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Mechanisms of Primary Ovarian Insufficiency

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Book cover Primary Ovarian Insufficiency

Abstract

Premature loss of ovarian follicles can occur due to several basic underlying causes: (1) Inadequate initial complement of follicles due to defects in germ cell location, proliferation, or retention prior to attainment of maximum follicle numbers in fetal life; (2) excessive loss of a normal complement of follicles due to pathological processes, genetic causes, or environmental toxins; and (3) iatrogenic destruction of ovarian follicles either through surgery, chemotherapy, or other causes. Recent advances in genetics have led to the discovery of a number of unique mutations that cause primary ovarian insufficiency (POI). Each individual mutation is relatively rare, but they have revealed important information about the processes of early ovarian development and follicle maintenance. New knowledge about the environmental effects of cigarette smoking and other potential endocrine-disrupting chemicals may also provide information about the etiology of some cases of POI. Finally, underlying infectious and invasive processes such as pelvic inflammatory disease and endometriosis, which can require repeated ovarian surgeries, also carry risks of premature loss of ovarian follicles. This chapter will review the current state of the science.

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References

  1. Nelson LM. Clinical practice. Primary ovarian insufficiency. N Engl J Med. 2009;360(6):606–14.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  2. Bachelot A, Rouxel A, Massin N, Dulon J, Courtillot C, Matuchansky C, et al. Phenotyping and genetic studies of 357 consecutive patients presenting with premature ovarian failure. Eur J Endocrinol. 2009;161(1):179–87.

    Article  CAS  PubMed  Google Scholar 

  3. Stochholm K, Juul S, Juel K, Naeraa RW, Gravholt CH. Prevalence, incidence, diagnostic delay, and mortality in Turner syndrome. J Clin Endocrinol Metab. 2006;91(10):3897–902.

    Article  CAS  PubMed  Google Scholar 

  4. Davenport ML. Approach to the patient with Turner syndrome. J Clin Endocrinol Metab. 2010;95(4):1487–95.

    Article  CAS  PubMed  Google Scholar 

  5. Bondy CA. Turner syndrome 2008. Horm Res. 2009;71 Suppl 1:52–6.

    Article  CAS  PubMed  Google Scholar 

  6. Gonzalez L, Witchel SF. The patient with Turner syndrome: puberty and medical management concerns. Fertil Steril. 2012;98(4):780–6.

    Article  PubMed Central  PubMed  Google Scholar 

  7. Zhong Q, Layman LC. Genetic considerations in the patient with Turner syndrome--45,X with or without mosaicism. Fertil Steril. 2012;98(4):775–9.

    Article  PubMed Central  PubMed  Google Scholar 

  8. Ogata T, Matsuo N. Turner syndrome and female sex chromosome aberrations: deduction of the principal factors involved in the development of clinical features. Hum Genet. 1995;95(6):607–29.

    Article  CAS  PubMed  Google Scholar 

  9. Conway GS, Conway E, Walker C, Hoppner W, Gromoll J, Simoni M. Mutation screening and isoform prevalence of the follicle stimulating hormone receptor gene in women with premature ovarian failure, resistant ovary syndrome and polycystic ovary syndrome. Clin Endocrinol. 1999;51(1):97–9.

    Article  CAS  Google Scholar 

  10. Pasquino AM, Passeri F, Pucarelli I, Segni M, Municchi G. Spontaneous pubertal development in Turner’s syndrome. Italian Study Group for Turner’s Syndrome. J Clin Endocrinol Metab. 1997;82(6):1810–3.

    CAS  PubMed  Google Scholar 

  11. Otter M, Schrander-Stumpel CT, Curfs LM. Triple X syndrome: a review of the literature. Eur J Hum Genet. 2010;18(3):265–71.

    Article  PubMed Central  PubMed  Google Scholar 

  12. Holland CM. 47, XXX in an adolescent with premature ovarian failure and autoimmune disease. J Pediatr Adolesc Gynecol. 2001;14(2):77–80.

    Article  CAS  PubMed  Google Scholar 

  13. Itu M, Neelam T, Ammini AC, Kucheria K. Primary amenorrhoea in a triple X female. Aust N Z J Obstet Gynaecol. 1990;30(4):386–8.

    Article  CAS  PubMed  Google Scholar 

  14. Tharapel AT, Anderson KP, Simpson JL, Martens PR, Wilroy Jr RS, Llerena Jr JC, et al. Deletion (X) (q26.1 → q28) in a proband and her mother: molecular characterization and phenotypic-karyotypic deductions. Am J Hum Genet. 1993;52(3):463–71.

    PubMed Central  CAS  PubMed  Google Scholar 

  15. Powell CM, Taggart RT, Drumheller TC, Wangsa D, Qian C, Nelson LM, et al. Molecular and cytogenetic studies of an X; autosome translocation in a patient with premature ovarian failure and review of the literature. Am J Med Genet. 1994;52(1):19–26.

    Article  CAS  PubMed  Google Scholar 

  16. Goswami D, Conway GS. Premature ovarian failure. Hum Reprod Update. 2005;11(4):391–410.

    Article  CAS  PubMed  Google Scholar 

  17. Portnoi MF, Aboura A, Tachdjian G, Bouchard P, Dewailly D, Bourcigaux N, et al. Molecular cytogenetic studies of Xq critical regions in premature ovarian failure patients. Hum Reprod. 2006;21(9):2329–34.

    Article  CAS  PubMed  Google Scholar 

  18. Rizzolio F, Pramparo T, Sala C, Zuffardi O, De Santis L, Rabellotti E, et al. Epigenetic analysis of the critical region I for premature ovarian failure: demonstration of a highly heterochromatic domain on the long arm of the mammalian X chromosome. J Med Genet. 2009;46(9):585–92.

