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ASERNIP-S REPORT NO. 39

December 2003

Australian Safety & Efficacy Register of New Interventional Procedures – Surgical

The Royal Australasian College of Surgeons

ASERNIP S Australian Safety and Efficacy Register of New Interventional Procedures-Surgical

Post-Vasectomy Testing to Confirm Sterility: A Systematic Review ISBN 0 909844 59 3 Published (December, 2003) This report should be cited in the following manner: Griffin TT, et al. Post-vasectomy testing to confirm sterility: a systematic review. ASERNIP-S Report No. 39. Adelaide, South Australia: ASERNIP-S, (December 2003). Copies of these reports can be obtained from: The Australian Safety and Efficacy Register of New Interventional Procedures - Surgical The Royal Australasian College of Surgeons PO Box 688, North Adelaide, South Australia 5006 AUSTRALIA Ph: 61-8-8239 1144 Fax: 61-8-8239 1244 E-Mail: [email protected] http://www.surgeons.org/asernip-s

The systematic review of post-vasectomy testing to confirm sterility was ratified by:

The ASERNIP-S Management Committee on November 11, 2003

The Executive of the Council of the Royal Australasian

College of Surgeons in December, 2003

Table of Contents Table of Contents............................................................................................................i Executive Summary ........................................................................................................i Explanation of the ASERNIP-S Classification System ............................................... iii Review Group Membership..........................................................................................iv Systematic Review of Post-Vasectomy Testing to Confirm Sterility............................1 1 OBJECTIVE.........................................................................................................1 2 INTRODUCTION................................................................................................1

2.1 Vasectomy......................................................................................................1 2.2 Safety and Efficacy ........................................................................................1 2.3 Postoperative Follow-Up Protocol.................................................................2

2.3.1 Post-Vasectomy Follow-Up...................................................................2 2.3.2 Issues in Postoperative Follow-Up Protocol..........................................2

2.4 Cost Considerations (in Australia).................................................................4 2.5 Questions of the Review ................................................................................4

3 METHODS...........................................................................................................5

3.1 Literature Search Protocol .............................................................................5 3.1.1 Inclusion Criteria ...................................................................................5

3.2 Literature Searches Strategies........................................................................5 3.2.1 Databases Searched and Search Terms Used.........................................5 3.2.2 Pearling ..................................................................................................6

3.3 Methods of the Review ..................................................................................6 3.3.1 Literature Database ................................................................................6 3.3.2 Data Extraction ......................................................................................7 3.3.3 Data Analysis .........................................................................................7

4 DESCRIPTION AND METHODOLOGICAL QUALITY OF STUDIES..........7

4.1 Designation of Levels of Evidence and Critical Appraisal............................7 4.1.1 Comparative Studies ..............................................................................8 4.1.2 Case Series and Reports.........................................................................8

5 RESULTS...........................................................................................................12

5.1 Post-Vasectomy Semen Analysis Protocols ................................................12 5.1.1 Criteria for Success ..............................................................................12 5.1.2 Testing..................................................................................................12 5.1.3 Histological Confirmation ...................................................................13

5.2 Compliance ..................................................................................................14 5.3 Outcomes .....................................................................................................19

5.3.1 Azoospermia ........................................................................................19 5.3.2 Persistent Non-Motile Sperm...............................................................22 5.3.3 Loss of Sperm Motility ........................................................................23 5.3.4 Reappearance of Sperm After Azoospermia........................................24 5.3.5 Recanalisation and Vasectomy Failure................................................24

6 DISCUSSION.....................................................................................................29 6.1 Compliance ..................................................................................................29 6.2 Outcomes .....................................................................................................29 6.3 Persistent Non-Motile Sperm.......................................................................30 6.4 Loss of Sperm Motility ................................................................................31 6.5 Sperm Reappearance, Recanalisation and Vasectomy Failure ....................31 6.6 Recommendations........................................................................................32

6.6.1 Recommended Post-Vasectomy Semen Analysis Protocol .................32 6.7 Cost Considerations in Australia .................................................................34

7 ACKNOWLEDGEMENTS ...............................................................................35 8 REFERENCES...................................................................................................36

List of Tables Table 1: Studies reporting surveys of practitioners and the post-vasectomy protocols employed. Table 2: Database and search terms used Table 3: Results of search Table 4: Included studies Table 5: The criteria for success of vasectomy used and number of studies utilising those criteria. Table 6: The minimum number of post-vasectomy semen analyses required by practitioners or clinics. Table 7: The timing of post-vasectomy semen analyses used by different practitioners for the first two tests, where reported. Table 8: Studies that routinely sent resected vas for histological examination. Table 9: Percentages of patients who complied with the post-vasectomy semen analysis testing protocol and those who failed to follow-up. Table 10: The median percentage of patients reaching azoospermia in studies where timing of tests was based on time since vasectomy and number of ejaculations since vasectomy. Table 11: Patients demonstrating persistent non-motile sperm after vasectomy. Table 12: Details of recanalisation and vasectomy failure (persistent motile sperm). Table 13: Details of the pregnancies reported. Table 14: Estimated costs of various post-vasectomy testing protocols. Table 15: Estimated costs of two different scenarios of post-vasectomy testing and the estimated savings with the proposed protocol.

List of Figures Figure 1: The median percentage of patients who fully complied with the PVSA protocol against the number of tests required in the protocol of the clinic they attended. Figure 2: The median percentage of patients supplying a first and second sample in 48 studies requiring 2 samples. Figure 3: The median percentage of patients who fully complied with the PVSA protocol against the time of the first sample required by the clinic they attended.

Figure 4: The median percentage of patients who fully complied with the PVSA protocol against the time of the last sample required by the clinic they attended. Figure 5: Median percentage of patients demonstrating azoospermia in first sample against time of first sample. Figure 6: Percentage of patients demonstrating azoospermia in first sample against number of ejaculations post-vasectomy (until first sample). Figure 7: The percentage of patients reaching azoospermia in the first and second test, for tests based on time since vasectomy (for 6 studies). Figure 8: The percentage of patients reaching azoospermia based on number of ejaculations after vasectomy. Figure 9: The percentage of motile sperm based on the number of days after vasectomy. Figure 10: The percentage of patients (of those providing a sample) who demonstrated a reappearance of sperm after azoospermia in a previous sample. Figure 11: Flow chart of the proposed post-vasectomy testing protocol.

List of Appendices Appendix A – Hierarchy Of Evidence Appendix B – Excluded Studies Appendix C – Use of Data Appendix D – Methodological Assessment and Data Extraction Tables Appendix D.1: Comparative studies Appendix D.2: Case series and reports Appendix D.3: Data summary table – Post-vasectomy protocols Appendix D.4: Data summary table – Compliance with post-vasectomy testing Appendix D.5: Data summary table – Outcomes of vasectomy Appendix D.6: Patients reaching azoospermia

Executive Summary Objective: To make evidence-based recommendations on the appropriate protocol for post-vasectomy testing to confirm sterility, on the basis of a systematic assessment of the peer reviewed literature.

Methods: Databases (OVID MEDLINE, Current Contents, Cochrane Library and EMBASE) were searched up to, and including, March 2003. Studies were included if they dealt with post-vasectomy testing to confirm sterility and contained data on at least one of the specified outcomes. Where appropriate, medians were calculated from the data and graphed. Specific outcomes were time to azoospermia, number of ejaculations to azoospermia, time to loss of sperm motility, pregnancy, repeat vasectomy, patient compliance with test protocol, sperm function post-vasectomy and histological analysis of vas specimens.

Results: There were 65 included studies of which 2 were comparative and 63 were case series or case reports. The quality of the available evidence was poor. The evidence-base was weakened by the lack of comparability between studies and losses to follow-up. There were large losses to follow-up with some studies reporting up to 66% loss. The median percentage of patients who fully complied with post-vasectomy testing was 77% (range: 33-100%, n=29). The median percentage of patients who failed to supply any samples was 19% (range: 0-63%, n=29). While compliance varied greatly between studies, it did not appear to depend on the number of tests in the post-vasectomy protocol or the timing of the first or last tests. There was high variability in the percentage of patients reaching azoospermia, even between studies that reported testing at the same time periods following vasectomy. However, the median percentage of azoospermic patients consistently stayed over 80% from three months onwards. When the timing of post-vasectomy testing was based on the number of ejaculations, more than 80% of patients showed azoospermia after 10 ejaculations (but this was only based on 3 studies). Seven studies reported the percentage of patients reaching azoospermia in the first and second tests. In each of these studies there was an increase in the percentage of patients who were azoospermic at the second test, and this increase got smaller when the first test was conducted later. A total of 205 from 14 845 (1.4%) patients (from 15 studies) demonstrated persistent non-motile sperm, although some of these eventually reached azoospermia. Ten studies reported the reappearance of sperm in patients who had previously demonstrated azoospermia. Temporary reappearance of motile sperm was reported in one study (and azoospermia was eventually reached). The reappearance of non-motile sperm was reported in seven studies, occurring up to 22 months post-vasectomy and 17 months after azoospermia was demonstrated.

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There were a total of 69 (<0.1%) pregnancies reported in 20 studies (from a pool of more than 92 000 vasectomies). Pregnancies where paternity was confirmed by DNA analysis showed that vasectomy failure can occur up to 10 years after vasectomy. Conclusions and Recommendations: The evidence presented in this review supports a post-vasectomy testing protocol with only one test (showing azoospermia) at three months post-vasectomy and after a minimum of 20 ejaculations. If the sample is positive at three months, then periodic testing can continue until azoospermia is reached. In patients who do not reach azoospermia after prolonged testing, cautious assurance of success could be given provided only low levels of non-motile sperm are present. No evidence was found to support a recommendation of histological testing of the excised vas deferens. The proposed protocol could considerably reduce costs of post-vasectomy testing. Important Note: The information contained in this report is a distillation of the best

available evidence located at the time the searches were completed, as stated in the review. Please consult with your medical practitioner if you have further questions relating to the information provided, as the clinical context may vary from patient to patient.

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Explanation of the ASERNIP-S Classification System Evidence Rating The evidence for ASERNIP-S systematic reviews is classified as Good, Average or Poor, based on the quality and availability of this evidence. High quality evidence is defined here as having a low risk of bias and no other significant flaws. While high quality randomised controlled trials are regarded as the best kind of evidence for comparing interventions, it may not be practical or ethical to undertake them for some surgical procedures, or the relevant randomised controlled trials may not yet have been carried out. This means that it may not be possible for the evidence on some procedures to be classified as good.

Good Most of the evidence is from a high quality systematic review of all relevant randomised trials or from at least one high quality randomised controlled trial of sufficient power. The component studies should show consistent results, the differences between the interventions being compared should be large enough to be important, and the results should be precise with minimal uncertainty.

Average Most of the evidence is from high quality quasi-randomised controlled trials, or from non-randomised comparative studies without significant flaws, such as large losses to follow-up and obvious baseline differences between the comparison groups. There is a greater risk of bias, confounding and chance relationships compared to high-quality randomised controlled trials, but there is still a moderate probability that the relationships are causal.

An inconclusive systematic review based on small randomised controlled trials that lack the power to detect a difference between interventions and randomised controlled trials of moderate or uncertain quality may attract a rating of average.

Poor Most of the evidence is from case series, or studies of the above designs with significant flaws or a high risk of bias. A poor rating may also be given if there is insufficient evidence.

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Review Group Membership ASERNIP-S Director

Professor Guy Maddern ASERNIP-S Royal Australasian College of Surgeons NORTH ADELAIDE SA 5006

Invited Member

Mr Mark Lloyd Staff Specialist, Division of Surgery The Queen Elizabeth Hospital Woodville Road Woodville SA 5011

Invited Member

Dr Kris Nowakowski RMO, Department of Surgery The Queen Elizabeth Hospital Woodville Road Woodville SA 5011

ASERNIP-S Researchers

Dr Tabatha Griffin and Dr Rebecca Tooher ASERNIP-S Royal Australasian College of Surgeons NORTH ADELAIDE SA 5006

Systematic Review of Post-Vasectomy Testing to Confirm Sterility 1 OBJECTIVE To make evidence-based recommendations on the appropriate protocol for post vasectomy testing to confirm sterility, on the basis of a systematic assessment of the peer reviewed literature. 2 INTRODUCTION 2.1 Vasectomy Vasectomy is a male surgical sterilisation procedure in which a segment of the vas deferens is removed preventing sperm from passing freely through the reproductive tract.1 Vasectomy is one of the most common methods of male contraception used worldwide, with the number of sterilised men estimated to be between 40 and 60 million, and is thought to account for between 5% and 10% of all contraceptive methods used.2,3 In Australia, the vasectomy rate is estimated to be between 7% and 15%4,5 whilst in New Zealand the prevalence is much higher, perhaps the highest in the world, with rates between 23% and 44% suggested.6,7

Vasectomy is performed by urologists, general practitioners, and general surgeons, usually as an outpatient procedure under local anaesthesia. Techniques for vasectomy differ in approach, occlusion technique and length of vas removed.

