Immunotherapy - Intralipids
All treatments below are at experimental stage. The medication administered has not been officially approved for infertility or pregnancy. Drugs may have severe side effects, while some of them are really expensive.
Low - dose aspirin (75mg per day) is administered to patients with antiphospholipid antibodies or NK cells either as monotherapy or in combination with heparin or steroids.
When a patient takes low - dose aspirin, the expected side effects are minimal. In regular dose, aspirin side effects are: nausea, stomach disturbance, blood in stool or, more rarely, allergic reaction. Patients with a history of side effects related to the gastrointestinal system take aspirin in enterosoluble tablets, which do not cause such problems.
More recent data sustain that aspirin increases miscarriage risk in early pregnancy and that, for that reason, patients should stop taking low-dose aspirin right before embryo transfer (in case of an IVF cycle) and for the first period of pregnancy.
Low - molecular - weight heparin is administered to patients with hereditary thrombophilia due to a mutation of factor V Leiden or of Protein C or S. Low – molecular - weight heparin is injected subcutaneously (in the abdominal area).
Contraindications for low – molecular - weight heparin:
• Known hypersensitivity
• Thrombocytopenia (low platelet count)
• Severe hypertension
Frequent side effects:
• Mild irritation at the injection site (pain, swelling, erythema).
• Osteoporosis after long – term use.
For that reason, it is recommended to take calcium supplement.
The patient must contact her doctor in case she has the following symptoms:
• Blood in urine or stool
• Bleeding that lasts for more than 15 minutes and doesn’t stop with pressure
• Swelling (not at the injection site)
The most frequently administered steroids are dexamethasone and prednisolone. They are prescribed with the aim to suppress the irregular function of the immune system (ΑΝΑ or anti-DNA antibodies).
Long-term use of steroids has a number of severe side effects, mainly fluid and electrolyte disorders, hypertension, tendency for diabetes and infections, peptic ulcer, osteoporosis, changes in behaviour etc. All side effects are impermanent and pass off after the end of the treatment. The treatment must stop gradually, or else various symptoms are observed. Numerous studies have demonstrated that steroids do not penetrate the placenta, thus they actually do not affect the embryo.
Intravenous immunoglobulin is administered as monotherapy or in combination with traditional immunotherapy (anticoagulants, immunosuppressants) to patients with recurrent miscarriage or infertility due to immunological problems.
Indications for administration:
• Increased number of NK cells
• High levels of ANA
• High levels of antiphospholipid antibodies
• To replace steroids in patients who experience side effects
• Active autoimmune disease (autoimmune thyroiditis, lupus erythematosus, rheumatoid arthritis)
Intravenous immunoglobulin is produced from human immunoglobulin (mainly IgG, in high concentration), from donors (8.000-13.000 per batch).
Immunoglobulin is controlled for diseases spread via the blood stream (hepatitis B and C, HIV) and no case of HIV transmission after having taken immunoglobulin has been reported until today. However, there have been reported cases of hepatitis transmission from batches that hadn’t been properly processed. IgA levels must be checked before administering immunoglobulin to patients, so as to avoid severe allergic reactions.
Humira belongs to a new category of medication, impeding the impacts of TNF (anti-TNF factors). It has been approved for patients with rheumatoid arthritis who do not respond to any other treatment. Recently, it has been shown that it may be effective in cases of recurrent miscarriage or implantation failures. It must be administered before the infertility treatment (e.g. IVF) in order to restore TNF at normal levels. It mustn’t be prescribed to pregnant women or to patients with active infections, e.g. tuberculosis.
Humira is the first entirely human monoclonic antibody. Its structure and function are identical to those of the antibodies normally produced in our system, thus no allergic reactions are expected. Humira is subcutaneously administered every 2 weeks. The usual side effects occur at the injection site (pain, swelling, itchiness). There have been reported cases of severe infections or reactivation of tuberculosis after taking anti-TNF factors. In approximately 10% of the patients, it fails to reduce TNF levels.
Intralipids is a rather novel treatment for couples with recurrent miscarriages or multiple failed IVF cycles. Fertility expert Dr Evripidis Mantoudis was one of the first doctors in Greece to use it. Intralipids help create a friendlier immunological environment for the embryo. This way, they are considered to increase implantation and ongoing pregnancy rates.
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Intralipids’ ingrediens are: 1.2% egg phospholipids, 20% soybean oil, 2.2% glycerol and water. They are administered intravenously (IV drip for 2 hours) prior to embryotransfer. Another dose is administered following a positive pregnancy test and then every 3-4 weeks, usually during the first trimester (so 4 doses in total). This way, the NK cells’ activity is controlled (these cells are considered ‘hostile’ to the pregnancy) and the immunological profile gets back to normal until the pregnancy is established. Intralipids is a much cheaper treatment compared to other alternatives, such as immunoglobulin. It is well tolerated and there are no adverse effects to the mother or the embryo. Clinical studies so far indicate encouraging results as to pregnancy rates.
‘Intralipids are suitable for patients who have suffered recurrent miscarriages or multiple failed IVF treatments, whose immunological profile is hostile to the pregnancy, for example elevated NK cells numbers’, Dr Mantoudis says.
What should a woman know before planning her next pregnancy after a miscarriage?
If you had 2 miscarriages or more, usually tests are carried out to identify the cause of those miscarriages.
The usual tests are the following:
• Hysterosalpingogram or hysteroscopy, so as to find out whether there are any uterine anomalies,
• Blood tests, to measure the levels of some hormones, such as progesterone,
• Blood test for antiphospholipid antibodies and other immune system factors,
• Blood tests for thrombophilias,
• Blood tests for sexually transmitted diseases,
• Karyotype test for the man and the woman, in order to examine whether there are any genetic anomalies.
Which therapeutic options do women with a history of recurrent miscarriage have?
Sometimes, it is possible to treat the problem that caused the miscarriage, e.g. remove a uterine diaphragm by hysteroscopic surgery or regulate a hormone disorder in patients with Polycystic Ovary Syndrom.
What are the odds of having a healthy baby after recurrent miscarriage?
Although the aforementioned tests aim at revealing the cause of recurrent miscarriage, no specific problem is diagnosed in a high percentage of couples.
If the cause of recurrent miscarriage is diagnosed, it is easy for someone to deal with it: there are effective treatments for specific endocrinologic problems or uterine anomalies. Even when no problem is detected and everything seems normal (tests showing no obvious cause), the good news are that the miscarriage issue is very often solved automatically. In that case, the odds for a healthy pregnancy exceed 60%.