Tuesday, August 07, 2012

All about eggs !

Human oocyte with surrounding granulosa cells

We all know that an older woman's eggs don't perform as well in the IVF lab as a young woman's do . This is frustrating for both doctors and for patients . It is especially true when the older woman grows a considerable number of eggs . She feels ( quite logically !) that because she has grown lots of eggs, she should get lots of good-quality embryos – and have as good a chance of having a baby as a younger woman. After all, doesn’t the fact that she had a good ovarian response means she has good ovarian reserve – and a biological clock which has a lot of time left on it ?

Unfortunately, this is not always true . If IVF specialists were allowed to select our patients, this is what our order of preference would be . Our first preference would be young women with lots of eggs ! We'd then like to deal with young women, even if they have fewer eggs, because often these eggs are of much better quality and have a much better rate of fertilisation , as compared to older women with a large number of eggs. This might seem paradoxical , but often the reason older women have a large number of eggs is because they have occult polycystic ovarian disease . They produce a large quantity of eggs, but often their quality leaves a lot to be desired . Of course , the prognosis is worst in older women with few eggs - they take a beating in both egg quantity and quality as well.

The biggest problem with eggs is that when we take them out of the ovarian follicles and look at them in the lab , they appear to be spherical blobs , which just lie there , doing nothing. This is in marked contrast to sperm, which appear to be full of life ! However, even though the sperm seem so active, it's actually the eggs which plays a far more important role in embryo development . However, we just don't have the tools to be able to check the competence of the egg , because the cytoplasm looks like a homogenous blob . We have no ways of testing the mitochondrial energy competence of the egg , which is why all eggs - both the good and the bad ones - look exactly the same . It's only when we do a fertilisation check the next day , do we know which the bad ones are - the ones which fail to fertilise. However, even if they do fertilize , it's only when we check for cleavage on day two that we can determine whether eggs have given rise to good-quality embryos.

You can only judge the quality of an egg based on its functional  competence - it's ability to create a good quality embryo ! Since we still cannot predict this proactively , we learn about egg quality only after 48 hours have gone , when we check the quality of the embryo in the lab . A poor quality egg will produce a poor quality embryo , with irregular and slow cell division, and lots of fragments .This is because even though the eggs looks perfect, the mitochondria within its X cytoplasm just do not have enough energy to be able to drive cell division . This is a very frustrating problem , and it's possible that in the future cytoplasmic donation may help to solve some of these issues . For now , most of these patients are best helped by using donor eggs, if they are willing to explore this option.

Remember that the only good egg is one which becomes an embryo – and the only good embryo is one which become a baby - but we can find this out only in retrospect ! A  useful way of measuring the efficiency of eggs would be to calculate the live birth per oocyte retrieved, in order to assess the efficacy of oocyte utilization during IVF treatment. This is called the oocyte utilisation rate. The 2 major variables which affect this are:  the age of the woman; and her ovarian response/ yield of eggs. A recent paper in Human Reproduction by Dr Stoop and his team ( Reproductive potential of a metaphase II oocyte retrieved after ovarian stimulation: an analysis of 23354 ICSI cycles) found that between the ages of 23 and 37, the oocyte utilization rate depends largely upon ovarian response, and to a much lesser extent on age. In contrast, from the age of 38 onwards, the utilization rates depends largely on age and to a much lesser extent on ovarian response.

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2 comments:

  1. Very informative post Dr! I learned a lot from this.

    Do cytoplasmic donation (mitochondrial donation!) alone can solve the problem of older women? It can be a boon for women who have mitochondrial DNA problem but I don't think it can be a cure for older women (40+). Eventhough if a older woman is provided cytoplasmic donation she can produce good quality embryos but not a genetically competent embryo which can develop into a baby - am I correct?

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  2. Anonymous3:40 PM

    I have been a regular 28days menstrual cycle but in the past 2months, my periods have been 32days apart. I am 40years old and have been having fertility problems for 12years. Please what can be responsible for the increase in length of days?

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