The opening lecture of the Session one on Genetics and Endocrinology in Fertility from Manuela Simoni was focused on the influence of polymorphisms of gonadotrophins and anti-mullerian hormone (AMH) receptors on response to ovarian stimulation. Available data suggest that follicle stimulating hormone receptor (FSHR) polymorphism could be useful in predicting ovarian response, but powerful, multicenter, retrospective genome-wide studies should evaluate the genetic factors involved in poor response and Ovarian Hyper-Stimulation Syndrome (OHSS). This presentation will soon be available as an online course on the SSIF website. The session was completed by Franck Tüttelmann, who showed how genes influence sperm production, and Richard Fleming’s review of the role of gonadotrophins, both in physiology and in ovarian stimulation protocols, and the presentation of some updates on the use of AMH as a marker of ovarian response, based on studies performed by his group.
Session two was dedicated to the optimization of ovarian stimulation. Ernesto Bosch started his talk introducing the criteria used to define poor response to ovarian stimulation. He continued by showing gonadotrophin trends in hyporesponsive women and reporting the results of ovarian stimulation protocols including rFSH and rLH. The next speaker, Renato Fanchin, critically reviewed the “mild stimulation” approach. Follicular recruitment is a limiting factor in the reproductive function, it is influenced by age and can contribute in inducing poor IVF outcomes. Norbert Gleicher gave a comprehensive overview of mechanisms involved and available clinical trials performed in this field and concluded: “We increasingly will be able to affect follicular recruitment and maturation, and by doing so, improve as well as extend female fertility”. Carlo Alviggi spoke about how to orientate the choice of ovarian stimulation protocol when the issue of poor response must be addressed. The speaker “guided” participants in the mass of available, sometimes contrasting, data to conclude with some practical suggestions about the use of a combination of rFSH and rLH in poor responders. The two last lectures of the session by Frank Broekmans and Richard Scott completed the picture of ovarian stimulation management, addressing prediction of ovarian response and management of OHSS.
The second day was dedicated to other aspects that can improve IVF outcomes. Session three was focused on laboratory procedures, like oocyte and embryo freezing, embryo selection as well as monitoring and management of endometrial receptivity. Claus Yding Andersen described the program of collection and storage of cryopreserved ovarian tissue implemented in Denmark that is one of the most advanced in the world. Arne Sunde’s lecture addressed complex topics such as criteria and procedures for embryo selection. Andrea Borini and Carlos Simon delivered two well-appreciated presentations addressing, respectively, cryopreservation methods and implantation.
The last session of this Symposium offered the opportunity to share with participants controversies on some of the most debated aspects of infertility management. In order to increase the involvement of the audience, in each part of the session a presenter introduced each topic, two discussants provided their opinion and, at the end, thanks to a voting system, the point of view of the audience was collected and discussed. Robert Fisher chaired the session and the topics covered were very stimulating: ethical issues in fertility preservation, the real value of PGS as well as diet and lifestyle in the prevention of ovulation disorders. In particular the latter topic, relatively new, provided participants with valued clues, both for clinical practice and research.
In conclusion this Symposium was a unique opportunity to receive highest level updates on the hottest topics.
Tommaso Sacco
In order to offer the high educational level characteristic of SSIF events, the faculty was composed of top level renowned experts that provided the audience with a state of the art overview of all the aspects of this disease.
The first presentation was from Olaf Bodamer with a review of the physiology of amino acid traffic in the whole body, from the intestinal absorption to the transport across the blood brain barrier. This lecture was the ideal introduction showing the mechanisms through which Large Neutral Amino Acid (LNAA) block phenylalanine (Phe) transport into brain tissue in PKU patients.
The other two lectures of this session were dedicated to the nutritional approach to PKU. The first, delivered by Denise Ney, was focused on the role of foods in the PKU diet made with Glycomacropeptide (GMP), an intact protein enriched in LNAA, while Kirsten Ahring reported the experience of the Kennedy Center in Denmark in the use of a diet based on LNAA.
The lectures of the second session entered the newest aspect of PKU management in last decades: the sapropterin treatment. The first speaker Amaya Bélanger Quintana, made a short history of the molecule development, from the early experiences in the eighties, to the approval by Food and Drug Administration in 2007. She also reported the experience in her Center with the drug and in particular showed interesting data on the response to treatment in terms of reduction of dietary restrictions, and spoke about genetic factors that influence sapropterin efficacy.
Rani Singh provided participants with further data on PKU patient treatment in her Center in Atlanta were the introduction of sapropterin has allowed the suspension of the dietary treatment in some subjects and the reduction of restrictions in others. The last lecture of the session, by Friedrich Trefz, addressed the long term use of the drug showing experience collected on patients treated for durations ranging from 24 to 110 months. He also analyzed the factors influencing phenylalanine fluctuation in sapropterin treated patients. The program of the first day of the Symposium included also four working groups focused on practical issues of PKU management, such as maternal PKU and follow-up and outcome of PKU, that allowed participants to share knowledge and experience with the chairmen.
