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Placebo effect in fertility: advantageous or false advertisement?

2013; Elsevier BV; Volume: 101; Issue: 1 Linguagem: Inglês

10.1016/j.fertnstert.2013.11.012

1556-5653

Kurt T. Barnhart,

Acupuncture Treatment Research Studies

Evidence-based medicine is an ideal and a goal. Scientifically supported evidence in reproductive medicine can lead to optimal success and minimal side effects in a cost effective fashion. However, innovation and medical care move quickly, while it takes time (and money) to provide evidence to support, or refute, utility of a novel therapy. Many therapies, especially in treatment of a couple with infertility, do not have evidence to demonstrate their efficacy. We in reproductive medicine have a herd mentality—one presentation at the meeting of the American Society for Reproductive Medicine, and the next year 20 centers are reporting their experience with the novel intervention. Therapies are rapidly and wildly implemented based on word of mouth from an "expert." Why is that? Is it because we believe these therapies will work based on a persuasive biological rationale underpinning the therapy? Is it to gain a competitive advantage? Or do we believe in the placebo effect? Many therapies remain controversial regarding their efficacy despite multiple clinical trials. One such example is the use of acupuncture to enhance ferity in conjunction with in vitro fertilization. There are many conflicting studies, some reviewed in this journal. Perhaps the best summary is exemplified by the recent Cochrane review. Acupuncture appears to enhance fertility in trials that have no control. However, acupuncture has no effect when compared to a sham acupuncture procedure. What is the explanation to this finding? One explanation is that "sham" acupuncture is actually active treatment. Alternatively, the efficacy of acupuncture in uncontrolled trials can be due to a placebo effect. A placebo effect is the tendency of any medication or treatment, even an inert or ineffective one, to exhibit results simply because the recipient believes that it will work. A placebo effect can be real, in this case resulting in a higher pregnancy rate. Thus, more women get pregnant when using placebo because they "believe" it works. Are we taking advantage of the placebo effect in myriad unproven or unstudied therapies offered to our patients? The list is long and new "therapies" are falling in and out of favor almost yearly. Some past well-intended but abandoned strategies include diagnostic laparoscopy for all women, the hemi-zona sperm penetration test, postcoital testing, luteal-phase biopsy, and embryo tubal cell co-culture. Contemporary strategies that lack evidence include luteal-phase estrace, endometrial scratching, and supplementation with DHEA, human chorionic gonadotropin, and/or growth hormone. Some unproven strategies are expensive and invasive, such as intracytoplasmic sperm injection (ICSI) for non-male factor and routine preimplantation genetic screening (PGS). Do we need evidence before we implement these new strategies in reproductive medicine? We are all familiar with the cliché that one does not need to conduct a randomized clinical trial to demonstrate that a parachute works. However, it is very likely that we do need evidence to demonstrate a change in material, size, or shape of the parachute is actually an improvement (and not a detriment). Should we conclude that a neoprene suit with wings under the arm is more effect and less dangerous simply because it is an advancement in parachute technology (and is marketed by an expert in the field)? Doesn't this analogy hold true for in vitro fertilization culture conditions and innovations in culture media? We try to treat our patients based on the Hippocratic Oath of do no harm, as well as using sound scientific rationale. That is our training and our profession. We also try to benefit our patients, especially the one in front of us. We cannot wait for years to see if a novel therapy works. Offering something novel to someone who has poor prognosis, with multiple failures, is only helping, right? How could it do harm? Perhaps it may make the difference, especially if I exude confidence in front of my patient. Are we trying to evoke a placebo effect, or is the underlying unrecognized motivation more sinister: competition and financial gain? Reproductive medicine is a competitive field. If my competitor offers something I do not, I will lose patients to that practice. If I offer something novel, I can slip into the consultation (and on my web site) how the practice down the street is not up on the latest therapies and how my practice is state of the art. How could that new patient even think of seeking care at that practice down the street! This sentiment is logical, but if followed to an extreme we can all be offering snake oil in no time at all. In fact, I think it is already happening. Of course, individually we believe that latest unproven therapy worked. Some of our poor prognosis patients get pregnant despite our unproven therapies. We remember our success, not our failure. The one case that works spurs us on and confirms our belief. If it did not work, it was a hopeless case and no one could have helped that couple. Of course, this is not evidence-based medicine. In fact, this biased recollection of our past experience is the reason for evidence-based medicine. If our "novel" therapy is really a placebo, then at worst we are practicing the old mantra of "hurry up and use the new therapy before we find out it does not work." Of course, the problem is unrecognized harm and reducing pregnancy rate, or increasing morbidity of the child conceived. There are significant issues. A second harm is taking advantage of a vulnerable population that would do almost anything to get pregnant. We all realize we get paid whether or not the patient successfully conceives. Often times we get paid more if we add on interventions like unnecessary ICSI or PGS. There is no question we practice in a field replete with unproven therapy. There is no shortage of new ideas, new rationales, and innovation. However, there is also no shortage of new excuses, new angles, and new competitive advantages. Often, treating an infertile couple is more business than medicine. It is difficult to uncover the motivation of an individual practitioner, or of a field in general, to adopt unproven strategies. However, it is clear that we are often not practicing evidence-based medicine. Financial conflicts are real and are compelling. We all need to examine our own motivation and practice. The practice of evidence-based medicine is not just an ideal. Rigorous study of our therapies is a necessity. As a field of reproductive endocrinology and infertility, we need to offer optimal proven therapy, do no harm, and we need to not take advantage of our patients for financial gain. We need to enroll our patients in clinical trials to find the truth about new intervention and therapies, not offer them simply because our competitor does. However, if our motivation to adopt unproven and untested therapy is to help patients by invoking a placebo effect, and that placebo effect can result in a higher pregnancy rate because the couple "believes" it is going to help, why should we not take advantage of it? Or, did I just expose the power of placebo (and thus lessen its effect) because I just wrote this article (and you just read it). Perhaps it is best if you do not share this with your patients.