The effects of acupuncture on rates of clinical pregnancy among women undergoing in vitro fertilization: a systematic review and meta-analysis

Abstract

BACKGROUND Recent systematic reviews of adjuvant acupuncture for IVF have pooled heterogeneous trials, without examining variables that might explain the heterogeneity. The aims of our meta-analysis were to quantify the overall pooled effects of adjuvant acupuncture on IVF clinical pregnancy success rates, and evaluate whether study design-, treatment- and population-related factors influence effect estimates. METHODS We included randomized controlled trials that compared needle acupuncture administered within 1 day of embryo transfer, versus sham acupuncture or no adjuvant treatment. Our primary outcome was clinical pregnancy rates. We obtained from all investigators additional methodological details and outcome data not included in their original publications. We analysed sham-controlled and no adjuvant treatment-controlled trials separately, but since there were no large or significant differences between these two subsets, we pooled all trials for subgroup analyses. We prespecified 11 subgroup variables (5 clinical and 6 methodological) to investigate sources of heterogeneity, using single covariate meta-regressions. RESULTS Sixteen trials (4021 participants) were included in the meta-analyses. There was no statistically significant difference between acupuncture and controls when combining all trials [risk ratio (RR) 1.12, 95% confidence interval (CI), 0.96-1.31; I(2) = 68%; 16 trials; 4021 participants], or when restricting to sham-controlled (RR 1.02, 0.83-1.26; I(2) = 66%; 7 trials; 2044 participants) or no adjuvant treatment-controlled trials (RR 1.22, 0.97-1.52; I(2) = 67%; 9 trials; 1977 participants). The type of control used did not significantly explain the statistical heterogeneity (interaction P = 0.27). Baseline pregnancy rate, measured as the observed rate of clinical pregnancy in the control group of each trial, was a statistically significant effect modifier (interaction P < 0.001), and this covariate explained most of the heterogeneity of the effects of adjuvant acupuncture across all trials (adjusted R(2) = 93%; I(2) residual = 9%). Trials with lower control group rates of clinical pregnancy showed larger effects of adjuvant acupuncture (RR 1.53, 1.28-1.84; 7 trials; 1732 participants) than trials with higher control group rates of clinical pregnancy (RR 0.90, 0.80-1.01; 9 trials; 2289 participants). The asymmetric funnel plot showed a tendency for the intervention effects to be more beneficial in smaller trials. CONCLUSIONS We found no pooled benefit of adjuvant acupuncture for IVF. The subgroup finding of a benefit in trials with lower, but not higher, baseline pregnancy rates (the only statistically significant subgroup finding in our earlier review) has been confirmed in this update, and was not explained by any confounding variables evaluated. However, this baseline pregnancy rate subgroup finding among published trials requires further confirmation and exploration in additional studies because of the multiple subgroup tests conducted, the risk of unidentified confounders, the multiple different factors that determine baseline rates, and the possibility of publication bias.

Keywords: acupuncture; assisted conception; complementary medicine; in vitro fertilization; systematic review.

Figures

Figure 1

Effects of acupuncture on clinical pregnancy, ongoing pregnancy and live birth outcomes. The centres of the squares represent estimates from individual trials, the centres of the quadrilaterals represent pooled estimates and the horizontal lines represent 95% CIs.

Figure 1

Continued.

Figure 2

Meta-regression subgroup analyses for the primary outcome (i.e. clinical pregnancy). The quadrilaterals represent pooled estimates from the trials included in the given subgroup. The estimated regression coefficient from each model was obtained by a weighted least squares meta-regression with RR of pregnancy as the dependent variable, using the modification to the variance of the estimated coefficient suggested by Knapp and Hartung (2003), and supported by Higgins and Thompson (2004). values indicate the proportion of the residual variation that is attributable to between-study heterogeneity. The adjusted R2 values indicate the proportion of between-study variance explained by the covariate. The P-values for test of interaction indicate whether the observed differences in results of trials within a given subgroup are compatible with chance alone. *The So 2010 trial was the only trial that used only one acupuncture treatment session. The Westergaard 2006 trial had two acupuncture treatment arms, one arm received two sessions and the other arm received three, and these arms were grouped separately for this subgroup analysis. †Incomplete outcome data were also prespecified as a methodological subgroup variable, but no trial had a high risk of bias due to incomplete outcome data for the clinical pregnancy outcome. ‡Only the Craig et al. trial was judged to have a co-intervention that was applied unequally across treatment group. Namely, in this trial, which evaluated off-site acupuncture, patients in the acupuncture group only were required to drive to and from the off-site acupuncturist's office both before and after the embryo transfer procedure.

Figure 3

Meta-regression with baseline clinical pregnancy rate as single continuous covariate. Outcome was RR of clinical pregnancy. Circle size represents weight each study was given in the meta-regression analysis. For this meta-regression, the adjusted R2 = 90% and the .

Figure 4

Funnel plot of trials meeting inclusion criteria. The intervention effect estimated from individual trials is plotted on the horizontal scale and a measure of the standard error of the intervention effect is plotted on the vertical axis. The control group success rate is included for each trial on the plot. The Egger test P-value for funnel plot asymmetry is 0.032.

Figure 5

Effects of acupuncture on spontaneous abortion outcome. The centres of the squares represent estimates from individual trials, the centres of the quadrilaterals represent pooled estimates, and the horizontal lines represent 95% CIs.