Professor Carlos Simón from IVI Valencia, Spain
Professor Carlos Simón from IVi Valencia, Spain, is the recipient of the 2011 SSIF Award in reproductive medicine. He received his award at a dedicated ceremony held at ESHRE 2011 in Stockholm on July 4, 2011.
Professor Simón was selected by the SSIF Award Committee members as the medical expert who has done most to drive medical education in reproductive medicine forward through his dedication to educational activities and academic and research work.
Professor Carlos Simon is Board Certified and Full Professor of Obstetrics and Gynecology at the University of Valencia, Scientific Director of the Fundación IVI and the Prince Felipe Research Center. To date he has organized many educational live events as a scientific organizer, spoken at more than 70 educational live events and held several educational courses as a tutor, academic teaching courses as lecture or professor, written nine books as editor and published more than 100 book chapters in international and national books in the past ten years. In addition, he has developed three website online courses and one open-access scientific database.
In 2012 the SSIF Award will be in the field of neurology. Applications can be made at the dedicated SSIF Award website: www.ssifaward.org
May 27-28, 2011; Copenhagen, Denmark
Manuela Simoni’s (Italy) lecture explored functional genetic polymorphisms FHS, LH and AMH and their receptors. Women undergoing ART with homozygous FSHR Ser 680 genotype require a higher number of ampoules for ovarian stimulation compared to the homozygous Asn 680 carriers, suggesting that the FSHR Ser 680 genotype is less sensitive to the FSH action in vivo. The FSHB gene, encoding the beta subunit of gonadotropin, posseses an interesting SNP in the promoter region. Recent studies in males have demonstrated that this SNP is significantly associated with serum FSH and testosterone levels and that the -221T allele variant has an increased prevalence in infertile men. A recent whole-genome analysis in patients with PCO identified the LHCGR as a candidate gene demonstrating a significant and consistent association with this disease. Concerning anti-Müllerian hormone and its type II receptors, it was suggested that polymorphisms are associated with follicular phase estradiol levels in normo-ovulatory women. It is still unclear if there is any association with menopause age, PCO or response to ovarian stimulation.
Signe Altmäe (Sweden) discussed estrogen receptor genes and ovarian response. ESR1 and ESR2 are in fact related to the mechanisms of FSH action. Estrogen extends the action of FSH on granulosa cells by promoting their proliferation and increasing their expression of FSH receptors. Moreover, estrogen receptors have an essential role in preparing the endometrium for embryo attachment and implantation. She showed recent findings on ESR1 and ESR2 involved in the outcome of controlled ovarian stimulation causing a disadvantage to certain patients undergoing IVF treatment.
Regarding male infertility, Kenneth Aston (USA) explained that numerous polymorphisms have been reported as potential risk factors for male infertility, however the majority of these exist only as single reports, and well-validated SNPs associated with male infertility are scarce. He emphasized the need for the development of multi-center collaborations in order to identify new genetic variants associated with spermatogenic defects.
The second session was focused on poor responders and premature ovarian failure. Peter Humaidan (Denmark) discussed the management of poor responders. Factors such as advanced age, high BMI, genetic predisposition, ovarian surgery and pelvic adhesions have all been reported to affect the ovarian response and several ovarian stimulations protocols have been suggested to improve the oocyte yield and the reproductive outcome, but the handling of the poor responder patient still represents a therapeutic challenge.
Kui Liu (Sweden) analyzed the genetic factors of premature ovarian failure (POF), defined as a primary ovarian defect characterized by premature depletion of ovarian follicles, or arrested folliculogenesis before the age of 40 years. The mutant mouse models suggest that lack of functional ovarian follicles, which may be due to defective processes of primordial germ cell (PGC) development, follicular formation, follicular activation or development, can all lead to POF. He suggested that developing reliable techniques for in vitro culture of premature follicles to obtain fertilizable ova could be a promising way to rescue the fertility of POF patients.
Lawrence M. Nelson (USA) gave a clinician’s perspective on management of primary ovarian failure and emphasized the need to (i) make a timely diagnosis, (ii) be a sensitive messenger when delivering the diagnosis, (iii) comfort the patient by providing accurate information and (iv) take approaches that will reduce stigma and illness uncertainty.
