Implementing new techniques, technologies and programs into an IVF clinic

Ronny Janssens - Quality Manager

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Summary

1. Why new technology?

2. How to choose?

3. How to implement into your practice?

4. Examples @ UZB

5. Conclusions

Why new technology?

Technological innovations are products of a society’s economy, a force for economic growth and are affected by a society's cultural traditions.

How do science concepts, engineering skills, and applications of technology improve the results?

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Sources of technological innovation (external)

Patients Industry Competitors Consultants Universities Publications, internet Exhibitions, fairs, seminars and conferences Certification/accreditation bodies Legislation

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Sources of technological innovation (internal)

Own R & D ICSI

Unexpected event Witness

Change of work process Day of transfer - Single step media

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Obstacles to new technology

No access Lack of time (to learn, to plan, ...) No budget or high costs Technical/IT problems Intimidating – non expert status Too many strategies to try now – one more

thing

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Summary

1. Why new technology?

2. How to choose?

3. How to implement into your practice?

4. Examples @ UZB

5. Conclusions

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Harper et al. Hum. Reprod. 2012

“Every procedure involving application to the human body should be defined as experimental until adequate scientific evidence is provided regarding its safety and efficacy”

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Definition of experimental procedures

The practice committe of the American Society for Reproductive Medicine. Fertil Steril, vol 99, 2013.

Procedures ...will be considered experimental or investigational until the published medical evicence regarding their risks, benefits, and overall safety and efficacy is sufficient to regard them as established medical practice. Relevant medical evidence can derive only from appropriately designed, peer-reviewed, published studies performed by several independent investigators, including a description of materials and methods sufficient to assess their scientific validity and to allow independent verification.

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Ask yourself what is...

Benefit? To patient To service

Safety? Has it been tested? Is it safe?

Where is the evidence? Efficiency?

Does it work in your service? Cost effective?

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What is the right equipment?

Define required performance characteristics Review functionality

Does it conform? Is it easy to use? Extra features?

Analyze risks Appropriate support? Employees’ motivation?

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What is the right equipment/procedure?

Use available information Literature External experts (universities, research

laboratories...) Discussion boards Conferences, workshops

Analyze with data

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Where is the evidence?

Evidence based medicine:“Sackett: Integrating individual expertise with the best available clinical evidence from systematic research.” Archie Cochrane

Founded in 1993 in the United Kingdom

Cochrane Database of Systematic Reviews

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Assisted reproductive technology: an overview of Cochrane Reviews Farquhart et al 2013

Effective interventions Low oxygen concentration for embryo culture SET US guided ET

Promising (more evidence needed) AH Brief co-incubation of sperm for IVF

Possibly ineffective IMSI

Ineffective PGS

No conclusion possible ICSI vs IVF for non-male infertility

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Be objective!

Recombinant vs. Urinary gonadotrophins No difference, known since mid 1990s

“It is obvious why 7339 patients were included in redundant trials: industry funding”

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Take home message

Does new technology increase productivity?

Focus on results, not technology

Be objective Is there enough evidence? Be aware of external pressure

Do you really need it?

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Summary

1. Why new technology?

2. How to choose?

3. How to implement into your practice? Validation Staff training

4. Examples @ UZB

5. Conclusions

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PDCA cycle - Implementation in practice

Plan Do: Installation

Installation qualification

Test phase Real time monitoring?

Check: Validation Operational

verification NC?

Act

Plan Do: Integration in

work flow SOP QC/QA Staff training

Check Equipment failures complaints

Act

5.5.1.1 Validation of examination procedures The laboratory shall only use examination

procedures that have been validated as suitable for their intended use.

The validation shall be as extensive as is necessary and confirm, through the provision of objective evidence (in the form of performance characteristics), that the specific requirements (in the form of performance specifications ) for the intented use of the examination have been fulfilled

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ISO 15189

ISO 15189

5.5.1.1 Note 2 The means to be used for the determination of the performance characteristics of a procedure may be one of or a combination of the following:a) Testing of calibration or reference measurement standards, or using

reference measurement procedures;

b) Internal quality control data;

c) Use of patient samples with properties defined for the examinand, stability, and homogeneity;

d) Comparison of results achieved with other methods;

e) Inter laboratory comparisons;

f) Systematic assessment of the factors influencing the results;

g) Presence of carryover of material from a preceding high concentration sample, when applicable, and

h) Presence of interferences or non-specificity that may be caused by, for example, metabolic or endogenous substances in the sample

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Validation of ART process

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Procedures – documents

SOPs• As primary training resources• To control process details• Standard layout

Forms• Data collection• Process control• Patienten ID verification• Operator ID & witnessing• Materials logging

• Mentality change: from oral to written culture

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Staff

Who – What – When?

Responsibility Functions Job descriptions Task assignments

Training

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Training plan

1. Observation

2. Work under supervision

3. Fully qualifiedObjective measurable criteria ! (>70%

fertilisation - ICSI)

4. Documented

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Summary

1. Why new technology?

2. How to choose?

3. How to implement into your practice?

4. Examples @ UZB PGD/PGS IMSI Time lapse Witness

5. Conclusions

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Not implemented Coculture PGS Spermatid injection PICSI Integrated workstations

Vitrosafe Ac-tive

Embryoglue Time lapse incubators

Biostation Embryoscope

IMSI LAISS

Implemented ICSI Extended culture PGD Oocyte imaging Laser Dry incubators RFID (Witnesss) Desktopincubators (G-

185) Blastocyst vitrification Embryo vitrification Oocyte vitrification

New technologies @ UZ Brussel

PGD/PGS @ UZB

2/93

Laser zona drilling

3/96 11/98 6/99

First PGD

Aspiration of blastomeres

Decompaction media

5/98 6/98

Acid Tyrode

Sequential media

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Comparison laser with Acid Tyrode

