Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Endocrine autoimmune diseases and female infertility

Nature Reviews Endocrinology volume 10, pages 37–50 (2014)Cite this article

Subjects

Key Points

  • 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

Abstract

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.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Rent or buy this article

Get just this article for as long as you need it

$39.95

Learn more

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Adrenal–ovarian function range in hypoandrogenic, normoandrogenic and hyperandrogenic states.

References

  1. Cho, J. H. & Gregersen, P. K. Genomics and the multifactorial nature of human autoimmune disease. N. Engl. J. Med. 365, 1612–1623 (2011).

    Article  CAS  PubMed  Google Scholar 

  2. Jasani, B. et al. Natural antibody status in patients with Hashimoto's thyroiditis. J. Clin. Lab. Immunol. 51, 9–20 (1999).

    CAS  PubMed  Google Scholar 

  3. Tagoe, C. E., Zezon, A. & Khattri, S. Rheumatic manifestations of autoimmune thyroid disease: the other autoimmune disease. J. Rheumatol. 39, 1125–1129 (2012).

    Article  CAS  PubMed  Google Scholar 

  4. MedlinePlus, US National Library of Medicine, NIH, National Institutes of Health. Autoimmune Diseases [online] (2013).

  5. Targher, G. et al. Prevalence of thyroid autoimmunity and subclinical hypothyroidism in persons with chronic kidney disease not requiring chronic dialysis. Clin. Chem. Lab. Med. 47, 1367–1371 (2009).

    CAS  PubMed  Google Scholar 

  6. Tzioufas, A. G. et al. Subclinical manifestations of autoimmune rheumatic diseases in primary Raynaud's phenomenon. Clin. Exp. Rheumatol. 3, 243–247 (1985).

    CAS  PubMed  Google Scholar 

  7. Carp, H. J., Selmi, C. & Shoenfeld, Y. The autoimmune bases of infertility and pregnancy loss. J. Autoimmun. 38, J266–J274 (2012).

    Article  CAS  PubMed  Google Scholar 

  8. Gleicher, N. Reproductive failure prior to the onset of clinical autoimmune disease. Rheumatology (Oxford) 38, 485–487 (1999).

    Article  CAS  Google Scholar 

  9. Practice Committee of the American Society for Reproductive Medicine. Definitions of infertility and recurrent pregnancy loss: a committee opinion. Fertil. Steril. 99, 63 (2012).

  10. Gleicher, N. & Barad, D. H. Gender as risk factor for autoimmune diseases. J. Autoimmun. 28, 1–6 (2007).

    Article  CAS  PubMed  Google Scholar 

  11. Practice Committee of the American Society for Reproductive Medicine. Ant-phospholipid antibodies do not affect IVF success. Fertil. Steril. 86 (Suppl. 1), S224–S225 (2006).

  12. Silverman, M. N. & Sternberg, E. M. Neuroendocrine-immune interactions in rheumatoid arthritis: mechanisms of glucocorticoid resistance. Neuroimmunomodulation 15, 19–28 (2008).

    Article  CAS  PubMed  Google Scholar 

  13. Tzioufas, A. G., Tsonis, J. & Moutsopoulos, H. M. Neuroendocrine dysfunction in Sjogren syndrome. Neuroimmunomodulation 15, 37–45 (2008).

    Article  CAS  PubMed  Google Scholar 

  14. Tanriverdi, F., Silveira, L. F. G., MacColl, G. S. & Boulox, P. M. G. The hypothalamic–pituitary–gonadal axis: immune function and autoimmunity. J. Endocrinol. 176, 293–304 (2003).

    Article  CAS  PubMed  Google Scholar 

  15. McGrogan, A., Seaman, H. E., Wright, J. W. & de Vries, C. S. The incidence of autoimmune thyroid disease: a systemic review of the literature. Clin. Endocrinol. (Oxf.) 69, 687–696 (2008).

    Article  Google Scholar 

  16. Fromont, A. et al. National estimate of multiple sclerosis incidence in France (2001–2007). Mult. Scler. 18, 1108–1115 (2012).

    Article  CAS  PubMed  Google Scholar 

  17. Ahlgren, C., Odén, A. & Lycke, J. High nationwide prevalence of multiple sclerosis in Sweden. Mult. Scler. 17, 901–908 (2011).

    Article  CAS  PubMed  Google Scholar 

  18. Minagar, A. et al. The thalamus and multiple sclerosis: modern view of pathology, imaging, and clinical aspects. Neurology 80, 210–219 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Greer, J. M., McCombe, P. A. Role of gender in multiple sclerosis: clinical effects and potential molecular mechanisms. J. Neuroimmunol. 234, 7–18 (2011).

    Article  CAS  PubMed  Google Scholar 

  20. Cavalla, P. et al. Fertility in patients with multiple sclerosis: current knowledge and future perspectives. Neurol. Sci. 27, 231–239 (2006).

    Article  CAS  PubMed  Google Scholar 

  21. Nielsen, N. M. et al. Reproductive history and risk of multiple sclerosis. Epidemiology 22, 546–552 (2011).

    Article  PubMed  Google Scholar 

  22. Alwan, S., Sadovnick, A. D. Multiple sclerosis and pregnancy: maternal considerations. Women's Health (Lond. Engl.) 8, 399–414 (2012).

    Article  CAS  Google Scholar 

  23. Cocco, E. et al. Frequency and risk factors of mitoxantrone-induced amenorrhea in multiple sclerosis: the FEMIMS study. Mult. Scler. 14, 1225–1233 (2008).

    Article  CAS  PubMed  Google Scholar 

  24. Martinelli, V., Radaelli, M., Straffi, L., Rodeghe, M. & Comi, G. Mitoxantrone: benefits and risks in multiple sclerosis patients. Neurol. Sci. 30 (Suppl. 2), S167–S170 (2009).

    Article  PubMed  Google Scholar 

  25. Correale, J., Farez, M. F. & Ysraelit, M. C. Increase in multiple sclerosis activity after assisted reproduction technology. Ann. Neurol. 72, 682–694 (2012).

