Estradiol waives in the follicular phase
Even though it is usually understood that estradiol gradually increases during the follicular phase and its peack
There are several hypotheses explaining declining fertility with age. One of them postulates that the decline is related to the shrinking pool of so-called primordial follicles from which ovulating follicles are recruited. But since women at any age ovulates only one follicle, this does not explain why the number of primordial follicles would be so critical.
Another hypothesis states that chromosomes of the eggs inside of the follicles, particularly their so-called telomeres, become damaged by free radicals. This leads to chromosomal errors in oocytes, which in its turn makes pregnancy less likely. Yet, there is an observation that still puzzles scientists, and contradicts this idea. Ionizing radiation is one of the most powerful DNA damaging agents. It is far more powerful than free radicals. One would fully expect that if DNA damage plays major role in female fertility, we would see the reduction in fertility rates after exposure to ionizing radiation, but surprisingly this has not been the case.
At the same time, there is another fact related to reproductive aging, which can give us an interesting clue. As we have seen earlier, the reduction in the duration of the follicular phase has a dramatic effect on fertility. It is known that the duration of the follicular phase has a clear tendency to shorten with age:
This shortening corresponds to the age-related drop in fertility:
As an egg does not control the duration of the cycle and therefore cannot be responsible for this shortening. The duration of the cycle depends on how long the follicle can survive during the follicular cycle, which in its own term is determined by the ability of the ovarian cortex to expand to accommodate follicle’s expansion from about 3 mm to 25 mm. The ovarian cortex’s elasticity diminishes with age and so its ability to accommodate the follicle’s growth. Since the pace of the follicle’s growth with age does not slow down, it will ovulate at a smaller size not allowing oocyte’s term maturation. Another possible reason for earlier ovulation with age is an elevated level of starting (baseline) FSH, which would tend to accelerate the pace of follicle’s expansion. Thus, two age related tendencies, reduced elasticity of cortext and elevated baseline FSH synergetically reduce the duration of the follicular phase. Importantly, both of them do not have any connection with intrinsic problems with the egg, which becomes the “victim” of outside influence.
The diminished ability of ovarian cortex to accommodate the follicle’s expansion is a well-known phenomenon in IVF, called “vanishing follicle.” It is considerably more prevalent in a woman of advanced reproductive age. Vanishing follicle simply means that the follicle seen at the previous ultrasound disappears due to the purely “mechanical reasons.”
This creates a possibility that the reduction of fertility seen in many women of advanced reproductive age is not entirely due to the intrinsic problem with their eggs. Instead, it may at least partially be due to the egg’s inability to reach full maturity (term maturation), because the ovarian cortex partially lost its elasticity and follicle pops prematurely. While we cannot improve the cortex elasticity, we can reduce inflammation which is accompanied the final stages of follicle’s development, and thus potentially extend the duration of the follicular phase to enable oocyte to reach term maturation.