As the human lifespan increases and the reproductive age of women delays, the contradictory issues of reproductive aging and fertility needs are beginning to emerge. The ovaries are like the female reproductive bank, but the wealth reserves are not inexhaustible. The depletion of the follicular pool makes it difficult for fertility doctors to cook without rice, and the central fountain of reproductive regulation is also facing the dilemma of depletion. We need to recognize, delay, maintain and save the withered reproductive aging with a scientific attitude. Reproductive aging, the fertility dilemma of withered roots before flowers If a woman’s face is like a flower, the reproductive system, which is the birthplace of life, is the root. Just as the roots die first when the tree is old, the “frozen age” appearance cannot stop the ageing of female fertility. The opening of the two-child policy and the postponement of the age of first delivery have made the conflict between the reproductive needs of older women and the aging of the reproductive system a major social and medical problem. Awareness of reproductive aging will help women to plan their fertility and actively improve and pursue their fertility opportunities in the advanced age state. The follicular pool in the ovary can be divided into two parts: the primary pool (resting follicle pool) and the dynamic pool (growing follicle pool), which are similar to the deposits in a bank and the cash on hand. The number of eggs in both the primary and dynamic pools decreases with age, and the rate of follicular decline accelerates significantly after age 35, as if there is a sudden steep descent down a hill, hence the term “stick-folding” phenomenon. For ovarian reserve assessment, the dynamic pool “inventory” can be reflected by ultrasound measurement of the sinus follicle count (AFC) or serum anti-Mullerian hormone (AMH) levels. There is no suitable clinical index to assess the volume of the protostriatal pool, but studies have suggested that the protostriatal pool is closely related to the dynamic pool and that the reserve status of the protostriatal pool is indirectly reflected in the assessment of the dynamic pool. The reserve status of the follicular pool varies from individual to individual, up to 20-fold, and different volumes of the follicular pool are associated with assisted conception outcomes. Therefore, when a woman embarks on the road to reproductive aging, not only does she face a very low probability of conceiving naturally, but she also has to accept the dilemma that assisted conception technology is “too difficult to cook without rice”. It is not only the number of eggs that declines with age, but also the quality of eggs. The decrease in egg quality is mainly due to: 1) abnormal oocyte meiosis, which leads to an increased probability of embryonic aneuploidy (wrong number of chromosomes); 2) a decrease in mitochondria, which are the source of energy for the egg, and a decrease in functional mitochondria in the oocyte, which leads to a buildup of oxidative free radicals and mutations in the mitochondrial genome, resulting in a lack of energy supply for the egg; and 3) a decrease in telomerase activity in the granulosa cells, which leads to an increase in follicular atresia. Our study found that in women undergoing IVF assisted conception, granulosa cell telomerase length and activity were positively correlated with implantation and pregnancy rates. Seeing the residual reserve in the nearly depleted follicular pool, scientists want to provide effective pregnancy support for women with reduced ovarian reserve, including: increasing the number of functional mitochondria with growth hormone and reducing mitochondrial peroxidation products. Studies suggest that the addition of growth hormone to IVF fertility aids increases live birth and pregnancy rates; and dehydroepiandrosterone (DHEA), a weak androgenic agent, has anti-aging effects in humans. Several studies have supported the use of DHEA pretreatment prior to assisted conception to increase the number of quality embryos, effectively reduce miscarriage rates, and improve pregnancy rates. A recent study published in the New Glenn Journal reported that the use of androgenic agents can increase telomerase length and treat diseases related to telomerase abnormalities; stem cell input, with its exosomal effects, regulates ovarian physiological functions and enhances anti-aging. However, its mechanism of action and clinical protocols are still in the research stage; Autologous germ line mitochondrial energy transfer (AUGMET) technology, which addresses egg quality in aging ovaries by implanting autologous-derived mitochondria into mature female eggs; Follicular in vitro activation (IVA), which activates and grows resting eggs in the protoplastic