Quality Management of an Andrology Laboratory

17
Quality Management of
an Andrology Laboratory
Kelly S Athayde, Alex C Varghese, Ashok Agarwal
ABSTRACT
Andrology laboratories make use of various methods necessary for the
assessment of human semen. Human semen assessments are designed to
diagnose pathological conditions and malformations of the reproductive system.
Many of the techniques used in the andrology laboratories are simple to follow
but lack of standardization of these methods makes it difficult to compare results
from different laboratories. This fact also affects the reliability and dependability
of the study results.
The quality management programs consisting of quality control, quality
assessment and quality improvement can be a solution for the standardization
of these methods.
This chapter explains the importance of the quality management program in
the andrology laboratories and helps in the development of a quality
management plan for the laboratory.
INTRODUCTION
Theoretically, routine semen analysis is simple to perform place a drop of
semen on a slide and determine the relative number, size/shape, and
mobility of the spermatozoa. In practice, however, careful analysis of sperm
concentration, movement, and morphology requires a great deal of technical
expertise, procedural care, and meticulous quality control. Andrology
procedures suffer from a lack of standardization, which has made semen
analysis inaccurate and unreliable. As such, results can vary widely within
and between laboratories. This has raised an urgent need for quality
management (QM) the integration of quality activities which include quality
control (QC), quality assurance (QA), and quality improvement (QI) into a
management philosophy.1
This chapter will provide readers with an overview of QM and some
basic tools that will help in the development of a QM plan in an andrology
laboratory.
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ANDROLOGY LABORATORY QM
The concept of QM, when applied to the andrology laboratory, can be
described as a systematic program that monitors and evaluates the quality
of the services that are being provided to patients. This includes identifying
problems and finding their solutions as well as ensuring the quality of the
laboratory services. Quality control in an andrology laboratory with
standard operating procedures (SOP) should begin before any sample is
collected and end with the presentation of results and communication to
the clinician.
QA activities help assure that a product or service will satisfy its required
quality characteristics. QC is the establishment of quality specifications for
each piece of equipment or procedure and involves ensuring that they
conform with established limits and standards. QI focuses on the
progressive increase in the quality and efficiency of each aspect of the work
and activities related to patient care and internal production.
Only a few publications on QM are available. De Jonge 2 numbered the
steps that are involved in implementing a total quality management (TQM)
program (market-in system): (1) define the service, (2) adopt and apply the
principles of TQM, (3) develop mission and vision statements, (4) employ
methods and tolls for continuous QI (Plan-Do-Check-Act cycle) and (5)
continually enhance quality through creativity and innovation. In the PlanDo-Check-Act cycle, the first step is planning, which is followed by
implementation. Results from the implementation are checked, and action
is taken to improve the process. This cycle facilitates QI, as it is a neverending and dynamic activity.
In 2002, the European Society of Human Reproduction and Embryology
(ESHRE) 3 initiated a standardized course on Basic Semen Analysis and
launched a Program for External Quality Assessment (EQA). The World
Health Organization (WHO) Manual, in its fourth edition, 4 discusses
technical QC issues for human semen evaluation. Mortimer, in 1994,
described basic concepts of QC and QA.5
The QM program covers all areas of the laboratory. It must include a
review of errors, complaints, number of incidents, patient satisfaction
(surveys), and employee complaints and suggestions during a certain period
pre-determined by the lab director (at least annually). Pre-analytic, analytic
and post-analytic variables must be evaluated. Pre-analytic processes
include any step involved in the process prior to the testing (e.g. physicians’
orders, patient instructions for semen collection, patient identification,
sample transport, specimen acceptance criteria, and specimen
identification). Post-analytic variables include any steps involved in the
completion of the analytic phase (examination of the specimen) and results
(e.g. turnaround time, quality and interpretability of reports).
