The human body has its own natural defense system against attacks from diseases. Pregnancy is a unique situation where the baby is attached to the uterus.
The human body has its own natural defense system against attacks from diseases. Pregnancy is a unique situation where the baby is attached to the uterus. During pregnancy, the baby is recognized by the immune system as “not me” or “alien” due to the mother’s different genetic characteristics. The mother’s immune system is very important for the pregnancy to last until birth. She should both be aware of this and accept this invasion. Therefore, the interaction between IVF and the immune system is also very important for us to have a healthy baby.
It is known that immune cells called natural killer cells eliminate foreign substances and cancer cells.
Natural killer cells in the blood are naturally occurring cells that play a vital role in the immune system. These are lymphocytes (white blood cells) produced in the bone marrow, spleen and other parts of the body before entering the bloodstream. The purpose of these cells is to recognize and target cells that do not belong in the body; tumors, viruses, bacteria.
Natural killer cells play an important role in pregnancy and make up 90% of the immune cells in the uterus. Women with fertility problems, recurrent miscarriages or recurrent IVF failures may have a problem with Natural killer cells. If there is high Natural killer cell activity in the mother’s body and uterus, this affects the baby’s attachment to the uterus and prevents this invasion, making it difficult to attach and eventually causing miscarriage. Natural killer cells lead to miscarriage and infertility. Preventing and treating this problem also increases fertility. Clinics that offer treatment for high Natural killer cells often offer this service in conjunction with IVF and other assisted reproductive technologies.
One of the most common causes of immune-related problems in IVF is the failure of the baby to implant in the uterus. In this case, it is the abnormalities in the mother’s immune system that interfere with successful implantation.
The levels of Natural Killer cells are not the same as those of someone who has had cancer or an autoimmune disease, for example. Women with high levels of Natural Killer cells produce too many immune factors that attack the embryo and prevent implantation.
If the aggressive Natural Killer activity is high, the embryo cannot implant, early pregnancies can end in miscarriage, and complications can occur for the mother or baby later on. Special tests can identify couples at risk of these problems. Treatment that stimulates the appropriate immune response in the mother (immunomodulation) can increase the chances of a successful pregnancy and birth.
How to test?
There are two types of Natural Killer cells.
1. Natural Killer Cells in the Blood (peripheral Natural Killer Cells).
2. Natural Killer Cells are found in the lining of the uterus and are called uterine Natural Killer cells. This can be determined by taking a sample of the lining of the uterus and sending it to a pathology laboratory for analysis.
The NATURAL KILLER diagnostic panel measures the number of natural killer cells in the peripheral blood, and the NATURAL KILLER cells in the uterus are measured in a biopsy of the uterus.
Usually, measurements of Natural Killer cells are taken from the counts of blood cells in the peripheral circulation via a venous blood sample. If tests are performed on the lining of the uterus by biopsy, there is no standardized method for testing. Natural Killer cell counts vary depending on the time in the menstrual cycle and the epithelial layer being tested. Studies show that the percentage of cells in the peripheral blood of normal healthy women is ‘elevated’ when it is above 12% and this situation requires follow-up and treatment.
In addition, the biological indicators of NATURAL KILLER cells, which play a vital role in infertility, recurrent miscarriage and unsuccessful IVF, can be measured with the TH1 TH2 panel. This situation negatively affects the baby’s attachment in every expectant mother whose biological indicators are outside the normal range.
Treatment options
It has been known since the 1950s that Natural Killer cells can play a role in pregnancy. In the 60s, it was discovered that cells with similar properties to Natural Killer cells in the endometrium are found, especially in the membrane between the mother and the baby. These cells perceive the embryo as foreign and begin a violent attack that can result in a risk of miscarriage. At this stage, clinicians often recommend steroid treatments, intralipids, or intravenous immunoglobulin. Women with recurrent miscarriage or IVF failure who have high NATURAL KILLER activity should be treated. Recommended treatments include immunosuppressive drugs such as steroids. Each case should be reviewed individually and an appropriate treatment plan should be prepared, including risks and side effects. Possible treatments include steroids and intravenous infusion of Intralipid. Intravenous immunoglobulin can be used in women with soy allergy. There are potentially serious adverse reactions to some drugs. Care should be taken to treat under close supervision. Consent from the couple is required for these treatments.
The main complications resulting from long-term treatment with steroids are fluid and electrolyte disturbances, hyperglycemia (high blood sugar levels), glycosuria (abnormal amounts of glucose in the urine), increased susceptibility to infection, peptic ulcer, osteoporosis, behavioral disorders, e.g. irritability, insomnia, mood swings, cataracts and striae (skin stretch marks). Symptoms return to normal when steroids are discontinued. Side effects can be prevented with the right treatment plan, e.g. diet, lifestyle and some medical support. Potassium supplementation, salt restriction in the diet and regular blood pressure monitoring are recommended. However, moderate doses are used in treatment. The placenta (the baby’s partner) does not pass the drug to the fetus (baby).
Intravenous Intralipid Infusion Therapy
Intralipid is an emulsion of soybean oil, egg phospholipids and glycerin. Data from both animal and human studies suggest that intravenous Intralipid administration may increase embryo implantation. Intralipid stimulates the immune system to reduce “danger signals” that can lead to pregnancy loss. In addition, recent evidence has confirmed that Intralipid reduces Natural Killer cytotoxicity, increasing implantation and allowing a sufficient time for the pregnancy to continue. Clinical studies using Intralipid have shown improved pregnancy and live birth rates in women with increased NATURAL KILLER activity and TH1/TH2 abnormalities in recurrent embryo implantation failure and recurrent miscarriage.
Studies comparing IVIg to Intralipid have confirmed that they all suppress NATURAL KILLER cell cytotoxicity with equal effectiveness. However, Intralipid has the advantage over iVIg in that it is not a blood product.
Nature and Duration of Procedure
Treatment is administered intravenously, and dosage and infusion protocols are determined based on laboratory tests and clinical responses. Treatment is usually performed while trying to conceive and during pregnancy. The procedure lasts at least two hours. The treatment process is monitored at intervals until delivery according to test results. Patients who are allergic to eggs or soybean oil should report this.
Side effects are rare and include fever and chills, nausea, vomiting (less than 1%). Other adverse effects are extremely rare, occurring in 1 in 1 million infusions. Hypersensitivity reactions (anaphylaxis, skin rash, and urticaria), respiratory symptoms (rapid breathing), circulatory effects (high or low blood pressure), abdominal pain, headache, and fatigue. The safety profile of Intralipid treatment is considered extremely good.
Preeclampsia (PE) in the period leading up to birth has been classically defined as a Th1/Th2 imbalance. High blood pressure, edema, and excess protein in the urine should be controlled with immune tests throughout pregnancy, and immune therapy should be continued at certain intervals until birth, with the test results being evaluated.
The relationship between in vitro fertilization and the immune system has been a topic of particular interest in recent years. Although there is no consensus or definitive evidence yet on the research tests and treatment methods that lead to failure or miscarriage in which patients, some of the ‘difficult’ couples can have babies as a result of these treatments.
I wish all expectant mothers to hold their babies in their arms in health.
