Participants Handbook for Reproductive Science Schemes

Participants Handbook for Reproductive Science Schemes 2012 Central Manchester University Hospitals NHS Foundation Trust. All rights reserved. Not to be reproduced in whole or in part without the permission of the copyright holder. V5 13/01/2012 Page: 1 of 28 PRH/DRM/NEQ/001 Authorised by Peter Goddard

1 Schemes provided... 4 2 Address for Correspondence... 4 3 Staff... 4 4 Scheme objectives... 4 5 Accreditation of Schemes... 5 6 Enrolment procedure... 5 7 Charges and charging period... 5 8 Scheme Organisation... 5 8.1 Laboratory Code Numbers... 5 8.2 Confidentiality... 6 9 Scheme Operation... 6 9.1 Specimens, images and video clips... 6 9.2 Safety precautions in handling semen specimens... 6 9.3 Schedule of distributions... 6 9.4 Semen specimens... 6 9.5 On line Morphology and Motility... 6 9.6 Embryo Morphology... 7 10 Processing UK NEQAS samples in your laboratory... 7 10.1. Receipt and analysis... 7 10.2. Return of results... 7 10.3. Failure to return results... 7 10.4. Late returns... 8 10.5. Blunders and their correction... 8 10.6. Amendments to results prior to reporting deadline... 8 10.7. UK NEQAS errors... 8 11 Performance Assessment... 8 11.1 Designated Values... 8 11.2 Calculation of Analytical Performance Scores - Semen Analysis Scheme. 8 11.3 Calculation of Analytical Performance Scores - Sperm Motility Scheme 9 11.4 Calculation of Analytical Performance Scores Online Morphology Scheme9 11.5 Calculation of Analytical Performance Scores Online Embryology Scheme 9 12 Performance criteria and persistent unsatisfactory performance... 9 13 Reports and their Interpretation... 10 13.1 Semen Analysis and Sperm Motility Schemes (MRBIS & MRVIS scoring) 10 13.2 Interpretation of MRBIS & MRVIS Performance Data... 10 14 Past UK NEQAS Specimens & DVD s... 11 15 Scheme Development & Scientific Support... 11 16 Communication, Comments and Complaints... 11 17 Annual Review of Schemes... 11 18 Terminology... 12 Figures 13 Figure 1 Sperm concentration (millions/ml)...13 Figure 2 Sperm Morphology (% normal)...14 V5 13/01/2012 Page: 2 of 28 PRH/DRM/NEQ/001 Authorised by Peter Goddard

Figure 3 Sperm Motility...15 Figure 4 Bias (%)...16 Figure 5 -Chosen Co-efficient of variation (CCV)...16 Figure 6 - BIAS INDEX SCORE (BIS) and VARIANCE INDEX SCORES (VIS)...16 Figure 7 Semen Analysis - Running Means...17 Figure 8 Sperm Motility Running Mean...17 Figure 9 Online Morphology Report...18 Figure 10 Online Morphology Summary...19 Figure 11 Embryology Scheme Report (part 1)...20 Figure 12 Embryology Scheme Report (part 2)...21 Appendix... 22 Appendix 1; Joint Working Group for Quality Assurance: Conditions of EQA Scheme Participation...22 Appendix 2, Membership of the Andrology Steering Committee...24 Appendix 3, Membership of the Embryology Steering Committee...25 Appendix 4: Membership of the National Quality Assurance Advisory Panel for Reproductive Science...26 Appendix 5A: Performance...27 Appendix 5B: Performance...28 V5 13/01/2012 Page: 3 of 28 PRH/DRM/NEQ/001 Authorised by Peter Goddard

