Quality in ART by Giles Palmer

Londonwomensclinic.com
• Quality in ART
• Giles Palmer
• Senior Clinical Embryologist
• Business & Quality Manager

Key learning
objectives
• Quality Management & the role of the Quality
Manager
• HFEA Code of Practice & requirements placed on
clinics
• Inspection process

Quality Standards

In the beginning…
• Lab manager based on
experience in cell culture
methodologies
• Apprentice system of learning
• No specialised equipment
• In house preparation of
culture media,
• Make shift equipment
• Little monitoring of
conditions, no good practise
guidelines & standardised
protocols

Rise of
Quality….
• “Continuous improvement through observation
& corrective action after testing & monitoring
laboratory equipment (Quality control or QC) has
led to improved culture conditions & increase IVF
success, moving clinical embryology from being
observational & subjective to an objective clinical
science “ Matson et al, 1998.
• Peer led guidelines
• Regulations & Legal framework
• International standards ( e.g. ISO)
• Consensus meetings & KPIs

Palermo et al. 1992, Devroey et al 1995
Present day
Highly qualified Embryologists
Structured learning
Strict regulation
Quality Management has become a cornerstone of modern embryology
Targets, success, excellence
QMS, QA, QC, Risk assessment, Audits, Document control etc.

What is Quality?
• Quality is a process of meeting the needs
& expectations of patients & health
service staff ( WHO 2000)
• Quality is the degree to which care
services influence the probability of
optimum patients outcomes ( American
Medical Association 1991).

What is
Quality? The
definitions
• QMS: Quality management system ensures the
quality of services. To achieve you need: Strategy,
policy, planning, objective setting, control &
assurance records, audit, evaluation &
improvement
• QA: Quality Assurance, the standards & processes in
laboratory practice.
• QC: Quality Control, continuous improvement
through observation & corrective action after
testing & monitoring laboratory equipment
• SOP: Standard Operating Procedure
• NCD: Non Conformity/Deviation from protocol.
• AI: Adverse incident
• CAPA: Corrective & Preventive Action, an important
part of a Quality Management System. Central to all
control points.
• Risk Assessment: a proactive measure of identifying
possible problems causing NCD or AI.

Tools of
Quality?
• Monthly clinical governance meetings
• Process mapping & SOPs
• NCD & AI: logged & reportable
• QA: Internal, External
• Quarterly QMR
• Complaint procedure, Patient surveys
• Review of QMS: Improvement
• Inspections

Role of
Quality
Manager?
• The QM ensures that the QMS is appropriately
established & functional.
• Reports to the PR.
• Works closely with the HFEA.
• Actively seeks to improve the system & ensures
the effectiveness of the QMS
• Communicates the strategy with staff & users
• Is not responsible for carrying out all quality
tasks.

“Buy in” to quality
This is a story about four
people named
Everybody, Somebody,
Anybody & Nobody.
There was an important
job to be done &
Everybody was sure that
Somebody would do it.
Anybody could have
done it, but Nobody did
it.
Somebody got angry
about that, because it
was Everybody’s job.
Everybody thought
Anybody could do it, but
Nobody realized that
Everybody wouldn’t do
it.
It ended up that
Everybody blamed
Somebody when Nobody
did what Anybody could
have..

Processes, Procedures &
SOPs

Monitoring
performance
• Key Performance Indicators or KPIs are an universal tool to help
you manage your business, clinic, laboratory.
• It is a piece of information about your work that you repeatedly
measure to check if it is changing or remaining constant
• Blastocyst Utilisation Rate = The percentage of 2PN embryos
that are either transferred or cryo-stored on day 5 or day 6
• ESHRE Special Interest Group of Embryology and Alpha Scientists in Reproductive Medicine,
2017. The Vienna consensus: report of an expert meeting on the development of ART
laboratory performance indicators. Reprod. Biomed. Online. 35, 494-510.
• Alpha Scientists In Reproductive Medicine. The Alpha consensus meeting on cryopreservation
key performance indicators and benchmarks: proceedings of an expert meeting. Reprod
Biomed Online. 2012 Aug;25(2):146-67

Monitoring performance
Reprod. Biomed. Online. 35, 494-510

Monitoring performance
Numbers egg collections FET survival
Embryo quality 3PN, 1PN & ICSI lyse rate

Document
control
• Document Control is document management
whose purpose is to enforce controlled
processes & practices for the creation, review,
modification, issuance, distribution &
accessibility of documents.
• Owner, Author, inception date, review date,
version number, document number, Only the
most up-to date version in circulation ( correct
only at time of printing), subject to review by
anybody & implemented by “ change request”
• Periodic review date & version distribution.
Approval needed.

