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Natural History of Diminished Ovarian Reserve

  • Orhan BukulmezEmail author
Chapter

Abstract

There are two proposed models for oocyte endowment in females. Both fixed cell and stem cell models acknowledge the depletion of oocyte pool with female aging. The ovarian cortical tissue-based models suggest that there is a very high number of primordial follicle loss in early life from birth to puberty. After the age of 20 years, the average number of follicles lost decreases with the lowest level observed as women approach menopause. It is believed that there is no specific female age after which the oocyte loss accelerates further. Actually, clinical evidence suggests that the decline in ovarian reserve after the peak loss point of around the age of 20 years is followed by gradual loss over the years. As the ovarian reserve decreases further, the number of primordial follicles lost may also decrease. Individual variation in menopausal age may also provide some clues that diminished ovarian reserve (DOR) may be due to a shift of the primordial or nongrowing follicle depletion curve to earlier age, which can be due to many genetic and environmental factors yet to be determined. The decrease in oocyte quality in parallel to ovarian reserve decline with female aging may be skewed in younger females with DOR. Therefore, age may still dictate the quality of oocytes regardless of the ovarian reserve. It is still not clear if fertility patterns are associated with the longevity or if DOR is a direct reflection of general aging.

Keywords

Diminished ovarian reserve Ovarian aging Models for ovarian aging 

References

  1. 1.
    Baker TG. A quantitative and cytological study of germ cells in human ovaries. Proc R Soc Lond B Biol Sci. 1963;158:417–33.PubMedCrossRefGoogle Scholar
  2. 2.
    McGee EA, Hsueh AJ. Initial and cyclic recruitment of ovarian follicles. Endocr Rev. 2000;21(2):200–14.PubMedGoogle Scholar
  3. 3.
    Fortune JE, Cushman RA, Wahl CM, Kito S. The primordial to primary follicle transition. Mol Cell Endocrinol. 2000;163(1–2):53–60.PubMedCrossRefGoogle Scholar
  4. 4.
    Hansen KR, Knowlton NS, Thyer AC, Charleston JS, Soules MR, Klein NA. A new model of reproductive aging: the decline in ovarian non-growing follicle number from birth to menopause. Hum Reprod. 2008;23(3):699–708.PubMedCrossRefGoogle Scholar
  5. 5.
    Johnson J, Canning J, Kaneko T, Pru JK, Tilly JL. Germline stem cells and follicular renewal in the postnatal mammalian ovary. Nature. 2004;428(6979):145–50.PubMedCrossRefGoogle Scholar
  6. 6.
    Bristol-Gould SK, Kreeger PK, Selkirk CG, Kilen SM, Mayo KE, Shea LD, et al. Fate of the initial follicle pool: empirical and mathematical evidence supporting its sufficiency for adult fertility. Dev Biol. 2006;298(1):149–54.PubMedCrossRefGoogle Scholar
  7. 7.
    Johnson J, Bagley J, Skaznik-Wikiel M, Lee HJ, Adams GB, Niikura Y, et al. Oocyte generation in adult mammalian ovaries by putative germ cells in bone marrow and peripheral blood. Cell. 2005;122(2):303–15.PubMedCrossRefGoogle Scholar
  8. 8.
    Lee HJ, Selesniemi K, Niikura Y, Niikura T, Klein R, Dombkowski DM, et al. Bone marrow transplantation generates immature oocytes and rescues long-term fertility in a preclinical mouse model of chemotherapy-induced premature ovarian failure. J Clin Oncol. 2007;25(22):3198–204.PubMedCrossRefGoogle Scholar
  9. 9.
    Zou K, Yuan Z, Yang Z, Luo H, Sun K, Zhou L, et al. Production of offspring from a germline stem cell line derived from neonatal ovaries. Nat Cell Biol. 2009;11(5):631–6.PubMedCrossRefGoogle Scholar
  10. 10.
    Gougeon A. Regulation of ovarian follicular development in primates: facts and hypotheses. Endocr Rev. 1996;17(2):121–55.PubMedCrossRefGoogle Scholar
