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An update on primary ovarian insufficiency

Abstract

Primary ovarian insufficiency (POI) occurs in about 1% of female population under the age of 40, leading to reproductive problems, an earlier encounter with menopausal symptoms, and complicated diseases. There are three presumable mechanisms involved in the development of POI, namely apoptosis acceleration, follicular maturation blocking and premature follicle activation, through the following studied causes: (i) chromosomal abnormalities or gene mutations: mostly involve X chromosome, such as FMR1 premutation; more and more potentially causal genes have been screened recently; (ii) metabolic disorders such as classic galactosaemia and 17-OH deficiency; (iii) autoimmune mediated ovarian damage: observed alone or with some certain autoimmune disorders and syndromes; but the specificity and sensitivity of antibodies towards ovary are still questionable; (iv) iatrogenic: radiotherapy or chemotherapy used in cancer treatment, as well as pelvic surgery with potential threat to ovaries’ blood supply can directly damage ovarian function; (v) virus infection such as HIV and mumps; (vi) toxins and other environmental/lifestyle factors: cigarette smoking, toxins (e.g., 4-vinylcyclohexene diepoxide), and other environmental factors are associated with the development of POI. The etiology of a majority of POI cases is not identified, and is believed to be multifactorial. Strategies to POI include hormone replacement and infertility treatment. Assisted conception with donated oocytes has been proven to achieve pregnancy in POI women. Embryo cryopreservation, ovarian tissue cryopreservation and oocyte cryopreservation have been used to preserve ovarian reserve in women undergoing cancer treatments.

References

  1. Nelson L M. Clinical practice. Primary ovarian insufficiency. N Engl J Med, 2009, 360: 606–614

    PubMed  PubMed Central  Google Scholar 

  2. Cooper A R, Baker V L, Sterling E W, et al. The time is now for a new approach to primary ovarian insufficiency. Fertil Steril, 2011, 95: 1890–1897

    PubMed  PubMed Central  Google Scholar 

  3. van Noord P A, Dubas J S, Dorland M, et al. Age at natural menopause in a population-based screening cohort: the role of menarche, fecundity, and lifestyle factors. Fertil Steril, 1997, 68: 95–102

    PubMed  Google Scholar 

  4. Coulam C B, Adamson S C, Annegers J F. Incidence of premature ovarian failure. Obstet Gynecol, 1986, 67: 604–606

    PubMed  Google Scholar 

  5. Skillern A, Rajkovic A. Recent developments in identifying genetic determinants of premature ovarian failure. Sex Dev, 2008, 2: 228–243

    PubMed  Google Scholar 

  6. Bachelot A, Rouxel A, Massin N, et al. Phenotyping and genetic studies of 357 consecutive patients presenting with premature ovarian failure. Eur J Endocrinol, 2009, 161: 179–187

    PubMed  Google Scholar 

  7. Rebar R W, Erickson G F, Yen S S. Idiopathic premature ovarian failure: clinical and endocrine characteristics. Fertil Steril, 1982, 37: 35–41

    PubMed  Google Scholar 

  8. Rebar R W, Connolly H V. Clinical features of young women with hypergonadotropic amenorrhea. Fertil Steril, 1990, 53: 804–810

    PubMed  Google Scholar 

  9. Nelson L M, Anasti J N, Kimzey L M, et al. Development of luteinized graafian follicles in patients with karyotypically normal spontaneous premature ovarian failure. J Clin Endocrinol Metab, 1994, 79: 1470–1475

    PubMed  Google Scholar 

  10. Bakalov V K, Anasti J N, Calis K A, et al. Autoimmune oophoritis as a mechanism of follicular dysfunction in women with 46,XX spontaneous premature ovarian failure. Fertil Steril, 2005, 84: 958–965

    PubMed  Google Scholar 

  11. Santoro N. Update in hyper- and hypogonadotropic amenorrhea. J Clin Endocrinol Metab, 2011, 96: 3281–3288

    PubMed  Google Scholar 

  12. Wellons M. Cardiovascular disease and primary ovarian insufficiency. Semin Reprod Med, 2011, 29: 328–341

    PubMed  PubMed Central  Google Scholar 

  13. Practice Committee of American Society for Reproductive Medicine. Current evaluation of amenorrhea. Fertil Steril, 2008, 90: S219–225