    Article  CAS  PubMed  Google Scholar 

  19. Persani L, Rossetti R, Cacciatore C, Bonomi M. Primary Ovarian Insufficiency: X chromosome defects and autoimmunity. J Autoimmun. 2009;33(1):35–41.

    Article  CAS  PubMed  Google Scholar 

  20. Prueitt RL, Chen H, Barnes RI, Zinn AR. Most X; autosome translocations associated with premature ovarian failure do not interrupt X-linked genes. Cytogenet Genome Res. 2002;97(1–2):32–8.

    Article  CAS  PubMed  Google Scholar 

  21. Bione S, Sala C, Manzini C, Arrigo G, Zuffardi O, Banfi S, et al. A human homologue of the Drosophila melanogaster diaphanous gene is disrupted in a patient with premature ovarian failure: evidence for conserved function in oogenesis and implications for human sterility. Am J Hum Genet. 1998;62(3):533–41.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  22. Castrillon DH, Wasserman SA. Diaphanous is required for cytokinesis in Drosophila and shares domains of similarity with the products of the limb deformity gene. Development. 1994;120(12):3367–77.

    CAS  PubMed  Google Scholar 

  23. Allingham-Hawkins DJ, Babul-Hirji R, Chitayat D, Holden JJ, Yang KT, Lee C, et al. Fragile X premutation is a significant risk factor for premature ovarian failure: the International Collaborative POF in Fragile X study—preliminary data. Am J Med Genet. 1999;83(4):322–5.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  24. Wittenberger MD, Hagerman RJ, Sherman SL, McConkie-Rosell A, Welt CK, Rebar RW, et al. The FMR1 premutation and reproduction. Fertil Steril. 2007;87(3):456–65.

    Google Scholar 

  25. Sullivan SD, Welt C, Sherman S. FMR1 and the continuum of primary ovarian insufficiency. Semin Reprod Med. 2011;29(4):299–307.

    Article  PubMed  Google Scholar 

  26. Willemsen R, Levenga J, Oostra BA. CGG repeat in the FMR1 gene: size matters. Clin Genet. 2011;80(3):214–25.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  27. Simpson JL. Genetic and phenotypic heterogeneity in ovarian failure: overview of selected candidate genes. Ann N Y Acad Sci. 2008;1135:146–54.

    Article  PubMed  Google Scholar 

  28. Persani L, Rossetti R, Di Pasquale E, Cacciatore C, Fabre S. The fundamental role of bone morphogenetic protein 15 in ovarian function and its involvement in female fertility disorders. Hum Reprod Update. 2014;20(6):869–83.

    Article  PubMed  Google Scholar 

  29. Di Pasquale E, Beck-Peccoz P, Persani L. Hypergonadotropic ovarian failure associated with an inherited mutation of human bone morphogenetic protein-15 (BMP15) gene. Am J Hum Genet. 2004;75(1):106–11.

    Article  PubMed Central  PubMed  Google Scholar 

  30. Persani L, Rossetti R, Cacciatore C. Genes involved in human premature ovarian failure. J Mol Endocrinol. 2010;45(5):257–79.

    Article  CAS  PubMed  Google Scholar 

  31. Crisponi L, Deiana M, Loi A, Chiappe F, Uda M, Amati P, et al. The putative forkhead transcription factor FOXL2 is mutated in blepharophimosis/ptosis/epicanthus inversus syndrome. Nat Genet. 2001;27(2):159–66.

    Article  CAS  PubMed  Google Scholar 

  32. Schmidt D, Ovitt CE, Anlag K, Fehsenfeld S, Gredsted L, Treier AC, et al. The murine winged-helix transcription factor Foxl2 is required for granulosa cell differentiation and ovary maintenance. Development. 2004;131(4):933–42.

    Article  CAS  PubMed  Google Scholar 

  33. Pal T, Keefe D, Sun P, Narod SA. Fertility in women with BRCA mutations: a case–control study. Fertil Steril. 2010;93(6):1805–8.

    Article  CAS  PubMed  Google Scholar 

  34. Oktay K, Kim JY, Barad D, Babayev SN. Association of BRCA1 mutations with occult primary ovarian insufficiency: a possible explanation for the link between infertility and breast/ovarian cancer risks. J Clin Oncol. 2010;28(2):240–4.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  35. Titus S, Li F, Stobezki R, Akula K, Unsal E, Jeong K, et al. Impairment of BRCA1-related DNA double-strand break repair leads to ovarian aging in mice and humans. Sci Transl Med. 2013;5(172):172ra21.

    Article  PubMed  CAS  Google Scholar 

  36. Qin Y, Choi Y, Zhao H, Simpson JL, Chen ZJ, Rajkovic A. NOBOX homeobox mutation causes premature ovarian failure. Am J Hum Genet. 2007;81(3):576–81.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  37. Rajkovic A, Pangas SA, Ballow D, Suzumori N, Matzuk MM. NOBOX deficiency disrupts early folliculogenesis and oocyte-specific gene expression. Science. 2004;305(5687):1157–9.

    Article  CAS  PubMed  Google Scholar 

  38. Bouilly J, Bachelot A, Broutin I, Touraine P, Binart N. Novel NOBOX loss-of-function mutations account for 6.2% of cases in a large primary ovarian insufficiency cohort. Hum Mutat. 2011;32(10):1108–13.

