Wypoczywająca kobieta w salonieThe number of oocytes decreases successively starting from the prenatal period until their exhaustion in the menopausal period. With age, the risk of genetic disorders in children of older women increases as well. Already in women aged 30, the percentage of abnormal egg cells approaches 40%, and in women aged 40 it reaches 80%. The level of FSH – the so-called ovarian reserve marker – rises significantly, probably due to the decreased inhibin secretion from aging ovaries. The rate of anovulatory cycles increases, and the luteal phase of the cycle – phase II – becomes shorter. The processes mentioned above as well as many others contribute to the age-related reduction of female fertility.

Currently, the mechanisms responsible for the age-related gradual decline in reproductive potential are not yet fully known. It is considered that the key and decisive role is played by ovaries, and the processes occurring in other organs are of secondary character.

Today, the need to develop professionally and the desire to achieve material stabilization prompt women to postpone the decision about having children. Information about the assisted reproductive technologies makes such decision even easier, giving hope of having a child in a chosen period of life. Late motherhood becomes increasingly common phenomenon in developed countries, although it is known that age is the basic factor limiting the reproductive potential. The peak of female fertility occurs between ages 20 and 25, then it slowly declines, and after the age of 37 it starts decreasing significantly. Poorer quality of oocytes and neuroendocrine changes related to the body’s biological aging have a decisive influence on the limitation on the reproductive options.

Not only pathologies which have direct or indirect impact on the reproductive system can lead to reduction in fertility. Changes accompanying the irreversible aging of the body more often prevent natural conception. The quality of oocytes depends on biological age.

Reduction in the number of ovarian follicles is associated with the increasing level of FSH in early follicular phase. This increase precedes menopause by over a decade. The number of mature follicles in response to stimulation with exogenous gonadotropins is also the indicator of ovarian reserve and is inversely proportional to the FSH level, regardless of a woman’s age.
In the perimenopausal period, the luteal phase of the cycle becomes shorter, which, in the case of pregnancy, is conducive to early miscarriages.

Changes causing the decrease in ovarian reserve affect also ovarian interstitial tissue. Cell degeneration, phagocyte accumulation, fibrosis occurs, which gives the macroscopic picture of decreased gonad volume. Total number of oocytes and number of mature oocytes diminishes. It has been observed that in women aged over 40, the inactivity of cumulus oophorus cells reduces the likelihood of egg fertilization and in consequence the rate of achieved pregnancies. The use of oocyte donation gives the similar pregnancy rates in young and in older women which is the indirect evidence that oocyte aging is the basic mechanism impairing fertility. Although the biological value of an egg cell is not full, pregnancy in a premenopausal woman is not absolutely impossible. If it occurs, however, one should take into account the increased risk of genetic disorders in children of older mothers. This relates chromosomal aberrations, in particular aneuploidies. Their main cause are disorders of the second meiotic division in egg cells. The most common anomaly is the trisomy of the 21st pair of chromosomes which is the cause of the Down syndrome in over 90% of cases. While the probability of the Down syndrome in a mother aged 25 is 1 to 250, in a mother aged 40 it is 1 to 106. The risk of other chromosomal abnormalities is also higher. In premenopausal women, also the abnormal control of proteins related to karyokinetic spindle over individual phases in the cell cycle of oocytes can be the cause of aneuploidies.

Furthermore, sensitivity of ovaries to stimulation with gonadotropins decreases with age. The fact is that although the number of follicles obtained in the result of hormonal stimulation is independent from age, the percentage of follicles capable of further development and ovulation is significantly lower in older women. Hormonal changes typical for the perimenopausal period (lower levels of estradiol and higher levels of LH and FSH) occur gradually already from 20 years of age onward. Moreover, it has been observed that the significant increase in FSH level is present in female blood serum much earlier than LH and E2 changes. It is believed that a factor responsible for the increase in the level of folliculotropin is reduced inhibin secretion from aging ovaries. This increased level of FSH can cause earlier development of preovulatory follicles and thereby earlier increase in estradiol level in relation to the day of ovulation. As a result of the lower total number of developing follicles, each of preovulatory follicles is forced to produce more estrogens and for a longer time, until their concentration needed to induce the LH peak is achieved.

Age-related decrease in fertility involves multiple factors and depends on changes in hypothalamus, pituitary, ovaries and uterus. It is considered, however, that the key and decisive role is played by ovaries, and the processes occurring in other organs are of secondary character. Damage of collagen fibers within the uterine muscle which increases with age is effectively inhibited by estrogens. Also the hormonal stimulation of endometrium can significantly increase the percentage of mitoses the number of which diminishes due to aging. Studies indicate that the appropriate hormone substance allows to create the environment favorable for embryo implantation, development of pregnancy and continuing to term.

It has been found on the basis of experimental studies in animals that the changes in pituitary and hypothalamic function which occur with age are secondary to the imbalance in the levels of ovarian hormones. Hypothalamus becomes less sensitive to estrogen positive feedback which is further intensified by chronic damaging effect exerted by ovarian steroid hormones on hypothalamic cells. Circulating ovarian hormones may promote degenerative processes in hypothalamic neurons, changing amounts of receptors in hypothalamus, pituitary gland, ovaries and uterus as well as many other target organs.

Furthermore, pathological processes which interfere with the function of the reproductive system can definitely worsen the prognosis of pregnancy in a premenopausal woman. This relates to concomitant endometriosis, chronic infections in the lesser pelvis and uterine fibroids, especially submucosal ones. The probability of these pathologies also increases with age. Despite the development of research methods and laboratory techniques, mechanisms responsible for the age-related gradual decline in reproductive potential are not yet clear or fully known.

Was it useful? 506 0

← Back
← Back to homepage
Published: 5 November 2015 Updated: 4 April 2017