1 Schemes provided SCHEME ANDROLOGY EMBRYOLOGY ANALYTES Semen Concentration Sperm Morphology (practical) Sperm Motility (DVD) Sperm Morphology (online) Sperm Motility (online) Embryo Morphology (online) 2 Address for Correspondence UK NEQAS Reproductive Science Scheme Department of Reproductive Medicine Andrology Laboratories Saint Mary s Hospital Oxford Road Manchester M13 9WL Tel No: +44 (0)161 276 6437 Fax No: +44 (0)161 276 6609 Email: repscience@ukneqas.org.uk Web Site: http://www.cmft.nhs.uk/saint-marys/our-services/ukneqasrepsci.aspx 3 Staff Scheme Organiser Mr. Gregory Horne BSc. M.Sc. F.R.C.Path Deputy Scheme Organiser Dr Diane Critchlow BSc. Ph.D. Dip.R.C.Path Scheme Manager Mr. Peter Goddard MIBMS Quality Manager Miss. Justine Hartley B.Sc. M.Sc. CSci. FIBMS Training Officer Mrs. Kathy Cumming CSci. FIBMS Health and Safety Officer Mr. Peter Goddard MIBMS Scheme Administrator Mrs. Diane Shearden 4 Scheme objectives UK NEQAS Reproductive Science aims to: Provide professionally led and scientifically based schemes with a primarily educational objective. Provide regular distributions of appropriate specimens. Provide rapid feedback of performance, with reports that are comprehensive and readily understood. Provide data on method performance. UK NEQAS Reproductive Science is part of the Department of Reproductive Medicine, St. Mary s Hospital, Manchester. There is a close working relationship between the diagnostic section and the EQA scheme. V5 13/01/2012 Page: 4 of 28 PRH/DRM/NEQ/001 Authorised by Peter Goddard

5 Accreditation of Schemes The Andrology scheme has full CPA accreditation. The online Embryology scheme is to apply for accreditation in 2012 6 Enrolment procedure The following Enrolment documents can be found under UK NEQAS Reproductive Science at the website :- Participants handbook Distribution schedule and price list Enrolment form Participation begins at the first distribution following acknowledged receipt of completed forms. Although the majority of participants are UK NHS diagnostic service laboratories, all laboratories, including non-uk, research and commercial laboratories are welcome to join. All UK clinical service laboratories must agree to current Joint Working Group (JWG) Conditions of Participation (Appendix 1). Participation of non-uk laboratories may be subject to the availability of suitable specimen transport. Manufacturers may participate on an information only basis, i.e. without receiving samples and returning results. They may also register methods under development. 7 Charges and charging period The scale of charges is published annually and is available on the web site. The charging period is 1 st April to 31 st March. Participants will be advised of each year s charges in advance. Participation is deemed to be continuous so participants do not need to renew their subscription annually. Participation may begin at any time during the year and charges for part year will in general be pro rata. Refunds of subscription charges are only payable under exceptional circumstances. 8 Scheme Organisation 8.1 Laboratory Code Numbers Participants are assigned a unique code number, which is common to other UK NEQAS Schemes in other disciplines. Please quote your laboratory code number in all communications. V5 13/01/2012 Page: 5 of 28 PRH/DRM/NEQ/001 Authorised by Peter Goddard

8.2 Confidentiality All information relating to your participation in the scheme such as raw data and performance scores are confidential between the individual laboratory and UK NEQAS staff, Chairman and members of NQAAP, and in specified circumstances the chairman of JWG on QA (appendix 1, section 4, page 17). 9 Scheme Operation 9.1 Specimens, images and video clips All specimens, images and video clips are of human origin. Semen specimens for concentration and morphology assessment are pooled specimens. DVDs are currently distributed for sperm motility, this is to be replaced by an online scheme in April 2012. Specimens are filmed at 37 C. The online Morphology scheme consists of images of stained sperm. The Embryology scheme consists of video clips of embryos and embryo development and is viewed online. 9.2 Safety precautions in handling semen specimens Semen specimens are preserved with 10% aqueous formaldehyde. Please handle EQA semen specimens with the same precautions as are normally adopted in the handling of patient specimens in accordance with your departmental safety arrangements. 9.3 Schedule of distributions Copies of the distribution schedule for the current year are available at http://www.cmft.nhs.uk/saint-marys/our-services/ukneqasrepsci.aspx. If semen specimens, DVDs and email notification of the online schemes do not arrive on time or are incorrect it is essential that participants inform the scheme Manager as soon as possible. Replacements will be sent. 9.4 Semen specimens Participation fees include basic postal rates. Semen specimens are distributed quarterly by first class post. Airsure or International signed for postal services are used for overseas participants at an additional cost. Alternatively non UK participants may want to arrange an international courier. The semen analysis specimens are used to estimate both sperm concentration and sperm morphology. 9.5 On line Morphology and Motility The online Morphology and Motility Schemes were launched to all users in April 2011. The online Motility scheme will replace the DVD scheme in April 2012. V5 13/01/2012 Page: 6 of 28 PRH/DRM/NEQ/001 Authorised by Peter Goddard

