IVF and Immunology: The Role of Immunologic Factors and Selective Immunotherapy

Few innovations in IVF have evoked the degree of controversy and bad press as has the thesis that reproductive immunologic factors play a role in unexplained IVF failure and recurrent pregnancy loss (RPL), and that immunotherapy presents a valid treatment of these problems. This despite the fact that thousands of women with repeated and unexplained IVF failure, and/or RPL have following diagnosis and selective immunotherapy, gone on to have healthy babies. The question then, is why is there a compulsion on the part of many to selectively criticize the role of an immunologic component in reproductive failure? Is it due to arogance, ignorance, politics or all three?

The most comon criticism is to claim that the whole concept of immunologic implantation dysfunction (IID) requies proof through randomized statistical trials and that without such proof there is no basis for teating such disorders. I would submit that this position is hypocritical and represents a "double standard". Consider the fact that were all procedures and therapies provided in the AR arena to be subjected to the same degree of scrutiny, there would virtually be no clinical AR service that could justifiably be offered and the entire discipline would fall apart. It is a fact that if the same criteria were required fo an AR procedure or treatment to be elligible for inclusion in a compedium of AR, the book would be less than a single page in length.

The truth is that given the multitude of variables that influence IVF outcome it would be impossible to control all variables other than the one being evaluated. That is why to todate, virtually all clinical treatments/processes currently in use in the AR arena have gained acceptance through a process of longitudinal efficacy testing (by trial and error), rather than through "gold standard", randomized and controlled statistical testing.

Consider the following: Embryo abnormalities account for 70%-80% of IVF failure, while implantation problems (including immunologic factors), only account for 20%-30%. One of the important reasons why in the past it has not been possible to reliably conduct randomized statistical trials in IVF is that to do so it would be necessary at the very least to confidently assess " embryo competency" (i.e. the ability of an embryo, upon reaching a receptive uterine environment to proagate a healthy pregnancy). Obviously to study the effect of variables such as immunologic implantation on IVF, it is essential that "embryo competency" first be known, otherwise how would one assess the impact of variations in the "lesser" variable (IID) on outcome. Alas, hitherto the use of Microscopic embryo grading and even preimplantation genetic diagnosis genetic diagnosis (PGD) using fluorescence in-situ hybridization (FISH) to accurately determining embryo "competency”, has been poor.

An important recent innovation introduced in 2006 by SIRM could change all this and open the door to evidence based statistical testing of the variables that affect IVF outcome. This breakthrough came with the recent introduction of a new genetic process known as comparative genomic hybridization (CGH) that through assessing all the embryos chromosomes can relatively reliably differentiate between chromosomally normal (“competent”) and abnormal (“incompetent”) embryos. me.

And so perhaps at last we will be able to better evaluate the role of immunologic factors in the genesis of implantation dysfunction as well as the benefit of selective immunotherapy, and thereby put this controversy to rest. Such a study is currently underway at SIRM , and while complete interpretation must await its completion and full statistical analysis, preliminary findings suggest that there indeed is likely to be a distinct benefit in selectively treating women with immunologic implantation dysfunction (IID)with Intralipid (IL) steroids (e.g. dexamethasone and prednisone) and/or heparin therapy.