The Procedure The vasectomy procedure involves entering the scrotum and occluding the vas deferens. There are two methods of scrotal entry, the conventional method and the ‘no-scalpel’ technique. The conventional method involves using a scalpel to make one or two 1-2cm incisions in the scrotal skin overlying the vas deferens (under local anaesthetic). After the vas deferens are occluded (see below), the incision is sutured. In many developing countries the ‘no-scalpel’ technique is used to deliver the vas. Developed in China8, the ‘no-scalpel’ technique involves the puncture of the scrotal skin over the vas by a ringed clamp and dissecting forceps. This is performed under vasal nerve block and no sutures are required.

After the vas deferens have been delivered through the scrotal skin by one of the above techniques, the vas are occluded (and usually cut). Techniques for occluding the vas include ligation with sutures, cautery, application of clips and fascial interposition.1,2 Combinations of cutting (and often removing a portion) and occluding the vas are commonly used. For example, the cut ends of the vas may be sealed using fascial interposition, in which a layer of the fascial sheath is sutured or clipped over the cut end of the vas, or they may be ligated with sutures. Alternatively the cut ends may be left open; this is purported to reduce damage to the epididymis caused by a build up of pressure.9 However, open-ended vasectomy has not been widely adopted.1

2.2 Safety and Efficacy Vasectomy is considered to be a very safe and effective method of contraceptive sterilisation, with failure rates generally quoted as between 0% and 2%.1,2

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Complications of vasectomy include bleeding or haematoma, infection, acute epididymitis, vasovagal reaction, toxicity from the anaesthesia, bruising, pain and swelling in the perioperative period. Longer term complications include sperm granuloma, chronic pain (possibly attributed to congestive epididymitis or epididymitis-orchitis).1,2 Other complications which have been reported include ligature abscess, cutaneous abscess, hydrocele, and vas cutaneous adhesion.3

2.3 Postoperative Follow-Up Protocol 2.3.1 Post-Vasectomy Follow-Up Measuring the success or failure of vasectomy is complicated by a lack of consistency in the appropriate postoperative follow-up protocol. In general, post-vasectomy semen analysis (PVSA) is accepted as the method for determining the success or failure of the procedure. However, the exact protocol used for PVSA is not universal, and in some developing countries there are no facilities for PVSA. It is also possible to examine the removed portion of vas histologically to confirm that portions of the vas have been removed.

PVSA PVSA is conducted to determine whether any motile sperm persist in the ejaculate of vasectomised men. Following an appropriate length of time, or after a certain number of ejaculations patients supply a semen sample which is examined under phase contract microscopy. Most recently, the British Andrology Society has recommended that at least 24 ejaculations and 16 weeks after vasectomy elapse before PVSA is conducted.10

Histological Examination of the Excised Vas While histological analysis of the excised specimen will confirm that the vas has been divided, it is not generally considered an indicator of vasectomy success or failure since the presence of motile sperm in PVSA is a clearer indicator. However, histological examination may detect surgical failures such as a failure to locate the vas or mistaking another structure for the vas.11

2.3.2 Issues in Postoperative Follow-Up Protocol Timing and Number of PVSA Tests As noted, there is no agreed protocol for PVSA testing. Table 1 shows the details of a number of studies that reported surveys of practitioners conducting vasectomy. The PVSA protocols vary substantially between practitioners in the endpoints accepted, number of tests and the timing of tests. Traditionally, two PVSA tests have been recommended at between 12 and 16 weeks post-vasectomy and after at least 20 ejaculations.2,10,12 However, a survey of 1800 vasectomy practitioners in the United States in 1995 found that more than 50% of practitioners only recommended one PVSA test, with 39% recommending two. Urologists were more likely to recommend two tests than either general physicians or general surgeons, who were more likely to recommend only one. Timing of PVSA also varied, with 34% of practitioners recommending that the sample be returned after six weeks, 22% recommending seven to nine weeks, and 10% recommending 10 to 12 weeks.13 Recently a number of authors have advocated the need for only one PVSA test after a much shorter time such as four weeks.14-18 In Australia, in addition to two PVSA tests demonstrating azoospermia, histological analysis of excised vas specimens is sometimes undertaken (G. Maddern 2003, personal communication).

Table 1: Studies reporting surveys of practitioners and the post-vasectomy protocols employed. Definition of

sterility/success Number of required

tests (%) Timing of tests (%) Number of ejaculations

required before first test (%)

Use of histological testing (%)

No author 197919 Survey of clinics where vasectomy performed in the USA.

46/50 (92%) azoospermia 4/50 (8%) accept occasional non-motile sperm

14/50 (28) 1 test Most of remainder 2 tests

Just under 1/3 [~16/50] (~32) require 1st test at 4-16 weeks. 2nd test 2-26 weeks after 1st sample

Approx 16/50 (~32) require tests after 8-30 ejaculations ** Just over 1/3 [~17/50] (~34) use combination of time since vasectomy and no. of ejaculations to determine when tests should be conducted

Babayan and Krane 198620 Survey of members of the New England Section, American Urological Association, Inc.

Not stated 1/281 (0.5) require no negative PVSA 143/281 (51) require 1 105/281 (37) require 2 10/281 (3.5) require >2

38/281 (13) obtain samples at 2-5 weeks 97/281 (35) at 6-8 weeks 87/281 (31) at >8 weeks

13/281 (5) obtain samples after 6-10 ejaculations 27/281 (9.5) after 11-20 ejaculations

135/281 (48) routinely sent excised segment of vas for histological examination

Bradshaw et al. 200112 Survey of urologists and general surgeons in a district general hospital

Azoospermia 2 consecutive azoospermic samples

3 and 4 months postoperatively.

Haws et al. 199813 Survey of urologists, family physicians and general surgeons in the USA.

Not stated 2/955 (0.2) require no negative PVSA 449/955 (47) require 1 444/955 (46.5) require 2 56/955 (6) require 3 4/955 (0.4) require 4

141/955 (15) obtain samples at <6 weeks 318/955 (33) 6 weeks 223/955 (23) 7-9 weeks 93/955 (10) 10-12 weeks 11/955 (1) >12 weeks

103/955 (11) obtain samples after <15 ejaculations 47/955 (5) after 15 47/955 (5) 16-19 35/955 (4) 20 24/955 (3) >20

Sivardeen and Budhoo 200121 Survey of consultant urologists and general surgeons of the North-West region of UK

81/85 request further samples if non-motile sperm present

4/85 (5) request 1 sample 77/85 (90) request 2 samples 4/85 (5) request 3 samples

6/85 (7) obtain 1st sample at 6 weeks 14/85 (16) 8 weeks 37/85 (44) 10 weeks 27/85 (32) 12 weeks 0/85 (0) 14 weeks 1/85 (1) 16 weeks

64/85 (75) routinely sent excised segment of vas for histological examination

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Endpoints There is a lack of agreement regarding the appropriate endpoint for determining vasectomy effectiveness. Post-vasectomy paternity appears to be a clear sign of vasectomy failure; however, it is difficult to be unequivocally certain of paternity without DNA confirmation, and this raises difficult ethical questions. Azoospermia (the absence of sperm in the semen), the current standard indicator of vasectomy success, is complicated by a lack of basic knowledge regarding time-to-azoospermia, number of ejaculations-to-azoospermia, and the significance of motility (time-to-immotility) post-vasectomy. Furthermore, studies of sperm function following vasectomy have led to the suggestion that sperm become non-functional significantly sooner than the time taken to reach azoospermia, that non-motile sperm detected in PVSA testing are unlikely to cause pregnancy, and that therefore patients should be able to rely on vasectomy for contraception before PVSA testing confirms azoospermia.1

2.4 Cost Considerations (in Australia) In the period from January 1994 to December 2002, 252 595 vasectomy procedures were processed through Medicare.22 This means an average of 28 066 vasectomies were processed by Medicare annually over the nine year period. This figure is an underestimate of the actual number of vasectomies performed as they do not include those performed by hospital doctors for public hospital patients or those that qualify for other types of benefits. Ford et al.23 reported 14 101 vasectomies for the period from July 1998 to June 1999 in public and private hospitals. It is difficult to determine an overall population-based estimate of the number of vasectomies per year in Australia as private patients are included in both data sets. Post-vasectomy semen analysis costs $9.50 per sample (cost to Medicare).24 Histological examination of the vas deferens costs $70 per case (i.e. includes the vas from each side).24 The cost of a post-vasectomy testing protocol consisting of two semen samples and histological examination of both vas deferens would be $89 per patient. Hence, a conservative estimate of the costs involved if all patients in Australia were to follow this protocol would be $2,497,874 (based on the 28 066 vasectomies processed by Medicare annually).

2.5 Questions of the Review The primary question of the review is:

• What is the appropriate post-vasectomy surveillance protocol for patients to be sufficiently confident that sterility has been achieved?

Secondary questions include: • What constitutes a negative post-vasectomy semen analysis test? Is the

motility of sperm significant? • Is more than one PVSA test advantageous? • Is histological testing of vas specimens necessary? • What are the risks of failure and cost implications of different post-vasectomy

surveillance protocols?

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3 METHODS 3.1 Literature Search Protocol 3.1.1 Inclusion Criteria Papers were selected for inclusion in this systematic review on the basis of the following criteria.

Participants Only human studies, specifically of patients undergoing vasectomy where the postoperative follow-up protocol included PVSA, were included.

Outcomes Studies which reported at least one of the following outcomes were included:

• pregnancy • repeat vasectomy • time-to-azoospermia • number of ejaculations-to-azoospermia • spacing of ejaculations-to-azoospermia • time-to-loss of motility • patient compliance with test protocol • sperm function post-vasectomy • histological analysis of vas specimens

Types of Studies

Historical and/or non randomised comparative studies, case series and case reports were included for review. Where appropriate, additional relevant published material, in the form of letters, commentary, editorials, abstracts and conference material, was included as background information.

Language Restriction Searches were conducted without language restriction. Foreign language papers were subsequently included on a case-by-case basis when they were considered to be likely to add information to the existing evidence-base. 3.2 Literature Searches Strategies 3.2.1 Databases Searched and Search Terms Used A search strategy was devised to ensure that a maximum number of relevant papers were retrieved across all of the databases (Table 2).

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Table 2: Database and search terms used Database Edition Search Terms

Cochrane Library 1966 – 2003 (Issue 1) vasectomy

Ovid Current Contents 1993 – 2003 (searched 21/3/03)

Ovid EMBASE 1974 – 2003 (searched 21/3/03)

Ovid MEDLINE 1984 – 2003 (searched 21/3/03)

1) vasectomy AND (sperm OR azoospermia* OR semen analysis OR non-motile sperm OR follow-up OR success OR failure)

2) NOT infertility OR IVF-ICSI OR (in-vitro OR invitro) OR contraception OR cancer OR obstruc* OR epididym* OR spermatogen* OR intracytoplasmic OR inject*

3) post vasectomy semen analysis OR post-vasectomy semen analysis OR PVSA

4) vas AND occlu* 5) male steriliz*

Note: * is a truncation character that retrieves all possible suffix variations of the root word e.g. surg* retrieves surgery, surgical, surgeon, etc. In Cochrane the truncation character is *; in Current Contents, Embase and Medline it is $. Abbreviations: IVF – in vitro fertilisation, ICSI – intracytoplasmic sperm injection. 3.2.2 Pearling The bibliographies of all publications retrieved were manually searched for relevant references that may have been missed in the database search. 3.3 Methods of the Review 3.3.1 Literature Database Articles were retrieved when they were judged to possibly meet the selection criteria. Two reviewers then independently applied the selection criteria to the retrieved abstracts and excluded articles that, on the basis of their abstract, did not meet the inclusion criteria. Any differences were resolved by discussion. The number of articles retrieved is shown in Table 3. In some cases when the full text of the article was retrieved (based on the abstract or when an abstract was not available), closer examination revealed that it did not meet the inclusion criteria specified by the protocol. Consequently these papers were not used to formulate the evidence-base for the systematic review (see Table 3 and Appendix B). However, relevant information contained in these excluded studies was used to inform and expand the review discussion.