    Google Scholar 

  14. Younis J S. Ovarian aging and implications for fertility female health. Minerva Endocrinol, 2012, 37: 41–57

    PubMed  Google Scholar 

  15. Goswami D, Conway G S. Premature ovarian failure. Hum Reprod Update, 2005, 11: 391–410

    PubMed  Google Scholar 

  16. Morita Y, Tilly J L. Oocyte apoptosis: like sand through an hourglass. Dev Biol, 1999, 213: 1–17

    PubMed  Google Scholar 

  17. Sullivan S D, Castrillon D H. Insights into primary ovarian insufficiency through genetically engineered mouse models. Semin Reprod Med, 2011, 29: 283–298

    PubMed  Google Scholar 

  18. Adhikari D, Zheng W, Shen Y, et al. Tsc/mTORC1 signaling in oocytes governs the quiescence and activation of primordial follicles. Hum Mol Genet, 2010, 19: 397–410

    PubMed  PubMed Central  Google Scholar 

  19. Johnson J, Canning J, Kaneko T, et al. Germline stem cells and follicular renewal in the postnatal mammalian ovary. Nature, 2004, 428: 145–150

    PubMed  Google Scholar 

  20. van Kasteren Y M, Hundscheid R D, Smits A P, et al. Familial idiopathic premature ovarian failure: an overrated and underestimated genetic disease? Hum Reprod, 1999, 14: 2455–2459

    PubMed  Google Scholar 

  21. Davis C J, Davison R M, Payne N N, et al. Female sex preponderance for idiopathic familial premature ovarian failure suggests an X chromosome defect: opinion. Hum Reprod, 2000, 15: 2418–2422

    PubMed  Google Scholar 

  22. Hunter J E, Epstein M P, Tinker SW, et al. Fragile X-associated primary ovarian insufficiency: evidence for additional genetic contributions to severity. Genet Epidemiol, 2008, 32: 553–559

    PubMed  PubMed Central  Google Scholar 

  23. Wittenberger M D, Hagerman R J, Sherman S L, et al. The FMR1 premutation and reproduction. Fertil Steril, 2007, 87: 456–465

    PubMed  Google Scholar 

  24. Murabito J M, Yang Q, Fox C, et al. Heritability of age at natural menopause in the Framingham Heart Study. J Clin Endocrinol Metab, 2005, 90: 3427–3430

    PubMed  Google Scholar 

  25. Simpson J L. Genetic and phenotypic heterogeneity in ovarian failure: overview of selected candidate genes. Ann N Y Acad Sci, 2008, 1135: 146–154

    PubMed  Google Scholar 

  26. Dixit H, Rao L, Padmalatha V, et al. Genes governing premature ovarian failure. Reprod Biomed Online, 2010, 20: 724–740

    PubMed  Google Scholar 

  27. Zinn A R. The X chromosome and the ovary. J Soc Gynecol Investig, 2001, 8: S34–36

    PubMed  Google Scholar 

  28. Hens L, Devroey P, Van Waesberghe L, et al. Chromosome studies and fertility treatment in women with ovarian failure. Clin Genet, 1989, 36: 81–91

    PubMed  Google Scholar 

  29. Kawano Y, Narahara H, Matsui N, et al. Premature ovarian failure associated with a Robertsonian translocation. Acta Obstet Gynecol Scand, 1998, 77: 467–469

    PubMed  Google Scholar 

  30. Burton K A, Van Ee C C, Purcell K, et al. Autosomal translocation associated with premature ovarian failure. J Med Genet, 2000, 37: E2

    PubMed  PubMed Central  Google Scholar 

  31. Gleicher N, Weghofer A, Kim A, et al. The impact in older women of ovarian FMR1 genotypes and sub-genotypes on ovarian reserve. PLoS ONE, 2012, 7: e33638

    PubMed  PubMed Central  Google Scholar 

  32. Allen E G, Sullivan A K, Marcus M, et al. Examination of reproductive aging milestones among women who carry the FMR1 premutation. Hum Reprod, 2007, 22: 2142–2152

