dependent on reproductive technologies, an Australian reproductive biologist says we must remain vigilant to avoid the spread of

genetic defects.

Expert calls for vigilance on IVF technology
By Anna Salleh for ABC Science Online
Posted 4 hours 30 minutes ago


As humans become more dependent on reproductive technologies, an Australian reproductive biologist says we must remain vigilant to avoid the spread of genetic defects.

The warning comes in an editorial by Professor John Aitken, of the University of Newcastle, in the current issue of Expert Review of Obstetrics and Gynecology.

"People shouldn't be too confident that just because the baby looks normal there is no damage there that won't appear later in life," he said.

"People underestimate how much genetic damage they're passing onto the embryos."
Professor Aitkin says one in every 35 babies born in Australia are a result of IVF.

"In some countries it's more like one in 20 and there are models that predict it will be one in 10 before too long," he said.

Professor Aitken says because IVF allows infertile men to reproduce, the more we use it the more it will be needed in the future.

"So we better make sure it's safe because a large proportion of the population will be generated in this way," he said.


Ageing sperm

Professor Aitken says a number of factors are known, or suspected, to cause genetic damage to sperm that do not necessarily cause defects obvious at birth.

For example, Professor Aitken says the sperm of ageing males is thought to contribute to conditions such as autism, schizophrenia and epilepsy.

He says there is strong evidence linking sperm DNA damage to smoking, which can lead to the development of childhood cancers.

Epigenetic changes to sperm DNA that can affect fertility through several generations have also been reported.

For example, several recent papers have shown that infertile men have a dramatically altered DNA methylation profile.Screening and monitoring

Professor Aitken says genetic problems mean it is important that reproductive clinics do a good job at screening sperm samples for genetic damage.

He is presenting the latest evidence on one screening technique he is developing with biotech company nuGEN at the Australian Research Council's Graeme Clark Research Outcomes Forum in Canberra next week.

But Professor Aitken says long-term monitoring of children born through IVF and other reproductive technologies is also essential, because such techniques can not pick up epigenetic damage.

"There are all kinds of things that can and could still go wrong," he said.

While he says IVF children are being monitored, he is concerned about complacency among clinics who celebrate their ability to produce normal looking babies from sperm with high levels of DNA damage.

IVF defended

Professor Michael Chapman of the Fertility Society of Australia, who also works for IVF Australia, says genetic damage is considered by IVF clinics.

"They're concerns that are shared within the IVF profession," he said.

Professor Chapman says one rare epigenetic disease has shown up in IVF children, at a rate of one in 1,500 versus one in 5,000 in the general population.

But he says Professor Aitken's "provocative" article overstates the problem since in the 20 years that IVF has been around, few long-term problems have arisen, despite thousands of children being monitored.

"I'm sure that if something starts to turn up, it will jump out at us," he said.

Sandra Hill, chief executive officer of ACCESS Australia, a group led by patients seeking IVF treatment, is confident that IVF is well-monitored, and she agrees this should continue.

But she says many of the concerns raised by Professor Aitken also apply to natural conception and she thinks the use of IVF should not be singled out.

She says it could be useful to educate men in general about the concerns raised by Professor Aitken - especially the need for men to have children before they get too old.

Professor Aitken says this may be so, but IVF still presents a unique challenge.

"With IVF you are facilitating the fertilisation of eggs with sperm that would otherwise be unsuccessful," he said.

Professor Aitken also says the rate of birth defects in IVF children are up to twice that of normally-conceived children, although he expects that to improve as techniques improve.

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Professor R. John Aitken ScD, FRSE
Director, ARC Centre of Excellence in Biotechnology and Development,
Professor of Biological Sciences,
School of Environmental and Life Sciences,
University of Newcastle
Callaghan
NSW 2308.