Session three, on the second day of the Symposium, opened with lectures on experimental procedures, like gene therapies and liver repopulation that are aimed to offer, in the future new therapeutic options in PKU management. Philip Laipis’s lecture described a protocol using recombinant adeno-associated-virus (AAV) vectors to restore a functional phenylalanine hydroxylase (PAH). In PKU mice, Phe serum concentrations reduction has been produced and sustained over some time. Beat Thöny showed the results of a study where an AAV vector containing the genes for PAH and for two key synthetic enzymes for BH4 was used to correct blood Phe in mice on a long term basis. Cary Harding showed interesting data on liver repopulation with 10–20% wild-type hepatocytes that provided complete correction of serum Phe concentrations in PKU.
The last session, “Giants in PKU”, was introduced by Ivar Følling, the son of one of the main investigators of PKU, and went through celebrating Richard Koch, that has been involved in research and clinical practice on phenylketonuria for more than fifty years. Nenad Blau, the Scientific Organizer that provided SSIF with a very valued help in planning and implementing the meeting, presented the Award and closed the Symposium announcing the 2010 SSIF PKU Symposium.
Tommaso Sacco
I am head of the Department of Gynecology at the Cliniques Universitaires Saint-Luc and Chairman of Obstretrics and Gynecology at the Catholic University of Louvain, Belgium.
2) You are the Scientific Organizer of the Congress of International Society of Fertilty Preservation which will be held in Brussels, Belgium, from December 10-12 2009. Can you tell us a little bit more about this event and what are your expectations?
Three years ago in Boston, I along with colleagues from Asia, Australia, Israel, the United States, Canada and Europe, decided to create a new society devoted to fertility preservation: the International Society for Fertility Preservation (www.isfp-fertility.org). We created this society to promote the concept of fertility preservation, especially in young women having to undergo chemo- or radiotherapy, which could lead to a premature menopause by destruction of the follicle reserve of the ovary.
The Board of Directors of the society decided to elect me as president and our first decision was to organize a world meeting in Brussels. This meeting will be held in December 2009 and with three main goals: Firstly to widely inform not only gynecologists, but also pediatricians, oncologists, and onco-pediatricians, that fertility preservation is possible and should be proposed to all young women facing the possible risk of premature ovarian failure due to their treatment. This is why a full day will be devoted to the relationship between treatment (chemotherapy or radiotherapy) and fertility preservation, to inform non-gynecologists treating such patients. Secondly to widely inform oncologists, gynecologists, biologists and researchers of new data from research studies and clinical application of fertility preservation in both females and males. Lastly, to allow young researchers to present their data.
3) What new methods could improve, in the next future, fertility preservation outcomes?
Fertility preservation so far includes embryo preservation, oocyte cryopreservation and ovarian tissue cryopreservation. There is no doubt that cryopreservation of embryos is the gold standard and has the highest success rate in terms of pregnancy to date. However, when a young adolescent is facing cancer that requires chemotherapy, there is often no male partner and it is thus impossible to cryopreserve embryos. On the other hand, the cryopreservation of oocytes still has a low success rate, although it is increasing. Moreover, very frequently, oncologists do not want to postpone chemotherapy, so when chemotherapy is required without delay, only ovarian tissue preservation can be proposed. In the future, there is no doubt that the success rate of cryopreservation of oocytes both mature and immature, followed by in vitro maturation continue to improve. Ovarian tissue cryopreservation and reimplantation has so far lead to six live births worldwide and there is no doubt that by improving the technique of cryopreservation and thawing, the success rate will increase further in the near future. Moreover, in our department, the technique of isolation of primordial follicles from cryopreserved ovarian tissue, has recently been improved, so that survival of good quality primordial follicles can be expected. Transplanting isolated follicles will also allow us to avoid the risk of reimplanting cancer cells. This risk does not exist in certain pathologies, but in pathologies like breast cancer and leukemia, this risk theoretically exists, which is why the technique of reimplanting primordial follicles (scaffold) is so promising.
4) How far orthotopic transplantation of ovarian cortex is form routinely implementation in clinical practice?
We have performed the first orthotopic reimplantation in 2003, although we started cryopreservation of ovarian tissue in 1996. So far, we have performed 10 cases of orthotopic reimplantation of cryopreserved ovarian tissue. All these women have demonstrated restoration of ovarian function. We really hope that a pregnancy will be announced in the future. So far, worldwide probably about 30 cases of orthotopic reimplantation have been carried out. Since there have been 6 live births, this means that the pregnancy rate is more or less 20%. Why are there so few orthotopic reimplantations when there are so many women who have their ovarian tissue cryopreserved? Simply because these women have had cancer and the majority of them were adolescent at the time. We must therefore wait for the patient to be in complete remission from the disease, and for the approval of the oncologist, which would allow the possibility of pregnancy. Above all, we must wait for the patient to express the desire to get pregnant.
