Talk delivered at "ART Experts & Merck - Shaping the Future of Fertility”, Rio de Janeiro, BRAZIL, April 27th, 2019.

1. Sandro C. Esteves, MD., PhD.
ANDROFERT & University of Campinas (UNICAMP)
Campinas, BRAZIL
MODERN REQUIREMENTS OF
AN ART CENTER OF
EXCELLENCE

2. Esteves, 2
Sandro Esteves, MD., PhD.
• Medical and Scientific Director, ANDROFERT, Campinas, BRAZIL
• Professor, Department of Surgery (Division of Urology), University of Campinas
(UNICAMP), BRAZIL
• Research Associate, American Center for Reproductive Medicine, Cleveland Clinic, USA
• Professor of Reproductive Endocrinology (Honorary), Faculty of Health, Aarhus
University, DENMARK
Declare receipt of honoraria for lectures from Merck, Besins, Lilly, and Gedeon-
Richter.
Affiliation & Disclosure

3. 1.Contextualize IVF success in a quality framework
2.Critical attributes of ART Centers of excellence
3.Role of quality management and clinical information
systems to achieve excellence
Lecture Outline
Esteves, 3

4. What is the
success track
record of your IVF
clinic?

5. n Established 2013
n 100 babies born
n Few credentials experience
n IVF first-line treatment
n Avoid to treat low prognosis pts.
n Record of errors/pt. complaints
n High rate of multiples
n Advertise a lot
n Established 1997
n >2,000 babies born
n Lots of credentials/experience
n All treatment options available
n Individualized approach
n Rare errors/patient complaints
n Low rate of multiples
n Educational marketing
Doctor ‘Look Good’
PR/cycle = 60%
Doctor ‘Look Bad’
PR/cycle = 30%
Practice patterns can lead to
high pregnancy rates at
expense of good patient care

6. üDelphi method (structured communication technique)
üDevelopment of 298 quality indicators
üTwenty-four indicators selected based on consensus of
importance; Six quality dimensions
ESTEVES, 6

7. 6Most Important Quality Dimensions in Infertility Care
1. Effectiveness
2. Efficiency
3. Safety
4. Patient centeredness
5. Timeliness
6. Equity
Success in ART goes far beyond pregnancy rate…
Dancet et al. Hum Reprod 2011; Mainz. Int J Qual Health Care 2003; Bento & Esteves 2016
Esteves, 7

8. Quality in IVF is how well the outputs of our processes comply
with a set of pre-defined requirements
Esteves, 8
Compliance with guidelines, regulations, and expected results
Meeting client’s needs and expectations
Continuous improvement
Dancet et al. Hum Reprod 2011; Mainz. Int J Qual Health Care 2003; Bento & Esteves 2016

9. Quality can be measured…
•Live birth rate per patient group; cumulative live birth rate; time to live birthEffectiveness
•No. staff & equipment per No. treatments; No. Oocyte/embryo as per OS protocol/patient
group; Website with information, contracts, informed consents; Clinical information system
allowing input of relevant info and extraction of reports, etc.; No. patients (relative to total)
taking throughout diagnostic phase to optimize effectiveness and safety
Efficiency
•No. ART cycles with (1) complications (OHSS, bleeding, infection, complaints of serious pain;
multiple pregnancy, ectopic pregnancy), (2) No. non-conformities (clinical mistakes, lab
incidents)
Safety
•No. clients (relative to total) who opinionated about their experiences (surveys,
questionnaires); No. psychological support offered; No. nurse support offered; Dropout rate
Patient
centeredness
•Average duration waiting time pre- and during various IVF sub-processesTimeliness
•Clear inclusion/exclusion criteria (eg. donation, surrogacy); transparent reporting of
outcomes; counselling about chances of success; provision of treatment/protocols as per
legislation/guidelines; provision of ethical vision of the clinic (experimental treatment, etc.)
Equity

10. Effectiveness Indicator: CLBR
The International Glossary on Infertility and Fertility Care
Zegers-Hochschild et al. FS 2017
Term Definition
Cumulative
delivery rate
per aspiration or
initiated cycle
with at least one
live birth
The number of deliveries with at least one
live birth resulting from one initiated or
aspirated ART cycle, including all cycles in
which fresh and/or frozen embryos are
transferred, until one delivery with a live
birth occurs or until all embryos are used,
whichever occurs first

11. The International Glossary on Infertility and Fertility Care, 2017
Zegers-Hochschild et al. FS 2017
Term Consensus
Time to
pregnancy
(TTP)
The time taken to establish a
pregnancy, measured in months
or in numbers of (menstrual)
cycles
Effectiveness Indicator: TTLB

