This item was produced as a reference for the interview of BBC R4 "You and Yours" programme
1. Chinese Medicine (CM) has a long history of gynaecological speciality. Regulating the menstrual cycle is seen as the key to promoting fertility in women.
2. Possible physiological mechanisms for acupuncture’s effects on fertility.
There’s been quite a lot of research on this, both in animals and humans. Three main mechanisms have been put forward:
- Mediates the release of neurotransmitters that affect the hypothalamus, and hence the pituitary, gonadotropin RF, the reproductive organs and hormones, and hence menstruation, ovulation and fertility.
- Stimulates blood flow to the uterus by inhibiting the sympathetic nervous system, leading to improved embryo implantation
[Anderson and Rosenthal 2014; Cochrane et al 2014].
3. Clinical Research overall
Reproductive dysfunction has not been well investigated: few clinical studies, most of which are flawed by poor design, hence hard to interpret.
4. Menstrual regulation
- There are few randomised controlled trials (RCTs) – and most have been in China, many of which are inaccessible to Western audiences
- Most studies have focused on PCOS. Acupuncture has been shown to reduce hyperandrogenism [Cochrane et al 2014] and improve menstrual frequency – meta-analysis of two RCTs [Lim et al 2016]
- Acupuncture improved menstrual frequency and other aspects in women with diminishing ovarian reserve, with similar effectiveness to oestradiol in a RCT [Tang et al 2015]
- Acupuncture has been found useful for amenorrhoea in case and cohort studies, and a few RCTs, but there is certainly insufficient research to date [Cochrane et al 2014]
- According to Chinese work acupuncture can reverse chronic anovulation in about 50% of cases and is especially effective if the problem is hypothalamic in origin. Non-RCT studies in the West have confirmed this for the specific area of PCOS. [Cochrane et al 2014].
- In a recent systematic review of RCTs acupuncture was superior to a relaxation control but statistically equivalent to sham acupuncture [Lim et al 2016].
NOTE. There is no satisfactory placebo control for acupuncture trials. Sham acupuncture is not inert but an active treatment in its own right – it’s like a mild version of acupuncture, or a reduced dose. Hence sham controlled trials are contentious and difficult to interpret.
6. Dysmenorrhoea and PMS
All aspects of the menstrual cycle would be seen as relevant to improving a woman’s fertility, including these. Systematic reviews for dysmenorrhoea have mostly produced positive outcomes for acupuncture though there is insufficient good data to be sure. Meta-analysis has found acupuncture to be superior to medication but with unclear results vs sham. [Cochrane et al 2014] For PMS, the reviews have found acupuncture to be better than both medication and sham acupuncture, but many of the trials were methodologically flawed. [Cochrane et al 2014].
7. Natural fertility
- There have been few RCTs, mostly Chinese
- An early European trial found ear acupuncture superior to controls for hormonal infertility [Gerhard and Postneek 1992]
- Cochrane et al (2014) report two Chinese trials with success in endometriosis-induced infertility and tubal infertility
- Various Chinese RCTs have found acupuncture to be superior to medication (usually clomiphene) [Yang et al 2005; Chen et al 2007; Song et al 2008; Li et al 2013; Jiang et al 2015].
- In the previously mentioned systematic review [Lim et al 2016], for PCOS, acupuncture was found statistically equivalent to sham for pregnancy rate (no live birth data), though the trend was positive.
NOTE. See comments above re problems with sham acupuncture. Also note that in order to establish statistical significance for a small effect, as with acupuncture compared to the dilute version of itself that is sham acupuncture, would require very large numbers much bigger than anything in the trials of reviews done to date.