Document control

Traceability

Audits
• “Centres must audit the activities &
processes authorised by this licence & other
activities carried out in the course of providing
treatment services against compliance with the
regulatory requirements & their own approved
protocols & quality”
• HFEA indicators: Mandatory audits
• These audits must be performed at least
every two years, by trained & competent staff &
in an independent way.
• Findings & corrective actions must be
documented & implemented.

Audits
Examples of audits:
• 85% of all vitrified eggs must survive after
warming
( Local, Scientific, KPI 85%)
• 90% of all patients eligible for eSET at the
time of embryo transfer should receive a single
embryo transfer
( Mandatory, Scientific, KPI 90%)
• 100% of all donors & patients should be
offered counselling prior to starting treatment (
Local, Counselling, KPI 100%)
• 100% of Non Conformities/Deviations from
established protocols should be reported to the
QA team immediately on discovery (Local, QA,
KPI 100%).

QMR
• Quality Management Review:
• Periodic review of how all aspects of Quality management
are performing.
• Review of previous meeting
• Staff updates & Information relevant to all staff
• NCDs & AI discussion
• Performance review using audits, KPIs & patient
satisfaction surveys

Risk Assessment
• Hazards: situations that have the potential to cause
harm;
• Risks: which are defined as the probability that a
specific adverse event will occur in a specific time
period or as a result of a specific situation
• Clinical Risk: is the chance of an adverse outcome
resulting from clinical investigation, treatment or
patient care.
• Identify all the individuals that are at risk of this hazard.
• Calculate the Risk Score Rating by multiplying score A &
score B.
• If the rating is over 4, immediate action is required to
improve existing control measures.
• If the rating is 4 or under, the risks are under adequate
control but should be carefully monitored.

Risk Assessment
• Hazards: situations that have the potential to cause
harm
• Risks: which are defined as the probability that a
specific adverse event will occur in a specific time
period or as a result of a specific situation
• Clinical Risk: is the chance of an adverse outcome
resulting from clinical investigation, treatment or
patient care.
• Identify all the individuals that are at risk of this hazard.
• Calculate the Risk Score Rating by multiplying score A &
score B.
• If the rating is over 4, immediate action is required to
improve existing control measures.
• If the rating is 4 or under, the risks are under adequate
control but should be carefully monitored.

Benefits of
External
Quality
Assessment
(EQA)
• Provides laboratory management with an insight
into their performance.
• Improves both national & local standards.
• Reveals unsuspected areas of difficulty.
• Provides an educational stimulus for improvement.
• Acts as a check on the efficacy of internal quality
control procedures.
• Demonstrates to colleagues & customers a
commitment to quality.
• Provides method performance evaluation (scheme
dependant).
• Provides independent evidence of performance for
accreditation bodies.
• EQA is an educational tool that allows participants
to monitor, evaluate & improve their own
performance.

External Quality
Assessment (EQA)
• Distributions
• Participants will receive four distributions a
year.
• Each distribution consists of:
• 4 semen samples for Concentration &
Morphology assessment.
• 4 online Motility videos (hosted by
http://gamete-expert.com).
• 24 online Morphology images (hosted by
http://gamete-expert.com)

External Quality
Assessment (EQA)
• Distributions Andrology and Embryology
• Promotes best practice.
• Comprehensive external quality assessment
• Ensures results are reliable and comparable

External Quality Assessment (EQA)

Quality Control in the Laboratory
Temperature control - pH control -Batch control

• Safety & Assurance • Benchmarking & Appraisal

• Safety & Assurance • Constant monitoring of products
• Constant monitoring of laboratory
conditions
• Benchmarking-evaluation of performance
• Trouble-shooting- dealing with problems
• Validation of equipment
• PPM: planned preventive maintenance
• Manual of all equipment, log faults,
service dates, technicians contact number
etc.
• Calibration of external measuring
equipment

The paperless lab
Clipboards & written lists
Must be acted upon!!
Electronic data recording
virtual lab.
Daily record keeping, audits
Fluctuation reports
e.g. Reflections App

Clipboards & written lists
Must be acted upon!!
Electronic data recording
virtual lab.
Daily record keeping, audits
Reflections App
The paperless lab

• Most parameter surround incubators and
warming surfaces
• Little uniformity to what consists in a lab
log.
• Importance of external independent
sensor
• A quality control diligence score: mean
average data points (MAD score) was
calculated for each laboratory
A comparison among 36 assisted reproduction laboratories monitoring the
environmental conditions & instrument parameters using the same quality
control application. Palmer et al 2019 RBMO In Press