A keynote lecture on luteal phase support (LPS) was given by M. Filicori. Little controversy surrounds the use of progesterone (P), which is applied in the majority of ART cycles. Different routes of administration can be used: the intramuscular route is preferred in the US, whereas the intravaginal route is preferred in Europe because side effects are more limited. He showed that the addition of estrogen in LPS is far more controversial; in the majority of patients there is no need for an estrogen supplementation after oocyte retrieval. Concerning low-dose hCG he emphasized that it had become almost obsolete due to the potential risk of contributing to ovarian hyperstimulation syndrome (OHSS). More studies are needed to assess the optimal hCG dose and regimen associated with good clinical results. He mentioned also the intermittent use of GnRH agonist after oocyte retrieval in GnRH antagonist cycles, but this experimental approach still needs to be evaluated on a larger scale.
At the end of this session the two case studies on practical management of infertility patients were introduced, two of them were presented by P. Humaidan and the last one by M. Nelson.
The third session focused on genetic testing for embryo selection. Marie Louise Grøndahl (Denmark) described quality markers and discussed the methods used for defining the developmental competence of follicles. Taking the complexity of the follicle into account, marker gene expression profiles rather than single marker genes seem reasonable.
William G. Kearns (USA) presented an overview of new genomic technologies in assisted reproduction. Pre-implantation genetic diagnosis (PGD), which identifies genetic abnormalities in embryos prior to ET, is for five distinct patient groups: (i) infertility related to recurrent miscarriages or unsuccessful IVF treatment, (ii) unexpected infertility, (iii) advanced maternal age, (iv) severe male factor infertility, and (v) couples at risk for transmitting a hereditary disease. To test single cells for structural or numerical chromosome abnormalities, he mentioned sophisticated techniques as SNP (single nucleotide polymorphism), CGH (comparative genomic hybridization), real-time PCR and FISH (multi-color fluorescent in situ hybridization), while the PCR (polymerase chain reaction), linkage analysis and DNA sequencing are used to analyze single cells for disease-specific DNA mutations.
Richard A. Anderson (UK) presented a keynote lecture on the epigenetics of male gametes. It is increasingly clear that epigenetic modification can be influenced by environmental factors which, if occurring in the germ line, may be transmitted to subsequent generations. There is also emerging information regarding abnormalities in epigenetic modifications associated with abnormal spermatogenesis. He also explained that the increasing use of abnormal gametes for conception in assisted reproduction raises the possibility, and perhaps even likelihood, that children thus conceived will also have imprinting abnormalities.
The last session presented an update on surgical matters related to IVF treatment. David Adamson (USA) discussed the management of endometriosis when associated with infertility. He presented the results of a literature review that showed that few endometriosis publications are randomized clinical trials (RCTs) and this has resulted in opinion and variable treatment regimens rather than evidence- and outcome-based medicine. Evaluation of the available data does allow general conclusions that help guide each individual’s treatment. For example RCTs show that ovarian suppression does not improve pregnancy rates compared to no treatment at all, including before or after surgery. The only exception providing some benefit is 2– 6 months ovarian suppression for severe/extensive disease before IVF. For minimal/mild endometriosis, surgical treatment is more effective than no treatment. A new Endometriosis Fertility Index (EFI) has high predictive value for pregnancy rates after surgical evaluation and treatment of endometriosis.
Rudi Campo (Belgium) reviewed the treatment and management of fibroids, an extremely common benign uterine pathology. The incidence increases with reproductive age and approximately 10% of women with infertility problems will present with a myoma. Evidence exists that subserosal myomas significantly decrease implantation rate. Unfortunately, the effect of intramural myomas upon reproduction outcomes remains unknown and until now no adequate diagnostic and therapeutic guidelines have been established. He showed some videos demonstrating different modern techniques of hysteroscopic myomectomy, new instrumentation, the tips and tricks, the possible complications and clinical outcomes.
Keith Isaacson (USA) analyzed all the uterine abnormalities including conditions such as polyps, adhesions, uterine septum, bilateral hydrosalpinx, tubal occlusion and adenomyosis providing surgical techniques to repair each previous diseases before IVF treatment.
May 30, 2011; Lisbon, Portugal
David Mann (UK) delivered the first lecture dedicated to pathological and molecular genetic correlates of frontotemporal lobar degeneration (FTLD). FTLD is the second most common neurodegenerative cause of presenile dementia after Alzheimer’s Disease and encompasses a number of neurodegenerative diseases affecting the frontal and temporal lobes. FTLD’s etiology is mostly unknown but, since 40% of people with FTD have a family history of dementia, genetics plays a crucial role. The three main clinical syndromes are: FTD, semantic dementia (SD), and primary progressive non-fluent aphasia (PNFA), and these phenoptypes are related to the location more than to the kind of damage affecting the brain. In fact, FTLD is also pathologically heterogeneous. About 35% of cases are positive for tau inclusions (FTLD-tau) while, in tau–negative forms, TDP-43 pathology, FUS pathology and pathology without defined inclusions have been observed. David Mann provided and detailed descriptions of pathological findings in the different forms.