Each motility distribution consists of four samples with several clips of sperm for each sample. The Online Morphology distributions consist of a series of images containing 24 sperm for assessment. 9.6 Embryo Morphology The Embryo Morphology distributions contain videos of embryos from four patients for assessment either under the microscope or using Embryoscope TM time lapsed videos. 10 Processing UK NEQAS samples in your laboratory 10.1. Receipt and analysis UK NEQAS distributions are intended to monitor your performance on routine patient specimens. Please process them through your normal reception, analytical and reporting procedure. 10.2. Return of results Semen motility (DVD) concentration & morphology Results must be returned by the due date, usually 4 weeks, if they are to be included in the report. Results are reported online at https//results.ukneqas.org.uk or alternatively via http//www.birminghamquality.org.uk, all labs will have been allocated a user name and password. Reports will be available from this site once the distribution has been closed and processed. Online Motility & Sperm Morphology Results must be entered while viewing the images/videos online at gamete-expert.com. Participants are allocated a username (usually an email address) and a password. This will not be the same username as for sperm concentration & motility. Reports will be available shortly after processing from http//www.birminghamquality.org.uk Embryo Morphology Results must be entered while viewing the images/videos online at gamete-expert.com. Participants are allocated a username (usually an email address) and a password. This will not be the same username as for sperm concentration & motility. Reports will be available shortly after processing from http//www.birminghamquality.org.uk 10.3. Failure to return results If your laboratory makes no response to a distribution by the due date (Nil return) your report will have a blank space for your result and you will receive an email from the scheme. Regular participation is important if adequate data is to be obtained. This is a criterion of satisfactory performance. V5 13/01/2012 Page: 7 of 28 PRH/DRM/NEQ/001 Authorised by Peter Goddard

Failure to return results will result in the Scheme Manager contacting you. Failure to return results for 2 distributions within the last 8 distributions will be regarded as unsatisfactory performance and the Scheme Organiser will contact the National Quality Assurance Advisory Panel (NQAAP) (see appendix 4). 10.4. Late returns Designated values are derived from a consensus of received results; therefore late returns cannot be accepted. 10.5. Blunders and their correction These are defined as errors (which may or may not be classified as outliers) and may be due to: Assaying the wrong samples Assaying the right samples in the wrong order Incorrectly entering laboratory results. 10.6. Amendments to results prior to reporting deadline Amendments to results can only be made prior to the closing date. Although results cannot be amended in the computer system after the reporting deadline an explanation will be kept in your file and this will be taken into account when assessing unsatisfactory performance. 10.7. UK NEQAS errors If you suspect that we have made an error please let us know immediately. We audit all such errors and it is important that we know about them so that we can improve our service. 11 Performance Assessment 11.1 Designated Values UK NEQAS attaches great importance to validation of designated values (DV). Designated values should be accurate and stable, but this is difficult to achieve where reference methods are unavailable. For the semen analysis scheme the ALTM is used for concentration (Fig 1). The method-related trimmed mean (MRTM), taken from results of laboratories reporting the use of WHO (1999) criteria is used for morphology (Fig 2) (this will change to the WHO 2010 when sufficient numbers of participants cite this as their method). ALTM is used for motility (Fig 3). 11.2 Calculation of Analytical Performance Scores - Semen Analysis Scheme. Laboratory performance is reported as a cumulative mean running bias index score (MRBIS) and a Mean Running Variance Index Score (MRVIS). Your BIAS is the difference between your result (YR) and the designated value (DV) expressed as a percentage (Fig 4) Both the Bias Index Score (BIS) and the Variance Index Score (VIS) are calculated for each specimen using a Chosen Co-efficient of Variation (CCV) (Fig 6). V5 13/01/2012 Page: 8 of 28 PRH/DRM/NEQ/001 Authorised by Peter Goddard

