Sex chromosomal anomalies, ICSI and ROSNI -LONG

Dr Jim Cummins cummins at POSSUM.MURDOCH.EDU.AU
Tue Oct 24 02:56:55 EST 1995

Concerning the round spermatid injection pregnancies reported earlier this
year by Sofikitis et al, there are two additional publications.   Fishel et
al (Lancet 345: 1641-2, June 24, 1995) report an ongoing pregnancy in
Nottingham, UK.  Tesarik et al (New England J Medicine 333: 325, August
1995) report the birth of a boy and another healthy ongoing pregnancy.

The French results prompted intense debate and the leader of the team
(Jacques Testart) has been attacked by Axel Kahn from the Cochin Institute
of Molecular Genetics in Paris with the statement that ROSNI constitutes
"the biggest ethical problem since the development of medially assisted
procreation" (Nature 28 September 1995: 277).   Kahn also argues that the
procedure contravenes the 1947 Nuremburg code of medical ethics starting
that experiments on humans should be preceded by animal experimentation.
"For the first time since the Nuremburg code was drafted, we have embarked
on human experiments aimed at creating humans without any great urgency for
such experiments".

The French national bioethics consultative committee last year advised that
ICSI (ROSNI hadn't yet hit the scene) should only be allowed after
comprehensive animal testing.  This was dismissed as irrelevant by Testart,
and his comment is accurate to the point that no good animal models exist
for spermatogenic arrest: the birth of live rabbits and mice following
spermatid injection tell us nothing about the genetic background or
implications for infertile men.

Ironically, in 1986 Testart called for a moratorium on embryo research and
on preimplantation genetic diagnosis.   Given that ICSI embryos from
severely infertile men do indeed have a higher risk of carrying sex
chromosomal anomalies as well as cystic fibrosis mutations (associated with
congenital absence of the vas deferens) one wonders whether he will
reconsider this position.  It is clear that we need to increase the rigour
of genetic screening for infertile men, and I for one think that
preimplantation genetic diagnosis is ethically essential if there is a
defined risk to the embryo.
Cummins, J.M., and Jequier, A.M. (1994). Treating male infertility needs
more clinical andrology, not less. Human Reproduction., 9, 1214-1219.

Cummins, J.M., and Jequier, A.M. (1995b). Concerns and recommendations for
ICSI treatment. Human Reprod., 10 Suppl. 1, "Andrology in the Nineties", In

de Kretser, D.M. (1995). The potential of intracytoplasmic sperm injection
(ICSI) to transmit genetic defects causing male infertility. Reproduction,
Fertility, & Development., 7, 137-142.

Martin, and Du, P.R. (1993). Causes hormonales de sterilite masculine et
leur traitement. Schweiz Rundsch Med Prax., 82, 934-7.

Martin, R.H. (1993). Detection of genetic damage in human sperm. Reprod
Toxicol., ,

Martin-Dupan, R.C., Sakkas, D., Stalberg, A., Bianchi, P.G., Deboccard, G.,
and Campana, A. (1995). Treatment of male infertility by intracytoplasmic
sperm injection - a critical evaluation [German]. Schweizerische
Medizinische Wochenschrift. Journal Suisse de Medecine., 125, 1483-1488.

Moosani, N., Pattinson, H.A., Carter, M.D., Cox, D.M., Rademaker, A.W., and
Martin, R.H. (1995). Chromosomal analysis of sperm from men with idiopathic
infertility using sperm karyotyping and fluorescence in situ hybridization.
Fertility & Sterility., 64, 811-817.

Sofikitis, N., Miyagawa, I., Sharlip, I., Hellstrom, W., Mekras, G., and
Mastelou, E. (1995). Human pregnancies achieved by intra-ooplasmic
injections of round spermatid (RS) nuclei isolated from testicular tissue
of azoospermic men. Las Vegas, Nevada: AUA Meeting Abstracts/PRISM
Productions, 0616.

Van der Zwalmen, P., Lejeune, B., Nijs, M., Segalbertin, G., Van Damme, B.,
and Schoysman, R. (1995). Fertilization of an oocyte microinseminated with
a spermatid in an in-vitro fertilization programme. Human Reproduction.,
10, 502-503.

Vogt, P., Chandley, A.C., Hargreave, T.B., Keil, R., Ma, K., and Sharkey,
A. (1992). Microdeletions in interval 6 of the Y chromosome of males with
idiopathic sterility point to disruption of AZF, a human spermatogenesis
gene. Hum Genet., 89, 491-6.

Vogt, P.H. (1995). Genetic aspects of artificial fertilization. Human
Reproduction., In Press,

Zuffardi, O., and Tiepolo, L. (1982). Frequencies and types of chromosome
abnormalities associated with human male infertility. In P. G. Crosignani,
& B. L. Rubin (ed), Genetic Control of Gamete Production and Function.
London, Academic Press, pp 261-273.

Jim "Spermatology rules o~ o~ o~ o~" Cummins

Associate Professor in Veterinary Anatomy
Murdoch University, Western Australia 6150
Tel +61-9-360 2668, Fax +61-9-310 4144
E mail <cummins at>
URL <>
The Penultimate Law "All general statements are false."

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