Pathogenesis of infertility and recurrent pregnancy loss in thyroid autoimmunity

• Published in: Journal of autoimmunity Vol. 38; no. 2; pp. J275 - J281
• Main Authors: Twig, Gilad, Shina, Avi, Amital, Howard, Shoenfeld, Yehuda
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.05.2012
• Subjects: Abortion, Habitual - immunology; Allergy and Immunology; Autoantibodies; Autoantibodies - immunology; Autoimmunity; Cross Reactions - immunology; Female; Humans; Hypothyroidism - immunology; Immunity, Humoral - immunology; Immunity, Innate - immunology; Infertility; Infertility - immunology; Miscarriage; Pregnancy; Pregnancy loss; Thyroglobulin antibodies; Thyroid; Thyroid Gland - immunology; Thyroid Gland - pathology; Thyroid peroxidase antibodies; Thyroid-stimulating hormone; Vitamin D; Autoimmunity; Thyroid-stimulating hormone; Thyroid peroxidase antibodies; Autoantibodies; Thyroglobulin antibodies; Vitamin D; Infertility; Miscarriage; Thyroid; Pregnancy loss
• ISSN: 0896-8411; 1095-9157
• DOI: 10.1016/j.jaut.2011.11.014

Abstract Thyroid autoimmunity is the most prevalent autoimmune state that affects up to 4% of women during the age of fertility. A growing body of clinical studies links thyroid autoimmunity as a cause of infertility and adverse pregnancy outcomes that includes miscarriage or preterm deliveries. Importantly, these adverse effects are persistent in euthyroid women. In the current review we elaborate on the pathogenesis that underlies infertility and increased pregnancy loss among women with autoimmune thyroid disease. Such mechanisms include thyroid autoantibodies that exert their effect in a TSH-dependent but also in a TSH-independent manner. The later includes quantitative and qualitative changes in the profile of endometrial T cells with reduced secretion of IL-4 and IL-10 along with hypersecretion of interferon-γ. Polyclonal B cells activation is 2–3 time more frequent in thyroid autoimmunity and is associated with increased titers of non-organ specific autoantibodies. Hyperactivity and Increased migration of cytotoxic natural killer cells that alter the immune and hormonal response of the uterus is up to 40% more common in women with thyroid autoimmunity. Lack of vitamin D was suggested as a predisposing factor to autoimmune diseases, and was shown to be reduced in patients with thyroid autoimmunity. In turn, its deficiency is also linked to infertility and pregnancy loss, suggesting a potential interplay with thyroid autoimmunity in the context of infertility. In addition, thyroid autoantibodies were also suggested to alter fertility by targeting zona pellucida, human chorionic gonadotropin receptors and other placental antigens.