    PubMed  Google Scholar 

  33. Murray A, Ennis S, Morton N. No evidence for parent of origin influencing premature ovarian failure in fragile X premutation carriers. Am J Hum Genet, 2000, 67: 253–254; author reply 256–258

    PubMed  PubMed Central  Google Scholar 

  34. Sullivan A K, Marcus M, Epstein M P, et al. Association of FMR1 repeat size with ovarian dysfunction. Hum Reprod, 2005, 20: 402–412

    PubMed  Google Scholar 

  35. Sullivan S D, Welt C, Sherman S. FMR1 and the continuum of primary ovarian insufficiency. Semin Reprod Med, 2011, 29: 299–307

    PubMed  Google Scholar 

  36. Allen E G, He W, Yadav-Shah M, et al. A study of the distributional characteristics of FMR1 transcript levels in 238 individuals. Hum Genet, 2004, 114: 439–447

    PubMed  Google Scholar 

  37. Bretherick K L, Fluker M R, Robinson W P. FMR1 repeat sizes in the gray zone and high end of the normal range are associated with premature ovarian failure. Hum Genet, 2005, 117: 376–382

    PubMed  Google Scholar 

  38. Bretherick K L, Hanna C W, Currie L M, et al. Estrogen receptor alpha gene polymorphisms are associated with idiopathic premature ovarian failure. Fertil Steril, 2008, 89: 318–324

    PubMed  Google Scholar 

  39. Vujovic S. Aetiology of premature ovarian failure. Menopause Int, 2009, 15: 72–75

    PubMed  Google Scholar 

  40. Otsuka F, McTavish K J, Shimasaki S. Integral role of GDF-9 and BMP-15 in ovarian function. Mol Reprod Dev, 2011, 78: 9–21

    PubMed  PubMed Central  Google Scholar 

  41. McNatty K P, Juengel J L, Reader K L, et al. Bone morphogenetic protein 15 and growth differentiation factor 9 co-operate to regulate granulosa cell function in ruminants. Reproduction, 2005, 129: 481–487

    PubMed  Google Scholar 

  42. Dube J L, Wang P, Elvin J, et al. The bone morphogenetic protein 15 gene is X-linked and expressed in oocytes. Mol Endocrinol, 1998, 12: 1809–1817

    PubMed  Google Scholar 

  43. Aaltonen J, Laitinen M P, Vuojolainen K, et al. Human growth differentiation factor 9 (GDF-9) and its novel homolog GDF-9B are expressed in oocytes during early folliculogenesis. J Clin Endocrinol Metab, 1999, 84: 2744–2750

    PubMed  Google Scholar 

  44. 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: 106–111

    PubMed  PubMed Central  Google Scholar 

  45. Di Pasquale E, Rossetti R, Marozzi A, et al. Identification of new variants of human BMP15 gene in a large cohort of women with premature ovarian failure. J Clin Endocrinol Metab, 2006, 91: 1976–1979

    PubMed  Google Scholar 

  46. Dixit H, Rao L K, Padmalatha V V, et al. Missense mutations in the BMP15 gene are associated with ovarian failure. Hum Genet, 2006, 119: 408–415

    PubMed  Google Scholar 

  47. Laissue P, Christin-Maitre S, Touraine P, et al. Mutations and sequence variants in GDF9 and BMP15 in patients with premature ovarian failure. Eur J Endocrinol, 2006, 154: 739–744

    PubMed  Google Scholar 

  48. Zhao Z Z, Painter J N, Palmer J S, et al. Variation in bone morphogenetic protein 15 is not associated with spontaneous human dizygotic twinning. Hum Reprod, 2008, 23: 2372–2379

    PubMed  PubMed Central  Google Scholar 

  49. Inagaki K, Shimasaki S. Impaired production of BMP-15 and GDF-9 mature proteins derived from proproteins WITH mutations in the proregion. Mol Cell Endocrinol, 2010, 328: 1–7

