This is the 7th in a series of 10 responses to common questions/concerns about IVF

#7 There are as many experts as there are opinions in IVF, so who am I to believe when it comes to issues such as the value of genetic testing and the role of immunology in IVF?

Undoubtedly, for many couples planning to undergo in vitro fertilization this is a very perplexing issue. There are so many conflicting opinions out there, which are often presented with an equal amount of fervor and conviction, so as to truly confuse even the most savvy patient. Who should be believed and who should not?

The problem is that IVF is as much an art as it is a science. Therefore, what may work best in the hands of one medical specialist might not be effective in the hands of another. A good analogy would be two different artists painting the same landscape. How likely is it that the two renditions would be the same? Very unlikely. It does not necessarily mean that the one rendition is better than the other, but rather that they express the independent experience and artistic interpretation of that particular artist. So it is with IVF; most of what we do is based upon our individual interpretation and expression of available scientific information.

Another issue is that more than 90% of published scientific data relating to IVF cannot be validated through gold standard statistical analyses, and thus lack reliability. I often say that if a textbook on IVF were to be confined to those things that have been proven through randomized statistical confirmation, it would probably be just a few pages in length. Why is this case? Well, there are two important variables that influence the success or failure of IVF. The first is the “competence” of the embryo and the second is the receptivity of the uterine lining. I often compare this to the relationship between a seed and the soil in which it is planted. In order for a healthy plant to grow a good seed must be planted in a receptive soil. In the case of human reproduction, for a healthy baby to result, a “competent” embryo (one that is chromosomally and genetically capable of making a baby) must find itself in a receptive uterus (one where the lining is both adequately prepared hormonally and is free of anatomical or immunologic impediments to implantation). The problem is that until recently there has been no reliable method for measuring embryo competence. Microscopic embryo grading and even preimplantation genetic diagnosis (PGD) using methods such as fluorescence in situ hybridization (FISH) are incapable of reliably defining the “competence” of an embryo. Consider the fact that a “pristine looking” top-grade day-3 embryo resulting from fertilization of a 31 year old’s eggs is approximately 10 times more likely to be genetically/chromosomally normal (competent) than an identical looking embryo derived from an egg of a 45 year old. Since more than 70% of the time it is “embryo competence” rather than uterine receptivity that will determine the success or failure of an embryo to implant and successfully develop into a healthy baby, absence of knowledge regarding the “competence” of an embryo makes it virtually impossible to evaluate the success of any procedure or process involved in treatment, in terms of an outcome. If embryo competence cannot be determined with confidence, how then is it possible to assess the relative benefits of the various protocols, processes and procedures in IVF. But, this all could change with the recent introduction of reliable genetic tests of embryo competence known as Comparative Genomic Hybridization (CGH).

Immunologic Causes of Infertility
There can surely be no area of greater controversy in the field of IVF than that which relates to the value of selective immunotherapy for immunologic causes of implantation dysfunction. In fact, there are those that do not even accept that immunology plays a role in orderly implantation and placental development. Since both embryo competence and uterine receptivity together determine the success of implantation, and since it has been difficult until recently to assess embryo competency, it has accordingly not been possible to prove the potential value immunotherapy might have in terms of IVF outcome. However, with the recent advent of reliable genetic assessment of embryo competence (i.e., CGH), all this is likely to change in the near future. Now, for the first time, we are able to control for this variable and so confirm or refute the benefit of such immunotherapy in IVF.

It is a fact that about 70% of women who undergo IVF are at or below their mid 30’s, have normally functioning ovaries, and have straightforward indications for undergoing the procedure. These women will usually respond well to standard “recipe” type protocols of ovarian stimulation, will produce an adequate number of mature eggs and will readily conceive following one or two attempts.

However, for the remaining 30% who fall outside the bell-shaped curve of normal distribution, such a straight forward simplistic approach will often fail. These are the very women that might well be candidates for an approach that takes into consideration a thorough immunologic evaluation and the need for an individualized approach to ovarian stimulation that would optimize egg and embryo quality. Against this background, it is easy to see how IVF statistics that are simply based on the woman’s age can be seriously flawed since they inevitably fail to take into consideration that there is a wide variation in patient clinical profiles, and that such variations often complicate matters severely.

So, when it comes to deciding whom to believe, the bottom line is that you need to a) be well informed by your physician as to what your options are and b) ask the right questions. To do so requires that you do your homework. This means communicating with others who have been treated by your physician for a similar problem, as well as speaking with other physicians. Many times, this can be facilitated through social networking channels such as blogs and discussion boards. Why go to such great lengths? Because it is against this background and ultimately, by your gut feeling, that you should make a final decision.