    Article  CAS  PubMed  Google Scholar 

  26. D'Hooghe, M. B., D'Hooghe, T. & De Keyser, J. Female gender and reproductive factors affecting risk, relapses and progression if multiple sclerosis. Gynecol. Obstet. Invest. 75, 73–84 (2013).

    Article  CAS  PubMed  Google Scholar 

  27. Quintanar, J. L., Salinas, E. & Quintanar-Stephano, A. Gonadotropin-releasing hormone reduces the severity of experimental autoimmune encephalomyelitis, a model of multiple sclerosis. Neuropeptides 45, 43–48 (2011).

    Article  CAS  PubMed  Google Scholar 

  28. Guzmaán-Soto, I., Salinas, E., Hernández-Jasso, I. & Quintanar, J. L. Leuprolide acetate, a GnRH agonist, improves experimental autoimmune encephalomyelitis: a possible therapy for multiple sclerosis. Neurochem. Res. 37, 2190–2197 (2012).

    Article  CAS  Google Scholar 

  29. Bellstella, A. et al. Subclinical diabetes insipidus. Best Pract. Res. Endocrinol. Metab. 26, 471–483 (2012).

    Article  CAS  Google Scholar 

  30. De Bellis, A. et al. Involvement of hypothalamus autoimmunity in patients with autoimmune hypopituitarism: role of antibodies to hypothalamic cells. J. Clin. Endocrinol. 97, 3684–3690 (2012).

    Article  CAS  Google Scholar 

  31. Gutiérrez Cruz, O. & Careaga Benitez, R. Diabetes insipidus and pregnancy. Ginecol. Obstet. Mex. 75, 224–229 (2007).

    PubMed  Google Scholar 

  32. Caturegli, P., Lupi I, Landek-Salgado, M., Kimura, H. & Rose, N. R. Pituitary autoimmunity: 30 years later. Autoimmun. Rev. 7, 631–637 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Glezer, A. & Bronstein, M. D. Pituitary autoimmune disease: nuances in clinical presentation. Endocrine 42, 74–79 (2012).

    Article  CAS  PubMed  Google Scholar 

  34. Mirocha, S., Elagin, R. B., Salamat, S. & Jaume, J. C. T regulatory cells distinguish two types of primary hypophysitis. Clin. Exp. Immunol. 155, 403–411 (2008).

    Article  CAS  PubMed  Google Scholar 

  35. Bellastella, G. et al. Predictive role of the immunostaining pattern of immunofluorescence and the titers of antipituitary antibodies at presentation for the occurrence of autoimmune hypopituitarism in patients with autoimmune polyendocrine syndrome over a five-year follow-up. J. Clin. Endocrinol. Metab. 95, 3750–3757 (2010).

    Article  CAS  PubMed  Google Scholar 

  36. Smith, C. et al. Identification of TPIT and other novel autoantigens in lymphocytic hypophysitis: immunoscreening of a pituitary cDNA library and development of immunoprecipitation assays. Eur. J. Endocrinol. 166, 391–398 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Shimatsu, A., Oki, Y., Fujisawa, I. & Sano, T. Pituitary and stalk lesions (infundibulo-hypophysitis) associated with immunoglobulin G4-related systemic disease: an emerging clinical entity. Endocr. J. 56, 1033–1041 (2009).

    Article  PubMed  Google Scholar 

  38. Lupi, I. et al. From pituitary expansion to empty sella: disease progression in a mouse model of autoimmune hypophysitis. Endocrinology 152, 4190–4198 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Landek-Salgado, M. A., Rose, N. R. & Caturegli, P. Placenta suppresses experimental autoimmune hypophysitis through soluble TNF receptor 1. J. Autoimmun. 38, J88–J96 (2012).

    Article  CAS  PubMed  Google Scholar 

  40. de Graaff, L. C., De Bellis, A., Bellastella, A. & Hokken-Koelega, A. C. Antipituitary antibodies in Dutch patients with idiopathic hypopituitarism. Horm. Res. 71, 22–27 (2009).

    CAS  PubMed  Google Scholar 

  41. Lupi, I. et al. Pituitary autoimmunity is associated with hypopituitarism in patients with primary empty sella. J. Endocrinol. Invest. 34, e240–e244 (2011).

    CAS  PubMed  Google Scholar 

  42. Yamamoto, M. et al. Adult combined GH, prolactin, and TSH deficiency associated with PIT-1 antibody in humans. J. Clin. Invest. 121, 113–119 (2011).

    Article  CAS  PubMed  Google Scholar 

  43. De Bellis, A. et al. Anti-hypothalamic and anti-pituitary antibodies may contribute to perpetuate the hypopituitarism in patients with Shehan's syndrome. Eur. J. Endocrinol. 158, 147–152 (2008).

    Article  CAS  PubMed  Google Scholar 

  44. De Bellis, A. et al. Detection of antipituitary and antihypothalamus antibodies to investigate the role of pituitary or hypothalamic autoimmunity in patients with selective idiopathic hypopituitarism. Clin. Endocrinol. (Oxf.) 75, 361–366 (2011).

    Article  Google Scholar 

  45. Gleicher, N. et al. Hypoandrogenism in association with diminished functional ovarian reserve. Hum. Reprod. 28, 1084–1091 (2013).

    Article  CAS  PubMed  Google Scholar 

  46. Alpañés, M., Sanchón, R., Martinez-Garcia, M. A., Martinez-Bermeio, E. & Escobar-Morreale, H. E. Prevalence of hyperprolactinemia in female premenopausal blood donors. Clin. Endocrinol. (Oxf.) 79, 545–549 (2013).

    Article  CAS  Google Scholar 

  47. Lee, D. Y., Oj, Y. K., Yoon, B. K. & Choi, D. Prevalence of hyperprolactinemia in adolescents and young women with menstruation-related problems. Am. J. Obstet. Gynecol. 206, e1–e5 (2012).

    Article  Google Scholar 

  48. Kasum, M. et al. Macroprolactinemia: new insights in hyperprolactinemia. Biochemia. Med. (Zagreb) 22, 171–179 (2012).