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A practical way to start a QM program in an Andrology Laboratory is to
establish and monitor key indicators of quality. These indicators reflect
activities critical to patient outcomes. The College of American Pathologists6
suggests some key indicators:
• Patient/specimen identification
• Test order accuracy
• Start test turnaround time
• Critical value reporting
Documentation—System Control
Within a QM program, the laboratory must keep and control documentation
involving numerous aspects that include but are not limited to the following:
• Organizational chart describing the relationship among the laboratory
director, supervisor, clinical consultant and all other personnel
• List of current equipment and location
• Updated floor plan
• Current policies and procedures (annually reviewed by the director)
• Documented employee reviews of current policies and procedures
related to their job activities
• Documentation of ongoing personnel meetings (employees and director)
(e.g. agenda and meeting minutes)
• Evidence of a continuing clinical laboratory education program
• Updated personnel files of current employees
• Maintenance of discontinued procedures and policies for a determined
period of time after date of retirement (local regulations may differ about
the time of documents quarantine)
• Maintenance of patient records and materials related to test results for
an appropriate length of time (local regulations may differ about the
period)
• Procedures and policies that contain dates of implementation or review
and identification of the reviewers
• The presence of an SOP manual that is easily accessible for employees
(nearby work bench)
• Laboratory computer services system control (system functionality and
reliability)
• Patient data (automated or manual: documentation, process and review
of reports)
• Inventory and storage of supplies (effective control system, e.g. quantity,
storage temperature monitoring)
• Safety policies that are periodically reviewed and readily available for
all employees (fire drills and fire extinguisher training may be required)
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• A chemical hygiene plan (CHP) that defines the safety procedures for
hazardous chemicals used in the laboratory
• A material safety data sheets (MSDS), which should be readily available
and current
• Policy for emergency power supply (to ensure preservation of patients’
specimens, e.g. refrigerators, freezers and incubators).
Proficiency Testing
Some laboratories may be required to participate in a proficiency testing
(PT). PT can be defined as “determination of laboratory testing performance by
means of inter-laboratory comparisons, in which a PT program periodically sends
multiple specimens to members of a group of laboratories for analysis; the program
then compares each laboratory’s results with those of other laboratories in the group
and/or with an assigned value”.6 Interlaboratory communication is prohibited,
and the PT samples should be integrated within the routine workload,
which means the PT sample should be treated as a patient sample. Personnel
who routinely test patient samples will be required to analyze the PT
samples using the same protocol. These services should be performed in
accordance with written procedures.
Laboratory Accreditation
The laboratory must have policies that ensure it is in compliance with
applicable state and local laws and regulations. Besides being in compliance
with regulations and having the required licenses to operate, some laboratories are required to be accredited by non-government organizations.
In the accreditation process, the lab will conduct self inspections and receive
peer-assessment by the selected authority. During these inspections, the
lab will be evaluated for compliance with pre-established standards
(specification and criteria) for practices, procedures, equipment (e.g.
calibration ranges maintenance), and reagents (e.g. expiration dates,
storage) involved in the procedures offered by the laboratory. The
accreditation process may include evaluation of the facility QM program,
proficiency testing, pre-analytic, analytic and post-analytic variables for
sample testing, test method validation, laboratory computer services,
personnel, physical facilities, and laboratory safety. Effective accreditation
schemes share the same basic characteristics (Figure 17.1).
ISO Standards
According to Mortimer and Mortimer1, the International Organization for
Standardization or ISO based in Geneva develops standards according to
the essential principles of: consensus, industry-wide solutions and voluntary
involvement. The ISO 15189:2003 Medical Laboratories—Particular
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Figure 17.1: Generic accreditation process (Adapted from Mortimer and Mortimer, 20051)
requirements for Quality Competence is the standard most relevant to
Andrology and in vitro fertilization (IVF) labs, and laboratory activities
must comply with this ISO. From the same source one can find information
about the European Tissues and Cells Directive that was passed on March,
31st of 2004-Directive 2004/23/EC. On setting standards of quality and safety
for the donation, procurement, testing, processing, preservation, storage and
distribution of human tissues and cells – which specifically includes
reproductive cells and stem cells for human transplantation. Article 6 of
this directive requires that all “tissue establishments,” where any of the
above mentioned activities are undertaken, are to be accredited, designated,
authorized, or licensed by a competent authority of the Member States for
the purpose of those activities, with legal compliance required no later than
April, 7th, 2006. Therefore, any laboratory in Europe that processes semen
for Intrauterine Insemination (IUI) is subjected to this regulation.