12. Poor quality of service, physical burden, and lack of
psychological support account for ~60% dropout
Patient centeredness indicator: Dropout Rates
Gameiro et al. Hum Reprod Update 2012
22 studies
21,453 patients
8 countries

13. Interplay between CLBR and dropout rates critical to
shorten TTLB

15. Patient engagement in care
• Treatment options and plan
• Self-care and assistance with self-care
• Patient education
Care coordination
• System to prevent errors, follow-up and support, patient adherence monitoring,
communication among care providers and patients (hotline, chats, etc.)
Clinical information system
• Ease of access to reports and results, satisfaction surveys, feedback
Publicly available information on practices
• Web based info (credentials, office location, hours, quality of care, etc.)
Davis et al. J Gen Intern Med 2005
Attributes of excellence in healthcare

16. Coordinated activities to direct and control an organization with
regard to quality
Service provided in a standardized way
Results analyzed
Improvements constantly made
To secure a service of excellence
with consistent and stable results

18. SOPs
• Mission
• Quality policies,
objectives & indicators
• Document control system
• Reviews, auditing,
retention
• How to register and
control non-conformities,
corrective & preventive
actions
• Auditing system
• Improvement system
• Laboratories
description
• Personnel, job
descriptions,
responsibilities
• Training program
• Safety instructions
• General rules
Quality Management System
Expresses the organizational structure, policies, procedures,
processes and resources used to implement quality actions
Technical
manual
Clinical and
laboratory
SOP manual
Quality
manual

19. Worldwide Tendency to Make QMS Mandatory
Australia Code of practice for assisted reproductive
technology units, Reproductive Technology
Accreditation Committee (RTAC)
Brazil RDC 23/2011, National Agency of Sanitary
Surveillance (ANVISA)
European Union EU directive 2004/23/EG, 2006/17/EG,
2006/86/EG
South Africa National Health Act 61/2003; Human Tissue
Act
USA CLIA for Andrology laboratories; FDA for
cryobiology

20. Brazilian Directive
Cells and Germinative Tissues
• Art.60 – quality
management
system
RDC 23, 27/May/2011
(revised RDC 72, 30/3/16)
QC Art. 41 Preventive maintenance &
equipment calibration
QC Art. 51 Daily record critical equipment
operation (incubators, freezers,
refrigerators)
QA Art. 9 e 58 Control of records
QA Art. 60 Periodic training
QA/QI Art. 60 Internal audits
QA Art. 12 e
60
Control of non-conformities and
corrective actions
QI Art. 50 Preventive actions
QC: quality control; QA: assurance; QI: quality improvement

21. Quality Management System
1996 – Androfert founded
2006 – QMS implementation started
2010 – ISO 9001:2008 certification
2013 – Recertification
2015 – Recertification
2017 – Recertification
2018 – ISO 9001:2015 certification
British Standards Institution

22. Other international standards
• ISO 15189: Medical laboratories
particular requirements for quality and competence
• ISO 17025: General requirements for the competence of
testing and calibration laboratories
• Clinical and Laboratory Standards Institute (CLSI)
• QMS model for health care (HSI-A2)
• QMS model for laboratory services (GP26-A3)

23. ISO* 9001 model easily adapted to ART Units
Customer service
Document control system
Personnel management
Audits
Procedures for detection, registration, correction and
prevention of errors and non-conformities
Risk management
System to evaluate and control materials and equipment
*ISO: International Standardization Organization

24. Bento & Esteves. MEDICALEXPRESS 2016;3(3):M160302
http://www.dx.doi.org/10.5935/MedicalExpress.2016.03.02

25. QMS - ISO 9001
Determine needs and expectations of customers and others
(legislation, professional societies, etc.)
Mission
Establish a quality policy, quality objectives, and quality
indicators for the organization
QM focus
Determine processes/procedures to achieve the quality
objectives; Identify and provide necessary resources
Process
Determine means to prevent nonconformities (NC) (variation)
and eliminate their causes; Register quality actions; Verify
compliance (auditing)
Registering &
Auditing
Establish and apply methods to measure
effectiveness/efficiency of each process
Monitoring
Establish and implement a process that involves all personnel
for continual improvement
Continual
improvement
Say what you do and what your
requirements are
Show how you do
Show how you ensure you follow
what you say you do
Show what you do to improve
what you do

26. • Very well-organized workflow
• Reduction of incidents/deviations
• Focus on customers needs/satisfaction
• Enhanced quality of services provided
• Increased operational efficiency and
profitability
• Continuous improvement
QMS Strategic decision to build up long term value for
patients/customers

