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Total quality management (TQM) in an IVF Centre. - eshre

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PRE-CONGRESS COURSE 12

Total quality management (TQM) in an IVF Centre. Task Force Management of Fertility Units in conjunction with the Special Interest Groups Andrology / Embryology / Reproductive Surgery & Safety and Quality in ART London - UK, 7 July 2013

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Covers_Pre congress courses.indd 12

21/05/13 11:53

       

 

         

Total quality management (TQM) in an  IVF Centre          London, United Kingdom  7 July 2013          Organised by  The Task Force Management of Fertility Units in conjunction with the Special  Interest Groups Andrology/Embryology/Reproductive Surgery & Safety and  Quality in ART 

   

   

Contents   

    Course coordinators, course description and target audience    Programme    Speakers’ contributions      Introduction: What is TQM? ‐ Luca Gianaroli ‐ Italy       Andrology lab ‐ David Mortimer ‐ Canada       Embryology ‐ Arne Sunde ‐ Norway       Reproductive surgery ‐ Rudi L. Campo ‐ Belgium       Complications related to ART ‐ Jan Gerris ‐ Belgium       Patient pathway and patient satisfaction ‐ Bart C.J.M. Fauser ‐ The    Netherlands       How to implement TQM ‐ Tonko Mardesic ‐ Czech Republic       The cost of quality: Example of the IVI approach to the continuous     improvement ‐ Carlos Blanes ‐ Spain       The role of the European Tissue Directive on TQM ‐ Edgar Vasile     Mocanu ‐ Ireland       Closing remarks ‐ Veljko Vlaisavljevic ‐ Slovenia     Upcoming ESHRE Campus Courses    Notes           

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Course coordinators    Paul Devroey (Belgium) and Luca Gianaroli (Italy) 

   

Course description     Total quality management or TQM is an integrative philosophy of management for continuously  improving the quality of services and processes. Through the years, this concept has become  fundamental in Healthcare, a field in which a high standard of treatment should constantly be  pursued. This Course focuses on all processes performed within Fertility Units and how they can be  influenced and improved by TQM in order to provide patients with the best and most safe  treatments and procedures available. The course will also investigate how TQM can be a useful tool  to improve efficacy and efficiency, also with reference to financial and administrative aspects. 

   

Target audience      ‐ Clinicians   ‐ Embryologists   ‐ Professionals involved in Quality Control and Total Quality Management   ‐ Managers of Fertility Units and public and academic hospitals 

 

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Scientific programme    08:45 ‐ 09:00   Introduction: What is TQM? Luca Gianaroli ‐ Italy     Part I: Impact of total quality management in:  Chairman: Luca Gianaroli ‐ Italy     09:00 ‐ 09:30   Andrology lab     David Mortimer ‐ Canada   09:30 ‐ 09:45   Discussion   09:45 ‐ 10:15   Embryology     Arne Sunde ‐ Norway   10:15 ‐ 10:30   Discussion     10:30 ‐ 11:00   Coffee break     Chairman: Paul Devroey ‐ Belgium     11:00 ‐ 11:30   Reproductive surgery     Rudi L. Campo ‐ Belgium   11:30 ‐ 11:45   Discussion   11:45 ‐ 12:15   Complications related to ART     Jan Gerris ‐ Belgium   12:15 ‐ 12:30   Discussion     12:30 ‐ 13:30   Lunch     Part II: The cycle of TQM   Chairman: Amparo Ruiz Jorro ‐ Spain     13:30 ‐ 14:00   Patient pathway and patient satisfaction     Bart C.J.M. Fauser ‐ The Netherlands   14:00 ‐ 14:15   Discussion   14:15 ‐ 14:45   How to implement TQM     Tonko Mardesic ‐ Czech Republic   14:45 ‐ 15:00   Discussion     15:00 ‐ 15:30   Coffee break     Chairman: Timur Gürgan ‐ Turkey     15:30 ‐ 16:00   The cost of quality: Example of the IVI approach to the continuous     improvement    Carlos Blanes ‐ Spain   16:00 ‐ 16:15   Discussion   16:15 ‐ 16:45   The role of the European Tissue Directive on TQM     Edgar Vasile Mocanu ‐ Ireland   16:45 ‐ 17:00   Discussion   17:00 ‐ 17:15   Closing remarks     Veljko Vlaisavljevic ‐ Slovenia 

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What is Total Quality Management (TQM)? L. Gianaroli, S. Sgargi, D. Barnabé S.I.S.Me.R. Reproductive Medicine Unit, Bologna (Italy)

www.iiarg.com

www.sismer.it

Management - Definition

Management in all business and organizational activities is the act of getting people together to accomplish desired goals and objectives using available resources efficiently and effectively. Management comprises planning, organizing, staffing, leading or directing, and controlling an organization (a group of one or more people or entities) or effort for the purpose of li hi R i th d l t and d accomplishing a goal.l Resourcing encompasses the deployment manipulation of human resources, financial resources, technological resources and natural resources.

Service Realization Purchasing and production processes

Planning

Control

Customer Communication

Control

Design and development

Control

Service Provision

Patient’s feedback

Control

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Management of an IVF Unit Characteristics of healthcare practices: • Consumers = patients • Product = specialized health services • Staff = varied educational and experience backgrounds • Owner = usually a Physician

Peculiar characteristics of IVF practices: • Patient population usually knowledgeable about treatments • Patient population highly motivated • Success rates important in the choice of practice and clinician • Patients have high expectations as they cover the majority of treatment expenses S. Gerson et al. Fertility and Sterility, 2004

Management of an IVF Unit Management of ITC and planning tools

Management of Human Resources

Financial Fi i l planning

Insurance cover

Communication

TQM

Integrated management of corporate activities Company - Organization Management activities

Quality Continuous quality improvement

Environment Compliance with Laws and continuous improvement p

Safety Compliance with Laws and continuous improvement p

Other activities Gains, market shares, personnel, processes, communication,,

ISO 9001

ISO 14001

OHSAS 18001

ETHICS

TOTAL QUALITY MANAGEMENT Total control of all corporate activities High corporate performance Customer and personnel satisfaction

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Total Quality Management

Performance Management

Quality Management

Risk Management

Total Quality Management Performance management

Performance management includes activities that endure that goals are consistently being met in an effective and efficient manner. organization a department, department a team, team an Can focus on the performance of an organization, employee.

Management – Quality Principles 1) Customer oriented approach 2) Leadership 3) Personnel involvement 4) Process approach 5) Systems approach to corporate management 6) Continuous improvement 7) Evidence-based decision making 8) Reciprocal beneficiary relationship with suppliers

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Risk management

No organization is immune from a crisis so all must do their best to prepare for one.

Crisis – any situation that is threatening or could threaten to harm people or property, seriously interrupt business, damage reputation or negatively impact share value.

Risk management

Crisis management organizational function.

is

a

critical

Failure to manage crisis can result in serious harm to partners/stakeholders, l losses f an organization for i ti or end d its it very existence If not properly managed, a disruptive event can escalate to an emergency, a crisis or even a disaster.

Risk management It includes strategies that allow to face possible damages limiting their consequences as much as possible  DIRECT DAMAGES Costs deriving from this kind of damage are immediate and quantifiable  INDIRECT DAMAGES They include al damages occurring between the prejudicial event and its solution  CONSEQUENTIAL DAMAGES They occur after the prejudicial event and they prolong themselves in time

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Damages

Mainly pecuniary losses

Visible

Direct Damages

Insurable Estimable

Deriving from unavailability of means

Indirect Damages Not visible Not insurable

Consequential Damages

Their effects continue also when pre-existing conditions are reestablished

Difficult to assess

Total Quality Management - Tools Evidence-based

Personnel Involvement

Decision making

Suggestion Programme

Employee Satisfaction Survey Su ey

Cost – Benefit Analysis a ys s

Planning

Business continuity planning

Take home message TQM = management philosophy and company practices that aim to harness the human and material resources of an organization in the most effective way to achieve the objectives of the organization and to pursue customer satisfaction

TQM in Healthcare = rigorous set of processes and techniques to measure, improve, and control the quality of care and service based on what is important to the patient

QUALITY OF ORGANIZATION = QUALITY OF CARE (Patients satisfaction + better outcome)

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IMPACT OF TQM IN THE ANDROLOGY LAB

Dr David Mortimer, PhD Oozoa Biomedical Inc, Vancouver, Canada

Learning Objectives 1. To recognize that TQM is fundamental to the efficient  and effective operation of the andrology laboratory. 2. To understand how the principles of TQM influence the  selection and implementation of technical methodology  for semen analysis. 3. To recognize that the principles of TQM require proper  operator training and verification of competence. 4. To understand how embracing TQM will lead to semen  analysis results that are more accurate and precise, and  hence more likely to have clinical relevance.

© Oozoa Biomedical Inc, July 2013

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Commercial Conflicts of Interest Disclosure David Mortimer has undertaken consulting work since 1986, and  has been a full‐time freelance consultant since October 1999. He is currently President and co‐owner of Oozoa Biomedical Inc, a  Vancouver‐based international consulting company providing  services in the reproductive biomedicine field since March 2000. He has performed work, on either commercial or a pro bono basis,  H h f d k ith i l b b i for many clients and groups including: assisted conception clinics  and sperm banks; biotechnology, pharmaceutical and ART  products companies; academic institutions; researchers;  government agencies; non‐government organizations;  professional associations and other bodies. No commercial or financial interest has influenced the statements  made in this presentation. © Oozoa Biomedical Inc, July 2013

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Keeping the Andrology Lab In Control  QC and QA are essential and must be routine  Environmental monitoring:  temperature, ventilation, 

      

oxygen depletion, air filtration (particulates, micro‐ organisms, VOCs), infection control Tolerance limits for quantitative technical procedures Monitoring of in‐process controls Monitoring reagents and supplies, includes traceability of  contact materials for therapeutic procedures as per EUTCD Monitoring of lab operational performance (e.g. via KPIs) Inspections and audits Protocol qualifications, verifications and validations Dealing with misconduct © Oozoa Biomedical Inc, July 2013

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TQM in the Andrology Lab  Scope of Activity:

Diagnostics, cryobanking, therapeutics

 Regulatory:

Regulatory compliance / licensing (EUTCD), accreditation (e.g. ISO 15189)

 Physical Facility:

Space size, layout, HVAC, cleaning, security

 Equipment:

Suitability for use, Installation Qualification, Operational Qualification (also after repair), Performance Qualification (QC) f Q lifi i (QC)

 Human Resources: Education, experience, aptitude, training, competence, CPD, adequate for peak workload

 Management:

Policies, systems and process management,  scheduling, efficiency, audits, QI (PDCA cycle), non‐conformity (“incident”) reporting

 Methodology:

Suitability for purpose, SOPs, QC, QA, EQAP

 Data & records:

Data entry verification, confidentiality, storage, security (access & backups), retention © Oozoa Biomedical Inc, July 2013

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Key Service Quality Requirements  Safety of the patients, specimens and staff  Patient identification, specimen labelling (2 unique 

identifiers), witnessing (human / Witness / Matcher)   Diagnostics:

– accuracy and precision of assessments – timeliness of reporting

 Cryobanking: – efficacy, safety and security of storage  Therapeutics: – timeliness, respecting the physiology

– avoiding iatrogenic damage – efficacy (quality of outcome)  Ability to cope with the workload without compromise to 

safety, quality of service, or outcomes  Customer satisfaction (patients and referrers) © Oozoa Biomedical Inc, July 2013

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Uncertainty of Measurement ISO Guide to the Expression of Uncertainty in  Measurement (1993)  Every measurement has an error associated with it, and 

without a quantitative statement of the error a  measurement lacks worth, even credibility.  The parameter that specifies the boundaries of the error  of a measurement is the “uncertainty of measurement”.  An uncertainty statement must have an associated  confidence level, most usually a 95% confidence interval,  i.e. effectively 2x the combined uncertainty.

© Oozoa Biomedical Inc, July 2013

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Quality of Sperm Assessments EXPECTATIONS  OF  ACCURACY  AND  PRECISION Traditional manual/visual methods (ESHRE, WHO)  Establishment of method:

<5% between replicates (precision)

 Training of new staff: Training of new staff:

<5% for 95% range of discrepancy <5% for 95% range of discrepancy

 Ongoing quality control:

<10% for 95% range of discrepancy

CASA methodology  Precision:

<5% between replicates

 Accuracy:

<10% for 95% range of discrepancy c.f. reference method © Oozoa Biomedical Inc, July 2013

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ISO Guide: Sources of Uncertainty 1.

Incomplete definition of the measurand.

2.

Incomplete realization of the definition of the measurand.

3.

Non‐representative sampling.

4.

Inadequate knowledge of the effects of environmental conditions  on the measurand (or imperfect measurement of those conditions).

5.

Personal bias in reading analog instruments  – or making subjective  assessments!

6.

Finite instrument resolution or discrimination threshold.

7.

Inexact values of measurement standards and reference materials.

8.

Inexact values of constants and other parameters obtained from         external sources.

9.

Approximations and assumptions incorporated in the measurement  method and procedure.

10. Variations in repeated observations of the measurand under  apparently identical conditions (“repeatability”). © Oozoa Biomedical Inc, July 2013

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SOPs are Key to Operator Competence 1. Define the exact methodology that has been selected 2. Method must be able to achieve the required accuracy  and precision 3. A method must include elements to control (minimize)  all sources of error and bias within practical limits 4. The SOP provides step‐by‐step instructions so that all  operators will perform the technique exactly as required 5. Operators are trained in the method before using it, and  their competence (ideally objectively defined) is verified 6. Internal QC, and effective participation in an External QA  programme (which includes QI functionality), are  essential © Oozoa Biomedical Inc, July 2013

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Goal Goal‐‐Orientated Training  Originally elaborated in Calgary during the 1980s to 

facilitate the training of new staff  Subsequently applied in Sydney, London, Stockholm, 

Boston, Bangkok, Vancouver, Halifax

© Oozoa Biomedical Inc, July 2013

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Goal Goal‐‐Orientated Training – Orientated Training – Example

© Oozoa Biomedical Inc, July 2013

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ESHRE SIG ESHRE SIG‐‐A Basic Semen Analysis Course

 The revised course (first held in Stockholm, June 2011) is 

not WHO5‐compliant, but it will educate participants on  where there are differences, and why they exist.  Text book for the course:  Björndahl et al., 2010. © Oozoa Biomedical Inc, July 2013

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ESHRE BSA Course Reference Textbook  Detailed, logical, unambiguous SOP‐type methods 

designed to minimize technical errors, avoid  unnecessary effort and facilitate quality control  Includes chapters on quality and 

risk management and  p p accreditation principles  Reference values section:  Defines prerequisites for 

interpretation  Provides cautionary notes 

regarding each characteristic  Considers the in‐vivo and in‐vitro 

significance of each characteristic  separately © Oozoa Biomedical Inc, July 2013

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Sperm Concentration Determination  Sample aliquot representative of ejaculate?  semen homogeneous (mixed)?  accurate sample aliquot (beware viscosity)?  duplicate aliquot?  Accurate dilution  volumes of sample aliquot and diluent?  storage (airtight) / sperm bind to vial? Secondary sampling  Secondary sampling   mixing of diluted aliquot?  duplicate aliquots?  Preparation of counting chambers   good chamber design/manufacture?  chamber loaded correctly &/or cover glass placed correctly?  adequate minimum number of cells?  repeatability of duplicate counts?  Calculations correct?  Precision of results?  Uncertainty of measurement known? © Oozoa Biomedical Inc, July 2013

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EQA for Sperm Concentration Sample 5:  60.1 ± 51.3 M/ml range = 3.6 – 240.0

Values are: mean ± SD (red) range (orange  diamonds, yellow  rectangles) for 20 labs

© Oozoa Biomedical Inc, July 2013

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Sperm Concentration Training

© Oozoa Biomedical Inc, July 2013

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Sperm Motility Assessments    

Are assessments performed at ~37°C? Have the definitions been implemented correctly? Are staff trained to classify progression?  Effect of temperature:  % motile (a+b+c) = minimal  % progressive (a+b) = slight  % rapid (a) = very large

        

Representative sample aliquots? Duplicate assessments? Adequate number of sperm counted? Repeatability of replicate counts? Calculations performed correctly? Precision of results? Uncertainty of results? Internal quality control? External quality assurance / proficiency testing? © Oozoa Biomedical Inc, July 2013

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WHO5 Abandons Grade “a” Motility  It is too subjective and cannot be assessed reliably by eye  (e.g. Yeung et al., Fertil Steril 67:1156, 1997; Handelsman & Cooper, Asian J Androl 12:118, 2010)

 But the quality of sperm motility is a prime factor to be 

considered in semen analysis.  Achievement of intra‐ and  inter‐observer standardization is essential in any method  used to assess sperm motility, and observers must be  properly trained (MacLeod & Gold, Fertil Steril 2:187‐204, 1951). ESHRE BSA Course held at CFAS 2005 (Montreal)

© Oozoa Biomedical Inc, July 2013

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Training To Assess Grade “a” Motility  Use reference video recordings and a calibrated overlay  Goal‐orientated iterative training % Rapid Progressive Training 95%

Training Series

1 2 3 4 5 6

0%

20%

40%

60%

80%

100%

% within 5% of reference value

© Oozoa Biomedical Inc, July 2013

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Motility Assessment Training

© Oozoa Biomedical Inc, July 2013

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Internal QC in Semen Analysis Mean ± SD% differences between 4 trained andrology scientists using  WHO manual/visual semen analysis methods on 60 determinations  (Calgary Diagnostic Semen Lab, ca 1990) Concentration

