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Thyroid Diseases and Female Infertility

  • Petrache Vartej
  • Ioana Vartej
Chapter
Part of the Reproductive Medicine for Clinicians book series (REMECL, volume 1)

Abstract

Thyroid diseases in women of reproductive age are associated with a broad spectrum of disorders, from menstrual irregularities, infertility to pregnancy loss. Negative association exist between thyroid autoimmunity without thyroid dysfunction and infertility and early miscarriage. Thyroid hormones play an important role in reproductive function, with direct effects on the ovarian follicles, endometrium, implantation and placentation. Both primary hypothyroidism and hyperthyroidism in women of reproductive age can produce altered sex hormones metabolism, disrupting the hypothalamic-pituitary-ovarian axis and resulting in inadequate ovulation. The prevalence of hypothyroidism overt or subclinical in women with infertility is increased. Autoimmune thyroid disease affect 5–20% of women in the childbearing period. Many studies indicate an increased prevalence of thyroid autoimmunity among women with infertility, especially in patients with ovulatory dysfunction, and significant increased risk of miscarriage in euthyroid women with thyroid autoimmunity following assisted reproduction technology. Women with infertility should be screened for thyroid dysfunction and thyroid antibodies. Treatment of thyroid dysfunction and restoration of euthyroidism can improve fertility. The upper limit of TSH of 2.5 mIU/L is proposed as a cut-off before assisted reproduction procedures, independent of thyroid antibody status, but controversies persist in treating subclinical hypothyroidism women.

