Report by - DAN O'CONNOR Churchill Fellow. To investigate the causes of Endometriosis

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1 Report by - DAN O'CONNOR Churchill Fellow To investigate the causes of Endometriosis I understand that the Churchill Trust may publish this Report, either in hard copy or on the internet or both, and consent to such publication. I indemnify the Churchill Trust against any loss, costs or damages it may suffer arising out of any claim or proceedings made against the Trust in respect of or arising out of the publication of any Report submitted to the Trust and which the Trust places on a website for access over the internet. I also warrant that my Final Report is original and does not infringe the copyright of any person, or contain anything which is, or the incorporation of which into the Final Report is, actionable for defamation, a breach of any privacy law or obligation, breach of confidence, contempt of court, passing-off or contravention of any other private right or of any law. Signed Daniel O Connor Dated 31 May

2 INTRODUCTION The Fellowship journey started with the VIII World Congress of Endometriosis in San Diego, USA, from the 24 th - 27 th February This meeting was attended by some 800 delegates world wide and the content was excellent, but the networking opportunities were splendid and links were established with workers in Endometriosis in the United States, Iceland, Holland, Belgium and Turkey. Existing links with other workers with whom I have been in contact were reinforced by one on one meetings at the Conference. A valuable new contact with a New Zealand colleague working on education programs for adolescents with endometriosis was established. The following aspects of the causes of endometriosis were pursued in depth - epidemiology, infertility in endometriosis, further work on the genetics of endometriosis, the role of dioxins in the cause of endometriosis, and the demography of endometriosis, in particular, the enlarging field of endometriosis in adolescent females. Centres visited to expand these areas of work were with Dr Dan Martin, Memphis, Tennessee; Professor Dan Cramer, Harvard University, Department of Obstetrics and Gynaecology, Boston; Dr Lindsay McMillan, London; Professor David Barlow and Dr Stephen Kennedy, Nuffield Department of Obstetrics and Gynaecology, Oxford University; Professor P S Boulter, Penrith, Cumbria; and Professor Philippe Koninckx, Catholic University, Leuven, Belgium. My sincere thanks due to the Selection Committee, Churchill Trust Queensland who believed in me and put my name forward and gave me the opportunity to achieve the Churchill Fellowship 2002, and my sincere thanks also due to each of my hosts, not just for their personal kindness and hospitality but for the great generosity in sharing with me new work, scientific discoveries of significance, and taking me into their various departments in most open and privileged ways. Everywhere I went people were very interested to hear of the Churchill Fellowship and the concept of an award that had no strings attached was something so novel as to be almost unbelievable to some of the more hard bitten scientific researchers. Two young researchers asked me somewhat tongue in cheek whether it was possible to extend Churchill Fellowships to both the United states and United Kingdom! Finally, acknowledgements to my wife and family who have been very patient with me during these various research activities and whose wholehearted support has made it possible for me to enjoy the experience. Also my hard working secretary, Julie Bennett, who did the hard miles in getting me organised and is now doing the even harder miles of restoring some cogent sense to my various notes.

3 EXECUTIVE SUMMARY DANIEL T O'CONNOR Gynaecologist Queensland Endometriosis Research Institute St Andrew's Place, 33 North Street, Spring Hill, Qld 4000 Ph: Fax: qeri@bigpond.com.auan investigation into the causes of endometriosis. Hypothesis = a percentage of women are born with a genetic predisposition to develop endometriosis and in the reproductive years "cofactors" operate causing the development of the full blown disease. It is possible that the disease known as endometriosis is in fact several diseases with different genetic profiles and different manifestations. HIGHLIGHTS OF FELLOWSHIP STUDY TOUR AND LESSONS LEARNED 1. Primarily Australia is in the forefront in research endeavours in endometriosis. 2. The Churchill Fellowship enhances the profile and reputation of recipients and is highly respected overseas opening many doors and offering exceptional opportunities to gain privileged information. 3. With regard to Causes of Endometriosis, the following important areas were covered with my hosts - It is important that further detailed epidemiological research into risk factors for endometriosis be carried out. The downstream research which will follow our Genes in Endometriosis project in Brisbane should produce amongst other things a possible blood screening test for endometriosis comparable to the detection of tumour markers in diseases such as ovarian cancer. There is increasing evidence that toxicants are probably contributing cofactors in the development of endometriosis and this is being pursued by the new Dioxins in Endometriosis research team established between the National Research Centre

4 for Environmental Toxicology and the Queensland Endometriosis Research Institute in Brisbane in January The contentious overseas claim that mothers may inadvertently give their daughters endometriosis by breast feeding them will require further investigation and this is already under way by the new research team in Brisbane. The concept that endometriosis causes infertility may need to be reversed and in fact infertility may lead to endometriosis, especially where progesterone deficiency is a factor. This is seen in polycystic ovary disease for instance and it is felt that progesterone protects against endometriosis. Surgery for ovarian endometriosis needs to minimise the threat of potential oocyte damage in the residual healthy ovarian tissue following removal of cysts. Various techniques have been studied with this in mind and will be introduced into clinical practice. Research into the reduction of adhesions following laparoscopic treatment for endometriosis shows that the addition of oxygen to the pneumoperitoneum gasses may be of great help in this regard. The Genes in Endometriosis research study started in Brisbane in 1993 is the world's largest such study ever undertaken and the recent collaboration with Oxford University Department of Obstetrics and Gynaecology in this regard will result in a major scientific contribution when the results are published later this year. The opportunity to forge bonds with our collaborative workers in Oxford is mutually advantageous and a major highlight of this trip. A significant personal highlight of the trip was time spent with Professor Peter Doherty at the St Jude Children's Cancer Hospital in Memphis and I was encouraged by the fact that he believes too many Australians retire too early at 65 and that very worthwhile research can and should be done by those who are over 65 if they are capable, believe in their project, have perseverance, and are passionate about what they are doing.

5 DISSEMINATION OF FRUITS OF MY FELLOWSHIP This will be via scientific papers in appropriate national and international journals; by using the media to provide information to the population at large; by incorporating information in my present role of lecturer in Continuing Medical Education meetings; and providing feedback to fellow researchers on the work we are doing in relation to what is happening overseas and for the planning of future research projects. I would recommend that Churchill Fellowships should be more widely advertised and the Churchill Trust should receive ongoing financial support from all areas of the community and government so that its funding basis is enhanced and more Fellowships can be awarded across all aspects of life in Australia. I would hope ultimately to be in a position to present research data to governments so that more funding can be made available for the detection and prevention of endometriosis. It is obviously preferable to be able to prevent endometriosis rather than needing to treat it surgically and until the cause of endometriosis is established, prevention cannot be accurately attempted. My final recommendation would be that the government and population at large must be made aware of the significance of endometriosis to the women in our community and I believe that they should be offered hope in the work we are doing looking for a cause for this condition.