  11. 11.
    Wang N, Satirapod C, Ohguchi Y, Park ES, Woods DC, Tilly JL. Genetic studies in mice directly link oocytes produced during adulthood to ovarian function and natural fertility. Sci Rep. 2017;7(1):10011.PubMedPubMedCentralCrossRefGoogle Scholar
  12. 12.
    Practice Committee of the American Society for Reproductive Medicine in collaboration with the Society for Reproductive Endocrinology, Infertility. Electronic address ASRM@asrm.org. Practice Committee of the American Society for Reproductive Medicine in collaboration with the Society for Reproductive Endocrinology, Infertility. Optimizing natural fertility: a committee opinion. Fertil Steril. 2017;107(1):52–8.Google Scholar
  13. 13.
    van Zonneveld P, Scheffer GJ, Broekmans FJ, Blankenstein MA, de Jong FH, Looman CW, et al. Do cycle disturbances explain the age-related decline of female fertility? Cycle characteristics of women aged over 40 years compared with a reference population of young women. Hum Reprod. 2003;18(3):495–501.PubMedCrossRefGoogle Scholar
  14. 14.
    Burger HG, Hale GE, Dennerstein L, Robertson DM. Cycle and hormone changes during perimenopause: the key role of ovarian function. Menopause. 2008;15(4 Pt 1):603–12.PubMedCrossRefGoogle Scholar
  15. 15.
    Broekmans FJ, Soules MR, Fauser BC. Ovarian aging: mechanisms and clinical consequences. Endocr Rev. 2009;30(5):465–93.PubMedCrossRefGoogle Scholar
  16. 16.
    Scheffer GJ, Broekmans FJ, Dorland M, Habbema JD, Looman CW, te Velde ER. Antral follicle counts by transvaginal ultrasonography are related to age in women with proven natural fertility. Fertil Steril. 1999;72(5):845–51.PubMedCrossRefGoogle Scholar
  17. 17.
    Hansen KR, Hodnett GM, Knowlton N, Craig LB. Correlation of ovarian reserve tests with histologically determined primordial follicle number. Fertil Steril. 2011;95(1):170–5.PubMedCrossRefGoogle Scholar
  18. 18.
    Lambalk CB, van Disseldorp J, de Koning CH, Broekmans FJ. Testing ovarian reserve to predict age at menopause. Maturitas. 2009;63(4):280–91.PubMedCrossRefGoogle Scholar
  19. 19.
    Charleston JS, Hansen KR, Thyer AC, Charleston LB, Gougeon A, Siebert JR, et al. Estimating human ovarian non-growing follicle number: the application of modern stereology techniques to an old problem. Hum Reprod. 2007;22(8):2103–10.PubMedCrossRefGoogle Scholar
  20. 20.
    Depmann M, Faddy MJ, van der Schouw YT, Peeters PH, Broer SL, Kelsey TW, et al. The relationship between variation in size of the primordial follicle pool and age at natural menopause. J Clin Endocrinol Metab. 2015;100(6):E845–51.PubMedCrossRefGoogle Scholar
  21. 21.
    Wallace WH, Kelsey TW. Human ovarian reserve from conception to the menopause. PLoS One. 2010;5(1):e8772.PubMedPubMedCentralCrossRefGoogle Scholar
  22. 22.
    Block E. A quantitative morphological investigation of the follicular system in newborn female infants. Acta Anat (Basel). 1953;17(3):201–6.CrossRefGoogle Scholar
  23. 23.
    Gougeon A, Chainy GB. Morphometric studies of small follicles in ovaries of women at different ages. J Reprod Fertil. 1987;81(2):433–42.PubMedCrossRefGoogle Scholar
  24. 24.
    Richardson SJ, Senikas V, Nelson JF. Follicular depletion during the menopausal transition: evidence for accelerated loss and ultimate exhaustion. J Clin Endocrinol Metab. 1987;65(6):1231–7.PubMedCrossRefGoogle Scholar
  25. 25.
    Forabosco A, Sforza C. Establishment of ovarian reserve: a quantitative morphometric study of the developing human ovary. Fertil Steril. 2007;88(3):675–83.PubMedCrossRefGoogle Scholar
  26. 26.
    Broer SL, Eijkemans MJ, Scheffer GJ, van Rooij IA, de Vet A, Themmen AP, et al. Anti-mullerian hormone predicts menopause: a long-term follow-up study in normoovulatory women. J Clin Endocrinol Metab. 2011;96(8):2532–9.PubMedCrossRefGoogle Scholar