    Article  CAS  Google Scholar 

  49. De Bellis, A., Bizzarro, A., Pivonello, R., Lombardi, G. & Bellastella, A. Prolactin and autoimmunity. Pituitary 8, 25–30 (2005).

    Article  CAS  PubMed  Google Scholar 

  50. Orbach, H. & Shoenfeld, Y. Hyperprolactinemia and autoimmune diseases. Autoimmun. Rev. 6, 537–542 (2007).

    Article  CAS  PubMed  Google Scholar 

  51. Shelly, S., Boaz, M. & Orbach, H. Prolactin and autoimmunity. Autoimmun. Rev. 11, A465–A470 (2012).

    Article  CAS  PubMed  Google Scholar 

  52. Parra, A. et al. Moderate hyperprolactinemia is associated with survival in patients with acute graft-versus host disease after allogeneic stem cell transplantation. Hematology 17, 85–92 (2012).

    Article  CAS  PubMed  Google Scholar 

  53. Sharma, N., Baliarsingh, S. & Kaushik, G. G. Biochemical association of hyperprolactinemia with hypothyroidism in infertile women. Clin. Lab. 58, 805–810 (2012).

    CAS  PubMed  Google Scholar 

  54. Praprotnik, S. et al. Prolactin's role in the pathogenesis of the antiphospholipid syndrome. Lupus 19, 1515–1519 (2010).

    Article  CAS  PubMed  Google Scholar 

  55. Unuane, D., Tournaye, H., Velkeniers, B. & Poppe, K. Endocrine disorders & female infertility. Best Pract. Res. Clin. Endocrinol. Metab. 25, 861–873 (2011).

    Article  CAS  PubMed  Google Scholar 

  56. Shibli-Rahhal, A. & Schlechte, J. Hyperprolactinemia and infertility. Endocrinol. Metab. Clin. North Am. 40, 837–846 (2011).

    Article  CAS  PubMed  Google Scholar 

  57. Berinder, K., Hulting, A. L., Granath, F., Hirschberg, A. L. & Akre, O. Parity, pregnancy and neonatal outcomes in women treated for hyperprolactinemia compared with a control group. Clin. Endocrinol. (Oxf.) 67, 393–397 (2007).

    Article  Google Scholar 

  58. Wang, H., Gorpudolo, N. & Behr, B. The role of prolactin- and endometriosis-associated infertility. Obstet. Gynecol. Surv. 64, 542–547 (2009).

    Article  PubMed  Google Scholar 

  59. Gleicher, N., el-Roeiy, A., Cofino, E. & Friberg, J. Is endometriosis an autoimmune disease? Obstet. Gynecol. 70, 115–122 (1987).

    CAS  PubMed  Google Scholar 

  60. Grattan, D. R., Jasoni, C. L., Liu, X., Anderson, G. M. & Herbison, A. E. Prolactin regulation of gonadotropin-releasing hormone neurons to suppress luteinizing hormone secretion in mice. Endocrinology 148, 4344–4351 (2007).

    Article  CAS  PubMed  Google Scholar 

  61. Ratner, L. D. et al. Short-term pharmacological suppression of the hyperprolactinemia of infertile hCG-overproducing female mice persistently restores their fertility. Endocrinology 153, 5980–5992 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Sonigo, C. et al. Hyperprolactinemia-induced ovarian acyclicity is reversed by kisspeptin administration. J. Clin. Invest. 122, 3791–3795 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. De Bellis, A. et al. Characterization of antipituitary antibodies targeting pituitary hormone-secreting cells in idiopathic growth hormone deficiency and autoimmune endocrine disease. Clin. Endocrinol. (Oxf.) 63, 45–49 (2005).

    Article  CAS  Google Scholar 

  64. De Bellis, A. et al. Autoimmunity as a possible cause of growth hormone deficiency. J. Endocrinol. Invest. 31, 1132–1134 (2008).

    Article  CAS  PubMed  Google Scholar 

  65. van Nieuwpoort, J. C. Dutch National Registry of GH treatment in adults: patient characteristics and diagnostic test procedures. Eur. J. Endocrinol. 164, 491–497 (2011).

    Article  CAS  PubMed  Google Scholar 

  66. Hall, R., Manski-Nankervis, J., Goni, N., Davies, M. C. & Conway, G. S. Fertility outcomes in women with hypopituitarism. Clin. Endocrinol. (Oxf.) 65, 71–74.

  67. Daniel, A., Ezzat, S. & Greenblatt, E. Adjuvant growth hormone for ovulation induction with gonadotropins in the treatment of a woman with hypopituitarism. Case Rep. Endocrinol. 2012, 356429 (2012).

    PubMed  PubMed Central  Google Scholar 

  68. Nelson, L. M. Clinical practice, primary ovarian insufficiency. N. Engl. J. Med. 360, 606–614 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Gleicher, N., Weghofer, A. & Barad, D. H. Defining ovarian reserve to better understand ovarian aging. Reprod. Biol. Endocrinol. 9 23 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  70. Gleicher, N., Weghofer, A., Oktay, K. & Barad, D. Do etiologies of premature ovarian aging (POA) mimic those of premature ovarian failure (POF)? Hum. Reprod. 24, 2395–2400 (2009).

    Article  CAS  PubMed  Google Scholar 

  71. Monnier-Barbarino, P., Forges, T., Faure, G. C. & Béné, M. C. Gonadal antibodies interfering with female reproduction. Best Pract. Res. Clin. Endocrinol. 19, 135–148 (2005).

    Article  CAS  Google Scholar 

  72. Zou, S. H., Zhang, P., Song, D. P. & Wu, R. Y. Impact of antiovarian antibodies (AOA) on ovarian responsiveness in vitro fertilization and embryo transfer. Neuro Endocrinol. Lett. 29, 949–952 (2008).

    PubMed  Google Scholar 

  73. Pires, E. S. et al. Can anti-ovarian antibody testing be useful in an IVF-ET clinic? J. Assist. Reprod. Genet. 28, 55–64 (2011).

