What has happened? where are we? Howard W.Jones Jr The Jones Institute for Reproductive Medicine, Eastern Virginia Medical School, Norfolk, VA23507, USA Downloaded from https://academic.oup.com/humrep/article/11/Supplement_5/7/669059 by guest on 01 October 2021 Introduction It is my very special privilege to open this colloquium. This gathering is the result of a chance encounter at the International Federation of Gynecology and Obstetrics (FIGO) meeting of Jean Cohen, Lars Hamberger, Howard Jones and Georgeanna Jones in Montreal in September 1994. In the Brownian movement which takes place between sessions, our respective paths happened to converge. The conversation lamented the huge size of the meeting with its attendant disadvantages and, particularly, the lack of opportunity for intimate challenge and discussion. This led to further lament about the size and disadvantages of our own international in-vitro fertilization (IVF) meetings and raised the question of whether there was still a role for small intimate colloquia. The vote of the four Brownian particles was unanimously 'aye', and here we are. The preference for the venue was easy. The four particles remembered the Bourn Hall meeting of 1981 when the camaraderie, the mutual respect, the absence of competition and the desire to solve a common problem was the order of the day, i.e. then it was simply to make the IVF system work and to understand why. It is astonishing to recall that, at that time, it was possible to count on the fingers of one hand the number of programmes throughout the world that had a continuing pregnancy, or the birth of a normal child from in vitro. The 1981 meeting was convened by Bob Edwards, Patrick Steptoe, and Jean Purdy. It took less than a minute in Montreal to agree that a meeting should be held and where it should be held, and less than a minute to think and hope that Ares­ Serono would be willing to make Bourn Hall available to sponsor the Cambridge and Bourn aspect of the meeting. Within another minute or so, Jean Cohen suggested that we talk to Isabelle Stilger, whom he had seen in Montreal. Isabelle agreed to discuss the matter with the appropriate people in the company and we are now able to express our appreciation to them and to Peter Brinsden, and to Bob and the staff here at Bourn for their role in this meeting. We can also thank Ares-Serono for the weighty and beautiful volumes on Italy which I interpret as a hint to hold subsequent meetings, if any, in Italy. Human Reproduction Volume 11 Supplement 1 1996 © European Society for Human Reproduction and Embryology 7 H.W.Jones Downloaded from https://academic.oup.com/humrep/article/11/Supplement_5/7/669059 by guest on 01 October 2021 Figure 1. The cover of the programme of the Bourn Hall meeting of 1981 (see Appendix I). The invitation list was a matter of considerable delicacy. The goal was to have a working group of world leaders where it would be possible to layout and to debate the potential of the future with those qualities of camaraderie, mutual respect, absence of competition, a desire to be mutually helpful and the challenge of benefiting by common opportunities. Hence, the invitees are the available descendants of the surviving programmes of 1981 supplemented by the principal innovators of the last decade. It needs to be observed that we are involved, not only in a scientific colloquium, but in an evaluation of the place in contemporary affairs of a meeting of this kind. I hope we will discuss this and perhaps, by the time we break up on Saturday evening, there will be a consensus one way or the other about the appropriateness of such small meetings and the usefulness of any publication if such meetings are held. If they are to take place in the future, it is obvious that young leadership must be involved. The old guard must be replaced by the new. An examination of the 1981 programme (see Appendix I) recalls that we were mainly grappling with the basic problem of understanding the inefficiency of the in-vitro process (Figure 1). It may be useful to spend a moment or two re-examining the 1981 programme session by session. However, let me insert a disclaimer. What you will hear are the recollections of one person. They may well be inaccurate and my impressions may need to be corrected and supplemented; but knowing this group, I am sure both will happen. Furthermore, the slides that I will use, with one exception, are from my collection of antiques from the era of 1981, and are, therefore, biased by our own data, but hopefully, they will serve the purpose of a take-off point for further discussion. 