This (CCV) varies dependent on the designated value (Fig 5). This is done to ensure that in cases of low DV clinical relevance outweighs statistical significance. Both BIS and VIS are the same value but BIS is assigned either a positive or negative value, whilst VIS is always positive. The mean of the 4 BIS scores and the mean of the 4 VIS values for each specimen are then plotted on the MRBIS and MRVIS running graphs. These graphs have data from 10 distributions displayed but the latest point is derived only from the last 6 distributions. The MRBIS and MRVIS are updated on a rolling record as new data is added (i.e. the oldest data is removed from your record as new data is added) (Figs 7 and 8). 11.3 Calculation of Analytical Performance Scores - Sperm Motility Scheme Laboratory Performance is reported in the same way as the Semen Analysis Scheme except that the BIS and VIS scores for Non-progressive and immotile are taken together on the respective MRBIS and MRVIS graphs (Fig 5). 11.4 Calculation of Analytical Performance Scores Online Morphology Scheme Laboratory Performance is not scored for this scheme. This will be reviewed by the Andrology Steering Committee in March 2012. An example of the report format is shown below (Fig 9 & 10). 11.5 Calculation of Analytical Performance Scores Online Embryology Scheme Laboratory Performance is not scored for this scheme. This will be reviewed by the Embryology Steering Committee in March 2012. An example of the report format is shown below (Fig 11 &12). 12 Performance criteria and persistent unsatisfactory performance Limits for acceptable performance are approved by the National Quality Assurance Advisory Panel (NQAAP) for Reproductive Science in consultation with the Andrology Steering Committee (ASC) and Embryology Steering Committee (ESC) where appropriate. The criteria include acceptable limits for BIAS and for return rate. The quarterly reports include figures to show your performance in relation to the relevant criteria. Laboratories should aim to maintain performance within these limits and are invited to contact us if problems appear to be developing, whether in analytical performance or in their ability to maintain regular returns. If a serious anomaly is found, the Scheme Manager will informally contact a participant. A laboratory is considered to be a persistent unsatisfactory performer for a given technique if: The cumulative performance is outside the prescribed limit on three distributions within the last 8 distributions. It fails to return results for two distributions within the last 8 distributions, without notifying the UK NEQAS Centre of a change in participation. A combination of the above. V5 13/01/2012 Page: 9 of 28 PRH/DRM/NEQ/001 Authorised by Peter Goddard

For concentration if your Bias Index Score (BIS) is + or - 100 or more in three of the four specimens of the distribution it will be noted as an unsatisfactory performance. If this happens on three distributions within the last 8 distributions, the laboratory will be contacted as a persistent unsatisfactory performer. For sperm motility if your Bias Index Score (BIS) is 100 or more for two of the three categories in three of the four specimens of the distribution it will be noted as an unsatisfactory performance. If this happens on three distributions within the last 8 distributions, the laboratory will be contacted as a persistent unsatisfactory performer. For Morphology (from semen samples) if your result is more than twice the designated value for three of the four specimens it will be noted and you will be contacted. If this happens on three distributions within the last 8 distributions, the laboratory will be contacted as a persistent unsatisfactory performer. We will generally make informal contact with any participant falling into the above categories. If performance fails to improve, the Chairman of the appropriate NQAAP will be notified. Advice is then offered to them in writing or, where appropriate, a visit to the laboratory from a NQAAP or ASC member or other appropriate expert (if agreed) may be arranged (See appendix 1). 13 Reports and their Interpretation 13.1 Semen Analysis and Sperm Motility Schemes (MRBIS & MRVIS scoring) The report format is common across many UK NEQAS schemes and contains the following sections: Summary. This shows your performance for all techniques on the current distribution, compared to designated values (DV). Details of performance for each technique. This shows method performance on the current distribution, and tabulates all your results for the six distributions to date. Consult this section if you need to review your performance, or if you need information on method performance. Pools. Each pooled set of samples is given a unique number and this is detailed on the report. Sometimes the same pool is sent out on more than one occasion. Consult the pool numbers, and check your results with the DV to review the consistence of your performance. Comments. This optional section amplifies the data in the sections above, or may describe the results of surveys, e.g. interpretation of results. 13.2 Interpretation of MRBIS & MRVIS Performance Data Calculation of the MRBIS and MRVIS is designed to make maximum use of the data. These should always be viewed with your current results in mind. Due to the fact that these graphs present results spanning the last 6 distributions, single errors even where these are significant, are unlikely to affect the overall appearance of the graph. Similarly V5 13/01/2012 Page: 10 of 28 PRH/DRM/NEQ/001 Authorised by Peter Goddard