Total motility

Prog motility

A

-2.3 ± 7.4

+0.3 ± 3.0

+0.4 ± 2.6

B

-1.7 ± 4.9

-0.8 ± 3.1

-0.8 ± 2.9

C

+4.5 ± 7.3

-1.0 ± 3.3

-0.6 ± 3.3

D

-0.5 ± 7.0

+1.6 ± 2.9

+1.0 ± 2.8

A, B = experienced semen analysis technicians C = lab supervisor D = most recent trainee © Oozoa Biomedical Inc, July 2013

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Quality of Semen Analysis Results

 Checklist includes:  Items #8–#11 concerning analytical methods  Item 16 concerning measurement uncertainty © Oozoa Biomedical Inc, July 2013

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Monitoring Andrology Lab Equipment  Design Qualification:  suitability for intended purpose or 

use  Installation Qualification for new equipment [engineer]  Preventive maintenance / servicing / calibration [users or 

engineers as appropriate]  Operational Qualification [engineer] verifies key aspects of 

instrument performance without any contributory effects  that could be introduced by a method  Performance Qualification [user] ascertains that an  instrument or process consistently performs according to  specification under routine conditions

© Oozoa Biomedical Inc, July 2013

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TQM for Cryotanks  Regular cryotank filling (e.g. weekly):  Measure LN2 levels before re‐filling  Document and plot on a control chart

 Low level / temperature alarms:  Connect to a dial‐out alarm or

time monitoring system  Real Real‐time monitoring system

 Cleaning / sanitization?  Quarantine / isolation tanks vs

effective biocontainment packaging?  Oxygen depletion sensor and alarms 

with extraction ventilation for the  cryobank © Oozoa Biomedical Inc, July 2013

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Monitoring Cryotank LN2 Levels

© Oozoa Biomedical Inc, July 2013

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Conclusions  –– Take Home Messages Conclusions    TQM (embracing quality management, risk management 





 

and process management) creates the environment for  effective and efficient lab operations, including “quality  results” (i.e. accurate, precise, low uncertainty). Quality must be inherent in every aspect of the  laboratory’s operation, it must be integral – it cannot be  “added on” like a coat of paint. Results lacking in quality are meaningless, and hence  clinically useless – perhaps even misleading or even  dangerous. How much of the “poor clinical relevance” of andrology  lab results might be due to their poor quality? How useful might more accurate results be in future  clinical andrology practice? © Oozoa Biomedical Inc, July 2013

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References Barratt CL et al., ESHRE special interest group for andrology basic semen  analysis course: a continued focus on accuracy, quality, efficiency and  clinical relevance. Hum Reprod 26:3207‐3212, 2011. Björndahl L et al., ESHRE basic semen analysis courses 1995‐1999:  immediate beneficial effects of standardized training. Hum Reprod  17:1299‐1305, 2002. Björndahl L et al., A Practical Guide to Basic Laboratory Andrology,  Cambridge University Press, 2010. MacLeod J & Gold RZ. The male factor in fertility and infertility. III. An  analysis of motile activity in the spermatozoa of 1000 fertile men and  1000 men in infertile marriage. Fertil Steril 2:187‐204 1951. Mortimer D, Practical Laboratory Andrology, Oxford University Press,  1994. Mortimer D & Mortimer ST, Quality and Risk Management in the IVF  Laboratory, Cambridge University Press, 2005. Sánchez‐Pozo MC et al., Proposal of guidelines for the appraisal of  SEMen QUAlity studies (SEMQUA). Hum Reprod 28:10‐21, 2013.

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Impact of total quality  management in Embryology Arne Sunde Fertility Clinic, St. Olav’s University Hospital  Norwegian University Of Science and Technology Trondheim, Norway

Commercial relationships

• Own shares in CellCura of Norway 

My background in ART • Head of a fertility clinic that is ISO 9001:2008  certified  – Certified by DNV ( Det Norske Veritas)

• Laboratory manager from 1983 to 2006 • I am a “believer”  in quality management. – It is worth the efforts!

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Why ISO certified? • Experience from other organizations that are  certified – Even Hot‐Dog stands are certified 

• The The EU‐Tissue Directive requires implementation  EU Tissue Directive requires implementation of professional quality management in the ART  lab – why don’t use an established standard?

• We’re still the only clinical unit in our hospital  that is ISO‐certified. 

Total quality management • Two important aspects • Technicalities – Standard operating procedures Standard operating procedures – Documentation, traceability..etc.

• Culture – Quality management culture is part of the group  identity

The Quality Circle

Culture

Leadership

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Building a Quality Culture • This is the most important goal – Technicalities is a tool

• If you succeed in building a quality culture, the rest is  downhill – Involve everyone – Listen to everyone – Show that you listen

• Act accordingly

Quality management of a human IVF‐ embryology laboratory • Building a quality culture takes time and can  be exhausting.. • It is easier to talk about technicalities, but  don’t forget that these are just a tools – ..not the goal

ISO 9001:2008 Quality management  systems — Basic Requirements  • Control of Documents – A system for tracking documents – SOPs, letters, patient information, …

• Control of Records – Clinical record must be complete – Procedures, date/time, operator, utensils,  consumables – Assessments and decisions…

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Quality management in IVF‐laboratory • Standard operating procedures (SOP) for  ”everything” – – – – –

Easily available Must be updated  Systems for checking that the correct version is used Removal of old version Document tracking and control

• This is the easy part.. 

ISO 9001:2008 Quality management  systems — Basic Requirements  • Internal Audits  • Very important to get going – Train people in the lab to be auditors – Do audits at regular intervals D di l i l • • • •

Dates and signatures Serology documented Documentation of equipment variables Decisions according to SOP?

ISO 9001:2008 Quality management  systems — Basic Requirements  • Control of Nonconforming Product / Service • This is essential..one of the core elements • Two aspects again: • Operational – Identify errors, flaws, mistakes, suboptimal SOPs..

• Culture – Quality focus – Every employee can contribute..and be seen

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ISO 9001:2008 Quality management  systems — Basic Requirements  • Corrective Action  – Correct mistakes and errors that has happened

• Preventive Action – Change of SOPs, routines to prevent mistakes and  errors to happen

Building a Quality Culture • Positively reinforce focus on errors and deviation • It is OK that someone tells you that you done a substandard job – It is a success when the youngest technician can tell the senior doctor  It is a success when the youngest technician can tell the senior doctor • ..well yesterday you…. and it had the following consequence..  • And the senior MD says.. you’re right.. thank you..

– It is  success when you’re criticised by a patient and you turn around  and say: • ”Thank you for bringing that up…we have focus on quality  and your comment  will help us in achieving that”

Quality management in IVF‐laboratory • Standardized training programs – New employees • Training log

– Employees that have been out of the lab for a  Employees that have been out of the lab for a while • Read all SOP’s, train manual skills

• Continuous education program for everybody – Minimum reguirements

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Quality management in IVF‐laboratory • Traceability – All consumables and utensils – Events, time points, operators

• Validation – Procedures d – Equipment

• Quality control – – – –

Ingoing material Equipment Production Output

Quality management in Embryology • Equipment

• Ingoing materials

– Validated for embryology?

– Validated for embryology? – CE‐mark? – References

• Specifications, design,  References

– Validated in you lab V lid t d i l b

• In‐house testing of ingoing  materials?

• Testing before use

– Continuous monitoring of  critical variables during use

• Monitoring – Fertilization, Implantation.. – Lot numbers, QC ‐certificates

• Temperature, CO2/O2

– All this documented

• All this documented

Quality management of a human IVF‐ embryology laboratory Manufacture Automated

Complex chain production Input

Gametes

Fertilization

Assessment

Selection

Transfer

Output

Cryo

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Quality management of a human IVF‐ embryology laboratory • Biological variation in..  – means biological variation out…

• Choose your quality control parameters with  care • Don’t select parameters that will hurt your  patients

Quality management of a human IVF‐ embryology laboratory • What’s your important quality parameters for  production control? – – – – – – – –

Fertilization rate? ”Good embryo” rate? Implantation rate? Pregnancy rate? Delivery rate? Multiple delivery rate? Cumulative delivery rate (fresh + frozen)? Healthy Children?

“A I want have very  good results” ‐ clinic  This is a real example • The clinics quality parameters: – Implantation rate per embryo above 30% – Monitor for every 50 transfer • Cause for attention: below 25% • Full overhaul: below 20% F ll h l b l 20%

• This happened too often – Likely cause each time was to many low prognosis  patients

• Solution: include only good prognosis patients

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“A I want have very  good results”  clinic  • Alternative solutions: • Change observation period – Less prone to random effects

• Choose and index population of good  prognosis patients – Age, infertility diagnosis, BMI?

A real world example

• The value of traceability of all materials used  that may come in contact with gametes and  h i ih d embryos (”critical use”)

Number of oocyte recoveries and embryo  replacements monthly IVF/ICSI

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Fertilization rate IVF and ICSI Relative to the rate in September‐11

Embryos replaced and/or cryopreserved (”good embryos) /2PN% Treatment Cycles with Cryopreservation of embryos%

Monthly pregnancy rate and implantation rates IVF/ICSI 85% single embryo transfer Crisis Meetings 

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Any relationship with materials used ? 

The culture oil problem • Cause

• TQM in an oil‐crisis

– Substances in the oil that will  generate peroxides in the  presence of hSA 

– Monitoring • Implantation rate below action  level

• oil‐medium interphase

– Action • Internal audit

– Was NOT picket up by the  MEA during manufacture QC

– Finding • Substandard ingoing material

– Clinics reported problems • Blastocyst rate down

– Alarm other TQM clinics – Indications of within‐batch  variations(?)

• Do they see the same thing?

Action • The recalled batches of oil were already used • All frozen embryos which have been in contact  with the recalled oil was discarded • Patients that were treated when we used batches  of oil that was recalled, were offered a new  treatment cycle free of charge • New supplier of culture oil

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Monthly pregnancy rate and implantation rates 85% single embryo transfer

Frozen embryo replacements Data by month (24‐56 FER/month) 

Certification or Accreditation? • Certification according to ISO 9001:2008 – You do what you say you should do • ..and you control and document it

– The ISO standard  does not specify how good you should  be in pregnancy rates or implantation rates • You need to specify that yourself..

– You can be certified  • ..and have lousy results.. • as long as that is what you aim for..

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Certification or accreditation? • Accreditation standards – ISO 17025 General requirements for the competence of testing  and calibration laboratories – ISO 15189 Medical laboratories — Particular requirements for  q f quality and competence – ISO 9000 requirements are generic and are intended to be  applicable to any type of organization – ISO 17025/15189 requirements are more specific to testing and  calibration laboratories. 

Certification or accreditation? • Medical biochemistry laboratories are often – ISO 9001 certified in general • AND 

– have accreditation for some of the tests they offer – External validation, ring testing… • You document that you are live up to the industry  standard  (target value, variance…)

• Some andrology laboratories are accredited

Certification or accreditation? • What about the IVF‐lab? – Human clinical embryology – Certified for sure..

• I’m not that convinced that the current accreditation standards are  useful for clinical embryology.. – Relevant universal performance standards that are independent of  biological input? – No general  agreement on success criteria in ART! – Performance and success criteria should be relevant to the patients

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Quality management • Useful‐ worth the efforts? – It takes time and efforts

• On a clinic level.. – Definitively – I have asked cleaning ladies, secretaries, nurses, MDs, lab technicians  and embryologists in our unit: – Shall we skip the ISO and go back to our previous management  model?

–Clear response..NO!!

Quality management • Useful‐ worth the efforts? – It takes time and efforts

• What about the IVF‐laboratory ‐ embryology – – – – – – – – – –

Results better? Consistency in results better? y Physical lab parameters better? Information flow better? Documentation better? Traceability better? Deviations and mistakes/errors identified more often? Corrective actions more swift and relevant? Training of new staff better ? …

Quality management in Embryology

• A lot of nice words… – but did help in terms of pregnancy rates..?

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IVF/ICSI

TQM

Frozen embryo replacement

TQM

Quality management in the IVF‐ laboratory • Implementation of TQM takes time and efforts – It does not come easily and you are never finished

• It is a tool  – not a goal in itself

• Quality culture makes our Lab more dynamic, flexible and adaptable Quality culture makes our Lab more dynamic flexible and adaptable – Not the opposite…

• In times of crisis – it is very useful to have “full traceability and documentation”

• No guarantee that you clinical results will improve – You have to define your success criteria and  quality parameters yourself – TQM is a tool to get there…

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Gynaecological Endoscopic Surgical  Education and Assessment

GESEA Program

Patient Safety study in The Netherlands Because of inacceptable amount of serious (lethal) complications in common  laparoscopic procedures within general surgery and gynaecology in the  Netherlands the ministry of health performed a major inspection regarding  patient safety with a report published in November 2007

To deal with the assurance of patient safety, it seems obvious, but not yet  implemented , that future Laparoscopic surgeons should possess objective  measurable theoretical knowledge and practical skills, prior to enter in a one  to one clinical training – teaching program.

Ref: http://www.igz.nl/publicaties/rapporten/2007/mic

Study in Belgium – May 18th, 2013

Dominance of the apprentice‐tutor model Self‐management philosophy of educational portfolio European or National Governement cannot interfere as the healthcare environment is by definition independent 

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Medical Education and surgical Quality control  in Europe is a young ‘science’ CME principles introduced since 1995 in some European countries on a  voluntary basis EEACME (European Accreditation Councel for CME) started in 1999,  unifying the accreditation and recognition  EEACME and AMA recognition signed in 2000 CPD (Continuous Professional Development) declared in 2001,  structuring the application of the medical knowledge, skills and attitude. 

Objectives of ESGE’s Testimonium (Diplomat) Program The main objective of the introduction of a testimonium scheme for endoscopic surgical competence is to: • Classify the available educational programs and offers  (courses, classes, conferences, programs, seminars,  lectures, …) in a staged framework • Structure an educational curriculum for mastering  endoscopic surgery 

Influences of ESGE’s Testimonium (Diplomat) Program

Facilitates Training Centers and educational initiatives  to position the courses and programs for a target  audience and to define the required access level di d t d fi th i d l l Encourages the physician to improve proficiency and  skills on the educational path 

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GESEA Program’s foundation principles The program is founded on 5 specific domains or  pillars of surgical professional competence available in  Europe and as such being recognized by the EBCOG. (European Board and College of the Obstetrics and Gynaecology) (European Board and College of the Obstetrics and Gynaecology)

Each of the 5 pillars has a recognized and  documented educational or training route and  appropriate stages for assessment. (in different phases of development)

5 Pilars of Surgical Professional Competence

Accessible  Learning

Specific  Endoscopic  Skills

Surgical  Practice  Curriculum

Surgical  Examination

Continuing  Medical  Education

GESEA Testimonium Program

1. Accessible learning  Is offered through an e‐learning platform covering all  surgical disciplines with tutorials on techniques,  pathology, experts’ opinions. j g instructed through   Each level has a series of subjects lectures and video material.   For each subject item, one needs to succeed in a five  (random) question test before the next subject is made  accessible.  Access to the e‐learning/e‐testing platform is free, only  profile registration is required

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E learning program in laparoscopic surgery GET

ASK

TEST WWW.WINNERSPROJECT.COM

2. Specific Endoscopic Skills LASTT®: Laparoscopic Skills Training and Testing Method A practical validated test to measure the competence level of an individual in the  basic laparoscopic psychomotor skills like camera handling, hand‐eye coordination  and bimanual handling in the pelvic environment.

SUTT®:Suturing Skills Training and Testing Method practical test on fine psychomotor skills related to stitching and knotting  operations. HYSTT®: Hystersocopic Skills Training and Testing Method practical validated test to measure the competence level of an individual in basic  hysteroscopic psychomotor skills like camera handling, hand‐eye coordination and  bi‐manual handling in the specific uterus environment.

A Gynaecological endoscopic surgeon needs  2  specific  practical skills. Gynaecological Endoscopic Surgeon

EPS Endoscopic Psychomotor Skills

Laparoscopic Instrument handling including the fine psychomotor skills to perform suturing and fine surgical acts.

ESS Endoscopic Surgical Skills

Surgical skills with knowledge of anatomy, pathology, treatment options, etc

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A Gynaecological endoscopic surgeon needs  2  specific  practical skills. EPS Endoscopic Psychomotor Skills

Computer game skills to learn in a skill lab No skiled tutor necessary Learning proces similar to swimming or biking

ESS Endoscopic Surgical Skills

One to one teaching Minimal LPS necessary to enter the training Skilled tutor necessary Learning proces similar to learning a language

Psychomotor Skills  • Are the practical skills for correct camera handling to deal with the  depth appreciation from 2D screen, remote handling of instruments  without tactile feedback, hands‐eyes coordination, working with long  instruments the fulcrum effect and more difficult and fine instruments, the fulcrum effect and more difficult and fine  psychomotor skills are necessary for surgical acts like stitching and  knotting. • Scientific evidence gathered by +he academy has defined exercises on  simple, cost friendly and reproducible inanimate models  to train and  test the LPS of an individual.

Individual certification of Laparoscopic practical skills Laparoscopic Skill Training and Testing method (LASTT®)

AIM: 

measuring the individual proficiency to deal with typical  laparoscopic psychomotor skills 

Positive test result should grant for perfect laparoscopic instrument  handling capabilities. Suturing Skill Training and Testing method (SUTT ®)

AIM: 

measuring the ability of fine and complex motor skills by  performing correct stitches and correct intracorporeal knots. 

Positive test result should result in perfect ability of laparoscopic  needle handling and intracorporeal knotting. 

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LAparoscopic Skills Training and Testing model .