    Article  PubMed  Google Scholar 

  74. Hoek, A., Schoemaker, J. & Drexhage, H. A. Premature ovarian failure and ovarian autoimmunity. Endocrine Rev. 18, 107–134 (1997).

    CAS  Google Scholar 

  75. Pires, E. Multiplicity of molecular and cellular targets in human ovarian autoimmunity: an update. J. Assist. Reprod. Genet. 27, 519–524 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  76. Mande, P. V. et al. Identification and validation of candidate biomarkers involved in human ovarian autoimmunity. Reprod. Biomed. Online 23, 471–483 (2011).

    Article  CAS  PubMed  Google Scholar 

  77. Edassery, S. L. et al. Autoantigens in ovarian autoimmunity associated with unexplained infertility and premature ovarian failure. Fertil. Steril. 94, 2636–2641 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Pires, E. S. & Khole, V. V. A block in the road to fertility: autoantibodies to heat-shock protein 90-β in human ovarian autoimmunity. Fertil. Steril. 92, 1395–1409 (2009).

    Article  CAS  PubMed  Google Scholar 

  79. Geva, E. et al. The possible role of antiovary antibodies in repeated in vitro fertilization failures. Am. J. Reprod. Immunol. 42, 292–296 (1999).

    Article  CAS  PubMed  Google Scholar 

  80. Shamilova, N. N., Marchenko, L. A., Dolgushina, N. V., Zaletaev, D. V. & Sukhikh, G. T. The role of genetic and autoimmune factors in premature ovarian failure. J. Assist. Reprod. Genet. 30, 617–622 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  81. Geva, E. et al. Circulating autoimmune antibodies may be responsible for implantation failure in in vitro fertilization. Fertil. Steril. 62, 802–806 (1994).

    Article  CAS  PubMed  Google Scholar 

  82. Hill, J. A. & Scott, R. T. Immunologic tests and IVF: “Please, enough already”. Fertil. Steril. 74, 439–442 (2000).

    Article  CAS  PubMed  Google Scholar 

  83. Goswami, R. et al. Prevalence of thyroid autoimmunity in sporadic idiopathic hyperparathyroidism in comparison to type 1 diabetes and premature ovarian failure. J. Clin. Endocrinol. Metab. 91, 4256–4259 (2006).

    Article  CAS  PubMed  Google Scholar 

  84. Kelkar, R. L., Meherji, P. K., Kadam, S. S., Gupta, S. K. & Nandedkar, T. D. Circulating auto-antibodies against the zona pellucida and thyroid microsomal antigen in women with premature ovarian failure. J. Reprod. Immunol. 66, 53–67 (2005).

    Article  CAS  PubMed  Google Scholar 

  85. Gleicher, N., Weghofer, A. & Barad, D. H. The role of androgens in follicle maturation and ovulation induction: friend or foe of infertility treatment? Reprod. Biol. Endocrinol. 9 116 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Sen, A. & Hammes, S. R. Granulosa cell-specific androgen receptors are critical regulators of ovarian development and function. Mol. Endocrinol. 24, 1393–1403 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Mande, P. V., Thomas, S., Khan, S., Jadhav, S. & Khole, V. V. Immunization with ovarian autoantigens leads to reduced fertility in mice following follicular dysfunction. Reproduction 143, 309–323 (2012).

    Article  CAS  PubMed  Google Scholar 

  88. Albertini, D. F. Searching for answers to the riddle of ovarian aging. J. Assist. Reprod. Genet. 29, 577–578 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  89. Altuntas, C. Z., Johnson, J. M. & Tuohy, V. K. Autoimmune targeted disruption of the pituitary-ovarian axis causes premature ovarian failure. J. Immunol. 177, 1988–1996 (2006).

    Article  CAS  PubMed  Google Scholar 

  90. Gleicher, N., Weghofer, A., Lee, I. H. & Barad, D. H. FMR1 genotypes with autoimmunity-associated polycystic ovary-like phenotype and decreased pregnancy chance. PLoS ONE 5, e15303 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Welt, C. K. Autoimmune oophoritis in the adolescent. Ann. N.Y. Acad. Sci. 1135, 118–122 (2008).

    Article  CAS  PubMed  Google Scholar 

  92. Tsigkou, A. et al. High serum inhibin concentration discriminates autoimmune oophoritis from other forms of primary ovarian insufficiency. J. Clin. Endocrinol. Metab. 93, 1263–1269 (2008).

    Article  CAS  PubMed  Google Scholar 

  93. La Marca, A. et al. Primary ovarian insufficiency: autoimmune causes. Curr. Opin. Obstet. Gynecol. 22, 277–282 (2010).

    PubMed  Google Scholar 

  94. Bats, A. S., Barbarino, P. M., Bene, M. C., Faure, G. C. & Forges, T. Local lymphocytic and epithelial activation in a case of autoimmune oophoritis. Fertil. Steril. 90, e5–e8 (2008).

    Article  Google Scholar 

  95. Page, K., Pagidas, K., Derosa, M. C. & Quddus, M. R. Eosinophilic perifolliculitis presenting as a painful cystic ovarian mass in a woman with fibromyalgia: a case report. J. Reprod. Med. 51, 141–144 (2006).

    PubMed  Google Scholar 

  96. Nelson, L. M. Autoimmune ovarian failure: comparing the mouse model and the human disease. J. Soc. Gynecol. Investig. 8 (1 Suppl. Proceedings), S55–S57 (2001).

    Article  CAS  PubMed  Google Scholar 

  97. del Rio, R., Sun, Y., Alard, P., Tung, K. S. & Teuscher, C. H2 control of natural T regulatory cell frequency in the lymph node correlates with susceptibility to day 3 thymectomy-induced autoimmune disease. J. Immunol. 186, 382–389 (2011).

    Article  CAS  PubMed  Google Scholar 

  98. Fu, L., Feng, W., Li, S. R. & Huang, B. Y. ZP3 peptides administered orally suppress murine experimental autoimmune ovarian disease. J. Reprod. Immunol. 75, 40–47 (2007).