where results have been unsatisfactory for some time, an improvement will take time to become obvious in this 6-distribution window. Low MRBIS, Low MRVIS: Your results are precise and giving results close to the DV. This is the desirable place to be, assuming the accuracy of the DV. Low MRBIS, High MRVIS: There is a wide scatter of your BIS/VIS on individual specimens although for the BIS the mean is near to unity with the DV. This can indicate a random error and so it would be wrong to be complacent about your low MRBIS. High MRBIS, High MRVIS: Both the BIS and VIS scores indicate a deviation from the DV. In this instance you should investigate for a systemic error. 14 Past UK NEQAS Specimens & DVD s We can sometimes provide aliquots of previously distributed issued specimens, DVDs together with Designated Values for laboratories wishing to check methodologies or evaluate new ones. It should be remembered that semen specimens even with preservative have a limited shelf life and so may not be available. An additional charge may be made for this service. Specimens may be available to manufacturers wishing to trouble-shoot existing methodologies or evaluate new ones. A charge will be made for this service. 15 Scheme Development & Scientific Support The Andrology Steering Committee (ASC) and Embryology Steering Committee (ESC) provide advice on strategic direction and scheme effectiveness and advises the schemes. 16 Communication, Comments and Complaints We take the opinions of our participants very seriously and welcome your views. If you have any comments or complaints about any aspect of the schemes, whether scientific or operational, general or specific, please contact the Scheme Manager or Scheme Organiser as detailed on page 3. In the event of day-to-day operational matters, please have at hand your laboratory number, together with the distribution or specimen number(s). We will then endeavour to address any issues as soon as possible. Additionally the UK NEQAS Reproductive Science Scheme operates an Annual Participants Meeting and Andrology Training Days where scheme staff are available to answer any questions. Participants using a distributor may contact the scheme directly or through their distributor or agency. 17 Annual Review of Schemes Each year the Scheme management team reviews all aspects of the service. Results of evaluation questionnaires and comments from participants are included in this review. A report of the UK NEQAS Reproductive Science scheme results, trends in participation V5 13/01/2012 Page: 11 of 28 PRH/DRM/NEQ/001 Authorised by Peter Goddard

etc is published annually and emailed to all participants. It is also available on the website. 18 Terminology ALTM: The all laboratory trimmed mean. This is the geometric mean of the entire set of trimmed results for a specimen. BIAS: The difference between your result and the designated value expressed as a percentage. BIS: The bias divided by a chosen co-efficient of variation (CCV) multiplied by 100. CCVs are selected to give more leeway to lower designated values so as better to reflect clinical relevance. Values can be either positive or negative. MRTM: The method related trimmed mean is a geometric mean of trimmed results from one methodology. MRBIS: The mean of BIS scores taken from the last 6 distributions. The value can be either positive or negative. This is useful to discover persistent systematic faults. It clearly shows where there is a negative or positive bias. MRVIS: The mean of variance index score taken over the last 6 distributions. All values are positive and so this will show up both random and systematic error. Pool: A bulk preparation of semen usually prepared from several different individual donations of defined characteristics. The same pool may be used more than once. Trimming: The effect of aberrant results that may be present is minimised by trimming the data prior to statistical analysis. The chosen method is that trimming occurs at 1.5 standard deviations (SD) from the overall mean. VIS: The bias divided by a chosen co-efficient of variation (CCV) multiplied by 100. CCVs are selected to give more leeway to lower designated values so as better to reflect clinical relevance. All values are positive. V5 13/01/2012 Page: 12 of 28 PRH/DRM/NEQ/001 Authorised by Peter Goddard