8 Where are we now? Of course, there is some danger in returning to 1981. The important thing in life is to look ahead, not backward, but there seems to be a thread of substance and attitude expressed in 1981 which indeed might be of benefit in 1995. We will see. Let us now turn to Session I of 1981. The conventional wisdom in 1980 was that we should use the natural cycle (Table I). There were certain tenets which Downloaded from https://academic.oup.com/humrep/article/11/Supplement_5/7/669059 by guest on 01 October 2021 were expressed, namely to use the natural cycle, that the in-vitro maturation of the oocyte was impossible from a useful point of view, although Bob Edwards himself had clearly shown that in the human, meiotic maturation was resumed by liberating the oocyte from the ovary. It was thought that a minimal interval from harvesting to insemination was desirable and that the transfer should occur at the 8- to 16-cell stage. As it turned out, what was state-of-the-art in 1980 quickly became passe. At the end of 1980, which was the year we started working in Norfolk, USA, we knew that there had been two live births from the natural cycle in Oldham, UK. We knew that there was one on-going pregnancy in Melbourne, Australia, which had been established in 1979; the child was eventually born in June 1980. These were the data at the beginning of 1980. In the same year, pregnancies were initiated at Bourn Hall. It was interesting that in Melbourne, although two pregnancies resulted from the 1979 experience with the same in 1980, no further pregnancies occurred. Nevertheless, we began with the natural cycle in March 1980. The beginning of the programme in Norfolk was actively opposed (Figure 2). Indeed, this experience was duplicated elsewhere, although we seemed to have had it in spades. There was a forum for this opposition because we required an official document, a so-called 'Certificate of Need', to inaugurate any new programme and it was the granting of this 'Certificate of Need' which offered an opportunity to the right-to-lifers and others. Suffice it to say that after about 5 or 6 months and numerous hearings, the laboratory was approved, but after that, we had a court battle to face in the form of an injunction, which was finally resolved. I introduce this sociologicial note because we need to come back to that later, as not only was in-vitro fertilization (IVF) introduced by Bob Edwards, but he also introduced ethical problems which society had never faced before. From a scientific point of view, we spent ou~ time early on working out what every programme had to work out, i.e. exactly when to do the laparoscopy to retrieve that precious single egg in the cycle using the tools available to that programme. We happened to have a 4 hour oestradiol assay and a 6 hour Table I. Conventional wisdom (January 1980) Use natural cycle In-vitro maturation of oocyte impossible Minimal interval from harvesting to insemination Transfer at 8-16-cell stage 9 H.W.Jones Downloaded from https://academic.oup.com/humrep/article/11/Supplement_5/7/669059 by guest on 01 October 2021 Figure 2. A page from the Norfolk newspaper The Ledger Star, reporting the public hearings necessary to obtain a 'Certificate of Need' to begin the in-vitro project. luteinizing hormone (LH) assay on blood serum which was worked out for us by George Wright, our Professor of Immunology at Eastern Virginia Medical School. Therefore, we studied cases with this technique and Figure 3 which was shown here at Bourn Hall in 1981 demonstrated the effort to track the ovulatory time in relation to the LH rise, 10 Where are we now? Downloaded from https://academic.oup.com/humrep/article/11/Supplement_5/7/669059 by guest on 01 October 2021 Figure 3. An example of the study designed to ascertain the relationship between the spontaneous luteinizing hormone (LH) surge and ovulation. Figure 4 shows the summation of these studies and it was from these data that, at least in the system we were using, it seemed that we needed to carry out the laparoscopy within about 28 h of the initiation of the LH rise. Nevertheless, in spite of doing the best we could in 1980, from 41 laparoscopies we obtained an egg in a little over half of these cases, transferred 13 cleaving pre-embryos, but no pregnancies resulted. A glance at the 1981 programme shows that in Melbourne they were using clomiphene, but over the Christmas holidays in 1980-81, Georgeanna Jones prevailed in her view that we should go to human menopausal gonadotrophin (HMG, Pergonal; Serono) although Bob had tried this quite extensively, unsuccess­ fully, prior to going back to the natural cycle.