report 309 pregnancies and 139 births through IVF, andpregnancy rates were expressed per cycle started, perlaparoscopy or per transfer. He explained howpregnancy rates can be monitored according to variousfactors. “Life table analysis” was introduced in hiscentre and this method estimates what would happento couples that have been followed up for further cycles.He stressed the importance of comparing “apples” with“apples” and not with “pears” and said that in the futurethe results would have to be standardize for patientpopulation (especially age), and we should aim toperform SET (single embryo transfer) most of the timewhen possible.

In the second lecture K. Venees (UK) explained thepatient point of view. She is a member of the “Infertility

network” in the UK, and is spokeswoman for patientsat IVF centres who have undergone the difficulttreatment of IVF to achieve the dream of a child. Sheshowed a movie about her family and explained theprocess involved before achieving the successful birthof a healthy daughter. After 12 months, she becamenaturally pregnant with her second child and she finally

2013 CME Annual meeting in reproductive medicine

Improving success in ART: howto define it and key strategies toget the best outcomes26-27 April 2013 - Athens, Greece

Different clinicians in different disciplines identifysuccess differently, and the clinical definition may notbe important to the patient. However, there is generalagreement about the goal: an individual, healthy, full-term infant.

SESSION IWhat is the most relevant standard of success in ART?

The first session started with an introduction fromthe scientific organisers regarding the flow of themeeting. Each lecture was preceded and followed by a

question regarding the topic of the lecture in order toevaluate the knowledge of the participants. This firstsession was dedicated to defining the meaning ofsuccess starting from the physician’s point of view. G.Kovacs (Australia) explained that during 30 years of ARTthe technique of IVF has changed and so has thedefinition of success in ART. By 1983 he was able to

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NEWSLETTERThe Serono Symposia International Foundation newsletter | Spring/Summer 2013

REPRODUCTIVE MEDICINE

Timing of conception: no limits?29-30 March 2013Moscow, Russian Federation ON PAGE 4

International School of Ultrasound inobstetrics and gynecologyTransvaginal evaluation of PCOSand dysfunctional ovarianpathologies24-25 May 2013 - Siena, Italy ON PAGE 5

6th Advanced course in embryology6 July 2013 - London, UK ON PAGE 6

29th Annual Meeting of the EuropeanSociety of Human Reproduction &Embryology (ESHRE)7-10 July 2013 - London, UK ON PAGE 7

IVF Preceptorship: The state ofthe ART2-3 August 2013 - Sao Paulo, Brazil ON PAGE 8

EDUCATIONALACTIVITIESHIGHLIGHTS

Online activities ON PAGE 10

SSIF Educational events - Autumn/winter programme 2013 ON PAGE 11

Satisfaction rate:% Very Satisfied / Satisfied: 99%

[ ]This SSIF CME annual meeting was a highly dynamic format andsuccessfully demonstrated how a mix of different educational approaches

can increase learner engagement and impact on their knowledge.

achieved the life she had dreamed of.A.M. Dlugi (USA) discussed the meaning of

success from the viewpoint of the healthcareorganisation. Between 1998 and 2008 themultiple birth ratio in the US increased nearly14%, compared to singleton births. That meansthat 62% of twins and 97% of ART triplets weredelivered preterm and the estimated relative costof each preterm infant is about $51,600; theestimated annual financial burden of ARTpreterm deliveries is $1bn. He showed thestrategies to reduce multiple pregnancies,starting from decreasing gonadotropin cycles forunexplained infertility or mild male factorinfertility, educating consumers regarding therisks of a multiple gestation, including twins andpromoting elective single embryo transfer (eSET).

The pediatrician’s point of view was discussedby M. Bonduelle (Belgium), who explored thetopic of complications in babies born after ART.She explained that 1 in 25 babies in westerncountries are conceived through ART, andemphasised the importance of identifying inadvance the complications mainly attributed toparental background, infertility per se, and to thehigh rate of multiple pregnancies. Regarding theperinatal outcome, most of the complications aredue to pregnancy complications such asprematurity risk in singletons <37 weeks ofgestations, low birth weight rate <2500g, 1500g.The most important causes of pregnancycomplications are pre-eclampisa, prematurerupture of membrane, placenta previa andgestational diabetes. Data regarding the neonataloutcome from twins born after ART and thegeneral population is comparable, and there areno obvious differences between IVF and ICSI.Regarding chromosomal abnormalities, babiesborn after ICSI have a higher rate than thegeneral population, mainly attributed to sexchromosomal abnormalities linked to spermparameters. There are no significant dataregarding congenital malformation between ICSIand IVF technique. There are studies of follow upafter 18 years that show normal physicaldevelopment compared to spontaneouslyconceived controls. She concluded that it is stillimportant to monitor health and psychosocial

development of this new generation of youngadults born after ART. The session concludedwith questions and discussion that allowed theparticipants to comment and further explore thecontent of the lectures.

SESSION IIHow to get the best results: stimulationprotocols

This session started with an innovation:debates on controversial topics. The first debatewas on stimulation protocols. F. Broekmans (TheNetherlands) argued for the use of the mildstimulation approach for all ART patients,showing how with reduction in the dosage ofgonadotropins it is possible to reach the efficacyof the treatment, reducing the cost andenhancing the convenience, and he emphasisedthat this approach is safe for the mother andchild. He showed data supporting that thereduction of FSH dosage leads to moderateovarian response and there are no differences inpregnancy rate for started cycles; in addition, theOHSS rate may be halved. He concluded that mildstimulation for all ART patients does notinfluence the oocyte quality, and that it is cheapand convenient and, moreover, safe. A. Pellicer(Spain) argued for the role of controlled ovarian

stimulation and (COS) and maximizing thesuccess rate in ART with tailored stimulationprotocols. He started with the definition ofconventional or standard COS that means the useof 225-250 UI day gonadotropins in normalresponders. The goal will be to obtain 15-20oocytes avoiding OHSS. He showed how theantagonist protocol can avoid OHSS andmaximize results. At the end of the debateSunkara addressed burning questions to bothdebaters and the audience consensus was infavour of COS protocols as best the approach toovarian stimulation.