27. A powerful “wedge”
Holds the gains achieved through the quality journey and prevent
good practices from slipping

28. 1. Treatment personalization
2. Reproductive andrology
3. Modern IVF laboratory
• Paper-free lab
• Clean room technology
• Time-lapse embryo culture
• Vitrification
4. Quality management system
Quality-centered strategies at Androfert

29. Treatment personalization from OS to LPS
The bottom line
• Evaluate properly
• Give a fair estimate of outcome
• Develop an effective, safe, patient-centered,
and time-limited treatment plan
Dancet et al. Hum Reprod 2011; Mainz. Int J Qual Health Care 2003; Esteves MedicalExpress 2015
Esteves, 29

30. Poseidon
G1 Poseidon
G2 Poseidon
G3 Poseidon
G4
Non
Poseidon
patients
Low Prognosis Patients
Gonadotropin starting dose and regimen can be determined in all patient
categories by Poseidon-based stratification
INDIVIDUALIZATION
Esteves, 30
Andersen et al. (eds.) Research Topic Frontiers in Endocrinology.
https://www.frontiersin.org/research-topics/6849/poseidons-stratification-of-low-prognosis-patients-in-art-the-why-the-what-and-the-how

31. What the critics say…
Esteves, 31

32. Esteves, 32
individualized
fixed

33. Esteves, 33Esteves, 17

34. What the supporters of individualization say…
Esteves, 34
Reduces variability in the number of retrieved oocytes
Increases the number of retrieved oocytes in poor responders
Optimize such numbers in hyper responders
Reduces the proportion of women with poor or hyper response
Reduces the risk of cycle cancellation
Increases the % of patients reaching an ET
Reduces the risk of OHSS
It achieves all that while maintaining
cumulative live birth rates

35. • Reduces wastage
• Increases efficiency
• Allows real time reporting and
analysis
• Information easily retrievable
from remote sites
• Fully integrated with QMS
concept
The modern IVF Clinic
ART software management system
http://www.clinisys.com.br/

36. http://www.clinisys.com.br/

37. • Online platform hosted in the Cloud
• High performance database
• Mobile connectiveness from any device
with internet
• End-to-end encryption for information
protection
• Dedicated, audited, and protected traffic
• Protection against DDoS attacks
• Daily backups stored separately in 3
different locations in addition to the primary
cloud server
• System logs of all user actions
• Compliance with NGS1 safety standards

38. http://www.clinisys.com.br/

39. http://www.clinisys.com.br/

40. http://www.clinisys.com.br/

41. http://www.clinisys.com.br/

42. http://www.clinisys.com.br/

43. http://www.clinisys.com.br/

44. http://www.clinisys.com.br/

45. Real time monitoring – QC, QA, Reports

46. http://www.clinisys.com.br/

47. http://www.clinisys.com.br/

48. http://www.clinisys.com.br/

49. http://www.clinisys.com.br/

50. http://www.clinisys.com.br/

51. …ease communication with patients and staff

53. ART Centers of excellence integrate objective quality
indications for all dimensions of health care
• Success is measured by how well quality indicators of infertility care are
achieved
• Focus on CLBR and dropout remains essential to enhance the beneficial
effect of treatment
Critical attributes of Excellence in healthcare include:
• Patient engagement in care (personalized treatments)
• Care coordination (QMS, clinical information system)
• Publicly available information on practices
CONCLUSIONS (1)

54. Novel state-of-the art tools & devices helping to improve
patient adherence and clinical outcomes
• iCOS, laboratory technology, and online connectedness
CONCLUSIONS (2)
Quality Management and clinical information systems
help to achieve excellence
• Allow systematic approach to implement, monitor, and improve quality
actions focused on the organizational structure, policies, procedures,
processes, resources, and risk management
• Customer-focused tools

55. Dr. Sandro C. Esteves
Dr. Marcelo Scandiucci
Dr. José Eduardo Orosz
Dr. Renan Andreollo
Fabiola Bento
Cristiane Medina
Sidney Verza Jr.
Camila Pompeu
Luciana Oliveira
Vanessa Moreno
Ellen Silva
Roseane Oliveira
Thais Paiva
Sarah Queiroz
Katia Pereira
Sandra Souza
Leila Simplicio
Shirley Machado
Jonathan Santos
Dr. Silval Zabaglia
Dra. Fabiana Nakano
Dr. Julio Voget
Dr. Ricardo Miyaoka
Dr. Ricardo Barini
Dr. Wail Margeotto
Dra. Cristiane Moreira
Dr. Arnaldo Gomes
Marisa Russo
Ivanete Santos
Sandra Santana
Ana Paula Barbosa
Ana Pastorelli
OBRIGADO GRACIAS THANK YOU