Fertility and the immune system: a dance of two
Over the past decades, it has become increasingly evident that immunological factors contribute substantially to infertility situations.
He The body's immune system has among its functions to distinguish between what is its own and what is foreign.. In this way, it is capable of identifying any invasion by foreign microorganisms - which could create an infection - or identifying cells that are not behaving as they should - which could trigger cancer.
In some cases, the immune system can make mistakes in this task. And when there is an error, it also begins to react against its own tissues, generating an autoimmune pathology.
Approximately 7% of the population suffers from an autoimmune disease at some point in their life. And some of them suffer from lifelong autoimmune diseases, such as insulin-dependent diabetes or rheumatoid arthritis.
The immune system has “memory”, it keeps a memory after each battle. It's as if you have a hard drive with a large database of identified criminals.
This is a very useful feature to gain effectiveness against future attacks.
Vaccines are based on this system: they teach how to respond effectively and efficiently to the immune system by confronting different attenuated pathogens. Once vaccinated, when said pathogen appears, the immune system will be better prepared to act.
This memory function resides in the so-called antibodies. This very useful memory system can become a problem when, if you suffer from an autoimmune pathology, antibodies are created to go against your own cells and tissues. In these cases, memory also acts and favors the perpetuation of the pathology.
Pregnancy and immune system
Pregnancy is a unique and very particular situation, which requires the immune system to limit itself in its functions.
A new cell, with at least one 50% of its composition from something “foreign” (man's genetic information) and growing abnormally rapidly, begins to invade and spread through the body's tissues.
On paper, this cell would undoubtedly be a target of the immune system. However, that is not the case.
For pregnancy to occur, the immune system must increase its immune tolerance enormously. The state of the mother's immune system is essential to establish a relationship between the mother and the fetus that is viable for both..
This immunological tolerance begins with a chip change. The immune system has two very different ways of acting.
Types of action of the immune system
This immunological tolerance begins with a chip change. The immune system has two very different ways of acting.
Type 1 or cellular and type 2, humoral or antibodies.
Depending on what type of invasion the body is receiving, the immune system uses one tool or another, as it sees fit.
During pregnancy, since the new cell is a foreign cellular agent, the body prioritizes the type 2 way of working and, in this way, the new cell will not be a target of the immune system. It will be able to implant and grow properly.
This chip change means that some autoimmune diseases, which involve a predominantly cellular immune reaction (type 1), such as rheumatoid arthritis, tend to improve during pregnancy. But it also means that autoimmune antibody diseases, such as lupus, can get worse. It has been seen that there are specific antibodies that can have harmful effects on both the placenta and the fetus.
Dictionary of immunological terms
The immune system is so broad that understanding it and its implications on fertility can be complicated. For this reason, it is interesting to decipher some of these terms in order to improve immunity and fertility.
Natural Killers or natural killer cells
There are two types of immune systems: the innate and the adaptive. The first is more ancestral and we could say that “it comes from the factory.” The second is, as its name indicates, learned, adaptive and specific.
It is formed as it faces foreign elements and forms the immunological memory.
The Natural Killers or natural killer cells They are a type of white blood cell (lymphocyte) that is part of the innate immune system. Its ability to kill is also closely related to cellular or type 1 immunity.
As such, they are potentially very threatening to a developing pregnancy.
However, they are the main type of immune cell found in the uterus. Their number increases throughout the menstrual cycle and reaches its peak at the time of implantation of an embryo. If an embryo implants, the number of Natural Killers It further increases to 70 percent of all cells.
The amount of Natural Killers begins to decrease at 20 weeks of pregnancy. Finally, they are non-existent at the end of pregnancy. This relationship makes it more than likely that these killer cells are intimately involved in the success or failure of embryo implantation, causing infertility and miscarriage.
However, this point has not yet been scientifically proven.
Antiphospholipid syndrome
In antiphospholipid syndrome (APS), women have “anticardiolipin antibodies” or the “lupus anticoagulant.” If these antibodies occur in women with reproductive failure and no other clinical problems, it is called primary APS. If there are also other autoimmune diseases, such as systemic lupus erythematosus or Sjögren's syndrome, it is called secondary APS.
It is not yet clear whether antiphospholipid antibodies have an effect on fertility. While they are more commonly found in women undergoing IVF, they can be found in 4% of the healthy population.
The problem is that they can directly attack placental cells. They are often used as markers of a possible immunological disorder, but are primarily evaluated in the context of pregnancy loss.
Consequences of the presence of antiphospholipid antibodies
Antiphospholipid antibodies are reliable predictors of adverse pregnancy outcomes and are associated with early and late fetal loss, pregnancy-induced hypertension, intrauterine growth retardation, prematurity, and arterial and venous thrombosis during pregnancy. However, we must emphasize that these associations are not observed in all women, nor in all pregnancies.
