Spermatozoa production takes place in the testicular seminiferous tubules and the process is known as spermatogenesis.  At the end of this process, a germ cell generates 4 mature spermatozoa which will survive in the human body for between 62 and 75 days.  The final stage in spermatogenesis, known as spermiogenesis, is a cell differentiation and maturation process consisting of the change from spermatids to spermatozoa.  As can be seen in the picture, the spermatids develop from secondary spermatocites and have already undergone Meiosis I and II division. They have a normal set of chromosomes (haploid) which means that fertilisation of a mature egg can take place. Therefore, and despite the fact that they are immature cells, they can be used in assisted reproduction techniques using ICSI when there are no mature sperm in samples taken from the ejaculate or testicles.

However, the use of spermatids is limited to patients who have no spermatozoa in the ejaculate (azoospermia) and who also have non-obstructive azoospermia due to maturation not continuing beyond that stage. In other words, less than 1% of infertile men can be helped with ICSI using spermatids. To this, we can add the fact that in around 50% of men with non-obstructive azoospermia, it will not be possible to collect neither spermatozoa nor spermatids following a testicular biopsy.

Sperm are generally classified as round (ROSI) or elongated (ELSI), depending on cytoplasmic immaturity. The results when ROSI sperm are used are clinically inefficient and have a pregnancy rate below 3% (Sousa et al., 2002) which means that they are not used in primary infertility treatment. Use of ELSI sperm gives clinical results comparable to those when testicular spermatozoa are used, with fertilisation rates of around 50% and pregnancy rates which come close to 30% (Sousa et al., 2002).

As well as poor clinical results, the safety of carrying out ICSO using immature haploid germ cells is a cause for great concern because of the possible genetic and epigenetic risks for babies born this way. Genomic imprinting takes place primarily during gametogeneisis and it could be incomplete or abnormal in spermatids. Epigenetic abnormalities in germ cells could become evident later on during adult life and/or lay dormant and be transmitted on to the next generation (Nikolettos et al., 2006).

Dr. Jorge TenDirector of the Reproduction Biology Unit at Instituto Bernabeu

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