  27. 27.
    Freeman EW, Sammel MD, Lin H, Boorman DW, Gracia CR. Contribution of the rate of change of antimullerian hormone in estimating time to menopause for late reproductive-age women. Fertil Steril. 2012;98(5):1254–9.e1–2.Google Scholar
  28. 28.
    Freeman EW, Sammel MD, Lin H, Gracia CR. Anti-mullerian hormone as a predictor of time to menopause in late reproductive age women. J Clin Endocrinol Metab. 2012;97(5):1673–80.PubMedPubMedCentralCrossRefGoogle Scholar
  29. 29.
    Sowers MR, Eyvazzadeh AD, McConnell D, Yosef M, Jannausch ML, Zhang D, et al. Anti-mullerian hormone and inhibin B in the definition of ovarian aging and the menopause transition. J Clin Endocrinol Metab. 2008;93(9):3478–83.PubMedPubMedCentralCrossRefGoogle Scholar
  30. 30.
    Nelson SM, Messow MC, McConnachie A, Wallace H, Kelsey T, Fleming R, et al. External validation of nomogram for the decline in serum anti-Mullerian hormone in women: a population study of 15,834 infertility patients. Reprod Biomed Online. 2011;23(2):204–6.PubMedCrossRefGoogle Scholar
  31. 31.
    Nelson SM, Messow MC, Wallace AM, Fleming R, McConnachie A. Nomogram for the decline in serum antimullerian hormone: a population study of 9,601 infertility patients. Fertil Steril. 2011;95(2):736–41.e1–3.Google Scholar
  32. 32.
    Dolleman M, Faddy MJ, van Disseldorp J, van der Schouw YT, Messow CM, Leader B, et al. The relationship between anti-Mullerian hormone in women receiving fertility assessments and age at menopause in subfertile women: evidence from large population studies. J Clin Endocrinol Metab. 2013;98(5):1946–53.PubMedCrossRefGoogle Scholar
  33. 33.
    Overbeek A, Broekmans FJ, Hehenkamp WJ, Wijdeveld ME, van Disseldorp J, van Dulmen-den Broeder E, et al. Intra-cycle fluctuations of anti-Mullerian hormone in normal women with a regular cycle: a re-analysis. Reprod Biomed Online. 2012;24(6):664–9.Google Scholar
  34. 34.
    La Marca A, Spada E, Grisendi V, Argento C, Papaleo E, Milani S, et al. Normal serum anti-Mullerian hormone levels in the general female population and the relationship with reproductive history. Eur J Obstet Gynecol Reprod Biol. 2012;163(2):180–4.PubMedCrossRefGoogle Scholar
  35. 35.
    Kumar A, Kalra B, Patel A, McDavid L, Roudebush WE. Development of a second generation anti-Mullerian hormone (AMH) ELISA. J Immunol Methods. 2010;362(1–2):51–9.PubMedCrossRefGoogle Scholar
  36. 36.
    Faddy MJ, Gosden RG, Gougeon A, Richardson SJ, Nelson JF. Accelerated disappearance of ovarian follicles in mid-life: implications for forecasting menopause. Hum Reprod. 1992;7(10):1342–6.PubMedCrossRefGoogle Scholar
  37. 37.
    Soules MR, Sherman S, Parrott E, Rebar R, Santoro N, Utian W, et al. Executive summary: Stages of Reproductive Aging Workshop (STRAW). Fertil Steril. 2001;76(5):874–8.PubMedCrossRefGoogle Scholar
  38. 38.
    Hansen KR, Craig LB, Zavy MT, Klein NA, Soules MR. Ovarian primordial and nongrowing follicle counts according to the Stages of Reproductive Aging Workshop (STRAW) staging system. Menopause. 2012;19(2):164–71.PubMedPubMedCentralCrossRefGoogle Scholar
  39. 39.
    Knowlton NS, Craig LB, Zavy MT, Hansen KR. Validation of the power model of ovarian nongrowing follicle depletion associated with aging in women. Fertil Steril. 2014;101(3):851–6.PubMedCrossRefGoogle Scholar
  40. 40.
    Faddy MJ, Gosden RG. A model conforming the decline in follicle numbers to the age of menopause in women. Hum Reprod. 1996;11(7):1484–6.PubMedCrossRefGoogle Scholar
  41. 41.
