Editorial

EGG QUALITY AND ITS SIGNIFICANCE ON THE OUTCOME OF ASSISTED REPRODUCTION TREATMENTS

 Nadir Ciray, MD, PhD, Senior Clinical Embryologist, Director, OvoScore Ltd. www.ovoscore.com and National Fertility Society Executive Team Member

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.

Are you going through the menopause?

Have you noticed that your libido, or sex drive as changed?

Some women may experience a decrease in libido, it is very common to have a lower libido during menopause is due to decreased hormone levels.  These decreased hormone levels can lead to vaginal dryness and tightness, which can cause pain during sex.  Menopause symptoms can also make you less interested in sex. These symptoms include: depression, mood swings, weight gain and hot flushes.

The Menopause can negatively affect libido in several ways. During menopause, your testosterone and oestrogen levels both decrease, which may make it more difficult for you to get aroused.  A decrease in oestrogen can also lead to vaginal dryness this is because the lower levels of oestrogen lead to a drop-in blood supply in the vagina, which can then negatively affect vaginal lubrication. It can also cause thinning of the vaginal wall, known as vaginal atrophy.  Vaginal dryness and atrophy often lead to discomfort during sex.

Other physical changes during menopause might also affect your libido. For example, many women gain weight during menopause, and are not comfortable with their new body this also can decrease their desire for sex. Hot flushes and night sweats are also common symptoms. These symptoms can leave you feeling too tired for sex. Other symptoms include mood symptoms, such as depression and irritability, which can turn you off from sex.

Different women will experience menopause at different times but if it arrives early then some women can feel quite cheated, and have many questions.

There is an expectation for women between 45 and 55 to go through the menopause, at last it is being spoken about publicly but it still remains a ‘taboo’ subject for many women and their partners.

How can you improve your sex drive?

Ellamuselle™ is a unique, patented food supplement with L-arginine, propionyl-L-carnitine, Muira puama, Damiana, Zinc, Black cohosh, Ginkgo biloba and Vitamin B3 especially designed for active women.  Normal female sexual function and sexual desire is the result of a complex interaction between physiological, psychological and social factors. Although low sexual desire affects women of all ages, its frequency increases with age and particularly at and after menopause. Low sexual desire can impact physical and emotional well-being and can be associated with low self-esteem, depression, and family problems. Unfortunately, women are often reluctant to report symptoms of low sexual desire, despite the fact that it is a prevalent and distressing condition and is associated with a range of negative effects on women’s health.

Your doctor may refer you and your partner to a health professional who specialises in sexual dysfunction.  Psychosexual counselling on an individual basis or with your partner, can be very successful, even when it is done on a short-term basis.

How does depression affect sexual function?

The brain is the body’s most sensitive “sex organ.” Sexual desire starts in the brain and works its way down. Chemicals called neurotransmitters help brain cells communicate to stimulate blood flow to the sex organs.  In a person with depression, these chemicals are out of balance. As a result, sexual desire is low or non-existent. In addition, low levels of certain neurotransmitters can dull the feelings of pleasure.  The strain that a depressive illness can place on a patient’s relationship can further interfere with sexual functioning and pleasure. For both men and women, being unable to start, participate in or enjoy sex can lead to a loss of self-confidence.

Sexual and relationship therapy can be helpful for an individual or couple who feel their difficulties are affecting their quality of life. It can be a big step to decide to embark on therapy.  The main point of Sexual and Relationship Therapy is to give you a safe space and regular time to talk about what is going on in your life.  The focus is on sexual or relationship issues, but these may be linked with what is going on in the rest of your life –  stress, problems at work, financial, family or physical difficulties.  It is fine to talk about these issues too.

The main thing to expect is to be talking about what is going on in your life. Counsellors are skilled at helping you to do this, some Counsellors may get you to keep a journal or notes between therapy sessions to remind you what you want to talk about.  When you go to therapy with someone you’re in a relationship with, the Counsellor may encourage you to talk to each other more than to them. This is because relationship therapy aims to help you to communicate well about your relationship.

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Family Nutrition Coach 

Optimum Nutrition and Health
Before, During, and After Pregnancy

Nutrition For Successful Fertility Treatment

Most dietitians and nutritional therapist will confirm that the best results are when you start about 3 months before beginning any ART.  When you are just thinking about starting a family.

The quality of the egg and sperm can be improved, and it helps to reduce the physical and emotional impact of the hormone treatments.  Many of my clients find that good nutrition therapy at this stage is sufficient to help them conceive naturally.

Once you have successfully conceived, a nutrition therapist or dietitian can help to ensure that the baby develops well by helping you to have optimum nutrition and health during the pregnancy.

Those first few weeks, even before you know you are pregnant, is when the most important structures and organs are being formed in the baby.

Nutritional Therapy should help clients to achieve fertility success by using strategies personalised to their individual and unique circumstances.

First, we clean up the diet.  What I mean by this is that dietitians and therapists will guide clients through a process whereby they systematically eliminate or reduce Harmful Substances that could be interfering with fertility.  For example removing endocrine disruptors, phytoestrogens, pesticides, alcohol and caffeine.   The food safety rules for pregnancy to help women avoid harmful bacteria is also important from the time egg is implanted to prevent miscarriage in the early stage of pregnancy.  So I will also cover this aspect with my clients.

