Immature sperm and ICSI:Maturation arrest what stage?

From: Androlog Mail (androlog)
Date: Tue Feb 17 1998 - 09:33:29 CST

Androlog Mail:

Dr Cummins writes.

> ........... from discussions at a Serono
> Symposium last week in Paris it is becoming increasing apparent that:
> (a) Nobody can distinguish human round spermatids from
> spermatogonia or even lymphocytes or Sertoli cell nuclei using current
> ICSI systems, at least not without resorting to phase contrast
> microscopy (when the acrosomal vesicle can be identified). If you
> can't be sure what you are microinjecting it's unethical
> even to offer it!
> (b) If a man has meiosis proceeding to round spermatids then he will
> almost certainly have elongating late spermatids or even maturing
> sperm. That's because the main blockage in spermatogenic failure is
> pre-meiotic. It's just a matter of hunting for them. This may be hard
> on small clinics but some groups reported searching for up to 5 hours
> through testicular macerates.

It appears that post meiotic spermatid arrest can occur in animals (rats)
after induced intratesticular testosterone suppression (McLachlan et al.,
Biol Reprod '94). One might argue that these rats are capable of producing
spermatozoa, therefore are able to complete meiosis and that is the reason
why we can stop the spermatogenesis in the spermatid stage after this
induced testosterone withdrawal. Spermatogenic arrest otherwise would occur
in a pre- meiotic stage. Certainly we agree that the main blockage in
spermatogenic failure is pre- meiotic. But why isn't there a possibility
that some of the spermatocytes escape this premeiotic blockage due to
microenvironmental factors (genetic, hormonal, sertoli cell, etc) but at the
same time cannot undergo spermiogenesis? Taking the above example of the
rats, one can't establish with certainty that there aren't some
intratesticular processes or factors that could stop the spermatogenesis in
the spermatid stage! From our experience at NYU some of the azoospermic
patients presented spermatids in their testicular biopsies and ejaculates
even though we never found spermatozoa or elongated spermatids (in the past
or in the present) after meticulous and time consuming (up to six hours X 2)
searching by two different experienced embryologists. These results were
confirmed histologically and by electron-microscopy of accompanying tissue
blocks. Additionally fluorescent in situ hybridization proved the haploid
status of these round cells. Although it is still theoretically possible
that there were some foci of complete spermatogenesis, even in our facility
we were unable to find those rare elongated spermatids or spermatozoa
described by Dr. Cummins, despite exhaustive tissue dissection and search.

Are these cells easy to identify under inverted microscope and are they
capable to fertilize an ovocyte with the same ease as spermatozoa do?
Certainly not!!

Recently we published an article giving some simple tips for the proper
reproducible identification of the round spermatid (Angelopoulos et al., Hum
Reprod '97). Besides the reliable identification of the round spermatid
other potential concerns with the use of round spermatid injection have been
raised by several authors (Fishel et al., Hum Reprod '96; Tesarik and
Mendoza., Mol Hum Reprod '96). There are nonetheless some additional
problems when dealing with the spermatids of patients who do not present any
spermatozoa in their testicular biopsies. These problems are mainly the
atypical morphology and the viability of those cells.

We are not advocating the routine use of round cells for ICSI but continued
prudent and responsible research in this area. It wasn't too long ago that
the mere thought of ICSI seemed far fetched. Let us maintain our scientific
curiosity in this very challenging subject.


Theofanis Angelopoulos, MD Research Post Doctoral Fellow Department of
Reproductive Endocrinology, NYU
Andrew R. McCullough, MD Department of Urology NYU
Lewis Krey, PhD Chief of Andrology and Reproductive Endocrinology
Jamie Grifo, MD, PhD Chief, Department of Reproductive Endocrinology

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