Table 3: Results of search Total saved to database 149

Total studies meeting inclusion criteria 65

Total studies excluded 84*

*Note: Of these, 44 were excluded after retrieval of the full text of the article. Reasons for exclusion are documented in Appendix B.

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3.3.2 Data Extraction One of the ASERNIP-S reviewers extracted data onto data extraction sheets designed a priori for this review and a second reviewer checked the data extraction. Data were only reported if stated in the text, tables, graphs or figures of the article, or could be accurately extrapolated from the data presented. If no data were reported for a particular outcome, no values were tabulated. This was done to avoid the bias caused by incorrectly assigning a value of zero to an outcome measure on the basis of an unverified assumption by the reviewer. All results are tabulated in Appendix C.

3.3.3 Data Analysis No included studies were suitable for meta-analysis or statistical pooling.

Many of the included studies did not contain data on every outcome covered in this review. Table 4 and Appendix C show what studies were included in each aspect of the review.

In some studies, although relevant information was reported, it was presented in such a way that outcomes could not be determined accurately. Hence, these studies could not be included in the relevant parts of the review and were only included in those sections where the data could be extracted (as shown in Table 4 and Appendix C).

Graphical Presentation of Results In an attempt to present the data in a way that made it possible to determine if any trends were present, medians* were generally calculated (as they are more robust when data are not normally distributed)25 and graphed using box and whisker plots (SPSS version 11.5.1, SPSS Inc., 1989-2002). In these plots, the median is the line within the box and the ends of the box represent the interquartile range (i.e. the 25th and 75th percentiles) while the whiskers represent the range. Whenever these figures have been generated, it has been made clear that they do not represent statistically pooled individual data, but are medians of studies. There were some studies with relevant information that could not be included in the figures as it was reported in such a way that it was not comparable to other studies. In these cases, the data were commented on in the text rather than included in the graphical presentation of results.

4 DESCRIPTION AND METHODOLOGICAL QUALITY OF STUDIES 4.1 Designation of Levels of Evidence and Critical Appraisal The evidence presented in the included studies was classified according to the National Health and Medical Research Council (NHMRC) Hierarchy of Evidence (see Appendix A). Study quality was assessed on a number of parameters such as the quality of methodological reporting, attempts made to minimise bias, sample sizes and their ability to measure ‘true effect’, applicability of results outside of the study sample as well as examining the statistical methods used to describe and evaluate the study data. The included studies are shown in Table 4. Several authors and/or centres have published numerous reports on their experience with post-vasectomy follow-up. As a result there are some studies published by the same group where there are very

* The median is a summary measure of central tendency where 50% of the data are less than the median and 50% are greater.

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likely to be common pools of patients. When the studies have reported the same outcome, the most recent study, or the study with the largest sample size has been used.

4.1.1 Comparative Studies There were two comparative studies included in this review (Table 4). One of these was a non-randomised comparative study with concurrent groups (Level III-2) comparing two different post-vasectomy testing protocols. It was not clear how patients were designated to groups, or why the two groups differed substantially in the number of patients allocated. The other comparative study was a retrospective comparison using chart review (Level III-3) which also compared two post-vasectomy testing protocols at two different hospitals. There was no explanation of the counselling process at these two hospitals and hence the level of instruction to patients may have differed between groups.

4.1.2 Case Series and Reports There were 63 Level IV studies included in the review, of which 53 were case series, six were case reports and four were abstracts or letters (Table 4). In some studies, it was difficult to follow patients from time of vasectomy to time of clearance. In these cases, it was not possible to include these studies in some of the outcomes measured (as described in section 3.3.3). Hence, these studies were only included in the parts of the review where the relevant data could be extracted.

Table 4: Included studies Study Follow-up Relevant Outcomes

Reported in Study N

Level III-2 (Concurrent Non-randomised Controls)

Badrakumar et al. 200014 up to 7 months • Follow-up protocol • Compliance • Outcomes of vasectomy* • Sperm reappearance

Group 1: 961 Group 2: 360

Level III-3 (Retrospective Historical Controls)

Smith et al. 199826

up to 8 months • Follow-up protocol • Histological confirmation • Compliance • Outcomes of vasectomy*

Hosp A: 245 Hosp A (pt 2): 87 Hosp B: 100

Level IV (Case Series)

Alderman 198927 Alderman 198811

up to 8.6 years • Follow-up protocol • Outcomes of vasectomy* • Sperm reappearance

5233

Arango et al. 199328 8 months • Follow-up protocol • Compliance • Outcomes of vasectomy*

313

Bedford and Zelikovsky 197929 19 days • Loss of sperm motility 82

Belker et al. 199030 18 – 38 months • Follow-up protocol • Compliance • Outcomes of vasectomy*

1029

Table continued overleaf…

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Table 4: Included studies (continued) Study Follow-up Relevant Outcomes

Reported in Study N

Benger et al. 199531 up to 36 months • Follow-up protocol • Histological confirmation

633

Black 200232 up to 14 weeks • Follow-up protocol • Compliance • Outcomes of vasectomy*

45123

Bradshaw et al. 200112 30 – 42 months • Follow-up protocol • Compliance • Outcomes of vasectomy* • Sperm reappearance

240

Burnight et al. 197533 at least 2 months

• Compliance 292

Chan et al. 199734 up to 70 weeks • Follow-up protocol • Compliance • Outcomes of vasectomy* • Sperm reappearance

574

Cortes et al. 199735 24 weeks • Outcomes of vasectomy* 38

DeKnijff et al. 199715 3 – 21 months • Follow-up protocol • Compliance • Histological confirmation • Outcomes of vasectomy* • Sperm reappearance

413

Denniston 198536 Up to 7 months • Outcomes of vasectomy*

Edwards 199316 Edwards 197737 Edwards and Farlow 197938

3 weeks – 18 months

• Follow-up protocol • Compliance • Outcomes of vasectomy*

3178

Elliot-Smith Clinic Philp et al. 198439 Davies et al. 199040 Haldar et al. 200041 O’Brien et al. 199542

various • Follow-up protocol • Sperm reappearance • Outcomes of vasectomy*

various

Esho and Cass 197843 Esho et al. 197444

up to 36 months • Follow-up protocol • Histological confirmation • Compliance • Outcomes of vasectomy* • Sperm reappearance

1527

Freund and Davis 196945 7 – 37 days • Outcomes of vasectomy* 13

Jackson et al. 197046 up to 38 weeks • Follow-up protocol • Compliance • Outcomes of vasectomy*

330

Jouannet and David 197847 up to 50 days • loss of sperm motility 76

Lehtonen and Juusela 197348 up to 18 months • Follow-up protocol • Histological confirmation

94

Lehtonen 197549 up to 3 months • Follow-up protocol • Compliance • Histological confirmation • Outcomes of vasectomy*

90


9


Reported in Study N

Leungwattanakij et al. 200150 12 weeks • Follow-up protocol • Compliance • Outcomes of vasectomy*

62

Lewis et al. 198451 3 days • Loss of sperm motility 9

Livingstone 197152 Not stated • Outcomes of vasectomy* 3200

Luke et al. 197953 6 months • Histological confirmation • Compliance • Outcomes of vasectomy*

580

Maatman et al. 199754 up to 12 months + annual tests


1892

Marshall and Lyon 197255 Marshall and Lyon 197256

up to 6 months • Outcomes of vasectomy* • Sperm reappearance

200

Milne et al. 198657 12 months • Follow-up protocol • Compliance • Outcomes of vasectomy*

200

Poddar and Roy 197658 up to ~270 days • Follow-up protocol • Compliance

~1200

Pugh et al. 196959 18 months • Outcomes of vasectomy* 7

Rageth and Leibundgut 198460 3 weeks – 1 year

• Compliance • Outcomes of vasectomy*

247

Rees 197361 up to 60 weeks • Follow-up protocol • Compliance • Outcomes of vasectomy*

903

Richardson et al. 198462 3 – 16 days • Loss of sperm motility 47

Santiso et al. 198163 1 – 3 years • Follow-up protocol • Compliance • Outcomes of vasectomy*

500

Scholmeijer 197564 3 years • Outcomes of vasectomy* 463

Smith 199665 2 years • Outcomes of vasectomy* • Sperm reappearance

850

Surabote 198966 up to 18 months • Follow-up protocol • Compliance • Outcomes of vasectomy*

870

Sherlock and Holl-Allen 198467 up to 4 months • Follow-up protocol 8

Sivanesaratnam 198568 1 – 6 months • Follow-up protocol • Histological confirmation • Outcomes of vasectomy*

916

Spencer and Charlesworth 197669 at least 16 weeks

• Follow-up protocol 831

Staff of Margaret Pyke Centre 197370 Marwood and Beral 197971

18 months • Follow-up protocol • Compliance • Outcomes of vasectomy* • Sperm reappearance

1000


10


Reported in Study N

Tailly et al. 198472 up to at least 296 days

• Follow-up protocol • Histological confirmation • Compliance • Outcomes of vasectomy*

357

Temmerman et al. 198673 6 months • Follow-up protocol • Compliance • Histological confirmation • Outcomes of vasectomy*

100

Thompson et al. 199174 at least 40 weeks


284

van Vugt et al. 198575 up to 48 weeks • Follow-up protocol • Compliance • Outcomes of vasectomy*

3150

Level IV (Case Reports)

Jina et al. 197776 3 years • Outcomes of vasectomy* 1

Khan and Cranston 199777 12 years • Outcomes of vasectomy* 1

Lo et al. 198078 374 days • Outcomes of vasectomy* 1

O’Reilly and Gradwell 200079 10 years • Outcomes of vasectomy* 1

Schirren 198480 7 weeks • Outcomes of vasectomy* 1

Thomson et al. 199381 5 years • Outcomes of vasectomy* 1

Level IV (Abstracts and Letters)

Eisner et al. 200182 at least 22 weeks


443

Lee and Paterson 200117 not stated • Follow-up protocol • Compliance • Outcomes of vasectomy*

462

Schraibman 197383 up to 15 months • Follow-up protocol • Outcomes of vasectomy*

223

Foley et al. 199884 at least 3 months

• Outcomes of vasectomy* 230

* Outcomes of vasectomy include the number of patients reaching azoospermia, azoospermia at first samples and second samples, loss of sperm motility, reappearance of sperm and pregnancy. Studies were used in each section when data was available (see Appendix C for more detail).

11

5 RESULTS 5.1 Post-Vasectomy Semen Analysis Protocols There were 34 studies that reported at least some detail of the PVSA test protocol used (see Table 4). The protocols used by different clinics and practitioners were highly variable. They differed in the criteria for success of the vasectomy procedure, the number of tests required, the timing of the tests and whether this timing was dependent on the time elapsed since vasectomy or number of ejaculations since vasectomy.

5.1.1 Criteria for Success Table 5 shows the success criteria in the 30 studies where this was reported. Multiple studies by one practitioner or clinic were pooled and treated as one study. Most clinics/practitioners (87%) required azoospermia as the endpoint for vasectomy. However, some (10%) gave clearance to patients who exhibited either azoospermia or only a few non-motile sperm. These outcomes are based on the protocols reported in the papers and not decisions made based on the results of PVSA. Hence, it does not include the four studies where “special clearance” was eventually given to patients with persistent non-motile sperm. 12,27,30,40

The studies were examined to determine if there was any trend by country or year of publication in the definition of sterility used. Studies from the UK accounted for 16 out of the 34 studies, all of which used azoospermia as the definition of sterility (although those practitioners from the Elliot-Smith clinic38-42,77,85 subsequently gave patients special clearance when persistent non-motile sperm were present). There did not appear to be any other trends.

