The variability of female reproductive aging

Department of Reproductive Medicine, University Medical Centre, Utrecht, The Netherlands.
Human Reproduction Update (Impact Factor: 10.17). 11/2001; 8(2):141-54.
Source: PubMed


The delay in childbearing is an important societal change contributing to an increasing incidence of subfertility. The prevailing concept of female reproductive ageing assumes that the decline of both quantity and quality of the oocyte/follicle pool determines an age-dependent loss of female fertility. There is an apparent discrepancy between the ability to maintain a regular ovulatory cycle pattern and the several years earlier cessation of female fertility. This latter is largely explained by an age-related increase of meiotic non-disjunction leading to chromosomal aneuploidy and early pregnancy loss, such that most embryos from women > or =40 years old are chromosomally abnormal and rarely develop further. The final stage of reproductive ageing-the occurrence of menopause-shows a huge variation between women. Age at last birth in natural fertility populations, which marks the end of female fertility, shows an identically wide variation as age at menopause, but occurs on average 10 years earlier. Given the high heritability for age at menopause, the variation in both age of menopause and last birth are probably under genetic control by the same set of genes. Some of those genes must carry heritable variants which modulate the rate of ovarian ageing and give rise to the wide age variations for the various phases of reproductive ageing.

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    • "Age related decline in reproductive performance in women is well documented [American College of Obstetricians and Gynecologists Committee on Gynecologic Practice; Practice Committee of the American Society for Reproductive Medicine 2014; Spira 1988; te Velde and Pearson 2002]. "
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    ABSTRACT: Age related decline in reproductive performance in women is well documented and apoptosis has been considered as one of the reasons for the decline of primordial follicle reserve. Recently we observed a decline in the efficiency of DNA repair ability in aged rat primordial follicles as demonstrated by decreased mRNA levels of DNA repair genes BRCA1 and H2AX. In the present study, a two-dimensional electrophoresis (2DE) proteomic approach was employed to identify differentially expressed proteins in primordial follicles isolated from ovaries of immature (∼20 days) and aged (∼400-450 days) rats. Using MALDI-TOF/TOF MS, we identified 13 differentially expressed proteins (p < 0.05) which included seven up-regulated and six down-regulated proteins in aged primordial follicles. These proteins are involved in a wide range of biological functions including apoptosis, DNA repair, and the immune system. Interestingly, the differentially expressed proteins such as FIGNL1 (DNA repair) and BOK (apoptotic protein) have not been previously reported in the rat primordial follicles and these proteins can be related to some common features of ovarian aging such as loss of follicle reserve and genome integrity. The quantitative differences of two important proteins BOK and FIGNL1 observed by the proteomic analysis were correlated with the transcript levels, as determined by semi-quantitative RT-PCR. Our results improve the current knowledge about protein factors associated with molecular changes in rat primordial follicles as a function of aging and our understanding of the proteomic processes involved in degenerative changes observed in aging primordial follicles.
    Systems biology in reproductive medicine 09/2015; DOI:10.3109/19396368.2015.1077903 · 1.60 Impact Factor
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    • "From a biological point of view, the optimal period for a woman to have children is between ages 18 and 30 years. Thereafter, the ability to conceive and have children declines progressively (Bongaarts, 1975; Wood, 1989) because of depletion and ageing of the pool of oocytes stored in the ovaries during the fetal period (te Velde and Pearson, 2002). The advent of reliable methods of contraception in the 1960s enabled women to postpone childbearing, to prevent the birth of not yet wanted children, and to plan the start of building a family (Goldin, 2006). "
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    ABSTRACT: Until what age can couples wait to start a family without compromising their chances of realizing the desired number of children? The latest female age at which a couple should start trying to become pregnant strongly depends on the importance attached to achieving a desired family size and on whether or not IVF is an acceptable option in case no natural pregnancy occurs. It is well established that the treatment-independent and treatment-dependent chances of pregnancy decline with female age. However, research on the effect of age has focused on the chance of a first pregnancy and not on realizing more than one child. An established computer simulation model of fertility, updated with recent IVF success rates, was used to simulate a cohort of 10 000 couples in order to assess the chances of realizing a one-, two- or three-child family, for different female ages at which the couple starts trying to conceive. The model uses treatment-independent pregnancy chances and pregnancy chances after IVF/ICSI. In order to focus the discussion, we single out three levels of importance that couples could attach to realizing a desired family size: (i) Very important (equated with aiming for at least a 90% success chance). (ii) Important but not at all costs (equated with a 75% success chance) (iii) Good to have children, but a life without children is also fine (equated with a 50% success chance). In order to have a chance of at least 90% to realize a one-child family, couples should start trying to conceive when the female partner is 35 years of age or younger, in case IVF is an acceptable option. For two children, the latest starting age is 31 years, and for three children 28 years. Without IVF, couples should start no later than age 32 years for a one-child family, at 27 years for a two-child family, and at 23 years for three children. When couples accept 75% or lower chances of family completion, they can start 4-11 years later. The results appeared to be robust for plausible changes in model assumptions. Our conclusions would have been more persuasive if derived directly from large-scale prospective studies. An evidence-based simulation study (as we did) is the next best option. We recommend that the simulations should be updated every 5-10 years with new evidence because, owing to improvements in IVF technology, the assumptions on IVF success chances in particular run the risk of becoming outdated. Information on the chance of family completion at different starting ages is important for prospective parents in planning their family, for preconception counselling, for inclusion in educational courses in human biology, and for increasing public awareness on human reproductive possibilities and limitations. No external funding was either sought or obtained for this study. There are no conflicts of interest to be declared. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology.
    Human Reproduction 07/2015; 30(9). DOI:10.1093/humrep/dev148 · 4.57 Impact Factor
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    • "Fertility significantly decreases with age, and the reduction of fertility is particularly noticeable after the age of 30 years; therefore, woman's age is one of the most important factors in determining fertility and ovarian reserve. As ovarian reserve physiologically decreases with age, the ovarian reserve according to the physiological age is lower than expected because of individual variability; this is known as diminished ovarian reserve (DOR) (Barad et al., 2007; Broekmans et al., 2009; te Velde and Pearson, 2002). The quality of oocyte also diminishes as a result of many factors during the lifetime , and leads to an increasing rate of aneuploidy. "
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    ABSTRACT: An increased accumulation of intracellular levels of reactive oxygen species with time may play an important role in the process of ageing. The antioxidant properties of resveratrol are dependent upon the up-regulation of endogenous cellular antioxidant systems. We evaluated whether resveratrol has protective antioxidant effects on ovarian damage related to oxidative stress in a rat model. Twenty-four female rats were randomly divided into three groups and were given saline (group 1: control); intraperitoneal cisplatin, 4.5 mg/kg, two weekly doses in total (group 2); or cisplatin, 4.5 mg/kg plus intraperitoneal resveratrol 10 mg/kg/day, 24 h before the administration of cisplatin (group 3). Serum anti-Müllerian hormone (AMH) concentrations were significantly lower in group 2 than in group 3 (P < 0.01 and P = 0.04, respectively). The evaluation of the atretic and antral follicle counts revealed statistically significant differences between the groups (P = 0.04 and P < 0.01, respectively). A statistically significant difference was observed in the follicle count positive for AMH between the groups (P = 0.01). Oxidative stress plays an important role in the process of ovarian ageing. Because of its natural antioxidant properties, resveratrol may be an effective option in protecting ovarian tissue against oxidative damage. Copyright © 2015 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.
    Reproductive biomedicine online 06/2015; 31(3). DOI:10.1016/j.rbmo.2015.06.007 · 3.02 Impact Factor
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