Tuesday, December 18, 2012

Is IMSI better than ICSI ?

English: Human sperm stained for semen quality...
Human sperm stained for semen quality testing in the clinical laboratory. 

Myth :  IMSI is better than ICSI
Fact :  This is another unproven claim in the field of ART , another logical fallacy !

A sperm is the smallest cell in a human body and an egg the largest. The union of the sperm and the egg brings the genetic material from the male and female together , to allow the creation of a new life.  A normal human semen sample consists of anywhere between 20 – 150 million sperms and not all sperms look alike ! Human sperms are very heterogeneous in their appearance and they have many different shapes. This is in sharp contrast to animals, most of whom have perfect looking sperm.  When we test a sperm sample in the lab, we check the shape ( morphology) of the sperm by staining them and examining them under high magnification. When studying male fertility , researchers were very interested to understand whether the shape of the sperm is in any way connected to the man’s fertility potential. This led to lots of studies aimed at determining what normal human sperm morphology is !

What does a normal (fertile man’s ) sperm look like ?

Actually, no one knows the answer ! A human semen sample consists of sperms which exhibit significant intra (within a single ejaculate) and inter variability (when ejaculates from different fertile men; and even ejaculates from the same fertile man at different times, are compared) in their morphology. Hence , determining the criteria to say whether a sperm is normal in its morphology is very difficult.  In the animal world, fertile animals have sperm which look identical , and this  makes it easy to determine what an abnormally shaped sperm looks like . Infertile animals have sperm which are abnormally shaped. On the other hand , when you compare the ejaculates of two fertile human males , their semen sample contains sperm of widely varying shapes, even though they are both fertile. As a result of this , it is hard to find a benchmark as to whether a particular sperm shape is normal or abnormal ! Hence characterizing the fertility potential of men based on sperm morphology became a hard task.

In earlier times , researchers observed human sperms under the microscope carefully. When they felt that a particular sperm looked very different from the rest,  they considered such a sperm as being abnormally shaped  and recorded such sperm shapes in the form of schematic representation and drawings (which lacked accurate details). By using such an approach , sperms which are not considered to be abnormal are considered as normal ; and normal sperms are thus identified as being normal by default , because of the absence of any gross defect. This method , which is used to classify sperms as being morphologically normal, is called the liberal approach.

Then came the method of identifying sperm morphology using strict criteria or Tygerberg criteria (Kruger’s strict criteria). According to this approach , the morphology of sperms which are found at the internal cervical os (the part of the cervix closest to the uterus) and the sperms which are found attached to the zona pellucida (egg coat) of the human egg are considered to be the gold standards for labeling a sperm as normal. The sperm present in the above places are found to be homogenous in their morphology , although they still exhibited differences in their head shapes. This method of sperm morphology evaluation also included the functional capability of the sperm , because sperms which are able to reach the egg are used as a benchmark for determining what normal sperm morphology is. This means that studying sperm morphology is still not perfect , and there are still several arguments as to the right approach!
Ref :PMID: 20111081

What is the cut-off value for evaluating normal sperm morphology in a semen sample?

The standard textbook for evaluating sperm is the WHO laboratory manual for the examination and processing of human semen. In the first World Health Organization (WHO) manual published in 1980 , the cut-off value for mean normal sperm morphology was 80.5%, with a range of 48.0%–98.0%. In the second WHO manual published in 1987 the cut-off was lowered to 50%. Both the cut-off values were determined based on the liberal approach for sperm morphology evaluation. In the third edition, the value for normal sperm morphology was changed to ≥ 30% morphologically normal spermatozoa , based on strict criteria for sperm morphology evaluation.  In the fourth  edition of the WHO manual , no cut-off value was provided but it stated that 'Multicentre population-based studies utilising the methods of morphology assessment in this manual are now in progress. Data from assisted reproductive technology programmes suggest that, as sperm morphology falls below 15% normal forms using the methods and definitions described in this manual, the fertilisation rate in vitro decreases.' And in the newest ( fifth ) edition the proposed cut-off value for normal sperm morphology is just 4% based on strict criteria for sperm evaluation!