Keywords

Thyroid Disease Autoimmune Female Infertility 

References

  1. 1.
    Hollowell JG, Staehling NW, Flanders WD, et al. Serum TSH, T(4), and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III). J Clin Endocrinol Metab. 2002;87:489–99.CrossRefGoogle Scholar
  2. 2.
    Vanderpump MP, Tunbridge WM, French JM. The incidence of thyroid disorders in the community: a twenty-year follow-up of the Whickham Survey. Clin Endocrinol (Oxf). 1995;43(1):55–68.CrossRefGoogle Scholar
  3. 3.
    Mc Grogan A, Seaman HE, Wright JW, DeVries C. The incidence of autoimmune thyroid disease: a systematic review of the literature. Clin Endocrinol (Oxf). 2008;69(5):687–96.CrossRefGoogle Scholar
  4. 4.
    Chiamolera MI, Wondisford FE. Minireview: thyrotropin-releasing hormone and the thyroid hormone feedback mechanism. Endocrinology. 2009;150:1091–6.CrossRefGoogle Scholar
  5. 5.
    Karapanou O, Papadimitriou A. Thyroid hormone transporters in the human. Hormones. 2011;10:270–9.CrossRefGoogle Scholar
  6. 6.
    Lazar MA. Thyroid hormone receptors: multiple forms, multiple possibilities. Endocr Rev. 1993;14:184–93.PubMedGoogle Scholar
  7. 7.
    Wakim AN, Marrero MA, Polizotto SL, et al. Thyroid hormones in human follicular fluid and thyroid hormone receptors in human granulosa cells. Fertil Steril. 1993;59:1187–90.CrossRefGoogle Scholar
  8. 8.
    Zhang SS, Carrillo AJ, Darling DS. Expression of multiple thyroid hormone receptor mRNAs in human oocytes, cumulus cells, and granulosa cells. Mol Hum Reprod. 1997;3:555–62.CrossRefGoogle Scholar
  9. 9.
    Wakim AN, Polizotto SL, Burholt DR. Augmentation by thyroxine of human granulosa cell gonadotrophin-induced steroidogenesis. Hum Reprod. 1995;10:2845–8.CrossRefGoogle Scholar
  10. 10.
    Maruo T, Hiramatsu S, Otani T, Hayashi M, Mochizuki M. Increase in the expression of thyroid hormone receptors in porcine granulosa cells early in follicular maturation. Acta Endocrinol (Copenh). 1992;127:152–60.CrossRefGoogle Scholar
  11. 11.
    Aghajanova L, Stavreus-Evers A, Lindeberg M, et al. Thyroid-stimulating hormone receptor and thyroid hormone receptors are involved in human endometrial physiology. Fertil Steril. 2011;95:230–7.CrossRefGoogle Scholar
  12. 12.
    Catalano RD, Critchley HO, Heikinheimo O, et al. Mifepristone induced progesterone withdrawal reveals novel regulatory pathways in human endometrium. Mol Hum Reprod. 2007;13:641–54.CrossRefGoogle Scholar
  13. 13.
    Kim CH, Ahn JW, Kang SP, et al. Effect of levothyroxine treatment on in vitro fertilization and pregnancy outcome in infertile women with subclinical hypothyroidism undergoing in vitro fertilization/intracytoplasmic sperm injection. Fertil Steril. 2011;95:1650–4.CrossRefGoogle Scholar
  14. 14.
    Colicchia M, Campagnolo L, Baldini E, et al. Molecular basis of thyrotropin and thyroid hormone action during implantation and early development. Hum Reprod Update. 2014;20(6):884–904.CrossRefGoogle Scholar
  15. 15.
    Oki NM. Effects of 3,5,3′-triiodothyronine on the invasive potential and the expression of integrins and matrix metalloproteinases in cultured early placental extravillous trophoblasts. J Clin Endocrinol Metab. 2004;89:5213–21.CrossRefGoogle Scholar
  16. 16.
    Redmond GP. Thyroid dysfunction and women’s reproductive health. Thyroid. 2004;14(Suppl 1):S5–S15.CrossRefGoogle Scholar
  17. 17.
    Pontikides N, Kaltsas TH, Krassas GE. The hypothalamic-pituitary-gonadal axis in hyperthyroid female patients before and after treatment. J Endocrinol Invest. 1990;13(2 Suppl):203.Google Scholar
  18. 18.
    Krassas GE, Poppe K, Glinoer D. Thyroid function and human reproductive health. Endocr Rev. 2010;31:702–55.CrossRefGoogle Scholar
  19. 19.
    Krassas GE, Pontikides N, Kaltsas T. Menstrual disturbances in thyrotoxicosis. Clin Endocrinol (Oxf). 1994;40:641–4.CrossRefGoogle Scholar
