Standard operating procedures (SOPs) are needed in assisted reproductive technology (ART) clinics to standardize complex lab tasks and prevent errors. The document discusses how to develop SOPs that integrate both the clinical and lab perspectives. Key points include determining tests based on clinical needs, writing SOPs that provide information for clinical decisions, and effective communication between clinics and labs to determine the best strategies for patients. Developing SOPs requires considering what information doctors need from lab results and how to handle abnormal values. SOPs must also address specific clinical questions and allow clinicians to make informed decisions.

1. Sandro C. Esteves, MD., PhD.
Director, ANDROFERT
Andrology & Human Reproduction Clinic
Campinas, BRAZIL
The Perfect Integration
Between Lab SOP and
Clinical Strategy
Life Summit 2014 - ART TQM Forum, CHINA
ISO 9001:2008

2. Outline
o What a lab SOP is and why it is needed in TQM
o What problems can be solved by a lab SOP
o What the key points of lab SOPs are for clinicians
o How to develop/update lab SOPs according to a
clinical perspective
o How to combine clinical and lab perspectives for
making right decisions
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3. Standard Operating Procedure
sequence of steps that have been
standardized to execute a task, which is
used every time a given task is done, to
ensure it is done the same way each time
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Detailed instructions to achieve uniformity
on the performance of a specific procedure
Usually written and hierarchical, but also
expressed as flowcharts or drawings

5. Key points of a Lab SOP
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I. General information:
• Name of test or procedure
• Principles (goals and general information)
II. Pre-analytic information:
• Patient instruction for test/procedure preparation
• Specimen collection instructions
• Specimen labeling, transport, referral
• Specimen acceptability (including rejection criteria)
III. Analytic information:
• Equipment, materials and reagents
• Conditions required (e.g. laminar flow cabinet)
• Instrument calibration and verification
• Quality control (negative/positive control if required)
• Step-by-step procedure description
• Assay/procedure performance limitations
• Troubleshooting
IV. Post-analytic
information:
• Calculations (if
required)
• Normal ranges
(reference intervals or
expected results)
• Policy for handling
alert or panic values
• Report
• References

6. Top 10 reasons why ART
practice needs Lab SOPs
1. Repetitive highly-complex critically
important tasks
2. Variation must be controlled
3. More than one person could perform
the same task
4. Safety risks are present
5. Quality control needs to be ensured
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7. Top 10 reasons why ART practice
needs Lab SOPs (cont.)
6. Many lab professionals have previous
(differing) or no experience
7. Training is much easier with SOPs
8. Changes can’t be made until next revision
9. Exclude operating procedure fault when
analyzing root-causes of poor outcome
10. Improve communication among team
members, and with managers
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8. Variation often reflects misuse of
equipment, poor lab technique
and human errors
Root causes:
•
Complexity of activity
• Insufficient education
and/or training
• Lack of attention
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9. Essential information to be
included
What problems can be solved by
Lab SOPs?
• Mismatching oocytes with sperm
• Performing ET in the wrong patient
What can
go wrong?
• Controlling critical steps during whole process
(patient identification, specimen labeling, gamete
reception, insemination, ET)
• Avoiding risky situations (manipulation of more than
one sample at a time, sharing workplaces)
How can
we prevent
harm?
Double-witnessing in critical steps, double-checking
in intermediate steps, specimen processing by same
operator, one case per incubator’s shelf
How it can
be
resolved?
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10. Double-checking (DC) and
Double-witness (DW)
Example (ET SOP; Androfert):
1. Identification by the nurse of the patient arriving at the
ET room.
2. Patient and husband fill out a form with their full names,
dates of gamete retrieval and transfer.
3. Nurse and doctor performing the ET check ID info (DC).
4. Doctor explains embryos development, and give
recommendation for ET.
5. Couple fill in the No. of embryos they allow to be
replaced and cryopreserved (in conformity with
legislation).
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11. Example (ET SOP; Androfert, cont.):
6. Doctor (or nurse) informs embryologist about No.
embryos for ET (and cryopreservation if applicable);
the latter checks info in the filled form. (DC)
7. Embryologist removes correct embryos from
incubator, and loads ET catheter, witnessed by a 2nd
embryologist. (DW)
8. Embryologist gives loaded catheter to doctor, tagged
with patient name and No. embryos to be replaced.
9. Doctor checks catheter info (DC), witnessed by nurse.
(DW)
Note: Permanent record of procedure is kept (identification,
type, date and time, signatures)
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Double-checking (DC) and
Double-witness (DW)