    Article  CAS  PubMed  Google Scholar 

  39. Bouilly J, Roucher-Boulez F, Gompel A, Bry-Gauillard H, Azibi K, Beldjord C, et al. New NOBOX Mutations Identified in a Large Cohort of Women With Primary Ovarian Insufficiency Decrease KIT-L Expression. J Clin Endocrinol Metab. 2015;100(3):994–1001.

    Article  CAS  PubMed  Google Scholar 

  40. Pangas SA, Choi Y, Ballow DJ, Zhao Y, Westphal H, Matzuk MM, et al. Oogenesis requires germ cell-specific transcriptional regulators Sohlh1 and Lhx8. Proc Natl Acad Sci U S A. 2006;103(21):8090–5.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  41. Tsuda M, Sasaoka Y, Kiso M, Abe K, Haraguchi S, Kobayashi S, et al. Conserved role of nanos proteins in germ cell development. Science. 2003;301(5637):1239–41.

    Article  CAS  PubMed  Google Scholar 

  42. Dong J, Albertini DF, Nishimori K, Kumar TR, Lu N, Matzuk MM. Growth differentiation factor-9 is required during early ovarian folliculogenesis. Nature. 1996;383(6600):531–5.

    Article  CAS  PubMed  Google Scholar 

  43. Elvin JA, Clark AT, Wang P, Wolfman NM, Matzuk MM. Paracrine actions of growth differentiation factor-9 in the mammalian ovary. Mol Endocrinol. 1999;13(6):1035–48.

    Article  CAS  PubMed  Google Scholar 

  44. Hanrahan JP, Gregan SM, Mulsant P, Mullen M, Davis GH, Powell R, et al. Mutations in the genes for oocyte-derived growth factors GDF9 and BMP15 are associated with both increased ovulation rate and sterility in Cambridge and Belclare sheep (Ovis aries). Biol Reprod. 2004;70(4):900–9.

    Article  CAS  PubMed  Google Scholar 

  45. Juengel JL, Hudson NL, Heath DA, Smith P, Reader KL, Lawrence SB, et al. Growth differentiation factor 9 and bone morphogenetic protein 15 are essential for ovarian follicular development in sheep. Biol Reprod. 2002;67(6):1777–89.

    Article  CAS  PubMed  Google Scholar 

  46. Palmer JS, Zhao ZZ, Hoekstra C, Hayward NK, Webb PM, Whiteman DC, et al. Novel variants in growth differentiation factor 9 in mothers of dizygotic twins. J Clin Endocrinol Metab. 2006;91(11):4713–6.

    Article  CAS  PubMed  Google Scholar 

  47. Laissue P, Christin-Maitre S, Touraine P, Kuttenn F, Ritvos O, Aittomaki K, et al. Mutations and sequence variants in GDF9 and BMP15 in patients with premature ovarian failure. Eur J Endocrinol. 2006;154(5):739–44.

    Article  CAS  PubMed  Google Scholar 

  48. Kaufman FR, Kogut MD, Donnell GN, Goebelsmann U, March C, Koch R. Hypergonadotropic hypogonadism in female patients with galactosemia. N Engl J Med. 1981;304(17):994–8.

    Article  CAS  PubMed  Google Scholar 

  49. Levy HL. Reproductive effects of maternal metabolic disorders: implications for pediatrics and obstetrics. Turk J Pediatr. 1996;38(3):335–44.

    CAS  PubMed  Google Scholar 

  50. Rubio-Gozalbo ME, Gubbels CS, Bakker JA, Menheere PP, Wodzig WK, Land JA. Gonadal function in male and female patients with classic galactosemia. Hum Reprod Update. 2010;16(2):177–88.

    Article  CAS  PubMed  Google Scholar 

  51. Forges T, Monnier-Barbarino P, Leheup B, Jouvet P. Pathophysiology of impaired ovarian function in galactosaemia. Hum Reprod Update. 2006;12(5):573–84.

    Article  CAS  PubMed  Google Scholar 

  52. Gubbels CS, Thomas CM, Wodzig WK, Olthaar AJ, Jaeken J, Sweep FC, et al. FSH isoform pattern in classic galactosemia. J Inherit Metab Dis. 2011;34(2):387–90.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  53. Waisbren SE, Potter NL, Gordon CM, Green RC, Greenstein P, Gubbels CS, et al. The adult galactosemic phenotype. J Inherit Metab Dis. 2012;35(2):279–86.

    Article  PubMed Central  PubMed  Google Scholar 

  54. Fridovich-Keil JL, Gubbels CS, Spencer JB, Sanders RD, Land JA, Rubio-Gozalbo E. Ovarian function in girls and women with GALT-deficiency galactosemia. J Inherit Metab Dis. 2011;34(2):357–66.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  55. Kristiansson B, Stibler H, Wide L. Gonadal function and glycoprotein hormones in the carbohydrate-deficient glycoprotein (CDG) syndrome. Acta Paediatr. 1995;84(6):655–9.

    Article  CAS  PubMed  Google Scholar 

  56. Conte FA, Grumbach MM, Ito Y, Fisher CR, Simpson ER. A syndrome of female pseudohermaphrodism, hypergonadotropic hypogonadism, and multicystic ovaries associated with missense mutations in the gene encoding aromatase (P450arom). J Clin Endocrinol Metab. 1994;78(6):1287–92.

    CAS  PubMed  Google Scholar 

  57. Ito Y, Fisher CR, Conte FA, Grumbach MM, Simpson ER. Molecular basis of aromatase deficiency in an adult female with sexual infantilism and polycystic ovaries. Proc Natl Acad Sci U S A. 1993;90(24):11673–7.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  58. Altuntas CZ, Johnson JM, Tuohy VK. Autoimmune targeted disruption of the pituitary-ovarian axis causes premature ovarian failure. J Immunol. 2006;177(3):1988–96.

