David R. Meldrum, MD
Australia to UCLA
After the world’s first IVF success (Louise Brown) by Patrick Steptoe and Bob Edwards in 1978 in England, followed by the first U.S. success in Norfolk, Virginia, it became clear to me that a new era had dawned in the care of infertility. I had already spent eight years using microsurgery to repair damaged fallopian tubes and of course had numerous successes, but many women had tubes that were too damaged to be able to function, and repair carried with it a substantial risk of a tubal pregnancy. Some couples had a male factor that made success unlikely even with a good surgical outcome.
Robert Edwards was the real pioneer, having spent 18 years of preparation in the lab. Together with Patrick Steptoe, a gynecologist, he achieved the world's first success in Oldham, England (Louise brown). Bob went on to be the first editor of Human Reproduction, the European counterpart of Fertility and Sterility, and was recently awarded a Nobel Prize for establishing IVF as the single most important advance in the care of infertile couples. I got to know Bob when we were speaking together at conferences and I will always cherish the dinner and evening Claudia and I spent with him during a conference in Nice, in southern France. Bob posed a conundrum to us that evening: “why is it that in the human female only about one out of five eggs is capable of development whereas lower animals produce a fertile egg every month?” I had no answer that evening, but emailed him after returning home that I thought it was because the human female, with her ability to be stressed by past and future as well as the present, was more likely to suffer constricted ovarian blood flow due to those stresses. Surprisingly, Bob did not answer, which was not characteristic of him. Sadly, that was probably an early indication of his Alzheimer’s, which progressed rapidly and left him with limited appreciation of the world’s gratitude expressed in Stockholm just a few years later. Bob also shared with us that after years of failed attempts to make IVF successful, he almost gave up to enter politics, so he might have been Prime Minister instead!
Two other pioneers were feverishly working toward the same goal down under in Melbourne, Australia and either could have turned out to be the Nobel Laureate had Steptoe and Edwards actually given up their quest. Alan Trounson (right), at Monash University and Alex Lopata at Royal Women’s Hospital across town were in stiff competition to achieve the first IVF success in Australia and Alex won out with Alan a close second. As a young UCLA faculty with some sabbatical credit, I packed up the family (the quads were only seven years old) and studied with both Alan and Alex for 3-4 months, gleaning what I thought was the best from each. While there I attended a course Alan had organized and I still have a picture of the "graduates", one of whom was Andre Van Steirteghem, the founder of one of the leading European groups in Brussels. I also visited a program in Adelaide that was using a pediatric incubator modified to control the level of carbon dioxide and thereby pH, as well as temperature and humidity. From the beginning of our IVF program I have used that technique and through our publications it is in common use around the U.S. Over the years since then, the importance of temperature control of the egg has been been more definitively demonstrated.
I owe a debt to Alan Trounson that I could never repay. His careful attention to detail gave me a grounding that still underlies the high success of our program at RPMG and offshoots like those of Bill Schoolcraft and Gabe Garzo. I also returned to Australia after Alan had established the first successful pregnancy in the world from embryo freezing, sitting at his elbow recording every detail to take back home. Shortly after starting embryo freezing we celebrated the birth of a "twin" born 2 years later (both now lovely "twin" young ladies). Alan, who is now president of our California Institute for Regenerative Medicine was one of two world IVF pioneers honored at our 25th anniversary of the Santa Barbara meeting. The advances being made in regenerative medicine using stem cells are mind-boggling. I have summarized the last year of Alan's monthly newsletters if you are interested (CIRM Trounson newsletters.pdf).
Very recently, one of Alan’s key lessons led me to further analyze a potential breakthrough published in F&S in December of 2011. A group of investigators in Egypt performed a well-designed (though not perfect) study to investigate whether injecting a dose of hCG into the uterus could improve implantation. The embryo is known to secrete signals to the lining of the uterus to make it more receptive, and hCG is one of those important ways the embryo converses with the endometrium. They found that implantation increased from 30 to 42%, which was statistically (and clinically) highly significant. Alan had taught me to always check anything that can come in contact with our eggs and embryos for toxicity using a sensitive mouse embryo assay. On my return to UCLA from Australia I ran that assay myself, stimulating and mating the mice, collecting their embryos, and checking culture dishes and media to be sure they lacked toxicity. When our current IVF lab prepared the hCG exactly as the authors had done, we found it halted the development of our mouse embryos. Then with the advice of one of our UCSD fellows we found a simple and inexpensive technique we demonstrated could remove the toxicity while maintaining the hCG potency. The intriguing question still to be answered is whether this new, purified hCG will lead to more benefit than the material used by the Egyptian group. Those investigators are good friends and would appreciate this further refinement of their technique. Of course I relayed the details to them so their patients will hopefully derive more benefit, and we will be presenting an abstract at the Pacific Coast Reproductive Society meeting so others will be alerted to this improved method. For the hCG treatment to become widely accepted in the U.S. we would have to do a randomized study under an investigative new drug (IND) protocol submitted to our Federal Drug Administration.
We don’t get to hear much from the “Ausies”, being so isolated from the world down where you move a light switch down to turn the light on. They are wonderfully open and friendly and shared everything freely with us. Just don’t ever go out drinking with them. I made that mistake before I was scheduled to give a grand rounds lecture the following morning. Not a good idea!