Comparison of the results of human embryo biopsy and outcome of PGD after zona drilling using acid Tyrode medium or a laser. Joris, H., De Vos, A., Janssens, R., Devroey, P., Liebaers, I., and Van Steirteghem, A. Hum. Reprod. 2003. The use of laser in cases of PGD is an easier procedure and

results more intact blastomers in comparison with using acid Tyrode medium.Since similar pregnancy rates are obtained ,it is adventageous to use laser for zona drilling

Laser confers less embryo exposure than acid tyrode for embryo biopsy in preimplantation genetic diagnosis cycles: a randomized study. Geber et al. Reprod Biol Endocrinol. 2011

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PGS by FISH at cleavage stage is not effective in improving live birth delivery rate per cycle

“This RCT provides no arguments in favour of PGD-AS for improving clinical outcome per initiated cycle in patients with AMA when there are no restrictions in the number of embryos to be transferred” Confirmed by Mastenbroeck et al., 2007 Example of introduction into clinical practice without

evidence

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IMSI

Bartoov et al. 2001                               N Engl J Med, vol. 345, N°14 Bartoov et coll, 2002                               J. Andrology 23:1-8 Bartoov et coll, 2003                               Fertil.steril.80:1413-1419

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„Standard Image“ ICSI

vacuoles

HOW DOES A GOOD SPERM LOOKS LIKE?

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Intracytoplasmic Morphologically-selected Sperm Injection (IMSI)

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Regular (ICSI) versus ultra-high magnification (IMSI) sperm selection for assisted reproduction

Teixeira DM, Barbosa MAP, Ferriani RA, Navarro PA, Raine-Fenning N, Nastri CO, Martins WP, July 25, 2013

“We concluded that the current evidence does not support using IMSI: there is no evidence of benefit for live birth and miscarriage, we are very uncertain of the beneficial effect of IMSI in clinical pregnancy, and there is no evidence of the effect of this intervention on congenital abnormalities“

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IMSI

“It is noteworthy that more prospective randomized trials are required to confirm the superiority of IMSI over conventional ICSI and to identify the causes of infertility that could benefit from the IMSI procedure.”

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IMSI: conclusion

Complex technology Learning curve Risks

Cooling Exposure to ambiant atmosphere

Expensive Bias? No evidence yet

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IMSI @ UZB

Benifit To patient? To service?

Safety? Has it been tested? Is it safe?

Where is the evidence? Efficiency

Does it work in your service? Cost effective?

Yes

No

No

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Time lapse imaging

Evidence? Cochran: 0 RCT: 1

Kirkegaard et al. Hum Reprod 2013 Pubmed: 14 references form 1 group

External pressure? “Further randomized prospective studies are being developed

at the moment to evaluate and confirm the power of embryo selection by time-lapse systems

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Time Lapse Systems @ UZB

Embryoscope (2010) Validation RCT (?) Conclusion: research only

Primo Vision (-) performance characteristics ?

MIRI TL incubator (2013) Prototype Validation in 2014

Incubator Culture coin Imaging

Witness @t UZ Brussel

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Two sources of biological material ( + = → ) Donor/acceptor cycles (X + Y = Z) Complex process over several days

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IVF = Living in the danger zone!

DO NOT MAKE A MISTAKE!

Identification errors

Experience is the name everyone gives to their mistakes (Oscar Wilde,1854 - 1900)

How often do you make mistakes?

When will it happen in your lab?

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ISO15189

Use only validated methods Risk analysisR = P x E X C = 1 x 6 x 7 = 42

P = unlikely but possible E = daily C = severe

R ≤ 20 acceptable very low risk, acceptable

20 < R ≤ 70 needs attention

70 < R ≤ 200 action needed

200 < R ≤ 400 immediate improvement required

R > 400 STOP

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Identification systems in IVF

Barcode identification

HFEA risk assessment Light and effect on gametes and embryos Errors can occur in the printed barcode label Barcode scanning can interrupt workflow

processes Possibility of circumvention

Novo et al., HR Vol 29, 2014 “it only allows the identification and traceability of

oocytes destined for ICSI and embryos. Thus, the traceability of all reproductive samples (oocytes destined for IVF and sperm) is not yet ensured”

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2011: Integration into Clinical Practice

Hardware: work area readers, PCs, monitors Ward: 2 admin readers Egg collection and transfer: 2 ID card readers Embryolab: 7 stereomicroscopes Semen lab: 3 semen prep antennas

Software Define witness flow chart Interface with hospital system

SOP Training (2 days for administrators + in-house sessions) Validation (20 cases with simultaneous manual

witnessing)

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Witness at UZ Brussels anno 2014

Administration 2 admin readers

Diagnostic semen lab 2 admin readers

Insemination rooms 3 admin readers

Therapeutic semen lab 7 sperm prep workstations

Eggcollection 2 ID card readers

Infectious lab 1 sperm prep workstation 3 stereomicroscopes

Embryology lab 1 and 2 2 x 7 stereomicroscopes

Embro replacement 2 ID card readers

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IVF Witness: employees’ motivation

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Before: Anxiety Less flexible Novel technology Changes in working

habits

After: Optimism Safe Easy to adapt Increased confidence

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Summary

1. Why new technology?

2. How to choose?

3. How to implement into your practice?

4. Examples @ UZB

5. Conclusions

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Conclusions

Do you really need the new technology? Choose the right equipment Focus on results, not technology

Be objective, look for evidence Does it work in your lab? Validate

Documentation Staff training

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For something completely different...

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Thank you!