In very simple terms, the woman’s age defines the probability — what are the chances that the egg can be successfully fertilized, that the egg turns into a viable blastocyst, an embryo which can divide up to day 5 or day 6. Also, the female age defines the chromosomal status inside the embryo — basically, if the embryo is suitable for embryo transfer, or if it shows a chromosomal error and is not suitable for embryo transfer. All those steps are defined by female age.
We were not even talking yet about the ovarian reserve, which we also know goes down with age, but ovarian reserve is more individual. We have patients with very good reserve, even at the age of 44, and we have patients with very low reserve at the age of 34 or 30. This is very individual. What is not individual and covers everybody is the female age, and the so-called blastulation rate and aneuploidy rate — it’s the same for everybody.
Age affects egg quality because, although women may have a good ovarian reserve even at age 40, the quality of eggs tends to decrease. This results in a higher rate of embryos with chromosomal disorders, even if they have good morphological quality. These embryos may not implant, or if they do, they can lead to a miscarriage in the first trimester.
The ovarian reserve naturally declines with age, as women are born with a fixed number of eggs, and this number decreases over time. As a result, not only does the number of eggs decrease, but their quality also diminishes, which impacts fertility and increases the likelihood of chromosomal abnormalities in the embryos.
A younger egg, any day, would have lesser genetic abnormalities as compared to the older again. That is the main difference between the younger egg and the older egg. I would like to go back two steps on the physiology part for a bit so, every woman is born with a fixed set of eggs unlike men who can form the de-novo sperms so, sperms can be present in the coming three-four months which were never present in their body a few months earlier because they are de-novo cells so they are created from the from the precursors but they are created de-novo. We, as women, are born with a fixed set of eggs and that decreases massively with age so, the central aspect is age. Over the age of 35 quality declines more steeply and then, after the age of 40 very steeply. After 43, even if the woman is pregnant with her own eggs, the percentage of the miscarriage is unfortunately 93% and that is the effect of age.
The age of the woman is very important. The quality of the eggs actually depends on the age of the woman and their quality is best between 20 and 30, then good until 35 and acceptable until 40. After 40 it gets really complicated and there’s hardly anything that you can do to improve that situation. So age is still crucial.
This is a central question in order to better understand biology aging for the oocyte. When considering oocyte quality we should always take into account that oocytes are sensitive cells, which are produced during fetal life and do not have the ability of self-renewal. This means that everything we do in our daily life could negatively impact oocyte quality and thus our reproductive potential. It is widely accepted that as maternal age increases oocyte quality is progressively compromised. This reduction regarding both oocyte quality and ovarian reserve starts approximately after 30 years of age, becomes more intense after 35 and peaks after 40. It is a natural process where the cellular and the molecular mechanisms regulating proper oocyte functionality are compromised in several levels. Thus, errors are observed mainly with regards to the mechanisms regulating chromosome segregation during the meiotic divisions. Meiosis is a special category of cell division, which takes place during gamete production in both females and males. Errors in meiosis affect the number of chromosomes for gametes and subsequently for embryos, finally leading to aneuploidy. Thus, women of advanced age have an increased risk of embryo aneuploidy such as trisomy 21, which is widely known as Down syndrome. Apart from errors during meiosis, oocyte aging can also cause telomere shortening. Telomeres constitute short DNA sequences found at the end chromosomes which protect the genetic information from damage. As maternal age increases telomere shortening is observed, making DNA more sensitive to damage. In the same context, during our lifespan several external and internal factors can cause damage to oocyte DNA, namely mutations. Oocytes are equipped with a perplexing network of molecular factors which can successfully locate and repair these damages. However, as maternal age increases, the efficiency of these repair mechanisms is significantly impaired resulting in mutation accumulation. These mutations negatively impact both oocyte quality and its competence. Oocyte competence refers to the ability of an oocyte to successfully support embryo development. Moreover, aged oocytes are characterized by impaired mitochondria functionality. Mitochondria are small subcellular compartments serving as the ‘’powerhouse’’ of a cell, producing chemical energy required for proper oocyte functionality. Moreover, mitochondria are able to protect oocytes from the damaging effects of reactive oxygen species, which are produced from several biological and environmental processes. Thus, aged oocytes are very sensitive to oxidative stress and cannot successfully support early embryo development. In summary, oocyte aging is a normal, albeit complex biological process which is associated with impaired embryo development, embryo aneuploidy and adverse obstetrical, perinatal and neonatal outcome. Despite the fact that we cannot avoid or reverse oocyte aging, we can adopt healthy lifestyle behaviors in order to improve aging-related deterioration of oocyte quality.
As we age, we have fewer mitochondria and our mitochondria function less well and the mitochondria are responsible for the resilience that the egg needs to get through those first three days of development.
It’s estimated that we are born with around one to two million follicles that hold the premature eggs in them when we are born. Therefore by the age of puberty they are estimating that we have about three to four hundred thousand follicles remaining because unfortunately our ovaries are not very efficient and a lot of these follicles that can contain the immature eggs will be disintegrated and lost by the age of puberty around 300 to 400 thousand of egg reservoir in most women.
Every month that we get our menstrual cycle, we go through our menstrual cycle and get our period, we have about seven hundred to a thousand follicles start developing in the ovary but only one of them wins the race and becomes the mature egg that we produce every month so really again we’re not very efficient through our menstrual cycle. We lose with every ovulation around 700 to 1000 follicles so if you think that this reservoir keeps going down with every period that we have no wonder that by the age of 35 we have less number of eggs available in our ovaries and by the age of 40 plus this reservoir goes down quite low.
We do not produce new eggs like men produce new sperm continuously.