  20. 20.
    Goldsmith RE, Sturgis SH, Lerman J, Stanbury JB. The menstrual pattern in thyroid disease. J Clin Endocrinol Metab. 1952;12:846–55.CrossRefGoogle Scholar
  21. 21.
    Krassas GE. Thyroid disease, menstrual function and fertility. Thyroid Int. 2000;1:1–15.Google Scholar
  22. 22.
    Vissenberg R, Manders VD, Mastenbroek S, et al. Pathophysiological aspects of thyroid hormone disorders/thyroid peroxidase autoantibodies and reproduction. Hum Reprod Update. 2015;21(3):378–87.CrossRefGoogle Scholar
  23. 23.
    Arojoki M, Jokimaa V, Juuti A, et al. Hypothyroidism among infertile women in Finland. Gynecol Endocrinol. 2000;14:127–31.CrossRefGoogle Scholar
  24. 24.
    Poppe K, Glinoer D, Van Steirteghem A, et al. Thyroid dysfunction and autoimmunity in infertile women. Thyroid. 2002;12:997–1001.CrossRefGoogle Scholar
  25. 25.
    Poppe K, Velkeniers B, Glinoer D. Thyroid disease and female reproduction. Clin Endocrinol. 2007;66(3):309–21.CrossRefGoogle Scholar
  26. 26.
    Abalovich M, Mitelberg L, Allami C, et al. Subclinical hypothyroidism and thyroid autoimmunity in women with infertility. Gynecol Endocrinol. 2007;23:279–83.CrossRefGoogle Scholar
  27. 27.
    Effraimidis G, Wiersinga WM. Autoimmune thyroid disease: old and new players. Eur J Endocrinol. 2014;170:R241–52.CrossRefGoogle Scholar
  28. 28.
    Gleicher N, Kushnir VA, Weghofer A, Barad D. How the FMR1 gene became relevant to female fertility and reproductive medicine. Front Genet. 2014;5:284.CrossRefGoogle Scholar
  29. 29.
    Janssen OE, Mehlmauer N, Hahn S, et al. High prevalence of autoimmune thyroiditis in patients with polycystic ovary syndrome. Eur J Endocrinol. 2004;150:363–9.CrossRefGoogle Scholar
  30. 30.
    Garelli S, Masiero S, Plebani M, et al. High prevalence of chronic thyroiditis in patients with polycystic ovary syndrome. Eur J Obstet Gynecol. 2013;169(2):248–51.CrossRefGoogle Scholar
  31. 31.
    Kachuei M, Jafari F, Kachuei A, Keshteli AH. Prevalence of autoimmune thyroiditis in patients with polycystic ovary syndrome. Arch Gynecol Obstet. 2012;285:853–6.CrossRefGoogle Scholar
  32. 32.
    Al-Saab R, Haddad S. Detection of thyroid autoimmunity markers in euthyroid women with polycystic ovary syndrome: a case-control study from Syria. Int J Endocrinol Metab. 2014;12(3):e17954.CrossRefGoogle Scholar
  33. 33.
    Novais Jde S, Benetti-Pinto CL, Garmes HM. Polycystic ovary syndrome and chronic autoimmune thyroiditis. Gynecol Endocrinol. 2015;31(1):48–51.CrossRefGoogle Scholar
  34. 34.
    Ott J, Aust S, Kurz C, et al. Elevated antithyroid peroxidase antibodies indicating Hashimoto’s thyroiditis are associated with the treatment response in infertile women with polycystic ovary syndrome. Fertil Steril. 2010;94(7):2895–7.CrossRefGoogle Scholar
  35. 35.
    Gleicher N, Barad D, Weghofer A. Functional autoantibodies, a new paradigm in autoimmunity? Autoimmun Rev. 2007;7:42–5.CrossRefGoogle Scholar
  36. 36.
    Pennel L, Galligan CL, Fish EN. Sex affects immunity. J Autoimmun. 2012;38:J282–91.CrossRefGoogle Scholar
  37. 37.
    Petta CA, Arruda MS, Zantut-Wittmann DE, et al. Thyroid autoimmunity and thyroid dysfunction in women with endometriosis. Hum Reprod. 2007;22:2693–7.CrossRefGoogle Scholar
  38. 38.
    Matarese G, De Placido G, Nikas Y, Alviggi C. Pathogenesis of endometriosis: natural immunity dysfunction or autoimmune disease? Trends Mol Med. 2003;9(5):223–8.CrossRefGoogle Scholar
  39. 39.
    Poppe K, Glinoer D, Tournaye H, et al. Impact of ovarian hyperstimulation on thyroid function in women with and without thyroid autoimmunity. J Clin Endocrinol Metab. 2004;89:3808–12.CrossRefGoogle Scholar
  40. 40.