Training of 3 essential exercises to acquire the laparoscopic  psychomotor skills.

Exercise 1 : Camera navigation Exercise 2 : Hand eyes coordination  Exercise 3 : Bimanual coordination Test proficiency should grant for perfect  laparoscopic instrument handling  capabilities.

LASTT exercise 1 : Camera navigation

LASTT exercise 2 : Hand eye coordination

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LASTT exercise 3 : Bimanual coordination

Results exercise 3 Novices versus Experts 30 repetitions

450 400

300 250 200 150 100 50 0 0

5

10

15

20

Repetitions

25

30

P<0.0001 

Correlation exposure to laparoscopy and E3 score  199 gynaecologists classified in three groups according to their exposure to laparoscopy  G1: no/little GREEN , G2: intermediate YELLOW , G3: large ORANGE.

225

70 r=-0.44 P<0.0001

200

60

175 50

150 125

Score

Score

Time (s seconds)

350

100

40

***

°°

30

75 20

50 25

10

0 0 0

1

2

3

4

5

6

7

8

9

Level of exposure to laparoscopy

10

11

12

G1

G2

G3

Groups

*** P<0.001 (G1 vs. G3); °° P<0.01 (G2 vs. G3)

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Construct validity testing of E 1‐3 on 283 Individuals Number of objects transported

12

1400

E1

1000 800 600

E2

11 10 9 8 7 6 5 4 3 2 1 0

Inexperienced laparoscopists

400

Experienced laparoscopists

10

200 0 Inexperienced laparoscopists

Experienced laparoscopists

P<0.0001 

Number of objects transported

Tim me (seconds)

1200

E3 8

6

4

2

0 Inexperienced laparoscopists

Experienced laparoscopists

Content validity Results 60 first year residents pre and post course

pre-course

post-course

SUTT 1 : Greek running suture  Start at red dot performing stitch   Needle should correctly be positioned in  the dots.  Change hand after each stitch   Be careful with tread transport not to  perform trauma  Time for the exercise is 15 min.

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SUTT 2 : Right hand dominant  Precise positioning of stitch on the predefined entry  (red dot) and exit point (black dot )  15 cm 2‐0, V‐20 ½ 26 mm needle.   1 Intra‐corporeal knot with flat knot, 1st locking 

SUTT 2

sequence and 2nd locking sequence 

The exercise is being timed till the participant  releases the thread at both ends at the end of the  knotting movements.

SUTT 3 : Left hand  Precise positioning of stitch on the predefined entry  (red dot) and exit point (black dot )  15 cm 2‐0, V‐20 ½ 26 mm needle.   1 Intra 1 Intra‐corporeal corporeal knot with flat knot, 1st locking  knot with flat knot, 1st locking sequence and 2nd locking sequence 

The exercise is being timed till the participant releases  the thread at both ends at the end of the knotting  movements.

SUTT 4 : Tissue approximation  Precise positioning of stitch on the predefined  entry and exit point with 15 cm 2‐0 Caprosyn V‐20 ½ 26 mm with dominant hand.   Correct approximation of tissue by performing  one Intra‐corporeal flat knot with 2 locking  sequences. The exercise is being timed till the participant  releases the thread at both ends at the end of  the knotting movements. 

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Structured program in laparoscopic skills The scientific work performed in the last years has put forward following evidence to  take into acount for a structured training program.  1 Training of only suturing exercises does not provide full proficiency in the  laparoscopic psychomotor skills. 2. Full acquisition of all 3 LASTT exercises  facilitates the acquisition of more complex  laparoscopic tasks (SUTT).   3. The psychomotor skills remains in time proving the similarity with swimming or  biking skills. 4. The presence and assistance of a tutor is less important than repetition (training)  of excercises to acquire the LPS skills. 

Hystersocopic Skills Training and Testing Method Practical test to measure the competence level of an individual in basic hysteroscopic psychomotor skills like camera handling, hand‐eye coordination and bi‐manual handling in the  specific uterus environment.

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3. Surgical Practice Curriculum The frequency of practical exposure to endoscopic procedures is recognized being  a criterion for the assessment of the professional level.  The grading is defined as: Level 1: exposure to 50 defined case of laparoscopy and/or hysteroscopy and Level 1: exposure to 50 defined case of laparoscopy and/or hysteroscopy and  having participated (with certification) to an ESGE recognized suturing workshop. For Level 2: exposure, as first surgeon, to 50 procedures ESGE Class 3 in  laparoscopy and/or ESGE Class 2 in hysteroscopy, within a period of max 5 years For Level 3: exposure, as first surgeon, to 50 procedures ESGE Class 4 in  laparoscopy and/or ESGE Class 3 in hysteroscopy, within a period of max 5 years

ESGE Procedure Classification ESGE Laparoscopic Procedure Classification

ESGE HYSTEROSCOPIC PROCEDURES CLASSIFICATION

First level (basic)

First level (basic)

   

 

Diagnostic Laparoscopy  Tubal Sterilization  Cyst Aspiration  Biopsies

Diagnostic hysteroscopy Simple procedures (excluding the use of laser or electro‐surgery): o Target biopsies o Removal of IUCD o Minor intrauterine adhesions

Second level (intermediate)     

Salpingotomy / salpingectomy  Salpingo‐oophorectomy  Cystectomy  Moderated Adhesiolysis Minimal/mild Endometriosis 

Second level (intermediate) • • • • •

Third level (advance)      

Hysterectomy  Myomectomy  Urinary Incontinence  Extensive Adhesiolysis Severe Endometriosis  Bowel or bladder lesions reparation 

Polyp resection  Resection of type 0 myoma Endometrial ablation Treatment of uterine septum Tubal canulation

Third level (advanced)  

Resection of type 1 and 2 myoma Major Asherman’s syndrome

Fourth level  • • •

Pelvic floor disorders  Oncology (Lymphadenectomy, radical hysterectomy, axiloscopy)  Recto‐vaginal endometriosis

Page 48 of 167

4. Surgical Examination For level 1 : theoretical exam only TESTT®:   validated test on theoretical knowledge on endoscopic anatomy, endoscopic  instrumentation and hardware, OR organization, and complication  management. management

4. Surgical Examination Predefined surgical procedures have to be performed in a OR (or equivalent) environment  for level 2 and level 3 of the program Model Animal Models

‐ ‐ ‐ ‐ ‐

Disadvantages ‐ ethical problems facilities costs validation animal model for reproductive surgery objectivation ‐ time consuming ‐ possibility of cheating initial investment ‐ only  skills  assessment ‐

Electronic assessment



software preparation

Live surgery

‐ ‐ ‐

time consuming costs unrealistic in case of a high ‐ ‐ number of applicants

Video

Simulator

‐ ‐ ‐ ‐

‐ ‐ ‐ ‐ ‐

Advantages Allows an immediate  assessment of surgical skills

assessment of surgical skills costs hardware lasts for a long time easily updatable objective cheap comparable fast assessment and validation of  surgical skills extremely realistic ACS (Anti Cheating System)

5. Continuing Medical Education The Standing Committee on CME/CPD (SCCPD) of the EBCOG is responsible in Europe  for establishing the guidelines on European targets in Gynaecological Endoscopy. The  working group is currently in charge of preparing a proposal for the GESEA program. Reporting and certification will be managed through the CME procedures of the  UEMS.

Page 49 of 167

Introducing 3 distinghuised levels of surgical skills  with different diplomas 1. Bachelor in Endoscopy (entrance to the training curriculum for Endoscopic Surgeon)

2. Gynaecological Laparoscopic surgeon.  Hysteroscopic surgeon  Reproductive  surgeon 3. Laparoscopic Pelvic Surgeon

GESEA Testimonium Program LEVEL

1

Accessible  learning

Winners  Bachelor        First 

*

Winners GLS  2

Second 

**

Winners EPS     3

Third 

***

Surgical  Examination

Continuing  Medical  Education 

Diploma

Exposure to 50  cases + Suturing  workshop

TESTT®

EBCOG Project  Definition

Bachelor in  Endoscopy

First Surgeon 50  ESGE Class 3

Under  Validation  ESHRE

Gynaecological  Laparoscopic  EBCOG Project  Hysteroscopic  Definition Reproductive  Surgeon

First Surgeon 50  ESGE Class 4

Under  Validation

EBCOG Project  Laparoscopic  Definition Pelvic Surgeon

Specific  Surgical Practice  Endoscopic Skills Curriculum

Testimonium Management 1. The Certification of the Specific Endoscopic Skills (LASTT / HYSTT / SUTT /  TESTT) will be supervised by an official certification body CERTENDO, in  process of creation and application for NBN EN ISO/IEC 17024  accreditation aligned to the NANDO European Act and open to recognition  under the MRA (Mutual Recognition Agreements) procedure with other  countries (Australia, Canada, Switzerland, United States, Japan, …) (or  equivalent)

2. The GESEA Testimonium Public Registry lists individual surgeons who have  successfully completed one of the three levels of the Program and the  corresponding certification program, the type of diploma and certificate  issue date; certificate and their respective validity.

Page 50 of 167

Rationale reproductive surgeon  Reproductive Surgery (RS) is crucial for Reproductive Medicine. In the last 10 years, there have been tremendous improvements in the infrastructure (settings and instrumentation) as well as in the developed capabilities of individuals and groups, in treating infertile women to become pregnant spontaneously and also increasing ART pregnancy rates.

There is enough experience and evidence based data that RS undertaken by well trained and experienced clinicians significantly improves and preserves fertility results, alleviates patients from pain and improves their quality of life. In addition, surgery performed by competent gynaecologists contributes to patients’ safety and secures the profession’s good reputation.

ESHRE SIG Reproductive Surgery

600 500 400

SIG RS 1st Choice SIG RS 2nd choice

300 200 100 0 n° members

Ways of examination – Practical and theoretical skills ESHRE Certification for Reproductive Surgeons

Level 1 Bachelor in  Endoscopy 

Level 2 Reproductive  Surgeon

(does not require  surgical skills)

(requires surgical skills)

Page 51 of 167

Surgical training Bachelor Certification

Applicants for bachelor certification will have to be exposed to 50 Hysteroscopies (25 Diagnostic Hysteroscopies + 25 Major or minor Hysteroscopies), to 20 diagnostic laparoscopies and to 30 operative laparoscopies

Reproductive Surgeon Certification

Applicants for reproductive surgeon certification will have to perform 50 hysteroscopies (of which at least 20 major ones) and 50 laparoscopies (of which at least 20 operative ones) as first operators within a time frame of 3 years.

Surgical Exam – Only for reproductive surgeons It will be composed of a theoretical part and of a practical part. The theoretical test will be the first part of the exam and it will be composed of multiple choice questions. The Committee will define the names of the clinicians in charge of preparing the questions, selected according to the criteria previously described. As far as the practical test is concerned, the working group dedicated a large amount of energy to a careful analysis of different models available, summarizing the pros and cons of each one of them. The practical test was deemed necessary considering the characteristics of the Certification.

Surgical Exam – Exam model After a long discussion, the WG unanimously agreed that the best option would be to  combine Video and Electronic Assessment.

The ESHRE WG will draft a document including the number of videos to be submitted b applicants by li and d the h number b off videos id to be b examined i d in i a random d way, plus l some potential extra questions to be asked to applicants. The WG will also elaborate a first draft of the electronic document of the test. The group agreed that in case of failure, applicants for certification will be entitled to request a site visit for a live surgery session for fee.

Page 52 of 167

ESHRE – Reproductive Surgery Accreditation Program and Certification  (ERSAPC)

Gynaecological Endoscopic Surgical  Education and Assessment

GESEA Program

Page 53 of 167

Complications related to ART ESHRE Pre-Congress Course “Total Quality Management (TQM) in an IVF Centre” d July 7th h 2013 London

Jan M.R. Gerris, MD, PhD Centre for Reproductive Medicine, Dept. Ob-Gyn, Ghent University - Belgium

This presentation is completely independent. I have no commercial relationships with any company.

Objectives of this presentation At the end of this presentation, participants will have a better understanding of (risks and) complications (R&C) of fertility enhancing treatments by - k knowing i what h t are the th clinically li i ll mostt relevant l t R&C before, b f during and after treatment; - understanding a rational approach towards prevention, minimizing their effects on treatment outcome; - understanding the complementarity between personal responsability in the clinic and the role of guidelines - understanding where future meaningful action is lying.

Page 54 of 167

World Health Organization (WHO) Definition of Health Health is a state of complete physical, mental and social well-being and not merely the absence of disease or infirmity

Safety is state of continuous technical, human and organizational proficiency resulting in the absence of incidents and accidents

Classification of R&C • Pre-treatment R&C – Poor selection – Pre-existing risks

• Treatment R&C – – – – –

Stimulation Oocyte retrieval Laboratory phase Embryo transfer Luteal phase

• Post-treatment R&C – Pregnancy – Late complications in non-pregnant patients – Long-term risks and complications

What are the R & C’s?

Page 55 of 167

P -treatment PrePre t t t R&C

Pre--existing risks Pre 

SYSTEMIC DISEASE – – – – – – –



IDDM Obesity/metabolic syndrome HyperHyper- and hypothyreosis LiverLiver- and kidneydisease Thrombophilia or previous DVT AutoAuto-immune diseases …

GYNECOLOGICAL PRECONDITIONS – – – – – – – –

Uterine myomatosis ( embolize or remove if cavitary ) Congenital anomalies of the uterus ( mSET ) Previous prematurity Isthmic insufficiency (Substantial )LLETZ Turner patient (2% rupture of aortic aneurysm) Age of both partners …

Uterus bicornis unicollis

Page 56 of 167

Uterus didelphys

Uterus unicornis

Multiple myomatosis

Pearl white hard myoma tissue

Page 57 of 167

Influence of myomas on reproductive function:: all locations function

 

Expected: lower pregnancy rate (PR), more miscarriages Expected: Evidence:: Evidence – Significantly lower PR, IR, LBR and higher MCR – No difference in verschil in Preterm Delivery Rate

Pritts EA et al. Fibroids and infertility: an updated systematic review of the evidence.Fertil Steril 2009; 91:1215-1223.

Influence of myomas on reproductive function:: intracavitary distorsion function

 

Expected: clear influence on PR, …. Expected: Evidence:: Evidence – Significantly lower PR, IR, LBR, higher MCR – No studies on PDR

Pritts EA et al. Fibroids and infertility: an updated systematic review of the evidence.Fertil Steril 2009; 91:1215-1223.

Influence of myomas on reproductive function function:: no intracavitary distorsion (IM and SS)

 

Expected: no/ Expected: no/little little influence on PR, …. Evidence Evidence:: – No difference in PR – Significantly lower IR, LBR and higher MCR – No difference in PDR (2 studies)

Pritts EA et al. Fibroids and infertility: an updated systematic review of the evidence.Fertil Steril 2009; 91:1215-1223.

Page 58 of 167

Influnce of myomas on reproductive function function:: SS

 

Expected:: no/little Expected no/little effect on PR, …. Evidence: Evidence: – No effect op PR, IR, LBR, AR en PDR!

Pritts EA et al. Fibroids and infertility: an updated systematic review of the evidence.Fertil Steril 2009; 91:1215-1223.

Influence of myomectomy on reproductive function:: SM (controls function (controls:: myoma in situ)

   

Expected: better resultats after myomectomy Indeed significantly higher PR No difference LBR and MCR (both just one study, near significance ̴ LBR!) No studies on IR and PDR

Pritts EA et al. Fibroids and infertility: an updated systematic review of the evidence.Fertil Steril 2009; 91:1215-1223.

Influence of myomectomy on reproductive function:: SM (controls function (controls:: no myoma)

  

Expected: equal results after myomectomy Indeed equal results ̴ PR, IR, LBR én AR No studies on PDR

Pritts EA et al. Fibroids and infertility: an updated systematic review of the evidence.Fertil Steril 2009; 91:1215-1223.

Page 59 of 167

Influence of myomectomy on reproductive function:: IM (controls function (controls:: myoma in situ)

  

Expected:: ? ((depending Expected depending on presence or absence of distorsion at hysteroscopy hysteroscopy)) No difference in PR, LBR and MCR (pos trends) No studies on IR en PDR

Pritts EA et al. Fibroids and infertility: an updated systematic review of the evidence.Fertil Steril 2009; 91:1215-1223.

Guidelines concerning myomas in women with subfertility (1) 

Subserosal myomas myomas:: remove only if symptomatic



Submucous (=intracavitary (=intracavitary)) myomen (type 0 and 1): – ≤4 cm: hysteroscopic resection (if needed in several times times)) – >4 cm:  Pretreatment with GnRH GnRH--analogues analogues,, then hysteroscopic resection  Quid embolisation? embolisation? Not in patients with subfertility

Guidelines concerning myomas in women with subfertility (2) 

Intramural myomas myomas:: perform voer hysteroscopy (and/or and/or HyFoSy) when slightest doubt regarding submucous HyFoSy) component p and/or and/or distorsion of the cavityy – If present: consider myomectomy myomectomy,, certainly if  myoma > 3 cm  Pt with repeated failures – If absent: no myomectomy

Page 60 of 167

Before and after treatment with GnRH agonists

Volume reduction 40%

Before and after treatment by retrograde embolization

Other concomittant diseases 

Anemia – Iron deficiency – Sickle cell – Hemoglobinopathias

     

H HIV V infection ect o Malaria Treponematosis Tuberculosis Undernutrition Other tropical diseases or issues

Page 61 of 167

The older patient

The decrease in (live born) MFR relative to the MFR of women aged 20-30 years

Haadsma et al., 2010

Model of ovarian non-growing follicle (NGF) decay

Hansen, K. R. et al. Hum. Reprod. 2008 23:699-708

Page 62 of 167

% abnormal oocytes 80%

30%

age 35

37

40

Clinical conclusion



Increasing age is an objective basis to consider multiple p embryo y transfer.