    Article  CAS  PubMed  Google Scholar 

  99. Tong, Z. B. & Nelson, L. M. A mouse gene encoding an oocyte antigen associated with autoimmune premature ovarian failure. Endocrinology 140, 3720–3726 (1999).

    Article  CAS  PubMed  Google Scholar 

  100. Otsuka, N. et al. Autoimmune oophoritis with multiple molecular targets mitigated by transgenic expression of mater. Endocrinology 152, 2465–2473 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Ting, J. P., Kastner, D. L. & Hoffman, H. M. CATERPILLERs, pyrin and hereditary immunological disorders. Nat. Rev. Immunol. 6, 183–195 (2006).

    Article  CAS  PubMed  Google Scholar 

  102. Alimohammmadi, M. et al. Autoimmune polyendocrine syndrome type 1 and NALP5, a parathyroid autoantigen. N. Engl. J. Med. 358, 1018–1028 (2008).

    Article  Google Scholar 

  103. Kojima, A. & Prehn, R. T. Genetic susceptibility to post-thymectomy autoimmune diseases in mice. Immunogenetics 14, 15–27 (1981).

    Article  CAS  PubMed  Google Scholar 

  104. Nair, S., Caspi, R. R. & Nelson, L. M. Susceptibility to murine experimental autoimmune oophoritis is associated with genes outside the major histocompatibility complex (MHC). Am. J. Reprod. Immunol. 36 107–110 (1996).

    Article  CAS  PubMed  Google Scholar 

  105. Teuscher, C., Wardell, B. B., Lunceford, J. K., Michael, S. D. & Tung, K. S. Aod2, the locus controlling development of atrophy in neonatal thymectomy-induced autoimmune ovarian dysgenesis, co-localizes with IL2, Fgfb, and Idd3. J. Exp. Med. 183, 631–637 (1996).

    Article  CAS  PubMed  Google Scholar 

  106. Dewhurst, C. J., de Koos, E. B. & Ferreira, H. P. The resistant ovary syndrome. Br. J. Obstet. Gynecol. 82, 341–345 (1975).

    Article  CAS  Google Scholar 

  107. Okoroh, E. M., Hooper, W. C., Atrash, H. K., Yusuf, H. R. & Boulet, S. L. Prevalence of polycystic ovary syndrome among the privately insured. United States, 2003–2008. Am. J. Obstet. Gynecol. 207, 299.e1–e7 (2012).

    Article  Google Scholar 

  108. Azziz, R. et al. The prevalence and features of the polycystic ovary syndrome in an unselected population. J. Clin. Endocrinol. Metab. 89, 2745–2749 (2004).

    Article  CAS  PubMed  Google Scholar 

  109. Yidiz, B. O., Bozdag, G., Yapici, Z., Esinler, I. & Yarali, H. Prevalence, phenotype and cardiometabolic risk of polycystic ovary syndrome under different diagnostic criteria. Hum. Reprod. 27, 3067–3073 (2012).

    Article  Google Scholar 

  110. Deligeoroglou, E. et al. Mediators of chronic inflammation in polycystic ovarian syndrome. Gynecol. Endocrinol. 28, 974–978 (2012).

    Article  CAS  PubMed  Google Scholar 

  111. Ebejer, K. & Calleja-Agius, J. The role of cytokines in polycystic ovary syndrome. Gynecol. Endocrinol. 29, 536–540 (2013).

    Article  CAS  PubMed  Google Scholar 

  112. Ojeda-Ojeda, M., Murri, M., Insenser, M. & Escobar-Morrealee, H. F. Mediators of low-grade chronic inflammation in polycystic ovary syndrome (PCOS). Curr. Pharm. Des. 19, 5775–5791 (2013).

    Article  CAS  PubMed  Google Scholar 

  113. Kahal, H. et al. Polycystic ovary syndrome has no independent effect on vascular, inflammatory or thrombotic markers when matched for obesity. Clin. Endocrinol. (Oxf.) 79, 252–258 (2013).

    Article  CAS  Google Scholar 

  114. Ezeh, U., Yidiz, B. O. & Azziz, R. Referral bias in defining the phenotype and prevalence of obesity in polycystic ovary syndrome. J. Clin. Endocrinol. Metab. 98, E1088–E1096 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. van Gelderern, C. J. & Gomes dos Santos, M. L. Polycystic ovarian syndrome. Evidence for an autoimmune mechanism in some cases. J. Reprod. Med. 38, 381–386 (1993).

    Google Scholar 

  116. Petriková, J. & Lazúrová, I. Ovarian failure and polycystic ovary syndrome. Autoimmun. Rev. 11, A471–A478 (2012).

    Article  CAS  PubMed  Google Scholar 

  117. Hefler-Frischmuth, K. et al. Serologic markers of autoimmunity in women with polycystic ovary syndrome. Fertil. Steril. 93, 2291–2294 (2010).

    Article  CAS  PubMed  Google Scholar 

  118. Katsas, G. A. et al. How common are polycystic ovaries and polycystic ovarian syndrome in women with Cushing's syndrome. Clin. Endocrinol. (Oxf.) 53, 493–500 (2000).

    Article  Google Scholar 

  119. Moro, F. et al. Psoriatic patients have an increased risk of polycystic ovary syndrome: results of a cross-sectional analysis. Fertil. Steril. 99, 936–942 (2013).

    Article  PubMed  Google Scholar 

  120. Kachuei, M., Jafari, F., Kachei, A. & Keshteli, A. H. Prevalence of autoimmune thyroiditis in patients with polycystic ovary syndrome. Arch. Gynecol. Obstet. 285, 853–856 (2012).

    Article  CAS  PubMed  Google Scholar 

  121. Benetti-Pinto, C. L., Berini Piccolo, V. R. S., Garmes, H. M. & Teatin Juliato, C. R. Subclinical hypothyroidism in young women with polycystic ovary syndrome: an analysis of clinical, hormonal, and metabolic parameters. Fertil. Steril. 99, 588–592 (2013).

