
        • Arnoldi M.
        • Diaferia D.
        • Cprbucci M.
        • Lauretis L.
        The role of acupuncture in patients at unfavourable reproductive prognosis in IVF.
        Hum. Reprod. 2010; 25: i257
        • Begg C.
        • Mazumdar M.
        Operating characteristics of a rank correlation test for publication bias.
        Biometrics. 1994; 50: 1088-1101
        • Benson M.
        • Elkind-Hirsch K.
        • Theall A.
        • Fong K.
        • Hogan R.
        • Scott R.
        Impact of acupuncture before and after embryo transfer on the outcome ofin vitro fertilization cycles: A prospective single blind randomized study.
        Fertil. Steril. 2006; 86: S135
        • Bovey M.
        • Lorenc A.
        • Robinson N.
        Extent of acupuncture practice for infertility in the United Kingdom: experiences and perceptions of the practitioners.
        Fertil. Steril. 2010; 94: 2569-2573
        • Chambers G.
        • Sullivan E.
        • Ishihara O.
        • Chapman M.
        • Adamson G.
        The economic impact of assisted reproductive technology: a review of selected developed countries.
        Fertil. Steril. 2009; 91: 2281-2294
        • Chang R.
        • Chung P.
        • Rosenwaks Z.
        Role of acupuncture in the treatment of female infertility.
        Fertil. Steril. 2002; 78: 1149-1153
        • Cheong Y.
        • Dix S.
        • Hung Yu Ng E.
        • Ledger W.
        • Farquhar C.
        Acupuncture and assisted reproductive technology.
        Cochrane Database Sys. Rev. 2013; 7CD006920
        • Craig L.
        • Rubin L.
        • Peck J.
        • Anderson M.
        • Marshall L.
        • Soules M.
        Acupuncture performed before and after embryo transfer: a randomized controlled trial.
        J. Reprod. Med. 2014; 59: 313-320
        • Cui W.
        • Li J.
        • Sun W.
        • Wen J.
        Effect of electroacupuncture on oocyte quality and pregnancy for patients with PCOS undergoingin vitro fertilization and embryo transfer.
        Zhongguo Zhen Jiu. 2011; 8: 687-691
        • Cummings M.
        Acupuncture and IVF.
        Acupunct Med. 2018; (18 June 2018)
        • de Lacey S.
        • Smith C.
        Acupuncture and Infertility treatment: Is there more to the outcome for women than pregnancy?.
        Med. Acupunct. 2013; 25: 195-199
        • de Lacey S.
        • Smith C.
        • Paterson C.
        Building resilience: A preliminary exploration of women's perceptions of the use of acupuncture as an adjunct toIn vitro Fertilization.
        BMC Complement Altern Med. 2009; 9
        • de Lacey S.
        • Smith C.
        • Sanderman E.
        Acupuncture in reproductive medicine: the motivations of infertile women to participate in a randomized controlled trial.
        J. Psychosom. Obstet. Gynaecol. 2017; 39: 112-120
        • Dieterle S.
        • Ying G.
        • Hatzmann W.
        • Neuer A.
        Effect of acupuncture on the outcome ofin vitro fertilization and intracytoplasmic sperm injection: a randomized, prospective, controlled clinical study.
        Fertil. Steril. 2006; 85: 1347-1351
        • Domar A.
        • Conboy L.
        • Denardo-Roney J.
        • Rooney K.
        Lifestyle behaviours in women undergoingin vitro fertilization: prospective study.
        Fertil. Steril. 2012; 97: 697-701
        • Domar A.
        • Meshay I.
        • Kelliher J.
        • Alper M.
        • Douglas Powers R.
        The impact of acupuncture onin vitro fertilization outcome.
        Fertil. Steril. 2009; 91: 723-726
        • Duval S.
        • Tweedie R.
        Trim and fill: A simple funnel-plot-based method of testing and adjusting for publication bias in meta-analysis.
        Biometrics. 2000; 95: 89-98
        • Dyer S.
        • Chambers G.
        • de Mouzon J.
        • Nygren K.
        • Zegers-Hochschild F.
        • Mansour R.
        • Adamson G.
        International Committee for Monitoring Assisted Reproductive Technologies world report: Assisted Reproductive Technology 2008, 2009 and 2010.
        Hum. Reprod. 2016; 31: 1588-1609
        • Emmons S.
        • Patton P.
        Acupuncture treatment for infertile women undergoing intracytoplasmic sperm injection.
        Med. Acupuncture. 2000; 12: 18-20
        • Calhaz-Jorge C.
        • De Geyter C.
        • Kupka M.
        • de Mouzon J.
        • Goossens V.
