Monday, July 25, 2011

Is it the egg ? or the sperm ?

Whenever an IVF cycle fails, the commonest question patients ask is - was there a problem with the eggs ? or with the sperm ?

Logically, one would expect the answer to be 50-50 - after all, both are gametes which contribute the 50% of the DNA to the embryo.

In fact, this is one of the reason there are so many tests for testing sperm "quality" - ranging from the zona free hamster egg penetration assay ( which is now obsolete) to the newer sperm DNA fragmentation tests ( which are very fashionable and popular right now, but will also soon get relegated to the dustbin).

However, these tests are useless in clinical practise.

Why do I say so ?

Let's consider a couple who does ICSI treatment for a low sperm count, and gets poor quality embryos . They are disheartened and upset, so they get a second opinion from another "expert"

This doctor does additional tests to show how much of an expert he is, and how much better he is than the original doctor ( who did not have the sense to do these advanced tests, because he is not as well-informed ! ) These tests are understandably very expensive and esoteric ( after all, they are not done frequently, because they are not very useful, which is why the lab charges more to do them !)

In many of these men, the lab will find the sperm has high DNA fragmentation. The expert says - Aha ! this is the reason for your poor quality embryos, which the earlier doctor missed !

This is highly logical and makes sense to the patient - after all, if the sperm have fragmented DNA, it's quite logical to expect them to make fragmented poor quality embryos !

The husband starts to beat up on himself; and the doctor congrats himself on making the right diagnosis and pinpointing the " problem". He then suggests that they need to use IMSI to solve the problem- even though the success rates with IMSI are lower than with ICSI !

However , in reality these new sperm function tests are often very unreliable , because they have not yet been adequately researched . They have not been standardised - and lots of fertile men have sperm with high DNA fragmentation levels ( and are blissfully unaware of this "defect" in their sperm because they have enough sense not to go to a doctor !)

New is not always better ! In reality, poor sperm do not contribute to poor quality embryos !

Just look at the image of the sperms and the egg above . The sperms are tiny, which means the sperm which fertilises the eggs has very little role to play in embryo cleavage after fertilisation has occurred ! The reason for fragmented embryos is usually an egg cytoplasm problem, because the mitochondria in the egg cannot prove enough energy to drive cell division.

What about the high DNA fragmentation report ? As I said, many fertile men have high DNA fragmentation rates - this does not correlate well with even in vivo fertility at all !

In theory ( or in a mouse lab), the right way to determine if the reason for the poor quality embryos lies with the egg or with the sperm could be performed by doing cross-testing. The wife's eggs could be fertilised with donor sperm; and donor eggs could be fertilised with the husband's sperm. The embryos could then be grown in the same incubator, to see which ones divide well, and which ones start to fragment.

However, it's extremely difficult to do this in real life, which is why we tell patients that if we have poor quality embryos after ICSI, 9 times out of 10 the problem ( based on years of experience) , the problem is with the egg and not the sperm !
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