Federica Agosta discussed the role of MRI in the diagnosis. She introduced the MRI diagnostic criteria for FTD and those proposed more recently for primary progressive aphasia (PPA). Impressive improvements in the understanding of dementia mechanisms have been obtained with advanced MRI techniques such as functional MRI (fMRI). The speaker showed impressive MRI images relating several different neurological disorders to specific localization of brain atrophy in PPA and claimed that ‘the scenario is even more complicated and challenging searching for relationships between MRI imaging and pathological findings’. She concluded that MRI’s ability to locate damage in FTA might become important as clinical trials with etiology-specific treatments become available.
Stefano Cappa, delivered the final lecture on the clinical heterogeneity of FTD. He explained that FTD is now conceived as a spectrum of clinical syndromes, reflecting a variety of pathological conditions and he introduced three variants of the frontotemporal spectrum: behavioral variant (bvFTD), progressive aphasia, and movement disorder variants. The first report of the international bvFTD Criteria Consortium recently proposed diagnostic criteria for behavioral variants. Moreover, the speaker’s group, in collaboration with colleagues from San Francisco, worked on a comprehensive experimental assessment of social cognition in FTD. Sketches used for this assessment and some of the outcomes were shown. The speaker referred to a paper published in February by Gorno-Tempini et al. which proposed a classification of PPA and its variants. Stefano Cappa reviewed also the characteristics of the right temporal variant of semantic dementia, and movement disorder variants. He concluded by reminding delegates that the relationship between the clinical and ’imaging’ phenotype of FTD is only probabilistic.
June 7- 9, 2011; Barcelona, Spain
Visits to the host’s facilities gave a useful insight into the Centre’s activities and procedures. Professionals from Centre d’Esclerosi Multiple de Catalunya (Cem-cat), as usual, formed the core of faculty, which also included the invited speakers who were top experts in the field, including Alan Thompson (UK), Eva Havrdovà (Czech Republic), Giancarlo Comi (Italy), Pablo Villoslada (Spain), Maria Pia Amato (Italy) and Angelo Ghezzi (Itay).
In the 2011 MSP, two distinguished scientists, Christiane Wegner (Germany) and Alexandre Prat (Canada) joined the faculty and delivered two excellent talks on, respectively, ‘The pathology of MS’ and ‘The treatments targeting the blood–brain barrier’.
Alan Thompson (UK) provided a detailed review of primary progressive MS , and Manuel Comabella (Spain) delivered two state-of-the art talks on MS genetics and pharmacogenomics. The program also included a series of comprehensive lectures addressing the complexity of the current and future therapeutic scenarios.
There was a lively panel discussion on cognition disorders, and case study sessions, where the use of a voting system allowed participants to provide their feedback on the different diagnostic and therapeutic options discussed.
The MS Preceptorship also showed that MS is best managed through team work involving physicians, psychologists, scientists, nurses and rehabilitators – speakers and chairmen all stressed how important it is to put the patient in the centre of a system where healthcare professionals interact to optimize their approach and improve the outcomes. The effectiveness of teamwork was also emphasized by the role-play session which, as in the previous MSP meetings, was stimulating and successful. Maria Jesus Arevalo (Spain) and Jaume Sastre-Garriga (Spain), together with an MS patient, presented some scenarios where key aspects of doctor/patient interaction were presented and discussed with participants.
Participants compared the different situations that doctors working in different countries have to deal with, and agreed on the need to improve adherence, and that careful consideration of the patient’s feeling and needs were essential in planning treatment.
July 2, 2011; Stockholm, Sweden
Regarding treatment strategies for poor and high responders, Dr E. Bosch (Spain), analyzed different approaches. For poor responders, the speaker showed that presumed protocols are able to provide a higher number of oocytes using GnRH agonist long protocol, including the use of GnRH antagonist and the increase in gonadotrophin doses. More recently a benefit has been shown for the use of letrozole or androgens for priming. The management of high responders is directly related to the prevention and treatment of the ovarian hyper-stimulation syndrome (OHSS). The first step is to recognize patients with risk factors, such as young age, low BMI, polycystic ovaries (PCO), high anti-Müllerian hormone levels (AMH) and background of previous OHSS. The choice of a GnRH agonist in this case will reduce the possibilities of OHSS, as will cryopreservation of all embryos for a later transfer and the use of dopamine agonist in the luteal phase.