Quality Control
QC in the andrology laboratory has been an issue for many years. Many
studies have discussed the lack of operational standards, discrepancy,
imprecision, and inconsistency involved in semen analysis.7-9
The accurate assessment of conventional semen tests remains
problematic even for the experienced technologist. Considerable inter- and
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intra-laboratory variability exists in regards to these assessments, partly
because a wide variety of techniques are used by different laboratories.
Secondly, the experience level of the technical personnel performing these
assessments varies. The use of uniform standardized laboratory techniques
aligned with the maintenance of a comprehensive quality control program
is warranted to reduce this variability in andrology services.
One of the first steps for introducing a QC system in an andrology
laboratory is to have an actual written QC program. It should start with a
complete SOP manual that will be followed by each and every employee
engaged in patient testing.
Well-trained employees are essential for the QA of an andrology
laboratory. Although descriptions of QC systems tend to focus almost
exclusively on the training of technicians to assure the quality of sample
analysis, operator error is only one component of the total analytical error
in any method.7 A well-trained technician can not produce precise and
accurate results using non-standardized, subjective, and non-repeatable
methods. Therefore, training each technician in a standardized manner
(based on well elaborated, objective and repeatable SOPs) will help establish
uniformity in the laboratory evaluation. Competency checks with feedback
and re-training in an ongoing manner is essential for an accurate assessment
and reproducibility of the techniques. A control system for results should
be implemented that includes recording test data, identifying each person
responsible for the evaluation, and trouble-shooting when required.
Practical Guide
The SOPs play an important role for any QC program. Their elaboration
should follow pre-established formats and standards published by local or
international institutes such as the “Clinical and Laboratory Standards
Institute, CLSI, NCCLS” or any other governing national requirements.
An efficient SOP needs to offer all the necessary information for the test to
be reproducible and to be performed efficiently. It could be, for an example,
schematized with the following topics:
SOP-model
• Name of the test
• Introduction
• Principle of procedure (goals and more general information about the
test)
• Specimen collection (patient’s instruction, transport, identification)
• Equipment and materials
• Reagents
• Quality control (negative and positive control if required)
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•
•
•
•
•
Procedure description (detailed, numbering and explaining step by step)
Calculations (if required)
Normal ranges (reference values for normality)
Panic values (if applicable)
Assay performance (inter and intra-assay, variability of the control,
sensitivity)
• References (articles published, current literature, in-house elaboration).
The following check list can be used to implement or complement an
andrology laboratory QC program. Each piece of equipment should contain
a binder or file that contains the QC sheets as well as records of maintenance
and possible occurrences (e.g. malfunctioning or breakage). Each check
should have the initials of the person performing the QC and the date.
QC Checklist
• Daily Check-QC tasks
– Temperatures (room, refrigerators, freezers, incubators)
– Liquid nitrogen tanks (levels and order refill)
– Microscopes (optics, cleaning, covering)
– Clean bench tops with 10% Clorox solution
– Morphology staining solutions (contamination, debris, change in
color).
• Weekly Check-QC tasks
– Incubators (change water in tray)
– Liquid nitrogen tanks (Fill)
– pH meter (level of KCl/AgCl in electrodes, calibration, change soak
solution)
– Automated semen analyzer (beads calibration, motility QC, review of
gate settings)
– Glassware washing (residual contamination)
– Waterbaths (temperature and levels as used)
– Endtz test working solution (contamination, debris, change in color)
– Tyrodes buffer solution (contamination, debris, change in color)
– Eye wash (testing water flow).
• Monthly Check-QC tasks
– Incubator (clean interior and exterior)
– Microscopes (mechanic system, illumination system, clean exterior and
phase contrast)
– Automated semen analyzer (clean interior and exterior)
– Spectrophotometer (wavelength, clean interior and exterior,
absorbance and linearity)
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•
•
•
•
•
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– Eosin-Nigrosin staining solutions (contamination, debris, change in
color)
– HOS solution (contamination, debris, change in color).
Quarterly Check-QC tasks
– Refrigerators/freezers (clean interior and exterior)
– Centrifuges (clean interior and exterior).
Bi-annually Check-QC tasks
– Balances (S class weights)
– Balances (blind spheres)
– Micropipettes and pipettes (calibration)
– Semi-annual environment cultures (workstations: semen wet
preparation and therapeutic).