Table 5: The criteria for success of vasectomy used and number of studies utilising those criteria.

Definition of sterility n=30 % Azoospermia 26 86.7 Azoospermia or a few non-motile sperm 3 10.0 ‘Negative’ samples 1 3.3

5.1.2 Testing The minimum number of tests requested of patients also differed considerably. Table 6 shows the minimum number of tests requested in the 32 studies where this aspect of the PVSA protocol was described. Patients were usually required to submit further specimens if the initial results did not comply with the clearance criteria of their practitioner/clinic but these additional tests are not included here. Many practitioners/clinics (72%) requested two initial tests (more if positive). However, 22% requested only one test and 6% requested three.

There did not appear to be any trends in the number of tests requested when comparing protocols from different countries or through time.

12

Table 6: The minimum number of post-vasectomy semen analyses required by practitioners or clinics.

Number of tests n=32 % 1 7 21.9 2 23 71.9 3 2 6.2

Note: Badrakumar 200014was counted in two different categories as two different groups used different protocols. DeKnijff 197715 required two tests, but only 2nd test needed to be negative. While the number of tests required varied among the studies, the timing of those tests (and what the timing is based on) also varied. Table 7 shows the timing of both the first and second test (where specified in the studies). Most studies (81%) required an initial test in the first 16 weeks post-vasectomy (34% for <12 weeks, 47% 12-16 weeks). Only 5% requested initial samples be provided more than 16 weeks post-vasectomy. The total proportion of studies where the PVSA timing was based on the time that had elapsed since vasectomy is 87%. The remaining practitioners based the timing of the initial sample on the number of ejaculations post-vasectomy (13%). Note that in two studies16,36,37 both time and number of ejaculations since vasectomy were used in combination to determine when samples should be provided (these studies are counted in all relevant categories in table 7).

Table 7: The timing of post-vasectomy semen analyses used by different practitioners for the first two tests, where reported.

Timing of tests n=38 % Test 1: <12 weeks 13 34.2 12-16 weeks 18 47.4 >16 weeks 2 5.2 after # of ejaculations 5 13.2 Test 2: n=27 <12 weeks 4 14.8 12-16 weeks 18 66.7 >16 weeks 5 18.5

Note: Some studies are counted in more than one category (Badrakumar et al. 200014(2 groups testing at different times), Smith et al. 199826 (2 hospitals testing at different times), Edwards 199316and Denniston36(tests based on time since vasectomy and number of ejaculations) and Jackson et al. 197046 (protocol changed over time)). 5.1.3 Histological Confirmation Only eight studies reported routine histological testing of resected vas (Table 8). One study reported that confirmation of the vas deferens being resected could not be made (in 4/92 patients) and repeat vasectomies were performed.48 One additional study (not tabulated) reported that one of the 32 repeat vasectomies performed at Southmead Hospital was due to a negative histological examination (however, histological examination was not performed routinely). Histological examinations were often used when repeat vasectomies were performed in an attempt to identify causes of vasectomy failure.15,61,67,76

13

Table 8: Studies that routinely sent resected vas for histological examination.

Study Results of examination

Smith et al. 199826 (2 hospitals)

Hospital A: histological examination not always conducted. Hospital B: one patient with motile spermatozoa at 6 months did not require re-exploration as histological examination was positive.

DeKnijff et al. 199715 Only results of repeat vasectomies reported.

Esho et al. 197444; Esho & Cass 197843

Only reports results of patients requiring repeat vasectomy (all positive for vas).

Lehtonen & Juusela 197348; Lehtonen 197549

Lehtonen & Juusela 1973: Confirmation could not be made with certainty on 1 side for 4/92 patients, repeat vasectomies performed and histological examinations were positive in all 4. Lehtonen 1975: Positive in all cases.

Luke et al. 197953 Not reported.

Sivanesaratnam 198568 Positive in all cases.

Tailly 198472 Not reported.

Temmerman 198673 Positive in all cases.

5.2 Compliance There were 29 of the 65 included studies (shown in Table 4) that provided information about patient loss from follow-up. Table 9 shows the proportions of patients who completely failed to comply (no samples provided), partially complied (some but not all samples provided) or fully complied with the post-vasectomy follow-up protocol. Between 33% and 100% of patients fully complied (median 77%). The median percentage of patients not providing any post-vasectomy samples was 19% (range 0-63%) and the median percentage of patients who partially complied was 5% (range 0-41%). The percentage of patients failing to follow-up at some point ranges from 0 to 66.8% (median 24%).

14

Table 9: Percentages of patients who complied with the post-vasectomy semen analysis testing protocol and those who failed to follow-up.

Loss to follow-up

Number of men with vasectomy

No follow-up

%

Partial follow-up

%

Total lost to follow-up

%

Fully complied

% Badrakumar et al 200014 Group 1 n = 961 15.7 0.6 16.3 83.7 Badrakumar et al 200014 Group 2 n = 1321 18.3 10 28.3 71.7 Smith et al. 199826 Hosp A n = 245 23.7 Not stated Not stated Not stated Smith et al. 199826 Hosp AII n = 87 20.7 0 20.7 79.3 Smith et al. 199826 Hosp B n = 100 24 0 24 76 Arango et al. 199328 n = 313 19.8 4.5 24.3 75.7 Belker et al. 199030 n = 1029 36.4 8.2 44.6 55.4 Black & Francome 200232 n = 45123 Not stated Not stated 7.3* 92.7 Bradshaw et al. 200112 n = 240 14.2 13.3 27.5 86 Burnight et al. 197533 n = 292 48.3 0 48.3 51.7 Chan et al. 199734 n = 574 5.9 4.5 10.5 89.6 DeKniff et al. 199715 n = 413 4.4 9.4 13.8 86.2 Edwards 199316 n = 3178 28.9 0 28.9 71.1 Eisner et al. 200182 n = 443 24.6 41.1 65.7 34.3 Esho et al. 197444; Esho and Cass 197843 n = 1527 13.8 0 13.8 86.3 Jackson et al. 197046 n = 200 6.0 4.0 10.0 90.0 Lee and Paterson 200117 n = 462 0 0 0 100 Lehtonen 197549 n = 90 0 0 0 100 Leungwattanakij et al. 200150 n = 62 22.6 0 22.6 77.4 Luke et al. 197953 n = 580 37.1 1.4 38.5 61.6 Maatman et al. 199754 n = 1892 34 32.7 66.8 33.3 Staff of Margaret Pyke 197370 n = 1000 Not stated Not stated 7.1* 92.9 Milne et al. 198657 n = 200 9.0 0 9.0 91.0 Poddar and Roy 197658 n =~1200 62.5 0 62.5 37.5 Rageth and Leibundgut 198460 n = 247 25.5 0 25.5 74.5 Rees 197361 n = 903 5.9 30.5 36.3 63.7 Santiso et al. 198163 n = 500 26.2 0 26.2 73.8 Surabote 198966 n = 870 59.8 0 59.8 40.2 Tailly et al. 198472 n = 357 9.8 2 11.8 88.2 Temmerman et al. 198673 n = 100 3 39 42 58 Thompson et al. 199174 n = 284 5.3 8.8 14.1 85.9 van Vugt et al. 198575 n = 3150 0 1.2 1.2 98.8 Median 19.05 1.2 24 77.4 Minimum 0 0 0 33.3 Maximum 62.5 41.1 66.8 100 Note that different groups from single studies were considered separately, hence 2 studies14,26 are counted twice in this data set. * Stage of loss from follow-up not reported.

15

To determine whether the number of tests in the various standard PVSA protocols for the different clinics influences the percentage of patients returning for follow-up, the studies reporting both the number of PVSA tests and the number of patients who complied with follow-up were considered. There were 24 studies that reported both of these details. Figure 1 shows the median percentage of patients who fully complied with the PVSA protocol against the number of tests required. There does not appear to be any difference in the compliance based on the number of tests in the PVSA protocol.

Some authors12,14 have argued that requiring a second test to confirm sterility further reduces the number of patients complying with the test protocol. To explore this further, the studies that reported the number of patients complying with a request for a second sample (19 studies) were compared to those complying with a request for a first sample (29 studies). The percentage of patients providing a first test and those providing a second test is shown in figure 2. A median of 81.7% patients supplied a first sample (range 40.2 – 100%) and a median of 86.2% patients supplied a second sample (range 33.2 – 100%). There was no decrease in compliance when a second sample was requested. It may be possible that patients who have had an initial positive sample are anxious to obtain a negative result and are more likely to provide a second sample, and this may offset the expected decrease in compliance. On closer inspection of the study by Surabote66, there is no clear indication as to why the compliance was so much lower compared to other studies.

1189N =

Minimum number of tests

321

% fu

ll co

mpl

ianc

e

100

80

60

40

20

Figure 1: The median percentage of patients who fully complied with the PVSA protocol against the number of tests required in the protocol of the clinic they attended. Boxes show interquartile range (i.e. 50% of the studies), error bars show range. N shows the number of studies.

16

13629N =

% p

rovi

ding

sam

ple

100

80

60

40

20

Surabote 1989

2nd test (B)

2nd test (A)

1st test

Figure 2: The median percentage of patients supplying a first and second sample in 48 studies requiring 2 samples. Boxes show interquartile range (i.e. 50% of the studies), error bars show range. Circle represents a study considered as an outlier (cases with values between 1.5 and 3 box lengths from the upper or lower edge of the box). N shows the number of studies. Note: Two types of studies were included in this graph: those requiring two tests and those requiring only one test to be cleared. 1st test: represents the 1st (or only) test irregardless of the number of tests required by the testing protocol. 2nd test (A): represents those patients submitting a 2nd test after a positive initial test when the protocol recommended only one test (% of patients of those who required a 2nd test). 2nd test (B): represents those patients submitting a 2nd test as recommended by a protocol of two tests. Figure 3 shows the median percentage of patients (for the studies) who fully complied with the test protocol of the clinic they attended against the time of the first post-vasectomy semen test. Again, although not tested statistically, the three categories appeared to be comparable. Note that only two studies were included in the 5-6 month category. Similarly, figure 4 shows the median percentage of patients who fully complied against the time of the last test in the standard PVSA protocol. The timing of the last test may be seen by patients as the earliest ‘official’ time that sterility could be confirmed. These results show a slight decrease in the percentage of patients complying when the timing of the final test was at 5-6 months post-vasectomy. Again, there is a lot of variability between the different studies, and the difference in medians is unlikely to be significant. Upon closer inspection of the two outlier studies, there is no obvious reason as to why the compliance in these studies are so different to the others.

17

2139N =

Time of first test (months)

5-63-40-2

% fu

ll co

mpl

ianc

e100

80

60

40

20

Figure 3: The median percentage of patients who fully complied with the PVSA protocol against the time of the first sample required by the clinic they attended. Boxes show interquartile range (i.e. 50% of the studies), error bars show range. N shows the number of studies.

3114N =

Time of last test (months)

5-63-40-2

% fu

ll co

mpl

ianc

e

100

80

60

40

20

Surabote 1989

Eisner et al. 2001

Figure 4: The median percentage of patients who fully complied with the PVSA protocol against the time of the last sample required by the clinic they attended. Boxes show interquartile range (i.e. 50% of the studies), error bars show range. Circles represent 2 studies considered as outliers. N shows the number of studies.

18

5.3 Outcomes The following sections investigate both azoospermia and the loss of sperm motility as vasectomy outcomes. 5.3.1 Azoospermia Table 10 shows the median number of patients demonstrating azoospermia when the timing of tests was based on either the time elapsed since vasectomy (30 studies) or number of ejaculations since vasectomy (5 studies). As shown in table 10, regardless of whether the PVSA test protocol was based on time elapsed since vasectomy or the number of ejaculations, nearly 100% of patients eventually demonstrated azoospermia. The minimum of 10.5% azoospermic patients in the studies based on number of ejaculations is due to one study starting PVSA after only 4 ejaculations. Table 10: The median percentage of patients reaching azoospermia in studies where timing of tests was based on time since vasectomy and number of ejaculations since vasectomy.