    PubMed  PubMed Central  Google Scholar 

  50. Spicer L J, Aad P Y, Allen D T, et al. Growth differentiation factor 9 (GDF9) stimulates proliferation and inhibits steroidogenesis by bovine theca cells: influence of follicle size on responses to GDF9. Biol Reprod, 2008, 78: 243–253

    PubMed  Google Scholar 

  51. Orisaka M, Tajima K, Tsang B K, et al. Oocyte-granulosa-theca cell interactions during preantral follicular development. J Ovarian Res, 2009, 2: 9

    PubMed  PubMed Central  Google Scholar 

  52. Dong J, Albertini D F, Nishimori K, et al. Growth differentiation factor-9 is required during early ovarian folliculogenesis. Nature, 1996, 383: 531–535

    PubMed  Google Scholar 

  53. Huang Q, Cheung A P, Zhang Y, et al. Effects of growth differentiation factor 9 on cell cycle regulators and ERK42/44 in human granulosa cell proliferation. Am J Physiol Endocrinol Metab, 2009, 296: E1344–1353

    PubMed  Google Scholar 

  54. Galloway S M, McNatty K P, Cambridge L M, et al. Mutations in an oocyte-derived growth factor gene (BMP15) cause increased ovulation rate and infertility in a dosage-sensitive manner. Nat Genet, 2000, 25: 279–283

    PubMed  Google Scholar 

  55. Hanrahan J P, Gregan S M, Mulsant P, 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: 900–909

    PubMed  Google Scholar 

  56. Nicol L, Bishop S C, Pong-Wong R, et al. Homozygosity for a single base-pair mutation in the oocyte-specific GDF9 gene results in sterility in Thoka sheep. Reproduction, 2009, 138: 921–933

    PubMed  Google Scholar 

  57. Montgomery G W, Zhao Z Z, Marsh A J, et al. A deletion mutation in GDF9 in sisters with spontaneous DZ twins. Twin Res, 2004, 7: 548–555

    PubMed  Google Scholar 

  58. Palmer J S, Zhao Z Z, Hoekstra C, et al. Novel variants in growth differentiation factor 9 in mothers of dizygotic twins. J Clin Endocrinol Metab, 2006, 91: 4713–4716

    PubMed  Google Scholar 

  59. Pisarska M D, Kuo F T, Bentsi-Barnes I K, et al. LATS1 phosphorylates forkhead L2 and regulates its transcriptional activity. Am J Physiol Endocrinol Metab, 2010, 299: E101–109

    PubMed  PubMed Central  Google Scholar 

  60. Matthews C H, Borgato S, Beck-Peccoz P, et al. Primary amenorrhoea and infertility due to a mutation in the beta-subunit of follicle-stimulating hormone. Nat Genet, 1993, 5: 83–86

    PubMed  Google Scholar 

  61. Aittomaki K, Lucena J L, Pakarinen P, et al. Mutation in the follicle-stimulating hormone receptor gene causes hereditary hypergonadotropic ovarian failure. Cell, 1995, 82: 959–968

    PubMed  Google Scholar 

  62. Liu J Y, Gromoll J, Cedars M I, et al. Identification of allelic variants in the follicle-stimulating hormone receptor genes of females with or without hypergonadotropic amenorrhea. Fertil Steril, 1998, 70: 326–331

    PubMed  Google Scholar 

  63. Takahashi K, Ozaki T, Okada M, et al. Increased prevalence of luteinizing hormone beta-subunit variant in patients with premature ovarian failure. Fertil Steril, 1999, 71: 96–101

    PubMed  Google Scholar 

  64. Lofrano-Porto A, Barra G B, Giacomini L A, et al. Luteinizing hormone beta mutation and hypogonadism in men and women. N Engl J Med, 2007, 357: 897–904

    PubMed  Google Scholar 

  65. Latronico A C, Chai Y, Arnhold I J, et al. 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: 442–450

    PubMed  Google Scholar 

  66. Chand A L, Harrison C A, Shelling A N. Inhibin and premature ovarian failure. Hum Reprod Update, 2010, 16: 39–50

    PubMed  Google Scholar 

  67. Prakash G J, Ravi Kanth V V, Shelling A N, et al. Mutational analysis of inhibin alpha gene revealed three novel variations in Indian women with premature ovarian failure. Fertil Steril, 2010, 94: 90–98

