Autoimmune Infertility

Autoimmune infertility is an emerging field in reproductive medicine, encompassing a range of conditions where the immune system interferes with fertility. Autoimmune infertility occurs when the immune system mistakenly targets reproductive tissues or sperm, leading to diminished fertility or infertility. Women with autoimmune diseases have an increased risk of premature ovarian failure. In addition, autoantibodies may play an important role in fertilization and embryo implantation rates as well as placental development. This increases the risk of embryo implantation failure, repeated miscarriage, as well as increased risks during pregnancy such as pre-eclampsia and preterm birth.

Fig.1 Immune mechanisms associated with male infertility.

Autoantibodies associated with infertility

• Anti-Phospholipid Antibodies (APA)
  Targets include cardiolipin and beta-2 glycoprotein I, etc. APAs are associated with antiphospholipid syndrome (APS), which can lead to recurrent pregnancy loss due to placental insufficiency and thrombotic events. They interfere with normal blood flow to the placenta, causing fetal growth restriction or miscarriage.

Fig.2 Antiphospholipid syndrome and recurrent miscarriage

• Anti-Beta-2 Glycoprotein I Antibodies
  Like anti-cardiolipin antibodies, these are linked to APS and can contribute to pregnancy complications and recurrent pregnancy loss.
• Anti-Sperm Antibodies
  Anti sperm autoantibodies (ASAs) have immobilizing and cytotoxic properties, impairing spermatogenesis, causing sperm agglutination, altering spermatozoa motility and acrosomal reaction, and thus preventing ovum fertilization. Infertility diagnosis requires a mandatory check for the ASAs. Major targets: Clusterin and prolactin-inducible protein (PIP).

Fig. 3 Origin of anti-sperm antibodies or AEAs

• Anti-Zona Pellucida Antibodies
  Target zona pellucida, a glycoprotein layer surrounding the egg. These antibodies may interfere with sperm-egg binding and fertilization, potentially leading to infertility or early embryo loss.
• Anti-Ovarian Antibodies
  Target ovarian tissue antigens. These antibodies can damage ovarian follicles, impairing ovulation and leading to premature ovarian failure. Autoimmune destruction of ovarian tissue can result in reduced hormone production, irregular menstrual cycles, reduced ovarian reserve, and infertility.
• Anti-Testicular Antibodies
  Testis antibodies are directed against various structures of the testes including seminiferous tubules and Leydig cells. These antibodies can affect spermatogenesis and lead to testicular inflammation, reducing sperm production and quality. Autoimmune testicular damage can result in compromised fertility.
• Anti-Thyroid Antibodies
  Target Thyroid peroxidase (TPO) and thyroglobulin, associated with autoimmune thyroid disorders. Autoimmune thyroid disease can affect reproductive health by causing menstrual irregularities and ovulatory dysfunction. Thyroid hormone imbalances influence ovarian function and overall fertility.
• Anti-Smooth Muscle Antibodies
  Anti-smooth muscle antibodies (ASMAs) attack proteins found in smooth muscle, which lines the inside of hollow organs. May be associated with autoimmune conditions affecting reproductive organs, potentially leading to pelvic inflammatory disease (PID) and infertility.