Letter regarding “Acupuncture—help, harm, or placebo?”

17 07 2013

To the Editors:

We read with interest the recent article, “Acupuncture—help, harm, or placebo?” by Meldrum et al. (1). We have one observation and one area of concern regarding the authors’ conclusions. The observation is focused on the dismissal of the efficacy of any impact of acupuncture on pregnancy rates as a placebo effect. First of all, the placebo effect is not to be taken lightly, and in fact may well be responsible for the efficacy of antidepressant medications, which appear to positively impact the psychological well-being of millions of Americans (2). Second, many of the randomized controlled trials on acupuncture do show a statistically significant impact on pregnancy rates. It is quite possible that acupuncture may only be effective with specific patient populations, analogous to assisted hatching (3). Finally, authors may influence the conclusions of any meta-analysis by shifting the criteria to include/exclude certain studies.

The area of concern is the recommendation, in the last paragraph, for patients to seek out education on lifestyle choices via a cited website rather than undergoing acupuncture treatment. There is a strong implication that the information provided on the website is more beneficial than acupuncture. It does not feel appropriate for an article in a peer-reviewed journal to be promoting a non-academic website. In addition, within the website are recommendations with links to purchase multiple products, including a wide range of supplements from a single manufacturer, such as fish oil, vitamin C, vitamin E, folic acid, green tea extract, and CoQ10, none of which have randomized controlled trials to support their efficacy to increase pregnancy rates in the infertile population. In the section on stress, the link is to a website that promotes a downloadable stress management program, which cites a pregnancy rate of 83%, despite the fact that there has never been a study utilizing the program.

We do agree with the authors that the research on acupuncture does not lead to clear recommendations for our patients. However, it is one of the few alternative treatments that does have data to support its efficacy with some patients. In addition, it seems, at least at the current time, based on the research available to us, that we should be far more inclined to recommend acupuncture than a commercial website.

Alice D. Domar, Ph.D.
Executive Director, Domar Center for Mind/Body Health, Boston IVF
Associate Clinical Professor of Obstetrics, Gynecology and Reproductive Biology, Harvard Medical School

Michael M. Alper, M.D.
Medical Director and President, Boston IVF
Associate Clinical Professor of Obstetrics, Gynecology and Reproductive Biology, Harvard Medical School


1. Meldrum DR, Fisher AR, Butts SF, Su HI, Sammel MD. Acupuncture—help, harm, or placebo? Fertil Steril 2013;99:1821-4.

2. Kirsch I. Antidepressants and the placebo response. Epidemiol Psychiatr Soc 2009;18:318-22.

3. Martins WP, Rocha IA, Ferriani RA, Nastri CO. Assisted hatching of human embryos: a systematic review and meta-analysis of randomized controlled trials. Hum Reprod Update 2011;17:438-53.

Published online in Fertility and Sterility doi:10.1016/j.fertnstert.2013.07.1970

The authors respond:

We did not intend to minimize the importance of the placebo effect of acupuncture, which is part of the total benefit of many widely accepted treatments documented to have benefits superior to placebo. At the same time, it would be highly unusual to suggest adoption of any significant intervention, whether a drug, a surgery, or a lesser intervention such as acupuncture, solely for its placebo effect, due to both potential risks and significant cost. If the reviewers of the original Paulus study (1) had insisted on a placebo control, the subsequent study by those authors that showed no significant benefit of acupuncture over placebo (2) might have been the first and only publication on acupuncture and IVF, rather than being merely published as an abstract. Because of their original study, we now have many subsequent randomized controlled studies, which to our analysis do appear to document a placebo effect, and sufficient studies with a valid placebo control to indicate that an effect beyond placebo appears doubtful. Because much larger amounts of data are necessary to exclude a true treatment effect of acupuncture, and acknowledging that it is widely used among IVF patients, we have recommended to not actively dissuade patients from availing themselves of acupuncture, but at the same time to be frank that insufficient data is available to document its efficacy. That approach allows patients who have inherent misgivings or fears regarding acupuncture to focus their limited resources on other promising techniques, such as mind/body programs or preimplantation genetic screening. As the authors point out, acupuncture may affect individual patients differently, and those who believe in it and find it relaxing are probably those most likely to benefit from it. Future studies on acupuncture should analyze patient characteristics relative to any treatment effect to answer that question.