Figures Figure 1 Sperm concentration (millions/ml) V5 13/01/2012 Page: 13 of 28 PRH/DRM/NEQ/001 Authorised by Peter Goddard

Figure 2 Sperm Morphology (% normal) V5 13/01/2012 Page: 14 of 28 PRH/DRM/NEQ/001 Authorised by Peter Goddard

Figure 3 Sperm Motility Reproductive Science V5 13/01/2012 Page: 15 of 28 PRH/DRM/NEQ/001 Authorised by Peter Goddard

Figure 4 Bias (%) BIAS is the difference between your result (YR) and the designated value (DV) expressed as a percentage. YR - DV = X X x 100 = BIAS DV 1 e.g. 45-54.97 = -9.97-9.97 x 100 = -18.13 (BIAS) 54.97 1 Figure 5 -Chosen Co-efficient of variation (CCV) CCV s vary depending on the designated value and were selected to give more error margin at lower DV s. Concentration Designated value Co-efficient of variation < 15 million/ml 50 15 30 million/ml 25 >30 million/ml 20 Motility Designated value Co-efficient of variation < 10% 40 10 20% 30 20 30% 25 >30% 20 Figure 6 - BIAS INDEX SCORE (BIS) and VARIANCE INDEX SCORES (VIS) BIS is the bias divided by Chosen Co-efficient of variation (CCV) x 100. e.g. BIAS x 100-18.13 x 100 = -90.65 CCV 20 1 Bias Index scores are always whole numbers, therefore BIS = -91. Both BIS and VIS are the same value but BIS is assigned either a positive or negative value, whilst VIS is always positive. V5 13/01/2012 Page: 16 of 28 PRH/DRM/NEQ/001 Authorised by Peter Goddard

Figure 7 Semen Analysis - Running Means Figure 8 Sperm Motility Running Mean V5 13/01/2012 Page: 17 of 28 PRH/DRM/NEQ/001 Authorised by Peter Goddard

Figure 9 Online Morphology Report V5 13/01/2012 Page: 18 of 28 PRH/DRM/NEQ/001 Authorised by Peter Goddard

Figure 10 Online Morphology Summary Reproductive Science V5 13/01/2012 Page: 19 of 28 PRH/DRM/NEQ/001 Authorised by Peter Goddard

Figure 11 Embryology Scheme Report (part 1) V5 13/01/2012 Page: 20 of 28 PRH/DRM/NEQ/001 Authorised by Peter Goddard

Figure 12 Embryology Scheme Report (part 2) V5 13/01/2012 Page: 21 of 28 PRH/DRM/NEQ/001 Authorised by Peter Goddard