Annually Check-QC tasks
– Thermometers (calibration)
– Timers (calibration)
– All equipment ground and mechanical check
Check-As used
– Laminar flow/safety cabinet hood (clean before and after use).
Check-As received
Supplies and reagents
– Receiving date
– Product characteristics (temperature during transportation and during
arrival)
– Opening date
– Expiration date
– Storage requirements
– Toxicity testing (for every new lot, e.g. sperm or mouse embryo
survival).
Hands-on Training
Ideally, training should be offered during one-on-one practice sessions.
For a basic training in seminal analysis, the following topics can be covered:
• Discussion about the subject and introduction of the techniques to be
learned (recent literature, test objective, and parameters to be analyzed)
• Microscope alignment (setting up and focusing, setting stage, calibration
and calculating count factor)
• Patient orientation (instructions for collection and sample transportation
if applicable)
• Specimen collection and handling (discuss viscous semen samples)
• Macroscopic parameter evaluation
• Sperm count evaluation (including different dilutions)
• Sperm progression and motility evaluation
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• Quality control on sperm count and motility (instructions, count forms,
use of monitor grids)
• Calculations of coefficient of variation and repeated analysis when
required (basic statistical analysis can be used, e.g. a 15% or less
coefficient of error for intra-tech variability (CV), and 15% or less for the
mean percentage difference from the standard could be required)
• Morphology slides preparation (semen smears: proper labeling, staining
and storage of slides)
• Morphology differential scoring by determined criteria WHO 10 or Strict11
as described in the SOP
• Calculations of coefficient of variation and repeated scoring when
required
• Different samples from patients and healthy semen donors should be
evaluated
• Troubleshooting (emphasis on sperm identification, proper mixing,
loading, counting, motility and prog-ression assessment, morphology
scoring and quality control)
• Training update and individual feedback
• Laboratory worksheets, source documents, and data entry
• Competency check: proficiency test slides
• Review of safety guidelines and good laboratory practices (GLP).
Staffing Issues
The QM program should be a philosophy of work for a laboratory. Strong
leadership is necessary before employees can embrace this philosophy. An
organization is only as good as its leadership, because a good leader
establishes unity of purpose, direction, and the internal environment in
which employees can become fully involved in achieving the organization’s
objectives.2 A healthy relationship among directors, supervisors and
technicians in which the concept of “team work” is applied improves
communication and productivity. Open communication and empowered
employees are ingredients for success. Staff issues such as insufficient,
poorly trained or inexperienced staff, overwork, and lack of guidance will
directly interfere with the quality of any program. A combination of these
factors can ruin any service.
REFERENCES
1. Mortimer M. Quality and Risk Management in the IVF Laboratory.
Cambridge: Cambridge University Press; 2005.
2. De Jonge C. Commentary: forging a partnership between total quality
management and the andrology laboratory. J Androl 2000;21(2):203-.5.
3. ESHRE. Manual on Basic Semen Analysis. European Society of Human
Reproduction and Embryology 2002.
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4. Kruger TF, Coetzee K. The role of sperm morphology in assisted reproduction.
Hum Reprod Update. 1999;5(2):172-78.
5. Mortimer D. Practical Laboratory Andrology. Oxford, editor. New York:
Oxford University Press 1994.
6. Francis Sharkey M, editor. Laboratory Accreditation Manual: College of
American Pathologists 2007.
7. Clements S, Cooke ID, Barratt CL. Implementing comprehensive quality
control in the andrology laboratory. Hum Reprod 1995;10(8):2096-106.
8. Macleod IC, Irvine DS, Masterton A, Taylor A, Templeton AA. Assessment
of the conventional criteria of semen quality by computer-assisted image
analysis: evaluation of the Hamilton-Thorn motility analyser in the context
of a service andrology laboratory. Hum Reprod 1994;9(2):310-19.
9. Mortimer D, Shu MA, Tan R. Standardization and quality control of sperm
concentration and sperm motility counts in semen analysis. Hum Reprod
1986;1(5):299-303.
10. World Health Organization: WHO Laboratory manual for the examination
of human semen and sperm-cervical mucus interaction. Cambridge:
Cambridge University Press; 1992 Contract No.: Document Number.
11. Kruger TF. Atlas of Human Sperm Morphology Evaluation. First ed. London:
Taylor & Francis 2004.