E mail: jaitken@mail.newcastle.edu.au
Tel: (+61 2) 4921 6143
Mobile: 0414 667 878
Fax: (+61 2) 4921 6308



John Aitken is currently Director of ARC Centre of Excellence in Biotechnology and Development and Professor of Biological Sciences at the University of Newcastle, NSW. His research interests focus on the cell biology of male germ cells, particularly the cell biology of human spermatozoa and the mechanisms regulating the formation and recruitment of primordial follicles within the ovary.





Qualifications: BSc (Special Hons) University of London

MSc University of Wales

PhD University of Cambridge

ScD University of Cambridge

Fellow of the Royal Society of Edinburgh



Positions:

1982-1987 Senior Scientist, Medical Research Council Reproductive Biology Unit, University of Edinburgh.

1987-1998 Special Appointment, Professorial Grade, Medical Research Council Reproductive Biology Unit, University of Edinburgh

1992- Honorary Professorship, Department of Obstetrics and Gynaecology, University of Edinburgh

1998- Professor of Biological Sciences, Faculty of Science and IT, University of Newcastle, NSW.

1998 Director of the Centre for Life Sciences, University of Newcastle, NSW.

2003 Director of the ARC Centre of Excellence in Biotechnology and Development


Honours:

1984 Honorary Fellow of the Faculty of Medicine,University of Edinburgh.

1985 Ayerst Lecturer, Pacific Coast Fertility Society,Caesar's Palace, Las Vegas.

1985 Ortho-McMaster Lecturer, McMaster University Medical Centre, Hamilton, Canada.

1985 Convener, Chairman and Editor, WHO symposium on The Zona-free Hamster Oocyte Penetration test in the Diagnosis of Male Infertility, Boston, Massachusetts, USA.

1986 The Walpole Prize, Society for the Study of Fertility, United Kingdom

1987 The Walpole Prize, Society for the Study of Fertility, United Kingdom

1989 1989 University of Catania Prize, Scientific Committee, Faculty of Medicine.

University of Catania, Italy.

1990 The Puvan Memorial Lecture. Opening Address of the 27th Malaysian Congress of Obstetrics and Gynaecology.

1990 The Jennifer Hallum Memorial Lecture. Royal College of Obstetricians and Gynaecologists,

1992 Honorary Professorship, Department of Obstetrics and Gynaecology, Faculty of Medicine, University of Edinburgh.

1994 Opening Address Thaddeus Mann Symposium. Seventh International Congress of Spermatology, Cairns, Australia.

1994 American Fertility Society State-of-the-Art Lecture. Annual Meeting, San Antonio, Texas,

1995 Elected a Fellow of the Royal Society of Edinburgh

1997 Plenary Lecture European Society of Human Reproduction and Embryology Congress 1997. Edinburgh Conference Centre.

1997 The Bruce Stewart Memorial Lecture 1997 American Urology Society Lecture, American Society for Reproductive Medicine, Cincinnati, OH, USA.

1998 The 1998 Amoroso Lecture. The human spermatozoon-a cell in crisis? Society for the Study of Fertility, Annual Meeting, University of Glasgow, UK

1998 Society for Male Reproduction/Urology Prize Paper. 16th World Congress on Fertility and Sterility/54th Annual Meeting of the American Society for Reproductive Medicine, San Francisco

1999 M.J. Edwards Lecture. Australian Birth Defects Society. University of Sydney.

2000 Best Poster Award. Combined meeting of the Society for Free Radical Research on Oxidants, Antioxidants and Nutrition and ComBio 2000. Wellington, New Zealand.

2002 Plenary Lecture, World Congress on Human Reproduction, Montreal, Canada

2003 Lloyd Cox memorial Lecture, University of Adelaide.

2004 The Founders Lecture, Society for the Study of Reproduction, Annual Meeting, Sydney.





Relevant Employment History:

1987-98 Special Appointment -Professorial Level

MRC Reproductive Biology Unit, University of Edinburgh,



1992-present Honorary Professorship, Faculty of Medicine, University of Edinburgh.



1982-1987 Senior Scientist

MRC Reproductive Biology Unit, University of Edinburgh.