It would be advisable to measure them in cases such as: two or more pregnancy losses in the first trimester, loss of one or more pregnancies in the second trimester, repeated or severe preeclampsia, intrauterine growth retardation, thromboembolic disease in pregnancy.
And, without a doubt, in any woman who has a systemic autoimmune disease and wants to get pregnant.
Treatment with aspirin and heparin (Clexane) has been shown to be safe and effective in women with recurrent pregnancy loss and reduces the risk of miscarriage. It is not known whether or not this therapy reduces the risk of preeclampsia or intrauterine growth retardation.
Antipaternal antibodies
The theory of antipaternal antibodies is still very much in question. These would be antibodies that would protect the embryo, so they should be high and not low.
But there are defenders and detractors.
On the one hand, there are studies that affirm that there are certain blocking antibodies against the partner's white blood cells. That is, they help the mother's immune system to tolerate the fertilized embryo, which contains both maternal and paternal molecules, and which could therefore be recognized as foreign.
If this were the case, it would generate an immune reaction that would make correct embryo implantation impossible. These antibodies can be promoted with an inoculation of paternal leukocytes before pregnancy as a vaccine.
This theory supports the idea that having sexual relations regularly promotes fertility, since the mother's immune system will be more capable of recognizing the male material as its own and not attacking to this paternal composition of the embryo.
On the other hand, there are detractors who claim that the activity of the immune system in the maternal-embryonic and maternal-fetal environment is very different from general immune activity and that these premises are not correct.
They say that these antibodies, if they had any toxic activity, would fall on the T lymphocytes. And today it seems to have been confirmed that immune tolerance in the face of embryonic implantation does not fall so much on the activity of these lymphocytes but rather on the Natural Killers we have mentioned before.
If this were the case, the efficiency of the anti-paternal vaccine would be called into question. Furthermore, they highlight that this vaccine could be an impediment to possible organ transplants to the woman by her husband (if compatible) or by many other people if necessary.
Anti-sperm antibodies
It is still impossible for science to prove how certain antibodies can cause damage to the tissues of the testicles and ovaries. Furthermore, these antibodies have been detected both in people with ovarian or testicular failure and in men and women without this pathology.
So it is not known if they are the cause or effect of the problem.
Its measurement is, furthermore, complex and not entirely reliable, which is why it has been relegated to a more theoretical than practical level. By the time these antibodies are identified, it is usually too late and the damage to the sexual organs is usually irreparable.
In this case, the problem would be having them too high. The therapies used for its treatment, until recently, included immunosuppressive therapy, sperm washing, followed by artificial insemination or IVF. However, in the setting of unexplained infertility, the current treatment of choice is ICSI (intracytoplasmic injection), where a single sperm is injected into a single egg.
Antibodies that affect the fetus
Another way in which autoimmunity can affect the fetus is through the passive transfer of an antibody that has pathogenic effects. Examples include neonatal thyrotoxicosis, neonatal lupus, and neonatal myasthenia gravis.
They all improve as the level of maternal antibodies decreases, so the treatment will involve treating the mother.
Women with lupus will need specific testing for specific antibodies that can cause fetal heart block and heart failure.
Treatment of immunological causes of infertility
Genetic bias for autoimmune pathologies exists and is difficult to avoid. Chinese medicine proposes a combination of acupuncture points for genetic filtering in month 3 and month 6 of pregnancy, so that genetic pathologies are not transmitted from parents to children.
This is ancestral knowledge, supported by the fact that it has survived to this day, but no scientific studies have been carried out to confirm or deny it.
On the other hand, to date, the only immunological condition that is widely accepted as a treatable diagnosis is antiphospholipid syndrome, which would be treated with aspirin and clexane.
Although, even though we are aware that both the test and the treatment are still very experimental, it can be very interesting to investigate the activity of the cells. Natural Killers in women with a history of infertility.
The treatment would consist of some type of immunosuppressive therapy, with everything that this can entail. During pregnancy these options would include progesterone, clexane, prednisolone, or intravenous immunoglobulin (IVIG).
On the other hand, if one of the functions of the immune system is to distinguish what is its own from what is foreign to the body, the creation of antibodies for its own cells or tissues is undoubtedly a failure in the immune function.
The hyperactivity of certain cells of the immune system such as Natural Killers, for its part, is also a failure in immune function.
There is a belief that the more work we give to the immune system, the more likely it is to make mistakes.
In this sense, leading a healthy life, in which there is no low-grade inflammation, in which there are no infections, in which the use of antibiotics is limited and in which the microbiota is taken care of, will help limit the work to which the immune system is exposed and will minimize its chances of making mistakes.
Live as healthy a life as possible for yourself and your fertility.
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