    Article  CAS  PubMed  Google Scholar 

  122. Garelli, S. et al. High prevalence of chronic thyroiditis in patients with polycystic ovary syndrome. Eur. J. Obstet. Gynecol. Reprod. Biol. 169, 248–251 (2013).

    Article  CAS  PubMed  Google Scholar 

  123. Nisar, S. et al. Association of polycystic ovary syndrome and Graves' disease: Is autoimmunity the link between the two diseases. Indian J. Endocrinol. Metab. 16, 982–986 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  124. Lewis, V. Polycystic ovary syndrome. A diagnostic challenge. Obstet. Gynecol. Clin. North Am. 28, 1–20 (2001).

    Article  CAS  PubMed  Google Scholar 

  125. Gleicher, N. et al. Is androgen production in association with immune system activation potential evidence for existence of a functional adrenal/ovarian autoimmune system in women? Reprod. Biol. Endocrinol. 11, 58 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. González, F., Sia, C. L., Stanczyk, F. Z., Blair, H. E. & Krupa, M. E. Hyperandrogenism exerts an anti-inflammatory effect in obese women with polycystic ovary syndrome. Endocrine 42, 726–735 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. Krassas, G. E., Poppe, K. & Glinoer, D. Thyroid function and human reproductive health. Endocr. Rev. 31, 702–755 (2010).

    Article  CAS  PubMed  Google Scholar 

  128. Klecha, A. J., Barreiro Arcos, M. L., Frick, L., Genaro, A. M. & Cremaschi, G. Immune-endocrine interactions in autoimmune thyroid diseases. Neuroimmunomodulation 15, 68–75 (2008).

    Article  CAS  PubMed  Google Scholar 

  129. Poppe, K., Velkeniers, B. & Glinoer, D. Thyroid disease and female reproduction. Clin. Endocrinol. (Oxf.) 66, 309–321 (2007).

    Article  CAS  Google Scholar 

  130. Gleicher, N., el-Roeiy, A., Confino, E. & Friberg, J. Is endometriosis an autoimmune disease? Obstet. Gynecol. 70, 115–122 (1987).

    CAS  PubMed  Google Scholar 

  131. Zhong, Y. P. et al. Relationship between antithyroid antibody and pregnancy outcome following in vitro fertilization and embryo transfer. Int. J. Med. Sci. 9, 121–125 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  132. Bellver, J. et al. The role of thrombophilia and thyroid autoimmunity in unexplained infertility, implantation failure and recurrent spontaneous abortion. Hum. Reprod. 23, 278–284 (2008).

    Article  PubMed  Google Scholar 

  133. Fumarola, A. et al. Thyroid function in infertile patients undergoing assisted reproduction. Am. J. Reprod. Immunol. 70, 336–341 (2013).

    Article  CAS  PubMed  Google Scholar 

  134. Busnelli, A. et al. In vitro fertilization outcomes in treated hypothyroidism. Thyroid 23, 1319–1325 (2013).

    Article  CAS  PubMed  Google Scholar 

  135. Kim, N. Y. et al. Thyroid autoimmunity and its association with cellular and humoral immunity in women with reproductive failure. Am. J. Reprod. Immunol. 65, 78–87 (2011).

    Article  CAS  PubMed  Google Scholar 

  136. Chen, L. & Hu, R. Thyroid autoimmunity and miscarriage: a meta-analysis. Clin. Endocrinol. (Oxf.) 74, 513–519 (2011).

    Article  Google Scholar 

  137. Twig, G., Shina, A., Amital, H. & Shoenfeld, Y. pathogenesis of infertility and recurrent pregnancy loss in thyroid autoimmunity. J. Autoimmun. 38, J275–J281 (2012).

    Article  CAS  PubMed  Google Scholar 

  138. Hutfless, S., Matos, P., Talor, M. V., Caturegli, P. & Rose, N. R. Significance of prediagnostic thyroid antibodies in women with autoimmune thyroid disease. J. Clin. Endocrinol. Metab. 96, E1466–E1477 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  139. Gleicher, N. Does the immune system induce labor? Lessons from preterm deliveries in women with autoimmune diseases. Clin. Rev. Allergy Immunol. 39, 194–206 (2010).

    Article  PubMed  Google Scholar 

  140. He, X. et al. Thyroid antibodies and risk of preterm delivery: a meta-analysis of prospective cohort studies. Eur. J. Endocrinol. 167, 455–464 (2012).

    Article  CAS  PubMed  Google Scholar 

  141. Karakosta, P. et al. Thyroid dysfunction and autoantibodies in early pregnancy are associated with increased risk of gestational diabetes and adverse birth outcomes. J. Clin. Endocrinol. Metab. 97, 4464–4472 (2012).

    Article  CAS  PubMed  Google Scholar 

  142. Vitacolonna, E. et al. Gestational diabetes and thyroid autoimmunity. Int. J. Endocrinol. 2012, 867415 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  143. Glinoer, D. et al. Pregnancy in patients with mild thyroid abnormalities: maternal and neonatal repercussions. J. Clin. Endocrinol. Metab. 73, 421–427 (1991).

    Article  CAS  PubMed  Google Scholar 

  144. Pratt, D. E., Kaberlein, G., Dudkiewicz, A., Karande, V. & Gleicher, N. The association of antithyroid antibodies in euthyroid nonpregnant women with recurrent first trimester abortions in the next pregnancy. Fertil. Steril. 60, 1001–1005 (1993).

    Article  CAS  PubMed  Google Scholar 

  145. Lazzarin, N., Moretti, C., De Felice, G., Vaquero, E. & Manfellotto, D. Further evidence on the role of thyroid autoimmunity in women with recurrent miscarriage. Int. J. Endocrinol. 2012, 717185 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  146. Stagnaro-Green, A. Maternal thyroid disease and preterm delivery. J. Clin. Endocrinol. Metab. 94, 21–25 (2009).

    Article  CAS  PubMed  Google Scholar 

  147. Negro, R. et al. Thyroid antibody positivity in the first trimester of pregnancy is associated with negative pregnancy outcome. J. Clin. Endocrinol. Metab. 96, E920–E924 (2011).