        • European IVF-monitoring Consortium, European Society of Human Reproduction and Embryology (ESHRE)
        Assisted reproductive technology in Europe, 2013: results generated from European registers by ESHRE.
        Hum. Reprod. 2017; 32: 1957-1973
        • Kupka M.
        • D'Hooghe T.
        • Ferraretti A.
        • de Mouzon J.
        • Goossens V.
        • European IVF-Monitoring Consortium (EIM), European Society of Human Reproduction and Embryology (ESHRE)
        Assisted reproductive technology in Europe, 2011: results generated from European registers by ESHRE.
        Hum. Reprod. 2016; 31: 2333-2348
        • Feliciani F.
        • Paesano C.
        • Pellizzaro E.
        • Magli M.
        • Gianaroli L.
        The role of acupuncture in ART: preliminary results of an ongoing prospective randomized study.
        Hum. Reprod. 2011; 26 (Abstract P281)
        • Fratterelli J.
        • Leondires M.
        • Fong K.
        • Theall A.
        • Locatelli S.
        • Scott R.
        Laser acupuncture before and after embryo transfer improves art delivery rates: results of a prospective randomized double-blinded placebo controlled five-armed trial involving 1000 patients.
        Fertil. Steril. 2011; 90: S267
        • Gillerman K.
        • Rehman N.
        • Dilgil M.
        • Homburg R.
        The impact of acupuncture on IVF success rates: a randomized controlled trial.
        Hum. Reprod. 2016; 31: i89
        • Higgins J.
        • Altman D.
        • Gotzsche P.
        • Jüni P.
        • Moher D.
        • Oxman A.
        The Cochrane Collaboration's tool for assessing risk of bias in randomized controlled trials.
        BMJ. 2011; 343: d5928
        • Hullender Rubin L.
        • Opsahl M.
        • Wiemer K.
        • Mist S.
        • Caughey A.
        Impact of whole systems traditional Chinese medicine onin vitro fertilization outcomes.
        Reprod. Biomed. Online. 2015; 30: 602-612
        • Ke R.
        • Xu M.
        • Kutteh W.
        Comparison of outcomes in women who accepted or rejected acupuncture treatment duringin vitro fertilization and embryo transfer (IVF).
        Fertil. Steril. 2011; 96: S267
        • Langevin H.
        • Wayne P.
        • MacPherson H.
        • Schyner R.
        • Milley R.
        • Napdow V.
        • Hammerschlag R.
        Paradoxes in acupuncture research: strategies for moving forward.
        Evid Based Complement Alternat Med. 2011; 2011180805
        • Lemmens G.
        • Vervaeke M.
        • Enzlin P.
        • Bakelants E.
        • Vanderschueren D.
        • D'Hooghe T.
        • Demyttenaere K.
        Coping with infertility: A body–mind group intervention program for infertile couples.
        Hum. Reprod. 2004; 19: 1917-1923
        • Madaschi C.
        • Braga D.
        • Figueira Rde C.
        • Iaconelli A.
        • Borges E.
        Effect of acupuncture on assisted reproduction treatment outcomes.
        Acupunct Med. 2010; 28: 180-184
        • Magarelli P.
        • Crdennda D.
        • Cohen M.
        Changes in serum cortisol and prolaction associated with acupuncture during controlled ovarian hyperstimulation in women undergoingin vitro fertilization-embryo transfer treatments.
        Fertil. Steril. 2009; 92
        • Manheimer E.
        • van der Windt D.
        • Cheng K.
        • Stafford K.
        • Liu J.
        • Tierney J.
        • Bouter L.
        The effects of acupuncture on rates of clinical pregnancy among women undergoingin vitro fertilization: a systematic review and meta-analysis.
        Hum. Reprod. Update. 2013; 19: 696-713
        • Manheimer E.
        • Zhang G.
        • Udoff L.
        • Haramati A.
        • Langenberg P.
        • Berman B.
        • Bouter L.
        Effects of acupuncture on rates of pregnancy and live birth among women undergoingin vitro fertilization: systematic review and meta-analysis.
        BMJ. 2008; 336: 545-549
        • Morin S.
        • Frattatelli J.
        • Franasiak J.
        • Juneau C.
        • Scott R.
        Laser acupuncture before and after embryo transfer Improvesin vitro Fertilization outcomes: a four-armed randomized controlled trial.
        Med Acupunct. 2017; 29: 56-65
        • Moy I.
        • Milad M.
        • Barnes R.
        • Confino E.
        • Kazer R.
        • Zhang X.
        Randomized controlled trial: effects of acupuncture on pregnancy rates in women undergoingin vitro fertilization.
        Fertil. Steril. 2011; 95: 583-587
        • Omodei U.
        • Piccioni G.
        • Tombesi S.
        • Dordoni D.
