Thursday, November 06, 2014

Total fertilization failure after ICSI



My last post discussed the distressing problem of total failed fertilization after IVF.  As I explained, failed fertilization after IVF is usually because of a sperm problem. By contrast, total fertilization failure after ICSI ( which is much less common) is usually very rarely because of a sperm problem.

This is not very intuitive – after all, since 50% of the DNA comes from the sperm, it’s logical to expect that 50% of fertilization failure after ICSI should be because of sperm problems ! Lots of patients believe this, and so do many IVF specialists. Another reason for this misconception is because ICSI is usually done for infertile men , who have a low sperm count, or poor sperm motility. Many of these men have abnormal sperm DNA, so it makes logical sense for both doctor and patient to conclude that failed fertilization is because of the abnormal sperm DNA in these men, which prevents the sperm from fertilising the eggs.  This is why a lot of doctors advise these men to consider using donor sperm.

However, this is bad advise. The truth is that once we’ve injected the sperm inside the egg, the embryologist has done most of the sperm’s work for it. The rest of the fertilization process is driven by energy which is provided by the powerhouses of the cells – the mitochondria, which are present in the cytoplasm of the egg. The sperm has very little role to play after the ICSI has been performed.

This has been proven by doing ICSI for these men using donor eggs. The fertilization rate is completely normal when this is done !
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Another reason why patients find it hard to understand this concept is because their eggs look completely normal. The truth is that most eggs look exactly the same ! They are basically simple spheres, and there is no way an embryologist can distinguish a normal egg from an abnormal one in the IVF lab.

The problem is that even though an egg maybe functionally incompetent, it looks anatomically perfect – and we have still not developed have any egg function tests to check the fertilising ability of the egg as yet. ( Note that ovarian function tests, which check for ovarian reserve, such as AFC and AMH levels are very crude, and don’t provide any information about the functional competence of the individual egg, which is a microscopic structure).

Failed fertilization comes as a shock – for both patient and doctor. Sadly, it’s one of those things which we just can't predict . It’s only when the embryologist does the fertilization check 16 hours after ICSI that he finds out ( to his dismay) that the eggs have not fertilized, and do not have any pronuclei.

Sometimes the problem could be because of the lab. Thus, incubator malfunction can damage the eggs; as can an infection in the culture medium. A clumsy embryologist can also damage and kill all the eggs when doing ICSI. However , these problems are very rare in a good IVF clinic.

Remember that failed fertilization after ICSI is usually because of an egg problem. This is why it is seen more often in older women; those with poor ovarian reserve; and those with a poor ovarian response. The best solution for this is to use donor eggs.

The major exception is the very rare man with globozoospermia. In these men, the absent acrosome means that their sperm cannot fertilise the eggs even after ICSI , unless they are treated with a calcium ionophore. This is an easy diagnosis to miss, but also one which is very easy to make if the sperm are stained and their morphology checked carefully in a good lab.

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