Timing of tests based on time (months) elapsed since vasectomy: % azoospermic

n = 30 studies median 98.23 minimum 80.73 maximum 100 Timing of tests based on number ejaculations since vasectomy:

n = 5 studies median 99 minimum 10.5 maximum 100

Note that the percentage of patients reaching azoospermia was calculated from those patients who supplied at least 1 post-vasectomy semen sample. Note that 1 study64 is included in both groups as both time elapsed and number of ejaculations were used to determine the timing of tests. Twenty-five studies reported the percentage of patients achieving azoospermia by the timing of the first PVSA test. Figure 5 shows the percentage of patients demonstrating azoospermia in their first sample against the time after vasectomy that the samples were provided. Many of these studies (44%, 11/25) tested men at 3 months post-vasectomy. In these 11 studies the percentage of patients reaching azoospermia ranged from 51% to 98% with a median of 81%. There were no clear time trends. Upon closer inspection of the outlier (Milne et al.57) there is no obvious reason why the percentage of patients reaching azoospermia at the first test in this study is so different to other studies. Figure 6 shows the percentage of patients demonstrating azoospermia in their first sample against the number of ejaculations since vasectomy for those studies where this was the criterion on which testing was based and where data could be extracted (n=3).

19

321112411N =

Time after vasectomy (months)

643.5321.51.5

% a

zoos

perm

ic

100

90

80

70

60

50

40

30

20

10

0

Milne et al. 1986

Figure 5: Median percentage of patients demonstrating azoospermia in first sample against time of first sample. Boxes show interquartile range (i.e. 50% of the studies), error bars show range. Circle represents a study considered as an outlier. N shows the number of studies. Note that % azoospermic was based on the number of patients who actually provided post-vasectomy samples. For those studies where a time range (for example 3 – 4 months) was stated, the upper limit of the range was used.

0

20

40

60

80

100

0 10 20 30 4

No. of ejaculations before 1st test

% a

zoos

perm

ic

0

Figure 6: Percentage of patients demonstrating azoospermia in first sample against number of ejaculations post-vasectomy (until first sample). Note that each point is a single study. Note that % azoospermic was based on the number of patients who actually provided post-vasectomy samples.

20

To examine the effect of requesting a second PVSA test on the percentage of azoospermic patients (i.e. to examine the value of a second test), the papers that reported the percentage of patients reaching azoospermia at the first and second test, as well as reporting the timing of these two tests, were considered (n=6; figure 7). All studies showed an increase in the percentage of patients reaching azoospermia when a second sample was provided. The largest increase in patients reaching azoospermia was 47.7%. This was between a first test at 0.5 months (6.7% azoospermic) and a second test at two months (54.4% azoospermic). The smallest increase in patients reaching azoospermia was 7.2%. This was the difference between a first test at three months (83.7% azoospermic) and a second test at five months (90.9% azoospermic). The maximum percentage of azoospermic patients after two tests was 97.5% (where the second test occurred four to five months post-vasectomy). The minimum was 54.4% after a second test that occurred only two months after vasectomy (and 1½ months after the first test).

0

20

40

60

80

100

0 1 2 3 4 5 6 7

% a

zoos

perm

ic

studies

Figure 7: The percentage of patients reaching azoospermia in the first (♦) and second test (■), for tests based on time since vasectomy (for 6 studies). The numbers above and below the points represent the number of months since vasectomy that testing occurred.

To determine the number of ejaculations required to reach azoospermia, those studies documenting the percentage of patients (who provided a number of tests over time) reaching azoospermia based on the number of ejaculations since vasectomy were considered (Fig 8, n=3 studies). There was not much overlap in the data provided by the three studies. However, it seems that between 11 and 20 ejaculations are probably required to reach azoospermia in 80% of patients.

Figure 8: The percentage of patients reaching azoospermia based on number of ejaculations after vasectomy.

0

20

4060

80

100

0 5 10 15 20 25 30

# ejaculations after vasectomy

% p

atie

nts

azoo

sper

mic

♦ Freund and Davis (1969) n = 13 patients ■ Marshall and Lyon (1972) n = 200 patients ▲ Lee and Paterson (2001) n = 462 patients

Key to studies

1. Lehtonen & Juusela 1973 2. Sivanesaratnam 1985 3. Esho & Cass 1978 4. Alderman 1989 5. Arango et al. 1993 6. Chan et al. 1997 0.5

2

2

2

3 4 - 554.53 - 4

33

1

21

5.3.2 Persistent Non-Motile Sperm Many studies reported patients who did not achieve azoospermia. Table 11 shows the number of patients who demonstrated persistent non-motile sperm after vasectomy (1.4%, 205/14 845). Some of these patients eventually reached azoospermia. Table 11: Patients demonstrating persistent non-motile sperm after vasectomy.

No. of patients

providing samples

No. of patients with

persistent non-motile sperm (%)

Time after vasectomy Details

COMPARATIVE STUDIES Smith et al. 199826 (Hosp A)

187 4 (2) 6 months 1/4 patients required re-exploration

Smith et al. 199826 (Hosp AII)

69 7 (10) 6 months All negative by 8 months

CASE SERIES Alderman 198811 8879* 10 (0.1) 8/8879 297 – 448

days 1/8879 14 months 1/8879 260 days

4/10 eventually cleared 5/10 given “cautious assurance” 1/10 not known

Arango et al. 199328

237 1 (0.4) 8 months

Belker et al. 199030 654 3 (0.5) 7 – 12.5 months 1/3 had repeat vasectomy at 7 months 1/3 had repeat vasectomy at 9 months 1/3 given special clearance at 12.5 months, eventually reached azoospermia at 32 months.

Bradshaw et al. 200112

206 4 (2) Not stated Were deemed infertile on the basis of intermittent azoospermic specimens.

Chan et al. 199734 540 2 (0.4) 26 and 44 weeks Both had repeat vasectomy Cortes et al. 199735 35 2 (6) 24 weeks 1/2 reached azoospermia at

7 months. 1/2 showed very low levels of non-motile sperm.

DeKnijff et al. 199715

395 4 (1) 5 – 10 months

Esho et al. 197444 770 1 (0.1) 7 months Had repeat vasectomy. Jackson et al. 197046

200 6 (3) 3/6 up to 38 weeks

Rageth and Leibundgut 198460

184 5 (3) > 1 year All eventually negative.

Schraibman 197383 223 3 (1) Reached azoospermia at

12, 14 & 15 months.

Sivanesaratnam 198568

916 4 (0.4) 6 months Repeat vasectomies performed.

Staff of Margaret Pyke Centre 197370

1000 143 (14) 6 – 18 months

Surabote 198966 350 6 (2) Reached azoospermia at 6, 7, 8, 9, 12 & 18

months

* No. of vasectomies performed. Loss from follow-up not reported.

22

5.3.3 Loss of Sperm Motility Four studies investigated the time taken after vasectomy for motile sperm to disappear from samples. Figure 9 shows the percentage of motile sperm in samples against the time since vasectomy. Motile sperm was found in the semen samples for up to (and including) 16 days after vasectomy. No motility was observed in any of these studies after this point.

0

20

40

60

80

100

0 10 20 30 40 50

time after vasectomy (days)

% s

perm

mot

ility

♦ Bedford and Zelikovsky (1979) n = 23, 50 & 5 patients at 3 different times ■ Jouannet and David (1978) n = 76 patients ▲ Lewis et al. (1984) n = 9 patients × Richardson et al. 1984 n = 40 patients

Figure 9: The percentage of motile sperm based on the number of days after vasectomy.

There were three studies that used loss of sperm motility as the criteria for sterility (Section 5.1.1). Edwards16 found that 95.1% (n=324) of patients were either azoospermic, or demonstrated only non-motile sperm, 3 weeks after vasectomy. Leungwattanakij et al.50 reported that 12 weeks post-vasectomy, 83.9% (n=62) of patients had no motile sperm in their samples. Van Vugt et al.75 reported that after 10 ejaculations 98% (n=3150) of patients were either azoospermic or had only non-motile sperm in their samples. Two studies investigated the ability of sperm from post-vasectomy samples to penetrate zona-free hamster eggs51,62 Lewis et al.51 tested the penetration of 8 post-vasectomy samples (that contained motile sperm) and reported that none of the sperm were successful in penetrating the zona-free hamster eggs. In seven of these eight cases, the sperm were no longer motile after the incubation period. Richardson et al.62 found a significant difference between the percentage of zona-free hamster eggs penetrated between pre- and post-vasectomy samples (pre-vasectomy, mean 49.7%, standard error 6.4; post-vasectomy, mean 20.6%, standard error 6.0; P<0.001). They reported that the ability to fertilise eggs was not correlated with post-vasectomy interval and that sperm capable of fertilising eggs were present for up to 8 or 12 days (although the vasectomy of the patient who provided the sample capable of penetrating eggs at 12 days was later deemed a failure).

23

5.3.4 Reappearance of Sperm After Azoospermia Ten studies reported the reappearance of sperm in patients who had demonstrated azoospermia in a previous sample.12,14,15,26,27,34, 41,44,56,70 Figure 10 shows the percentage of patients who had a reappearance of sperm after azoospermia against the time since vasectomy. In those studies where the reappearance of motile sperm occurred after azoospermia had been demonstrated, the vasectomy was either deemed a failure (by the practitioner/clinic) or recanalisation was assumed to have taken place. These studies were not included in the graph. In one study,56 seven patients were found to have reappearance of motile sperm at up to 4.25 months after azoospermia had been shown and in all cases azoospermia was eventually reached. It was suggested that spontaneous recanalisation had occurred followed by spontaneous reocclusion of the vas deferens, probably by scar formation. Temporary reappearance of motile sperm was not reported in any of the other included studies. The reappearance of non-motile sperm after azoospermia was reported in seven studies.12,15,27,34,44,56,70 Non-motile sperm reappeared up to 22 months post-vasectomy and up to 17 months after azoospermia was demonstrated.

■ non-motile sperm ▲ motility not reported

0

2

46

8

10

0 10 20 30 40

Time since vasectomy (months)

% p

atie

nts

with

spe

rm

Figure 10: The percentage of patients (of those providing a sample) who demonstrated a reappearance of sperm after azoospermia in a previous sample. Some studies are represented by more than one point as reappearance may have been detected at different times. Reappearance of motile sperm is not shown (see text for explanation).

5.3.5 Recanalisation and Vasectomy Failure To investigate the incidence and timing of recanalisation and vasectomy failure, studies reporting these aspects were considered (Table 12). Pregnancies were not included (see section 5.3.6) except in cases where it led to further testing of the patient’s semen. Failures that were due to patients not following instructions regarding use of contraception before sterility was achieved (‘user failures’) were not included. Cases of persistent non-motile sperm that were not considered failures (by the authors) were also not included (see section 5.3.2). There were 28 studies that reported a total of 183 failures or recanalisation. It is difficult to distinguish between some cases of failure (where azoospermia was never reached) and early recanalisation as initial test results were not always reported. It is also difficult to determine the point of diagnosis given the variability in the time it takes to reach azoospermia.

24

Table 12: Details of recanalisation and vasectomy failure (persistent motile sperm)

No. of patients

providing samples

No. of recanalisations or failures (%)

Time after vasectomy and details

CASE SERIES Alderman 198811

5331 97 (1.8) 32 ‘early overt failures’ (continuous significant number of sperm or any motile sperm later than 4 months after vasectomy, motility not known), 3

had initial negative tests. 4 spontaneous recanalisations, 4.5 – 8.6 years post-

vasectomy. 61 ‘technical failures’ (non-significant,

<100x106/L, 59 with persistent non-motile sperm since vasectomy eventually given ‘cautious

assurance’ of success, other 2 had initial clearance before reappearance of non-motile sperm (‘late

technical failures’).

Belker et al. 199030

654 1 (0.2) Initial test never submitted, motile sperm found at 67 months post-vasectomy.

Benger et al. 199531

633 1 (0.2) Late recanalisation.


206 2 (1) Timing not reported.

Chan et al. 199734

574 4 (0.7) 2 had persistent non-motile sperm; 2 had persistent motile sperm;

all diagnosed as failures. Cortes et al. 199735

38 1 (2.6) Testing (after pregnancy) at 5 months showed motile sperm, recanalisation.


