Process of women’s reproductive ageing – causes, evaluation and possible clinical usage

Czech version

Authors: M. Huser; I. Crha ; J. Žáková; P. Ventruba
Authors‘ workplace: Gynekologicko-porodnická klinika LF MU a FN, Brno, přednosta prof. MUDr. P. Ventuba, DrSc.
Published in: Ceska Gynekol 2010; 75(4): 353-358

Overview

Women’s fertility steeply decreases with increasing age, but the intensity of the decrease is individually significantly variable. The main cause of fertility drop is rapid decrease of ovarian follicle count. Deletion of ovarian follicles happens mainly by the mechanism of cell apoptosis. Nevertheless in the whole process participates also others exogenous and endogenous factors. At present new major steps in the complex ovarian ageing process has been identified and some innovative therapeutic strategies have been suggested to influence this process. At the end this paper evaluates currently available markers of ovarian reserve and its abilities to be used in routine clinical practice.

Key words:
fertility, menopause, ovary, ovarian follicle, ovarian reserve, reproductive age, apoptosis.

Sources

1. Faddy, MJ., Gosden, RG., Gougeon, A., et al. Accelerated disappearance of ovarian follicles in mid-life: implications for forecasting menopause. Human Reprod (Oxford, England) 1992, 7, p. 1342-1346.

2. Cibula, D. Základy gynekologické endokrinologie. Praha: Grada Publishing, 2002, s. 340.

3. Rebar, RW. Premature ovarian failure. Obstet Gynec 2009, 113, p. 1355-1363.

4. Sills, ES., Alper, MM., Walsh, AP. Ovarian reserve screening in infertility: practical applications and theoretical directions for research. Eur J Obstet Gynec Reprod Biol 2009, 146, p. 30-36.

5. Faddy, MJ., Gosden, RG. A mathematical model of follicle dynamics in the human ovary. Human Reprod (Oxford, England) 1995, 10, p. 770-775.

6. de Bruin, JP., Bovenhuis, H., van Noord, PA., et al. The role of genetic factors in age at natural menopause. Human Reprod (Oxford, England) 2001, 16, p. 2014-2018.

7. van Dooren, MF., Bertoli-Avellab, AM., Oldenburg, RA. Premature ovarian failure and gene polymorphisms. Curr Opin Obstet Gynec 2009, 21, p. 313-317.

8. Gougeon, A., Chainy, GB. Morphometric studies of small follicles in ovaries of women at different ages. J Reprod Fertil 1987, 81, p. 433-442.

9. Block, E. Quantitative morphological investigations of the follicular system in women; variations at different ages. Acta anatomica 1952, 14, p. 108-123.

10. Gaulden, ME.. Maternal age effect: the enigma of Down syndrome and other trisomic conditions. Mutation Res 1992, 296, p. 69-88.

11. de Bruin, JP., Dorland, M., Spek, ER., et al. Age-related changes in the ultrastructure of the resting follicle pool in human ovaries. Biol Reprod 2004, 70, p. 419-424.

12. Park, JS., Sharma, LK., Li, H., et al. A heteroplasmic, not homoplasmic, mitochondrial DNA mutation promotes tumorigenesis via alteration in reactive oxygen species generation and apoptosis. Human molecular genetics 2009, 18, p. 1578-1589.

13. Sauer, MV. The impact of age on reproductive potential: lessons learned from oocyte donation. Maturitas 1998, 30, p. 221-225

14. Chrobak, A., Sieradzka, U., Sozanski, R., et al. Ectopic and eutopic stromal endometriotic cells have a damaged ceramide signaling pathway to apoptosis. Fertil Steril 2009, 92, p. 1834-1843.

15. Gude, DR., Alvarez, SE., Paugh, SW., et al. Apoptosis induces expression of sphingosine kinase 1 to release sphingosine-1-phosphate as a “come-and-get-me” signal. Faseb J 2008, 22, p. 2629-2638.

