A fascinating view on immunological infertility

Recurrent implantation failure. Three words that are so hard to hear and bear for couples who are striving to conceive a child with the help of reproductive medicine. But this scenario happens in IVF procedures and doctors from all over the world are trying to understand how this happens and what can they do to prevent it. Among these world renowned experts there is Prof. Dr. Tayfun Bağış, the Head of the Assisted Reproduction Department from ACIBADEM Altunizade Hospital. Professor Bağış is famous for his assidous work on the immunological infertility theory. A very short description of it would be that in many cases, the experts believe, the woman’s body rejects the embryo just like a transplant patient does not accept the new organ. What is the exact mechanism and what can be done about it, we will find out in the following material.

With thousands of patients from all over the world, and 15.000 IVF procedures performed, Prof. Dr. Tayfun Bağış is a reference in the Assisted Reproduction field. Many couples arrive at the ACIBADEM hospital at Istanbul for a consultation with him after seeing multiple specialists and having faced many implantation failures.

“First of all, you should know that there are two parts involved in the success or failure of the implantation. One part is the embryo, his quality, his survival. And one part is the woman’s body. So when you have unsuccessful IVF, you have tried three times, four times, and you didn’t succeed, and you are asking about the problem, we think that the problem is eithe in the embryo, either in the body. If I see from the patient's history that the problem is in the embryo, I don't do anything, I just change the protocols. Maybe it’s the IVF center problem, maybe it's not the patient's problem. Nobody talks about this topic, nobody says, Yes, this is my center problem, it's not your problem. So, first of all you should be sure of the quality of the embryo. At least from a morphological manner. If the patient has a history of giving very good quality embryos and everything seems ok, then you can think about an implantation problem”.

The following theory – the immunological infertility – is a theory that preoccupies Professor Bağış, who works a lot in this area and has become famous in many parts of the world for his beliefs on this matter and the trials that he has made.

“We know that, for example, when you perform a renal transplantation or a liver transplantation you have to find right person to take liver or kidney, you have to have compatibility. Our body acts very actively against foreign, let's say, microbes or antigens. But how does the body know which one are his antigens and which are not. Our immune system, knows that is part of our body and it should not attack it. Now, let's see what's happening during embryo transfer. The embryo - one part is the woman’s egg and one part sperm. Sperm is from a different body. It's coming from another person, it's not from your brother, it's your husband’s. You are not coming from the same family. When you put sperm here, this becomes a semiallogeneic transplantation how the medicine calls it. After that we are putting the embryo in the endometrium. The body, if it works properly, you think that basically, it should throw it, it should reject it, this is not part of me, I will attack this embryo. So what's happening? We don't know exactly, but we do know that some system acts different in the endometrium and in the rest of the body. And maybe there is something like soldiers that are observing all the move, and when they see the enemy, they kill it, but maybe there some helpers also – the first ones are very aggressive, and the others are less aggressive. At the time of implantation, these less aggressive increase their numbers and the aggressive ones drop in number. This is how the body acts. So before ovulation and after ovulation is a whole different system. Some women cannot change this system, cannot make the switch. The number of high aggressive cells remains high and when the embryo comes, they kill it, they reject it. This is immunological infertility. Immunological, because it’s related to immunology, to the immune response. If you ask all of the doctors if there is an immunological role in this process, they would say yes“.

It may sound like the problem is identified and maybe solvable. But…

“The problem is actually how we are going to diagnose these women that have this immunological problem. I work in this area a lot. Previously I was looking only at the natural killer cells, but we learned that only natural killers are not enough. The natural killes in the periphery are of one kind, and in the uterus, so inside, are different. Nearly 8 years ago, I saw a medical paper coming from probably United States, I am not sure about it, but they had made a study together with England in one center where they are dealing with reproductive immunology. A reproductive immunologist is very very rare. In Turkey, for example, there is no reproductive immunologist. The specialist from the study that I have mentioned were looking for TH1 - TH2 levels - I told you there are aggressive and less aggressive natural killer cells. And if the woman has a very aggressive response, they try to suppress this TH1 - TH2 levels. So I really appreciated the results and I have studied the method, very very carefully. One point was very attractive, it impressed me: they have implanted good quality embryos, good quality blastocyst, two blastocyst, and they have suppressed the immune system, and they have achived nearly 100% succes rate. Sometimes I know that people could lie, they want to be hero, but no one can lie like this, 100%. It is very impressive. So at this point I started to think what can I do. In their study, they have used TNF alpha inhibitors, used in some rheumatismal disease, but it is a expensive and may be dangerous becomes for example it can activate tuberculosis. And then I have read one more medical paper coming from, probably, Japan, where they have used one drug, Tacrolimus, an immunosuppressive drug. I have learned that many patients used this drug after transplantation, and they use it all of their life. So I looked if there's any problem during pregnancy, and I found out that we can use it during pregnancy also, it is not dangerous. And it is cheaper. Intralipids are also of a good use because we have learned that they suppress TH1-TH2 levels and many have said ok, so we are going to start using intralipids, but there is no program, no guide, how are we going to know if we should use it before the embryo transfer, after the embryo transfer, immediately after a woma has become pregnant, how do we know whether we should repeat the dose or not, things were not very clear”.

The Professor has started his own protocol trial, a trial that had amazing results.

We have started to give patients intralipids at the time of the embryo transfer and we have start the program after oocyte pick-up and some many patients that had implantation failures 5 times, 6 times, 8 times before, they have become pregnant! Now I have nearly a hundred or more patients, among these the number of previous tries, the average number is 5.8, and nearly 65% of them have become pregnant. But I couldn't publish it, it is not very easy, you can have many critics about it. In medicine, when you send this trials to journals, there are a lot of conditions, you have to randomize the patients and how can I do randomization? How can I say to a patient you have tried 5 times, but this time I will not try anything, you will just be a participant, with no benefits. It's not possible, not for me”.

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