    Article  CAS  PubMed  Google Scholar 

  59. Welt CK. Autoimmune oophoritis in the adolescent. Ann N Y Acad Sci. 2008;1135:118–22.

    Article  CAS  PubMed  Google Scholar 

  60. La Marca A, Brozzetti A, Sighinolfi G, Marzotti S, Volpe A, Falorni A. Primary ovarian insufficiency: autoimmune causes. Curr Opin Obstet Gynecol. 2010;22(4):277–82.

    PubMed  Google Scholar 

  61. Carp HJ, Selmi C, Shoenfeld Y. The autoimmune bases of infertility and pregnancy loss. J Autoimmun. 2012;38(2–3):J266–74.

    Article  CAS  PubMed  Google Scholar 

  62. Antiovarian antibodies: specificity, prevalence, multiple antigenicity and significance in human ovarian autoimmunity. Eusebio S Pires and Vrinda V Khole. Current Paradigm of Reproductive Immunology, 2009: 159-190 ISBN: 978-81-308-0373-9. Research Sign Post publishing house, Trivandrum, India .2009.

    Google Scholar 

  63. Hoek A, Schoemaker J, Drexhage HA. Premature ovarian failure and ovarian autoimmunity. Endocr Rev. 1997;18(1):107–34.

    CAS  PubMed  Google Scholar 

  64. Gleicher N, Weghofer A, Barad DH. A pilot study of premature ovarian senescence: II. Different genotype and phenotype for genetic and autoimmune etiologies. Fertil Steril. 2009;91(5):1707–11.

    Article  CAS  PubMed  Google Scholar 

  65. Vallotton MB, Forbes AP. Antibodies to cytoplasm of ova. Lancet. 1966;2(7457):264–5.

    Article  CAS  PubMed  Google Scholar 

  66. Luborsky JL, Visintin I, Boyers S, Asari T, Caldwell B, DeCherney A. Ovarian antibodies detected by immobilized antigen immunoassay in patients with premature ovarian failure. J Clin Endocrinol Metab. 1990;70(1):69–75.

    Article  CAS  PubMed  Google Scholar 

  67. Damewood MD, Zacur HA, Hoffman GJ, Rock JA. Circulating antiovarian antibodies in premature ovarian failure. Obstet Gynecol. 1986;68(6):850–4.

    CAS  PubMed  Google Scholar 

  68. Tong ZB, Nelson LM. A mouse gene encoding an oocyte antigen associated with autoimmune premature ovarian failure. Endocrinology. 1999;140(8):3720–6.

    Article  CAS  PubMed  Google Scholar 

  69. Pires ES, Khole VV. A block in the road to fertility: autoantibodies to heat-shock protein 90-beta in human ovarian autoimmunity. Fertil Steril. 2009;92(4):1395–409.

    Article  CAS  PubMed  Google Scholar 

  70. Mantzavinos T, Dalamanga N, Hassiakos D, Dimitriadou F, Konidaris S, Zourlas PA. Assessment of autoantibodies to the zona pellucida in serum and follicular fluid in in-vitro fertilization patients. Clin Exp Obstet Gynecol. 1993;20(2):111–5.

    CAS  PubMed  Google Scholar 

  71. Papale ML, Grillo A, Leonardi E, Giuffrida G, Palumbo M, Palumbo G. Assessment of the relevance of zona pellucida antibodies in follicular fluid of in-vitro fertilization (IVF) patients. Hum Reprod. 1994;9(10):1827–31.

    CAS  PubMed  Google Scholar 

  72. Mori T, Nishimoto T, Kitagawa M, Noda Y, Nishimura T, Oikawa T. Possible presence of autoantibodies to zone pellucida in infertile women. Experientia. 1978;34(6):797–9.

    Article  CAS  PubMed  Google Scholar 

  73. Sacco AG, Moghissi KS. Anti-zona pellucida activity in human sera. Fertil Steril. 1979;31(5):503–6.

    CAS  PubMed  Google Scholar 

  74. Shivers CA, Dunbar BS. Autoantibodies to zona pellucida: a possible cause for infertility in women. Science. 1977;197(4308):1082–4.

    Article  CAS  PubMed  Google Scholar 

  75. Kamada M, Daitoh T, Mori K, Maeda N, Hirano K, Irahara M, et al. Etiological implication of autoantibodies to zona pellucida in human female infertility. Am J Reprod Immunol. 1992;28(2):104–9.

    Article  CAS  PubMed  Google Scholar 

  76. Betterle C, Volpato M. Adrenal and ovarian autoimmunity. Eur J Endocrinol. 1998;138(1):16–25.

    Article  CAS  PubMed  Google Scholar 

  77. Haller-Kikkatalo K, Salumets A, Uibo R. Review on autoimmune reactions in female infertility: antibodies to follicle stimulating hormone. Clin Dev Immunol. 2012;2012:762541.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  78. Anderson JR, Goudie RB, Gray K, Stuart-Smith DA. Immunological features of idiopathic Addison’s disease: an antibody to cells producing steroid hormones. Clin Exp Immunol. 1968;3(2):107–17.

    PubMed Central  CAS  PubMed  Google Scholar 

  79. Dal Pra C, Chen S, Furmaniak J, Smith BR, Pedini B, Moscon A, et al. Autoantibodies to steroidogenic enzymes in patients with premature ovarian failure with and without Addison’s disease. Eur J Endocrinol. 2003;148(5):565–70.

    Article  CAS  PubMed  Google Scholar 

  80. Falorni A, Laureti S, Candeloro P, Perrino S, Coronella C, Bizzarro A, et al. Steroid-cell autoantibodies are preferentially expressed in women with premature ovarian failure who have adrenal autoimmunity. Fertil Steril. 2002;78(2):270–9.