16. Sukhotnik, I., Voskoboinik, K., Lurie, M., et al. Involvement of the bax and bcl-2 system in the induction of germ cell apoptosis is correlated with the time of reperfusion after testicular ischemia in a rat model. Fertil Steril 2009, 92, p. 1466-1469.

17. Scorrano, L., Oakes, SA., Opferman, JT., et al. BAX and BAK regulation of endoplasmic reticulum Ca2+: a control point for apoptosis. Science 2003, 300, p. 135-139.

18. Huang, YH., Zhao, XJ., Zhang, QH., Xin, XY. The GnRH antagonist reduces chemotherapy-induced ovarian damage in rats by suppressing the apoptosis. Gynecol Oncol 2009, 112, p. 409-414.

19. Tilly, JL., Kolesnick, RN. Realizing the promise of apoptosis-based therapies: separating the living from the clinically undead. Cell death and differentiation 2003, 10, p. 493-495.

20. Takai, Y., Canning, J., Perez, GI., 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, p. 69-74.

21. Rucker, EB. 3rd, Dierisseau, P., Wagner, KU., et al. Bcl-x and Bax regulate mouse primordial germ cell survival and apoptosis during embryogenesis. Molecular endocrinology (Baltimore) 2000, 14, p. 1038-1052.

22. Kolesnick, RN., Kronke, M. Regulation of ceramide production and apoptosis. Ann Rev Physiol 1998, 60, p. 643-665.

23. Nieuwenhuis, B., Luth, A., Kleuser, B. Dexamethasone protects human fibroblasts from apoptosis via an S1P(3)-receptor subtype dependent activation of PKB/Akt and Bcl(XL). Pharmacol Res 2009.

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

25. Oktay, K. Spontaneous conceptions and live birth after heterotopic ovarian transplantation: is there a germline stem cell connection? Human Reprod (Oxford) 2006, 21, p. 1345-1348.

26. Chung, MY., Fang, PC., Chung, CH., et al. Comparison of neonatal outcome for inborn and outborn very low-birthweight preterm infants. Pediatr Int 2009, 51, p. 233-236.

27. Westhoff, C., Murphy, P., Heller, D. Predictors of ovarian follicle number. Fertil Steril 2000, 74, p. 624-628.

28. Joiner, LL., Robinson, RD., Bates, W., Propst, AM. Establishing institutional critical values of follicle-stimulating hormone levels to predict in vitro fertilization success. Military Med 2007, 172, p. 202‑204.

29. Kwee, J., Elting, ME., Schats, R., et al. Ovarian volume and antral follicle count for the prediction of low and hyper responders with in vitro fertilization. Reprod Biol Endocrinol 2007, 5, p. 9.

30. Hendriks, DJ., Kwee, J., Mol, BW., et al. Ultrasonography as a tool for the prediction of outcome in IVF patients: a comparative meta-analysis of ovarian volume and antral follicle count. Fertil Steril 2007, 87, p. 764-775.

31. Yong, PY., Baird, DT., Thong, KJ., et al. Prospective analysis of the relationships between the ovarian follicle cohort and basal FSH concentration, the inhibin response to exogenous FSH and ovarian follicle number at different stages of the normal menstrual cycle and after pituitary down-regulation. Human Reprod (Oxford) 2003, 18, p. 35-44.

32. van Rooij, IA., Broekmans, FJ., Scheffer, GJ., et al. Serum antimullerian hormone levels best reflect the reproductive decline with age in normal women with proven fertility: a longitudinal study. Fertil Steril 2005, 83, p. 979-987.

33. Smeenk, JM., Sweep, FC., Zielhuis, GA., et al. Antimullerian hormone predicts ovarian responsiveness, but not embryo quality or pregnancy, after in vitro fertilization or intracyoplasmic sperm injection. Fertil Steril 2007, 87, p. 223-226.

34. Sowers, MR., Eyvazzadeh, AD., McConnell, 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, p. 3478-3483.