    PubMed  Google Scholar 

  68. MacNaughton J, Banah M, McCloud P, et al. Age related changes in follicle stimulating hormone, luteinizing hormone, oestradiol and immunoreactive inhibin in women of reproductive age. Clin Endocrinol (Oxf), 1992, 36: 339–345

    Google Scholar 

  69. Petraglia F, Hartmann B, Luisi S, et al. Low levels of serum inhibin A and inhibin B in women with hypergonadotropic amenorrhea and evidence of high levels of activin A in women with hypothalamic amenorrhea. Fertil Steril, 1998, 70: 907–912

    PubMed  Google Scholar 

  70. Soules M R, Battaglia D E, Klein N A. Inhibin and reproductive aging in women. Maturitas, 1998, 30: 193–204

    PubMed  Google Scholar 

  71. Waggoner D D, Buist N R, Donnell G N. Long-term prognosis in galactosaemia: results of a survey of 350 cases. J Inherit Metab Dis, 1990, 13: 802–818

    PubMed  Google Scholar 

  72. Schuh-Huerta S M, Johnson N A, Rosen M P, et al. Genetic variants and environmental factors associated with hormonal markers of ovarian reserve in Caucasian and African American women. Hum Reprod, 2012, 27: 594–608

    PubMed  PubMed Central  Google Scholar 

  73. Christin-Maitre S, Pasquier M, Donadille B, et al. Premature ovarian failure. Ann Endocrinol (Paris), 2006, 67: 557–566

    Google Scholar 

  74. Cordts E B, Christofolini D M, Dos Santos A A, et al. Genetic aspects of premature ovarian failure: a literature review. Arch Gynecol Obstet, 2011, 283: 635–643

    PubMed  Google Scholar 

  75. Forges T, Monnier-Barbarino P, Leheup B, et al. Pathophysiology of impaired ovarian function in galactosaemia. Hum Reprod Update, 2006, 12: 573–584

    PubMed  Google Scholar 

  76. Kaufman F R, Kogut M D, Donnell G N, et al. Hypergonadotropic hypogonadism in female patients with galactosemia. N Engl J Med, 1981, 304: 994–998

    PubMed  Google Scholar 

  77. Rubio-Gozalbo M E, Gubbels C S, Bakker J A, et al. Gonadal function in male and female patients with classic galactosemia. Hum Reprod Update, 2010, 16: 177–188

    PubMed  Google Scholar 

  78. Levy H L. Reproductive effects of maternal metabolic disorders: implications for pediatrics and obstetrics. Turk J Pediatr, 1996, 38: 335–344

    PubMed  Google Scholar 

  79. Gubbels C S, Kuppens S M, Bakker J A, et al. Pregnancy in classic galactosemia despite undetectable anti-Mullerian hormone. Fertil Steril, 2009, 91: 1293–1296

    PubMed  Google Scholar 

  80. Sanders R D, Spencer J B, Epstein M P, et al. Biomarkers of ovarian function in girls and women with classic galactosemia. Fertil Steril, 2009, 92: 344–351

    PubMed  PubMed Central  Google Scholar 

  81. Gubbels C S, Thomas C M, Wodzig W K, et al. FSH isoform pattern in classic galactosemia. J Inherit Metab Dis, 2011, 34: 387–390

    PubMed  PubMed Central  Google Scholar 

  82. Hoek A, Schoemaker J, Drexhage H A. Premature ovarian failure and ovarian autoimmunity. Endocr Rev, 1997, 18: 107–134

    PubMed  Google Scholar 

  83. Smith J A, Vitale S, Reed G F, et al. Dry eye signs and symptoms in women with premature ovarian failure. Arch Ophthalmol, 2004, 122: 151–156

    PubMed  Google Scholar 

  84. Husebye E S, Lovas K. Immunology of Addison’s disease and premature ovarian failure. Endocrinol Metab Clin North Am, 2009, 38: 389–405