C. Alviggi (Italy) showed how predictivebiomarkers could be used to facilitate treatmentdecisions and to tailor therapy to increase thechances of achieving pregnancy. Among thehormonal biomarkers, anti-Mul̈lerian hormone(AMH) has been shown to have the highestpredictive value, and it also modulates the activityof follicle-stimulating hormone (FSH) in antralfollicles during the FSH-dependent growth stage.Antral follicle count (AFC) is a well-knownfunctional biomarker that is used to predictovarian response to stimulation. It is also animportant factor in determining the optimalstarting dose of FSH for ART. Recent lines ofresearch also reinforce the hypothesis thatovarian resistance (hyporesponse) to exogenousFSH can be related to specific genepolymorphisms as receptor and LHpolymorphism. These data support the idea of atailored administration of gonadotropins basedon a pharmagenomic approach.

The last lecture was focused on managementof complications and new strategies to avoidOHSS. J.A. Garcia-Velasco (Spain) showed howOHSS in the 21st century remains an iatrogeniccomplication during COS. Prevention has reliedon the awareness of the importance of clinicalparameters such as age, BMI, AFC, serumestradiol levels or number of developed follicles.Different strategies have been evaluated forOHSS prevention including withholding humanchorionic gonadotrophin (hCG) to coasting, andvitrification of the oocyte/embryo. More recently,dopamine agonist administration and theantagonist protocols provide the use of GnRhagonist to trigger final oocyte maturation.

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SESSION IIIHow to get the best results: oocytes qualityversus quantity

S.K.R. Sunkara (UK) showed data thatdemonstrated that there is strong associationbetween the number of oocytes retrieved and livebirths following IVF. The optimum number ofoocytes needed to maximize IVF outcomes is stillcontroversial. COS should be tailored to theindividual phenotype, maximizing the ocytes yieldfor poor responders and fine-tuning for hyperresponders. She demonstrated how GnRHantagonist regimens optimise oocytes retrievedand maximise live births in all ART cycles. A.Sunde (Norway) explained the relationshipbetween oocyte/embryo quality and stimulationprotocols. Much data have demonstrated therelationship between observable oocyte/embryoparameters and outcomes in terms ofpregnancies but none is particularly good inpredicting oocyte/embryos quality. Severalstudies suggest a relationship between ovarianstimulation and oxygen consumption in oocytes,cumulus cell expression, implantation anddelivery rates.

Genetic quality and the relationship withnumber of oocytes was the subject of S. Munné’s(USA) presentation. He explained howchromosome analysis of human embryos hasevolved considerably in the last few years, fromusing fluorescence in situ hybridization (FISH)with 5-12 probes and mostly performing polarbody or day-3 biopsy PGSv1 (preimplantationgenetic screening) to analysing all chromosomeswith arrays from blastocyst biopsies (PGS v2).With the advent of the PGS technique the errorrate of diagnoses has been reduced from 7.50%,depending on the laboratory, to 3%. Pregnancyoutcomes have significantly improved. Datasupport that using PGSv2 there are no differencesin chromosome aneuploidy rates, irrespective ofthe cohort size produced. Aneuploidy increaseswith maternal age and does not decrease withcohort size.

In contrast, F. Fiorentino (Italy) showed thathigher oocyte yield is associated with anincreased error rate and that this might beexplained by unphysiological ovarian stimulationinterfering with chromosome segregationbehavior during maternal meiosis. Other studieshave demonstrated that the incidence ofaneuploidy in embryos may be affected by ovarianstimulation regimens employed in IVF, and thatthe mild stimulation is associated with areduction in the number of oocytes retrieved andembryos generated compared with moreintensive protocols. He presented data showingthat an increased incidence of aneuploid embryosseems to be associated with a higher number ofoocytes produced by ovarian stimulation.

The controversies section featured a debatebetween Munné and Fiorentino regarding embryobiopsy day-3 against day-5. Munné showed howblastocyst biopsy has more advantages with moreDNA, lower error rate, and reduced impact onembryo biopsy, which means fewer embryos toprocess, because not all reach the blastocyststage. He showed data regarding micro array

CGH on day 3 and on day 5; the results of thestudy have shown that the implantation afterembryo biopsy day 5 is 50% instead of 40% withday 3 biopsy, and pregnancy rate per transfer is63% instead of 52% with biopsy day 3. Fiorentinoremarked that embryo biopsy day 3 is still usefulbecause at cleavage stage it is not detrimental forthe embryo and is still useful for patient with alow embryo development rate to blastocystestage. The debate outcome demonstrated thatthis topic remains controversial and emphasisedthe need for more data.