This does not contradict the need for eSET in young women in first attempts

Evolution of maternal age in dizygotic twins in The Netherlands 1995 - 2006

Are these iatro-genic or socio-genic twins? If yes: prevention of infertility (treatment)

Lambalk, 2007

Page 63 of 167

Male partner: one clinical suggestion ~risks and complications



Amniocentesis from the age of 50 years onwards because

– Increase in Down syndrome – Increase in some monogenic dominant anomalies

t t R&C Treatment

Ovarian hyperstimulation syndrome Powerful drugs lead sometimes to excessive stimulation…

Figuur 1 Het traject van de zaadcellen naar de eicel.

… development of several tens of ovarian follicles

Page 64 of 167

OHSS Prevention The best prevention method is 1) To detect patients at risk 2)To adapt the selected stimulation 3) To closely monitor the patient

OHSS Risk factors Young age Low body weight  PCO or PCOPCO-like patients  High number of resting follicles (« necklace sign »)  History of OHSS  

OHSS Prevention methods     

Withholding hCG Coasting IV albumin / macromolecules Antagonists + GnRHGnRH-a Total embryo freezing & segmentation

Page 65 of 167

Miscellaneous complications

Literature data on complication rates after ART Baber

Bergh

Roest

Serour

Govaerts

N cycles OHSS + hosp Bleeding Adnex torsion Infection

600 1.3% 0.5%

10,125 0.7% 0.7% 0.3%

2,495 0.7% 0.1% 0.3%

3,500 1.7% 0.1% 0.3%

1,500 1.8% 0.2% 0.1% 0.4%

Total

1.8%

1.7%

1.1%

2.1%

2.5%

Bleeding following pickpick-up    

Vaginal hemorrhage in 5-10% Significant (>100 ml) blood loss in 0.8% of all TV/US OPU Very serious bleeding in 0.1% (retroperitoneal ovarian, sacral / iliacal vessels), leading to laparoscopy //--tomy Blood loss after 24h normally ~230 ml (Dessole ‘01): – a drop in Hct of 5% or of Hb of 1.6 g% = normal – if blood loss is “normal”, any postoperative acute abdomen must be infectious in origin



Prevention: – limit vaginal puncture sites to two – leave risky follicles untouched

Page 66 of 167

Infections after egg retrieval Incidence: 0.6%, sometimes with abscess formation abscesses:: often asymptomatic, late diagnosis (until six abscesses weeks later or even later)  culture culture:: E. Coli, B. fragilis or Enterococcus sp. in mixed cultures, often negative  Rare cases of infections after OPU: appendicitis, vertebral osteomyelitis  

Tubo-ovarian abscess Vaginal puncture of anaerobic pus due to infected puncture

Special case: Puncture of endometriotic cyst * Interrupt treatment if relapse during stimulation * Avoid puncturing endometriotic cysts * If puncture: IV antibiotics at the time of OPU

Page 67 of 167

Infections after egg retrieval 

DO NOT puncture endometriotic cysts (consider laparoscopic OPU), pseudocysts or hydrosalpinges on purpose



DO NOT administer routinely antibiotics prophylactically (?); only when (suspicion of) inadvertent puncture > fluoroquinolones/ fluoroquinolones/tetracyclins



DO NOT desinfect vagina (Betadin (Betadin:: 17.2% vs 30.3% PR (Van Os Os,, ‘92) but cleanse with physiological water

Complications after TESE

   

Bleeding (scrotal hematoma) h ) Infection Pain and dysfunction Androgen deficiency?

Adnexal (sub)torsion



Typical of stimulated cycles Incidence 0.1% of all ART cycles.



If pregnant 1/162



If OHSS 7.5% R/ laparoscopic untwisting (even after ischemia, no removal !) optionally after puncturing  R/ transvaginal puncture  

Page 68 of 167

Torsion of hyperstimulated ovary without necrosis

Torsion of hyperstimulated ovary with reversible necrosis

Torsion of ovarian cyst with irreversible necrosis

Page 69 of 167

Thrombotic complications related to the ovarian stimulation (without OHSS) 

Thrombosis < hypercoagulability in all stimulated women ( due to E2E2-rise )



A (underreported) number of severe cases of DVT have been described in hyperstimulated women

Family / personal history taking and heparin prophylaxis if indicated  Do not pretreat patients at risk with estrogen containing COC (either natural cycle or postpost-POP start) 

P Post Postt-treatment t t t R&C

Multiple pregnancy

Page 70 of 167

Cumulative singleton gestation weeks for IVF & ICSI <= 42 weeks 20000 15000 10000 5000 0 Cumulative singleton gestation weeks

24

25

26

27

28

29

30

31

41

41

68

99

134

145

188

227

32

33

34

35

36

37

331

462

727

1056

1963

3815

38

39

40

41

42

9028 11003 15535 8563

2428

Gestation weeks

Cumulative twin gestation weeks for IVF & ICSI <=42 weeks 5000 4000 3000 2000 1000 0 Cumulative twin gestation weeks

24

25

26

27

28

29

30

31

45

58

107

118

219

235

331

451

32

33

34

35

36

37

38

39

40

41

42

683

883

1368

1843

2928

3906

3985

1159

402

52

17

Gestation weeks

Cumulative triplet gestation weeks <= 42 weeks 300 250 200 150 100 50 0 Cumulative triplet gestation weeks

24

25

26

27

28

29

30

31

34

35

36

37

38

39

40

41

42

5

5

14

18

31

65

84

96 158 234 283 Gestation weeks

32

33

209

128

29

15

4

3

0

2

TWINS  

« A nice chance to have 2 babies at once ! » « …to make up for lost time » BUT      

Maternal mortality Transfer in ICU Severe prematurity SFGA Infant mortality Cerebral Palsy

X 2 or 3 X 15.5 X4 X4 X5 X 5 to 10

Maternal Morbidity Multiple (n=44,674) vs singleton pregnancy (n=165,188) RR (95% CI) Pre-eclampsia

2.8 (2.7-2.9)

Gestational diabetes

1.1 (1.9-1.2)

Myocardial infarction

3.7 (2.3-5.8)

Heart failure

12.9 (2.7-62.3)

Venous thromboembolism

2.7 (2.0-3.5)

Pulmonary edema

7.1 (4.5-11.3)

Post partum haemorrhage

1.9 (1.8-1.9)

Caesarean delivery

2.2 (2.1-2.2)

Hysterectomy

2.3 (1.7-3.2)

Page 71 of 167

The clinical tools … in IVF: SET  

in nonnon-IVF: SOFT

Judicious single embryo transfer Both for nearnear-elimination of triplets and for drastic reduction of twins

 

Judicious use of ovulation iinduction d ti ffor single i l ovarian follicle treatment in non-IVF

BELGIAN REIMBURSEMENT REGULATION •Six IVF/ICSI cycles (= oocyte harvests) reimbursed in a life-time •1182€ per cycle for laboratory costs ( gamete procurement and handling ) •Including cryocycles •Up to the age of 43 years

Linked to a rational transfer strategy ≤ 36 years 11st trial i l ever or 11st trial i l after f previous IVF/ICSI-delivery: always one fresh embryo; 2nd trial: one embryo if of sufficient quality; two if of insufficient quality; ≥3rd trial: maximum 2 embryos.

>36 - ≤39 years

> 39 years

11st and d 2nd 2 d trial: i l maximum 2 embryos;

N maximum No i number b of embryos to transfer is dictated

≥3rd trials: maximum 3 embryos.

CRYOCYCLES: 1 or 2 embryos

Page 72 of 167

Evolution of the number of twin pregnancies ( as % of total deliveries ) in Flanders

Evolution of the % of twin pregancies after ART treatment before and after the legal arrangement of July 2003

Live birth rate per randomized couple comparing cleavage stage with day 5 embryos (Papanikolaou et al., Hum. Reprod. (2008) 23 (1): 91-99).

Papanikolaou E G et al. Hum. Reprod. 2008;23:91-99

Page 73 of 167

Forrest plots showing the odds ratios of eSET versus DET for the separate trials and the pooled odds ratios for Mc Lernon et al., Lancet, 2010

Live birth Study or Subgroup Bhattacharya Davies Gerris

b)Lukassen

Martikainen Thurin 2004 Thurin 2005 van Montfoort

eSET DET Events Total Events Total Weight 6 3 9 14 22 91 4 32

Total (95% CI)

11 13 26 54 75 330 20 154 683

6 5 19 19 28 142 7 59

12 14 27 54 69 331 22 154

Odds Ratio M-H, Fixed, 95% CI

1.3% 1.8% 5.9% 6.8% 9.9% 49.4% 2.6% 22.5%

1.20 [0.23, 6.19] 0.54 [0.10, 2.93] 0.22 [0.07, 0.71] 0.64 [0.28, 1.47] 0.61 [0.30, 1.21] 0.51 [0.37, 0.70] 0.54 [0.13, 2.21] 0.42 [0.25, 0.70]

683 100.0%

0.50 [0.40, 0.63]

Total events 181 285 Heterogeneity: Chi² = 4.09, df = 7 (P = 0.77); I² = 0% Test for overall effect: Z = 5.92 (P < 0.00001)

Study or Subgroup

Multiple Live birth

Bhattacharya Davies Gerris Lukassen Martikainen Thurin 2004 Thurin 2005 van Montfoort Total (95% CI)

Odds Ratio M-H, Fixed, 95% CI

0.05 0.2 1 5 20 Favours DET Favours eSET

eSET DET Events Total Events Total Weight 2.1% 6 1 6 0 1.6% 5 1 3 0 5.2% 19 6 9 1 8.2% 19 6 14 0 28 14.0% 11 22 1 142 54.0% 46 91 1 1.6% 7 1 4 0 59 13.3% 12 32 0 181

285 100.0%

84 3 Total events Heterogeneity: Chi² = 5.39, df = 7 (P = 0.61); I² = 0% Test for overall effect: Z = 5.82 (P < 0.00001)

Odds Ratio M-H, Fixed, 95% CI

Odds Ratio M-H, Fixed, 95% CI

0.28 [0.01, 8.42] 0.43 [0.01, 14.08] 0.27 [0.03, 2.68] 0.07 [0.00, 1.40] 0.07 [0.01, 0.63] 0.02 [0.00, 0.17] 0.48 [0.02, 14.70] 0.06 [0.00, 1.02] 0.07 [0.03, 0.17] 0.01 0.1 1 10 100 Favours eSET Favours DET

Page 74 of 167

Page 75 of 167

DET > eSET unless one adds the cryocycles OR is it not so much a question of how many embryos but which embryo?

Prerequisites for a particular centre to implement esET • 1. Excellent results (the better the centre, the higher the % of eSET) • 2. 2 Willingness to decrease a very high MP rate • 3. Willingness to invest in optimization of a freeze/thaw programme • 4. eSET must be compatible with specific societal circumstances in which the centre works

Five pillars for eSET • Creating awareness • International agreement on patient and embryo characteristics prior to SET • Marketing the idea • In-depth counseling • Appropriate funding

Page 76 of 167

Reducing the number of twin births: 1st step

Single embryo transfer in selected cases

Twin-prone patient selection

Embryo selection

Reducing the number of twin births: 2nd step

Single embryo transfer in all cases except

In patients with poor prognosis

If only poor quality embryos are available

Take home message The ideal candidate for SET: 1. Young woman (<35 years old) 1 2. First or second attempt 3. With a choice of embryos to transfer/freeze (producing big oranges) 4. Blastocyst

Page 77 of 167

2009

Extrauterine E t t i pregnancy

Ectopic Pregnancy



~ 4% of all ART pregnancies



risk factors: – damaged tubes – previous myomectomy (uterine contractility ?)



OR for E.P. after difficult transfer = 3.91 (1.49(1.49-10.23)

Page 78 of 167

Ampullary ectopic

Interstitial / Cornual Pregnancy 2 to 6% of all ectopic localizations, may be combined with intrauterine pregnancy  difficult diagnosis, often late  beware: rupturing, acute hemorrhage and shock (even leading to hysterectomy ! )  typical after salpingectomy (rupturing later in pregnancy possible in these patients) 

Page 79 of 167

Cornual pregnancy after IVF

Cervical pregnancy

Low-cervical amniotic sac Uterus 15 x 8 x 4 cm Cervix 8,5 x 8cm wide Cervical tissue invaded by placental tissue = placenta increta Endometrium with pseudodecidualisation

Heterotopic Pregnancy  

1-3% of all ART pregnancies risk factors: same as for ectopics + number of transferred embryos

diagnosis: often late (think heterotopic !)  symptoms: abdominal pain, bleeding, shock at rupture -> surgery  72 72..5% of intrauterine pregnancies : live birth 

Page 80 of 167

Heterotopic Pregnancy: localization tubal

88%

cornual abdominal cervical ovarian 1% 2%

3%

6%

Pregnancy of Unknown Location

PUL Transient rise in HCG without clinical nor sonographic indication of localisation of implantation: - Diagnostic dilemma: academic (tubal abortion or tubal miscarriage) - Therapeutic dilemma: by clinical symptoms; do not overtreat

“Look beyond the most obvious diagnosis and always expect the unexpected unexpected” Think ectopic, think heterotopic !

Page 81 of 167

What should we do about the R & C’s?

Keep the beast under control

Safety = “zero tolerance”? • Total absence of an undesired phenomenon • Can/should we maintain it in (reproductive) medicine? • “Do-no-harm” instead of “Zero-tolerance” because there is a benefit (most of the time)?

Principles

Page 82 of 167

Number of deaths by traffic accidents in the EU-25 1996-2005

Belgium: 1996 ~1400 deaths 2005 ~1020 deaths 2009 ~ 750 deaths ( 1/3 of all ART children) Let’s go for “ZERO”

Number of deaths and heavy injured by traffic accidents in Belgium 1970-2006

“Let’s go for zero!” High cost due to: * police actions * automatic speed control by road cameras (n=?) * citizens paying a fortune in fines * increased insurance contracts

… But nobody says: stop the traffic!

Air traffic 2008 502 deaths in 109 accidents = 1 death/1,3 million flights = 1 death/7,7 million passengers

Yet, nobody says: Stop flying!

Page 83 of 167

Except…

Because of “concern with PAX safety”? • In fact: because fear for more risk than usual when flying ( annual mortality = extremely low ) • As long g as no “absolute” safety yg guarantee could be given, no airline dared to fly for fear of public perception not to care for the PAX safety • Up to the point that …

!

Page 84 of 167

• AIR TRAFFIC

• ART

“Absolute” safety comes with a price …

In ART too safety has a price…

When the price rises too high, safety concerns laxen …

When the price rises too high, risks are taken (multiples)…

People WANT to fly … There appears to be a balance

People WANT children…

There is a trade-off between desired outcome and risks

Zero – tolerance is is theoretical: impossible: nobody says Zero-tolerance nobody says stop ART! stop flying!

The Columbia Accident Investigation Board

“In our view, the NASA organizational culture had as much to do with this accident as the foam. Organizational culture refers to the basic values, norms, beliefs, and practices that characterize the functioning of an institution. At the most basic level, it defines the assumptions that employees make as they carry out their work. It is a powerful force that can persist through reorganizations and the change of key personnel.”

Nuclear Safety

Nevertheless 11-12/03/2011 Earthquake & tsunami in Japan

Page 85 of 167

Conclusion

In sectors where we expect zero-tolerance, e.g. international space flight and nuclear energy production, we still see major “risks and complications”, e.g. Columbia/Tsjernobyl/Fukushima

My questions to you • In (reproductive) medicine, is the goal “zero-tolerance” or minimal risk? • What level of safety (quantitative) do you want in reproductive medicine? • What kind of experiences do you really learn from? • How can we foster a prevention culture? • How can you change cultures? • How can ESHRE contribute to the safety of your work?

Let us state ourselves what we rationally consider as “safe” Safety issue

Zero tolerance level (ZTL)

Realistic lowest tolerance level (RLTL)

Multiple pregnancies Monozygotic MPs OHSS (severe) Bleeding at OPU Infection after OPU Congenital anomalies Cytogenetic abnormalities Effects of freezing & vitrification Epigenetic effects (media) Oncological effects Maternal deaths Fetal reduction Psychosocial effects Future fertility of ART-children Laboratory errors

Page 86 of 167

Let us state ourselves what we rationally consider as “safe” Safety issue

Zero tolerance level

Realistic lowest tolerance level

Multiple pregnancies Monozygotic MPs

0.9% 0.3%

<10% <1%

OHSS (severe) Bleeding at OPU Infection after OPU Congenital anomalies Cytogenetic abnormalities Effects of freezing & vitrification Epigenetic effects (media) Oncological effects Maternal deaths Fetal reduction Psychosocial effects Future fertility of ART-children Laboratory errors

Let us state ourselves what we rationally consider as “safe” Safety issue

Zero tolerance level

Realistic lowest tolerance level (?)

Multiple pregnancies Monozygotic MPs

0.9% 0.3%

<10% <1%

OHSS (severe)

0.0%

<0.5%

Bleeding at OPU Infection after OPU Congenital anomalies Cytogenetic abnormalities Effects of freezing & vitrification Epigenetic effects (media) Oncological effects Maternal deaths Fetal reduction Psychosocial effects Future fertility of ART-children Laboratory errors

Let us state ourselves what we rationally consider as “safe” Safety issue

Zero tolerance level

Realistic lowest tolerance level

Multiple pregnancies Monozygotic MPs

0.9% 0.3%

<10% <1%

OHSS (severe)

0.0%

<0.5%

Bleeding at OPU

0.0%

?

