To the Editor:
It is widely known that embryo quality affects pregnancy and live birth rates. Nevertheless, in their article, “Increase of success rate for women undergoing embryo transfer by transcutaneous electrical acupoint stimulation: a prospective randomized placebo-controlled study,” Zhang et al. do not mention the quality of transferred embryos at all (1). In addition, there is no information about ovarian stimulation protocols (GnRH agonist? GnRH antagonist? Recombinant or urinary FSH?), length of stimulation, endometrial thickness or day of embryo transfer. One might expect day-5 cycles to be different, for better or worse, considering that the interval between intervention [transcutaneous electrical acupoint stimulation (TEAS)] and embryo implantation would have been shorter.
Another question: why were patients who previously submitted to acupuncture excluded from the study? The authors state that the TEAS parameters in the mock group were “too weak to produce a therapeutic effect.” On the other hand, they say that such parameters produced a “feeling of intermittent tingling sensation.” If there is sensation, there is neural stimulation, so how can one exclude possible “therapeutic” effects for the mock group? This mild stimulation should be considered and discussed as well. I understand that it is difficult to have a perfect control group for acupuncture studies, but I do not believe this particular kind of control “makes the conclusion more convincing and reliable.”
There are many factors that can influence outcomes in ART cycles. This study does not seem to have considered all (or even most) of them. As an ART physician and acupuncturist, I do not feel comfortable, at this point, mentioning the results reported by Zhang et al. to my patients.
Sergio P. Gonçalves, M.D.
São Paulo, Brazil
1. Zhang R, Feng X-J, Guan Q, Cui W, Zheng Y, Sun W, Han J-S. Increase of success rate for women undergoing embryo transfer by transcutaneous electrical acupoint stimulation: a prospective randomized placebo-controlled study. Fertil Steril 2011; 96:912-6.
Published online in Fertility and Sterility doi:10.1016/j.fertnstert.2011.12.052
The Authors Respond:
We welcome Dr Gonçalves’comments on our study. The answers to his questions are as follow:
1. Concerning embryo quality, only high quality embryos were chosen for transfer. No significant differences were found in the number of high quality embryos among the three groups (mock TEAS: 4.8±4.1; single TEAS 5.5±3.3; double TEAS 5.2±4.4).
2. All participants involved in this study used a GnRH agonist regimen, lasting for 10 days. Recombinant FSH was used in the first five days, and recombinant FSH plus urinary FSH in the second five days. The endometrial thickness was around 9-11 mm, and there were no significant differences among the three groups (mock TEAS: 1.1±0.3; single TEAS: 1.0±0.1; double TEAS: 0.9±0.1). The embryo transfer was executed 3 days after oocyte retrieval. Since the regimen mentioned above is regular procedure in most reproduction centers, we did not describe it in detail. We have compared all factors that might affect the pregnancy rate to confirm the uniformity in the three groups. For details, please see Table 1.
3．Patients who were previously treated with acupuncture were excluded from the study because we used the placebo transcutaneous electrical acupoint stimulation (TEAS) as a control for the real TEAS. Subjects who have experienced acupuncture may notice the difference between the two types of stimulation, thereby making the placebo design inapplicable. Secondly, previous exposure to acupuncture may affect the results of the current study. Therefore we only recruited acupuncture-naïve subjects for the present study.
4. There are several ways to design a control group for acupuncture research. The easiest way is to place the needle or electrodes on the same anatomical site, but limit the intensity of the stimulation to a very low level. However, if the intensity is near zero, it would not produce any feeling and the subject would guess that he or she is in the control group. If the stimulation is reduced by only 1-2 fold, the mild stimulation per se may produce a therapeutic, albeit weak, effect. In the present study, we used a minimal stimulation by a 9-fold reduction, i.e., the intensity is reduced by 3-fold (5 mA vs 15 mA), and the time of stimulation is reduced by 3-fold (10 seconds on and 20 seconds off). Most subjects said, “I do feel something come and go.” Therefore, the psychological effect remained while the physiological effect became negligible (1).
5. As we mentioned in the introduction and discussion, one key factor in the effect of acupuncture is the timing of intervention. Consistent with previous findings (2,3), treatment on the day of embryo transfer (ET) is effective, but not at some other times (4). That is why we performed TEAS intervention 24 hours before and 30 minutes after ET.
Rong Zhang, M.D., Ph.D.
Ji-Sheng Han. M.D.
Neuroscience Research Institute
1. Lambert C, Berlin I, Lee TL, Hee SW, Tan ASL, Picard D, Han JS. A standardized transcutaneous electric acupoint stimulation for relieving tobacco urges in dependent smokers. Evidence-based Complementary and Alternative Medicine. 2009;1-9.
2. 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.
3. Westergaard LG, Mao Q, Krogslund M, Sandrini S, Lenz S, Grinsted J. Acupuncture on the day of embryo transfer significantly improves the reproductive outcome in infertile women: a prospective, randomized trial. Fertil Steril 2006; 85: 1341-6.
4. Wang W, Check JH, Liss JR, Choe JK. A matched controlled study to evaluate the efficacy of acupuncture for improving pregnancy rates following in vitro fertilization-embryo transfer. Clin Exp Obstet Gynecol 2007; 34: 137-8.
Published online in Fertility and Sterility doi:10.1016/j.fertnstert.2011.12.053