Appendix. Reproductive Science Appendix 1; Joint Working Group for Quality Assurance: Conditions of EQA Scheme Participation The Joint Working Group for Quality Assurance (JWG) is a multidisciplinary group accountable to the Royal College of Pathologists for the oversight of performance in external quality assurance schemes (EQA) in the UK. Membership consists of the Chairmen of the National Quality Assurance Advisory Panels (NQAAPs), and representatives from the Institute of Biomedical Sciences, the Independent Healthcare Sector, the Department of Health and CPA (UK) Ltd. 1. The Head of a laboratory is responsible for registering the laboratory with an appropriate accredited EQA scheme. 2. The laboratory should be registered with available EQA schemes to cover all the tests that the laboratory performs as a clinical service. 3. EQA samples must be treated in exactly the same way as clinical samples. If this is not possible because of the use of non-routine material for the EQA (such as photographs) they should still be given as near to routine treatment as possible. 4. Changes in the test methodology of the laboratory should be notified in writing to the appropriate scheme organiser and should be reflected in the EQA schemes with which the laboratory is registered. 5. Samples, reports and routine correspondence may be addressed to a named deputy, but correspondence from Organisers and NQAAPs concerning persistent poor performance (red see below) will be sent directly to the Head of the laboratory or, in the case of the independent healthcare sector, the Hospital Executive Director. 6. The EQA code number and name of the laboratory and the assessment of individual laboratory performance are confidential to the participant and will not be released by Scheme Organisers without the written permission of the Head of the laboratory to any third party other than the Chairman and members of the appropriate NQAAP and the Chairman and members of the JWG. The identity of a participant (name of laboratory and Head of Department) and the tests and EQA schemes for which that laboratory is registered (but not details of performance) may also be released by the Scheme Organiser on request to the Health Authority, Hospital Trust/Private Company in which the laboratory is situated after a written request has been received. 7. A NQAAP may, with the written permission of the Head of a laboratory, correspond with the Authority responsible for the laboratory, about deficiencies in staff or equipment V5 13/01/2012 Page: 22 of 28 PRH/DRM/NEQ/001 Authorised by Peter Goddard

which, in the opinion of the NQAAP members, prevent the laboratory from maintaining a satisfactory standard. 8. Laboratories EQA performance will be graded using a traffic light system; green will indicate no concerns, amber poor performance, red persistent poor performance, with black being reserved for the tiny number of cases that cannot be managed by the Organiser or NQAAP and that have to be referred to the JWG. The criteria for poor performance (amber) and persistent poor performance (red) are proposed by the EQA scheme Steering Committee in consultation with the EQA Provider/Scheme Organiser and approved by the relevant NQAAP. 9. When a laboratory shows poor (amber) performance the Organiser will generally make contact with the participant in accordance with the Scheme Standard Operating Procedure for poor performance. Within 2 weeks of a laboratory being identified as a persistent poor performer (red), the Organiser will notify the Chairman of the appropriate NQAAP together with a resume of remedial action taken or proposed. The identity of a persistently poor performing laboratory (red) will be made available to members of the NQAAP and JWG. The NQAAP Chairman should agree in writing any remedial action to be taken and the timescale and responsibility for carrying this out; if appropriate, this letter will be copied to accreditation/regulatory bodies such as CPA (UK) Ltd, UKAS and HFEA who may arrange an urgent visit to the laboratory. Advice is offered to the Head of the Laboratory in writing or, if appropriate, a visit to the Laboratory from a NQAAP member or appropriate agreed expert may be arranged. 10. If persistent poor performance remains unresolved (black), the NQAAP Chairman will submit a report to the Chairman of the JWG giving details of the problem, its causes and the reasons for failure to achieve improvement. The Chairman of the JWG will consider the report and, if appropriate, seek specialist advice from a panel of experts from the appropriate professional bodies to advise him/her on this matter. The Chairman of the JWG will be empowered to arrange a site meeting of this panel of experts with the Head of the Department concerned. If such supportive action fails to resolve the problems and, with the agreement of the panel of experts, the Chairman of the JWG will inform the Chief Executive Officer, or nearest equivalent within the organisation of the Trust or Institution, of the problem, the steps which have been taken to rectify it and, if it has been identified, the cause of the problem. The Chairman of the JWG also has direct access and responsibility to the Professional Standards Unit of the Royal College of Pathologists. Should these measures fail to resolve the issues, the laboratory will be referred to the Care Quality Commission for further action. 11. Problems relating to EQA Schemes, including complaints from participating laboratories, which cannot be resolved by the appropriate Organiser, Steering Committee or NQAAP, will be referred to the Chairman of the JWG. Joint Working Group for Quality Assurance in Pathology, August 2010. V5 13/01/2012 Page: 23 of 28 PRH/DRM/NEQ/001 Authorised by Peter Goddard