5) What should be done to widen the offer of fertility preservation to patients that undergo treatments that threaten their reproductive function?
I think that we need to widely inform pediatricians, oncologists and radiotherapists that fertility preservation exists and should be proposed to all women facing the risk of premature ovarian failure. Grants should also be provided to promote active research and elaborate new protocols on cryopreservation as well as extend means and facilities to work on cryopreservation, so that everybody in the world can have access in the future to this new mode of fertility preservation. Furthermore, there is a need to stimulate new research protocols for young researchers and promote the creation of teams of researchers. Lastly, organize more meetings like the Brussels meeting to allow junior and senior researchers to share their experience.
Thank you.
The lecture delivered by Martin Evans was an outstanding example of how a health care professional can be informed in a simple way on an extremely complex topic. The presentation was a history of research on stem cells and a State of the Art that overviewed the most recent study trends. The subsequent sessions went through the different areas of stem cell research.
Session I addressed the mechanisms that control the differentiation of stem cells and factors that influence these phenomena. Ian Chambers described “The paradox of embryonic stem cell cultures” based on the need to maintain differentiation capacity and self-renewal attitude at the same time. The control of stem cell culture is based on knowledge and manipulation of molecules that are involved in the differentiation processes, like Nanog. Ian Gallicano went through the mechanisms that control the pluripotency of embryonic stem cells focusing on the signal transduction pathways involved in their differentiation and, in particular, on microRNAs.
In Session II, on the second day of the meeting, Kaomei Guan described protocols developed to establish pluripotent stem cells from adult mouse testis, defined as “multipotent adult germline stem cells (maGSCs)”. These cells develop both in vivo and in vitro to differentiated cells from all three embryonic germ layers and maGSCs-derived cardiomyocytes showed functional properties of embryonic cardiac cells. As a confirmation Kaomei Guan presented a movie where cells culture showed their contractile properties. The next speakers, Tiziana Brevini and Lorenza Lazzari, addressed two very interesting aspects of research on stem cells: parthenogenesis and characteristics of cells detectable in amniotic fluid.
Session III focused further on how cells are programmed towards differentiation and how it is possible to influence these mechanisms. Alexander Meissner described the role of bivalent, repressive/activating factors and stressed the relevance of loss of DNA methylation “as a step forward in the recovery of pluripotency”. The outcomes of research on reprogrammation of cells that Sheng Ding showed were so interesting that Martin Evans defined the information as "hot". An important topic covered by Amanda Fisher was the reprogrammation of embryonic stem cells.
After tackling stem cells for the therapy of infertility, the last two sessions were dedicated to future applications of stem cells in the management of diseases that now are controlled but not healed. Bruno Peault reported his experiences with Perivascular Multipotent Progenitor Cells that can be used as a source of adult mesenchimal stem cell and Giulio Cossu showed data on the evaluation of mesoangioblasts for the cell therapy for muscular dystrophy. Christine Mummery Human presented her experience in embryonic stem cell cardiomyocytes in cardiac repair and drug discovery.
In session VI, Tiziano Barberi, Elena Cattaneo and Gianvito Martino covered different aspects of stem research aimed at finding therapeutic solutions for neurodegenerative diseases. Alan Trounson with a lecture on the translation of the basic research of today in therapeutic tools tomorrow closed this first SSIF Symposium on stem cells.
In commentating the event, Giancarlo Comi, President of the SSIF Scientific Committee, mentioned that despite being a difficult topic, "SSIF's mission is to do CME and to do it in a correct and ethical manner that is why we are proud to have organized such an important appointment for the future of research".
Tommaso Sacco
Giancarlo Comi opened the first session highlighting that MS active phases are many and more prolonged than clinical manifestation would have us believe. He also suggested that MS is probably a two-stage disease, with the second stage, progression, reflecting neural degeneration. Then the speaker reviewed known mechanisms of neurological dysfunction related to both acute and chronic damage.
This presentation was followed by Hartmut Wekerle who described the role of immune system disregulation in inflammation and axon degeneration. In particular he addressed the role of B cells in MS pathology. Alexandre Prat opened his lecture suggesting that his task was to convince the audience that manipulating the blood brain barrier (BBB) will lead to new therapeutic approaches. He showed mechanisms of leucocyte transmigration across BBB and the molecules involved.
