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Thyroid Dysfunction and Infertility

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Abstract

Female fertility is a cumulative process of ovarian function, oocyte development, endometrial receptivity, and male factors. This chapter examines the relationship between thyroid dysfunction and female reproductive potential. Hypothyroidism is associated with changes in menstrual patterns, including decreased menstrual cycle frequency and increased volume of menses. Thyroid hormone, thyroid hormone transporters, and nuclear thyroid hormone receptors have been found in ovarian follicles and in oocytes. Thyroid hormone receptors are also found at the surface of the endometrium and are thought to be involved in the interaction between the endometrium and the blastocyst at the time of implantation. There continues to be debate on whether subclinical hypothyroidism is associated with infertility. Evidence suggests that subclinical hypothyroidism and thyroid antibodies, in addition to overt hypothyroidism, may be associated with negative outcomes among women undergoing treatment with assisted reproductive technology.

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References

  1. Vissenberg R, Manders VD, Mastenbroek S, Fliers E, Afink GB, Ris-Stalpers C, et al. Pathophysiological aspects of thyroid hormone disorders/thyroid peroxidase autoantibodies and reproduction. Hum Reprod Update. 2015;21(3):378–87.

    Article  CAS  Google Scholar 

  2. Krassas GE, Poppe K, Glinoer D. Thyroid function and human reproductive health. Endocr Rev. 2010;31(5):702–55.

    Article  CAS  Google Scholar 

  3. Dittrich R, Beckmann MW, Oppelt PG, Hoffmann I, Lotz L, Kuwert T, et al. Thyroid hormone receptors and reproduction. J Reprod Immunol. 2011;90:58–66.

    Article  CAS  Google Scholar 

  4. 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(7):555–62.

    Article  CAS  Google Scholar 

  5. Aghajanova L, Lindeberg M, Carlsson IB, Stavreus-Evers A, Zhang P, Scott JE, et al. Receptors for thyroid-stimulating hormone and thyroid hormones in human ovarian tissue. Reprod Biomed Online. 2009;18(3):337–47.

    Article  CAS  Google Scholar 

  6. Liu J, Tian Y, Ding Y, Heng D, Xu K, Liu W, et al. Role of CYP51 in the regulation of T3 and FSH-induced steroidogenesis in female mice. Endocrinology. 2017;158(11):3974–87.

    Article  Google Scholar 

  7. Verga Falzacappa C, Mangialardo C, Patriarca V, Bucci B, Amendola D, Raffa S, et al. Thyroid hormones induce cell proliferation and survival in ovarian granulosa cells COV434. J Cell Physiol. 2009;221(1):242–53.

    Article  CAS  Google Scholar 

  8. Tian Y, Ding Y, Liu J, Heng D, Xu K, Liu W, et al. Nitric oxide-mediated regulation of GLUT by T3 and follicle-stimulating hormone in rat granulosa cells. Endocrinology. 2017;158(6):1898–915.

    Article  Google Scholar 

  9. Colicchia M, Campagnolo L, Baldini E, Ulisse S, Valensise H, Moretti C. Molecular basis of thyrotropin and thyroid hormone action during implantation and early development. Hum Reprod Update. 2014;20(6):884–904.

    Article  CAS  Google Scholar 

  10. Aghajanova L, Stavreus-Evers A, Lindeberg M, Landgren B-M, Sparre LS, Hovatta O. Thyroid-stimulating hormone receptor and thyroid hormone receptors are involved in human endometrial physiology. Fertil Steril. 2011;95(1):237.e1–2.

    Article  Google Scholar 

  11. Detti L, Uhlmann RA, Fletcher NM, Diamond MP, Saed GM. Endometrial signaling pathways during ovarian stimulation for assisted reproduction technology. Fertil Steril. 2013;100(3):889–94.

    Article  CAS  Google Scholar 

  12. Practice Committee of the American Society for Reproductive Medicine. Subclinical hypothyroidism in the infertile female population: a guideline. Fertil Steril. 2015;104(3):545–53.

    Article  Google Scholar 

  13. Alexander EK, Pearce EN, Brent GA, Brown RS, Chen H, Dosiou C, et al. 2017 guidelines of the American Thyroid Association for the diagnosis and Management of Thyroid Disease during Pregnancy and the postpartum. Thyroid. 2017;27(3):315–89.