SESSION IVHow to define the best strategy and thetechnologies to make it happen

A. Sunde (Norway) explained how difficult it isto define strategies to achieve the results.Calculating the success of ART is far morecomplicated than just pregnancy rate per embryoreplacement. Success criteria may also bedifferent in different regulatory and financialenvironments. In states where the cost of ART iscovered by the government or health insurance,the health provider will focus on total cost and canintroduce economic incentives or regulations toincrease the use of elective single embryotransfer (eSET). The role of embryo selection isdependent on the success criteria used. If thepregnancy rate after transfer is the mostimportant success criterion, then a selectionalgorithm is needed that identifies the embryoswith the highest developmental potential in agiven cohort, but the algorithm will not influencecumulative delivery rates.

L. Rienzi (Italy) discussed how the use oftechnologies maximizes the success. One of themajor hurdles to improving the overall efficiencyof fertility treatments is the lack of objective toolsto identify gametes with the highest viability andembryos with the highest implantation potential.The system commonly used in andrology andembryology laboratories is based mainly onsubjective morphological criteria. She reviewedall techniques available in the laboratory toassess the quality of gametes and embryo frommorphokinetics to embryo biopsy and suggestedthat the future will be an automation and

technology combination from evaluation ofcumulus cells of oocyte, IVF and ICSI procedures,followed by dynamic morphological evaluationuntil biopsy and evaluation of trophectodermcells.

N.G. Puchalt (Spain) showed recent data onsperm evaluation using mRNA microarraytechnology. Evidence suggests a requirement ofsperm-delivered mRNA for adequate embryoformation, thus using a specific mRNA signatureobtained from sperm samples from which apregnancy was obtained to define male fertilitycould be useful as a gold standard. His researchgroup initiated the Sperm Fertility Assay (SFA)project, which aims to determine the optimaltranscriptomic signature in sperm for each ART.The aim is to develop a microarray-based spermdiagnostic tool to be clinically employed incounseling for couples and also to develop spermselection strategies.

Uterine environment and endometriumreceptivity was discussed by C. Simon (Spain).This period refers to a hormone-limited period inwhich the endometrial tissue acquires afunctional and transient ovarian steroid-dependent status allowing blastocyst adhesion.Studies have demonstrated that endometrialreceptivity is an active process involving up-anddown-regulation of hundreds of genes. His grouphas developed the endometrial receptivity array(ERA) tool, a customized array of 238 genes.Preliminary data supporting the ERA methodsuggest that about 15% of all patients can benon-receptive. More data are needed todemonstrate and to support previous results.

SESSION VUnsession

The unsession was dedicated to reinforcingthe aim and the learning objectives of themeeting. All the speakers concluded with a take-home message summary of their point of view.This session was also important for reviewing theconclusions of the debates and the answers givenby the participants during the real time survey toevaluate if their knowledge was enhanced afterthe meeting.

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Timing of conception: no limits?29-30 March 2013 - Moscow, Russian Federation

The course was focused on the effect ofadvancing age on clinical infertility and how it ismanifested in the pattern of ovarian response tocontrolled ovarian stimulation (COS). How femaleage reduces implantation efficiency and increasesspontaneous abortion rate was also considered.The course was interactive and featureddiscussion sessions to focus participant attentionand interest.

SESSION IMaternal age and ovarian reserve

The first session was dedicated to maternalage and ovarian reserve. S.K. Sunkara (UK)explained how the demographics and the age ofchildbearing in women have been changing overthe decades, although the physiology of femalefertility remains unchanged. Human ovaries havea finite number of oocytes endowed before birthand there is a constant depletion of the oocyte poolfrom that time. This exponential decline in oocytequantity and a parallel decline in oocyte qualityhas an impact in female fertility. Epidemiologicalobservations in natural fertility populations haveshown declining fecundity with maternal age. Sheshowed different therapeutic approaches tostimulation protocols as GnRH agonist versusantagonist regimen and explained that publisheddata show no significant different between agonistlong protocol and antagonist regimens in poorresponders. The antagonist regimen has thebenefit of compliance and cost effectiveness.

S. Nelson (UK) focused his lecture on markersof ovarian reserve and the association with ovarianaging. Assessment of ovarian reserve includesmeasurement of serum follicle stimulatinghormone (FSH), anti-Mul̈lerian hormone (AMH),and inhibin-B. Ultrasound determination of antralfollicle count (AFC), ovarian vascularity andovarian volume can also have a role. In infertilewomen, ovarian reserve markers can be used topredict low and high oocyte yield and treatmentfailure in women undergoing in vitro fertilization.The main objective of individualization oftreatment in IVF is to offer every single woman thebest treatment tailored to her own uniquecharacteristics, thus maximizing the chances ofsuccess and eliminating the iatrogenic andavoidable risks resulting from ovarian stimulation.The starting point is to identify whether a womanis likely to have a normal, poor or a hyperresponse and choose the ideal treatment protocoltailored to this prediction. The data shown fromthe literature demonstrated that AFC and AMHare the most sensitive markers of ovarian reserve,and are ideal in planning personalized COSprotocols.

The role of LH supplementation in poorresponders was presented by S. Nelson (UK). In

younger women a poor response to ovarianstimulation may also be observed, but their overallsuccess rates will be less adversely affected thanin their older counterparts. Strategies to improve

success rates in women with a reduced ovarianreserve have been limited, but LHsupplementation would appear to be beneficialand easily achieved. He explained which patientsbenefit from LH supplementation in ART: patientswith hypogonadotropic-hypogonadism, poorresponders, and women older than 35 years. Atthe end of this session the participants weredivided into groups to analyse the differenttherapeutic approaches with the help of casestudies prepared by the speakers.