    Article  CAS  PubMed  Google Scholar 

  148. Vasudevan, N., Ogawa, S. & Paff, D. Estrogen and thyroid hormone receptor interaction: physiological flexibility and molecular specificity. Phsyiol. Rev. 82, 923–944 (2002).

    Article  CAS  Google Scholar 

  149. Lee, Y. L. et al. Increased fetal abortion rate in autoimmune thyroid disease is related to circulating to autoantibodies in an autoimmune thyroiditis animal model. Fertil. Steril. 91, 2104–2109 (2009).

    Article  PubMed  Google Scholar 

  150. Betterle, C. & Morlin, L. Autoimmune Addison's disease. Endocr. Dev. 20, 161–172 (2011).

    Article  CAS  PubMed  Google Scholar 

  151. Lahera Vargas, M. & da Costa, C. V. Prevalence, etiology and clinical findings of Cushing's syndrome [Spanish]. Endocrinol. Nutr. 56, 32–39 (2009).

    Article  PubMed  Google Scholar 

  152. Medvei, V. C. The history of Cushing's disease: a controversial tale. J. R. Soc. Med. 84, 363–366 (1991).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  153. Baker, P. R. et al. Predicting the onset of Addison's disease: ACTH, renin, cortisol and 21-hydroxylase autoantibodies. Clin. Endocrinol. (Oxf.) 76, 617–624 (2012).

    Article  CAS  Google Scholar 

  154. Mitchell, A. L. & Pearce, S. H. Autoimmune Addison disease: pathophysiology and genetic complexity. Nat. Rev. Endocrinol. 8, 306–316 (2012).

    Article  CAS  PubMed  Google Scholar 

  155. Bratland, E., Hellesen, A. & Husebye, E. S. Induction of CXCL10 chemokine in adrenocortical cells by stimulation through toll-like receptor 3. Mol. Cell. Endocrinol. 365, 75–83 (2013).

    Article  CAS  PubMed  Google Scholar 

  156. Bernecker, C. et al. MicroRNA expression in PMBCs, CD4+, and CD8+ T-cells from patients suffering from autoimmune Addison's disease. Horm. Metab. Res. 45, 599–604 (2013).

    Article  CAS  PubMed  Google Scholar 

  157. Falorni, A., Minarelli, V. & Morelli, S. Therapy of adrenal insufficiency: an update. Endocrine 43, 514–528 (2013).

    Article  CAS  PubMed  Google Scholar 

  158. Kim, S. S. & Brody, K. H. Dehydroepiandrosterone replacement in Addison's disease. Eur. J. Obstet. Gynecol. Reprod. Biol. 97, 96–97 (2011).

    Article  Google Scholar 

  159. Mavrangi, C. P., Schini, M., Gravani, F., Kaltsas, G. & Moutsopoulos, H. M. Brief report: adrenal autoimmunity in primary Sjögren's syndrome. Arthritis Rheum. 64, 4066–4071 (2012).

    Article  CAS  Google Scholar 

  160. Simunkova, K. et al. Adrenocortical function in young adults with diabetes mellitus type 1. J. Steroid. Biochem. Med. Sci. 122, 35–41 (2010).

    Article  CAS  Google Scholar 

  161. Azziz, R., Chang, W. Y. & Stancyk, F. Z. Effect of bilateral oophorectomy on adrenocortical function in women with polycystic ovary syndrome. Fertil. Steril. 99, 599–604 (2013).

    Article  CAS  PubMed  Google Scholar 

  162. González, F. Adrenal dysfunction in polycystic ovary syndrome: has it been lost to follow up? Fertil. Steril. 99, 352–353 (2013).

    Article  PubMed  Google Scholar 

  163. Dite, P., Novotny, I., Trna, J. & Sevcikova, A. Autoimmune pancreatitis. Best Pract. Res. Clin. Gastroenterol. 22, 131–143 (2008).

    Article  CAS  PubMed  Google Scholar 

  164. Bauman, B., Salem, H. H. & Boehm, B. O. Anti-inflammatory therapy in type 1 diabetes. Curr. Diab. Rep. 12, 499–509 (2012).

    Article  CAS  Google Scholar 

  165. Pietropaolo, M., Towns, R. & Eisenbarth, G. S. Humoral autoimmunity in type 1 diabetes: prediction, significance, and detection of distinct disease subtypes. Cold Spring Harb. Perspect. Med. 2, Pii: a012831 (2012).

    Article  CAS  Google Scholar 

  166. Skog, O., Korsgren, S., Melhus, A. & Korsgren, O. Revisiting the notion of type 1 diabetes being a T-cell mediated autoimmune disease. Curr. Opin. Endocrinol. Diabetes Obes. 20, 118–123 (2013).

    Article  CAS  PubMed  Google Scholar 

  167. Kanczkowski, W., Ziegler, C. G., Zacharowski, K. & Bornstein, S. R. Toll-like receptors in endocrine disease and diabetes. Neuroimmunomodulation 15, 54–60 (2008).

    Article  CAS  PubMed  Google Scholar 

  168. Beauquis, J., Homo-Delarche, F., Revsin Y, de Nicola, A. F. & Saravia, F. Brain alterations in autoimmune and pharmacological models of diabetes mellitus: focus on hypothalamic-pituitary-adrenocortical axis disturbances. Neuroimmunomodulation 15, 61–67 (2008).

    Article  CAS  PubMed  Google Scholar 

  169. Lee, J. S. et al. B7x in the periphery abrogates pancreas-specific damage mediated by self-reactive CD8 T cells. J. Immunol. 189, 4165–4175 (2012).

    Article  CAS  PubMed  Google Scholar 

  170. Stumpf, M., Zhou, X. & Bluestone, J. A. The B7-independent isoform of CTLA-4 functions to regulate autoimmune diabetes. J. Immunol. 190, 961–969 (2013).

    Article  CAS  PubMed  Google Scholar 

  171. Livshits, A. & Seidman, D. S. Fertility issues in women with diabetes. Women's Health (Lond. Engl.) 5, 701–717 (2009).