Infection after OPU Congenital anomalies Cytogenetic abnormalities Effects of freezing & vitrification Epigenetic effects (media) Oncological effects Maternal deaths Fetal reduction Psychosocial effects Future fertility of ART-children Laboratory errors

Page 87 of 167

Let us state ourselves what we rationally consider as “safe” Safety issue

Zero tolerance level

Realistic lowest tolerance level

Multiple pregnancies Monozygotic MPs

0.9% 0.3%

<10%<1%

OHSS (severe)

0.0%

<0.5%

Bleeding at OPU

0.0%

?

Infection after OPU

0.0%

?

Congenital anomalies Cytogenetic abnormalities Effects of freezing & vitrification Epigenetic effects (media) Oncological effects Maternal deaths Fetal reduction Psychosocial effects Future fertility of ART-children Laboratory errors

Let us state ourselves what we rationally consider as “safe” Safety issue

Zero tolerance level

Realistic lowest tolerance level

Multiple pregnancies Monozygotic MPs

0.9% 0.3%

<10% <1%

OHSS (severe)

0.0%

<0.5%

Bleeding at OPU

0.0%

?

Infection after OPU

0/0%

?

Congenital anomalies

~ natural conception (3 (3-4%) 4%) ~ natural conception (3 (3-4%) 4%)

Cytogenetic abnormalities Effects of freezing & vitrification Epigenetic effects (media) Oncological effects Maternal deaths Fetal reduction Psychosocial effects Future fertility of ART-children Laboratory errors

Let us state ourselves what we rationally consider as “safe” Safety issue

Zero tolerance level

Realistic lowest tolerance level

Multiple pregnancies Monozygotic MPs

0.9% 0.3%

<10% <1%

OHSS (severe)

0.0%

<0.5%

Bleeding at OPU

0.0%

?

Infection after OPU

0/0%

?

Congenital anomalies

~ natural conception (3-4%) (3 4%) ~ natural conception (3-4%) (3 4%)

Cytogenetic abnormalities

~ natural conception (5-6%) ~ natural conception (5-6%)

Effects of freezing & vitrification Epigenetic effects (media) Oncological effects Maternal deaths Fetal reduction Psychosocial effects Future fertility of ART-children Laboratory errors

Page 88 of 167

Let us state ourselves what we rationally consider as “safe” Safety issue

Zero tolerance level

Realistic lowest tolerance level

Multiple pregnancies Monozygotic MPs

0.9% 0.3%

<10% <1%

OHSS (severe)

0.0%

<0.5%

Bleeding at OPU

0.0%

?

Infection after OPU

0/0%

?

Congenital anomalies

~ natural conception (3-4%) (3 4%) ~ natural conception (3-4%) (3 4%)

Cytogenetic abnormalities

~ natural conception (5-6%) ~ natural conception (5-6%)

Effects of freezing & vitrification None

?

Epigenetic effects (media) Oncological effects Maternal deaths Fetal reduction Psychosocial effects Future fertility of ART-children Laboratory errors

Let us state ourselves what we rationally consider as “safe” Safety issue

Zero tolerance level

Realistic lowest tolerance level

Multiple pregnancies Monozygotic MPs

0.9% 0.3%

<10% <1%

OHSS (severe)

0.0%

<0.5%

Bleeding at OPU

0.0%

?

Infection after OPU

0/0%

?

Congenital anomalies

~ natural conception (3-4%) (3 4%) ~ natural conception (3-4%) (3 4%)

Cytogenetic abnormalities

~ natural conception (5-6%) ~ natural conception (5-6%)

Effects of freezing & vitrification None

?

Epigenetic effects (media)

?

None

Oncological effects Maternal deaths Fetal reduction Psychosocial effects Future fertility of ART-children Laboratory errors

Let us state ourselves what we rationally consider as “safe” Safety issue

Zero tolerance level

Realistic lowest tolerance level

Multiple pregnancies Monozygotic MPs

0.9% 0.3%

<10% <1%

OHSS (severe)

0.0%

<0.5%

Bleeding at OPU

0.0%

?

Infection after OPU

0/0%

?

Congenital anomalies

~ natural conception (3-4%) (3 4%) ~ natural conception (3-4%) (3 4%)

Cytogenetic abnormalities

~ natural conception (5-6%) ~ natural conception (5-6%)

Effects of freezing & vitrification None

?

Epigenetic effects (media)

None

?

Oncological effects

None

probably none

Maternal deaths Fetal reduction Psychosocial effects Future fertility of ART-children Laboratory errors

Page 89 of 167

Let us state ourselves what we rationally consider as “safe” Safety issue

Zero tolerance level

Realistic lowest tolerance level

Multiple pregnancies Monozygotic MPs

0.9% 0.3%

<10% <1%

OHSS (severe)

0.0%

<0.5%

Bleeding at OPU

0.0%

?

Infection after OPU

0/0%

?

Congenital anomalies

~ natural conception p ((3-4%)) ~ natural conception p ((3-4%))

Cytogenetic abnormalities

~ natural conception (5-6%) ~ natural conception (5-6%)

Effects of freezing & vitrification None

?

Epigenetic effects (media)

None

?

Oncological effects

None

probably none

Maternal deaths

None

unrelated to ART

Fetal reduction Psychosocial effects Future fertility of ART-children Laboratory errors

Let us state ourselves what we rationally consider as “safe” Safety issue

Zero tolerance level

Realistic lowest tolerance level

Multiple pregnancies Monozygotic MPs

0.9% 0.3%

<10% <1%

OHSS (severe)

0.0%

<0.5%

Bleeding at OPU

0.0%

?

Infection after OPU

0/0%

?

Congenital g anomalies

~ natural conception (3-4%) (3 4%) ~ natural conception (3-4%) (3 4%)

Cytogenetic abnormalities

~ natural conception (5-6%) ~ natural conception (5-6%)

Effects of freezing & vitrification None

?

Epigenetic effects (media)

None

?

Oncological effects

None

probably none

Maternal deaths

None

unrelated to ART

Fetal reduction

None

?

Psychosocial effects Future fertility of ART-children Laboratory errors

Let us state ourselves what we rationally consider as “safe” Safety issue

Zero tolerance level

Realistic lowest tolerance level

Multiple pregnancies Monozygotic MPs

0.9% 0.3%

<10% <1%

OHSS (severe)

0.0%

<0.5%

Bleeding at OPU

0.0%

?

Infection after OPU

0/0%

?

Congenital anomalies

~ natural conception (3-4%) (3 4%) ~ natural conception (3-4%) (3 4%)

Cytogenetic abnormalities

~ natural conception (5-6%) ~ natural conception (5-6%)

Effects of freezing & vitrification None

?

Epigenetic effects (media)

None

?

Oncological effects

None

probably none

Maternal deaths

None

unrelated to ART

Fetal reduction

None

?

Psychosocial effects

None

limited

Future fertility of ART-children Laboratory errors

Page 90 of 167

Let us state ourselves what we rationally consider as “safe” Safety issue

Zero tolerance level

Realistic lowest tolerance level

Multiple pregnancies Monozygotic MPs

0.9% 0.3%

<10% <1%

OHSS (severe)

0.0%

<0.5%

Bleeding at OPU

0.0%

?

Infection after OPU

0/0%

?

Congenital g anomalies

~ natural conception (3-4%) (3 4%) ~ natural conception (3-4%) (3 4%)

Cytogenetic abnormalities

~ natural conception (5-6%) ~ natural conception (5-6%)

Effects of freezing & vitrification None

?

Epigenetic effects (media)

None

?

Oncological effects

None

probably none

Maternal deaths

None

unrelated to ART

Fetal reduction

None

?

Psychosocial effects

None

limited

Future fertility of ART-children

None

??

Laboratory errors

Let us state ourselves what we rationally consider as “safe” Safety issue

Zero tolerance level

Realistic lowest tolerance level

Multiple pregnancies Monozygotic MPs

0.9% 0.3%

<10% <1%

OHSS (severe)

0.0%

<0.5%

Bleeding at OPU

0.0%

?

Infection after OPU

0/0%

?

Congenital g anomalies

~ natural conception (3-4%) (3 4%) ~ natural conception (3-4%) (3 4%)

Cytogenetic abnormalities

~ natural conception (5-6%) ~ natural conception (5-6%)

Effects of freezing & vitrification None

?

Epigenetic effects (media)

None

?

Oncological effects

None

probably none

Maternal deaths

None

unrelated to ART

Fetal reduction

None

?

Psychosocial effects

None

limited

Future fertility of ART-children

None

??

Laboratory errors

None

≠0

Practice

Page 91 of 167

Determinants of practice conduction

Complexity level of practice

(personal) ethics & economics

Individual

peers with shared values/agreements Fertility centre + culture & societal norms

Regional

+ data from registries & politics (laws)

National

+ data from professional bodies (e.g. EIM, SART, …)

Supranational

Monitoring outcome (efficacy and safety)

Global

+ data with a world perspective (e.g. ICMART)

EUROPE Assisted reproductive technology in Europe, 1997-2006: results generated from European registers by ESHRE by The European IVF-monitoring (EIM) Consortium