SESSION IIMaternal age and oocyte/embryo quality

This session addressed oocytes and embryoquality. S. Nelson (UK) described how age relatesto decline in oocyte quantity and quality, and isassociated with the risk of a poor ovarianresponse and aneuploidy. He explored whetheryounger women with a reduced ovarian reservealso have a concomitant reduction in oocyte

quality that contributes to their lower successrates. He showed studies that suggest that theywill continue to have improved outcomes relativeto their older counterparts even if they produce

the same oocyte yield, suggesting that quantityand quality are independent determinants ofoutcome, with age being the principaldeterminant of quality. He emphasised that oocyteand embryo aneuploidy are age dependent, andthat milder stimulation gives fewer oocytes to testand runs the risk of poor response. He explainedthat stimulation may alter aneuploidy, in factGnRh antagonist cycles show similar aneuploidyto natural cycles.

SESSION IIIMaternal age and pregnancy after ART

R. Fischer (Germany) introduced the topic ofluteal phase support. He described themechanism of the corpus luteum, which is anovarian endocrine gland that develops afterovulation and characterizes the luteal phasefollowing ovulation. It actively secretes steroidhormones, particularly progesterone, and isfundamental for the maintenance of early

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Satisfaction rate:% Very Satisfied / Satisfied: 98%

[ ]The learners were extremely satisfied and demonstrated ahigh interest in the workshop format: they were extremelyactive during the working groups, speakers’ case studies

presentation and discussions.

pregnancy. Progesterone prepares theendometrium for pregnancy by stimulatingproliferation in response to human chorionicgonadotropin (hCG). Luteal-phase gonadotropindependent dysfunction can lead to corpus luteumdysfunction and reduced female fertility. Hencechanges in the endocrine pattern due to thegonadotrophins used for ovarian stimulation arethought to underlie the corpus luteum dysfunctionassociated with IVF cycles. In ART, progesteroneproduction by the corpus luteum is reduced sothat the luteal phase is supported, improving theimplantation rate and thus pregnancy rates. Theluteal support can be done with progesterone,hCG or gonadotropin releasing hormone (GnRH)agonists. He presented some recent systematicreviews that showed a significant effect in favourof progesterone for luteal phase support, and

favouring synthetic progesterone over micronizedprogesterone.

S. Sunkara explained the process ofimplantation and how it is influenced by complexinteractions involving maturational events in theembryo, synergism of the endometrium, maternalhormonal changes and immune responses. Theadvent of IVF has provided a unique opportunity tostudy factors affecting human embryoimplantation. The negative impact of advancedfemale age on implantation has beendemonstrated by IVF studies. Whilst, it wasaccepted that female age influences implantationit was initially debated whether this was a resultof the embryonic or endometrial factors. Studiesof oocyte donation involving young donors andolder recipients confirmed that the former wasthe main contributory factor to reduced

implantation with advanced female age. There ismounting evidence that the increased risk ofmiscarriage in older women, including womenundergoing ART, is a result of chromosomalaneuploidy as a consequence of oocyteaneuploidy.

The management of pregnancy after ART wasdiscussed by S. Sunkara. She suggested thatsuccess in ART should be defined as achieving ahealthy live birth at term. However the advent ofART has brought complications in pregnancy dueto a multiplicity of factors. ART carries the risk oflate onset ovarian hyperstimulation syndrome(OHSS) in early pregnancy. It has been a matter ofdebate whether there is an increased incidence ofearly pregnancy complications such as early/latemiscarriages and ectopic pregnancy followingART.

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In recent years the combination of transvaginal sonography with advancedDoppler techniques (color/power) and three-dimensional (3D-US)approaches has made transvaginal ultrasound an indispensable tool in thediagnosis of gynecological diseases. The introduction into clinical practiceof the modern high-frequency endovaginal probe has allowed gynecologiststo achieve a high diagnostic accuracy in the study of ovarian cysts, bothdysfunctional and physiological. The differential diagnosis betweenfunctional and organic ovarian cysts is crucial in choosing the mostappropriate treatment. The dysfunctional ovarian cysts are caused byhormonal imbalances in the ovulatory cycle, probably as a result of anexaggerated ovarian response to hormones. They are benign, transitionaland in any case susceptible to medical therapy. They are typical ofreproductive age and they can be divided into follicular, luteal andhemorrhagic cysts. The polycystic ovarian syndrome (PCOS) is a commoncause of anovulation and infertility, clinically manifested by hirsutism andacne. Ultrasound has a very important role in the diagnosis of this conditionas this technique can identify the typical ovarian features representing oneof the three criteria used to make the diagnosis.

Satisfaction rate: % Very Satisfied / Satisfied: 100%

International School of Ultrasound in obstetrics and gynecology

Transvaginal evaluation of PCOS anddysfunctional ovarian pathologies24-25 May 2013 - Siena, Italy

This educational course was developed incollaboration with ALPHA: scientists inreproductive medicine. It focused on the impactof new laboratory technologies on success ratesin IVF and delivered with three sessions and afinal debate on “who is the most important in theIVF scenario between clinician and embryologist”.This challenging topic allowed active participationby the audience with the winner the embryologist.However it was recognised that the success of anIVF programme depends on the synergistic actionof different professional figures, and on the highlevel of staff motivation.

SESSION INew technologies in reproductive medicine

In the first lecture, E. Borges (Brazil)highlighted the role of real-time highmagnification observation of spermatozoa, called“motile sperm organelle morphologyexamination” MSOME. This system permits theidentification of vacuoles in the sperm nucleus,whose role in sperm function is not completelyclear. Furthermore, the incorporation of MSOMEin ICSI procedures has allowed the introductionof IMSI (intracytoplasmic morphologicallyselected sperm injection). A positive correlationbetween IMSI and high quality embryos,implantation, pregnancy and live birth rates wasobserved mainly in cases of previous implantationfailures, high sperm DNA fragmentation rates,male factor, advanced maternal age andunexplained infertility.