    Article  PubMed  Google Scholar 

  81. Meyer WR, Lavy G, DeCherney AH, Visintin I, Economy K, Luborsky JL. Evidence of gonadal and gonadotropin antibodies in women with a suboptimal ovarian response to exogenous gonadotropin. Obstet Gynecol. 1990;75(5):795–9.

    CAS  PubMed  Google Scholar 

  82. Platia MP, Bloomquist G, Williams RF, Hodgen GD. Refractoriness to gonadotropin therapy: how to distinguish ovarian failure versus pseudoovarian resistance caused by neutralizing antibodies. Fertil Steril. 1984;42(5):779–84.

    CAS  PubMed  Google Scholar 

  83. Meskhi A, Seif MW. Premature ovarian failure. Curr Opin Obstet Gynecol. 2006;18(4):418–26.

    Article  PubMed  Google Scholar 

  84. Cejtin HE, Kalinowski A, Bacchetti P, Taylor RN, Watts DH, Kim S, et al. Effects of human immunodeficiency virus on protracted amenorrhea and ovarian dysfunction. Obstet Gynecol. 2006;108(6):1423–31.

    Article  PubMed  Google Scholar 

  85. Ohl J, Partisani M, Demangeat C, Binder-Foucard F, Nisand I, Lang JM. Alterations des marqueurs de la reserve ovarienne chez les femmes infectees par le virus de l'immunodeficience humaine [Alterations of ovarian reserve tests in Human Immunodeficiency Virus (HIV)-infected women]. Gynecol Obstet Fertil. 2010;38(5):313–7.

    Article  CAS  PubMed  Google Scholar 

  86. Panay N, Kalu E. Management of premature ovarian failure. Best Pract Res Clin Obstet Gynaecol. 2009;23(1):129–40.

    Article  PubMed  Google Scholar 

  87. Maclaran K, Panay N. Premature ovarian failure. J Fam Plann Reprod Health Care. 2011;37(1):35–42.

    Article  PubMed  Google Scholar 

  88. Nippita TA, Baber RJ. Premature ovarian failure: a review. Climacteric. 2007;10(1):11–22.

    Article  CAS  PubMed  Google Scholar 

  89. Boekelheide K, Darney SP, Daston GP, David RM, Luderer U, Olshan AF, et al. NTP-CERHR Expert Panel Report on the reproductive and developmental toxicity of 2-bromopropane. Reprod Toxicol. 2004;18(2):189–217.

    Article  CAS  PubMed  Google Scholar 

  90. Koh JM, Kim CH, Hong SK, Lee KU, Kim YT, Kim OJ, et al. Primary ovarian failure caused by a solvent containing 2-bromopropane. Eur J Endocrinol. 1998;138(5):554–6.

    Article  CAS  PubMed  Google Scholar 

  91. Gallicchio L, Miller S, Greene T, Zacur H, Flaws JA. Premature ovarian failure among hairdressers. Hum Reprod. 2009;24(10):2636–41.

    Article  CAS  PubMed  Google Scholar 

  92. Xia Y, Zhu P, Han Y, Lu C, Wang S, Gu A, et al. Urinary metabolites of polycyclic aromatic hydrocarbons in relation to idiopathic male infertility. Hum Reprod. 2009;24(5):1067–74.

    Article  CAS  PubMed  Google Scholar 

  93. Mikkelsen TF, Graff-Iversen S, Sundby J, Bjertness E. Early menopause, association with tobacco smoking, coffee consumption and other lifestyle factors: a cross-sectional study. BMC Public Health. 2007;7:149.

    Article  PubMed Central  PubMed  Google Scholar 

  94. Jurisicova A, Taniuchi A, Li H, Shang Y, Antenos M, Detmar J, et al. Maternal exposure to polycyclic aromatic hydrocarbons diminishes murine ovarian reserve via induction of Harakiri. J Clin Invest. 2007;117(12):3971–8.

    PubMed Central  CAS  PubMed  Google Scholar 

  95. Chang SH, Kim CS, Lee KS, Kim H, Yim SV, Lim YJ, et al. Premenopausal factors influencing premature ovarian failure and early menopause. Maturitas. 2007;58(1):19–30.

    Article  PubMed  Google Scholar 

  96. Di Prospero F, Luzi S, Iacopini Z. Cigarette smoking damages women’s reproductive life. Reprod Biomed Online. 2004;8(2):246–7.

    Article  PubMed  Google Scholar 

  97. Kinney A, Kline J, Kelly A, Reuss ML, Levin B. Smoking, alcohol and caffeine in relation to ovarian age during the reproductive years. Hum Reprod. 2007;22(4):1175–85.

    Article  CAS  PubMed  Google Scholar 

  98. Schuh-Huerta SM, Johnson NA, Rosen MP, Sternfeld B, Cedars MI, Reijo Pera RA. Genetic variants and environmental factors associated with hormonal markers of ovarian reserve in Caucasian and African American women. Hum Reprod. 2012;27(2):594–608.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  99. Nardo LG, Christodoulou D, Gould D, Roberts SA, Fitzgerald CT, Laing I. Anti-Mullerian hormone levels and antral follicle count in women enrolled in vitro fertilization cycles: relationship to lifestyle factors, chronological age and reproductive history. Gynecol Endocrinol. 2007;23(8):486–93.

    Article  CAS  PubMed  Google Scholar 

  100. Matikainen T, Perez GI, Jurisicova A, Pru JK, Schlezinger JJ, Ryu HY, et al. Aromatic hydrocarbon receptor-driven Bax gene expression is required for premature ovarian failure caused by biohazardous environmental chemicals. Nat Genet. 2001;28(4):355–60.