Main CPI’s reflecting safety in fresh IVF + ICSI 1997-2006

Multiple pregnancies

Main CPI’s for fresh IVF + ICSI 1997-2008 IVF/ICSI

nETs

N countries

%1e

%2e

%3e

%≥4e

x2

+50%

-50%

1/7

nDEL

+20% CPR/ET

%twin

%trip

CPR/OPU

-20%

1/3

IVF

ICSI

IVF

ICSI

28.5

28.7

32.5

31.9 33.0

2008 N=36

315.287

22.4

53.2

22.3

2.1

73.024

20.7

1.0

2007 N=33

264022

21.4

53.4

22.7

2.5

72493

21.3

1.0

29.1

28.6

32.8

2006 N=32

222354

22.1

57.3

19.0

1.6

58725

20.8

0.9

29.0

29.9

32.4

33.0

2005 N=30

236480

20.0

56.1

21.5

2.3

47966

21.0

0.8

26.9

28.5

30.3

30.9

2004 N=29

225480

19.2

55.3

22.1

3.3

45128

21.7

1.0

26.6

27.1

30.1

29.8

2003 N=28

234142

15.7

55.9

24.9

3.5

47212

22.0

1.1

26.1

26.5

29.6

28.7

2002 N=25

203877

13.7

54.8

26.9

4.7

42827

23.2

1.3

26.0

27.2

29.5

29.4

2001 N=23

189549

12.0

51.7

30.8

5.5

37467

24.0

1.5

25.1

26.2

29.0

28.3

2000 N=22

171301

12.1

46.7

33.3

6.8

36066

24.4

2.0

24.7

26.6

28.4

28.7

1999 N=22

132979

11.9

39.2

39.6

9.3

25085

24.0

2.2

24.2

26.1

27.7

27.9

1998 N=18

141251

11.5

37.2

42.0

9.4

22859

23.9

2.3

23.2

24.8

27.0

26.8

1997 N=18

103125

11.5

35.9

38.3

14.2

24516

25.6

3.3

NA

NA

26.1

26.4

Page 92 of 167

Main CPI’s for fresh IVF + ICSI 1997-2006 IVF+ ICSI

nETs

nDEL

222354

58725

236480

47966

225480

45128

N countries

2006

CPR/OPU

CPR/ET

IVF

IVF

ICSI

ICSI

N=32

2005 N=30

2004 N=29

2003

234142

47212

203877

42827

189549

37467

171301

36066

132979

25085

141251

22859

103125

24516

N=28

2002 N=25

2001 N=23

2000 N=22

1999 N=22

1998 N=18

1997 N=18

Main CPI’s for fresh IVF + ICSI 1997-2006 IVF+ ICSI

nETs

%1e

%2e

%3e

%≥4e nDEL %twin

%trip

N countries

2006

222354

58725

236480

47966

225480

45128

CPR/OPU

CPR/ET

IVF

IVF

ICSI

ICSI

N=32

2005 N=30

2004 N=29

2003

234142

47212

203877

42827

189549

37467

171301

36066

132979

25085

141251

22859

103125

24516

N=28

2002 N=25

2001 N=23

2000 N=22

1999 N=22

1998 N=18

1997 N=18

Main CPI’s for fresh IVF + ICSI 1997-2006 IVF+ ICSI

nETs

%1e

%2e

%3e

%≥4e nDEL %twin

%trip

N countries

2006

222354

58725

236480

47966

225480

45128

CPR/OPU

CPR/ET

IVF

ICSI

IVF

ICSI

NA

NA

26.1

26.4

N=32

2005 N=30

2004 N=29

2003

234142

47212

203877

42827

189549

37467

171301

36066

132979

25085

N=28

2002 N=25

2001 N=23

2000 N=22

1999 N=22

1998

141251

22859

N=18

1997

103125

11.5

35.9

38.3

14.2

24516

25.6

3.3

N=18

Page 93 of 167

Main CPI’s for fresh IVF + ICSI 1997-2006 IVF+ ICSI

nETs

%1e

%2e

%3e

%≥4e nDEL %twin

%trip

N countries

2006

222354

58725

236480

47966

225480

45128

CPR/OPU

CPR/ET

IVF

IVF

ICSI

ICSI

N=32

2005 N=30

2004 N=29

2003

234142

47212

203877

42827

189549

37467

171301

36066

N=28

2002 N=25

2001 N=23

2000 N=22

1999

132979

25085

N=22

1998

141251

11.5

37.2

42.0

9.4

22859

23.9

2.3

23.2 24.8

27.0

26.8

103125

11.5

35.9

38.3

14.2

24516

25.6

3.3

NA

26.1

26.4

nETs

%1e

N=18

1997

NA

N=18

Main CPI’s for fresh IVF + ICSI 1997-2006 IVF+ ICSI

%2e

%3e

%≥4e nDEL %twin

%trip

N countries

2006

222354

58725

236480

47966

225480

45128

CPR/OPU

CPR/ET

IVF

IVF

ICSI

ICSI

N=32

2005 N=30

2004 N=29

2003

234142

47212

203877

42827

189549

37467

N=28

2002 N=25

2001 N=23

2000

171301

36066

N=22

1999

132979

11.9

39.2

39.6

9.3

25085

24.0

2.2

24.2 26.1

27.7

27.9

141251

11.5

37.2

42.0

9.4

22859

23.9

2.3

23.2 24.8

27.0

26.8

103125

11.5

35.9

38.3

14.2

24516

25.6

3.3

NA

26.1

26.4

nETs

%1e

N=22

1998 N=18

1997

NA

N=18

Main CPI’s for fresh IVF + ICSI 1997-2006 IVF+ ICSI

%2e

%3e

%≥4e nDEL %twin

%trip

N countries

2006

222354

58725

236480

47966

225480

45128

CPR/OPU

CPR/ET

IVF

IVF

ICSI

ICSI

N=32

2005 N=30

2004 N=29

2003

234142

47212

203877

42827

N=28

2002 N=25

2001

189549

37467

N=23

2000

171301

12.1

46.7

33.3

6.8

36066

24.4

2.0

24.7 26.6

28.4

28.7

132979

11.9

39.2

39.6

9.3

25085

24.0

2.2

24.2 26.1

27.7

27.9

141251

11.5

37.2

42.0

9.4

22859

23.9

2.3

23.2 24.8

27.0

26.8

103125

11.5

35.9

38.3

14.2

24516

25.6

3.3

NA

26.1

26.4

N=22

1999 N=22

1998 N=18

1997

NA

N=18

Page 94 of 167

Main CPI’s for fresh IVF + ICSI 1997-2006 IVF+ ICSI

nETs

%1e

%2e

%3e

%≥4e nDEL %twin

%trip

N countries

2006

222354

58725

236480

47966

225480

45128

CPR/OPU

CPR/ET

IVF

IVF

ICSI

ICSI

N=32

2005 N=30

2004 N=29

2003

234142

47212

203877

42827

N=28

2002 N=25

2001

189549

12.0

51.7

30.8

5.5

37467

24.0

1.5

25.1 26.2

29.0

28.3

171301

12.1

46.7

33.3

6.8

36066

24.4

2.0

24.7 26.6

28.4

28.7

132979

11.9

39.2

39.6

9.3

25085

24.0

2.2

24.2 26.1

27.7

27.9

141251

11.5

37.2

42.0

9.4

22859

23.9

2.3

23.2 24.8

27.0

26.8

103125

11.5

35.9

38.3

14.2

24516

25.6

3.3

NA

26.1

26.4

nETs

%1e

N=23

2000 N=22

1999 N=22

1998 N=18

1997

NA

N=18

Main CPI’s for fresh IVF + ICSI 1997-2006 IVF+ ICSI

%2e

%3e

%≥4e nDEL %twin

%trip

N countries

2006

222354

58725

236480

47966

225480

45128

CPR/OPU

CPR/ET

IVF

IVF

ICSI

ICSI

N=32

2005 N=30

2004 N=29

2003

234142

47212

N=28

2002

203877

13.7

54.8

26.9

4.7

42827

23.2

1.3

26.0 27.2

29.5

29.4

189549

12.0

51.7

30.8

5.5

37467

24.0

1.5

25.1 26.2

29.0

28.3

171301

12.1

46.7

33.3

6.8

36066

24.4

2.0

24.7 26.6

28.4

28.7

132979

11.9

39.2

39.6

9.3

25085

24.0

2.2

24.2 26.1

27.7

27.9

141251

11.5

37.2

42.0

9.4

22859

23.9

2.3

23.2 24.8

27.0

26.8

103125

11.5

35.9

38.3

14.2

24516

25.6

3.3

NA

26.1

26.4

nETs

%1e

N=25

2001 N=23

2000 N=22

1999 N=22

1998 N=18

1997

NA

N=18

Main CPI’s for fresh IVF + ICSI 1997-2006 IVF+ ICSI

%2e

%3e

%≥4e nDEL %twin

%trip

N countries

2006

222354

58725

236480

47966

CPR/OPU

CPR/ET

IVF

IVF

ICSI

ICSI

N=32

2005 N=30

2004

225480

45128

N=29

2003

234142

15 7 15.7

55 9 55.9

24 9 24.9

35 3.5

47212

22 0 22.0

11 1.1

26 1 26.5 26.1 26 5

29 6 29.6

28 7 28.7

203877

13.7

54.8

26.9

4.7

42827

23.2

1.3

26.0 27.2

29.5

29.4

189549

12.0

51.7

30.8

5.5

37467

24.0

1.5

25.1 26.2

29.0

28.3

171301

12.1

46.7

33.3

6.8

36066

24.4

2.0

24.7 26.6

28.4

28.7

132979

11.9

39.2

39.6

9.3

25085

24.0

2.2

24.2 26.1

27.7

27.9

141251

11.5

37.2

42.0

9.4

22859

23.9

2.3

23.2 24.8

27.0

26.8

103125

11.5

35.9

38.3

14.2

24516

25.6

3.3

NA

26.1

26.4

N=28

2002 N=25

2001 N=23

2000 N=22

1999 N=22

1998 N=18

1997

NA

N=18

Page 95 of 167

Main CPI’s for fresh IVF + ICSI 1997-2006 IVF+ ICSI

nETs

%1e

%2e

%3e

%≥4e nDEL %twin

%trip

N countries

2006

222354

CPR/OPU

CPR/ET

IVF

IVF

ICSI

29.8

ICSI

58725

N=32

2005

236480

47966

N=30

2004

225480

19.2

55.3

22.1

3.3

45128

21.7

1.0

26.6 27.1

30.1

234142

15 7 15.7

55 9 55.9

24 9 24.9

35 3.5

47212

22 0 22.0

11 1.1

26 1 26.5 26.1 26 5

29 6 29.6

28 7 28.7

203877

13.7

54.8

26.9

4.7

42827

23.2

1.3

26.0 27.2

29.5

29.4

189549

12.0

51.7

30.8

5.5

37467

24.0

1.5

25.1 26.2

29.0

28.3

171301

12.1

46.7

33.3

6.8

36066

24.4

2.0

24.7 26.6

28.4

28.7

132979

11.9

39.2

39.6

9.3

25085

24.0

2.2

24.2 26.1

27.7

27.9

141251

11.5

37.2

42.0

9.4

22859

23.9

2.3

23.2 24.8

27.0

26.8

103125

11.5

35.9

38.3

14.2

24516

25.6

3.3

NA

26.1

26.4

nETs

%1e

N=29

2003 N=28

2002 N=25

2001 N=23

2000 N=22

1999 N=22

1998 N=18

1997

NA

N=18

Main CPI’s for fresh IVF + ICSI 1997-2006 IVF+ ICSI

%2e

%3e

%≥4e nDEL %twin

%trip

N countries

2006

222354

CPR/OPU

CPR/ET

IVF

IVF

ICSI

ICSI

58725

N=32

2005

236480

20.0

56.1

21.5

2.3

47966

21.0

0.8

26.9 28.5

30.3

30.9

225480

19.2

55.3

22.1

3.3

45128

21.7

1.0

26.6 27.1

30.1

29.8

234142

15 7 15.7

55 9 55.9

24 9 24.9

35 3.5

47212

22 0 22.0

11 1.1

26 1 26.5 26.1 26 5

29 6 29.6

28 7 28.7

203877

13.7

54.8

26.9

4.7

42827

23.2

1.3

26.0 27.2

29.5

29.4

189549

12.0

51.7

30.8

5.5

37467

24.0

1.5

25.1 26.2

29.0

28.3

171301

12.1

46.7

33.3

6.8

36066

24.4

2.0

24.7 26.6

28.4

28.7

132979

11.9

39.2

39.6

9.3

25085

24.0

2.2

24.2 26.1

27.7

27.9

141251

11.5

37.2

42.0

9.4

22859

23.9

2.3

23.2 24.8

27.0

26.8

103125

11.5

35.9

38.3

14.2

24516

25.6

3.3

NA

26.1

26.4

nETs

%1e

N=30

2004 N=29

2003 N=28

2002 N=25

2001 N=23

2000 N=22

1999 N=22

1998 N=18

1997

NA

N=18

Main CPI’s for fresh IVF + ICSI 1997-2006 IVF+ ICSI

2006

%2e

%3e

%≥4e nDEL %twin

%trip

CPR/OPU

CPR/ET

+20% +50% -50%

1/10

-20%

1/3

IVF

IVF

ICSI

222354

22.1

57.3

19.0

1.6

58725

19.9

0.9

29.0 29.9

32.4

33.0

236480

20.0

56.1

21.5

2.3

47966

21.0

0.8

26.9 28.5

30.3

30.9

225480

19.2

55.3

22.1

3.3

45128

21.7

1.0

26.6 27.1

30.1

29.8

234142

15 7 15.7

55 9 55.9

24 9 24.9

35 3.5

47212

22 0 22.0

11 1.1

26 1 26.5 26.1 26 5

29 6 29.6

28 7 28.7

203877

13.7

54.8

26.9

4.7

42827

23.2

1.3

26.0 27.2

29.5

29.4

189549

12.0

51.7

30.8

5.5

37467

24.0

1.5

25.1 26.2

29.0

28.3

171301

12.1

46.7

33.3

6.8

36066

24.4

2.0

24.7 26.6

28.4

28.7

132979

11.9

39.2

39.6

9.3

25085

24.0

2.2

24.2 26.1

27.7

27.9

141251

11.5

37.2

42.0

9.4

22859

23.9

2.3

23.2 24.8

27.0

26.8

103125

11.5

35.9

38.3

14.2

24516

25.6

3.3

NA

26.1

26.4

x2

N countries

ICSI

N=32

2005 N=30

2004 N=29

2003 N=28

2002 N=25

2001 N=23

2000 N=22

1999 N=22

1998 N=18

1997

NA

N=18

Page 96 of 167

Main CPI’s for fresh IVF + ICSI 1997-2008 IVF/ICSI

nETs

%1e

%2e

%3e

%≥4e

x2

+50%

-50%

1/7

N countries

nDEL

+20% CPR/ET

%twin

%trip

CPR/OPU

-20%

1/3

IVF

ICSI

IVF

ICSI

28.5

28.7

32.5

31.9 33.0

2008 N=36

315.287

22.4

53.2

22.3

2.1

73.024

20.7

1.0

2007 N=33

264022

21.4

53.4

22.7

2.5

72493

21.3

1.0

29.1

28.6

32.8

2006 N=32

222354

22.1

57.3

19.0

1.6

58725

20.8

0.9

29.0

29.9

32.4

33.0

2005 N=30

236480

20.0

56.1

21.5

2.3

47966

21.0

0.8

26.9

28.5

30.3

30.9

2004 N=29

225480

19.2

55.3

22.1

3.3

45128

21.7

1.0

26.6

27.1

30.1

29.8

2003 N=28

234142

15.7

55.9

24.9

3.5

47212

22.0

1.1

26.1

26.5

29.6

28.7

2002 N=25

203877

13.7

54.8

26.9

4.7

42827

23.2

1.3

26.0

27.2

29.5

29.4

2001 N=23

189549

12.0

51.7

30.8

5.5

37467

24.0

1.5

25.1

26.2

29.0

28.3

2000 N=22

171301

12.1

46.7

33.3

6.8

36066

24.4

2.0

24.7

26.6

28.4

28.7

1999 N=22

132979

11.9

39.2

39.6

9.3

25085

24.0

2.2

24.2

26.1

27.7

27.9

1998 N=18

141251

11.5

37.2

42.0

9.4

22859

23.9

2.3

23.2

24.8

27.0

26.8

1997 N=18

103125

11.5

35.9

38.3

14.2

24516

25.6

3.3

NA

NA

26.1

26.4

Main CPI’s for fresh IVF + ICSI 1997-2015 Where are we heading? IVF+ ICSI

nETs

%1e

%2e

%3e

%≥4e nDEL %twin

%trip

N countries

2015

CPR/OPU

CPR/ET

IVF

ICSI

IVF

ICSI

~33 33

~34 34

~35 35

50

35

14

1

<10? 10? <5?

0.1

~32 32

22.4

53.2

22.3

2.1

20.7

1.0

28.5 28.7

N=max

2010 N=?

2011 N=?

2008

32.5 31.9

N=36

This is work in progress to which we all contribute

Complications at OPU 2000-2008 in ESHRE (N=36) Year

Total cycles

OHSS

All compl. to OPU

Bleeding

Infection

Maternal death

Fetal reduction

2008

525640

2947 (0.6%)

976 (0.19%)

652 (0.12%)

49 (0.09%0)

1

394

2007

492442

2470 (0.5%)

991

574

64

3

364

2006

459170

2753 (0.8%)

938

544

42

0

466

2005

418111

3347 (1.2%)

1048

523

207

0

436

2004

367066

2858 (0.8%) (0 8%)

1125

520

362

4

526

2003

365103

2646 (0.7%)

NA

799

135

2

480

2002

324238

2148 (0.7%)

1156

622

227

2

461

2001

289690

1851 (0.6%)

569

395

0

0

397

2000

279267

1586 (0.6%)

652 (0.23%)

388 (0.14%)

36 (0.13%0)

0

256

Irregular data due to incomplete reporting Differences of definition >>> differences of practice

Page 97 of 167

Other risks and complications of ART • • • • • • • •

Congenital anomalies Genetic anomalies Epigenetic anomalies ( culture media, …) Cryopreservation of embryo’s Vit ifi ti off embryo’s Vitrification b ’ Vitrification of oocytes Long term fertility effects on ART-offspring …

Data from individual studies or meta-analyses are reassuring but more longitudinal data are needed before we can be sure about the absence of or the size of an effect

What effect do these registries have on daily practice? • Very long-term reporting tools with long lag time ( 5 years ) • Big oil tanker: once a direction is taken, they move slowly but surely with strong impact on general opinion • They give an indication of the direction we are moving i iin (e.g. ( + MPR; MPR e.g. – IUI) • Sensitive to: – (in)completeness – Differences in definition, reporting units (CPR, LBR, “BESST” practice …) – Averaging out wide differences between countries – Rubbish in rubbish out

IUI-H and IUI-D 2001-2008 IUI with partner sperm <40years

IUI with donor sperm

>40years

<40years

DR

2

3

DR

2

3

10.5

11.0

0.8

5.5

8.8

0.0

>40years

DR

2

3

DR

2

3

2008

13.5

9.5

0.3

6.6

3.7

0.0

10.2

11.7

0.5

6.3

9.9

0.0

2007

14.6

10.2

0.5

6.1

6.5

0.0

9.2

10.6

0.6

4.4

8.9

0.0

2006

13.3

10.5

0.6

4.1

6.5

0.0

12.6

11.0

1.1

7.4

4.9

0.7

2005

18.9

10.8

1.2

9.2

6.5

0.0

12.6

11.9

1.3

8.2

10.4

0.3

2004

18.7

11.1

0.8

8.4

7.1

1.4

12.2

11.4

2.2

8.8

6.2

0.0

2003

16.7

10.6

1.2

6.3

2.9

0.0

11.6

10.2

1.1

6.9

8.9

1.1

2002

16.6

9.6

0.6

6.7

5.8

1.2

12.8

10.2

1.1

9.7

3.8

0.0

2001

17.1

9.4

1.2

8.0

7.3

0.0

<40 years * recent decrease in delivery rate (DR)! * twinning has remained stable, triplets down

>40 years * recent decrease in DR! * twinning stable, triples down!

Page 98 of 167

Large databases (EIM, SART, ICMART …)

• Do not tell us HOW to improve on efficacy or safety in individual practice of single centres • For that purpose we need specific methods and tools • Long-time: methods = clinical studies • Short time: monitoring = dashboard of CPIs

We need a speedboat with a dashboard

• Showing easy-tomeasure-and-followup key performance indicators (KPIs) of: – Clinical excellence – Laboratory excellence – Operational business excellence

Embryo Utilization Rate (EUR)

EUR =

N of embryos N of embryos transferred (A) + cryopreserved (B) ____________________________________ N of 2 PNs (C)

A = indicator of ET policy (clinical ) B = indicator of cleanroom quality (laboratory) C = indicator of fertilization efficacy (laboratory)

Page 99 of 167

III. Labo KPIs Embryo Util Rate (#embr ET) + (# embr frozen) / #2pn * 100 70,00 60,00 50,00 40,00 %

Embryo util  rate

30,00 20,00 Inhuizing clean‐room verlaagde zuurstof cultuur

10,00 0,00 jan 

febr  maart  april

mei 

juni juli  2010

aug 

sept 

okt

nov

dec

© 2008 Universitair Ziekenhuis Gent

9

Are the data available and is it affordable? • Data available? – Yes for the major issues, with lag period – Incomplete for the less frequent issues – Data collection has begun in “big tanker databases”

• Affordable? – We do what we can – We need more dedicated staff in each individual centre for surveillance of quality and safety – This has a price: are we entitled to financial support?

Concluding remarks k

Page 100 of 167

Quality is more than safety (=absence of errors or complications) • = (Cost)-efficiency, i.e. lowest cost for highest outcome • = Accessibility (financially and geographically) • = Safety ((“do do no harm harm” vs. vs “zero-tolerance”) zero tolerance ) • = Timeliness • = Satisfaction in patients’, partners’ and collaborators’ • = Innovation & renovation – Infrastructure – Instruments & tools – Techniques and procedures

• = Structured quality control

Do you recognize any of the following symptoms? • Belief to belong to the best performers (production) – complacency • Focus on technical rather than management and people Issues • Organizational Insularity and Ineffective QA programme • Lack of Effective Corporate Oversight and centre safety oversight • Continuous Management Directional Changes and Cost cutting • Lack of competence in human performance evaluation • Repeated Problems distracting attention from safety issues • General Dissatisfaction of Regulatory Authority

They suggest shortcomings in your safety management

Prevention (of errors, risks and complications) Not only reactive prevention = Learning from events and making improvements Also proactive prevention = The mindset and ability to identify the nature and causes of developing problems and to develop a strong safety culture nurtured by leadership

Page 101 of 167

What can ESHRE do about it? • SIG SQART – Identification of potential safety hazards – Reflection on what level of safety for each hazard is the goal ( theory vs. practice ) – Edit guidelines on how to achieve this – Help devise CPI’s in dashboards • Clinical CPI’s • Laboratory CPI’s • Operational (&financial) CPI’s

• INTERESTED? JOIN US ([email protected] and [email protected])

Have a safe journey!

Page 102 of 167

IVF; patient pathways and patient satisfaction Prof.Dr. Bart CJM Fauser University y Medical Center,, Utrecht, The Netherlands

Lecture outline

Patient pathways Patient satisfaction

Global IVF paradox Insufficient access to treatment Expensive No health insurance coverage

Tendency Overtreatment in Western societies Varying indications for treatment Commercial environment / consumer behaviour

Page 103 of 167

F&S 2012

FS 2005

HR 2012

Page 104 of 167

Berg Brigham, HR 2012

2010

standard of success in assisted reproduction (debate series, n=16: Hum Reprod 2004) ‘BESST, birth emphasizing a successful singleton at term’ (Min) ‘Narrow to infant outcomes with optimal prognosis’ (Schieve) ‘Healthy lower order birth’ (Dickey) ‘Informed Informed choice by couple after appropriate counselling’ counselling (Buckett) ‘Elective SET rate per center’ (Land) ‘BESST with other denominator’ (Davies) ‘Three parameters; oocyte #, implantation or deliveries/embryo’ (Pinborg) ‘Consider outcomes per treatment rather than cycle’ (Heijnen) ‘Singleton live births also including preterm births’ (Wennerholm) ‘Value cryopreservation on cumulative pregnancy rates’ (Tiitinen) ‘Cumulative singleton/twin delivery rate / oocyte pick-up’ (Germond) Discussion closed (Barlow)

Page 105 of 167

Pitfalls in the success per IVF cycle paradigm

Optimal children outcomes not well defined A cycle can be extremely long and complex Treatment burden / drop outs NOT considered Complications NOT considered Cost NOT considered Assess outcomes per started treatment or per given period of time

Lecture outline

Patient pathways Patient satisfaction

NEJM 2012

Page 106 of 167

NEJM 2012

In order to minimise drop-out

00own 17 180018

Percentage cause of drop-out

100% 90% Financial Financial Age (woman Woman age Gave p Gaveup up End optio Endoftreatment Health Healthprob problems Reject RejectIVF IVF Relationship Relationship Rejectfertil treatment Reject Poorprogno prognosis Poor Distress d Emotional

80% 70% 60% 50% 40% 30% 20% 10% 0%

< Work-up During work-up < Treatment Conventional < 3less IVF/ICSI before during before conventional 3 33oror> IVF/ICSI more work-up work-up treatment treatment IVF/ICSI IVF/ICSI

Ovarian hyperstimulation for IVF - the bigger picture

Drop out cost

complex

Burden of treatment

Ovarian O i stimulation

contribute to success?