M. Bungum (Sweden) spoke about thecontroversial relationship between the spermDNA fragmentation and miscarriages. Indeed,although male partners of couples experiencingrecurrent pregnancy loss have increased spermDNA fragmentation rates compared to controls,

the evidence for a direct association iscontradictory. Probably, it depends on thedifferent methodologies used for detecting spermDNA fragmentation and on the different aspectsof DNA damage measured (single stranded ordouble stranded DNA breaks). New large-scale

studies differentiating between the different typesof DNA damage are needed, to improvecounseling for patients with infertility andrecurrent pregnancy loss.

J. Van Blerkom (USA) evaluated themitochondrial activity during oocyte and embryodevelopment. Mitochondria in the cell do notproduce only ATP but have different pleiotropicand regulatory functions (such asmacromolecular modifications, steroidogenesis,intracellular signaling and signal transduction).For blastocysts, the mitochondrial developmentis accompanied by increased capacity to generate

ATP. Furthermore, it has been described thatdisproportionate segregation of mitochondriabetween blastomeres during early cleavagestages and abnormal regulation of free calciumhomeostasis can determine reproductive failure.This could represent an important but

unrecognized factor impacting on IVF success.H. J. Leese (UK) highlighted the nutritional

requirements for oocytes and pre-implantationembryos, demonstrating that the early stages ofembryo development are quiescent in terms ofnutrient and oxygen consumption. The blastocyst,instead, is characterized by a sharp increase inmetabolic activity, in protein synthesis and Na+K+ ATPase activity, due to the high energy requestfor blastocoel formation. Interestingly, theturnover of amino acids has been correlated toembryo viability, showing that viable embryoshave an amino acids depletion and appearance

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Satisfaction rate:% Very Satisfied / Satisfied: 100%

6th Advanced course in embryology6 July 2013 - London, United Kingdom

[ ]Learners had the opportunity to express their own views andopinions on new diagnostic tools for male infertility and how tomodify the routine clinical activity necessary to deliver quality

procedures in IVF laboratory.

within a lower range than the arrested ones. Theaddition of creatine to embryo culture media mayimprove cytokinesis, a crucial process forembryo-cleavage but further research is neededto assess this topic.

N. Macklon (UK) spoke about the role ofendometrial receptivity evaluated by a newapproach called secretomics. This procedure,through the aspiration of endometrial fluids, maybe performed immediately prior to embryotransfer in IVF cycles, with no detrimental effecton the implantation and pregnancy rates asalready demonstrated. Some preliminary reportsidentify an “endometrial fingerprint”, constitutedby pro-inflammatory and anti-inflammatorycytokines, chemokines, growth factors andsignaling factors. Interesting in-vitro studiesshowed that the endometrial cell migration isdirectly related to the embryo viability, being morepronounced in good quality embryos and reducedin poor quality embryos. This selective capacity ofthe endometrium is absent in patients withrecurrent miscarriages, opening new researchpossibilities on this topic. The endometriumseems to play an active role in implantationprocess.

SESSION IIFrom subjective to objective criteria in embryoselection: where are we?

P. Zsolt Nagy (USA) discussed the newtechnologies developed for assessing embryoviability in ART laboratories. The crucial objectiveof ART treatments is to provide the highestchance of pregnancy but, at the same time, toreduce the risks of multiple pregnancies. Theseaims can be achieved with the transfer of a singleembryo with the highest implantation potential.Nevertheless, the identification of objectivecriteria for embryo viability assessment iscertainly difficult. Different invasive and non-

invasive procedures may have an important rolefor this objective. Concerning the invasivemethods, the blastocyst-stage biopsy with array-CGH seems to be very promising but randomizedcontrolled trials need to demonstrate its efficacy.Among the non-invasive methods, the “-omics”technologies (including the microarray analysisof the cumulus cells which surround the oocyte,metabolomics and proteomics) and the time-lapse technology may provide additionalinformation for assessing embryo viability andimproving the success rates in IVF.

The topic of Pre-implantation GeneticScreening (PGS) was discussed by D. Wells (UK).The rationale for proposing this procedure duringan IVF cycle depends on the fact that oocytes andembryos are frequently chromosomallyabnormal, with a direct correlation with the ageof the woman (70% of blastocyst aneuploidies inwomen aged 40-42). Furthermore, thechromosome abnormalities have little effects onembryo morphology. Nevertheless, the clinicaluse of PGS has been controversial. New, moreefficient technologies for comprehensivechromosomal analysis have been introduced inthe last few years. Different randomized studiesdemonstrated that second-generation PGSimproves pregnancy rates and reducesmiscarriage rates. These results will certainlyopen new possibilities for a wider clinicalapplication of PGS in IVF cycles.

K. Turner (UK) spoke about the QualityManagement System which should be adoptedby all IVF laboratories, following the 2006European Tissue Directive. The QualityManagement System (QMS) consists of qualityassurance, risk management and qualityimprovement and describes a program forevaluating the quality of care using a variety ofmethodologies and techniques. Regarding IVF,QMS involves every clinical process in terms of

best practice (medications, risk factors, technicalprocedures, team communication, educationalstaff assessment). It is crucial to control andmeasure the processes involving gametes andembryos within the laboratory, with audit ifappropriate. In this way, the areas consideredcritical may be checked appropriately andeventually amended.