395 5 (1.3) Persistent unchanged concentrations of non-motile sperm at 12 weeks, considered failures. 3 had motile sperm at 12 weeks, early

recanalisation diagnosed. Denniston 198536

2500 9 (0.4) 1 had motile sperm at 7 months, timing of recanalisation or failure not known.

5 had persistent motile sperm, technical failures. 3 had persistent motile sperm but had not followed

instructions. Edwards 197737 183 1 (0.5) 11 weeks, recanalisation diagnosed, repeat

vasectomy performed. Edwards 199316 2260 5 (0.2) Case 1: 6 & 16 weeks, operative failure.

Case 2: 6, 10, 14 & 16 weeks, early recanalisation. Case 3: 26 & 29 weeks, early recanalisation. Case 4: 5, 8 & 12 weeks, late recanalisation.

Case 5: 18 months, timing of failure or recanalisation unknown.

Esho et al. 197444

770 9 (1.2) 6 diagnosed as early recanalisations, sperm present in all samples (initial tests at 2, 3 or 5 months).

3 diagnosed as late recanalisations, sperm present at 9, 11 & 13 months.

Haldar et al. 200041 Elliot Smith Clinic

2250 2 (0.1) 1 underwent repeat vasectomy and sperm granuloma found, results of other case not

reported.

Lehtonen and Juusela 197348

94 5 (5.3) Initial tests showed sperm (at 1, 6 (x2), 9 & 12 months), recanalisation confirmed histologically in 2 patients.


25

Table 12: Details of recanalisation and vasectomy failure (persistent motile sperm) (continued)

No. of patients

providing samples

No. of recanalisations or failures (%)

Time after vasectomy and details

Lehtonen 197549

90 1 (1.1) Normal numbers of sperm at 2 months, recanalisation found.

Livingstone 197152

3200 vasectomies

(loss to follow-up not stated)

4 (0.1) 1st failure: 2 months post-vasectomy, sperm present after pregnancy reported. 2nd failure: recanalisation, timing not reported. 3rd & 4th cases: persistent sperm present, timing not reported.

Maatman et al. 199754

1248 21 (1.7) Persistent sperm present, 6 pregnancies reported, all considered failures and underwent repeat vasectomies.

Marshall and Lyon 1972a56

400 7 (1.8) 2, 3, 4, 6, 8, 9 & 17 weeks, temporary reappearance of motile sperm, all reverted to azoospermia.

Milne et al. 198657

172 8 (4.7) Patients never reached azoospermia, motility not reported, considered failures, reasons not reported.

Philp et al. 198439 Elliot Smith Clinic

14,047 vasectomies

(loss to follow-up not stated)

6 (0.04) Recanalisation discovered after pregnancies reported at 16, 20, 21, 34 (x2) & 36 months. Motile sperm found in 5/6, non-motile sperm found in 1/6 (but test delayed in this case).

Pugh et al. 196959

Not stated 7 Case 1: sperm present at 6 & 13 weeks. Case 2: sperm present at 4 & 12 weeks. Case 3: sperm present at 10 months after pregnancy reported. Case 4: sperm present at 3 & 4 months. Case 5: sperm present at 5 months. Case 6: sperm present at 10 months after pregnancy reported. Case 7: occasional perm present at 3 months (pregnancy reported at 1 month). All underwent repeat vasectomy.

Rees 197361 850 3 (0.4) Persistent sperm in samples, histological examination confirmed recanalisation.

Sherlock and Holl-Allen 198467

Not reported 8 All showed motile sperm after pregnancy reported at 3.5 (x2), 4, 4.5, 5 (x2), 5.5 & 6 years post-vasectomy. Sperm granulomas found in 1 side in all patients.

Staff of Margaret Pyke Centre70

1000 6 (0.6) 1 patient had 3rd vas deferens, 5 showed granuloma; all had motile sperm at 3 or more months.

Surabote 198966 350 4 (1.1) Motile sperm in samples, diagnosed as recanalisation, timing not reported.

Temmerman et al. 198673

97 2 (2.1) Motile sperm found at 6 months, both underwent repeat vasectomy.

van Vugt et al. 198575

3150 19 (0.6) 1 diagnosed at 6 weeks, no sperm (or non-motile) at 1st test, then motile. Other 18 had motile sperm from 1st test (after 10 ejaculations), failures.

CASE REPORTS Jina et al. 197776

Not stated 1 Sperm found in sample after pregnancy reported at 3 years post-vasectomy.

Khan and Cranston 199777

Not stated 1 Sperm found in sample after pregnancy reported at 12 years post-vasectomy.

Note: cases of persistent non-motile sperm (see Table 11) and pregnancy (although pregnancy led to the discovery of some failures) (see Table 13) not included in this table.

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Pregnancy Table 13 shows the details of pregnancies reported. There were a total of 69 pregnancies reported in 20 studies (14 case series and 6 case reports). When considering the studies in which the number of vasectomies performed was reported, there were 60 pregnancies after 92,184 vasectomies (0.07%).

In 27 of the 69 pregnancies, patients had demonstrated azoospermia in at least one PVSA test. Only seven of the pregnancies (from two studies) had paternity confirmed by DNA analysis. Further semen analyses were reported for 22 patients after pregnancy was confirmed. Motile sperm was found in 10 of these cases, and non-motile sperm in two.

Table 13: Details of the pregnancies reported.

No. of vasectomies

No. of pregnancies

(%)


CASE SERIES Alderman 198811 5331 4 (0.08)

2 (0.04)

4.5 – 8.6 years

3 & 9 years

All had provided 2 consecutive azoospermic tests. All showed motile sperm. 1 patient had 1 negative test (only submitted 1); showed azoospermia at time of pregnancy but occasional non-motile sperm 3 months later. 2nd patient showed occasional non-motile sperm.

Belker et al. 199030

1029 2 (0.19) 29 and 67 months

Neither had submitted PVSA samples; 1 patient showed many motile sperm (67 months); 2nd patient refused further testing.

Black 200232 45,123 15 (0.03) Not stated 13/15 had provided 2 consecutive azoospermic samples.

Cortes et al. 199735

38 2 (5.26) 1 & 5 months

One patient discontinued PVSA while motile sperm still present (1 month); 2nd patient azoospermic at weeks 2, 3 & 4.


413 1 (0.24) Not stated Unprotected intercourse before 12 week PVSA.

Edwards 199316 3178 2 (0.06) Not stated 1 was late recanalisation; 1 patient had not supplied PVSA sample.

Livingstone 197152

3200 1 (0.03) 2 months Had initial negative PVSA.

Maatman et al. 199754

1892 8 (0.42) Not stated None of these patients met criteria for sterility.

Marshall and Lyon 197256

400 1 (0.25) 4 months Had histological confirmation. Had provided 2 consecutive azoospermic samples (last at 2 months). Motile sperm present when pregnancy confirmed, then returned to azoospermia.

Philp et al. 198439

16,796 6 (0.04) 16, 20, 21, 34, 34 &

36 months

All had provided 2 consecutive azoospermic samples.


27

Table 13: Details of the pregnancies reported (continued)

No. of vasectomies

No. of pregnancies

(%)


Pugh et al. 196959 ? 3 1, 10 & 10 months

Occasional sperm present in 1st patient at 1 month; 2nd patient was azoospermic at 2 months, sperm in sample when pregnancy confirmed; 3rd patient azoospermic at 10 & 12 weeks, sperm in sample when pregnancy confirmed.

Santiso et al. 198163

500 9 (1.8) 5 in 1st year, 1 in 2nd year, 3 in 3rd year or more.

Not stated.

Smith 199665 14,000 6 (0.04) All DNA proven with negative semen analyses.

Thompson et al. 199174

284 1 (0.35) 4 months Patient was given clearance.

CASE REPORTS Jina et al. 197776 1 1 3 years Patient had normal number motile

sperm. Khan and Cranston 199777

1 1 (twice) 18 months and then 12 years

2 azoospermic tests at 16 & 18 weeks, pregnancy at 18 months, 2 subsequent tests negative, another pregnancy at 12 years, sperm count 14 x 106/ml.

Lo et al. 198078 1 1 8 weeks Patient resumed intercourse before motile sperm disappeared from semen.

O’Reilly and Gradwell 200079

1 1 10 years Paternity confirmed by DNA analysis, semen analysis after birth negative for sperm.

Schirren 198480 1 1 48 days No post-vasectomy samples requested, accusation (by patient) of PVSA not carried out, poor consultation.

Thomson et al. 199381

1 1 3 years 2 azoospermic samples at 12 and 18 weeks, 5 subsequent samples showed small numbers of non-motile spermatozoa, azoospermic 5 years post-vasectomy.

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6 DISCUSSION Most of the included studies (63 of 65) were of Level IV evidence. The other two studies were Level III-2 and III-3. Overall, the evidence-base is rated as poor.

One of the major limitations in this review was the lack of comparability of the included studies. Many of the studies used different post-vasectomy testing protocols and reported different outcomes. The poor compliance in some studies also made it difficult to determine the outcomes of those patients and whether the results of missing patients have been similar or different to those who complied. In many cases it was possible to use only a small subset of the studies to investigate various aspects of post-vasectomy semen testing. This makes it difficult to formulate strong conclusions about these aspects.

6.1 Compliance There were large losses to follow-up in many studies with some studies reporting up to 66% loss. Patients may fail to follow-up for a variety of reasons including embarrassment, inconvenience, certainty of sterility/trust in the surgeon, inadequate understanding of the protocol and forgetfulness.74,86 The variability in follow-up did not appear to be related to the number of PVSA tests, the time of the first test or the time of the last test. It is difficult to ascertain why some clinics/practitioners obtained higher compliance rates than others but it is possible the rates were influenced by the counselling and reminder services offered. Although some authors12,14 have suggested that requesting a second sample reduces compliance, the evidence shows that there was no substantial difference in the proportion of patients supplying first and second samples. There was a slight increase in the patients who submitted a second test after a positive initial test (when the protocol recommended only one test). It is possible that the expected decrease in patients complying with a second test is offset by those patients more anxious for a second test because of an initial positive result. These results suggest that patients who are going to comply, do so regardless of the protocol. 6.2 Outcomes There was high variability in the percentage of patients reaching azoospermia at the first sample, even between studies at the same periods in time. For example, for first tests at three months, the percentage of azoospermic patients ranged from 51% to 98%. Although there was high variability, the median consistently stayed over 80% from three months onwards. The variability in the time that patients took to reach azoospermia was expected. It has been suggested that the time taken to reach azoospermia may depend on the age of the patient55,71 and the number of ejaculations since vasectomy (see below). It is possible that there is some interaction between age and number of ejaculations needed to

29

achieve azoospermia. Marshall and Lyon55 showed that younger patients reached azoospermia with fewer ejaculations than older patients. Marwood and Beral71 found that the frequency of ejaculation affected the time taken to reach azoospermia more in older patients than in younger patients, although a frequency of more than three times a week was associated with rapid clearance regardless of age. The age and number or frequency of ejaculations have not been accounted for in many of the studies included above and this may have contributed to the large amount of variability. Other studies also reported that age had a significant effect on the time taken to reach azoospermia.28,34,69 When the timing of the first test was based on the number of ejaculations, more than 80% of patients showed azoospermia after 10 ejaculations. However, only three studies could be included in this aspect of the review and so caution must be exercised when considering these results. Also, age could again be a factor that has not been considered. The studies that reported the percentage of patients reaching azoospermia in repeated tests based on the number of ejaculations showed that more than 20 ejaculations are probably required to achieve azoospermia in 80% of patients. However, once again, this evidence is based on only three studies, with little overlap at any point, and so caution must be exercised when interpreting these results. There were seven studies that reported the percentage of patients demonstrating azoospermia at the first and second tests. In each of these studies there was an increase in the percentage of patients who were azoospermic in the second test, regardless of the timing of the tests. However, this increase tended to get smaller when the tests were conducted later. For example, the largest increase in the percentage of azoospermic patients was between an initial test conducted at two weeks and a second test conducted at two months. The increase was much smaller when the initial tests were performed at three to four months and second tests were performed at four to five months. This is due to the higher percentage of patients demonstrating azoospermia at the first test. The increase in azoospermic patients would obviously get smaller as more tests are conducted until all (or most) patients demonstrate azoospermia. 6.3 Persistent Non-Motile Sperm Table 11 showed that of the patients who supplied post-vasectomy semen samples, 1.4% percent failed to achieve azoospermia. Some of these were failed vasectomies (where motile sperm was still present) but some were cases of patients who persistently demonstrated non-motile sperm in their samples. Some authors have argued that these patients can be considered infertile and should be given a “special clearance”.15,27,30,37,40,58,72 The British Andrology Society10 recommends that patients who have low numbers of non-motile sperm (<100,000/ml) after seven months and at least 24 ejaculations should be given “special clearance”.

