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    Immunological Problems

    The main function of the immune system is to protect the organism from infections. It “rejects”, i.e. repels, invaders (viruses, bacteria) perceived as “foreign bodies”.
    In some cases, the immune system does not function properly, which leads to various health problems. Concerning reproduction, it is clear today that many miscarriages at early stages of pregnancy are caused by the irregular activity of the woman’s immune system.
    Scientific research has shown that, in a normal pregnancy, the woman’s immune system functions under “special conditions”, in order to protect the embryo and let it grow. If this mechanism doesn’t work, the embryo may fail to implant, a miscarriage may be caused or complications for the mother or the embryo may occur during pregnancy. Today, there still is no cure, however, various treatments (immunotherapy) are proposed by research centres abroad (mainly in the U.S.), aiming at restoring the “proper” function of the mother’s immune system, so as to increase possibilities of a normal pregnancy.
    Patients must understand and accept that immunotherapy against infertility still is at a research/ experimental stage, as there are no clinical studies concerning large numbers of patients, with statistically significant and reliable results. For that reason, immunotherapy is not acceptable to everyone. Moreover, the administered medication hasn’t been officially approved to treat infertility. Until then, immunotherapy must be applied in isolated cases. At “gennima”, we cooperate with specialised hematologists- immunologists, aiming at integrally informing the patient, based on the latest scientific research findings.

    Deficient protection of embryo by immune system

    In a normal pregnancy, the embryo that carries the genes of the father (recognised by the mother’s immune system as “foreign”) survives and grows in the uterus, because the immune system of the mother functions under “special conditions” with regards to the uterus and the embryo. Thus, the embryo is not rejected as a “foreing body” (as for example it happens with transplanted kidneys). This happens because the fertilised oocyte activates a protective reaction of the maternal immune system, which enables embryo implantation and growth.
    In couples with very similar genetic material, this reaction of the maternal immune system is not activated and the embryo is rejected (miscarried).
    A treatment widely used a few years ago entailed the so-called “anti-parental vaccines”, a therapeutic approach that has given rise to many questions, objections and doubts. Theoretically, when the mother is exposed to the foreign genetic material (of the father), her immune system is activated, to protect the embryo when she gets pregnant. This may be achieved by isolating blood cells of the father and injecting the mother with them. Although theoretically, the anti-parental vaccines treatment seems to be scientifically substantiated, it was widely used in the U.S. with no evidence of offering substantial benefits. A few years ago, this led FDA (Food and Drug Administration) in the U.S., to legally abolish such treatments. Today, the administration of anti-parental vaccines only serves research purposes concerning the treatment of recurrent miscarriage.
    Based on his personal experience and clinical research, Mr. Evripidis Mantoudis at “gennima” believes that only a very limited number of couples could benefit from this treatment. In the U.K. though, the anti-parental vaccines treatment has never been widely used.

    Antiphospholipid antibodies

    Phospholipids are necessary in embryo implantation and placenta development. In case of an antiphospholipid antibodies (APA) attack, embryo implantation and development are adversely affected. The mechanism by means of which APA harm pregnancy entails clot formation and blood vessel blockage, which impede normal blood circulation towards the embryo.
    The main antiphospholipid antibodies with a confirmed impact on recurrent miscarriage are anti-cardiolipin antibodies (IgG and IgM). Lupus anticoagulant is also important, as it acts similarly to APA (i.e. forming clots). The existence of APA can be detected by means of a blood test. As those tests are particularly sensitive, it is recommended that the patient repeats them in case of a positive result. There are two treatments that include the administration of either low – dose aspirin and heparin (which impede excessive blood clotting) or a steroid (and heparin), aiming to suppress the maternal immune sytem, which produces those “abnormal” antibodies. These are the only treatments proved to reduce miscarriages.

    Antinuclear antibodies

    Some patients develop antibodies against the genetic material (DNA) of the embryo, called antinuclear antibodies (ANA). Therapy consists in administering a steroid and an anticoagulant treatment.

    Increased ΝΚ (Natural Killer) cells

    ΝΚ cells are cells of the immune system, which, among others, prevent the body from developing cancer cells, by producing the Tumor Necrosis Factor (TNF). ΝΚ cells help the system fight infections. These cells have been accused of being responsible for attacking the developing embryo, which leads to miscarriage. It has been found that in 12% of patients with a history of 3 or more miscarriages and in 35% of patients with 3 or more failed IVF cycles, the number of NK cells is increased. In those women, an increased amount of TNF is produced and attacks the embryo, thus impeding implantation.
    ​Many doctors recommend tests to measure NK levels in the blood. In case the number of NK cells is increased, treatments are recommended to suppress NK cell activity. Steroids or low - molecular - weight heparin or intravenous immunoglobulin or anti-TNF factors (Humira) are administered.
    However, there are doctors who do not adopt this approach, because:
    • It is not clear whether NK cells detected in the blood attack the embryo.
    • It hasn’t been proved whether the control and subsequent suppression of NK cells in the blood decisively affect the chances of having a normal pregnancy.
    Although in some difficult cases of infertility or recurrent miscarriage, we recommend tests and adopt treatments against NK cells, their effectiveness and usefulness have not been proved yet. In any case, they are applied after the patient is fully informed.

    Please read below more from the HFEA (Human Fertilisation and Embryology Authority) of the U.K.: http://www.hfea.gov.uk/fertility-treatment-options-reproductive-immunology.html

    Gennima | Gynaecology & Reproduction Center

    346 Kifisias Avenue, 15233 Chalandri - Athens, Hellas
    +30 210 68 16 100
    +30 210 68 30 321 (fax)
    info[at]gennima[.]eu

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