    Article  CAS  PubMed  Google Scholar 

  101. Kokcu A. Premature ovarian failure from current perspective. Gynecol Endocrinol. 2010;26(8):555–62.

    Article  PubMed  Google Scholar 

  102. Mayer LP, Devine PJ, Dyer CA, Hoyer PB. The follicle-deplete mouse ovary produces androgen. Biol Reprod. 2004;71(1):130–8.

    Article  CAS  PubMed  Google Scholar 

  103. Takai Y, Canning J, Perez GI, Pru JK, Schlezinger JJ, Sherr DH, et al. Bax, caspase-2, and caspase-3 are required for ovarian follicle loss caused by 4-vinylcyclohexene diepoxide exposure of female mice in vivo. Endocrinology. 2003;144(1):69–74.

    Article  CAS  PubMed  Google Scholar 

  104. Christin-Maitre S, Ronci-Chaix N, Bouchard P. Genes de l’ovaire et pathologie moleculaire [Ovary genes and molecular pathology]. J Soc Biol. 2002;196(3):207–16.

    CAS  PubMed  Google Scholar 

  105. De Miguel MP, Cheng L, Holland EC, Federspiel MJ, Donovan PJ. Dissection of the c-Kit signaling pathway in mouse primordial germ cells by retroviral-mediated gene transfer. Proc Natl Acad Sci U S A. 2002;99(16):10458–63.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  106. Hoyer PB, Devine PJ, Hu X, Thompson KE, Sipes IG. Ovarian toxicity of 4-vinylcyclohexene diepoxide: a mechanistic model. Toxicol Pathol. 2001;29(1):91–9.

    Article  CAS  PubMed  Google Scholar 

  107. Kappeler CJ, Hoyer PB. 4-vinylcyclohexene diepoxide: a model chemical for ovotoxicity. Syst Biol Reprod Med. 2012;58(1):57–62.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  108. Sharara FI, Seifer DB, Flaws JA. Environmental toxicants and female reproduction. Fertil Steril. 1998;70(4):613–22.

    Article  CAS  PubMed  Google Scholar 

  109. Beranger R, Hoffmann P, Christin-Maitre S, Bonneterre V. Occupational exposures to chemicals as a possible etiology in premature ovarian failure: a critical analysis of the literature. Reprod Toxicol. 2012;33(3):269–79.

    Article  CAS  PubMed  Google Scholar 

  110. Bolon B, Bucci TJ, Warbritton AR, Chen JJ, Mattison DR, Heindel JJ. Differential follicle counts as a screen for chemically induced ovarian toxicity in mice: results from continuous breeding bioassays. Fundam Appl Toxicol. 1997;39(1):1–10.

    Article  CAS  PubMed  Google Scholar 

  111. Kok HS, van Asselt KM, van der Schouw YT, van der Tweel I, Peeters PH, Wilson PW, et al. Heart disease risk determines menopausal age rather than the reverse. J Am Coll Cardiol. 2006;47(10):1976–83.

    Article  PubMed  Google Scholar 

  112. Verratti V, Berardinelli F, Di Giulio C, Bosco G, Cacchio M, Pellicciotta M, et al. Evidence that chronic hypoxia causes reversible impairment on male fertility. Asian J Androl. 2008;10(4):602–6.

    Article  PubMed  Google Scholar 

  113. Armenti AE, Zama AM, Passantino L, Uzumcu M. Developmental methoxychlor exposure affects multiple reproductive parameters and ovarian folliculogenesis and gene expression in adult rats. Toxicol Appl Pharmacol. 2008;233(2):286–96.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  114. Rodriguez HA, Santambrosio N, Santamaria CG, Munoz-de-Toro M, Luque EH. Neonatal exposure to bisphenol A reduces the pool of primordial follicles in the rat ovary. Reprod Toxicol. 2010;30(4):550–7.

    Article  CAS  PubMed  Google Scholar 

  115. Michalakis K, Coppack SW. Primary ovarian insufficiency: relation to changes in body composition and adiposity. Maturitas. 2012;71(4):320–5.

    Article  PubMed  Google Scholar 

  116. Amato P, Roberts AC. Transient ovarian failure: a complication of uterine artery embolization. Fertil Steril. 2001;75(2):438–9.

    Article  CAS  PubMed  Google Scholar 

  117. Farquhar CM, Sadler L, Harvey SA, Stewart AW. The association of hysterectomy and menopause: a prospective cohort study. BJOG. 2005;112(7):956–62.

    Article  PubMed  Google Scholar 

  118. Siddle N, Sarrel P, Whitehead M. The effect of hysterectomy on the age at ovarian failure: identification of a subgroup of women with premature loss of ovarian function and literature review. Fertil Steril. 1987;47(1):94–100.

    CAS  PubMed  Google Scholar 

  119. Busacca M, Riparini J, Somigliana E, Oggioni G, Izzo S, Vignali M, et al. Postsurgical ovarian failure after laparoscopic excision of bilateral endometriomas. Am J Obstet Gynecol. 2006;195(2):421–5.

    Article  PubMed  Google Scholar 

  120. Raffi F, Metwally M, Amer S. The impact of excision of ovarian endometrioma on ovarian reserve: a systematic review and meta-analysis. J Clin Endocrinol Metab. 2012;97(9):3146–54.