30

6.4 Loss of Sperm Motility In Australia, Edwards16,37 has strongly advocated that only a loss of sperm motility is necessary to deem a patient infertile, rather than complete azoospermia. The time taken to achieve loss of sperm motility is variable. However, the evidence suggests that after 16 days post-vasectomy, motile sperm is no longer present in the ejaculate (unless caused by spontaneous recanalisation). Again, this is based on only a few studies. The studies that investigated the ability of sperm to fertilise zona-free hamster eggs demonstrated that sperm were able to fertilise eggs for at 8-12 days post-vasectomy (although the longer time frame was probably due to a vasectomy failure). Although this is based on only two studies, it appears that sperm lose their fertilising potential and motility in a similar time frame. Longer term studies reporting the follow-up of patients who had been given “special clearance” (i.e. contained persistent non-motile sperm in their post-vasectomy semen samples) did not provide evidence of non-motile sperm causing pregnancy.38,40 6.5 Sperm Reappearance, Recanalisation and Vasectomy Failure The reappearance of sperm after azoospermia can be due to a number of factors56 such as spontaneous recanalisation, the incomplete emptying of the vas deferens, or the failure to detect sperm in earlier samples leading to the false conclusion of azoospermia. Obviously, reappearance can only be detected if more than one test is conducted. The temporary reappearance of motile sperm occurred seven times (from 400 patients) and up to 4.25 months after vasectomy. In all cases, azoospermia was eventually reached again. These cases were either due to a failure to detect sperm in earlier samples or the temporary spontaneous recanalisation of the vas deferens. These cases were all from a single study56, and no other study reported a similar occurrence. Reappearance of non-motile sperm was reported in eight different studies and occurred up to 22 months post-vasectomy. The highest rate of sperm reappearance (non-motile) was eight percent (n=184) at four months post-vasectomy.12 Many of the cases of reappearance of non-motile sperm eventuate in azoospermia and hence the reappearance of non-motile sperm is probably due to either the incomplete emptying of the vas deferens or the failure to detect sperm in earlier samples. It is probably not due to recanalisation as the resulting sperm would be expected to be motile. It is difficult to determine the most common timing of early recanalisation. Sperm was shown in initial tests as early as one month post-vasectomy in cases where early recanalisation was diagnosed. Late recanalisation was diagnosed up to 12 years post-vasectomy. Pregnancy The paternity of the pregnancies were confirmed by DNA analysis in very few cases, hence, pregnancy alone is not a very reliable indicator of vasectomy failure. However, it often leads to further PVSA tests, which can demonstrate failure. The pregnancies

31

that were confirmed by DNA analysis demonstrated that vasectomy failure can occur in the long term (10 years for example), regardless of the PVSA protocol employed. These failures are most likely attributable to spontaneous recanalisation.

6.6 Recommendations

There are four main concepts to consider when attempting to make an evidence-based recommendation on the appropriate post-vasectomy testing protocol:

1. The appropriate endpoint of vasectomy (loss of motility or azoospermia?).

Azoospermia is probably the ideal endpoint of vasectomy as measuring loss of motility relies heavily on the patient delivering the sample within a short time of producing it. It also depends on the clinic or laboratory having the necessary resources to examine the samples in the required time interval. Azoospermia is a realistic outcome for the majority of patients.

2. The time taken (or number of ejaculations needed) to clear the vas deferens of existing sperm after vasectomy.

The evidence suggests that approximately 80% of patients are azoospermic after three or four months and after about 20 ejaculations. The timing is variable however, and appears to be dependent on age.

3. The reappearance of sperm (motile or non-motile, permanent or temporary).

Reappearance of motile sperm is likely to be due to spontaneous recanalisation. Reappearance of non-motile sperm can be due to storage of sperm in the vas deferens or the failure to detect sperm in an earlier test. The reappearance of sperm will only be detected if a second test is performed. Only a small proportion of patients demonstrate the reappearance of sperm, and in many cases it is temporary with azoospermia eventually reached.

4. Recanalisation (early and late).

It is difficult to determine the most likely time for early recanalisation to occur. However, it appears that motile sperm have usually been present at the initial post-vasectomy semen tests when early recanalisation was eventually diagnosed. Late recanalisation can occur at any point after azoospermia has been reached.

6.6.1 Recommended Post-Vasectomy Semen Analysis Protocol Figure 11 shows a flow chart of the recommended testing protocol. The evidence presented in this review supports a post-vasectomy testing protocol with only one azoospermic test at three months and after a minimum of 20 ejaculations. If the sample is azoospermic at three months, the patient can be considered sterile and no further follow-up is necessary. If a sample is positive at the three month test, further tests are required. If motile sperm are present, the vasectomy is probably a failure and another test one month later will confirm this (and a decision can be made about re-vasectomy). If non-motile sperm are present, further tests should be performed

32

Vasectomy

Single test at 3 months and after at least 20

ejaculations

Negative No further testing

required

Positive Further testing

required

Non-motile sperm Monthly† testing

required

Motile sperm Probably vasectomy failure.

A 2nd test performed 1 month later will confirm

Positive “Special clearance” if: - 2 consecutive tests show no motile sperm - concentration of non-motile sperm < 100,000/ml - at least 7 months post-vasectomy‡

Motile sperm Vasectomy failure

confirmed

Negative No further testing required

(only 1 negative test required)

~ 80% of patients ~ 20% of patients

Figure 11: Flow chart of the proposed post-vasectomy testing protocol.

† The proposal of monthly testing after a positive sample is not evidence-based. It is an arbitrary time period chosen to potentially allow enough time and ejaculations to clear the vas deferens of any remaining sperm. ‡ The pre-requisites for special clearance in this proposal have been based on those in the British Andrology Society guidelines of post-vasectomy semen analysis.10

33

monthly until either an azoospermic sample is provided or “special clearance” (due to persistent non-motile sperm) can be given. Special clearance could be given when the patient has provided two consecutive samples containing < 10,000 sperm/ml (non-motile) at least seven months post-vasectomy.

Approximately 80% of patients would be cleared after one test and the remaining 20% can continue follow-up until cleared, as described above. Vasectomy failures will be detected at the three month test and hence, histological testing of the vas deferens are not necessary (however, they may be useful in a training situation).

Further research with consistent testing at three months post-vasectomy and with confirmation of at least 20 ejaculations would confirm the overall percentage of patients who reach azoospermia by that point in time. This would allow further development of the most effective post-vasectomy testing protocol.

6.7 Cost Considerations in Australia The post-vasectomy semen analysis protocol recommended in this review has the potential to reduce costs considerably. Table 14 shows the costs of two conventional post-vasectomy testing protocols (protocols 1 and 2) and the proposed protocol based on the evidence presented in this review (protocol 3). In cases where the post-vasectomy testing protocol includes histological confirmation of the resected vas deferens, the potential savings of the recommended protocol are substantial. Where routine histological confirmation of the vas deferens is not part of the protocol, cost savings can still be made by reducing the number of post-vasectomy semen analyses. It is difficult to determine the true cost saving as there is no standard post-vasectomy testing protocol in Australia on which to base the current cost estimate. The inability to determine the true number of vasectomies performed each year also inhibits the estimate of cost saving. Table 15 shows the estimated costs and savings based on two different testing scenarios. In scenario 1, if we assumed that 10% of patients followed protocol 1 and the remaining 90% followed protocol 2, then the potential savings using the proposed protocol would be $409,794 (56%) annually (based on 28 066 patients per year22). In scenario 2, the potential savings would be even more if we assumed 50% of patients followed protocol 1 and the remaining 50% followed protocol 2. The proposed protocol, in this case, would save $1,195,614 (79%) annually.

34

Table 14: Estimated costs of various post-vasectomy testing protocols.

Protocol Semen

analysis $9.50*

Histological testing

$70.00*

Cost per patient

Patients per year 28 066†

Total cost per year‡

1 2 semen analyses + histological confirmation

$19.00 $70.00 $89.00 28 066 $2,497,874

2 2 semen analyses (no histological confirmation)

$19.00 $0.00 $19.00 28 066 $533,254

3

1 semen analysis for 80% of patients + 2 semen analyses for 20% of patients (no histological confirmation)

$9.50

$19.00

$0.00

$0.00

$9.50

$19.00

22 453

5 613

$213,302

$106,647 TOTAL

$319,950 *This is the cost to Medicare, taken from the Medicare Benefits Schedule book24 †Based on the average number of vasectomies processed through Medicare annually22 ‡The total costs per year presented in the table assumes that no patients require more tests than the number stated in the protocol to confirm sterility, therefore they are a slight underestimate. Table 15: Estimated costs of two different scenarios of post-vasectomy testing and the estimated savings with the proposed protocol.

Scenario 1 Scenario 2

Protocol Cost per patient*

Patients per year (total: 28 066)†


Patients per year (total: 28 066)†


1 2 semen analyses + histological confirmation

$89.00

10% 2 807 $249,823 50% 14 033 $1,248,937

2 2 semen analyses (no histological confirmation)

$19.00 90% 25 259 $479,921 50% 14 033 $266,627

Total: $729,744 Total: $1,515,564

3

1 semen analysis for 80% of patients + 2 semen analyses for 20% of patients (no histological confirmation)

$9.50

$19.00

100% 28 066 $319,950 100% 28 066 $319,950

Savings: $409,794 Savings: $1,195,614 * This is the cost to Medicare, taken from the Medicare Benefits Schedule book24 †Based on the average number of vasectomies processed through Medicare annually22 ‡The total costs per year presented in the table assumes that no patients require more tests than the number stated in the protocol to confirm sterility, therefore they are a slight underestimate. 7 ACKNOWLEDGEMENTS The authors wish to acknowledge the invaluable contribution of Dr Wendy Babidge, Ms Philippa Middleton and Ms Clarabelle Pham during the preparation of this review. The ASERNIP-S project is funded by the Australian Commonwealth Department of Health and Ageing.

35

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28. Arango TO, Andolz PP, Llado CC, Bielsa GO, Bielsa Carrion MA, Gelabert MA. Post-vasectomy semen in 313 males. Statistical analysis, medical aspects, legal implications. Archivos Espanoles de Urologia. 1993;46(1):29-34.

29. Bedford J and Zelikovsky G. Viability of spermatazoa in the human ejaculate after vasectomy. Fertility & Sterility. 1979;32(4):460-463.

30. Belker AM, Sexter MS, Sweitzer SJ, Raff MJ. The high rate of noncompliance for post-vasectomy semen examination: medical and legal considerations. Journal of Urology. 1990;144:284-286.

31. Benger JR, Swami SK, Gingell JC. Persistent spermatozoa after vasectomy: a survey of British urologists. British Journal of Urology. 1995;76(3):376-379.

32. Black T and Francome C. The evolution of the Marie Stopes electrocautery no-scalpel vasectomy procedure. Journal of Family Planning & Reproductive Health Care. 2002;28(3):137-138.

33. Burnight RG, Muangmun V, Cook MJ. Male sterilization in Thailand: a follow-up study. Journal of Biosocial Science. 1975;7(4):377-391.

34. Chan J, Anderson R, Glasier A. Post-vasectomy semen analysis: Unnecessary delay or belt and braces? British Journal of Family Planning. 1997;23(3):77-79.

35. Cortes M, Flick A, Barone MA, Amatya R, Pollack AE, OteroFlores J, Juarez C, McMullen S. Results of a pilot study of the time to azoospermia after vasectomy in Mexico City. Contraception. 1997;56(4):215-222.

37

36. Denniston GC. Vasectomy by electrocautery: outcomes in a series of 2,500 patients. Journal of Family Practice. 1985;21(1):35-40.

