This Thesis is the product of nearly 40 years of continuous study and research by me in the field of Reproductive Medicine.
My research commenced with a study of Immunological Infertility in the 1 970s. I investigated the occurrence of immunity to human seminal plasma antigens among infertile women and prostitutes and demonstrated a significant occurrence of antibodies to these antigens which appeared after bacterial action on seminal plasma. The detector system used for this reactivity was counterimmunoelectrophoresis and I initially investigated its sensitivity, which was high, using human serum albumin as antigen. The seminal plasma antigens appeared to be associated with subfertility. Characterization of these antigens found them to be of high molecular weight glycoproteins in nature. My further Immunological Infertility studies involved the development of a sperm micro-immobilization test for cervical mucus for the detection of anti- sperm antibodies which had a greater relevance to infertility owing to its local immunological effects.
My research then proceeded to Pelvic Microsurgery of the Female in the 1 980s with the development of techniques of pelvic tidy-up of inaccessible ovaries in preparation for laparoscopic egg retrieval. I also proceeded to apply microsurgical techniques for the repair of fallopian tubes, removal of ovarian cysts, especially endometriotic cysts, and myomectomies of large fibroids.
The scene changed with the advent of operative videolaparoscopy. I proceeded to develop the technique of Laparoscopic Varicocoelectomy for the treatment of male infertility due to the varicocoele, which accounts for 40% of the causes of male factor infertility. The Thesis describes as many as 800 patients operated, with beneficial results and improvement of sperm quality, and the achievement of pregnancy. These studies commenced in the 1 990s.
Around the same time, I developed Laparoscopic Myomectomy Techniques for the treatment of large uterine fibroids which regularly would have been operated by laparotomy. I demonstrated the feasibility of performing operations on these large fibroids without morbidity and with excellent results. I also studied Hysteroscopic Myomectomy and Fertiloscopy.
Going back to the early 1980s I pioneered IVF technology in Adelaide and was the third Centre in the world to achieve pregnancy after Cambridge and Melbourne. I proceeded to achieve world's firsts, chronologically with the delivery of the world's first IVF triplets in 1 983, delivery of the world' s first frozen egg pregnancy in 1 986, and Asia's first set of sextuplets in 1998. The beneficial effect of a high starting dose of Gonadotrophins in some poor responders was investigated as part of my contribution to the Clinical Aspects of IVF.
After establishing human IVF technology using the murine model in the 1 980s, I made significant scientific contributions through ultrastructural studies of sperm-egg fusion in human IVF. Of great significance was the discovery that fertilization occurred 3 hours after exposure of the egg to sperm. Pregnancy rates were improved in IVF using my technique of assisted hatching and delayed embryo transfer. Further research into IVF proceeded with normal birth after microsurgical enucleation of tripronuclear zygotes, rescue ICSI of oocytes that failed to extrude the second polar body 6 hours after insemination in NF, and improvement in implantation and pregnancy rates in NF, following short coincubation of the gametes in vitro. I then studied pronuclear zygote morphology and early cleavage status of zygotes as selection criteria for the selection of Day 3 embryos, and also how to overcome difficult embryo transfers.
Research into Cryopreservation of Human Embryos proceeded using a modified embryo cryopreservation method which increased post-thaw survival with a concomitant increase in implantation rates. Cryopreservation of embryos by vitrification showed promise.
Details of Oocyte Cryopreservation are described in the Thesis. My historical pioneering work paved the way for the establishment of human oocyte freezing in many Centres around the world today.
An attempt was made to study the fate of embryos after embryo transfer in NF before pregnancy could be detected by ßhCG. I found that the Early Pregnancy Factor could be detectable after embryo transfer. When pregnancy became established EPF detectablility persisted, whereas, EPF activity subsided when the embryos failed to survive.
The Thesis also describes Miscellaneous Aspects of my infertility research, including the cryopreservation of human spermatotozoa and the establishment of Singapore's and Asia's first National Sperm Bank. I also touched on causes of early reproductive loss, and the use of prenatal diagnosis of genetic defects which is widely practiced today. My endeavours extended also into the area of ultrasonography in gynaecology and infertility, and described a method of outpatient management of ovarian cysts by transvaginal ultrasound aspiration.
In conclusion, I feel that I have made outstanding contributions to the knowledge and advancement of the field of Reproductive Medicine in the work embodied in this Thesis.