    PubMed  Google Scholar 

  85. Cheng M H, Nelson L M. Mechanisms and models of immune tolerance breakdown in the ovary. Semin Reprod Med, 2011, 29: 308–316

    PubMed  Google Scholar 

  86. La Marca A, Brozzetti A, Sighinolfi G, et al. Primary ovarian insufficiency: autoimmune causes. Curr Opin Obstet Gynecol, 2010, 22: 277–282

    PubMed  Google Scholar 

  87. Luborsky J. Ovarian autoimmune disease and ovarian autoantibodies. J Womens Health Gend Based Med, 2002, 11: 585–599

    PubMed  Google Scholar 

  88. Dragojevic-Dikic S, Marisavljevic D, Mitrovic A, et al. An immunological insight into premature ovarian failure (POF). Autoimmun Rev, 2010, 9: 771–774

    PubMed  Google Scholar 

  89. Donnez J, Dolmans M M, Pirard C, et al. Allograft of ovarian cortex between two genetically non-identical sisters: case report. Hum Reprod, 2007, 22: 2653–2659

    PubMed  Google Scholar 

  90. Howard-Anderson J, Ganz P A, Bower J E, et al. Quality of life, fertility concerns, and behavioral health outcomes in younger breast cancer survivors: a systematic review. J Natl Cancer Inst, 2012, 104: 386–405

    PubMed  Google Scholar 

  91. Fleischer R T, Vollenhoven B J, Weston G C. The effects of chemotherapy and radiotherapy on fertility in premenopausal women. Obstet Gynecol Surv, 2011, 66: 248–254

    PubMed  Google Scholar 

  92. Clowse M E, Behera M A, Anders C K, et al. Ovarian preservation by GnRH agonists during chemotherapy: a meta-analysis. J Womens Health (Larchmt), 2009, 18: 311–319

    Google Scholar 

  93. Meirow D, Biederman H, Anderson R A, et al. Toxicity of chemotherapy and radiation on female reproduction. Clin Obstet Gynecol, 2010, 53: 727–739

    PubMed  Google Scholar 

  94. Nicosia S V, Matus-Ridley M, Meadows A T. Gonadal effects of cancer therapy in girls. Cancer, 1985, 55: 2364–2372

    PubMed  Google Scholar 

  95. Meirow D, Dor J, Kaufman B, et al. Cortical fibrosis and blood-vessels damage in human ovaries exposed to chemotherapy. Potential mechanisms of ovarian injury. Hum Reprod, 2007, 22: 1626–1633

    PubMed  Google Scholar 

  96. Read M D, Edey K A, Hapeshi J, et al. The age of ovarian failure following premenopausal hysterectomy with ovarian conservation. Menopause Int, 2010, 16: 56–59

    PubMed  Google Scholar 

  97. Amato P, Roberts A C. Transient ovarian failure: a complication of uterine artery embolization. Fertil Steril, 2001, 75: 438–439

    PubMed  Google Scholar 

  98. Api M. Is ovarian reserve diminished after laparoscopic ovarian drilling? Gynecol Endocrinol, 2009, 25: 159–165

    PubMed  Google Scholar 

  99. Prinz W, Taubert H D. Mumps in pubescent females and its effect on later reproductive function. Gynaecologia, 1969, 167: 23–27

    PubMed  Google Scholar 

  100. Morrison J C, Givens J R, Wiser W L, et al. Mumps oophoritis: a cause of premature menopause. Fertil Steril, 1975, 26: 655–659

    PubMed  Google Scholar 

  101. Cejtin H E, Kalinowski A, Bacchetti P, et al. Effects of human immunodeficiency virus on protracted amenorrhea and ovarian dysfunction. Obstet Gynecol, 2006, 108: 1423–1431

    PubMed  Google Scholar 

  102. Ohl J, Partisani M, Demangeat C, et al. Alterations of ovarian reserve tests in Human Immunodeficiency Virus (HIV)-infected women. Gynecol Obstet Fertil, 2010, 38: 313–317

    PubMed  Google Scholar 

  103. Hoyer P B, Devine P J, Hu X, et al. Ovarian toxicity of 4-vinylcyclohexene diepoxide: a mechanistic model. Toxicol Pathol, 2001, 29: 91–99