    Article  Google Scholar 

  172. Holstein, A., Patzer, O., Tiemann, T., Vortherms, J. & Kovacs, P. Number and sex ratio of children and impact of parental diabetes in individuals with type 1 diabetes. Diabet. Med. 29, 1268–1271 (2012).

    Article  CAS  PubMed  Google Scholar 

  173. Whitworth, K. W., Baird, D. D., Stene, L. C., Skjaerven, R. & Longnecker, M. P. Fecundability among women with type 1 and type 2 diabetes in the norwegian mother and child cohort study. Diabetologia 54, 516–522 (2011).

    Article  CAS  PubMed  Google Scholar 

  174. Codner, E. et al. Ovulation rate in adolescents with type 1 diabetes mellitus. Fertil. Steril. 95, 197–202 (2011).

    Article  PubMed  Google Scholar 

  175. Murphy, H. R. et al. Obstetric and perinatal outcomes in pregnancies complicated by type 1 and type 2 diabetes: influences of glycemic control, obesity and social disadvantage. Diabet. Med. 28, 1060–1067 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  176. Al-Agha, R. et al. Outcome of pregnancy type 1 diabetes mellitus (T1DMP): results from combined diabetes-obstetrical clinics in Dublin in three university teaching hospitals (1995–2006). Ir. J. Med. Sci. 181, 105–109 (2012).

    Article  CAS  PubMed  Google Scholar 

  177. Riskin-Mashiah, S. & Auslander, R. Quality of medical care in diabetic women undergoing fertility treatment: we should do better! Diabetes Care 34, 2164–2169 (2001).

    Article  Google Scholar 

  178. Vargas, R., Repke, J. T. & Ural, S. H. Type I diabetes mellitus and pregnancy. Rev. Obstet. Gynecol. 3, 92–100 (2010).

    PubMed  PubMed Central  Google Scholar 

  179. Ramin, N. et al. Maternal diabetes impairs gastrulation and insulin and IGF-1 receptor expression in rabbit blastocysts. Endocrinology 151, 4158–4167 (2010).

    Article  CAS  PubMed  Google Scholar 

  180. Wang, W., Lin, Y., Zeng, S. & Li, D. J. Improvement of fertility with adoptive CD25+ natural killer cell transfer in subfertile non-obese diabetic mice. Reprod. Biomed. Online 18, 95–103 (2009).

    Article  CAS  PubMed  Google Scholar 

  181. Guma, M. & Firestein, G. S. IgG4-related diseases. Best Pract. Res. Clin. Rheumatol. 26, 425–438 (2012).

    Article  CAS  PubMed  Google Scholar 

  182. Watanabe, T. et al. Clinical features of a new disease concept of IgG4-related thyroiditis. Scand. J. Rheumatol. 42, 325–330 (2013).

    Article  CAS  PubMed  Google Scholar 

  183. Neufeld, M., Maclaren, N. & Blizzard, R. Autoimmune polyglandular syndromes. Pediatr. Ann. 9, 154–162 (1980).

    Article  CAS  PubMed  Google Scholar 

  184. Betterle, C., Dal Pra, C., Mantero, F. & Zanchetta, R. Autoimmune adrenal insufficiency and autoimmune polyendocrine syndromes: autoantibodies, autoantigens, and their applicability in diagnosis and disease prediction. Endocr. Rev. 23, 327–364 (2002).

    Article  CAS  PubMed  Google Scholar 

  185. Betterle, C. & Zanchetta, R. Update on autoimmune polyendocrine syndromes (APS). Acta Biomed. 74, 9–33 (2003).

    PubMed  Google Scholar 

  186. Eisenbarth, G. S. & Gottlieb, P. A. Autoimmune polyendocrine syndromes. N. Engl. J. Med. 350, 2068–2079 (2004).

    Article  CAS  PubMed  Google Scholar 

  187. Michels, A. W. & Gottlieb, P. A. Autoimmune polyglandular syndromes. Nat. Rev. Endocrinol. 6, 270–277 (2010).

    Article  CAS  PubMed  Google Scholar 

  188. Gleicher, N., Weghofer, A. & Barad, D. Female infertility due to abnormal autoimmunity: frequently overlooked and greatly underappreciated. Part II. Expert Rev. Obstet. Gynecol. 2, 465–475 (2007).

    Article  CAS  Google Scholar 

  189. Cushman, R. A. Evidence that the autoimmune regulator gene influences thymic production of ovarian antigens and prevents autoimmune-mediated premature reproductive senescence. Biol. Reprod. 86, 109 (2012).

    Article  CAS  PubMed  Google Scholar 

  190. Jasti, S. et al. The autoimmune regulator prevents premature reproductive senescence in female mice. Biol. Reprod. 86, 110 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  191. Gleicher, N., Weghofer, A. & Barad, D. Do etiologies of premature ovarian aging (POA) mimic those of premature ovarian failure (POF)? Hum. Reprod. 24, 2395–2400 (2009).

    Article  CAS  PubMed  Google Scholar 

  192. Unuanae, D., Tournaye, H., Velkeniers, B. & Poppe, K. Endocrine disorders & female infertility. Best Pract. Res. Clin. Endocrinol. Metab. 25, 861–873 (2011).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The authors would like to acknowledge the support of The Center for Human Reproduction.

Author information

Authors and Affiliations

  1. The Center for Human Reproduction (CHR), 21 East 69th Street, New York, 10021, NY, USA

    Aritro Sen, Vitaly A. Kushnir, David H. Barad & Norbert Gleicher

Authors
  1. Aritro Sen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Vitaly A. Kushnir
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. David H. Barad
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Norbert Gleicher
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

A.S. and N.G. researched data for the article, provided a substantial contribution to discussion of the content, wrote the article and reviewed and edited the manuscript before submission. V.A.K. and D.H.B. contributed to writing the article and reviewing and editing the manuscript before submission.

Corresponding author

Correspondence to Norbert Gleicher.

Ethics declarations

Competing interests

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.

PowerPoint slides

Rights and permissions

Reprints and Permissions

About this article

Cite this article

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

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrendo.2013.212

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing