Despite mounting evidence for close interconnectivity, the clinical association of autoimmunity with female infertility has remained a subject of considerable controversy
Following implantation, the female immune system usually induces tolerance towards the embryo, whereas tolerance induction is incomplete in a hyperactive immune system, reducing fertility and increasing the risk of miscarriage
Autoimmunity can adversely affect female fertility by prematurely diminishing ovarian reserve, adversely affecting fertilization and implantation, and by increasing the risk of miscarriage and of various pregnancy complications
Similar to other autoimmune diseases, autoimmune endocrine diseases affect reproduction, including fertility and miscarriage risk, even at prodromal clinical stages, often months to years before diagnosis of the disease
Androgen supplementation in hypoandrogenic conditions of low ovarian reserve (whatever the aetiology) established a treatment paradigm, expanding interventions from the gonadotropin-sensitive stage (last 2 weeks) into earlier follicle maturation stages
Insufficient knowledge about the interplay between autoimmunity and reproduction suggests that reproductive immunology is an urgent target area for multi-specialty research by reproductive biologists, rheumatologists, immunologists and endocrinologists
An increasing body of evidence suggests that immune-mediated processes affect female reproductive success at multiple levels. Crosstalk between endocrine and immune systems regulates a large number of biological processes that affect target tissues, and this crosstalk involves gene expression, cytokine and/or lymphokine release and hormone action. In addition, endocrine–immune interactions have a major role in the implantation process of the fetal (paternally derived) semi-allograft, which requires a reprogramming process of the maternal immune system from rejection to temporary tolerance for the length of gestation. Usually, the female immune system is supportive of all of these processes and, therefore, facilitates reproductive success. Abnormalities of the female immune system, including autoimmunity, potentially interfere at multiple levels. The relevance of the immune system to female infertility is increasingly recognized by investigators, but clinically is often not adequately considered and is, therefore, underestimated. This Review summarizes the effect of individual autoimmune endocrine diseases on female fertility, and points towards selected developments expected in the near future.
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The authors would like to acknowledge the support of The Center for Human Reproduction.
N. Gleicher and D. H. Barad are listed as co-owners of a number of already awarded and still pending U.S. patents. Awarded patents relate to beneficial therapeutic effects of androgen supplementation on female infertility in women with low ovarian reserve. Pending patents relate to diagnostic claims that the FMR1 gene can be utilized to assess ovarian ageing patterns, and to predict fertility treatment chances in association with in vitro fertilization. N. Gleicher is a shareholder in Fertility Nutraceuticals, LLC, and owner of the Center for Human Reproduction (CHR). The CHR supported this manuscript through salary support to all authors. N. Gleicher and D. H. Barad receive patent royalties from Fertility Nutraceuticals, LLC. A. Sen and V. A. Kushnir have no potential conflicts to report.
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Sen, A., Kushnir, V., Barad, D. et al. Endocrine autoimmune diseases and female infertility. Nat Rev Endocrinol 10, 37–50 (2014). https://doi.org/10.1038/nrendo.2013.212
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