    Article  Google Scholar 

  14. Surks MI, Ortiz E, Daniels GH, Sawin CT, Col NF, Cobin RH, et al. Subclinical thyroid disease: scientific review and guidelines for diagnosis and management. JAMA. 2004;291(2):228–38.

    Article  CAS  Google Scholar 

  15. Abalovich M, Mitelberg L, Allami C, Gutierrez S, Alcaraz G, Otero P, et al. Subclinical hypothyroidism and thyroid autoimmunity in women with infertility. Gynecol Endocrinol. 2007;23(5):279–83.

    Article  CAS  Google Scholar 

  16. Poppe K, Glinoer D, Van Steirteghem A, Tournaye H, Devroey P, Schiettecatte J, et al. Thyroid dysfunction and autoimmunity in infertile women. Thyroid. 2002;12(11):997–1001.

    Article  Google Scholar 

  17. Lincoln SR, Ke RW, Kutteh WH. Screening for hypothyroidism in infertile women. J Reprod Med. 1999;44(5):455–7.

    CAS  PubMed  Google Scholar 

  18. Feldthusen A-D, Pedersen PL, Larsen J, Toft Kristensen T, Ellervik C, Kvetny J. Impaired fertility associated with subclinical hypothyroidism and thyroid autoimmunity: the Danish general suburban population study. J Pregnancy. 2015;2015:132718.

    Article  Google Scholar 

  19. Plowden TC, Schisterman EF, Sjaarda LA, Zarek SM, Perkins NJ, Silver R, 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.

    Article  CAS  Google Scholar 

  20. Yoshioka Y, Amino N, Ide A, Kang S, Kudo T, Nishihara E, et al. Thyroxine treatment may be useful for subclinical hypothyroidism in patients with female infertility. Endocr J. 2015;62(1):87–92.

    Article  CAS  Google Scholar 

  21. Verma I, Sood R, Juneja S, Kaur S. Prevalence of hypothyroidism in infertile women and evaluation of response of treatment for hypothyroidism on infertility. Int J Appl Basic Med Res. 2012;2(1):17–9.

    Article  CAS  Google Scholar 

  22. La Vignera S, Vita R, Condorelli RA, Mongioì LM, Presti S, Benvenga S, et al. Impact of thyroid disease on testicular function. Endocrine. 2017;58(3):397–407.

    Article  Google Scholar 

  23. Rajender S, Monica MG, Walter L, Agarwal A. Thyroid, spermatogenesis, and male infertility. Front Biosci (Elite Ed). 2011;3:843–55.

    Google Scholar 

  24. Lotti F, Maseroli E, Fralassi N, Degl’Innocenti S, Boni L, Baldi E, et al. Is thyroid hormones evaluation of clinical value in the work-up of males of infertile couples? Hum Reprod. 2016;31(3):518–29.

    Article  CAS  Google Scholar 

  25. Cai Y, Zhong L, Guan J, Guo R, Niu B, Ma Y, et al. Outcome of in vitro fertilization in women with subclinical hypothyroidism. Reprod Biol Endocrinol. 2017;15(1):39.

    Article  Google Scholar 

  26. Chai J, Yeung W-YT, Lee C-YV, Li H-WR, Ho PC, Ng H-YE. Live birth rates following in vitro fertilization in women with thyroid autoimmunity and/or subclinical hypothyroidism. Clin Endocrinol. 2014;80(1):122–7.

    Article  CAS  Google Scholar 

  27. Liu H, Shan Z, Li C, Mao J, Xie X, Wang W, et al. Maternal subclinical hypothyroidism, thyroid autoimmunity, and the risk of miscarriage: a prospective cohort study. Thyroid. 2014;24(11):1642–9.

    Article  CAS  Google Scholar 

  28. Kim CH, Ahn J-W, Kang SP, Kim SH, Chae H-D, Kang B-M. 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(5):1650–4.

    Article  CAS  Google Scholar 

  29. Abdel Rahman AH, Aly Abbassy H, Abbassy AAE. Improved in vitro fertilization outcomes after treatment of subclinical hypothyroidism in infertile women. Endocr Pract. 2010;16(5):792–7.

    Article  Google Scholar 

  30. Wang S, Teng WP, Li JX, Wang WW, Shan ZY. Effects of maternal subclinical hypothyroidism on obstetrical outcomes during early pregnancy. J Endocrinol Investig. 2012;35(3):322–5.