Complications (OHSS) Intense monitoring

Page 107 of 167

HR 2010

Aim

Collect information regarding death within 1 year (and related to) IVF, 1984-2008, The Netherlands

Total ~100.000 IVF treatment cycles 6 death directly related to IVF pick-up) ((3 OHSS,, 3 thombosis and sepsis p after oocyte y p p)

Results

17 death directly related to IVF pregnancy (pre-eclampsia, cerebral hemorrhage, sepsis, vascular dissection, pulmonary embolism, liver failure, portal hypertension)

8 death unrelated to IVF

Conclusions

Overall mortality related to IVF pregnancy higher than general population World-wide underreporting IVF related mortality Underling national registry and reporting

Recent papers in favour of mild stimulation IVF

Page 108 of 167

F&S 2010

Objective

Design

Why insured patients drop out of IVF in the USA ? Women < 40 yrs, private clinic, insured, not pregnant, who did not return 39% of termination due to stress - toll on couples relationship - too anxious or depressed

Results

Conclusions

Suggestion for patient support - written information on how to deal with psychological stress - easy access to psychologist or social worker US patients similar reasons for terminating IVF compared to Europe and Australia

F&S 2011

Accessibility Information and communication Respect and autonomy Continuity of care Emotional support Partner involvement

Page 109 of 167

2012

Percentage of the three most selected categories of reasons for discontinuation (overall and accoridng to treatment stage)

Gameiro, HRU 2012

2013

Page 110 of 167

HR 2012

“hospitality…”

Boivin, HR 2012

Causes of burden and associated interventions (Boivin, HR 2012)

Page 111 of 167

Considerations concerning drop outs

Frequency of discontinuation of treatment in other areas in medicine? Balance IVF outcomes per cycle versus per treatment strategy paradigm Balance burden of treatment versus efficacy Introduce support by social worker / psychologist Implement concept of hostmanship in team

CONCLUSION: IVF patient pathways and patient satisfaction Cost-effective Woman Access to treatment (burden of treatment)

Society Couple C l (successful)

Future health Of child

Page 112 of 167

How to implement TQM Ass.Prof. T.Mardesic PhD. Institute Pronatal, Prague, Czech Republic

ESHRE PCC London 2013

Presenting author has no commercial and/or  financial relationships with manufacturers of  pharmaceuticals laboratory supplies and/or pharmaceuticals, laboratory supplies and/or  medical devices

ESHRE PCC London 2013

Implementing TQM ‐ learning objectives ‐

• Presentation should offer an overwiew about  current position of TQM in healthcare  systems, its basic principles and introduction systems, its basic principles and introduction  into practical implementing  of TQM    

ESHRE PCC London 2013

Page 113 of 167

Implementing TQM • • • • • • •

Introduction What is TQM Why to implement TQM Principles of TQM How to implement TQM Advantages and disadvantages of TQM Conclusions ESHRE PCC London 2013

Implementing TQM • Interest in healthcare systems • Increasing allocation of national and  i international resources for both private and  i l f b h i d public sector in management systems • Healthcare providers across the globe are  progressively implementing TQM ESHRE PCC London 2013

Why to implement TQM • In the past, errors were the integral part of definition of quality (reporting non‐conformities followed by  corrective measures, risk management)

• Over time, the definition of quality has  transformed to „zero‐defect“ status by the process known as Continuous Improvement Process (CIP) • What is excellent today may be inferior tomorrow there is always room for improvement ESHRE PCC London 2013

Page 114 of 167

Why to implement TQM • • • •

Improve efficiency Provide high quality patient care Reduce costs TQM as a part of hospital´s „competitive  strategy“ (TQM placing an emphasis on improved  customer satisfaction offers the prospect of great market  share and profitability)

ESHRE PCC London 2013

What is TQM • TQM is a comprehensive and structured approach to  organizational management that seeks to improve the quality of products and services through ongoing refinements in response to continuous feedback. • TQM is a holistic approach to long term success that views i continuous ti i improvement t in all i ll aspects t off an organization as a process and not as a short term goal. • TQM is a structured system for meeting and exceeding customer (patient´s) needs and expectations by  creating organization‐wide participation in the planning and implementation of improvement processes. ESHRE PCC London 2013

What is TQM TQM is a philosophy in which core focus is  meeting the customer´s (patient´s) needs and  ensuring their satisfaction ensuring their satisfaction

ESHRE PCC London 2013

Page 115 of 167

What is TQM • 1/Commitment and direct involvement of highest‐level executives in setting quality goals and policies,  allocation of resources and monitoring of results • 2/realization that transforming an organization means fundamental changes (everyone´s job) • 3/ building quality into services from the beginning • 4/ understanding changing needs of patients and satisfying them in a cost‐effective manner • 5/ instituting leadership in place of mere supervision so that everyone performs in the best manner to improve quality and productivity thereby continually reducing total cost ESHRE PCC London 2013

What is TQM • 6/  eliminating barriers between people and  departments, so they work as teams to achieve  common objectives • 7/  instituting flexible programs for training and  education

ESHRE PCC London 2013

Principles of TQM • A central principal of TQM is that mistakes  may be made by people, but most of them are  caused, or at least permitted, by faulty  systems and processes.

ESHRE PCC London 2013

Page 116 of 167

ESHRE PCC London 2013

TQM –key principles

Management commitment     Employee empowerment Fact based decision  making Continuous improvement Customer  (patient´s needs and  expectations)   focus

ESHRE PCC London 2013

Principles of TQM 1

Customer focused organization

Understanding current and future patient´s  needs Strategic decisions are „customer driven“ Society is an important customer of bussiness: business ethics,  safety, environment

2

Leadership

Leaders establish the unity of y purpose and direction.  Responsibility for strategic planning with strong future orientation.

3

Involvement of people

People at all levels are the essence of an organization, health care  institute´s success depends increasingly on the knowledge,  skillls and motivation of its work force

ESHRE PCC London 2013

Page 117 of 167

Principles of TQM 4

Process approach

Activities and related resources should be managed as a process

5

System approach to management

Identifying, understanding and managing a system of interrelated processes as a system contribute´s  to the organization´s effectiveness and efficiency

6

C ti Continual l improvement i t

Permanent objective Permanent objective of the organization, a part of management of all processess

7

Factual approach to decision making

Effective decisions are based on  the analysis of data and informations

8

Mutually beneficial supplier relationship

Organization and suppliers nare interdependent and a mutually beneficial relationship enhances the ability of both to create value

ESHRE PCC London 2013

How to implement TQM Number of TQM models that organization can  use  • ISO quality management standards • European Foundation for Quality Management • Malcolm Baldridge Criteria for Performance  Excellence • Deming Application Prize

ESHRE PCC London 2013

How to implement TQM Quality Management System VISION Background

Legislation EconomicaL potential Quality of services Education, research, organization

Strategy

Evaluation

Objective evaluation (scoring)

ESHRE PCC London 2013

Page 118 of 167

How to implement TQM Quality Management System Responsibility of management

Management of resources

Management of processes

Analysis and quality improvement

Strategy and QC

Human resources

QM and risk  assessment

Measurabel criteria for:

Organization g and structure of the clinic Standardization of procedures Atmosphere and working conditions

Space p conditions, , equipment

Organization g Internals standards Payments Supplier´s  evaluation

Management  g system Process evaluation Services / products Quality control Health care quality assurance

Evaluation (patients, partners,  colleagues) 

Software, data  protection archivation

Development of new products and services

System of continual improvement Internal audits

ESHRE PCC London 2013

How to implement TQM ISO 9000 standards and TQM • ISO 9000 does not define quality or provide any  specifications of products or processes • ISO 9000 assures that the organization has in place a  well‐operated QMS that conforms to the ISO 9000  standards • Does not guarantee a quality product. No inspection  of the product is involved in certification • Consequently, an organization may be certified but  still produce poor quality products (results)

ESHRE PCC London 2013

A simple model of TQM Customer Focus Planning Process

Total Participation

Process Improvement

Process Management

ESHRE PCC London 2013

Page 119 of 167

How to implement TQM A preliminary step in TQM implementation is to  assess the organization´s current reality • Unstable funding base, weak administrative  bl f di b k d i i i systems, lack of managerial skill, poor  employee morale                 TQM would not be  appropriate

ESHRE PCC London 2013

How to implement TQM Companies are not very likely to adopt practices related to  TQM if: • Employes are not really disciplinned in their work • Absence or lack of orientation towards teamwork • Lack of cultural or demographic homogeneity • Preference for fixed woring rules and little initiative • Poor opinion or acceptance of training • Staff members generally unaccustomed to relating salary and fulfillment of the company performance or results TOXIC WORKPLACE

ESHRE PCC London 2013

How to implement TQM Steps in managing the transition Identifying tasks to be done

Assessing current reality Creating a model of the desired state (TQM) Securing outside consultation and training someone „in house“

Creating necessary management  structures

Management must be heavily involved

Developing strategies for building commitment

Visionary leadership needed

Designing mechanisms to communicate the change

Mechanisms beyond existing processes will need to be developed

Assigning resources

Outside consultants will always be required

ESHRE PCC London 2013

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Commitment from employees

Executive control

Quality improvement culture

Focus on customer requirements

Continuous improvement of processes Co‐operation from employees

ESHRE PCC London 2013

How to implement TQM

PDCA circle Plan: define problem collect data Plan:  define problem, collect data Do: develop and implement a solution Check: confirm the results through before‐and‐ after data comparison Act: document results, inform  others about changes, recommendations for the  problem to be adressed in the next PDCA  cycle ESHRE PCC London 2013

How to implement TQM • TQM is a way of thinking, it involves cultural  shift, it encompasses all aspects of an  organization

ESHRE PCC London 2013

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Advantages and disadvantages of TQM • TQM is commonly understood to encompass  concepts such as customer (patient´s)  satisfaction, continuous improvement,  management by fact or data and employee management by fact or data and employee  involvement • While these concepts are easily understood, in  practice many companies and clinics fail to  adopt and implement TQM ESHRE PCC London 2013

Advantages and disadvantages of TQM • According to recent figures only 20‐36% of  organizations that have attempted to  implement a TQM program have achieved  some sort of significant or even tangible some sort of significant or even tangible  improvements in quality, productivity,  competitivness or financial return

ESHRE PCC London 2013

Advantages and disadvantages of TQM • It has been suggested that the implementation of TQM results in an over‐emphasis on customer (patient´s) satisfaction with a relative neglect of the pursuit of profits • The major problem with TQM is that there is a  disconnection between management systems designed to measure customer satisfaction and those designed to measure business profitability,  and this has often led to unwise investments in  quality ESHRE PCC London 2013

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Advantages and disadvantages of TQM • The disadvantages of TQM is that it can lead to bureaucracy • The money needed to implement TQM principles adds to  costs • Some managers and employee groups might be hesitant to  change into a TQM based approach if the company is doing  well now well now • Also the benefits of TQM are not guaranteed to be  successful simply based on a complete implementation.  Customers (patients) themselves will decide upon the  success of the company • Also the costs of inspection of processes as well as research and development projects might be too costly

ESHRE PCC London 2013

TQM ‐ Conclusions • Quality in today´s health care can and must be  managed • Processes, not people, are the problem • Every employee is responsible for quality l i ibl f li • Quality must be measurable • Quality improvements must be continuous • Quality is a long term investment ESHRE PCC London 2013

TQM ‐ Conclusions • Quality management  can only be described  as „Total“  when all  employees and  managers become  engaged in the effort  and think of quality not  as one‐off program but  as an ongoing, integral  part of daily practice ESHRE PCC London 2013

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THE COST OF QUALITY Example of the IVI approach to the continuous improvement

Carlos Blanes [email protected]

www.ivi.es PÁG.1

Session Objectives

• Understand the difference between the investment in quality and the cost of non-quality. • To

understand

that

managing

quality

means

managing

processes. • To know the philosophy of KAIZEN as a commonsense approach to quality management.

2

Cost and Quality

• There is a strong relation between quality and cost because: − It cost to produce and serve with quality y − It cost to control and maintain q quality − It cost to have non-quality

3

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Cost and Quality

• The cost of quality should be calculated as the addiction of the following cost: Prevention cost

Q lit Quality Evaluation cost

Internal faults cost

Non Quality External faults cost

4

Cost and Quality

€ TOTAL COST

COST

Quality cost

Failures cost

Non Quality (0% OK)

Quality (100% OK)

Optimal cost

Improvement area Indifference area High evaluation cost area 5

Identifying non-quality

CONTACT WITH PATIENT

%

APPOINTMENT

%

FIST VISIT IN THE CLINIC

%

REPRO LABORATORY

% OVARIAN ESTIMULATION

%

OVUM PICK-UP

%-nº emb THAWED EMBRYO TRANSFER

PREGNANCY

%

EMBRYO VITRIFICATION

%

EMBRYO TRANSFER

PREGNANCY

6

Page 125 of 167

Identifying non-quality

• Key elements when evaluating the non-quality cost of the process: −Measurable cost • Material lost • Drop out rate before the appointment • Drop out rate before the visit • Drop out rate before the treatment • Drop out rate after a failure

−Non measurable cost (Other non-quality cost) • Clinical complications • Image damage • Psychological cost • Market lost • Low satisfaction of the Patient •…

7

Cost and Quality

Measurable cost (quality + failure)

Non Measurable cost (non-quality)

8

Cost and Quality

“Quality is a cost”

Vs.

“Non-Quality is a cost”

Quality should be evaluated as an investment to eliminate the cost of nonquality

9

Page 126 of 167

CONCLUSION

• Is important to evaluate the investment in quality in order to improve in the quality indicators.

Q li oriented Quality i d management is i worthy

10

Introduction to Quality Management

TQM

TQC

Six Sigma

Lean

KAIZEN

EFQM

Continuous Improving to improve Quality and meet or exceed the Customer Expectations

11

Introduction to KAIZEN

KAIZEN

KAI = CHANGE

ZEN = GOOD

Masaaki Imai 12

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Introduction to KAIZEN

KAIZEN strategy basic concepts1: • Kaizen and Management Functions • Process versus Results • PDCA / SDCA cycles • Putting quality first • Speak with data • The next process is the customer

(1) Gemba KAIZEN. Masaaki Imai 1997

13

Process as a link between Strategy and Operations

?

PROCESS 14

Administration Department

IVF Department

Mediical Department

Nurse ery Department

Patient Serv vice Department

Processes in IVF Clinic

PROCESS OF MEDICAL ATENTION

15

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Kaizen and Management

From the traditional management perspective, Management has two major functions: • Maintenance • Improvement

From the KAIZEN perspective, improvement can be classified as: • Kaizen • Innovation

Slide Source: Captures from the book, Gemba KAIZEN. Masaaki Imai 1997

16

Kaizen and Management

WHY?

17

The Continuous Improvement Process: PDCA / SDCA Cycles • How can we deal with the Improvement Process? • Steps in the process:  PDCA Cycle (Plan, Do, Check, Act)  SDCA Cycle (Standardize, Do, Check, Act)

Improvement

PDCA

PDCA

SDCA

SDCA

PDCA SDCA

Time

18

Page 129 of 167

The Lean perspective

Replace waste for value-added…

Value added

waste WORK

WORK

… not working or consuming more resources Same Work  Better Outcome

19

The Lean perspective

Transport unused human talent Defects

Over Processing

Inventory

8W

Motion

Waiting Overproduction

20

Start spinning the wheel of improvement

But when analyzing the processes, how can we identify the problems, wastes or the improvement issues??

21

Page 130 of 167

Start spinning the wheel of improvement

Identifying the root of the problem: • •

Visual management:

• •

5s • Shine • Standardize • Straighten • Sort • Sustain Control Panels Kanban

5 Whys Ishikawa diagrams (Fishbone) and 5 Ms

Source: Capture from the book, Gemba KAIZEN. Masaaki Imai 1997

Working with process: • •

Quality circles Risk Management (incluir cuadro)

22

Speaking with data • Speaking with data is the only way not to make a feelings-driven management • These measures are known as Key Performance Indicators (KPI) • Shewhart Control Charts, trend analysis or variation analysis can be done to control the outcome 0,7

0,6

0,5

0,4

0,3

p



0,2

0,1 200303

200401

200411

200509

200607

200705

200803

200901

“What cannot be measured cannot be managed” “Everything that is measured improves” (Peter Drucker) 23

Summary • KAIZEN is a business (and not only business) philosophy that chase continuous improvements to meet customer expectations by applying a cycle process that consist of: − Planning what to do and how to do it − Doing the plan g the outcome Measure − Checking − Adjust to improve next time and standardize

• Kaizen will use methods and techniques for evaluating problems and improve processes • And Remember

“Improvement is infinite” 24

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Example of the IVI approach

25

THANK YOU 26

Further Reading • Break-even Analyses: Basic Model, Variants, Extensions (Marcell Schweitzer, Ernst Trossmann , Gerald H. Lawson) • Activity-Based Costing: Making it Work for Small and Mid-Sized Companies (Douglas T. Hicks) • Activity-based Cost Management: An Executive's Guide ((Gary y Cokins)) • Costes de calidad y no calidad (Oriol Amat i Salas) • Gemba KAIZEN. (Masaaki Imai)

27

Page 132 of 167

The role of the European Tissue Directive on TQM Edgar V. Mocanu MD RCSI and HARI, Rotunda Hospital, Dublin

ESHRE 2013-Total quality management in an IVF centre

Learning objectives

• Discuss if EUTC Directive and TQM have common ground. • Understand how the EUTCD facilitates the implementation of a TQM programme in an IVF unit.

DISCLAIMER

THE SPEAKER HAS NO CONFLICT OF INTEREST.