pool through in vitro ovarian tissue fragmentation and pro-activation to The news that “eggs are available” and that “oocytes” can be grown by inducing pluripotent stem cell differentiation was published in Nature on October 17 of this year is encouraging! However, it is still in the research stage and is expected to be translated into clinical applications. II. Aging of the reproductive axis The hypothalamic-pituitary-ovarian axis is an integrated and coordinated neuroendocrine system. Previously, scholars focused on the critical role of accelerated follicular depletion in reproductive aging, ignoring the fact that increasing age is accompanied by brain decline. Recent studies have found that brain GnRH pulse frequency gradually decreases with age and that pituitary responsiveness to brain GnRH decreases; in the fraction of perimenopausal women with surviving estrogen peaks, only half of them can observe LH pulses, indicating that the hypothalamic-pituitary system’s response to positive estrogen feedback is diminished to absent. Our study found that in IVF-assisted women, elevated basal FSH/LH levels were associated with poor assisted conception outcomes. This suggests that not only the ovaries are aging during reproductive aging, but also the regulation of the reproductive axis in the brain is diminished. However, it is not known who is responsible for reproductive aging, but it is assumed that this “aging”, which begins with neuromodulation, is irresistible but not unregulated. 1. What are the signs of aging in the reproductive axis? In the early stages of aging of the hypothalamic-pituitary-ovarian axis, ovarian ovulation is present and regular menstruation occurs, but early menstruation may occur. At this time, women may notice a gradual shortening of the menstrual cycle with an increasing number of days of early periods, ranging from 1 to 7 days; a gradual decrease in menstrual volume; and an increase in minor menstrual-related problems, such as discomfort before and after menstruation, including breast tenderness, irritability and irritability, headache, depression, and irregular bleeding before and after menstruation. These symptoms are not specific, and even if you go to the hospital for examination, no disease is found, so it is not easy to cause alarm about aging. 2. What can be done to slow down the aging of the reproductive axis? As mentioned above, the depletion of ovarian reserve is natural and irreversible. There are also many external factors that can accelerate the depletion of ovarian reserve such as radiation, chemotherapy, viral infection, ovarian surgery trauma, alcohol and tobacco addiction, and environmental compounds. In addition, poor lifestyle patterns of modern people can also accelerate reproductive aging, such as late nights, stress and trauma that inhibit hypothalamic-pituitary function, which can impair neuroendocrine regulation and accelerate reproductive axis aging. Maintaining a healthy mental and physical state may avoid this early decline in neuroendocrine regulation, and may even slow down the process of reproductive axis function decline. According to Chinese medicine, “the kidney is the master of reproduction” and female infertility is closely related to kidney deficiency. The Yellow Emperor’s Classic of Internal Medicine records that “the two seven days of seborrhea, the monthly events to the time, so there is a child …… seven seven days of the Ren pulse deficiency, the days of seborrhea exhaustion, the form of bad and childless”. On the basis of the previous work, TCM gynecologists proposed the concept of “Kidney-Tian Kuei-Chong Ren-Uterus axis”, which corresponds to the hypothalamus-pituitary-ovary-uterus axis. Kidney supplementation to promote pregnancy is gradually integrated into modern assisted reproduction techniques. The results of a recent multicenter randomized double-blind controlled clinical study involving 19 fertility centers nationwide showed that the use of Chinese herbal medicines with kidney tonifying effects significantly improved pregnancy outcomes in women over 35 years of age. It is suggested that the therapeutic principles of TCM of tonifying the kidney and strengthening the spleen and benefiting the qi and nourishing the vital energy are beneficial for the improvement of neuroendocrine regulation of reproduction and for fertility outcomes. In conclusion, reproductive aging is an irreversible process and women have a limited “expiration date” for fertility, so we advocate age-appropriate fertility. Older women with fertility needs need to actively seek the help of a fertility specialist to assess the “expiration date” and try to “rush” to have a successful birth before the deadline. The maintenance of female fertility is a “project” that should be initiated from a woman’s early years.