‘Omne vivum ex ovo’ (All living things come from eggs)
William Harvey (1578 – 1657)
What Is Egg Quality?
The ovulated egg is the biggest cell of the human body. This single cell has the capacity to create a complex system made up from millions of cells with various functions. It is therefore not surprising that the egg stores a pool of encoded biological material which, when triggered by the sperm entry, is capable of initiating a cascade of cellular, metabolic and genetic events leading to formation of an organism.
As William Harvey, the famous English physician, pointed out nearly five centuries ago, it is established today that the capacity of the embryo to produce pregnancy is determined by the quality of the egg even before it is fertilised by the sperm. During the first days of conception embryo development is predominantly dependent on the contents of the ovulated cell with the exception of the machinery that enables division of the fertilised egg to two cells, which is delivered by the sperm. Besides providing the embryo half of its genetic material and almost all cellular determinants, the egg is equipped with a capacity that compensates for compromised sperm quality. ‘Egg quality’ refers to all of these features, it is a collective description of the characteristics of the egg, which enables it to be fertilised and support embryo development to produce and maintain a pregnancy.
The Life Cycle Of Eggs Is Reflected To Their Quality
Similar to all living things eggs have a life cycle. Women are born with a stock of immature eggs in their ovaries. With every menstrual cycle a group of eggs starts to grow from this pool, resulting in usually one reaching to the stage of maturation to be discharged at ovulation. If not fertilised and subsequently produce a pregnancy the egg starts to age, eventually dies and expelled from the body through menstruation. Other eggs of the cohort accompanying the ovulated one are also consumed as their capacity to be fertilised is vanished.
The quality of the egg is correlated to its age. It is mostly determined during foetal life probably due to inherent characteristics, which operate subsequently during growth and maturation of the cell. However, these characteristics are susceptible to deterioration in later life through acquired mechanisms; e.g., hormonal imbalances, life style and nutrition, exposure to toxic substances etc. At ovulation, they are exposed to await fertilisation, if not, egg quality gradually diminishes concomitant to aging of the cell.
Similar to individual sperm cells produced by a man, there is diversity in the quality of the eggs of a woman. This is probably one of the reasons that even fertile couples practising unprotected intercourse have a conception probability of around 25%.
With advanced age the number of immature eggs remaining in the ovaries, i.e., ovarian reserve decreases. Furthermore they age in years, which causes deterioration in their quality. Therefore, reduction in the number of reserve eggs accompanied by diminished quality creates a significant problem in delayed motherhood. There is not much women can do to preserve their egg quality, except for being cautious of their general well being and maintaining a healthy life style. There is no scientific evidence for any agent improving egg quality that is accessible to women.
What Are The Structures And Mechanisms Of The Eggs That Are Associated With Their Quality?
The short answer to that question is ‘we don’t know!’ It is known that to attain the capacity to be fertilised and to support pregnancy, eggs need to accomplish two essential pathways occurring within two cellular compartments during the course of growth and maturation. Understanding egg quality relies on elaborating both of these pathways. The first one taking place in the nucleus is called genetic maturation and it ensures that the number of chromosomes is halved (the other half will be brought by the sperm). The second pathway occurs in the cytoplasm (i.e., the compartment of the cell remaining between the nucleus and the cell membrane) and it is called developmental maturation. Although less is known as compared to the former, it determines the capacity of the egg to support embryo development probably through accumulation of molecules and organisation of cellular structures.
Although genetic state can be assessed with the currently available technology, there are no tools to predict the developmental capacity of the egg. Furthermore, genetic maturation is spontaneously completed in almost all eggs at fertilisation, yet most of these cells are not capable to support embryo development as less than 10% of the eggs retrieved from women yield a new born (also see below).
Therefore, lack of understanding in the mechanisms underlying developmental maturation of the egg appears to be the limiting factor for the overall success of assisted reproduction treatments.
Lack Of Predictive Quality Parameters Causes Overconsumption Of Eggs During IVF Treatment
The embryo is the end product of input from two cells: the egg and the sperm. After merging at fertilisation their characteristics (that determine their quality) begin to interact during the course of embryo development, with a delay of the contribution of the sperm relative to the egg (see above). Therefore, occurrence of natural conception or outcome of infertility treatment, among other parameters such as the receptivity of the womb, is a consequence of a gradually increasing interaction between the qualities of the egg and the sperm; it can be achieved when a high quality egg is fertilised by a sperm whose quality it compensates (see above). And vice versa, when the sperm quality is high (and this is not always correlated to conventional semen assessment parameters like concentration, motility or shape of cells), then occurrence of conception does not require an egg possessing a high compensation capacity. This is why infertility professionals prefer using the term ‘infertile or sub-fertile couple’; in majority of the cases, both partners contribute to the cause of infertility to a certain extent.
Current IVF treatment operates through production of a number of embryos, if possible, whose ‘qualities’ or capacities to produce pregnancy can be predicted through relatively established selection criteria. However, this approach is not ideal because it suffers from the prerequisite that women need to produce many eggs. Furthermore, scientific data repeatedly showed that today’s technology is capable of producing less than 10 infants for every 100 eggs retrieved from women. Hence, majority of the eggs, which are highly valuable biological material due to their limited availability during the lifetime of women, are consumed during the procedure.
The obligation to utilise such a low efficient approach as the choice of treatment is due to the lack of knowledge to predict the developmental quality of the egg. If there were tools to predict the egg quality before they were inseminated, then it would be possible to develop treatment strategies that yield improvement in egg quality, and consequently, reduce their wastage.
How To Assess Egg Quality: The Pre-Requisites
Through various technological approaches scientists are working on identification of parameter(s) predictive of developmental quality of eggs. Such tools need fulfil all of the following criteria:
1. Objectivity and repeatability: the parameters must be quantifiable and consistent among measurements,
2. Safety, non-toxicity and non-disruptive: the egg should remain available for utilisation and its biological characteristics should not be altered after application of such parameters,
3. Real-time monitoring: the parameters should yield data at the time of measurement to reflect the real-time state due to the correlation among the age and quality of the egg,
4. Practicality and financial feasibility: the parameters need to be easy to apply to routine practise and should not be very expensive to enable their extensive utilisation.
Take Home Messages
• The capacity of the embryo to produce an infant is determined by the quality of the egg before it is fertilised.
• The features of the egg that determine its quality is mostly inherited but other parameters acquired later in life may negatively influence these characteristics. A healthy life style probably helps minimising such risks.
• There is not any parameter that predicts the capacity of the egg to support pregnancy. This is due to the limited knowledge on the mechanisms that attain the egg such characteristic. Hence, today’s IVF technology relies on embryo selection strategy at the cost of production of many eggs by the women, of which more than 90% will eventually be wasted.
• Research that identifies robust, objective, safe and affordable real-time parameter(s) that predict egg quality will contribute to the improvement of overall efficacy of IVF treatment and reduce the consumption of valuable biological material.