A comparison among 36 assisted reproduction laboratories
monitoring the environmental conditions & instrument parameters
using the same quality control application. Palmer et al 2019 RBMO
In Press

http://kustodian.co.uk/

Internal Quality Control
program
Internal Quality Assurance
Program
External Proficiency External Laboratory
inspection, Validation
& Accreditation
Daily weekly & monthly &
periodic equipment
monitoring, maintenance,
adjustments & verification.
Semi-Annual instrument &
facility calibration, testing
maintenance, validation,
mouse embryo testing,
Sperm survival testing
Daily, monthly & annual
statistical evaluation of
embryology, clinical,,
Administration.
Monthly statistical evaluation
of outcome data ( pre-
analytical, analytical & post
analytical). Tolerance limits.
Monthly internal proficiency
testing-interprofessional
comparisons & testing.
Daily, monthly & annual skills
assessment & continuing
education.
Media & material quality
controls testing, sperm survival,
pH, Co2,O2 per batch
NEQAS, periodic
distributions –
operator & clinic based
assessment.
HIW
HFEA
ISO
National School of
Healthcare science (STP)
Royal College of Pathologist
DipRCPath
(Diploma of RCPath)

HFEA
• Regulation making sure fertility clinics &
research centres comply with the law & the
rules & standards we set to ensure high
quality care & research.
• All fertility clinics & human embryo research
centres in the UK must comply with: the
Human Fertilisation & Embryology (HFE) Act
1990 (as amended) the HFE Act 2008, & a
number of related pieces of legislation.
• HFEA provide guidance to clinics & research
centres on how to meet their legal
requirements in our Code of Practice.

HFEA
• Clinics must have a licence from HFEA to
operate.
• Grant licences for up to four years.
• Inspections are carried out every two years.
• Set standards to ensure high quality care.
• Before granting a new licence, or renewing an
existing one, HFEA conduct an inspection to
make sure their services are up to standard in
line with our Code of Practice.
• The findings are presented to our Licence
Committee, which makes a decision on
whether to grant a licence (& if so for how
long), refuse the licence, or, if they feel the
quality of service needs to be better, put
conditions on the licence which ensure it only
remains in place if improvements are made.

Quality Management System (HFEA):
• A Quality Management System ensures that patients receive an agreed
standard of care throughout their treatment & that centres continually
improve the way the service is delivered, ensuring consistency throughout
• Relevant provisions of Quality review (quality management system,
investigations, corrective action, and reviews)
• The centre must put in place a quality management system & implement
this system to continually improve the quality & effectiveness of the
service provided in accordance with the conditions of this licence & the
guidance on good practice as set out in the HFEA’s Code of Practice.

HFEA & Quality
• The following documentation must form part
of the quality management system:
• a. a quality manual
• b. standard operating procedures (SOPs) for
all activities authorised by this licence &
other activities carried out in the course of
providing treatment services that do not
require a licence
• c. guidelines
• d. training & reference manuals
• e. reporting forms.
• Required standards of quality & safety, in the
form of quality indicators for all activities
authorised by this licence & other activities
carried out in the course of providing
treatment services that do not require a
licence, must be established.

Risk Grading
Matrix
• Incident Reporting
• Legal requirement
• Duty of PR to notify the HFEA of any incident &
near miss.
• Duty of PR to provide the HFEA with a report
analysing the cause & the outcome.
• Risk level estimator

Determine the likelihood
1 Almost impossible Difficult to believe it could happen again
2 Unlikely Not expected to happen but possible
3 Possible May occur occasionally
4 Likely Probable but not persistent
5 Almost certain Likely to occur on many occasions

Determine the severity
Level Severity Actual or potential impact on individual Actual or potential impact on ART
service provision
1 Insignificant No injury or adverse outcome No affect
2 Minor Short term injury, avoidable risk, loss of 1 of
many samples for a patient
Minor damage or minimal risk to
organisation
3 Moderate Partial loss of gametes / embryo for many or all
patients or total loss for gametes / embryos for
one patient / couple,
Reportable to another regulator,
compensation costs (complimentary
cycle)
4 Major Partial loss of gametes / embryos for many or
all patients or total loss for a few patients, birth
of child with a serious genetic disease,
significant breach of patient confidentiality
Significant number of procedures
cancelled, reputation damage,
impact on morale of staff
5 Severe Death of patient, total loss of all gametes /
embryos for many or all patients, birth of child
with a life- threatening genetic disease
Complete shutdown / closure of the
centre. All procedures cancelled,
multi-agency investigation,
prosecution

Risk level estimator

Grading
System
• Grade A: involves severe harm to one person
(such as a death, being implanted with the
wrong embryo or birth of an affected child
following genetic testing) or major harm to many
(such as the failure of a frozen storage unit
containing the embryos of many patients).
• Grade B: involves serious harm to one person
(such as the loss or damage of embryos for one
patient) or moderate harm to many (such as
sensitive personal data about more than one
patient being sent to the wrong recipient).
• Grade C: involves minor harm, such as one of
many eggs being rendered unusable in the
laboratory.