SESSION IIISuccess in IVF: debate on who is the mostimportant?

In the final session, there was a debate on whois the most important between the clinician andthe embryologist. L. Rienzi (Italy) spoke about thecrucial role of the embryologist in determiningthe success rates in the IVF scenario, showingthat all the most important changes in clinicalactivities in IVF during the last few years derivedfrom embryology. She concluded that cliniciansmust recognize the importance of high-laboratory standards with highly qualifiedpersonnel and appropriate investment.

The counter view was taken by G. Grudzinskas(UK), who emphasized the role of the clinician inmotivating staff, in having a general view of theproblems, including legal ones and in leading thegroup in an organised way. He said that continuedtechnical improvements in the lab are absolutelynecessary for providing the best success rates forpatients but are not sufficient without a clearvision of the overall complexity of the clinicalproblems.

The debate was won by the embryologist butall the participants realized that the success of anIVF programme depends on the synergistic actionof clinicians and embryologists accompanied bya high level of staff motivation. In a definitive way,the most important actor in IVF scenario is thepatient with her individual needs and hopes.

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The SSIF presence at EuropeanSociety of Human Reproduction &Embryology (ESHRE) London2013, one of the majorreproductive medicine events ofthe year was a great success. Asteady flow of visitors carne to theSSIF stand during the four dayswe were open, with 300registrations to the SSIF website. On the stand were RobertFischer, from SSIF's ScientificCommittee and medical directorat Hamburg Fertility Centre,Chloé Xilinas, senior projectmanager Reproductive Medicine,and Simona Pantaleoni, associateproject manager. lt was anopportunity to promote a number

of events including the Top Ten inReproductive Medicine inFlorence from 20-21 September2013 and the “twin site” IVFpreceptorship we are holding inMadrid and Valencia also inSeptember. A range of materialswere on hand for visitors to takeaway, including questions andanswers from the ReproductiveMedicine Annua! Meeting inAthens this April and brochuresfor upcoming events such as thelnternational School ofUltrasound in Obstetrics andGynaecology in Siena and the IVFpreceptorship in lstanbul thisSeptember.

29thAnnual Meeting of theEuropean Society of Human Reproduction & Embryology7-10 July 2013 - London, United Kingdom

SESSION IControlled ovarian stimulation: a tailoredapproach

G. Kovacs (Australia) explained that during 30years of ART the technique of IVF has changedand so has the definition of success in ART. Hedescribed the factors affecting success in the IVFcycle beginning with the patient preparation. Themost important tools for individualization includemeasurement of biochemical-AMH, thyroidscreening and ultrasound of the pelvis, with AFC(antral follicle count), and detection of fibroids,polyps, sinechia. It is important to identify casesthat need laparoscopy or hysteroscopy, ifpathology is suspected. Laparoscopy is requestedif hydrosalpinges, endometrioma, or dermoidsare present. He explained how stimulationregimens are based on these previously

evaluated biomarkers and that the selection ofappropriate COH protocol may be one of the mostimportant steps to achieve success.

E. Papanikolaou (Greece) described thesources and effects of increase in P(progesterone) level, including the mechanismsand potential strategies to prevent its elevationduring ovarian stimulation. The origin ofproduction of P in the early follicular phase isadrenal, with a shift toward the ovaries prior toovulation. Several factors contribute to theetiology of P level increase including the numberof multiple follicles, the gonadotropins and poorovarian response. Nowadays, the influence of thepreovulatory P rise on IVF outcome remainscontroversial. Several authors have failed todemonstrate any negative impact, while othershave reported a detrimental effect associatedwith the rise of P. To prevent a rise in P level itmight be preferable to use an earlier trigger ofovulation, cryopreservation of all embryos andtransfer in the natural cycle. He showed datafrom 26 different expression genes in theendometrium; the results from microarrayanalysis suggest a different capability ofendometrial receptivity in the implantationwindow in patients with progesterone levelshigher than normal patients. This may be one ofthe reasons for the lower pregnancy rate inelevated P patients in the day of HCGadministration.

At the end of this session the participants used

Satisfaction rate:% Very Satisfied / Satisfied: 96%

case studies to analyse these differenttherapeutic approaches.

SESSION IITechnologies and laboratory

M. Meseguer (Spain) in his lecture on embryoselection and laboratory techniques explainedthat single embryo replacement using a healthyembryo with the highest chance of implantationwhich results in a single healthy baby at term isthe ultimate goal of ART treatment. This impliesthe ability to screen the embryos in the lab inorder to ascertain which embryo has the highestchance of implantation. PGS has so far beenemployed for this purpose but, in the future, non-invasive methods of embryo screening could be

preferred including time-lapse, oxygenconsumption, proteomics or metabolomics withthe ultimate goal of identifying a high-qualityembryo. A tool has been developed and evaluatedfor the selection of viable embryos based on theexact timing of embryo development eventstogether with morphological patterns by using anautomatic time-lapse system to monitor embryodevelopment.

