Sunday, February 21, 2010

The sperm or the egg ?

Oogamy in animals: small, motile sperm on the ...Image via Wikipedia

One of the biggest problems in an IVF clinic is the patient with poor quality embryos. The question we then need to answer is - are the poor quality embryos because of a sperm problem ? or an egg problem ?

In a mouse lab , it would be very easy to answer whether the problem is with the egg or the sperm scientifically ! We would do crossover testing, using donor egg plus husband's sperm versus donor sperm plus wife's eggs in the same incubator. This would allow us to pinpoint what the problem is easily. Unfortunately, it's not practical to do this in a human IVF clinic !

Step number one should be to rule out a lab problem first ! Are the other patients' embryos of good quality ? Or are everyone's embryos fragmenting ? This suggests a lab problem - for example, because of a bad batch of IVF culture medium. While this phenomenon has been well documented, it is very hard for patients to get accurate information about this because labs are very unlikely to accept the fact that they have had a global problem. Unfortunately, this is often something which is still covered up.

If a lab problem has been ironed out, then we need to drill a little deeper. If IVF has been done, and the problem is total failure of fertilisation, then this usually means this is because of a sperm problem - the sperm are functionally incompetent and are not capable of fertilising the eggs. Sadly, it is often not possible to identify this problem prior to treatment and the only reliable ( and admittedly very expensive !) way to make the diagnosis of sperm dysfunction is by doing an IVF treatment cycle. The good news is that it can be corrected by doing ICSI in the next treatment cycle.

What happens if there is a low fertilisation rate after ICSI ? We need to analyse the problem closely. Have a lot of the eggs been damaged or killed ? If so, then this suggests a technical problem, either because of embryologist inexpertise or micromanipulator technical malfunction. However , if the embryologist is an expert, and the eggs have not been damaged because of technical issues, then poor fertilisation after ICSI usually suggests an egg problem. This is because once the sperm have been delivered into the egg with ICSI, their job is mostly done. It is the egg which is then responsible for the rest of the dramatic events which unfold. This is because it is the egg cytoplasm which contains the mitochondria , the energy powerhouse of the cell, which are responsible for powering the process of fertilisation.

What about problems on Day 2 ? Embryo problems at this stage could present in one of two ways.
1. Poor quality ( low grade) embryos , with lots of fragmentation
2. Embryos which have arrested ( failed to develop beyond a particular stage).
Often both these problems will go hand in hand.

In these cases as well , the problem is usually an egg problem because it is the mitochondria which provide the energy needed for cleavage. Unfortunately, there is no test available for this; and this could happen in young patients , with normal ovarian reserve and normal FSH, AMH levels and normal antral follicle counts. This is because the clinical tests for ovarian reserve only estimate egg quality and quantity and cannot allow us to assess mitochondrial function in the eggs.

This means that if we start with good looking eggs and end up with poor quality embryos, the problem is either in the lab; or with the eggs. Often the diagnosis is one of exclusion. Does the problem recur in another cycle ? Does the problem recur in another lab ? If so, then we can confidently say we are dealing with an egg problem - though we can never prove this.

What is a practical plan of action for these heart-sink patients ? The next step is to repeat the IVF cycle with a more aggressive superovulation protocol. If the problem persists, then it's a good idea to try another IVF lab. If the problem recurs, then the best option is to consider using donor eggs.

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1 comment:

  1. Consequently when it is established that poor ova quality is involved, recipients are encouraged to consider human egg donation to conceive.

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