    Ayuandari S, Winkler-Crepaz K, Paulitsch M, Wagner C, Zavadil C, Manzl C, et al. Follicular growth after xenotransplantation of cryopreserved/thawed human ovarian tissue in SCID mice: dynamics and molecular aspects. J Assist Reprod Genet. 2016;33(12):1585–93.PubMedPubMedCentralCrossRefGoogle Scholar
  42. 42.
    Silber S. Ovarian tissue cryopreservation and transplantation: scientific implications. J Assist Reprod Genet. 2016;33(12):1595–603.PubMedPubMedCentralCrossRefGoogle Scholar
  43. 43.
    van Noord-Zaadstra BM, Looman CW, Alsbach H, Habbema JD, te Velde ER, Karbaat J. Delaying childbearing: effect of age on fecundity and outcome of pregnancy. BMJ. 1991;302(6789):1361–5.PubMedPubMedCentralCrossRefGoogle Scholar
  44. 44.
    Bongaarts J. Involuntary childlessness with increasing age. Res Reprod. 1982;14(4):1–2.PubMedGoogle Scholar
  45. 45.
    Bongaarts J. Infertility and age: not so unresolved: a reply. Fam Plann Perspect. 1982;14(5):289–90.PubMedCrossRefGoogle Scholar
  46. 46.
    Bongaarts J. Infertility after age 30: a false alarm. Fam Plann Perspect. 1982;14(2):75–8.PubMedCrossRefGoogle Scholar
  47. 47.
    Treloar AE. Menstrual cyclicity and the pre-menopause. Maturitas. 1981;3(3–4):249–64.PubMedCrossRefGoogle Scholar
  48. 48.
    Chang Y, Li J, Li X, Liu H, Liang X. Egg quality and pregnancy outcome in young infertile women with diminished ovarian reserve. Med Sci Monit. 2018;24:7279–84.PubMedPubMedCentralCrossRefGoogle Scholar
  49. 49.
    Nelson LM. Clinical practice. Primary ovarian insufficiency. N Engl J Med. 2009;360(6):606–14.PubMedPubMedCentralCrossRefGoogle Scholar
  50. 50.
    Voorhuis M, Onland-Moret NC, Fauser BC, Ploos van Amstel HK, van der Schouw YT, Broekmans FJ. The association of CGG repeats in the FMR1 gene and timing of natural menopause. Hum Reprod. 2013;28(2):496–501.PubMedCrossRefGoogle Scholar
  51. 51.
    Murray A, Schoemaker MJ, Bennett CE, Ennis S, Macpherson JN, Jones M, et al. Population-based estimates of the prevalence of FMR1 expansion mutations in women with early menopause and primary ovarian insufficiency. Genet Med. 2014;16(1):19–24.PubMedCrossRefGoogle Scholar
  52. 52.
    Pastore LM, Young SL, Manichaikul A, Baker VL, Wang XQ, Finkelstein JS. Distribution of the FMR1 gene in females by race/ethnicity: women with diminished ovarian reserve versus women with normal fertility (SWAN study). Fertil Steril. 2017;107(1):205–11.e1.PubMedCrossRefGoogle Scholar
  53. 53.
    Practice Committee of the American Society for Reproductive Medicine. Testing and interpreting measures of ovarian reserve: a committee opinion. Fertil Steril. 2015;103(3):e9–e17.Google Scholar
  54. 54.
    Huang Y, Li J, Zhang F, Liu Y, Xu G, Guo J, et al. Factors affecting the live-birth rate in women with diminished ovarian reserve undergoing IVF-ET. Arch Gynecol Obstet. 2018;298(5):1017–27.PubMedPubMedCentralCrossRefGoogle Scholar
  55. 55.
    Jiang X, Yan J, Sheng Y, Sun M, Cui L, Chen ZJ. Low anti-Mullerian hormone concentration is associated with increased risk of embryonic aneuploidy in women of advanced age. Reprod Biomed Online. 2018;37(2):178–83.PubMedCrossRefGoogle Scholar
  56. 56.
    Ben-Meir A, Yahalomi S, Moshe B, Shufaro Y, Reubinoff B, Saada A. Coenzyme Q-dependent mitochondrial respiratory chain activity in granulosa cells is reduced with aging. Fertil Steril. 2015;104(3):724–7.PubMedCrossRefGoogle Scholar
  57. 57.
    Duncan FE, Jasti S, Paulson A, Kelsh JM, Fegley B, Gerton JL. Age-associated dysregulation of protein metabolism in the mammalian oocyte. Aging Cell. 2017;16(6):1381–93.PubMedPubMedCentralCrossRefGoogle Scholar
  58. 58.
    Nguyen AL, Drutovic D, Vazquez BN, El Yakoubi W, Gentilello AS, Malumbres M, et al. Genetic Interactions between the Aurora Kinases Reveal New Requirements for AURKB and AURKC during Oocyte Meiosis. Curr Biol. 2018;28(21):3458–68. e5PubMedCrossRefGoogle Scholar