Robin Franklin’s lecture was the first of a series on mechanisms of neural repair. In particular, he tried to explain why the physiologic repair mechanisms may fail in patients with MS. Martin Kerschensteiner covered the topic of mechanisms through which neuroprotective therapies for MS would specifically neutralize the damage-inflicting pathways. The next lecture, by Catherine Lubetzki, showed the results of research on guidance molecules involved in neural repair mechanisms and, in particular, on semaphorins. Siddharthan Chandran and Frederik Barkhof delivered the last two lectures of this session focusing, respectively, on the role of stem cells in myelin repair and MRI techniques for assessment of neuroprotection.
Ralf Gold, in opening Session III, emphasized that much damage appears in the early inflammatory stages of MS and that early treatment delays the appearance of clinically definite MS. Roland Liblau opened his talk by asking two basic questions: is it rational to target B cells for MS treatment and, if so, how could we effectively do so? Then he provided several data that support the relevance of the role of B cells and of therapies that directly or indirectly target these cells. Patrick Vermersch provided the audience with the rationale of targeting lymphocytes in the management of MS, emphasizing that CD4+, CD8+ and B cells all appear to have key roles. Among the drugs targeted on lymphocytes, he mentioned recent data from his research group concerning the use of cladribine. Antonio Uccelli closed the Session addressing the use of haematopoietic stem cells in MS.
The last session of the Symposium offered a comprehensive overview of some of the most relevant issues that specialists have to deal with in managing MS patients, both in research and clinical practice. Ludwig Kappos began by stressing the need of disease definition in order to choose best treatments. Sub classification of MS forms might inform about prognosis and possibly influence choices of individualized therapy. Moreover the speaker suggested that modern “omics” technologies – genomics, proteomics, metabonomics – could yield useful information for the classification of MS subtypes. Maria Pia Sormani opened by discussing the current standard in trial design, which is the randomized controlled trial of a new drug versus placebo, and went through suggesting approaches aimed at optimizing clinical trial design.
Xavier Montalbán emphasized the relevance of identification of responders to DMDs and of patients at higher risk of adverse events and suggested that phamacogenomics could provide physicians with the prediction of patient response to drugs and susceptibility to adverse events. Fred Lublin’s presentation was focused on the choice to treat immediately after a first demyelinating event, or, in some cases, even before the first demyelinating event. The need of prognostic markers, but also the need for early treatment aimed to influence long-term disease evolution, was extensively addressed by this seaker.
Mark Freedman closed the Symposium with a lecture on patient tailored treatment. The best benefit-to-risk ratio of available therapies, the relevance of the “window of opportunity” for the use of current first-line treatments and the prognostic significance of early MS years were some of the topics that he covered providing valued suggestions to implement the patient tailored approach in daily practice.
Thanks to a very high level Faculty and to a balanced mix of lectures dedicated to basic research outcomes and clinical aspects, the multiple sclerosis SSIF Symposium confirmed to be one of main educational events in this field.
Tommaso Sacco
Advanced Course in Human Reproduction and Embryology; June 26, 2009; Amsterdam, Netherlands
The objective of this course is to provide participants with the most updated knowledge on IVF procedures and with skills useful in IVF practice using an interactive format with a strong emphasis on discussions between the faculty and the participants.
There is a special registration dedicated to oncologists, paediatricians, radiotherapists to attend December 10 (only 1st day meeting). For more information click here for oncologists and here for paediatricians.
The increasing knowledge on the pathogenesis and genetics of neurodegenerative disorders are showing that despite the categorization into a general definition, the disease patterns are very different one from another. In some case, the differences are so marked that it can support the hypothesis that each neurodegenerative disorder includes a cluster of disease. The aim of the symposium is to summarize evidences this approach is based on and stimulate the discussion.
This is an educational programme created to encourage the dissemination of scientific knowledge in the field of MS. It will stress the benefits of new diagnostic tools for defining the natural history of MS and disease activity monitoring. Current diagnostic criteria for MS will also be reviewed in the light of new medical evidence. A review of recent clinical trials and treatment optimisation guidelines will also be presented.
This is an educational program created to encourage the dissemination of scientific knowledge among nurses from all over the world in the field of MS.
This two day event will be centered on GH deficiency in childhood, adolescence and adulthood where the best tools to diagnose these disorders, how to follow-up the patients’ transition from adolescence to adulthood and the optimal treating strategies will be discussed. Futhermore, the detrimental long term effects of GH deficiency on cardiovascular and metabolic health and the role of GH therapy in ameliorating these effects will be also critically reviewed as well as the transition from adolescence to adulthood in girls with Turner syndrome and the evaluation of the role of GH and estrogens in post puberty.
Present and future efforts on phenylketonuria (PKU) treatment will be discussed in this event particularly with regard to new pharmacological approaches, such as enzyme substitution and cofactor administration. The importance of patient management will also be highlighted, both in PKU as well as in tetrahydrobiopterin deficient patients. Furthermore, the workshop sessions will offer the possibility to discuss knowledge and experiences on six major aspects of PKU management.