Common Practices in Reproductive Endocrinology and Infertility Supported by Weak or No Evidence

Orhan Bukulmez, MD

Initially, I was not exactly sure how to describe the main theme that I would like to propose to our editor Dr. Carr. For more than two decades, I have been exposed to reproductive endocrinology and infertility practice in both sides of the Atlantic Ocean. Since my medical school years which started in 1983, I have been trained and worked at various institutions of higher education. Therefore, most of the clinical care–based discussions either at curb side or during formal conferences were about evidence-based medicine although most of the common applications or the most current recommendations or procedures of that particular time were always supported by weak or no evidence. This was very true especially for very new technologies or approaches since the genuine excitement associated with such therapies were usually the main theme of scientific meetings or journal articles, although many would fail when strict evidence-based medicine principles were applied. Systematic reviews and the evidence-based collaborations have become a norm. However, after more than two decades of experience in reading meta-analyzes and systematic reviews, each conclusion from these documents created even more need to wait for the next review since the quality of the published research was quoted to be limited. It seemed that an ideal study on many common practices in the field of reproductive endocrinology and infertility could never be done. It would always be very difficult to control confounders while assuring the sample size needed. Any randomized controlled trial had to focus on a single outcome measure which may or may not be relevant to the main research question. Meta-analyzes had to include both retrospective or observational and prospective randomized controlled studies and therefore the reached conclusions seemed to be very cross-sectional, mostly relevant to that very time point that the analysis was performed. Majority of us believe that this approach is necessary to urge the need to have better and more decisive studies. Some authors criticized performing meta-analysis for new concepts very early.[1] Others stated that systematic reviews seldom address the complex context of clinical practice.[2] In response, others claimed that the clinical decisions cannot be made based on biased and misleading narrative reviews.[3] Perhaps some multi-subtitled narrative reviews might be needed though to assess the quality and relevance of published in meta-analyzes. Furthermore, considering many restrictions from the governmental funding agencies for research support in human-assisted reproduction and embryology, we may have to decide on how to proceed by considering commonly applied and scientifically sound, commonsense approaches while ensuring the best possible clinical outcome. Many of us continue to practice in a way we feel that it would benefit the patient care most while minimizing any potential harm while considering the best available evidence. Sometimes if the perceived harm is minimal to none, many professionals proceed with recommending some empirical approaches to the patients. While making these decisions, cost concerns and patient-specific factors are all considered as well. We also follow the consensus documents from relevant societies, although majority of these recommendations are always here to change in the very near future. In some of the areas such as human in vitro fertilization (IVF) laboratory protocols or human IVF-related research, again due to the issues of lack of appropriate funding and ethical concerns, a prospective randomized controlled trial cannot be easily conducted. Hence, many applications would follow the previous ones but with various improvements, tested only by enhanced patient outcome reporting parameters such as live birth rates. Therefore, we have decided to dedicate this issue of Seminars in Reproductive Medicine to common applications in reproductive endocrinology and infertility supported by weak or no evidence. Although it sounds like we try to present non–evidence-based medicine, once the articles are read, it would easily be conceived that all the reviews were put together with an evidence-based medicine perspective by a distinguished group of faculty practicing in different institutions, countries, and continents. Hence these reviews may provide some context about how strong the scientific evidence is on some of the entities that we come across on an everyday clinical practice.

From Istanbul, Turkey, Drs. Urman and Oktem provided the available scientific information on food and drug supplements perceived to be enhancing fertility outcomes; Drs. Elter and Oral reviewed surgery performed to enhance IVF outcomes; Dr. Yarali's group from Ankara, Turkey reviewed whether best protocol for controlled ovarian hyperstimulation exist or not; Basak Balaban from American Hospital IVF program along with Drs. Sakkas from Boston, MA, and Gardner from Melbourne, Australia, provided an excellent review on human embryology laboratory protocols; our group from Dallas, TX, chose to revisit intracytoplasmic sperm injection indications; and Drs. Tiras and Ozcan reviewed the practice of embryo transfer. Drs. Zeyneloglu and Onalan reviewed the approaches for recurrent implantation failure. Dr. Ku's group from Seoul National University, Korea, contributed our issue with an article on the commonly used technique of intrauterine insemination. The fertility urologist of this issue, Dr. Parekattil and his group from Orlando, FL, covered the important topic of medical management of male infertility when there is no specific diagnosis. Drs. Whitley and Ural from Penn State University, Hershey, PA, reviewed the approaches for patients with idiopathic recurrent miscarriages. Dr. Bhagavath's group from University of Rochester, NY, graciously put together a great article on the use of insulin sensitizers in patients with polycystic ovary syndrome. We believe that we could cover most but not all of the everyday practice items faced by fertility professionals or reproductive endocrinologists in general. I hope this issue can be received as an important update for common clinical applications while our community will continue to seek relentlessly to find the best possible evidence by conducting more meaningful translational and clinical studies.

• References

• 1 Humaidan P, Kol S, Engmann L, Benadiva C, Papanikolaou EG, Andersen CY ; Copenhagen GnRH Agonist Triggering Workshop Group. Should Cochrane reviews be performed during the development of new concepts?. Hum Reprod 2012; 27 (1) 6-8
• 2 Greenhalgh T. Outside the box: Why are Cochrane reviews so boring?. Br J Gen Pract 2012; 62 (600) 371
• 3 Fahey T, Smith SM, van de Laar F, Kenealy T, Arroll B. Cochrane reviews: relevant more than ever. Br J Gen Pract 2013; 63 (606) 10