Reproductive immunology: the relevance of laboratory research to clinical practice (and vice versa)

In this issue of Human Reproduction, the paper by Gu et al. represents a landmark in reproductive immunology research. A new mechanism for evasion of maternal immune attack is described, one which explains an older theory but also itself represents part of a newer understanding of the maternal– fetal relationship. Although some of the methods may be relatively unfamiliar to many readers of this journal, the scientific endeavour is extraordinary and it is stimulating to consider how this is placed in the context of current theory and practice of reproductive immunology. In particular, this paper demonstrates, as an example, that there is a whole lot more to reproductive immunology than natural killer (NK) cells and immune therapy. Thefield of reproductive immunologyoftenarousesunusuallyemotive and diverse responses amongst clinicians, scientists and patients. At its core is the concept of the relationship between mother and conceptus which is critical for human reproduction. It is indisputable that the nature of the maternal– fetal interface determines the success or failure of pregnancy. However, our understanding of that interface, and our attempts to alter or improve it, are the cause of the controversy. So why the controversy? Everyone has the same goal of trying to increase knowledge and improve outcome for patients. Clinical outcomes are the basis of all medical intervention, and the unfortunate truth is that some couples suffer apparently unexplained infertility or repeated miscarriage or IVF failure. Even with the most advanced genetic screening IVF produces, at best, 70% success rates when chromosomally normal embryos are transferred. It is perfectly reasonable to wonder if we are missing something. And from a patient perspective, is it not natural to want to do whatever could be possible to improve outcome next time? So there are considerable emotional, physical and financial costs driving the desire for immune testing and therapy. Clinicians, by their nature, are simply trying to help too. Reproductive medicine has a long history of immune therapy, almost all empirical and unproven (in terms of randomized trials). But in the words of Peter Medawar, father of reproductive immunology, ‘If a person a) is poorly, b) receives treatment intended to make him better, and c) gets better, no power of reasoning known to medical science can convince him that it may not have been the treatment that restored his health’. Problems arise when excessive claims are made, leading to patients potentially doing more expensive and even dangerous treatments where benefit is unlikely. Research scientists are rigorous and objective, but often not involved in clinical care. There have, at times, been heated arguments between those interested in understanding, and those interested in treating. In reality, we must accept that there is currently a gap between the two. But we all do our patients no service whatsoever to pretend that we lie wholly in one camp or the other, and that one is somehow more relevant than the other. Clinicians and scientists (and their patients) need to appreciate the complexities and needs of each side, and this new scientific paper in this journal should be a catalyst for more open debate by all.