Appendix 2, Membership of the Andrology Steering Committee 1. Chair: Dr. Allan Pacey Senior Lecturer in Andrology, University of Sheffield. 2. Deputy Chair: Mr. Alan Webster Chief Biomedical Scientist, Wythenshawe Hospital, Manchester. 3. Mrs. Beverley Duffy Senior Biomedical Scientist, Whiston Hospital, Merseyside. 4. Mrs. Trudy Johnson Departmental Manager, Queen Elizabeth Hospital, Gateshead. 5. Dr. D. Iwan Lewis-Jones Senior Lecturer and Consultant Clinical Andrologist,, Liverpool Women s Hospital. 6. Dr. Kevin Lindsay Principal Clinical Scientist in Andrology, Hammersmith Hospital, London. 7. Dr. Debbie Falconer Principal Clinical Embryologist, Manchester Fertility Services Ltd 8. Mr. Paul Hancock Head of Andrology, Somerset Pathology Services, Yeovil District Hospital. Societies represented by members of the Steering Committee. Association of Biomedical Andrologists (ABA) Association of Clinical Embryologists (ACE) British Andrology Society (BAS) British Fertility Society (BFS) European Society for Human Reproduction & Embryology (ESHRE) Institute of Biomedical Science (IBMS) V5 13/01/2012 Page: 24 of 28 PRH/DRM/NEQ/001 Authorised by Peter Goddard

Appendix 3, Membership of the Embryology Steering Committee 1. Chair: Dr. Stephen Harbottle Lead Embryologist, Cambridge IVF. 2. Miss Ella Clapham Embryologist, Newcastle Centre for Life. 3. Dr. Rachel Gregoire Senior Clinical Embryologist, Liverpool Women s Hospital. 4. Dr. Emma Stephenson Embryologist, Guy s Hospital, London. 5. Dr. Helen Clarke Senior Clinical Embryologist, Jessop Wing, Sheffield Teaching Hospital. 6. Sue Barlow Laboratory Directort, Midland Fertility Services. Societies represented by members of the Steering Committee. Association of Clinical Embryologists (ACE) Association of Biomedical Andrologists (ABA) British Andrology Society (BAS) British Fertility Society (BFS) European Society for Human Reproduction & Embryology (ESHRE) V5 13/01/2012 Page: 25 of 28 PRH/DRM/NEQ/001 Authorised by Peter Goddard

Appendix 4: Membership of the National Quality Assurance Advisory Panel for Reproductive Science 1. Chair: Dr. Kevin Lindsay Association of Clinical Biochemists 2. Dr. D. Iwan Lewis-Jones British Andrology Society 3. Mr. Alan Webster Institute of Biomedical Sciences 4. Dr. Paul Bishop Royal College of Pathologists 5. Mrs. Joanne Adams Association of Biomedical Andrologists 6. Dr. Rachel Gregoire Association of Clinical Embryologists V5 13/01/2012 Page: 26 of 28 PRH/DRM/NEQ/001 Authorised by Peter Goddard

Appendix 5A: Performance Reproductive Science Lab joins scheme Distribution of samples Yes Distribution results received No E-mail sent to lab indicating poor performance Yes Acceptable results No 1 non return in the previous 7 distributions No E-mail sent to lab indicating poor performance 2 non acceptable results in the previous 7 distributions No Yes Yes Pro forma sent asking for action plan - Received within one month Yes No Report to Andrology Steering Committee (ASC) Evidence of improvement or active steps evident to correct poor performance Refer to National Quality Assurance Advisory Panel (NQAAP) Yes No V5 13/01/2012 Page: 27 of 28 PRH/DRM/NEQ/001 Authorised by Peter Goddard

Appendix 5B: Performance Refer to National Quality Assurance Advisory Panel (NQAAP) NQAAP contacts unit and requests remedial action for improvement Unit responds to NQAAP Yes No Unit is referred back to the Organiser for improvements to be monitored and ASC is informed NQAAP contacts the unit either by telephone or site visit to discuss problems with the Laboratory Manager or Chief Executive Yes Unit responds to NQAAP visit No NQAAP refers unit To Joint Working Group on Quality Assurance (JWG) Yes Unit responds to JWG intervention No V5 13/01/2012 Page: 28 of 28 PRH/DRM/NEQ/001 Authorised by Peter Goddard