From the Guidelines
The follicular reserve decreases significantly with age, with the number of retrieved oocytes reducing from 15.4 ± 8.8 in women <26 years of age to 9.9 ± 8.0 in women 36-40 years of age, as reported in a recent study 1. This decline in follicular reserve is a natural process that occurs throughout a woman's reproductive years, with the rate of follicle loss accelerating after age 37-38. The factors contributing to this decline include:
- Continuous follicular recruitment
- Atresia (programmed cell death of follicles) These processes occur regardless of pregnancy, contraceptive use, or other hormonal interventions. The quality of remaining oocytes also diminishes with age, leading to increased chromosomal abnormalities, which is supported by a study that found a cumulative live birth rate of 61.9% if 12 oocytes were cryopreserved in women 35 years of age and 43.4% if 10 oocytes were cryopreserved in women >35 years of age 1. The age-related decline in follicular reserve is the primary reason why fertility decreases with advancing maternal age, particularly after 35, and why assisted reproductive technologies become less successful as women age. Anti-Müllerian hormone (AMH) levels and antral follicle counts serve as clinical markers to estimate remaining follicular reserve, though they cannot predict exact time to menopause or guarantee pregnancy success. Other factors such as chemotherapy-induced ovarian failure and radiation therapy can also impact follicular reserve, with studies showing that ovarian irradiation of ≥ 10 Gy and exposure to alkylating agents can increase the risk of primary ovarian failure 1. However, the natural decline in follicular reserve with age remains the primary concern for women's reproductive health. In clinical practice, it is essential to consider the age-related decline in follicular reserve when counseling women about their reproductive options and to prioritize fertility preservation strategies, such as oocyte and embryo cryopreservation, for women at risk of premature ovarian failure or those delaying childbearing until an older age.
From the Research
Follicular Reserve Changes with Age
- The number of follicles in the ovary decreases with age, leading to a decline in fertility [(2,3,4,5)].
- This decline is exponential, with an acceleration in the rate of follicle loss in the decade preceding menopause [(3,5)].
- The follicular reserve is depleted to a critical level with age, leading to increased infertility, spontaneous abortion, and conception of trisomic offspring 2.
Mechanisms of Follicular Depletion
- Atresia is the major form of follicular expenditure at all stages of ovarian development 4.
- The decline in follicular reserve is perhaps the immediate thrust that increases the rate of follicle depletion during the final phase of ovarian life 4.
- Elevated FSH levels observed in normal women in the decade preceding menopause may be responsible for the apparent acceleration in the rate of follicle loss 3.
Age-Related Changes in Follicle Populations
- The population of non-growing follicles (NGF) and early-growing follicles (EGF) decreases with age 5.
- The decay rate of NGF and EGF increases with age, with a significant relation between a woman's age and the corresponding NGF count decay rate 5.
- The changing points for NGF and EGF decay rates are around 38-39 years of age, after which the decay rate accelerates 5.