Then dietitians and nutritional therapists will correct nutritional deficiencies through a healthy balanced diet that is rich in those nutrients that help to support healthy sperm and eggs.  For example minerals such as iodine, zinc, iron, and selenium; the right balance of omega-3 and omega-6 essential fatty acids, the right amount of good quality protein (vegetarians or non-vegetarians); B-vitamins like B6, B12, and folate.  A little-known fact is that B-vitamin deficiency in the fathers’ diet can produce sperm look normal but have an increase the risk of causing miscarriages.

Clients should be helped to switch from high glycaemic index foods, the kind of carbs that bound your blood sugar around and throw your metabolism out of whack.  And helped to replace them with low glycaemic index foods, the healthy carbs that help to regulate your metabolism.  Because some of the hormones that are important for fertility need carbs, so if you only just cut out the carbs you might actually be harming your fertility.

For many of my clients, they find that their weight tends to naturally move to a healthy level as they make the changes in stages 1 and 2.  However, for some clients, they need additional support to either lose or gain weight in a way that does not compromise fertility.  Achieving a weight before starting fertility treatment can significantly improve its success.  We need a certain amount of body fat to support healthy hormone levels, good quality sperm and eggs, and mother need it to support the healthy development of the baby during pregnancy.  However, too much body fat increases the number of inflammatory chemicals in the body, causes insulin resistance, and excess oestrogen levels.  These changes reduce fertility and increase the risk of something going wrong during pregnancy.

The process of cleaning up the diet to clear out harmful substances from your body, correcting nutritional deficiencies, and achieving a healthy weight can take about 2-3 months.

So most Dietitians and Nutritional Therapists will recommend that if you are planning to have fertility treatment, you should begin a nutrition program about 3 months before you start treatment.

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What are the chances of getting pregnant? 

Explaining Fertility. 

Fertilisation basics.

An egg is released from the ovary once in a menstrual cycle. If it meets with sperm while it is travelling down the fallopian tube then fertilisation and then pregnancy can start. If a sperm meets an egg at this stage then there is a 33% chance of fertilisation. Fertilised eggs then need to stick to the lining of the womb in order for a pregnancy to start. The egg dies around 20 hours after being released. After that it is not possible to get pregnant until the next egg is released in the next cycle.

So, as you can see, it’s harder than you might think to get pregnant.

Also there’s is a time of the month when you can’t get pregnant. How to work that out though? Well it’s very difficult because it’s all about the menstrual cycle.

How the menstrual cycle works.

Day one of a menstrual cycle is the first day of a period. Periods last for a few days and this varies. Eggs are released from the ovary (ovulation) around half way through the cycle. In order for pregnancy to start, an egg has to be fertilised within a 20 hour time slot when the egg is alive. As sperm can live inside someone for 5 – 7 day a good time for sperm getting into the vagina is from day 9 to 15. Once the egg has died it’s not possible to get pregnant until another egg is released which happens after the next period.

Can Stress affect getting pregnant? 

Stress can interfere with conception. In fact, if you are having a hard time getting pregnant, people may have already said to you, “Just relax and it will happen.” This may feel not helpful at all, however because stress can affect the functioning of the hypothalamus the gland in the brain that regulates your appetite and emotions, as well as the hormones that tell your ovaries to release eggs. If you’re stressed out, you may ovulate later in your cycle or not at all. So if you’re only having sex around day 14, thinking that you’re about to ovulate, you may miss your opportunity to conceive. While stress itself doesn’t cause infertility although if can cause you to miss periods, you won’t be ovulating it is associated with behaviours which can impact on your chances of conceiving – such as eating badly, weight gain (or loss) and insomnia.

Sandra says getting the right Support for your mental health while trying to get pregnant, is as important as getting the right medical help.

2018 Fertility Tips

Well 2018 is here, how many of us have made resolutions? What were they? Get fit, get organised, learn a new hobby, or a healthy lifestyle.

If your trying for a baby let’s start with the healthy lifestyle because research has proven that if you are trying to conceive then it is very important for a woman and a man to maintain a healthy lifestyle and being physically and mentally fit is of utmost importance.

Let’s think about what we eat and when: 

Too many of us are eating too late in the day or when we go to bed at night, eating at the right time is as important as what we eat. It is very important for a woman to have a balanced diet which is full of multi vitamins and minerals. Vitamin C is very important for women who are planning a baby as it significantly increases the pregnancy rate; Protein in your diet is very important for your fertility as it helps to maintain blood sugar balance also include more salads and fruits in your diet.

Keeping fit:

I’m not keen on the gym, but a good way of keeping fit is walking, walking is an ideal pre-conception exercise. It is a great cardiovascular exercise especially if you step to a reasonable pace and it also helps to tone your legs, back and tummy. All these are very important in treating infertility as being fit is the most integral part of your conception plan. So, go for a regular walk in the morning and evening.

Mental health:

Your mental is also very important, finding time out for yourself will allow you to clear you mind and allow you to focus better. Just a tip is to find a quiet area, focus on your breathing for at least 10 to 20 minutes. Try to do it daily, so you give your body a physical and mental rest. Listening to some soothing sounds like sea movement, waterfalls and rain forest noises, can also eliminate stress.

Your lifestyle:

Things we do can all impact on our fertility, but significantly it’s often how stress impacts on our sex drive that increases the time it takes us to conceive. It stands to reason as when we’re stressed we don’t tend to be in the mood for intercourse.

Let’s help ourselves:

Sandra’s tips are to take time to relax, eat healthily, regular walking/exercise and enjoy making love regularly, every two or three days.