Developmental and endocrine aspects of normal ovarian aging

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Abstract

Supplies of follicles are established during early fetal life and decrease exponentially thereafter by a process called atresia. Subfertility only starts at a mean age of about 30–31 years, when the remaining follicle reserve has become a fraction of its original number. Thereafter, a further decrease in both oocyte quantity and quality dictates the subsequent reproductive events including decrease of fertility, increased abortion rate, the end of fertility, the beginning of cycle irregularity and, when almost no follicles are left, the occurrance of menopause. The same remarkable variation of age at menopause almost certainly is also present for the preceding reproductive events. When quantity and quality of antral follicles drop below a critical threshold, there is a subsequent drop in inhibine B resulting in the selective FSH rise at a mean age of 37–38 years. This FSH rise explains the accelerated follicle depletion, the increased proportion of growing follicles reaching the selectable stage, the shortening of the follicular phase and the increased incidence of dizygotic twinning. The concurring decrease of oocyte quality is in line with the increased incidence of abortions and chromosomal aberrations after age 35.

Introduction

Increasing educational levels and increasing labour force participation, but also voluntary childlessness and postponement of childbearing, are reflections of growing female emancipation (Te Velde, 1991). These societal changes gained momentum during the early seventies when oral contraceptives became widely available. Fortunately, women are free now to choose their own fate, career and time of having children. However, they sometimes have to pay a price for this freedom: that of subfertility or even infertility. Reproductive aging due to delaying the period in life to have children, considerably contributes to the growing proportion of subfertility (Mosher et al., 1991). This review will try to summarize and interpret present knowledge on developmental and endocrine changes related to ovarian aging.

Section snippets

Disappearing follicles and reproductive events.

Supplies of follicles (oocytes surrounded by granulosa cells) in human ovaries are established during fetal life (Gosden et al., 1985, Richardson et al., 1993, Te Velde et al., 1993, Gougeon et al., 1996). At an early stage of embryo development germ cells separate from somatic cells. Some 1000–2000 migrate to the gonadal ridge where they multiply until about week 20 of gestation when a maximum number of about 7 million has been reached. This stock has to serve the needs of reproduction for the

Dynamics of follicle growth and FSH

The dynamics of follicle growth from the resting or premordial stage until ovulation is depicted in Fig. 4 and is based on the work of Gougeon (Gougeon et al., 1996). Antral follicles measuring 2–8 mm are observed at all stages of the menstrual cycle. They always go into atresia, unless they reach the late luteal or early follicular stage, when they may be ‘rescued’ by the intercycle rise in serum FSH levels by which they are stimulated to further growth. From this cohort of so called

Endocrine events related to ovarian aging

Early follicular FSH levels of normal, cycling women start to rise significantly between age 35 and 40 (Sherman et al., 1976, Reyes et al., 1977, Musey et al., 1987, Lee et al., 1988, Fitsgerald et al., 1994, Klein et al., 1996a). Although this is the first endocrine sign of reproductive aging, it comes relatively late because the number of resting follicles has dropped to about one tenth of the number present at menarche. The FSH rise is not restricted to the early follicular phase, but is

Age-dependant developmental and endocrine changes related to ovarian aging: an attempt to synthesis.

Supplies of follicles are established during early fetal life and decrease exponentially thereafter by a process called atresia. Subfertility only starts at a mean age of about 30–31, when the remaining follicle reserve has become a fraction of its original number. Thereafter, a further decrease in both oocyte quantity and quality dictates the subsequent reproductive events including decrease of fertility, increased abortion rate, the end of fertility, the beginning of cycle irregularity and,

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