Concerning strategies for couples with severe male factor infertility, Prof. A. Agarwal (USA) showed that 20% of the severe male factor infertility (SMFI) cases are caused by severe oligozoospermia, non-obstructive azoospermia, severe asthenospermia or severe alterations of the three main semen parameters (count, motility and morphology). He also described new approaches to dealing with men with frequent failures in ICSI cycles, including selection of the best sperm, and modifications of ICSI.
The last lecture dealt with the ovarian hyper-stimulation syndrome (OHSS) and was delivered by Prof. A. Pellicer (Spain) who explained the pathophysiology of the OHSS. His studies have shown how important it is to choose the right protocol, or at least cancel the cycle in those patients who are at serious risk of developing OHSS (i.e. serum E2> 4000pg/ml and/or >30 follicles developed). Other studies have shown that the use of dopamine agonist as quinagolide (QN) may be associated with a significant reduction in the frequency of moderate/severe early OHSS.
The afternoon session was focused on laboratory issues and started with the lecture given by Prof. D. Wells (UK) on PGD (pre-implantation genetic diagnosis), as an alternative to prenatal testing. PGD aims to provide families at high risk of transmitting inherited disorders with unaffected children, and has been applied to the diagnosis of more than 200 distinct genetic disorders. It is widely applied for the purpose of detecting chromosome abnormalities in oocytes or embryos produced by carriers of chromosome rearrangements, thus helping to reduce the high risk of miscarriage. He also explained how the recent introduction of whole genome amplification and microarray analysis has opened up new possibilities for genetic testing.
Prof. J. Donnez (Belgium) discussed the issue of fertility preservation. He analyzed the different cryopreservation options available in cancer patients such as embryo, oocyte and ovarian tissue cryopreservation. The only established method of fertility preservation is embryo cryopreservation, but this requires the patient to be of pubertal age, have a partner and be able to undergo a cycle of ovarian stimulation. Tissue cryopreservation is the only option available for pre-pubertal girls and for women who cannot delay the start of chemotherapy.
Dr T. Freour (France) discussed the assessment of oocyte quality and highlighted that the study of its morphology can give some useful information on its nuclear and/or cytoplasmic maturation. New routes are also currently being explored, based on functional evaluation of the oocyte, such as: oocyte surroundings, cumulus cells and various soluble markers released in the follicular fluid during the oocyte maturation.
In his lecture on embryo culture, Dr D. Gardner (Australia), clearly showed factors that directly impact embryo development and viability, such as the use of reduced oxygen tension, an appropriate incubation system and an adequate pre-screening of all contact supplies such as oils and plastic ware. This has translated clinically into higher implantation and pregnancy rate, decreased pregnancy loss and the ability to transfer single embryos confidently.
The last lecture given by Dr J.A. Horcajadas (Spain) covered the endometrium receptivity, a topic that has recently attracted the experts’ attention but still has not been properly elucidated. His laboratory has created a molecular tool called ERA (Endometrial Receptivity Array) using microarray technology and determining the transcriptomic signature of the endometrium during the window of implantation (WOI).
Reproductive Medicine
A window into the reproductive era research
September 30, 2011 - October 1, 2011; Milan, Italy
IVF Preceptorship: current practice in the 21st century
December 1, 2011 - December 2, 2011; Madrid, Spain
Individualized controlled ovarian stimulation and objective gamete and embryo selection
December 7, 2011; Yokohama, Japan
Neurology
Cognition disorders in MS
September 30, 2011 - October 1, 2011; Florence, Italy
MS Academia: Multiple sclerosis advanced course
October 18, 2011; Amsterdam, Netherlands
13th MS Nurse international workshop
October 18, 2011; Amsterdam, Netherlands
Management in multiple sclerosis: integrating revised diagnostic criteria with newer treatments
November 5, 2011; Toronto, Canada
MS Preceptorship Fall 2011
November 7, 2011 - November 9, 2011; Barcelona, Spain
Satellite symposium WFN 2011
December 12, 2011; Shanghai, China
Endocrinology and metabolism
Genomics and pharmacogenomics of growth disorders
October 27, 2011 - October 28, 2011; Buenos Aires, Argentina
2nd Dietitians Workshop on PKU
March 22, 2012; Rome, Italy
4th European Phenylketonuria Group (EPG) Symposium: Advances and Challenges in PKU
March 23, 2012 - March 24, 2012; Rome, Italy
Oncology
9th Latin American Medical Education Workshop
November 4, 2011 - November 5, 2011; Santiago, Chile
PKU Academy and PKU Masters