Grades of
Incidents
• HFEA classify incidents in clinics into three
grades of severity: A, B & C.
• Hold information about ‘near misses’ in which
only luck prevented an incident from occurring.
• Incidents deemed serious must be reported to
HFEA within 12 hours of detection & all other
incidents & near misses must be reported within
24 hours.
• HFEA require this reporting to encourage a
culture of openness, transparency & learning.
• HFEA monitor the number & nature of
incidents/near misses & have a rigorous process
for reporting, handling & investigating them.
• Ensures that clinics understand the ‘root cause’
of the incident & think about how clinics can
change their practice to prevent a recurrence.

Examples: Likelihood x Severity = Grade
A letter inviting a couple for an initial consultation is sent to an incorrect address.

A letter inviting a couple for an initial consultation is sent to an incorrect address.
2X3=B

5 of 10 eggs not inseminated

5 of 10 eggs not inseminated
1X4=C

A child is born with a serious genetic condition (donor sperm used & screened
appropriately)

A child is born with a serious genetic condition (donor sperm used & screened
appropriately)
1X5=A

Loss of one oocyte during ICSI procedure (12 oocytes remain for the patient)

Loss of one oocyte during ICSI procedure (12 oocytes remain for the patient)
2X4=B

Embryo development was compromised when the gas mixture supplying a
bench-top incubator appears to have been faulty/interrupted (9 embryos for 1 pt
& 12 embryos for a second pt)

Embryo development was compromised when the gas mixture supplying a
bench-top incubator appears to have been faulty/interrupted (9 embryos for 1 pt
& 12 embryos for a second pt)
1X5=A

Adverse
incidence
• 517 adverse incidents reported to the HFEA in
2015:
• No Grade A: events such as the death of a
patient, being implanted with the wrong
embryo, or something that affects a large
number of patients such as a storage unit
malfunction
• 200 classed Grade B, which include loss of
embryos, breaches of confidentiality or
equipment failure
• Administration errors accounted for 141 cases.
HFEA notes in its report that there has been a
significant change in the number of times
patient confidentiality has been breached,
increasing from 59 out of 102 administrative
errors in 2014 to 124 in 2015.

Information
Governance
& GDPR
• General Data Protection Regulation ( GDPR): Law
came into force 25th May 2018
• Handling of sensitive information:
…Processed in a manner that ensures
appropriate security of the personal data,
including protection against unauthorised or
unlawful processing & against accidental loss,
destruction or damage, using appropriate
technical or organisational measures
• Penalties for non compliance
• There are two tiers of administrative fines that
can be levied:
• 1) Up to €10 million, or 2% annual global
turnover – whichever is higher.
• 2) Up to €20 million, or 4% annual global
turnover – whichever is higher.

Take home messages
• Cornerstone of Clinical Embryology
• Continuing cycle of Plan -Do -Check -Act
• Not an expensive additional burden
• Ensures reproducibility & consistency throughout Clinic
• Picks up problems before they affect your program
• Benefits the whole team, involves whole team