  59. 59.
    Sun F, Sebastiani P, Schupf N, Bae H, Andersen SL, McIntosh A, et al. Extended maternal age at birth of last child and women’s longevity in the Long Life Family Study. Menopause. 2015;22(1):26–31.PubMedPubMedCentralCrossRefGoogle Scholar
  60. 60.
    Gagnon A. Natural fertility and longevity. Fertil Steril. 2015;103(5):1109–16.PubMedCrossRefGoogle Scholar
  61. 61.
    Mueller U. Does late reproduction extend the life span? Findings from European royalty. Popul Dev Rev. 2004;30(3):449−+.Google Scholar
  62. 62.
    Helle S, Lummaa V, Jokela J. Are reproductive and somatic senescence coupled in humans? Late, but not early, reproduction correlated with longevity in historical Sami women. Proc Biol Sci. 2005;272(1558):29–37.PubMedPubMedCentralCrossRefGoogle Scholar
  63. 63.
    Gielchinsky Y, Laufer N, Weitman E, Abramovitch R, Granot Z, Bergman Y, et al. Pregnancy restores the regenerative capacity of the aged liver via activation of an mTORC1-controlled hyperplasia/hypertrophy switch. Genes Dev. 2010;24(6):543–8.PubMedPubMedCentralCrossRefGoogle Scholar
  64. 64.
    Yi Z, Vaupel J. Association of late childbearing with healthy longevity among the oldest-old in China. Popul Stud (Camb). 2004;58(1):37–53.CrossRefGoogle Scholar
  65. 65.
    Pal L, Zhang K, Zeitlian G, Santoro N. Characterizing the reproductive hormone milieu in infertile women with diminished ovarian reserve. Fertil Steril. 2010;93(4):1074–9.PubMedCrossRefGoogle Scholar
  66. 66.
    Brodin T, Bergh T, Berglund L, Hadziosmanovic N, Holte J. Menstrual cycle length is an age-independent marker of female fertility: results from 6271 treatment cycles of in vitro fertilization. Fertil Steril. 2008;90(5):1656–61.PubMedCrossRefGoogle Scholar
  67. 67.
    Quinn MM, Cedars MI. Cardiovascular health and ovarian aging. Fertil Steril. 2018;110(5):790–3.PubMedCrossRefGoogle Scholar
  68. 68.
    van Zonneveld P, te Velde ER, Koppeschaar HP. Low luteal phase serum progesterone levels in regularly cycling women are predictive of subtle ovulation disorders. Gynecol Endocrinol. 1994;8(3):169–74.PubMedCrossRefGoogle Scholar
  69. 69.
    Eissa MK, Obhrai MS, Docker MF, Lynch SS, Sawers RS, Newton JR. Follicular growth and endocrine profiles in spontaneous and induced conception cycles. Fertil Steril. 1986;45(2):191–5.PubMedCrossRefGoogle Scholar
  70. 70.
    Zegers-Hochschild F, Gomez Lira C, Parada M, Altieri Lorenzini E. A comparative study of the follicular growth profile in conception and nonconception cycles. Fertil Steril. 1984;41(2):244–7.PubMedCrossRefGoogle Scholar
  71. 71.
    Xu X, Chen X, Zhang X, Liu Y, Wang Z, Wang P, et al. Impaired telomere length and telomerase activity in peripheral blood leukocytes and granulosa cells in patients with biochemical primary ovarian insufficiency. Hum Reprod. 2017;32(1):201–7.PubMedGoogle Scholar
  72. 72.
    Hanna CW, Bretherick KL, Gair JL, Fluker MR, Stephenson MD, Robinson WP. Telomere length and reproductive aging. Hum Reprod. 2009;24(5):1206–11.PubMedPubMedCentralCrossRefGoogle Scholar
  73. 73.
    Telomeres Mendelian Randomization Collaboration, Haycock PC, Burgess S, Nounu A, Zheng J, Okoli GN, et al. Association between telomere length and risk of cancer and non-neoplastic diseases: a Mendelian randomization study. JAMA Oncol. 2017;3(5):636–51.Google Scholar

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© Springer Nature Switzerland AG 2020

Authors and Affiliations

  1. 1.Division of Reproductive Endocrinology and Infertility, Fertility and Advanced Reproductive Medicine Assisted Reproductive Technologies Program, Department of Obstetrics and GynecologyUniversity of Texas Southwestern Medical CenterDallasUSA

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