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Robinson Research Institute, University of Adelaide and Fertility SA, Adelaide SA 5000, AustraliaRepromed Auckland, 105 Remuera Road, Auckland 1050, New Zealand
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.
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.
). 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 (
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 (
Effect of acupuncture on the outcome ofin vitro fertilization and intracytoplasmic sperm injection: a randomized, prospective, controlled clinical study.
). 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 (
). 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
Database
Search string
Search limits
Records 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/ Keywords
4187
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”)
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 (
). 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 (
) 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 (
). 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 (
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 (
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 (
Effect of acupuncture on the outcome ofin vitro fertilization and intracytoplasmic sperm injection: a randomized, prospective, controlled clinical study.
Influence of acupuncture on the outcomes ofin vitro fertilization when embryo implantation has failed: a prospective randomized controlled clinical trial.
Effect of transcutaneous electrical acupuncture point stimulation on endometrial receptivity in women undergoing frozen-thawed embryo transfer: a single-blind prospective randomized controlled trial.
Increase of success rate for women undergoing embryo transfer by transcutaneous electrical acupoint stimulation: a prospective randomized placebo-controlled study.
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.
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 (
). 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 (
Influence of acupuncture on the outcomes ofin vitro fertilization when embryo implantation has failed: a prospective randomized controlled clinical trial.
Influence of acupuncture on the outcomes ofin vitro fertilization when embryo implantation has failed: a prospective randomized controlled clinical trial.
Effect of acupuncture on the outcome ofin vitro fertilization and intracytoplasmic sperm injection: a randomized, prospective, controlled clinical study.
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 (
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.
) 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.
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) (
) 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 4Effect of acupuncture versus control on clinical pregnancy.
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) (
), 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) (
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-analysis
Heterogeneity
Comparisons
Risk ratio
95% CI
P-value
I2
P-value
Number of acupuncture treatments (<3 or >3)
21
1.21
1.06
1.38
0.006
65.9
>0.001
Fresh cycle vs frozen cycle
16
1.11
0.94
1.31
0.22
64.1
>0.001
Embryo stage at transfer
14
1.16
0.95
1.41
0.15
69.2
>0.001
Women's age at time of transfer (<38 or >38)
17
1.15
0.97
1.37
0.102
67.8
>0.001
Type of sham (invasive vs non-invasive)
9
1.01
0.86
1.19
0.91
65.4
0.003
Type of protocol (Paulus vs modified)
21
1.15
1.0
1.32
0.041
65.9
>0.001
Timing of treatment (post day of ET vs no further treatment)
21
1.18
1.02
1.36
0.024
65.9
>0.001
Baseline pregnancy rate in control group (under 32% or 32% and over)
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 (
). 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 (
). 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 (
). 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 (
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 (
). 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 (
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 (
), 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 (
). 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 (
). 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 (
). The beneficial effects found when acupuncture was compared with no adjunctive treatment may be explained by previous studies suggesting an improved uterine blood flow (
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
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 (
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 (
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.
Effect of acupuncture on the outcome ofin vitro fertilization and intracytoplasmic sperm injection: a randomized, prospective, controlled clinical study.
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.
Changes in serum cortisol and prolaction associated with acupuncture during controlled ovarian hyperstimulation in women undergoingin vitro fertilization-embryo transfer treatments.
Effect of transcutaneous electrical acupuncture point stimulation on endometrial receptivity in women undergoing frozen-thawed embryo transfer: a single-blind prospective randomized controlled trial.
Influence of acupuncture on the outcomes ofin vitro fertilization when embryo implantation has failed: a prospective randomized controlled clinical trial.
Increase of success rate for women undergoing embryo transfer by transcutaneous electrical acupoint stimulation: a prospective randomized placebo-controlled study.
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.
Article info
Publication history
Published online: January 02, 2019
Accepted:
December 21,
2018
Received in revised form:
September 5,
2018
Received:
August 4,
2018
Declaration: The authors report no financial or commercial conflicts of interest.
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.
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