– no clear effect on live birth rate
This blog was first published on 18th June 2018 on https://blogs.bmj.com/aim/
Acupuncture has become very popular within the field of assisted reproduction, and particularly as an intervention within IVF (In-Vitro Fertilisation). In an editorial from 2015 in Acupuncture in Medicine, David Carr lists 12 meta-analyses on the subject in just 6 years, including a total of 34 RCTs. There was no clear conclusion from the reviews – most outcomes showed no benefit for acupuncture, but some did. In general we see quite large benefits over control in open studies, and no effects in blinded sham control studies.
It is worth noting that in one high quality double blind study (n=370), the sham acupuncture group had a significantly better outcome than the real acupuncture group (live birth rate 38.4% versus 29.7% respectively). The research team from Hong Kong went on to test the same protocol (treatment before and after embryo transfer – ET) in frozen-thawed cycles (FET; n=226). The results were very similar (live birth rate 35.4% with sham versus 29.2% with real), significantly favouring sham in all outcomes. Following directly on from this the team decided, logically but rather surprisingly, to test sham versus sham: a single session of sham acupuncture after ET with sham before and after ET, as in the original protocol. This trial was presented in a meeting at The Hague in 2011, where it won a research prize (I was part of the awarding committee), and I remember discussing the topic with the first author of the paper – Emily So. There was no significant difference in pregnancy outcomes, but the two-session protocol conferred a significant benefit in terms of anxiolysis (details from the abstract submitted to the meeting, 2011).
So where am I going with this? Well it seems likely that acupuncture or sham acupuncture confer a context-related benefit in terms of supportive care mediating anxiolysis. But beyond this, it seems possible that real acupuncture has some potential disadvantages when performed around embryo transfer. In brief, strong somatic stimulation in the segments related to the uterus, or indeed outside those segments, may influence contractile behaviour of the uterus. This is mostly harmless of course, but increasing contractions after ET in an otherwise quiescent uterus may expel the embryo. Equally, contractions initiated by the instrumentation during ET may be suppressed by acupuncture, which might prevent expulsion of the embryo. It was on the latter basis that Paulus first used the technique around ET (personal communication, Irina Szmelskyj). A panel of experts presenting at the BMAS Spring meeting in Newcastle (2015) concluded that acupuncture should be avoided around ET and implantation unless the woman had symptoms that might be ameliorated with acupuncture – abdominal cramps for example.
…it seems possible that real acupuncture has some potential disadvantages when performed around embryo transfer.
The paper that stimulated this blog was published in JAMA in May 2018. I heard the results presented in a meeting in Berlin a year before, and discussed them with the lead author Caroline Smith. Essentially it is the largest sham controlled trial of acupuncture within IVF to date (n=824), and it failed to demonstrate any benefit of acupuncture over sham. The live birth rate was 18.3% in the acupuncture group versus 17.8% in the sham group. The clinical pregnancy rate was marginally higher in the acupuncture group at 25.7% versus 21.7%, but this was negatively offset by an increased rate of pregnancy loss.
Given what I said above about Emily So’s research, the results are not particularly surprising. The rates of live birth appear much lower, but that is likely related to the fact that nearly half of the women in Caroline Smith’s study had already failed 2 or more cycles of IVF, whereas the majority in Emily So’s research were on their first cycle.
I was particularly interested to see in the supplementary data of Caroline Smith’s huge multicentre trial that in two of the 15 sites there was a significant benefit of sham over real acupuncture, and at no site was there a significant benefit for real over sham. Data was pooled from 4 sites, leaving 12 comparisons in the forest plot (see figure below). Using 95% confidence intervals we would only expect a type I statistical error (a significant difference in the sample data when there is no real difference between the populations sampled) to occur 5% of the time ie 1:20. So 2 occurrences in 12 comparisons does not seem likely by chance alone. This adds some weight to my comments above regarding potential risks associated with the somatovisceral reflex effects of real acupuncture.
Does acupuncture have a role in fertility or not? The majority of the clinical trial data comes from within IVF cycles, and more specifically either side of ET. I have always thought this was a long shot from a physiological point of view, since acupuncture generally requires a course of regular treatments to mediate measurable effects in clinically relevant outcomes. So I am pleased that this trial will probably place the last nail in the coffin for this very limited technique. But is there any role for acupuncture in fertility? Well we have also seen a very large negative trial from China on segmental electroacupuncture (EA) versus clomiphene for ovulation induction in PCOS: the subject of a previous blog. I still hold out some hope that we will find a useful place for the technique since Elisabet Stener-Victorin first opened the whole chapter in 1996 with her trial on the influence of segmental EA on uterine artery impedance.
In terms of acupuncture research and practice I think the focus should be outside IVF.
Either for couples with unexplained infertility and no male factor (unless treatment is aimed at the man of course – that’s another topic entirely), or in the weeks and months prior to an IVF cycle. This phase, theoretically at least, has always held the greatest promise, but because of the trial by Paulus in 2002, the research, in my opinion, went on a very loud and frantic wild goose chase.
After posting this blog I decided to email the team to ask about the live birth rate in the third of Emily So’s studies – the one comparing sham with sham. I emailed the senior author Ernest Hung Yu Ng, and to my surprise he answered with a further abstract describing more unpublished research from his team. They had gone on to test sham acupuncture either side of ET in an open pragmatic trial against no additional acupuncture in 800 women undergoing IVF! Live birth rate was not included in the abstract, but the on-going pregnancy rate was 32.3% in the sham acupuncture group and 33.3% in the no acupuncture group.
This is very useful addition data that clearly now points to the fact that sham acupuncture around ET is not beneficial, and therefore implies that real acupuncture may sometimes confer risks when applied at ET. This does not apply to acupuncture performed at other times, and further encourages me to promote the testing of acupuncture performed in the lead up to IVF rather than during the process.
- Carr D. Somatosensory stimulation and assisted reproduction. Acupunct Med 2015;33:2–6. doi:10.1136/acupmed-2014-010739
- So EWS, Ng EHY, Wong YY, et al. A randomized double blind comparison of real and placebo acupuncture in IVF treatment. Hum Reprod 2009;24:341–8. doi:10.1093/humrep/den380
- So EWS, Ng EHY, Wong YY, et al. Acupuncture for frozen-thawed embryo transfer cycles: a double-blind randomized controlled trial. Reprod Biomed Online 2010;20:814–21. doi:10.1016/j.rbmo.2010.02.024
- Paulus WE, Zhang M, Strehler E, et al. Influence of acupuncture on the pregnancy rate in patients who undergo assisted reproduction therapy. Fertil Steril 2002;77:721–4.
- Smith CA, de Lacey S, Chapman M, et al. Effect of Acupuncture vs Sham Acupuncture on Live Births Among Women Undergoing In Vitro Fertilization: A Randomized Clinical Trial. JAMA 2018;319:1990–8. doi:10.1001/jama.2018.5336
- Stener-Victorin E, Waldenström U, Andersson SA, et al. Reduction of blood flow impedance in the uterine arteries of infertile women with electro-acupuncture. Hum Reprod 1996;11:1314–7.