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When an IVF cycle fails , patients want to know what they need to do differently next time. Was there a problem with the eggs ? or with the sperm ? or with the uterus ? While it can be very hard to pinpoint the problem precisely , it's important to think through these questions intelligently.

When an IVF cycle fails , patients want to know what they need to do differently next time. Was there a problem with the eggs ? or with the sperm ? or with the uterus ? While it can be very hard to pinpoint the problem precisely , it's important to think through these questions intelligently.

In the vast majority of patients, if fertilization has been achieved, there is very little role which the sperm have to play. In one sense , sperm are just missiles which carry the husband's DNA ; and once they have fertilized the eggs, there is not much which they contribute to further embryonic development. This is why pregnancy rates even for men with extremely abnormal sperm are very good when we use techniques such as ICSI. If the sperm DNA fragmentation test is abnormal, this causes a lot of anxiety and many doctors will blame a high level of sperm DNA fragmentation for IVF failure , claiming that it's the fragmented sperm DNA which is causing genetic abnormalities in the embryos, as a result of which they fail to implant, but this is not a hypothesis I subscribe to, because there is no evidence to support it.

Evaluating the endometrium in fairly easy , because if it is trilaminar and more than 8 mm thick on an ultrasound scan , we usually assume that it is ripe and receptive. Admittedly, this is a fairly crude test, but one which seems to work well in clinical practice. The newer endometrial function tests ( such as testing for integrins ) are experimental and clinically unproven.

The egg is still the biggest mystery of all, and is the cause for a lot of unexplained IVF failures in my opinion , simply because it is such an important role in embryonic development. We still do not have markers to assess the integrity of either the egg DNA or its mitochondria ( which provide the energy to drive embryo cleavage ) .

In a mouse lab, it would be fairly simple to identify where the problem arises, by doing cross testing - fertilizing donor eggs with the sperm ; and the eggs with donor sperm, to see which works better. However, since this is not possible in the human setting, we often have to use rules of thumb ( based on experience and intuition) when we advice our patients. Patients need to understand that the quality of our advice is often limited by the fact that the technology is still imperfect ; and we don't have answers to these basic questions because we still don't have useful egg, sperm and endometrial function tests.

However , it's not for lack of trying. It's extremely hard to develop these tests. For example, in the past there was a zona free hamster egg test developed to check sperm function . This was extremely popular ( and very expensive) , but soon fell out of favor when clinicians realized that there was very little correlation between the test results and what actually happened in clinical practice. This seems to be true for most of the advanced reproductive technology tests available today, whether they are used for checking sperm DNA fragmentation or endometrial function. They become popular because they're actively propagated by the inventors , who publish their results in the most popular medical journals and give a number of lectures on the conference circuit, as they are talking about something which is " new and improved" . Since these are frustrating problems , most doctors happy to try out these new tests in the hope that they will finally provide an answer to questions which we've been grappling with for many years. However, over time we realized that these tests have many deficiencies and are not very useful when applied to the individual patient , even though they may provide information which may be statistically useful when applied to groups of patients. The tests then stop being used, until a new generation of cleverer researchers comes up with newer tests.

This is why , when an IVF cycle fails , you may often gets conflicting information from the doctor , because he himself may not be very sure as to exactly where the defect lies. Patients at the end of the spectrum of normality are fairly easy to cancel. Thus, for example , if you have a persistent thin uterine lining which is less than 3 mm, it's easy for the doctor to tell you that your embryos did not implant because of poor endometrial receptivity, and he can advise surrogacy. However , it's possible that there is a subset of patients who have a beautiful looking endometrium on the ultrasound scan , but whose endometrium doesn't function properly , which is why the embryos do not implant. However, we still don't have the tests to be able to identify these patients prospectively , which is why we often need to continue using a trial and error method in the IVF clinic, causing frustration both to patients and to doctors.

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