G. Huszar (USA) explained how to select thebest sperm. In the first approach, in his laboratorythe sperm creatine kinase content is assessed,which reflects incomplete sperm cytoplasmicextrusion and surplus cytoplasm. Hisexperiments provided three insights: (i) spermthat failed cytoplasmic extrusion show reduced

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IVF Preceptorship: The state of the ART2-3 August 2013 - Sao Paulo, Brazil

[ ]The first SSIF CME IVFpreceptorship was a neweducational initiative

targeted at Latin Americanhealth care professionals.

binding in the zona pellucida, and incompletecytoplasmic extrusion affects chromatindevelopment, DNA integrity, and frequency ofchromosomal aneuploidies; (ii) sperm-oocyteinteraction is regulated primarily by the attributesof the spermatozoa; and (iii) there is a spermplasma membrane remodeling in terminalspermiogenesis. This remodeling facilitates theformation of the zona pellucida and hyaluronicacid binding site(s). Sperm-hyaluronic acidbinding is the first objective assay in the andrologylaboratory which provides an objectiveassessment that sperm in an ejaculate are ableto bind to the zona pellucida. Another spermbiomarker is the chaperone protein HspA2, whichis part of the synaptonemal complex, and also akey element of intracellular transport of DNArepair enzymes in the developing spermatozoa.In couples treated with intrauterine inseminationor with IVF, elevated levels of sperm creatinekinase predicted the failure of pregnancies,independent of normal sperm concentration andmotility

S. Munné (USA) described the advancedresearch into preimplantation genetic diagnosis(PGD). He explained how chromosome analysisof human embryos has evolved considerably inthe last few years, from using fluorescence in situhybridization (FISH) with 5-12 probes and mostlyperforming polar body or day-3 biopsy PGSv1(preimplantation genetic screening) to analysingall chromosomes with arrays from blastocystbiopsies (PGS v2). With the advent of the PGStechnique the error rate in diagnoses has beenreduced from 7-50% to 3% depending on thelaboratory. Pregnancy outcomes havesignificantly improved. Data support that usingPGSv2 there are no differences in chromosomeaneuploidy rates, irrespective of the cohort sizeproduced. Aneuploidy increases with maternalage and does not decrease with cohort size.

SESSION IIINew milestones in ART

C. Simon (Spain) discussed the topic of theendometrium and implantation. Theendometrium is a hormonally regulated organthat is non-adhesive to embryos throughout mostof the menstrual cycle in humans. Endometrialreceptivity refers to a hormone-limited period inwhich the endometrial tissue acquires afunctional and transient ovarian steroid-dependent status allowing blastocyst adhesion.Functional genomics studies of humanendometrium in natural cycles havedemonstrated that endometrial receptivity is anactive process involving up- and down-regulationof hundreds of genes. He explained that, althoughpersonalized medicine is a well-acceptedconcept in reproductive medicine, theendometrial factor is still neglected. He showeddata from his laboratory on ERA (endometrialreceptivity array), a customized array of 238 genescoupled to a computational predictor capable ofdiagnosing a functionally receptive endometriumregardless of its histological appearance. Theaccuracy of the diagnostic tool ERA has beendemonstrated to be superior to endometrialhistology and results are completely reproducible

29 to 40 months later. The presentation focusedon demonstrating the diagnostic and therapeuticefficiency of the ERA in patients with implantationfailure (IF), through personalization of the day ofembryo transfer (pET)

The role of vitrification and its application wasdiscussed by Z. P. Nagy (USA). Cryopreservationof reproductive tissue and cells are essentialcomponents of assisted reproduction treatment.Historically, the slow- freezing procedure wasused to cryopreserve ovarian tissue, oocyte andembryo. However, the efficiency of slow-freezingis low, especially for the cryopreservation ofoocytes. Recently, vitrification has beenintroduced as an alternative technique that

provides greatly improved success rates.Vitrification requires the use of higherconcentrations of permeating and non-permeating cryoprotectants, as well as a veryhigh speed of cooling – close to 20,000 Celsiusper minute (in sharp contrast to the 0.3 Celsiusper minute cooling rate for slow-freezing). As aconsequence of the improved survival ratesfollowing vitrification, new options for patienttreatment have emerged. Fertility preservationfor both medical and social reasons is nowpossible by applying vitrification to eggs (or insome cases vitrification of the ovarian tissue).Vitrification today is also replacing slow- freezing

for the purpose of embryo cryopreservation,because of increased efficiency. He showed avideo on crypreservation techniques.

Z.P. Nagy (USA) also discussed QMS (qualitymanagement systems) in ART and focused onhow to get accreditation and certification in theIVF laboratory. There are several differentterminologies related to QMS: Regulation /Licensing / Certification / Accreditation. Theseterms are fundamentally different concepts /approaches. For a truly effective system ofgovernance they must all work together.Regulations are legal requirements to which anorganization or individual must conform in orderto operate. Compliance is often verified by

inspection (examination for individuals) andconfirmed by issuing a license; failure to complywith regulation results in penalties. Licensing isthe process whereby an organization (orindividual) is identified as being compliant withrequired regulations. Certification is the processwhereby an organization (or individual) isidentified as meeting one or more selected“standards”. Accreditation is a collegial processbased on self- and peer-assessment, whereby anauthoritative body (usually a non-governmentorganization) gives formal recognition that anorganization is in voluntary compliance with oneor more standards set by the authoritative body.

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Serono Symposia International Foundation (SSIF) has launched a resource centre on theRBM Online website: www.ssifrbmoresourcecenter.com

The resource centre inform users of RBM Online about forthcoming SSIF meetings, andprovide meeting summaries as well as access to SSIF podcasts, videos, CME onlinecourses and SSIF news.

