Figure 1 shows details of the selection process. Seven randomised controlled trials with a total of 1366 participants met inclusion criteria (table).w1-w7 All trials were published in English since 2002, and conducted in four different Western countries. Four were published as full reportsw2 w4 w6 w7 and three as abstracts,w1 w3 w5 in two of the leading reproductive medicine journals. We obtained unpublished methodological information for all seven and unpublished outcome data on live births for three.w2 w4 w5
Fig 1 Flow of studies through selection process
Characteristics of included trials in meta-analysis of studies on acupuncture and in vitro fertilisation
All seven trials used a pragmatic design,17
including typical clinical populations and using typical interventions before and after randomisation. All included a broad selection of women undergoing in vitro fertilisation, with a wide range of ages, diagnostic categories of infertility, durations of infertility, and numbers of previous treatment cycles. The only difference in the inclusion criteria was that two trialsw4 w5
included only women with good quality embryos whereas the five others included women with embryos of varying quality. All trials reported use of intracytoplasmic sperm injection for some women.w1-w7
The timing of the acupuncture sessions relative to embryo transfer differed somewhat among trials (table). In all trials, however, women received acupuncture immediately before or immediately after the embryo transfer.
In all trials, the acupuncture protocol and selection of acupuncture points was designed for the sole purpose of improving rates of pregnancy. All trials used a fixed selection of acupuncture points for all patients for the sessions before and after embryo transfer. The fixed selection of points for these sessions was similar in all but one trial,w2 and the points selected were largely based on the points selected in the first published trial that evaluated acupuncture as an adjuvant to embryo transfer.w4 Three trials also included one extra acupuncture session, in addition to the sessions before and after the embryo transfer.w2 w6 w7 Six trials used ear acupuncture as a supplement to body acupuncture,w1-w6 and one of these stimulated the true and sham ear acupuncture points using a Chinese herb rather than a needle.w2
In all the trials the acupuncture sessions lasted 25-30 minutes. Five trials reported that the “de qi” needling sensation was sought,w2 w4-w7 whereas the two others did not report on de qi.w1 w3 No trial used electro-acupuncture.
For all trials, there were no significant differences between the randomised groups in the mean numbers of embryos transferred.
Methodological quality of included studies
The trials generally had high internal validity, in terms of randomisation procedures (table) and follow-up of participants. For all trials but two,w2 w3
investigators confirmed no losses to follow-up (which is usual for in vitro fertilisation cycles28
). For one of the two trials with drop outs,w2
these were limited to two women in the sham group with ongoing pregnancies, both of whom we assumed to have had live births.17
In two other trials,w6 w7
some randomised women began the in vitro fertilisation process but did not complete the treatment (that is, no embryo transfer); however, as noted, these women were still included in the meta-analyses.
Three of the trials used a sham acupuncture control,w2 w5 w6
with one trialw2
using needles that penetrated the skin at acupuncture points selected not to influence fertility29 30
and twow5 w6
using non-penetrating sham needles. For the four other trials,w1 w3 w4 w7
women in the control group received no adjuvant treatment (table).
Six trialsw1-w4 w6 w7 reported their source of funding: three were funded by the in vitro fertilisation clinic,w1 w2 w4 one by government support,w7 one jointly by clinic and university support,w6 and one by a company that manufactures fertility drugs.w3 Four trials did not report on calculation of sample size.w1 w3-w5
Our primary analysis is based on results from all included trials because dividing trials according to control group (sham acupuncture and no adjuvant care) increased, rather than reduced, heterogeneity. Embryo transfer with acupuncture was associated with a higher pooled odds for clinical pregnancy (1.65, 95% confidence interval 1.27 to 2.14), ongoing pregnancy (1.87, 1.40 to 2.49), and live birth (1.91, 1.39 to 2.64) (fig 2). The pooled rate differences were 0.11 (0.06 to 0.16) for clinical pregnancy, 0.12 (0.07 to 0.17) for ongoing pregnancy, and 0.12 (0.06 to 0.18) for live birth. The numbers needed to treat (rounded up to the next whole number, as recommended31
) were 10 (7 to 17) for clinical pregnancy, 9 (6 to 15) for ongoing pregnancy, and 9 (6 to 17) for live birth. For the clinical pregnancy outcome, I2
values were 16% and 4% for the odds ratio and rate difference effect measures, respectively. All of the heterogeneity was caused by a single trial,w3
which reported only the clinical pregnancy outcome.
Fig 2 Effects of acupuncture on clinical pregnancy, ongoing pregnancy, and live birth outcomes
Of the nine subgroup analyses (seven prespecified) on clinical and methodological variables, only the subgroup analysis on the rates of clinical pregnancy in the control group showed a significant effect modification (P=0.04). Restriction to the three trials with the higher rates of clinical pregnancy in the control group suggested a smaller non-significant benefit of acupuncture (odds ratio 1.24, 0.86 to 1.77). No other subgroup restriction resulted in a change to a non-significant effect.
There were no significant adverse effects of acupuncture reported in the two trials that reported on this outcome.w2 w6