        • Fallo L.
        • Ghilardi F.
        Effect of acupuncture on rates of pregnancy among women undergoingin vitro fertilization.
        Fertil. Steril. 2010; 94: P-266
        • Park J.
        • Sohn Y.
        • White A.
        • Lee H.
        The safety of acupuncture during pregnancy: a systematic review.
        Acupunct Med. 2014; 32: 257-266
        • Pastuszek E.
        • Liss J.
        • Kulwikowska P.
        • Wiśniewska J.
        • Łukaszuk .
        Using propensity score matching to evaluate the effect of complementary medicine on clinical and embryologic outcomes of in vitro fertilization.
        Polish Annals of Medicine. 2013; 20: 117-123
        • Paulus W.
        • Zhang M.
        • Strehler E.
        • El-Danasouri I.
        • Sterzik K.
        Influence of acupuncture on the pregnancy rate in patients who undergo assisted reproduction therapy.
        Fertil. Steril. 2002; 77: 721-724
        • Paulus W.
        • Zhang M.
        • Strehler E.
        • Seybold B.
        • Sterzik K.
        Placebo-controlled trial of acupuncture effects in assisted reproduction therapy.
        Hum. Reprod. 2003; 18: 18-19
        • Porat-Katz A.
        • Eldar-Geva T.
        • Kahane A.
        • Paltiel O.
        Using propensity score matching to evaluate the effect of complementary medicine on clinical and embryologic outcomes ofin vitro fertilization.
        Int. J. Gynaecol. Obstet. 2017; 138: 212-218
        • Qian Y.
        • Xia X.
        • Ochin H.
        • Huang C.
        • Gao C.
        • Gao L.
        • Meng Y.
        Therapeutic effect of acupuncture on the outcomes ofin vitro fertilization: a systematic review and meta-analysis.
        Arch. Gynecol. Obstet. 2017; 295: 543-558
        • Quintero R.
        • Centre G.
        A randomized, controlled, double-blind, crossover study evaluating acupuncture as an adjunct to IVF.
        Fertil. Steril. 2004; 81: 11-12
        • Rashidi B.
        • Tehrani E.
        • Hamedani N.
        • Pirzadeh L.
        Effects of acupuncture on the outcome ofin vitro fertilization and intracytoplasmic sperm injection in women with polycystic ovarian syndrome.
        Acupunct Med. 2013; 31: 151-156
        • Rayner J.
        • McLachlan H.
        • Forster D.
        • Cramer R.
        Australian women's use of complementary and alternative medicines to enhance fertility: exploring the experiences of women and practitioners.
        BMC Complement Altern Med. 2009; 9
        • Rayner J.
        • Willis K.
        • Burgess R.
        Women's use of complementary and alternative medicine for fertility enhancement: a review of the literature.
        J Altern Complement Med. 2011; 17: 685-690
        • Shen C.
        • Wu M.
        • Shu D.
        • Zhao X.
        • Gao Y.
        The role of acupuncture inin vitro fertilization: a systematic review and meta-analysis.
        Gynecol. Obstet. Invest. 2015; 79: 1-12
        • Shuai Z.
        • Lian F
        • L P.
        • Yang W.
        Effect of transcutaneous electrical acupuncture point stimulation on endometrial receptivity in women undergoing frozen-thawed embryo transfer: a single-blind prospective randomized controlled trial.
        Acupunct Med. 2014; 33: 9-15
        • Smith C.
        • Armour M.
        • Betts D.
        Treatment of women's reproductive health conditions by Australian and New Zealand acupuncturists.
        Complement Ther Med. 2014; 22: 710-714
        • Smith C.
        • Coyle M.
        • Norman R.
        Influence of acupuncture stimulation on pregnancy rates for women undergoing embryo transfer.
        Fertil. Steril. 2006; 85: 1352-1358
        • Smith C.
        • de Lacey S.
        • Chapman M.
        • Ratcliffe J.
        • Norman R.
        • Johnson N.
        • Fahey P.
        Effect of acupuncture versus sham acupuncture on live births among women undergoingin vitro fertilization: a randomized clinical trial.
        JAMA. 2018; 319: 1990-1998
        • Smith C.
        • Zaslawski C.
        • Cochrane S.
        • Zhu X.
        • Zheng Z.
        • Loyeung B.
        • Fahey P.
        Reliability of the NICMAN Scale: an instrument to assess the quality of acupuncture administered in clinical trials.
        Evid Based Complement Alternat Med. 2017; 5694083https://doi.org/10.1155/2017/5694083
        • So E.
        • Ng E.
        • Wong Y.
        • Lau E.
        • Yeung W.
        • Ho P.
        A randomized double blind comparison of real and placebo acupuncture in IVF treatment.
