By Zaira Salvador BSc, MSc (embryologist).
Last Update: 06/21/2018

Immune system disorders and autoimmune diseases can cause infertility in both males and females.

Oftentimes, diagnosing immunological infertility is complicated. However, it is estimated that about 20 percent of the cases of unexplained infertility are due to immunological causes.

Infertility due to immunological causes can manifest in many different ways, including by destroying the reproductive cells of the person affected, preventing embryo implantation, or even causing recurrent miscarriages.

Role of the immune system

The immune system is composed of multiple cells, molecules, and mechanisms that protect the body from external agents like viruses, bacteria, and other infectious agents that cause diseases or illnesses in humans.

Out of the different immune cells present in our bodies, one of the most important ones are lymphocytes or white blood cells (WBCs). They are capable of recognizing our own structures, but also of producing antibodies that attack agents that they detect as external.

Unfortunately, our immune system is not perfect, and sometimes it fails to distinguish between what’s ours and what’s not. As a result, it attacks our own body’s cells. And it is this abnormality which causes the so-called autoimmune diseases.

Pregnancy

A pregnancy is a special, exceptional situation in a woman’s body, as it is forced to be home for a “foreign body” for 9 months.

The immune system of embryos is different from that of the pregnant woman, as it contains genes from the father as well, which are unknown to the immune system of the mother.

For a pregnancy to be normal, the woman’s immune system develops a mechanism of immune tolerance in order not to attack the embryo.

In fact, it is the embryo itself which “warns” the pregnant woman through the expression of the HLA-G Antigen, which function is to erase the cells of the immune system in order for the embryo to continue growing in the womb.

Immune infertility symptoms

The most obvious symptoms of immunological infertility is the impossibility to conceive. Typically, when a woman or couple has been trying to conceive for at least 1 year without luck, they visit a reproductive endocrinologist to find the possible causes.

If you have never received a diagnosis of an autoimmune disease and you are experiencing trouble conceiving along with any of the following symptoms, perhaps something is not working properly in your immune system:

  • Allergies
  • Poor digestion
  • Extreme fatigue
  • Skin rashes
  • Hypoglycemia (blood sugar issues)
  • Muscle and joint pain
  • Concentration difficulties

Several scientific studies have shown that autoimmune diseases are commonly linked to common reproductive disorder like PCOS, endometriosis, unexplained infertility, and premature ovarian aging (POA).

Types of immune infertility

There exist multiple immunological alterations, and unfortunately many of them can affect male and/or female fertility, especially the latter.

A woman’s body can recognize the sperms of her partner and/or the embryo as a foreign body, which can lead to implantation failure or miscarriage in the first trimester of pregnancy.

What follows is a list of the main types of immunological infertility in females.

Antisperm antibodies

It is the most common type of immune infertility in males. Antisperm antibodies are a group of proteins that stick to sperms and affect their ability to move forward and fertilize the egg.

Moreover, when antisperm antibodies stick to sperms, the body identifies them as invaders, and targets them in order to damage or kill them.

This type of antisperm antibodies can be present in both the man’s or woman’s organism. The causes are different depending on the case:

In males
The blood–testis barrier breaks due to varicocele, seminal infections, testicular torsion, etc. Antisperm antibodies can be present in blood and semen.
In females
Due to sexually transmitted diseases (STDs), rectovaginal endometriosis, cervicitis, etc. Antisperm antibodies can be found present in cervical mucus and block the sperm’s journey to the egg.

Hereditary thrombophilias

Thrombophilia is an autoimmune disease that causes the body to develop abnormal blood clots in the vessels (veins and/or arteries). It is due to a dysfunction in the mechanism that prevent excessive blood clotting.

In particular, the cause of thrombophilia is due to the absence of natural anticoagulants, as well as the presence of mutations in anticoagulant systems or in fibrinolytic mechanisms.

Based on the cause, there exist various types of thrombophilias:

  • Factor V G1691A (FV-Leiden) mutation
  • Prothrombin G20210A mutation
  • C677T mutation in the MTHFR gene
  • Antithrombin deficiency
  • Protein C deficiency
  • Protein S deficiency
  • Dysfibrinogenemia
  • Homozygous homocystinuria

Antiphospholipid syndrome (APS)

Antiphospholipid antibodies are a type of cells from the immune system that can be found in maternal blood and cause a state of hypercoagulability. It leads to the formation of thrombi in the placenta and subsequently to miscarriage.

There exist more that 20 types of antiphospholipid antibodies, being the lupus anticoagulant, anticardiolipin antibodies, and beta-2 Glycoprotein 1 Antibodies the most important ones. All of them alter the function of phospholipids, a group of substances that are necessary for vital functions such as blood circulation and clotting.