    CAS  Google Scholar 

  31. Ain KB, Mori Y, Refetoff S. Reduced clearance rate of thyroxine-binding globulin (TBG) with increased sialylation: a mechanism for estrogen-induced elevation of serum TBG concentration. J Clin Endocrinol Metab. 1987;65(4):689–96.

    Article  CAS  Google Scholar 

  32. Yoshimura M, Hershman JM. Thyrotropic action of human chorionic gonadotropin. Thyroid. 1995;5(5):425–34.

    Article  CAS  Google Scholar 

  33. Gracia CR, Morse CB, Chan G, Schilling S, Prewitt M, Sammel MD, et al. Thyroid function during controlled ovarian hyperstimulation as part of in vitro fertilization. Fertil Steril. 2012;97(3):585–91.

    Article  CAS  Google Scholar 

  34. Busnelli A, Somigliana E, Benaglia L, Sarais V, Ragni G, Fedele L. Thyroid axis dysregulation during in vitro fertilization in hypothyroid-treated patients. Thyroid. 2014;24(11):1650–5.

    Article  CAS  Google Scholar 

  35. Karmon AE, Batsis M, Chavarro JE, Souter I. Preconceptional thyroid-stimulating hormone levels and outcomes of intrauterine insemination among euthyroid infertile women. Fertil Steril. 2015;103(1):258–63.

    Article  CAS  Google Scholar 

  36. Unuane D, Velkeniers B, Bravenboer B, Drakopoulos P, Tournaye H, Parra J, et al. Impact of thyroid autoimmunity in euthyroid women on live birth rate after IUI. Hum Reprod. 2017;32(4):915–22.

    CAS  PubMed  Google Scholar 

  37. Seungdamrong A, Steiner AZ, Gracia CR, Legro RS, Diamond MP, Coutifaris C, et al. Preconceptional antithyroid peroxidase antibodies, but not thyroid-stimulating hormone, are associated with decreased live birth rates in infertile women. Fertil Steril. 2017.; pii: S0015–0282(17)31748-X.

    Google Scholar 

  38. Baker VL, Rone HM, Pasta DJ, Nelson HP, Gvakharia M, Adamson GD. Correlation of thyroid stimulating hormone (TSH) level with pregnancy outcome in women undergoing in vitro fertilization. Am J Obstet Gynecol. 2006;194(6):1668–74. discussion 1674–5

    Article  CAS  Google Scholar 

  39. Fumarola A, Grani G, Romanzi D, Del Sordo M, Bianchini M, Aragona A, et al. Thyroid function in infertile patients undergoing assisted reproduction. Am J Reprod Immunol. 2013;70(4):336–41.

    Article  CAS  Google Scholar 

  40. Reh A, Grifo J, Danoff A. What is a normal thyroid-stimulating hormone (TSH) level? Effects of stricter TSH thresholds on pregnancy outcomes after in vitro fertilization. Fertil Steril. 2010;94(7):2920–2.

    Article  CAS  Google Scholar 

  41. Zhong Y, Ying Y, Wu HT, Zhou CQ, Xu YW, Wang Q, et al. Relationship between antithyroid antibody and pregnancy outcome following in vitro fertilization and embryo transfer. Int J Med Sci. 2012;9(2):121–5.

    Article  CAS  Google Scholar 

  42. Karacan M, Alwaeely F, Cebi Z, Berberoglugil M, Batukan M, Ulug M, et al. Effect of antithyroid antibodies on ICSI outcome in antiphospholipid antibody-negative euthyroid women. Reprod Biomed Online. 2013;27(4):376–80.

    Article  CAS  Google Scholar 

  43. Wang H, Gao H, Chi H, Zeng L, Xiao W, Wang Y, et al. Effect of levothyroxine on miscarriage among women with normal thyroid function and thyroid autoimmunity undergoing in vitro fertilization and embryo transfer: a randomized clinical trial. JAMA. 2017;318(22):2190–8.

    Article  CAS  Google Scholar 

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Bhatt, S.J., Holden, E.C., Seungdamrong, A. (2019). Thyroid Dysfunction and Infertility. In: Eaton, J. (eds) Thyroid Disease and Reproduction. Springer, Cham. https://doi.org/10.1007/978-3-319-99079-8_9

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  • DOI: https://doi.org/10.1007/978-3-319-99079-8_9

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  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-99078-1

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