Overall, our study confirms that the chosen acupuncture regimen appears to increase pregnancy rates in IVF patients. When we model the relationship of this acupuncture regimen to pregnancy success, women with acupuncture were 3.0-times more likely to become pregnant. However, the confidence interval is extremely large and overlaps 1 CI (0.5–17.9). One commonly reported action of acupuncture is stress reduction. Given that a stress response causes vasoconstriction16
, which could acutely decrease uterine perfusion, it seems plausible that excessive stress on the day of embryo transfer could lower pregnancy rates. It also seems that techniques that elicit the relaxation response, leading to vasodilation, at the time of ET could improve pregnancy rates. Future studies could evaluate other relaxation techniques at the time of embryo transfer.
Those who received this protocol of acupuncture had both higher rates of pregnancy, and lower levels of stress both before and after embryo transfer. The vast majority of acupuncture patients had been receiving acupuncture prior to the day of ET, which could explain why the pre-ET stress scores were lower. However, the particular acupuncture protocol we used in this study did not seem to lower stress scores significantly from before embryo transfer to after embryo transfer. Therefore, the mechanism by which pregnancies were increased with this protocol remains unknown. Because this is not an attention-controlled study, it is possible that merely having the attention from acupuncture, rather than the actual acupuncture, resulted in lower stress scores. Based on the results of this study, it would be interesting to try new acupuncture protocols targeted at reducing stress levels at the time of ET.
When subjects in either group had a significant reduction in stress from before the embryo transfer to after it, pregnancy rates increased. It is possible that those who had a reduction in perceived stress scores had that reduction because they had excellent quality embryos, whereas those who had increased stress did so because they were less optimistic about their outcome. Thus, the decrease in stress could have occurred because the chances of pregnancy were higher, not that the decrease in stress resulted in higher pregnancy rates. However, when we examined this, embryo quality was not related to the change in stress scores (p=0.78), the pretest scores (p=0.97), or the post-test scores (p=0.91).
One limitation to this study is that it is small, with only 57 subjects. Previous studies have indicated that acupuncture improves pregnancy rates; however, the selection bias for acupuncture is unknown. If poor prognosis patients tend to choose acupuncture, then an improvement in pregnancy rates is very important. If good prognosis patients choose acupuncture, then a high pregnancy rate is less impressive. We found that donor oocyte recipients were more likely to choose acupuncture when compared with non-donor oocyte patients. We believe this is due to our clinical donor program, where the patients have a one-on-one relationship with the donor coordinator, and are more likely to hear all the options available to them.
Another major limitation is that this study is not-randomized, blinded, or placebo-controlled. Given the large financial and emotional investment in IVF, it is difficult to recruit for a randomized, placebo-controlled trial. Lack of a placebo arm means that this study is testing the whole acupuncture regimen, not just needling of the specific points. Also, while the measurement of the stress scores was prospective, the chart review for the variables was retrospective. Thus, some variables, such as the use of ICSI, was not collected prospectively and was difficult to obtain reliably from a clinical chart review. Another weakness of the study is that we did not control for the amount of acupuncture that the subjects received prior to the day of ET. Some received it only on the day of ET, whereas others had multiple sessions of acupuncture. This study is too small to determine a dose-response relationship, but future studies should explore this possibility. Lastly, the acupuncture protocol used was the Paulus protocol, and it was the same used for all subjects. It is possible that individualizing acupuncture, rather than using a formulaic approach, would lead to different results. We chose this protocol because it is commonly used on the day of ET, and when modifications are made to this protocol with respect to point selection or timing of acupuncture, or the protocol is individualized based on TCM diagnosis, the results appear to be less positive than using the Paulus protocol5, 15, 17
. Our results only refer to the acupuncture regimen chosen; other acupuncture regimens might have different results.
Although more involved questionnaires might be useful to provide additional information, we chose a short, validated questionnaire to have minimal burden on the subject and the healthcare team. This study did not have a funded research recruiter, so we needed to be able to enroll subjects with minimal disruption to clinical care. Future studies could investigate serial cortisol concentrations, anxiety measurements, and measurements of autonomic function, such as heart rate variability.
One of the strengths of this study is that it is innovative. It is the first study to investigate the effects of acupuncture on perceived stress at time of ET, and we believe it is the first study to investigate the effects of perceived stress at the time of ET on pregnancy rates. In addition, our study assessed subjects based on what is done in clinical care, where some patients choose acupuncture and others do not, although the acupuncture regimen in clinical care is not uniform for all subjects, as it was in this study.
Finally, even with our small sample size, we were able to demonstrate that acupuncture was associated with less stress both before and after embryo transfer, and that acupuncture may improve pregnancy rates. It is possible that lower perceived stress at the time of embryo transfer may plan a role in an improved pregnancy rate. Future studies should investigate a dose-response relationship, mechanisms of action, and the types of biases and directions of the biases that may confound the relationship between acupuncture and pregnancy success.