- in a recent Australian pilot trial [Cochrane et al 2016] acupuncture delivered the same pregnancy rate as the controls but they conceived in half the time
[7 Nov 2016. Since this summary was written an abstract has been published for a multi-centre Chinese-Swedish-US RCT with 1000 women who have infertility with PCOS. Clomiphene found to be effective for live birth rate, but not acupuncture. It’s a complex, 4-arm study with both drug and acupuncture placebos. There isn’t a no-treatment arm, nor a direct comparison of clomiphene and acupuncture, so it’s impossible to be clear as to what the effect of the acupuncture is, but the headline conclusions do not look good. This was presented last month at the American Society for Reproductive Medicine conference]
- There have been more than 50 RCTs and many reviews to aggregate and summarise them. They have conflicting results, so the nature of the effect of adjunctive acupuncture is debateable [Nandi et al 2014; Cochrane et al 2014]
- Overall we can say that the acupuncture effect is on the borderline of being significantly superior to controls [Shen et al 2015], with variable results depending exactly which trials are included/excluded and how the analysis is done
- The comparison tends to favour acupuncture more when compared to no acupuncture controls, but tends more to non-significance compared to sham controls [Shen et al 2015].
NOTE. See comments above re sham acupuncture. Consider also that a milder version of acupuncture may not be a bad thing when used for women who are probably under a great deal of stress (about which, more below).
- As well as the issue of sham comparators, there are other substantial problems with virtually all of the trials to date. Another generic one is that the same formula of points (and treatment as a whole) is delivered to each participant, regardless of their particular symptoms and other characteristics. For best practice, patients should be individually diagnosed, treated and advised.
- Other serious issues are more specific to the nature of IVF and the acupuncture protocols used in the trials. Most of the RCTs have provided just one or two acupuncture sessions, around the time of embryo transfer (ET). This is not at all in accord with good practice for traditional acupuncture, either in the number of sessions or their timing. Traditionally we look to regulate women’s reproductive systems as a whole, indeed all of their systems as a whole, centred here on the menstrual cycle, so protocols delivering acupuncture just at one particular point in the IVF cycle do not hold water. Also two treatments is an insufficient dose, whatever stage it is given at. Furthermore, even if one was going to intervene at only one stage in the process this (i.e. at ET) is probably not the best time. Some trials have used acupuncturists who are not sufficiently well trained to deliver this intervention; even people who are not acupuncturists. Treatment should include tailored lifestyle advice, especially around diet. It may also be advisable to include Chinese herbs.
- Taken together we can say that the acupuncture provided in IVF RCTs has been suboptimal on several counts, which may have had significant effects on the results and their interpretation. Some evidence to support this exists already but as yet very few studies have strayed from the familiar, suboptimal, approach: see below.
- A meta-analysis of trials where treatment was given at other stages in the IVF cycle as well as ET found acupuncture to be superior to controls (whereas this was not the case for those centred just on ET) [Shen et al 2015].
- Some recent RCTs, not yet included in systematic reviews, have delivered the treatment over a larger part of the IVF cycle, or even leading up to IVF. A Chinese trial for women with declining ovarian reserve found acupuncture better than no acupuncture for clinical pregnancy rate [Zhou et al 2016]. Notably, at the Homerton Hospital in the UK, there are preliminary results on the first 127 women, presented at the 2016 conference of the European Society of Human Reproduction and Embryology, with 46% pregnancy rate with acupuncture vs only 22% without.
- A cohort study of 1231 women going through IVF in the US were given either whole systems Traditional Chinese Medicine, which could incorporate herbs, acupuncture and dietary/lifestyle advice, extending over the whole cycle, or the usual ET-based acupuncture, or nothing extra. The whole systems approach delivered significantly better live birth outcomes [Hullender Rubin 2015].
- Acupuncture may help by reducing anxiety levels, as IVF tends to be a high stress, high anxiety experience for the women (and their partners). Acupuncture has been found to be effective for situational anxiety in systematic reviews, especially in peri-operative situations [Pilkington et al 2007; Bae et al 2014; Au et al 2015]. It reduced anxiety and improved IVF outcomes vs controls in a recent RCT of reasonable size (Qu et al 2014]. Also the levels of neuropeptide Y (associated with resilience in stressful situations) in the follicular fluid were elevated.
Acupuncture has a very strong safety record [Witt et al 2009] in general and with respect to fertility treatment. In particular it helps to reduce or avoid ovarian hyperstimulation syndrome [Hong et al 2014]