Of course when no specific benefit has been proven, any risk is extremely pertinent. As we have pointed out, the stress of having acupuncture appears to have resulted in decreased pregnancy success in some studies. We have therefore emphasized caution in using acupuncture clinically or in designing future studies to be sure that the patient is not inadvertently subjected to stress during a critical time of her IVF procedure.

Throughout medicine, including IVF, placebo effects may occur due to such factors as the patient’s confidence in her physician and the ancillary personnel caring for her, the efficient organization of the treatment, and readily available answers to the patient’s questions and concerns. In IVF, specific placebo effects may occur due to seeing the embryo transfer catheter in the proper location in the uterine fundus, or by being given a Polaroid image of the air bubble that accompanied the embryo/s. A fully additive effect of all these placebos, including acupuncture, is unlikely. In a prior meta-analysis, a benefit of acupuncture was not observed in programs with high success rates (3).

It was entirely appropriate to question our mention of lifestyle factors that patients could attend to, which can give them a feeling of regaining some personal control over their infertility, since the quoted website does suggest some possible commercial benefit. Unfortunately, the website has been an expensive hobby for DRM. The huge effort in assembling the material and constructing the website was only justifiable as a means to provide information to patients in his practice, and in particular to allow them to discover information regarding excessive body weight and infertility, a subject difficult to broach in the office. Please note that most of the statements made on the website are referenced with links to PubMed abstracts so as to take an evidence-based approach to this expanding topic. We hope that other IVF programs and their patients can also benefit from the efforts expended.
We fully agree that the conclusions of any meta-analysis depend on the choice of studies to be included. We are confident that there is no justification for including studies in which control groups received interventions that could have a negative impact, studies in which a drug was combined with acupuncture, multiple-arm studies in which other treatments such as laser acupuncture were applied, or a cohort study within a meta-analysis of randomized controlled studies (4). We hope our reanalysis of the most recent meta-analysis by Zheng et al. (5) emphasizes precisely that point.

David R. Meldrum, M.D., Reproductive Partners Medical Group, Redondo Beach, California
Andrew R. Fisher, B.S.E., Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
Samantha F. Butts, M.D., M.S.C.E., Division of Infertility and Reproductive Endocrinology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
H. Irene Su, M.D., M.S.C.E., Division of Reproductive Endocrinology and Infertility, University of California, San Diego, California
Mary D. Sammel, Sc.D., Center for Clinical Epidemiology and Biostatistics, Philadelphia, Pennsylvania


1. Paulus WE, Zhang M, Strehler E, El-Danasouri I, Sterzik K. Influence of acupuncture on the pregnancy rate in patients who undergo assisted reproduction therapy. Fertil Steril 2002;77:721-4.

2. Paulus WE, Zhang M, Strehler E, Seybold B, Sterzik K. Placebo-controlled trial of acupuncture effects in assisted reproduction therapy. Hum Reprod 2003;18:S18.

3. Manheimer E, Zhang G, Udoff L, Haramati A, Langenberg B, Berman BM, et al. Effects of acupuncture on rates of pregnancy and live birth on women undergoing in vitro fertilization: systematic review and meta-analysis. BMJ 2008;336:545-9.

4. Meldrum DR, Fisher AR, Butts SF, Su HI, Sammel MD. Acupuncture—help, harm, or placebo? Fertil Steril 2013;99:1821-4.

5. Zheng CH, Huang GY, Zhang MM, Wang W. Effects of acupuncture on pregnancy rates in women undergoing in vitro fertilization: a systematic review and meta-analysis. Fertil Steril 2012;97:599-611.

Published online in Fertility and Sterility doi:10.1016/j.fertnstert.2013.07.1971




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