    Article  CAS  PubMed  Google Scholar 

  121. Api M. Is ovarian reserve diminished after laparoscopic ovarian drilling? Gynecol Endocrinol. 2009;25(3):159–65.

    Article  CAS  PubMed  Google Scholar 

  122. Rebar RW. Premature ovarian “failure” in the adolescent. Ann N Y Acad Sci. 2008;1135:138–45.

    Article  CAS  PubMed  Google Scholar 

  123. Byrne J, Fears TR, Gail MH, Pee D, Connelly RR, Austin DF, et al. Early menopause in long-term survivors of cancer during adolescence. Am J Obstet Gynecol. 1992;166(3):788–93.

    Article  CAS  PubMed  Google Scholar 

  124. Lower EE, Blau R, Gazder P, Tummala R. The risk of premature menopause induced by chemotherapy for early breast cancer. J Womens Health Gend Based Med. 1999;8(7):949–54.

    Article  CAS  PubMed  Google Scholar 

  125. Blumenfeld Z. Preservation of fertility and ovarian function and minimalization of chemotherapy associated gonadotoxicity and premature ovarian failure: the role of inhibin-A and -B as markers. Mol Cell Endocrinol. 2002;187(1–2):93–105.

    Article  CAS  PubMed  Google Scholar 

  126. Meirow D, Lewis H, Nugent D, Epstein M. Subclinical depletion of primordial follicular reserve in mice treated with cyclophosphamide: clinical importance and proposed accurate investigative tool. Hum Reprod. 1999;14(7):1903–7.

    Article  CAS  PubMed  Google Scholar 

  127. Chiarelli AM, Marrett LD, Darlington G. Early menopause and infertility in females after treatment for childhood cancer diagnosed in 1964–1988 in Ontario, Canada. Am J Epidemiol. 1999;150(3):245–54.

    Article  CAS  PubMed  Google Scholar 

  128. Letourneau JM, Ebbel EE, Katz PP, Oktay KH, McCulloch CE, Ai WZ, et al. Acute ovarian failure underestimates age-specific reproductive impairment for young women undergoing chemotherapy for cancer. Cancer. 2012;118(7):1933–9.

    Article  PubMed Central  PubMed  Google Scholar 

  129. Schover LR. Premature ovarian failure and its consequences: vasomotor symptoms, sexuality, and fertility. J Clin Oncol. 2008;26(5):753–8.

    Article  PubMed  Google Scholar 

  130. De Vos M, Devroey P, Fauser BC. Primary ovarian insufficiency. Lancet. 2010;376(9744):911–21.

    Article  PubMed  Google Scholar 

  131. Meirow D, Biederman H, Anderson RA, Wallace WH. Toxicity of chemotherapy and radiation on female reproduction. Clin Obstet Gynecol. 2010;53(4):727–39.

    Article  PubMed  Google Scholar 

  132. Meirow D. Reproduction post-chemotherapy in young cancer patients. Mol Cell Endocrinol. 2000;169(1–2):123–31.

    Article  CAS  PubMed  Google Scholar 

  133. Petrek JA, Naughton MJ, Case LD, Paskett ED, Naftalis EZ, Singletary SE, et al. Incidence, time course, and determinants of menstrual bleeding after breast cancer treatment: a prospective study. J Clin Oncol. 2006;24(7):1045–51.

    Article  PubMed  Google Scholar 

  134. Wallace WH, Kelsey TW. Human ovarian reserve from conception to the menopause. PLoS One. 2010;5(1), e8772.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  135. Desmeules P, Devine PJ. Characterizing the ovotoxicity of cyclophosphamide metabolites on cultured mouse ovaries. Toxicol Sci. 2006;90(2):500–9.

    Article  CAS  PubMed  Google Scholar 

  136. Yucebilgin MS, Terek MC, Ozsaran A, Akercan F, Zekioglu O, Isik E, et al. Effect of chemotherapy on primordial follicular reserve of rat: an animal model of premature ovarian failure and infertility. Aust N Z J Obstet Gynaecol. 2004;44(1):6–9.

    Article  PubMed  Google Scholar 

  137. Petrillo SK, Desmeules P, Truong TQ, Devine PJ. Detection of DNA damage in oocytes of small ovarian follicles following phosphoramide mustard exposures of cultured rodent ovaries in vitro. Toxicol Appl Pharmacol. 2011;253(2):94–102.

    Article  CAS  PubMed  Google Scholar 

  138. Ben-Aharon I, Bar-Joseph H, Tzarfaty G, Kuchinsky L, Rizel S, Stemmer SM, et al. Doxorubicin-induced ovarian toxicity. Reprod Biol Endocrinol. 2010;8:20.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  139. Rosendahl M, Andersen CY, la Cour FN, Juul A, Lossl K, Andersen AN. Dynamics and mechanisms of chemotherapy-induced ovarian follicular depletion in women of fertile age. Fertil Steril. 2010;94(1):156–66.

    Article  CAS  PubMed  Google Scholar 

  140. Ben-Aharon I, Meizner I, Granot T, Uri S, Hasky N, Rizel S, et al. Chemotherapy-induced ovarian failure as a prototype for acute vascular toxicity. Oncologist. 2012;17(11):1386–93.

    Article  PubMed Central  PubMed  Google Scholar 

  141. Fleischer RT, Vollenhoven BJ, Weston GC. The effects of chemotherapy and radiotherapy on fertility in premenopausal women. Obstet Gynecol Surv. 2011;66(4):248–54.