        Hum. Reprod. 2009; 24: 341-348
        • So E.
        • Ng E.
        • Wong Y.
        • Yeung W.
        • Ho P.
        Acupuncture for frozen-thawed embryo transfer cycles: a double-blind randomized controlled trial.
        Reprod. Biomed. Online. 2010; 20: 814-821
        • Stener-Victorin E.
        • Waldenström U.
        • Andersson S.
        • Wikland M.
        Reduction of blood flow impedance in the uterine arteries of infertile women with electro-acupuncture.
        Hum. Reprod. 1996; 11: 1314-1317
        • Stener-Victorin E.
        • Waldenström U.
        • Nilsson L.
        • Wikland M.
        • Janson P.
        A prospective randomized study of electro-acupuncture versus alfentanil as anaesthesia during oocyte aspiration in in-vitro fertilization.
        Hum. Reprod. 1999; 14: 2480-2484
        • Stener-Victorin E.
        • Waldenström U.
        • Wikland M.
        • Nilsson L.
        • Hägglund L.
        • Lundeberg T.
        Electro-acupuncture as a peroperative analgesic method and its effects on implantation rate and neuropeptide Y concentrations in follicular fluid.
        Hum. Reprod. 2003; 18: 1454-1460
        • Teshima D.
        • Nune s.C.
        • Chedid-grieco S.
        The effect of acupuncture in assisted reproduction techniques.
        Fertil. Steril. 2007; 88: S329-S330
      1. The Nordic Cochrane Centre, and The Cochrane Collaboration. (2014). Review Manager 5 (RevMan 5) Version 5.3 [Computer program]. Copenhagen.

        • Udoff L.
        • McClamrock H.
        • Chen K.
        • Zhang G.
        The effect of acupuncture on pregnancy outcomes in in-vitro fertilization (IVF): a randomized controlled trial.
        Fertil. Steril. 2014; 102: e333
        • Udoff L.
        • Zhang G.
        • Patwardhan S.
        • Wei Z.
        • McClamrock H.
        The effect of acupuncture on outcomes in in-vitro fertilization (IVF).
        Fertil. Steril. 2006; 86: S145
        • Villahermosa D.
        • Santos L.
        • Nogueira M.
        • Vilarino F.
        • Barbosa C.
        Influence of acupuncture on the outcomes ofin vitro fertilization when embryo implantation has failed: a prospective randomized controlled clinical trial.
        Acupunct. Med. 2013; 31: 157-161
        • Wang W.
        • Check J.
        • Liss J.
        • Choe J.
        A matched controlled study to evaluate the efficacy of acupuncture for improving pregnancy rates followingin vitro fertilization-embryo transfer.
        Clin. Exp. Obstet. Gynecol. 2007; 34: 137-138
        • Westergaard L.
        • Mao Q.
        • 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, randomized trial.
        Fertil. Steril. 2006; 85: 1341-1346
        • Witt C.
        • Pach D.
        • Brinkhaus B.
        • Wruck K.
        • Tag B.
        • Mank S.
        Safety of acupuncture: results of a prospective observational study with 229,230 patients and introduction of a medical information and consent form.
        Forsch Komplementmed. 2009; 16: 91-97
        • Youran D.
        • Bopp B.
        • Colver R.
        • Reuter L.
        • Adaniya G.
        Acupuncture performed before and after embryo transfer improves pregnancy rates.
        Fertil. Steril. 2008; 90: S240-S241
        • Zhang C.
        • Tan H.
        • Zhang G.
        • Zhang A.
        • Xu e.C.
        • Xie Y.
        Placebo devices as effective control methods in acupuncture clinical trials: a systematic review.
        PLoS. One. 2015; 10e0140825
        • Zhang R.
        • Feng X.
        • Guan Q.
        • Cui W.
        • Zheng Y.
        • Sun W.
        Increase of success rate for women undergoing embryo transfer by transcutaneous electrical acupoint stimulation: a prospective randomized placebo-controlled study.
        Fertil. Steril. 2011; 96: 912-916
        • Zijlstra F.
        • van den Berg-de Lange I.
        • Huygen F.
        • Klein J.
        Anti-inflammatory actions of acupuncture.
        Mediators. Inflamm. 2003; 12: 56-69

      Biography

      Professor Caroline Smith is based at NICM Health Research Institute, Western Sydney University, and leads the Healthy Women research theme and a team of postdoctoral researchers and higher degree candidates. Caroline is a clinical researcher with extensive experience with the conduct of multicentre randomized controlled trials and systematic reviews.
      Key message
      Acupuncture may be effective when compared to no adjunctive treatment with increasing clinical pregnancies and live births, but is not an efficacious treatment when compared with sham controls.