This means a man needs only 4% of normal shaped sperms in his semen to achieve a pregnancy(PMID: 1550422). This evolution of cut-off value for evaluating normal sperm morphology clearly shows the confusion which exists in determining what a normal looking sperm is ; and with the strict criteria which are used now for sperm evaluation , more and more sperms are classified as being abnormal. Actually the decline in the cut-off value for morphologically normal sperm doesn’t mean that the semen quality is declining, it just means that the sperm morphology evaluation criteria have changed ! Sperms which were considered normal in the 1980s are considered abnormal now ( the field of sperm morphology evaluation is very confusing !)

Can a sperm shape predict the quality of DNA it is carrying?

It is tempting to assume that an ugly sperm (morphologically abnormal sperm) carries defective DNA , which is not competent enough to create a beautiful baby. But looks can be deceiving as always. A high amount of morphologically abnormal sperm might indicate poor sperm function but it doesn’t automatically mean that a morphologically normal sperm  is functionally competent , or that the DNA it carries is normal. It also doesn’t mean that sperms with abnormal morphology carry chromosomal defects.
With this background in mind, let’s see what IMSI is !

What is IMSI ?

Intracytoplasmic morphologically selected sperm injection (IMSI) is a new technique which is also called as ‘super ICSI’.  In IMSI technique,  the sperms are magnified 7000X (whereas in ICSI the sperms are magnified only 400X).  Evaluation of sperm morphology at this high magnification enables the embryologist to select sperms which are devoid of any obvious morphological defects. For example any defect in (DNA compaction) is visible in the form of vacuoles in the sperm’s head , and the IMSI technique identifies such ‘defective’ sperm (those are the sperms which are supposed to carry a defect in their DNA !) . Such sperms are excluded from being used for fertilizing the egg. Selecting a sperm which is morphologically perfect from a semen sample high contains a high number of abnormal sperms is thought to help in achieving and maintaining pregnancy via ART technique. This is what the IMSI technique promises us.
Isn’t it logical to use IMSI in place of ICSI ?

Theoretically , it appears logical to use IMSI , but this is not true in real life for a variety of reasons :

1)    Just because a sperm is morphologically normal doesn’t guarantee that its DNA is normal. Similarly, just because the sperm is morphologically abnormal doesn’t mean that its DNA integrity is compromised and that it will fail to give rise to a healthy baby. You can’t judge a book by its cover !

2)    Sperm DNA integrity is not as important as we think. It is a well-established fact that sperm contribute only 10% to embryo aneuploidy ( abnormal chromosomal content) ; and that 90% of aneuploidy defects in embryos arise as a result of abnormal eggs. It has also been proven that the sperm’s DNA is extensively repaired (any defects in sperm DNA integrity is set right) and remodeled by the egg’s ‘error correction’ machinery after fertilization(PMID: 21546611)(PMID: 22541549)(PMID: 17978187). Although it is surprising to know that such a mechanism exists , it is very logical from nature’s point of view. Nature provide an egg with much more power to control the embryo’s development ! A woman is the one who is going to carry the baby to term and take care of the baby until it becomes independent. This is perhaps why nature has given the egg an upper hand in deciding a baby’s developmental fate ! An egg from a young woman can efficiently repair damaged DNA of a sperm ! So when the egg is young , even poor sperms can give rise to healthy babies.

3)    There is no solid scientific proof to say IMSI is better than ICSI! There are no well-controlled randomized studies to prove this claim.

IMSI is not a magical solution for couples with multiple IVF failures, with poor sperm morphology or with recurrent pregnancy loss. In fact, abnormal sperm morphology cannot even be the only indication for performing ICSI because men labeled as having abnormal sperm morphology are able to father a child without any medical help many a time ! Today, a man who has 96% abnormal sperms and only 4% normal sperms is still considered to be fertile . If your husband has only 2% normal sperm morphology ,then should he be labeled as infertile ? My logical answer will be a ‘NO’. Can 96% abnormal sperm and 98% abnormal sperm really make a difference ?

 You can email Manju at [email protected]

Her blog is at www.myselfishgenes.blogspot.com
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