    Article  PubMed  Google Scholar 

  142. Sonmezer M, Oktay K. Fertility preservation in female patients. Hum Reprod Update. 2004;10(3):251–66.

    Article  PubMed  Google Scholar 

  143. Ash P. The influence of radiation on fertility in man. Br J Radiol. 1980;53(628):271–8.

    Article  CAS  PubMed  Google Scholar 

  144. Wallace WH, Thomson AB, Kelsey TW. The radiosensitivity of the human oocyte. Hum Reprod. 2003;18(1):117–21.

    Article  CAS  PubMed  Google Scholar 

  145. Wallace WH, Thomson AB, Saran F, Kelsey TW. Predicting age of ovarian failure after radiation to a field that includes the ovaries. Int J Radiat Oncol Biol Phys. 2005;62(3):738–44.

    Article  PubMed  Google Scholar 

  146. Bath LE, Critchley HO, Chambers SE, Anderson RA, Kelnar CJ, Wallace WH. Ovarian and uterine characteristics after total body irradiation in childhood and adolescence: response to sex steroid replacement. Br J Obstet Gynaecol. 1999;106(12):1265–72.

    Article  CAS  PubMed  Google Scholar 

  147. Wallace WH, Anderson RA, Irvine DS. Fertility preservation for young patients with cancer: who is at risk and what can be offered? Lancet Oncol. 2005;6(4):209–18.

    Article  PubMed  Google Scholar 

  148. Wallace WH, Shalet SM, Crowne EC, Morris-Jones PH, Gattamaneni HR. Ovarian failure following abdominal irradiation in childhood: natural history and prognosis. Clin Oncol (R Coll Radiol). 1989;1(2):75–9.

    Article  CAS  Google Scholar 

  149. Stillman RJ, Schinfeld JS, Schiff I, Gelber RD, Greenberger J, Larson M, et al. Ovarian failure in long-term survivors of childhood malignancy. Am J Obstet Gynecol. 1981;139(1):62–6.

    CAS  PubMed  Google Scholar 

  150. Aittomaki K, Lucena JL, Pakarinen P, Sistonen P, Tapanainen J, Gromoll J, et al. Mutation in the follicle-stimulating hormone receptor gene causes hereditary hypergonadotropic ovarian failure. Cell. 1995;82(6):959–68.

    Article  CAS  PubMed  Google Scholar 

  151. Danilovich N, Javeshghani D, Xing W, Sairam MR. Endocrine alterations and signaling changes associated with declining ovarian function and advanced biological aging in follicle-stimulating hormone receptor haploinsufficient mice. Biol Reprod. 2002;67(2):370–8.

    Article  CAS  PubMed  Google Scholar 

  152. Meduri G, Touraine P, Beau I, Lahuna O, Desroches A, Vacher-Lavenu MC, et al. Delayed puberty and primary amenorrhea associated with a novel mutation of the human follicle-stimulating hormone receptor: clinical, histological, and molecular studies. J Clin Endocrinol Metab. 2003;88(8):3491–8.

    Article  CAS  PubMed  Google Scholar 

  153. Layman LC, Lee EJ, Peak DB, Namnoum AB, Vu KV, van Lingen BL, et al. Delayed puberty and hypogonadism caused by mutations in the follicle-stimulating hormone beta-subunit gene. N Engl J Med. 1997;337(9):607–11.

    Article  CAS  PubMed  Google Scholar 

  154. Matthews CH, Borgato S, Beck-Peccoz P, Adams M, Tone Y, Gambino G, et al. Primary amenorrhoea and infertility due to a mutation in the beta-subunit of follicle-stimulating hormone. Nat Genet. 1993;5(1):83–6.

    Article  CAS  PubMed  Google Scholar 

  155. Latronico AC, Chai Y, Arnhold IJ, Liu X, Mendonca BB, Segaloff DL. A homozygous microdeletion in helix 7 of the luteinizing hormone receptor associated with familial testicular and ovarian resistance is due to both decreased cell surface expression and impaired effector activation by the cell surface receptor. Mol Endocrinol. 1998;12(3):442–50.

    Article  CAS  PubMed  Google Scholar 

  156. Lofrano-Porto A, Barra GB, Giacomini LA, Nascimento PP, Latronico AC, Casulari LA, et al. Luteinizing hormone beta mutation and hypogonadism in men and women. N Engl J Med. 2007;357(9):897–904.

    Article  CAS  PubMed  Google Scholar 

  157. Namnoum AB, Merriam GR, Moses AM, Levine MA. Reproductive dysfunction in women with Albright’s hereditary osteodystrophy. J Clin Endocrinol Metab. 1998;83(3):824–9.

    CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Washington Hospital Center, Georgetown University Hospital, 110 Irving Street, NW Suite 5B-63, Washington, DC, 20010, USA

    Nicole Doyle MD, PhD

  2. Combined NICHD/Federal Fellowship in Reproductive Endocrinology, 10 Center Drive, Room 1-3140, Bethesda, MD, 20892, USA

    Nicole Kay Banks MD

  3. Unit on Reproductive and Regenerative Medicine, NICHD, 10 Center Drive, Building 10, Room 9N119, Bethesda, MD, 20892, USA

    Erin Foran Wolff MD

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  1. Nicole Doyle MD, PhD
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  2. Nicole Kay Banks MD
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  3. Erin Foran Wolff MD
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Correspondence to Nicole Doyle MD, PhD .

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Editors and Affiliations

  1. Obstetrics and Gynecology, University of Colorado, Aurora, Colorado, USA

    Nanette F. Santoro

  2. Obstetrics and Gynecology, Washington University, St. Louis, Missouri, USA

    Amber R. Cooper

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Doyle, N., Banks, N.K., Wolff, E.F. (2016). Mechanisms of Primary Ovarian Insufficiency. In: Santoro, N., Cooper, A. (eds) Primary Ovarian Insufficiency. Springer, Cham. https://doi.org/10.1007/978-3-319-22491-6_5

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