APS is considered a type of acquired thrombophilia. In fact, it is the cause of approximately 15% of the cases of recurrent pregnancy loss.

Recommended for you: What is the Antiphospholipid Syndrome (APS)?

Alloimmune implantation dysfunction

The immune system of the pregnant woman recognizes the embryo as an invader, and creates antibodies against the tissue that expresses proteins from paternal origin as a response.

As a consequence, embryo implantation cannot take place or, if it happens, it typically ends up in miscarriage.

These patients have elevated levels of Natural Killer (NK) cells, a type of lymphocytes that can destroy those organisms detected as “invaders”.

Potential treatment options to fight this infertility cause are still being investigated.

Assisted reproduction

Amongst the different causes of immunological infertility described above, assisted reproduction will be necessary in all cases of antisperm antibodies.

Depending on the location of antisperm antibodies and the severity, we can use one of the following treatments:

Intrauterine Insemination (IUI)
If antibodies that stick to sperm are found in the cervical mucus, especially in the cervix. With IUI, the sperm sample is inserted directly into the uterine fundus using a catheter. By doing this, the sperms don’t get in touch with the sperm antibodies, and the cells of the immune system won’t attack them. In other words, they will be able to reach the egg.
In Vitro Fertilization (IVF)
If the amount of antisperm antibodies is greater or they are spread across the female reproductive system. If IVF/ICSI is the treatment of choice, a sperm cell is injected directly into the egg cell, thereby eliminating every chance of interaction between sperm and antisperm antibodies.

Thrombophilias, along with other alterations of the immune system, may require a fertility treatment to achieve pregnancy. However, if there is no other fertility issue, you can get pregnant and carry the child until birth thanks to a treatment based on anticoagulant drugs.

If you need to undergo IVF to become a mother, we recommend that you use "The Calculator". In 3 simple steps, it will show you a list of clinics that fit your preferences and meet our strict quality criteria. Moreover, you will receive a report via email with useful tips to visit a fertility clinic for the first time.

Also, the report will inform you about the promotions or special prices that the clinics selected offer so you can benefit from them as well.

FAQs from users

What types of autoimmune diseases cause miscarriage?

By Zaira Salvador BSc, MSc (embryologist).

Antiphospholipid syndrome (APS) is associated with recurrent miscarriages and fetal death, as it causes the affected person’s immune system to mistakenly make antibodies to substances that are normally involved in blood clotting. Diabetes mellitus is associated with miscarriage as well.

What does testing for immunological infertility involve?

By Zaira Salvador BSc, MSc (embryologist).

On the one hand, it involves a series of tests for thrombophilia, including lupus anticoagulant, cardiolipin antibodies, testing for antiphospholipid antibodies, etc.

Then, performing a immunological study of antibodies, NK cells, cytokines, HLA-KIR compatibility, etc.

Does autoimmune thyroiditis cause infertility?

By Zaira Salvador BSc, MSc (embryologist).

Yes, autoimmune thyroiditis, also known as Hashimoto’s disease, is the most common cause of hypothyroidism. The woman’s body makes antibodies that attack the thyroid gland. As a result, a decrease in the amount of thyroid hormones occurs, causing irregularities in the menstrual cycle, among others.

You may also enjoy some further information reading this: Impact of Thyroid Hormones on Female Fertility.

Can celiac disease affect fertility?

By Zaira Salvador BSc, MSc (embryologist).

Although the causes why celiac disease affects fertility are still unknown, there exist many theories on why this may occur. In women affected by celiac disease who don’t follow a gluten-free diet, it is more likely that they are deficient in folic acid, selenium, iron, zinc, etc.

Suggested for you

Oftentimes, unexplained infertility is the cause of miscarriage because the body recognizes the fetus as an invader. To learn more, read: What Is Recurrent Miscarriage? – Causes, Symptoms & Treatment.

There exist one more cause of infertility due to immunological causes. Although it is a rare condition, a woman may have allergy to semen. This anomaly forces couples to have no choice but to use condoms and, for this reason, a pregnancy won’t be possible. Read more: Can You Be Allergic to Your Partner’s Sperm? – Causes & Treatment.

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Authors and contributors

 Zaira Salvador
BSc, MSc
Embryologist
Bachelor's Degree in Biotechnology from the Polytechnic University of Valencia (UPV). Embryologist specializing in Assisted Procreation, with a Master's Degree in Biotechnology of Human Assisted Reproduction from the University of Valencia (UV) and the Valencian Infertility Institute (IVI). More information
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