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Online activities

Serono Symposia International Foundation’s online continuing medicaleducation (CME) combines timely, insightful content with the

convenience of home or workplace study. Courses are available toanyone wishing to participate. Participants who obtain a satisfactory

score on the post-test can obtain a certificate of completion. To know more: reproductive-medicine.seronosymposia.org>

Predictors of IVF outcomeFaculty: C. Alviggi (Italy)

The pediatrician's point of view : baby born after ART, complications and futureFaculty: M. Bonduelle (Belgium)

Producing more oocytes decreases genetic quality?Faculty: F. Fiorentino (Italy)

Definition of successful treatments in ARTFaculty: G. Kovacs (Australia)

Producing more oocytes does not decrease genetic qualityFaculty: S. Munne (USA)

Sperm evaluation using mRNA microarray technology: future perspectivesFaculty: N. Garrido Puchalt (Spain)

Technologies needed to maximise success: the future ART laboratoryFaculty: L. Rienzi (Italy)

The uterine environment and endometrial receptivity: new frontiers of ARTFaculty: C. Simón (Spain)

Can different ovarian stimulation protocols affect oocyte and embryo morphology and quality?Faculty: A. Sunde (Norway)

Management of complications: new strategy to avoid OHSSFaculty: J.A. García Velasco, Spain

The patient's point of view: a take-home babyOne patient's personal experience of the IVF processFaculty: K. Veness (UK)

Visit the reproductive medicine section of the new Serono SymposiaInternational Foundation (SSIF) website.

www.reproductive-medicine.seronosymposia.org

Register to access free e-learning activities and receive updates on newevents and resources.

Take a look at the SSIF reproductive medicine website

E-learning programmes: Video interviews Online video lectures Online courses Video presentations

Live educational events

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SSIF EDUCATIONAL EVENTS - AUTUMN/WINTER PROGRAMME 2013

IVF Preceptorship Istanbul

12-13 September 2013 - Istanbul, TurkeyScientific organizer: R. Fischer (Germany)

This important conference looking at one of the most important causes of female infertility is being held bySerono Symposia International Foundation (SSIF). POR (poor ovarian response) occurs for several key reasons,including advanced maternal age, a previous POR or an abnormal ovarian reserve test. SSIF is collaboratingwith the Amerikan Hastanesi Hospital in Istanbul to provide new insights into a disease which producessymptoms in 5-10% of women of reproductive age.

In collaboration with the American Hospital Istanbul.

The top ten in reproductive medicine: Debating break-through basic and clinical papers withtheir authors

20-21 September 2013 - Florence, ItalyScientific organizer: C. Simon (Spain)

This programme will focus on the presentation, discussion and follow-up of the top ten most important clinicaland basic contributions in reproductive medicine during the last two years. The concept is to create a highquality meeting that will serve the key opinion leaders of the clinical and scientific community in reproductivemedicine.

7th IVF Preceptorship: current practice in the 21th century

26-27 September 2013 - Madrid and Valencia, SpainScientific organizers: E. Bosch (Spain), J.A. García Velasco (Spain), A. Requena (Spain)

The two-day programme, focusing on infertility treatments and on new laboratory techniques, will be deliveredusing an innovative mix of traditional lectures, interactive working groups managed by young speakers andcase studies submitted by participants.

International school of ultrasound in obstetrics and gynecologyIn partnership with the University of Siena

28-29 September 2013 - Siena, ItalyScientific organizer: F.M. Severi (Italy)

Each course (lectures and practical sessions) is designed to improve the practical skills and interpretation ofthe operators who perform ultrasound for diagnostic purposes in the field of obstetrics and gynecology, byusing latest generation ultrasound equipment. At the end of each course, trainees will be able to performadvanced ultrasound examinations, will be well oriented in the choice of the correct ultrasound approach touse in different clinical situations and will be able to correctly understand all the different sonographic featuresthat they will have to face in the clinical practice.

IVF Preceptorship Madrid

November 2013 - Madrid, SpainScientific organizer: R. Fischer (Germany)Scientific co-organizers: J.A. Zafra (Spain), R.N. Calonge (Spain)

This live educational course offers an overview on ovarian stimulation and on new laboratory technologiesfor in vitro fertilization cycles. This meeting is dedicated to providing new insights on these topics, with aninteractive programme where each lecture is followed by specific cases studies or working groups. The aimis to provide learners with both up-to-date knowledge and the possibility to share their experiences with eachother and with the speakers.

In collaboration with the Tambre Clinic.

Editors: Michèle Piraux, Michael Withers, Chloé Xilinas

Contributors: Angelo Marino, Irene Zerbetto

At SSIF we are always keen to talk to health professionals about the continuingmedical education we provide. You can email us at info@seronosymposia.orgWant to know more?

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IMPROVING THE PATIENT'S LIFE THROUGH MEDICAL EDUCATION

Welcome to the Serono SymposiaInternational Foundation website!

Home About Medical Education Quality, impact and excellence Specialist areas Newsroom

Register for even more benefits:

• free e-learning activities• a comprehensive library of abstracts, books, andslide presentations from leading academics in theirfields

• follow up activities, extending SSIF teaching courses• special interest groups to join – building onfriendships made and knowledge gained at liveevents

• all that is new in accredited continuing medicaleducation

… and if you cannot attend a live event use the SSIFwebsite for video lectures and podcasts straight fromthe conference floor.

At Serono Symposia International Foundation we havea reputation for being at the forefront of continuingmedical education. Our website is at the heart of all wedo – promoting and supporting our live events andproviding a gateway to online learning. Our vision is to enable you to deliver better care andbetter outcomes for your patients. The SSIF websitewill help you to make that a reality.

Visit the RM section of the SSIF website www.reproductive-medicine.seronosymposia.org

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