Page 133 of 167

ART practice

Offering the right expertise for the achievement of a pregnancy in the most efficient, safe and cost effective way

Facilitate the conception of a healthy child with the smallest possible risktheto couple for both the couple and clinic

Beginning

Patient assessment

Pregnancies

Staff

ART reality • started without a safety record approval • developed to more than 1 million cycles worldwide per year • Established techniques • IVF and ICSI • Embryo slow freeze freeze and thaw • Sperm cryopreservation • Vitrification • Oocyte cryopreservation • Experimental • ovarian tissue cryopreservation • in vitro maturation of oocytes • ovarian tissue re-implantation

Page 134 of 167

ART practice maturing

Safety Patient assessment

Outcome Pregnancies

Protocols Staff

Need for implementing TQM GOOD Investigating patients Handling queries Handling complaints Treating couples = deciding upon treatment = monitoring patients = surgical procedures = laboratory care = transfer and follow-up = talking to couples Obtaining results

NOT THAT GOOD Saying what we do Documenting it Reviewing it regularly Proving that we do the right thing Opening communication lines with regulators Handling media Finding time to organise the above

ART – internal and external pressures • Services need to reassure stakeholders that ART is: • Safe • Monitored • Audited • Self-improving • Accessible • Recognized medical treatment

Page 135 of 167

Relevance

26th March 2013

• “total quality management, IVF” • “TQM, IVF, EUTCD”

134,000 results 7 results

DIRECTIVES • 2004/ 23/ EC (Mother Directive) • Standards of quality and safety for human tissues and cells intended for human application (donation, procurement, testing, processing, preservation, storage, distribution)

• Prevent the transmission of diseases • 2006/ 17/ EC (Technical Directive 1) • Donation (procurement, donation, testing) of human tissues and cells intended for human application

• 2007/ 86/ EC (Technical Directive 2) • Cell and tissues (coding, processing, preservation, storage and distribution) of human tissues and cells intended for human applications

Learning objectives

• Discuss how EUTC Directive and TQM have common ground. • Understand how the EUTCD facilitates the implementation of a TQM programme in an IVF unit.

Page 136 of 167

Provision of the quality and safety of tissues and cells EUTC Directive • • • •

Quality management Person Responsible Personnel TC

• • • • •

Reception Processing Storage Labelling, documentation Distribution

• Relation with 3rd parties • Coding

ISO • • • • •

Customer focus Leadership Involvement of people Process approach System approach to management

• Continuous improvement • Factual approach to decision making

• Mutual beneficial supplier relationship

Guidance

• Was the Directive based on the principles of ISO accreditation and Quality management?

Page 137 of 167

EUTC Directive

TQM in ART

• Reassure the public

• Excellent patient care

• Highest level of protection

• Highest success rates

• Safeguard public health

• Policies and protocols

• Establish standards for

• Continuous improvement

processes

EUTC Directive

TQM in ART

• TE accreditation

• ISO accreditation

• Notification system

• Continuous assessment

• Inspection

• Certified training

• Inspector training

• Re-certification

• Traceability

EUTC Directive

• Quality system based on good practice • SOP • Guidelines • Training and reference

TQM in ART

• Quality system and CI • All enumerated

manuals

• Reporting forms • Donor records • Information on destination of TC

Page 138 of 167

Quality/ EUTC LEAP

Streamlined treatment Safety Patient assessment

Feedback Outcome Pregnancies

Quality systems Protocols Staff

Learning objectives

• Discuss if EUTC Directive and TQM have common ground. • Understand how the EUTCD facilitates the implementation of a TQM programme in an IVF unit.

ART steps

Testing

Acceptance

Procurement

Processing

Partner donation Oocyte recovery

Partner processing -insemination -culturing

Negative Acceptance into th programme the

Distribution Storage

Embryo transfer Embryo y Freeze Embryo storage

Oocyte donation Non-partner processing -insemination -culturing

Viral screen Sperm donation

Positiveexclusion from programme

Referral to Units that treat positive patients

Page 139 of 167

Quality management • Quality assurance (QA) the total sum of all planned and systematic activities required in order to establish sufficient trust that a product or service meets the quality requirements as determined

• Quality control (QC) the operational techniques and activities which are carried out in order to meet the quality requirements

• Quality improvement (QI) risk management quality management SAE/SAR management

TQM

“a system of management based on the principle that every member of staff must be committed to maintaining high standards of work in every aspect of a company’s operations”

TQM focus areas

• Leadership • Processes • Policies • Staff St ff development d l t and d ffeedback db k • Partnership (customers, suppliers, etc) • Customer feedback • Adverse events • KPI’s

Page 140 of 167

ART quality systems • Cover all areas of the service • CLINICAL (doctors, nurses, auxiliaries) • ADMINISTRATION • LABORATORY • RESEARCH • ONCOFERTILITY SERVICES • TRAINING

• Many standards • ISO 9001 • ISO 15198 • ART TQM Certification??

• Quality Manager

EUTCD • Reproductive cells = all tissues and cells intended to be used for the purpose of assisted reproduction.

• All TE (ART Units) have to fulfil safety and quality criteria: • Procurement, testing, donation • Processing, coding, preservation, storage and distribution.

• Should be: • Accredited • Designated • Authorized • Licensed

by a National Competent Authority

• Have a quality system based on principles of good practice

EUTC Directive - CLINICAL • Serological testing (HIV, HBV, HCV, Syphilis, Chlamydia) • Within 2 months of initial procurement and (if quality systems in place) every 24 months afterwards

• Personnel should be qualified to perform tasks and be provided with training

• Procurement is carried out by persons with appropriate training and experience

• Testing of donors is carried out by qualified staff

• Notification of SAR/ SAE • Confidentiality • Data storage

Page 141 of 167

Clinical TQM in ART • Definition of procedures (processes) • Standard operating procedures (SOP’s) = Guidelines • • • •

Every process Simple and descriptive (flow charts best) “Write what you do and do what is written!” Involve the other groups as “outsiders” as they have priceless opinions

• Staff training, retraining and CPD, (recorded, signed) • Similar to ESHRE Embryology Diploma

• Reporting of adverse events • Audit and change

EUTC Directive – Laboratory

• • • • • •

Quality management system Storage Processing materials Traceability Coding SAE/ SAR

EUTC Directive Staff

• Optimum number of staff/ procedures performed • Certified training records • Regular re-certification/ competency assessment ESHRE Embryology Certification Diploma

Processing

• Air quality, microbial colony and particle counts

Page 142 of 167

EUTC Directive Storage

• safe (monitored, locked, certified tanks) • registration of stored material, • separate storage for different risk patient groups

Traceability

• from the donor to the recipient • data storage for 30 years (paper or electronic) • Contact of reproductive material with processing devices and substances

EUTC Directive Coding

• European code • Identification of reproductive material

Donation identification: • Unique ID number • Identification of the tissue establishment Product identification: • Product code (basic nomenclature) • Split number (if applicable) • Expiry date

Donation identification ISO Country Identifier

TE Code

Unique Donation Number

2 characters

6 characters

13 characters

(alphabetic)

(alpha/numeric)

(alpha/numeric)

Product identification Coding System  Identifier 1 character

Product Code

Split Number

Expiry Date

7 characters

3 characters

8 characters

(alphabetic)

(alpha/numeric)

(alpha/numeric)

(numeric)

Page 143 of 167

XX000048000000S101397 E000002100120140802

GB009876G999911123456 A00S113400120110124

Laboratory TQM in ART

• Processes (defined and categorised) • Standard operating procedures (SOP’s) guidelines • Simple and descriptive (flow charts best) • “Write what you do and do what is written!”

• Staff training, retraining and CPD • Stock taking • Equipment validation • Document control

Page 144 of 167

QUALITY SYSTEM DATABASE Kelly P et al., Fertil Steril 2008

Document control Training and development Continuous improvement Assets management

Document management • Paper • Computerised quality database • Q-Pulse • Windows or Mac platform

• Contains • All protocols • All contracts • All training records • All KPI’s • All minutes of meetings

Quality systems EUTC Directive

TQM

• Quality manager

• Quality manager

• SOP

• Regular staff meetings

• Guidelines

• Adverse events, incidents • Non-conformances • Quality masterplan + KPI’s

• Training and reference manuals • Reporting forms • Donor records • Information on final destination

• Development plan • Training and CPD

• Data stored for 30 years

• Strategic plans

of TC

Page 145 of 167

Administration TQM in ART • Orders and purchasing • Suppliers and supplies • Costs

• SOP’s • Patient handling • Communication with customers

• Complaints • Suggestions • Positive feedback

• Training, retraining, CPD

EUTC Directive • Reactions • Infections (bacterial, viral) transmitted through ART • Diseases (malignant, others) • Reactions to medication

• Events • Human error (loss of reproductive material, mix-up) • Equipment failure

Risk management

Testing

Acceptance

Procurement

Processing

Partner donation Oocyte recovery

Partner processing -insemination -culturing

Negative Acceptance into th programme the

Distribution Storage

Embryo transfer Embryo y Freeze Embryo storage

Oocyte donation Non-partner processing -insemination -culturing

Viral screen Sperm donation

Positiveexclusion from programme

Referral to Units that treat positive patients

Page 146 of 167

SAR-E • Report all: • Adverse events • Adverse reactions • Admissions to hospital • OHSS • Bleeding • Infection • Unexpected surgery • Incidents • Non-conformances

SAR-SAE All practice scenarios where an aspect of ART care resulted or could result in patient harm. Processing Laboratory based infection with a proven human pathogen Culture media event Distribution Mix-up of gametes and embryos Infection from non-partner donation Storage

Tank failure during cryopreservation storage, loss of gametes, embryos

Offspring

Genetic condition in the offspring after non-partner donation

Infection in the offspring after non-partner donation in a previously seronegative mother Clinical

Severe reaction to a drug resulting in death Events after cross border reproductive care OHSS

Adverse events = positive lessons

• Analyse in depth

(team)

• Address in time

(with all staff)

• Learn from mistakes • Positive corrective actions • Preventative action plan

• Not a matter of WHO but WHAT!

Page 147 of 167

EUTC Directive serves as a platform for implementing TQM in ART

SHOULD WE STOP HERE?

ART NIRVANA (TQM)

Satisfied stakeholders Streamlined treatment Safetyy Patient assessment

Excellence Feedback Outcome Pregnancies

Accreditation Quality systems Protocols Staff

Page 148 of 167

Quality leadership • Vision • Goals • Trust • Inspiring

Leadership • Departmental heads • Weekly meeting • Agenda • To do and confirmed done • M Monthly thl meeting ti • Quality review • Data collected • Paper • 40-50 pages

Buy in from all staff

Page 149 of 167

Analysis of laboratory processes

Aims: remove variation and waste in the IVF laboratory make efficient and effective use of the available laboratory space reduce the inventory holding costs

Kelly P et al. Hum Reprod 2009

A structured walk-through each process Start

Identify the inputs and outputs of the process

Continue to update & classify process map!

Document entire flow of the process selected

Identify all value and non-value added operations

“Staple yourself to the patient” Classify/characterize process parameters into 3 main factors

Develop initial list of process parameters along with current operating conditions

Identify/classify the scope of the process

Identify/classify measurements t taken on product & process parameters

Identify/Classify upstream In-process product parameters

 Noise factors (N)  Standard operating procedures (S)  Controllable process parameters (C)

Kelly P et al., IFS 2010

Results? • 62% reduction in the value of media and consumables stored • 40% reduction in paper records • 36% improvement in laboratory air quality • 8% increase in usable space within the laboratory • the roadmap standardised processes and procedures leading to easier identification of process non-conformances with prompt actions based on newly devised visual controls.

Page 150 of 167

Perfection in culture environment? Closed System: 52 Hour Culturing Process

6 hrs insemination

24Hrs Fert Check

0Hr Oocyte Recovery

Temperature variations in IVF microenvironments Kelly P et al., IFS 2010

49Hrs Cleavage Ass

52Hrs Embryo Transfer

Kelly P., et al., IFS 2010  A thermocouple linked to a datalogger was used to measure the temperature of media contained within culture dishes throughout the 52 hour culturing cycle. Temperature was measured every 30 seconds throughout 52 hour culturing cycle. This was repeated 6 times; 3 times using closed microenvironments for the culturing, assessment and processing of the samples and 3 times using semi-closed microenvironments. For safety reasons the test dish did not contain embryos but it followed a randomly selected dish containing embryos through each stage of the culturing process. The closed environment Cook K-MINC-1000 direct heat incubator for culturing and a Mobile IVF-1 Chamber (Humidi Crib) for assessment and processing. The semi-closed environment Heracell 240 indirect heat incubator for processing and a MiniTub HT50 heated stage fixed to a Nikon Inverted Microscope for assessment and processing.

Open System: 52 Hour Culturing Process

0Hr Oocyte Recovery

6Hrs Insemination

49Hrs Clevage Ass

24Hrs Fert Check

52Hrs Embryo Transfer

Page 151 of 167

How quick does temperature recover after door opening? COMPARISON OF INCUBATOR TEMPERATURES 37.1 37 36.9 36.8 36.7 36.6 36.5 T1: Indirect Heat (Heracell) probe in media

36.4

T3: Direct Heat(MINC) probe in media

36.3 36.2

0:35

0:34

0:33

0:32

0:31

0:30

0:29

0:28

0:27

0:26

0:25

0:24

0:23

0:22

0:21

0:20

0:19

0:18

0:17

0:16

0:15

0:14

0:13

0:12

0:11

0:10

0:09

0:08

0:07

0:06

0:05

0:04

0:03

0:02

0:01

36.1

Max Temperature drop after door open Direct heat 0.3 Degrees C Indirect Heat 0.6 Degrees C

Recovery Time after door open Direct heat 24 Minutes Indirect Heat 47 Minutes

How long does it take for culture temperature to recover? HUMIDI CRIB VS HEATED STAGE TEMPERATURE COMPARISON 37.5 37 36.5 36 35.5 35 34.5

Mobile IVF-1 Chamber (Isolette): Probe in media

34 33.5

Microscope Heated Stage

33

0: 16

0: 15

0: 14

0: 14

0: 13

0: 12

0: 11

0: 11

0: 10

0: 09

0: 08

0: 08

0: 07

0: 06

0: 05

0: 05

0: 04

0: 03

0: 02

0: 02

0: 01

0: 00

32.5

TIME

Max Temperature drop after move from incubator Direct heat 0.2 Degrees C Indirect Heat 2.6 Degrees C

Time for temperature to recover Direct heat 2 Minutes Indirect Heat >40 Minutes

TEMPERATURE CHANGES AT DISTRIBUTION COMPARISON OF LAMINAR AIR FLOW AND HUMIDI CRIB 37.5 37 36.5 36 35.5 35 34.5 34

HUMIDI CRIB

33.5 HEATED STAGE 33 32.5 1

6

11

16

21

26

31

36

41

46

51

56

61

TIME

Max Temperature drop after move from incubator Direct heat 0.3 Degrees C Indirect Heat 3.0 Degrees C

Page 152 of 167

PDCA

TQM - ART Nirvana

Reduce or eliminate • Non-value added time • Long processes in the laboratory • Paper • Unproven procedures • Unjustified interventions • Badly designed facilities

As such……

TQM is achieved, not when there is nothing more to add, but when there is nothing left to take away.

Edgar Mocanu

Page 153 of 167

Toyota – “the best build cars in the world”

ART- “pregnant with healthy singleton delivery”

• Never be satisfied • There’s got to be a better way • Reform business when business is good • No change is bad

Primary physician Oncology services

Hospital

Endocrine Urology

Regulators

Couple Academic institutions

Suppliers

Professional bodies

Media

Insurers

Legal team

Special thanks

• Padraig Kelly (Quality Manager) • Gerri Emerson (Person Responsible) • Ciara Hughes (Laboratory Director)

Page 154 of 167

Aim at perfection in everything, though in most things it is unattainable. However, they who aim at it, and persevere, will come much nearer to it than those whose laziness and despondency make them give it up as unattainable. Lord Chesterfield

Page 155 of 167

TQM Conclusion Veljko Vlaisavljevic Department of Reproductive Medicine and Gynecologic Endocrinology University Medical Centre Maribor Slovenia

Running of IVF Center • 10% clinical skills 30% scientific skills • 30% scientific skills • 60% sheer organization TQM= the scientific way of doing bussines

From: Mortimer D& Mortimer S.T. : Quality and risk management in the IVF laboratory.  Cambrdge University Press, 2005

What is TQM ?

• Total               → everyone is involved in y nouousely improving   y p g • Quality           →con service to patients • Management → with data and profound  knowledge  Ron Fotzgerald

Page 156 of 167

The quality cycle

From:  Frances Hill, Queen‘s University in Belfast,1999

Andrilogy laboratory Embriology laboratory  Reproductive surgery Complications

Patients pathway & satisfaction TQM implementation Cost of quality European Tissue Directives

Page 157 of 167

PATIENTS

Future ?

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You can now register for these upcoming ESHRE Campus events:

• Application and challenges of emerging technologies in preimplantation and prenatal diagnosis 12-13 September 2013 - Prague, Czech Republic • Female genital tract congenital malformations: new insights in an old problem 27-28 September 2013 - Thessaloniki, Greece • Introducing new techniques into the lab 4-5 October 2013 - Barcelona, Spain • Polycystic ovary syndrome: A new look at an old subject 25-26 October 2013 - Rome, Italy • Infections from conception to birth: role of ART 7-8 November 2013 - Berlin, Germany • Endoscopy in reproductive medicine 20-22 November 2013 - Leuven, Belgium • From early implantation to later in life 28-29 November 2013 - Brussels, Belgium Mark your calendar for: • Premature ovarian insufficiency 6-7 December 2013 - Utrecht, The Netherlands

www.eshre.eu (see “Calendar”) Contact us at [email protected]

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Total quality management (TQM) in an IVF Centre. - eshre

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