1977-1982 Research Scientist Grade 1

MRC Reproductive Biology Unit, University of Edinburgh.



1976-1977 Chargé de Recherche

Faculte de Medicine, Universitie de Bordeaux.



1975-1976 Consultant Scientist

Human Reproduction Programme, World Health Organisation, Geneva.



1973-1975 MRC Post-Doctoral Fellowship

Department of Genetics, University of Edinburgh.



Publications and Presentations:
More than 350 peer review publications and more than 300 presentations at national and international meetings. Examples:



Angell, R.R., Aitken, R.J., Van Look, P.F.A., Lumsden, M.A. & Templeton, A.A. (1983) Chromosome abnormalities in human embryos after in vitro fertilization. Nature, 303, 336-338.



Aitken, R.J. & Clarkson, J.S. (1987) Cellular basis of defective sperm function and its association with the genesis of reactive oxygen species by human spermatozoa. Journal of Reproduction and Fertility, 83, 459-469.

This article was awarded the Walpole Memorial Prize and Lecture by the Society for the Study of Fertility



Henderson, C.J., Hulme, M.J. & Aitken, R.J. (1988) Contraceptive potential of antibodies to the zona pellucida. Journal of Reproduction and Fertility, 8, 325-343.

This article was awarded the Walpole Memorial Prize and Lecture by the Society for the Study of Fertility



Nasr-Esfahani, M, Aitken, R.J. & Johnson, M.H. (1990) The measurement of H2O2 levels in preimplantation embryos from blocking and non-blocking strains of mice. Development, 109, 501-507.



Aitken, R. J., M. Paterson, H. Fisher, D.W. Buckingham & Van Duin, M. (1995) Redox regulation of tyrosine phosphorylation in human spermatozoa is involved in the control of human sperm function. Journal of Cell Science, 108, 2017-2025.





Aitken, R. J., Buckingham, D.W. & Irvine, D.S. (1996) The extragenomic action of progesterone on human spermatozoa: evidence for a ubiquitous response that is rapidly down-regulated. Endocrinology 137, 3999-4009.



Twigg, J., Fulton, N., Gomez, E, Irvine D. S. & Aitken, R. J. (1998) Analysis of the impact of intracellular reactive oxygen species generation on the structural and functional integrity of human spermatozoa: lipid peroxidation, DNA fragmentation and effectiveness of antioxidants. Human Reproduction 13, 1429-1437. Featured as an ‘Outstanding Article’ by the journal



Aitken, R. J., Harkiss, D., Knox, W., Paterson, M. and Irvine, D. S. (1998) A novel signal transduction cascade in capacitating human spermatozoa characterized by a redox-regulated, cAMP-mediated induction of tyrosine phosphorylation. Journal of Cell Science 111, 645-656.



Aitken, R. J. (1999) The human spermatozoon: a cell in crisis? The Amoroso Lecture. Journal of Reproduction and Fertility 115, 1-7.



Aitken, R.J. & Marshall Graves, J. A. (2002) The Y chromosome, oxidative stress and the future of sex. Nature 415, 963.



Ecroyd, H., Asquith, K., Jones, R.C. & Aitken R.J. (2004) The development of signal transduction pathways during epididymal maturation is calcium dependent. Developmental Biology 268, 53-63.



Baker, M.A., Hetherington, L., Ecroyd, H. & Aitken, R.J. (2004) Analysis of the mechanism by which calcium negatively regulates the tyrosine phosphorylation cascade associated with sperm capacitation. Journal of Cell Science 117, 211-222.



Asquith, K. L., Baleato, R. M. McLaughlin, E. A., Nixon B. & Aitken R.J. (2004) Analysis of the mechanisms by which tyrosine phosphorylation regulates sperm-zona recognition in the mouse, a chaperone-mediated event? Journal of Cell Science 117, 3645-3657.



Aitken, R.J., Koopman, P. & Lewis S. E. (2004). Seeds of concern. Nature. 432, 48-52.