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Rethinking Implantation Failure: CHR's Approach
What are the real causes of implantation failure? There are many theories about why a woman may have trouble achieving implantation of an embryo in her uterus, but CHR is rethinking the traditional therapeutic approach to these cases.Want to Consult Dr. Gleicher?
Hello. I would like today to talk to you about implantation failure and what can be done about it clinically. In the previous video, I tried to explain what implantation really is all about and let me quickly rehash. It's basically a little parasite trying to be allowed to enter into the maternal environment. The embryo is half paternal (meaning genetically this half from the father) and if the woman were to get from her partner let's say a mini kidney transplant, she would violently reject the transplant. Yet, that little transplant, that little sucker called an embryo, that is trying to get in and to dig into the wall of the uterus (what we call implantation), that little embryo is usually allowed to come in and do its job. Except in some cases, of course, and when we believe that this process (this normal process of implantation) doesn't work right, then we call this an implantation failure patient. That is very important to understand that we do not have a test. We cannot draw blood. We cannot do an X-ray. We cannot do anything to say with certainty that this patient has implantation failure. The diagnosis of implantation failure is done kind of in reverse. It is done if a patient over an extended time period even though she was treated appropriately, usually in IVF had a good number of great-looking embryos transferred, that is still not pregnant, then the assumption is made that it is not the embryos which are the major cause of IVF failure, but that it may be the implantation process. So the diagnosis of implantation failure is a hypothetical diagnosis that in many cases may be actually wrong. There may be another reason why pregnancy doesn't occur, but the diagnosis is made by exclusion. And once the diagnosis is made, the next obvious question that comes up is what can we do to overcome this problem? And that is an even bigger issue because once you cannot be sure about a diagnosis, it is even more difficult to design appropriate treatments because your patient populations and studies are usually contaminated by patients who don't even have the problem. And it is for that reason that the area of "implantation failure" and its treatment has remained highly controversial and really to a large degree unresolved. And therefore I want to give you quickly a few very simple principles. You may have heard all kinds of stuff about implantation failure. You may have heard that NK cells (so-called natural killer cells) cause implantation failure. You may have heard auto-immunity causes implantation failure. You may have heard that immunization caused implantation failure. All of that is likely incorrect. And the reason why it is incorrect is because as we now increasingly understand how implantation happens, we understand that the reason why a woman with autoimmune problems has more difficulty in implanting and has more miscarriages is not because she has auto immunity, but because women with auto-immunity and with other conditions that result in a hyper-active immune system do not have the ability to reprogram their immune system from rejecting that invading foreign body to tolerating it. In other words, that switch in the immune system from rejection to tolerance doesn't work well. And therefore as a consequence in women with hyper-active immune systems, when that embryo is trying to implant, it is still viewed as a foreign invader and is attacked. So it is not an auto-immune response, but in allo-immune response that the immune system mounts against the implanting fetus that can cause implantation failure and miscarriage. And that is important for treatment because what this means is that we are not treating an autoimmune process, but we're treating an allo-immune process. In other words, we are not treating something like lupus, but we're treating something like organ rejection after a transplant. And therefore we have to start rethinking our therapeutic approach when we really believe that a patient suffers from implantation failure and, in its extension, from increased risk for miscarriages.
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