12. Key points
SOP defines a sequence of steps that have
been standardized to execute a task, thus
ensuring it is done the same way each time
Lab SOP is an integral element of ART’s
processes
Lab SOP intelligent design can prevent harm
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13. How to develop and update
Lab SOPs according to
clinical perspective
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14. What are the key points of a Lab
SOP from a clinical perspective?
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IV. Post-analytic information:
• Normal ranges (reference intervals or expected results)
• Policy for handling alert or panic values
• Report
clinical interpretation
and decision

15. Basic questions:
1. Does SOP address specific clinical
question?
2. Does SOP post-analytical information
help determining what to do?
3. Does SOP provide solution for panic/
alert values?
Designing/Updating Lab SOPs
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16. Designing Lab SOPs
Clinical Needs
Determine tests/
procedures
Write SOP (if
test/procedure
done internally)
Provide the
information for
clinical decision
What does the
doctor need to
know?
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17. Designing a Lab SOP
Example 1
Does the patient
have high sperm
DNA
fragmentation?
SDF Testing using
Sperm Chromatin
Dispersion Test
(SCD)
High SDF if
results >30%
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What does the
doctor need to
know?
Determine test
Lab SOP with
post-analytical
info for clinical
decision

18. Clinical decision based on Lab
SOP information
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19. Designing a Lab SOP
Example 2
How can I avoid
unnecessary
surgical sperm
retrieval in men
with NOA?
Semen analysis
at sperm retrieval
day
Presence of
sperm for ICSI
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What does the
doctor need to
know?
Determine test
Lab SOP with
post-analytical
info for clinical
decision

20. How can I avoid
unnecessary
surgical sperm
retrieval in men
with NOA?
Semen analysis
at sperm retrieval
day
Presence of
sperm for ICSI
Does SOP provide solution for
panic/alert values?
Panic value: No
sperm
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What to do next?
eg.: Centrifugation

21. Clinical
decision
based on Lab
SOP
information

22. How to adapt Six Sigma when
designing/updating Lab SOPs
Define the process and analyze its design
Identify where SOPs are needed and assess
relevant clinical question/needs
Design and implement Lab SOPs
Control (verify conformity)
Improve (update SOPs)
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23. What the Lab team needs to consider
when designing/updating a SOP
Key points
WHAT is a given test/procedure for?
Clinical objectives
WHAT results (post-analytical information)
provide information for clinical decision?
Clinical interpretation
Clinical management
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24. How to combine clinical
and lab perspective for
making decisions
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25. Lab perspective determining
clinical decision – Example 1
What to do?
Patient failed
to ejaculate
No sperm on
ejaculate
Immotile
sperm only
Collect again
TESA
Use cryopreserved
specimen banked
in advance
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26. Lab perspective determining
clinical decision – Example 2
No oocytes on
FF examination
Flush follicles
Check aspiration
pump inline filter/
vacuum pressure/
flow rate
Check
compliance to
hCG
administration
What to do?
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27. Clinical perspective determining
Lab SOPs – Example 1
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0%
10%
20%
30%
40%
50%
60%
fresh I warming II warming
Livebirthrates
Oocyte banking by vitrification
38-40 yr
41-43 yr
+
17%
+
43%
Adapted from Ubaldi, et al. Hum Reprod, 2010
Poor responder in
1st IVF cycle
Lab SOP for
oocyte freezing by
vitrification
Oocyte
freezing

28. Clinical perspective determining
Lab SOPs – Example 2
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IVF cycle
involving partner
with high SDF
Lab SOP for
handling
ejaculated sperm
in cases of high
SDF
Short ejaculatory
abstinence and
post-processing
sperm incubation
Gosálbez et al. Fertil Steril 2011

29. GnRH-agonist vs hCG
LH trigger
Fresh autologous cycles
Moderate/
severe OHSS
OR 0.10,
(0.01 to 0.82)
Live birth
OR 0.44
(0.29 - 0.68)
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Youssef et al. Cochrane Database Syst Rev. 2011
Patients at
risk of OHSS
Lab SOP for
embryo
vitrification
Freeze all
embryos
Clinical perspective determining
Lab decision – Example 3

30. How to combine clinical and lab
perspectives for making decisions
Key points
Clinical
perspective
determining lab
SOPs
Lab SOPs
determining
clinical decision
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Effective communication as per TQM guidance is the
key to integrate both sectors, and will determine
best strategy to meet patients’ needs

31. Thank you
Rio de Janeiro, BRAZIL