    PubMed  Google Scholar 

  104. Christin-Maitre S, Ronci-Chaix N, Bouchard P. Ovary genes and molecular pathology. J Soc Biol, 2002, 196: 207–216

    PubMed  Google Scholar 

  105. De Miguel M P, Cheng L, Holland E C, et al. Dissection of the c-Kit signaling pathway in mouse primordial germ cells by retroviral-mediated gene transfer. Proc Natl Acad Sci USA, 2002, 99: 10458–10463

    PubMed  PubMed Central  Google Scholar 

  106. Kappeler C J, Hoyer P B. 4-vinylcyclohexene diepoxide: a model chemical for ovotoxicity. Syst Biol Reprod Med, 2012, 58: 57–62

    PubMed  PubMed Central  Google Scholar 

  107. Di Prospero F, Luzi S, Iacopini Z. Cigarette smoking damages women’s reproductive life. Reprod Biomed Online, 2004, 8: 246–247

    PubMed  Google Scholar 

  108. Chang S H, Kim C S, Lee K S, et al. Premenopausal factors influencing premature ovarian failure and early menopause. Maturitas, 2007, 58: 19–30

    PubMed  Google Scholar 

  109. Kinney A, Kline J, Kelly A, et al. Smoking, alcohol and caffeine in relation to ovarian age during the reproductive years. Hum Reprod, 2007, 22: 1175–1185

    PubMed  Google Scholar 

  110. Nardo L G, Christodoulou D, Gould D, et al. Anti-Mullerian hormone levels and antral follicle count in women enrolled in in vitro fertilization cycles: relationship to lifestyle factors, chronological age and reproductive history. Gynecol Endocrinol, 2007, 23: 486–493

    PubMed  Google Scholar 

  111. Matikainen T, Perez G I, Jurisicova A, et al. Aromatic hydrocarbon receptor-driven Bax gene expression is required for premature ovarian failure caused by biohazardous environmental chemicals. Nat Genet, 2001, 28: 355–360

    PubMed  Google Scholar 

  112. Sharara F I, Seifer D B, Flaws J A. Environmental toxicants and female reproduction. Fertil Steril, 1998, 70: 613–622

    PubMed  Google Scholar 

  113. Klein P, Serje A, Pezzullo J C. Premature ovarian failure in women with epilepsy. Epilepsia, 2001, 42: 1584–1589

    PubMed  Google Scholar 

  114. Testa G, Chiaffarino F, Vegetti W, et al. Case-control study on risk factors for premature ovarian failure. Gynecol Obstet Invest, 2001, 51: 40–43

    PubMed  Google Scholar 

  115. Proetto Menopausa Italia Study Group, et al. Premature ovarian failure: frequency and risk factors among women attending a network of menopause clinics in Italy. BJOG, 2003, 110: 59–63

    Google Scholar 

  116. Henzl M R, Loomba P K. Transdermal delivery of sex steroids for hormone replacement therapy and contraception. A review of principles and practice. J Reprod Med, 2003, 48: 525–540

    PubMed  Google Scholar 

  117. Jones S C. Subcutaneous estrogen replacement therapy. J Reprod Med, 2004, 49: 139–142

    PubMed  Google Scholar 

  118. Nelson H D. Commonly used types of postmenopausal estrogen for treatment of hot flashes: scientific review. JAMA, 2004, 291: 1610–1620

    PubMed  Google Scholar 

  119. Popat V B, Vanderhoof V H, Calis K A, et al. Normalization of serum luteinizing hormone levels in women with 46,XX spontaneous primary ovarian insufficiency. Fertil Steril, 2008, 89: 429–433

    PubMed  PubMed Central  Google Scholar 

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Jin, M., Yu, Y. & Huang, H. An update on primary ovarian insufficiency. Sci. China Life Sci. 55, 677–686 (2012). https://doi.org/10.1007/s11427-012-4355-2

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Keywords

  • primary ovarian insufficiency
  • genetic aberrations
  • environmental factors
  • hormone replacement therapy
  • ovary preservation