References:
• Books:
• Elder, K., Van den Bergh, M., Woodward, B., 2015. Troubleshooting
and Problem-Solving in the IVF Laboratory. Cambridge University
Press.
• Esteves, S., Sandro, C., Agarwal, A. (Eds.) Quality Management in
ART Clinics A Practical Guide. Springer Publications. New York,
pp.79-127.
• Hreinnson, J., 2013. Quality Management, in: Vargese, A.,C.,
Sjoblom, P., Jayaprakasan, K. (Eds), A Practical Guide to Setting Up
an IVF Lab, Embryo Culture Systems and Running the Unit. Jaypee
Publishers, New Delhi, pp 87-93.
• Mortimer, D., Mortimer, S.T., 2015. Quality and Risk Management
in the IVF Laboratory latest. Cambridge University Press
• Pool, T.B., Schoolfield, J., D Han, D., 2012. Human Embryo Culture
Media Comparisons, in: Smith G., D., Swain, J., E., Pool, T., B. (Eds),
Embryo Culture: Methods and Protocols, Humana Press, New York.
367-386. DOI 10.1007/978-1-61779-971-6_21
• Wiemer, K.L., 2017. Setup Procedures for optimizing performance
in the IVF laboratory, in: Montag, M.H.M., Morbeck, D.E., (Eds.),
Principles of IVF Laboratory Practice: Optimizing Performance and
Outcomes, Cambridge University Press pp. 88-96.
• Guidelines:
• ASRM Practice committee, 2008. Revised guidelines for human
embryology and andrology laboratories. Fertil.Steril. 90, S45-59.
• ASRM Practice committee, 2014. Revised minimum standards for
practices offering assisted reproductive technologies: a committee
opinion. Fertil. Steril. 102, 682-686.
• De los Santos , M.J., Apter, S., Coticchio, G., Debrock, S., Lundin, K.,
Plancha, C.E., Prados, F., Rienzi, L., Verheyen, G., Woodward, B.,
Vermeulen, N., 2015. Revised guidelines for good practice in IVF
laboratories. Hum. Reprod. 31, 685- 686.
http://humrep.oxfordjournals.org/
• ESHRE Special Interest Group of Embryology and Alpha Scientists in
Reproductive Medicine, 2017. The Vienna consensus: report of an
expert meeting on the development of ART laboratory
performance indicators. Reprod. Biomed. Online. 35, 494-510.
• Gianaroli, L., Plachot, M., van Kooij, R., Al-Hasani, S., Dawson, K.,
DeVos, A., Magli, M.C., Mandelbaum, J., Selva, J., van Inzen, W.,
2000. ESHRE guidelines for good practice in IVF laboratories.
Committee of the Special Interest Group on Embryology of the
European Society of Human Reproduction and Embryology. Hum.
Reprod. 10, 2241-2246.
• Magli,C., Van den Abbeel, E., Lundin, K., Royere,D., Van der Elst, J.,
Gianaroli, L., 2008. Revised guidelines for good practice in IVF
laboratories. Hum. Reprod. 23, 1253–1262.
• Mortimer, D., Cohen, J., Mortimer, S.T., Fawzy, M., McCulloh,
D.H., Morbeck, D.E., Pollet-Villard, X., Mansour, R.T., Brison, D.R.,
Doshi, A., Harper, J.C., Swain, J.C., Gilligan, A.V., 2018. Cairo
consensus on the IVF laboratory environment and air quality:
report of an expert meeting. Reprod. Biomed. Online. 36, 658-674.

References:
• Regulations:
• Anonymous, 2004. Directive 2004/23/EC of the European
Parliament and the Council on Setting Standards of quality
and safety for the donation, procurement, testing,
processing, preservation, storage and distribution of human
tissues and cells. Official Journal of the European Union, 102,
48-58.
•
• Human Fertilisation and Embryology Authority, 2017. Code
of Practice Edition 8.0 https://www.hfea.gov.uk/code-of-
practice/
• Human Fertilisation and Embryology Act 2008
https://www.legislation.gov.uk/ukpga/2008/22/contents
• Human Fertilisation & Embryology (HFE) Act 1990
http://www.legislation.gov.uk/ukpga/1990/37/contents
• Miscellaneous:
• Anifanis, G., 2013. Temperature variations inside commercial
IVF incubators. J. Assist. Reprod. Genet. 30, 1587–1588
Dawson, K.J., 1997. Quality control and quality assurance in
IVF laboratories in the UK. Hum. Reprod. 12, 2590–2591.
• Matson, P.L., 1998. Internal quality control and external
quality assurance in the IVF laboratory. Hum. Reprod. 13,
156-164.
• Morbeck, D.E, 2015. Air quality in the assisted reproduction
laboratory: a mini-review. J Assist Reprod Genet 2015 Jul;
32(7): 1019–1024.
• Pool, T.B., Schoolfield, J., D Han, D., 2012. Human Embryo
Culture Media Comparisons, in: Smith G., D., Swain, J., E.,
Pool, T., B. (Eds), Embryo Culture: Methods and Protocols,
Humana Press, New York. 367-386. DOI 10.1007/978-1-
61779-971-6_21
• https://www.hfea.gov.uk/media/2437/hfea_state_of_the_s
ector_report_tagged.pdf
• http://www.fertaid.com/IVFBenchMark/BEnchMark_AboutK
PI.asp
• A comparison among 36 assisted reproduction laboratories
monitoring the environmental conditions and instrument
parameters using the same quality control application.
Palmer et al 2019 RBMO In Press

Quality in ART by Giles Palmer

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