    Geva E, Vardinon N, Lessing JB, et al. Organ-specific autoantibodies are possible markers for reproductive failure: a prospective study in an in vitro fertilization-embryo transfer programme. Hum Reprod. 1996;11(8):1627–31.CrossRefGoogle Scholar
  41. 41.
    Negro R, Formoso G, Coppola L, et al. Euthyroid women with autoimmune disease undergoing assisted reproduction technologies: the role of autoimmunity and thyroid function. J Endocrinol Invest. 2007;30(1):3–8.CrossRefGoogle Scholar
  42. 42.
    Toulis KA, Goulis DG, Venetis CA, et al. Risk of spontaneous miscarriage in euthyroid women with thyroid autoimmunity undergoing IVF: a meta-analysis. Eur J Endocrinol. 2010;162:643–52.CrossRefGoogle Scholar
  43. 43.
    Poppe K, Glinoer D, Tournaye H, et al. Assisted reproduction and thyroid autoimmunity: an unfortunate combination? J Clin Endocrinol Metab. 2003;88(9):4149–52.CrossRefGoogle Scholar
  44. 44.
    Monteleone P, Parrini D, Faviana P, et al. Female infertility related to thyroid autoimmunity: the ovarian follicle hypothesis. Am J Reprod Immunol. 2011;66:108–14.CrossRefGoogle Scholar
  45. 45.
    Busnelli A, Paffoni A, Fedele L, Somigliana E. The impact of thyroid autoimmunity on IVF/ICSI outcome: a systematic review and meta-analysis. Hum Rep Update. 2016;22(6):775–90.CrossRefGoogle Scholar
  46. 46.
    Negro R, Mangieri T, Coppola L. Levothyroxine treatment in thyroid peroxidase antibody-positive women undergoing assisted reproduction technologies: a prospective study. Hum Reprod. 2005;20:1529–33.CrossRefGoogle Scholar
  47. 47.
    Plowden TC, Schisterman EF, Sjaarda LA, et al. Subclinical hypothyroidism and thyroid autoimmunity are not associated with fecundity, pregnancy loss or live birth. J Clin Endocrinol Metab. 2016;101(6):2358–65.CrossRefGoogle Scholar
  48. 48.
    Kelkar RL, Mejerji PK, Kadam SS, et al. Circulating auto-antibodies against the zona pellucida and thyroid microsomal antigen in women with premature ovarian failure. J Reprod Immunol. 2005;66:53–67.CrossRefGoogle Scholar
  49. 49.
    Kilic S, Tasdemir N. The effect of anti-thyroid antibodies on endometrial volume, embryo grade and IVF outcome. Gynecol Endocrinol. 2008;24:649–55.CrossRefGoogle Scholar
  50. 50.
    Zhong YP, Ying Y, Wu HT. Relationship between antithyroid antibody and pregnancy outcome following in vitro fertilization and embryo transfer. Int J Med Sci. 2012;9:121–5.CrossRefGoogle Scholar
  51. 51.
    Seror J, Amand G, Guibourdenche J, et al. Anti-TPO antibodies diffusion through the placental barrier during pregnancy. PLoS One. 2014;9:e8464.CrossRefGoogle Scholar
  52. 52.
    Thangaratinam S, Tan A, Knox E, et al. Association between thyroid autoantibodies and miscarriage and preterm birth: meta-analysis of evidence. BMJ. 2011;342:d2616.CrossRefGoogle Scholar
  53. 53.
    De Groot L, Abalovich M, Alexander EK, et al. Management of thyroid dysfunction dyring pregnancy and postpartum. J Clin Endocrinol Metab. 2012;97(8):2543–65.CrossRefGoogle Scholar
  54. 54.
    Garber JR, Cobin RH, Gharib H, et al. Clinical practice guidelines for hypothyroidism in adults: cosponsored by the American Association of Clinical Endocrinologists and the American Thyroid Association. Endocr Pract. 2012;18:988–1028.CrossRefGoogle Scholar
  55. 55.
    Practice Committee of the American Society for Reproductive Medicine. Subclinical hypothyroidism in the infertile female population: a guideline. Fertil Steril. 2015;104:545–53.CrossRefGoogle Scholar

Copyright information

© IAHR (International Academy of Human Reproduction) 2018

Authors and Affiliations

  • Petrache Vartej
    • 1
  • Ioana Vartej
    • 2
  1. 1.Department of Obstetrics and GynecologyUniversity of Medicine and Pharmacy “Carol Davila”, University HospitalBucharestRomania
  2. 2.Altnagelvin Area Hospital Western Trust HSCLondonderryUK

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