Fertility issues in men and women sometimes originate from autoimmune diseases and immune system disorders. Diagnosing them is complicated, with nearly 20% of the unexplained cases of fertility issues being because of immunological reasons. These disorders may affect fertility in different ways, including killing reproductive cells, hindering embryo impregnation or causing frequent miscarriages. Therefore, accurate diagnosis and treatment are critical for a successful pregnancy.
The immune system comprises many molecules, cells and processes that protect the body from infectious agents like bacteria, viruses and other foreign agents that can cause illnesses. Among the many immune cells, the WBCs (white blood cells) or lymphocytes recognise foreign substances and produce antibodies by understanding their structure.
However, in some people, the immune system cannot differentiate between the foreign cells and themselves and acts against their body’s cells. This causes autoimmune diseases.
The immune system prevents attacks by pathogens and other harmful agents. Sometimes, it turns against your body and becomes an attacker instead of a protector. A malfunctioning immunity disrupts many processes and may cause immunological infertility. A woman’s body may produce antibodies to attach her egg cells or prevent fertilisation by fighting sperm. On the other hand, a man may produce antibodies to destroy the sperm’s genetic material and cause immunological infertility.
Pregnancy is an exceptional situation in women’s bodies, during which a ‘foreign body’ is allowed to develop for nine months. The embryo’s immune system differs from the mother’s, as the father’s genes are combined. This is unknown to the mother’s immune system. Under normal conditions, the mother’s immune system creates an immune tolerance mechanism that prevents attacks on the embryo. The embryo releases HLA-G antigens that suppress the mother's immune response, allowing it to develop safely. However, in women with autoimmune disorders, this immune tolerance is compromised, leading to pregnancy complications such as placental dysfunction, recurrent miscarriages, and fetal development issues.
Many immune system alterations can affect female and male fertility, affecting females more than men. A woman’s body may identify an embryo and/or sperm as a foreign agent, which can lead to implantation failures or first-trimester miscarriages. Here are some common immunological infertility types.
This is a common form of immune fertility issue in males. Antisperm antibodies, a protein that attaches to the sperm, impact their motility and fertilising an egg. When it binds with spermatozoa, the immune system thinks of them as foreign objects and attacks them to kill them. This anti-sperm antibody type can be produced in females and males. The causes are as follows:
● For Males: Blood-testicular barrier ruptures because of testicular torsion, varicocele or seminal infection. These antibodies appear in semen and blood.
● For Females: Endometriosis, STIs (sexually transmitted infections), cervicitis, etc. These antibodies are present in cervical mucus and do not allow the sperm to move to the uterus.
Thrombophilia makes the body develop abnormal clots in the blood vessels. This autoimmune disorder is due to a malfunction of a process that prevents excess blood clotting. This happens because of a lack of natural coagulants and mutations in fibrinolytic mechanisms or anticoagulant systems. Genetic alterations may not seriously impact women who have them, but blood clots in the blood may reach the placenta and prevent fetal development.
Antiphospholipid antibodies are immune cells in the mother’s blood that cause hypercoagulability. It leads to the formation of placental thrombi and miscarriage. There are more than 20 antiphospholipid antibody types, with beta-2 Glycoprotein 1, lupus anticoagulant, and anticardiolipin antibodies being the most important. These alter the functioning of the phospholipids (substances needed for clotting and blood circulation). APS is an acquired thrombophilia and is among the common causes of pregnancy loss.
A pregnant woman’s immune system identifies the embryo as an attacker and produces antibodies against it. That results in the failure of embryo implantation or recurrent pregnancy loss. These women have high levels of Natural killer cells that destroy substances they detect as invaders.
● Immunophenotype from blood: This test determines the proportion and number of lymphocytes.
● Congenital hypercoagulability Gene Test: It determines the presence of heredity thrombophilia and checks genetic predisposition to blood clots, a common cause for immune infertility.
● MTHFR Variant Determination: A genetic test for gene mutations in MTHFR that cause hypercoagulability and malfunction of folic acid metabolism.
● APA testing: This is specifically for men to determine polymorphism, which increases miscarriage risks.
● MET PCR: This test checks the presence of a gene that causes hypercoagulability.
● Allo MLR: Test to check the presence of Allo MLR antibodies, which treat the embryo as a foreign object.
● Microcytotoxicity test: This test checks a woman’s blood for antibodies that fight the lymphocytes of her partner.
● Antibodies analysis: It detects antiphospholipid syndrome, which causes immune infertility and miscarriages.
● HLA-C: It checks HLA-C tissue for antigens. It also determines if an embryo is a potential danger in the womb.
● ANA 1,2,3: Test to check for antibodies. Their presence shows autoimmune disorders.
● Homocysteine: This test is done to check the presence of thrombotic diseases.
● Inhibin B: Determine the concentration of this protein, which helps diagnose immune infertility.
● Karyotype: A genetic test to check the chromosomes for their size, structure and number. Abnormalities in this can affect the immune system and cause immune infertility.
Assisted reproduction may become necessary for most of the above immune infertility types. Depending on the severity and the anti-sperm antibody location, one of the following treatments may be recommended:
In IUI, the sperm is inserted into the uterus directly so that the sperm does not come in contact with the antibodies, and the immune cells do not attack them. In simpler terms, the sperm reaches the egg without being attacked.
If the anti-sperm antibodies are more or spread throughout a woman’s reproductive system, IVF is an option. In this treatment, the sperm cell is injected into the egg cell, removing any interaction between the anti-sperm antibodies and the sperm.
People with immune system disorders like thrombophilias may need fertility treatment to get pregnant. However, if there are no fertility issues, women can get pregnant and deliver using anticoagulant drugs.
The inability to conceive a child can cause concern for many. Immunological causes can be one of the reasons for unexplained fertility issues, as the immune system identifies the embryo as an attacker. However, the good news is that with proper diagnosis and treatment, the chances of successfully conceiving a healthy baby increase tremendously. So, consult a qualified healthcare specialist to receive personalised guidance and thorough testing and explore the best possible treatment options.
Anti-phospholipid syndrome, celiac disease and Endometriosis are some common autoimmune conditions linked to immunological infertility.
Yes. It can be diagnosed through blood tests that detect antibodies.
Natural killer cells prevent embryo implantation or cause recurrent pregnancy loss.