37. Edwards IS. Vasectomy: a simple postoperative regimen. Medical Journal of Australia. 1977;1(22):814-817.

38. Edwards IS and Farlow JL. Non-motile sperms persisting after vasectomy: do they matter? British Medical Journal. 1979;1(6169):1019.

39. Philp T, Guillebaud J, Budd D. Late failure of vasectomy after two documented analyses showing azoospermic semen. British Medical Journal Clinical Research Ed. 1984;289(6437):77-79.

40. Davies A, Sharp R, Cranston D, Mitchell R. The long-term outcome following "special clearance" after vasectomy. British Journal of Urology. 1990;66:211-212.

41. Haldar N, Cranston D, Turner E, MacKenzie I, Guillebaud J. How reliable is a vasectomy? Long-term follow-up of vasectomised men. Lancet. 2000;356(9223):43-44.

42. O'Brien TS, Cranston D, Ashwin P, Turner E, MacKenzie IZ, Guillebaud J. Temporary reappearance of sperm 12 months after vasectomy clearance. British Journal of Urology. 1995;76(3):371-372.

43. Esho JO and Cass AS. Recanalization rate following methods of vasectomy using interposition of fascial sheath of vas deferens. Journal of Urology. 1978;120(2):178-179.

44. Esho JO, Ireland GW, Cass AS. Recanalization following vasectomy. Urology. 1974;3(2):211-214.

45. Freund M and Davis JE. Disappearance rate of spermatozoa from the ejaculate following vasectomy. Fertility & Sterility. 1969;20(1):163-170.

46. Jackson P, Phillips B, Prosser E, Jones HO, Tindall VR, Crosby DL, Cooke ID, Rees RW, McGarry JM. A male sterilization clinic. British Medical Journal. 1970;4(730):295-297.

47. Jouannet P and David G. Evolution of the properties of semen immediately following vasectomy. Fertility & Sterility. 1978;29(4):435-441.

48. Lehtonen T and Juusela H. Experiences of vasectomy for voluntary sterilisation of males. Scandinavian Journal of Urology & Nephrology. 1973;7(2):123-126.

49. Lehtonen T. Vasectomy for voluntary male sterilisation. Scandinavian Journal of Urology & Nephrology. 1975;9(3):174-176.

50. Leungwattanakij S, Lertsuwannaroj A, RatanaOlarn K. Irrigation of the distal vas deferens during vasectomy: does it accelerate the post-vasectomy sperm-free rate? International Journal of Andrology. 2001;24(4):241-245.

51. Lewis EL, Brazil CK, Overstreet JW. Human sperm function in the ejaculate following vasectomy. Fertility & Sterility. 1984;42(6):895-898.

52. Livingstone ES. Vasectomy: a review of 3200 operations. Canadian Medical Association Journal. 1971;105(10):1065.

53. Luke M, Stolberg B, Christensen TH. Follow-up study of outpatient vasectomy. Ugeskrift for Laeger. 1979;141(28):1913-1914.

38

54. Maatman TJ, Aldrin L, Carothers GG. Patient noncompliance after vasectomy. Fertility & Sterility. 1997;68(3):552-555.

55. Marshall S and Lyon RP. Variability of sperm disappearance from the ejaculate after vasectomy. Journal of Urology. 1972;107(5):815-817.

56. Marshall S and Lyon RP. Transient reappearance of sperm after vasectomy. JAMA. 1972;219(13):1753-1754.

57. Milne R, Munro A, Scott R, Loudon N. A follow up study of 200 men after vasectomy. Health Bulletin. 1986;44(3):137-142.

58. Poddar AK and Roy S. Disappearance of spermatozoa from semen after vasectomy. Journal of Population Research. 1976;3(2):61-70.

59. Pugh RC and Hanley HG. Spontaneous recanalisation of the divided vas deferens. British Journal of Urology. 1969;41(3):340-347.

60. Rageth JC and Leibundgut B. Follow-up study of 247 vasectomies. Helvetica Chirurgica Acta. 1984;51(3-4):441-445.

61. Rees RW. Vasectomy: problems of follow up. Proceedings of the Royal Society of Medicine. 1973;66(1):52-54.

62. Richardson DW, Aitken RJ, Loudon NB. The functional competence of human spermatozoa recovery after vasectomy. Journal of Reproduction & Fertility. 1984;70(2):575-579.

63. Santiso R, Pineda MA, Marroquin M, Bertrand JT. Vasectomy in Guatemala: a follow-up study of five hundred acceptors. Social Biology. 1981;28(3-4):253-264.

64. Scholtmeijer RJ. Sperm studies following sterilization by vasectomy. How often and how long after the intervention. Nederlands Tijdschrift voor Geneeskunde. 1975;119(35):1351-1353.

65. Smith JC, Cranston D, O'Brien T, Guillebaud J, Hindmarsh J, Turner AG. Fatherhood without apparent spermatozoa after vasectomy. Lancet. 1996;344(8914):30

66. Surabote A. An analysis of 870 bilateral vasectomies. Journal of the Medical Association of Thailand. 1989;72(4):230-233.

67. Sherlock DJ and HollAllen RT. Delayed spontaneous recanalization of the vas deferens. British Journal of Surgery. 1984;71(7):532-533.

68. Sivanesaratnam V. Onset of azoospermia after vasectomy. New Zealand Medical Journal. 1985;98(778):331-333.

69. Spencer B and Charlesworth D. Factors determining the rate of disappearance of sperm from the ejaculate after vasectomy. British Journal of Surgery. 1976;63(6):477-478.

70. Staff of the Margaret Pyke Centre. One thousand vasectomies. British Medical Journal. 1973;4(5886):216-221.

71. Marwood RP and Beral V. Disappearance of spermatozoa from ejaculate after vasectomy. British Medical Journal. 1979;1(6156):87.

39

72. Tailly G, Vereecken RL, Verduyn H. A review of 357 bilateral vasectomies for male sterilization. Fertility & Sterility. 1984;41(3):424-427.

73. Temmerman M, Cammu H, Devroey P, Amy JJ. Evaluation of one-hundred open-ended vasectomies. Contraception. 1986;33(6):529-532.

74. Thompson B, MacGregor JE, MacGillivray I, Garvie WH. Experience with sperm counts following vasectomy. British Journal of Urology. 1991;68(3):230-233.

75. van Vugt AB, van Helsdingen PJ, te VJ. [Sperm analysis following vasectomy: when to perform a revasectomy?]. [Dutch]. Nederlands Tijdschrift voor Geneeskunde. 1985;129(33):1579-1582.

76. Jina RP, Jain DP, Nagar AM, Gupta RL. Spontaneous recanalization of the vas deferens. International Surgery. 1977;62(10):557-558.

77. Khan M and Cranston D. Recanalization of the vas following vasectomy. British Journal of Urology. 1997;79:484.

78. Lo CN, Mumford SD, Atwood RJ. Postvasectomy residual sperm pregnancy. Fertility & Sterility. 1980;33(6):668-669.

79. O'Reilly PH and Gradwell M. Fatherhood with no apparent spermatozoa. BJU International. 2000;86(3):407.

80. Schirren C. Sperm centrifugation in azoospermia?. Andrologia. 1984;16(4):381-384.

81. Thomson J, Lincoln P, Mortimer P. Paternity by a seemingly infertile vasectomised man. British Medical Journal. 1993;307(6899):299-300.

82. Eisner B, Schuster T, Smith G, Ohl D. Monitoring for azoospermia following vasectomy: time course and patient compliance. Fertility & Sterility. 2001;76(3 Suppl 1):S187-S188.

83. Schraibman IG. Letter: One thousand vasectomies. British Medical Journal. 1973;4(5889):418-419.

84. Foley SJ, Lewin JM, Adamson A, Smith AG, Crooks J, Singh NP, Scott R, Lloyd SN. Is the timing of post vasectomy seminal analysis important? British Journal of Urology. 1998;82(1):166.

85. Philp T, Guillebaud J, Budd D. Complications of vasectomy: review of 16,000 patients. British Journal of Urology. 1984;56(6):745-748.

86. Smucker DR, Mayhew HE, Nordlund DJ, Hahn WK, Jr., Palmer KE. Postvasectomy semen analysis: why patients don't follow-up. Journal of the American Board of Family Practice. 1991;4(1):5-9.

40

APPENDIX A – HIERARCHY OF EVIDENCE

41

Appendix A –Hierarchy Of Evidence

Level of Evidence Study Design

I Evidence obtained from a systematic review of all relevant randomised controlled trials.

II Evidence obtained from at least one properly designed randomised controlled trial.

III-1 Evidence obtained from well-designed pseudo-randomised controlled trials (alternate allocation or some other method).

III-2

Evidence obtained from comparative studies (including systematic reviews of such studies) with concurrent controls and allocation not randomised, cohort studies, case-control studies, or interrupted time-series with a control group.

III-3 Evidence obtained from comparative studies with historical control, two or more single arm studies, or interrupted time series without a parallel control group.

IV Evidence obtained from case-series, either post-test or pre-test/post-test.

42

APPENDIX B – EXCLUDED STUDIES

43

Appendix B – Excluded Studies The following papers were excluded from the methodological assessment as outlined in section 3.3 of the review.

44

Appendix B – Excluded studies Study Level of Evidence N Reason for exclusion

No author 19851 NA NA Opinion.

No author 19792 NA NA Survey of practitioners.

Alderman 19683 NA NA Opinion.

Babayan and Krane 19864 NA NA Survey of practitioners.

Bergsma 19775 NA 44 Psycho-social outcomes.

Berthelsen 19756 NA 81 Survey of post-operative sequelae.

Boyce 19737 IV 502 Comparison of specimen process methods.

Cornes 19738 NA 5 Comparison of specimen process methods.

Cranston et al 19979 IV ? Summary of another study.

Cruickshank et al. 198710 IV 182 Vasectomy reversal.

Devine 197811 NA NA Opinion / reversal of vasectomy.

Dodds 197212 NA NA Opinion.

Edwards 197313 NA NA Opinion.

Egelund et al. 198014 NA 302 Survey of social / demographic aspects.

Gandotra et al. 197815 IV 200 General wellbeing/health post-vasectomy.

Gatenbeck and Dahlgren 198516 NA NA Opinion.

Goldacre et al. 197817 IV 1764 Safety/ no relevant outcomes reported.

Goldstein 198318 IV 4 Technique.

Hancock and McLaughlin 200219 NA NA Guideline.

Haws et al. 199820 NA NA Survey of practitioners.

Hellsten and Andersson 198521 NA NA No relevant outcomes reported.

Hole 199422 NA NA Opinion.

Jackson and Avant 198223 NA 2000 Survey regarding postoperative wellbeing.

Jina and Kumar 197924 IV 42 Vasectomy reversal.

Kaplan and Huether 197525 IV 26 Technique.

Kropman 199926 NA NA Opinion / technique.

Lindsay et al. 199527 NA NA No relevant outcomes reported.

Makler et al 197928 NA NA No relevant outcomes reported.

Mellin et al. 198029 NA NA Review / opinion.

Moss 198530 NA NA Opinion / technique.

Mumford et al. 198231 NA NA Review. Continued overleaf…

45

Appendix B – Excluded Studies (continued) Study Level of Evidence N Reason for exclusion

Nelson and Bunge 197432 IV 390 Sperm function / no relevant outcomes reported.

Reimann-Hunziker and Reimann-Hunziker 196233 NA 180 Survey of post-operative satisfaction.

Ronquist et al. 198534 IV 36 Sperm function.

Saksena 197435 NA 607 Survey of attitudes and motivation leading to vasectomy.

Schloss 197536 NA NA Opinion.

Schulhof and Marshall 197337 NA NA Opinion.

Schmidt 197338 NA NA Technique.

Schmidt 198539 NA NA Opinion.

Sivardeen and Budhoo 200140 NA NA Survey of practitioners.

Smucker et al 199141 NA 141 Survey regarding compliance.

Sobrero and Kohli 197442 NA 236 Survey regarding social characteristics and motivational factors leading to vasectomy.

Wethelund and Wendelboe Nielsen 198543 IV 120 No relevant outcomes reported.

Whitby et al. 197544 NA 960 Survey of social characteristics and postoperative satisfaction / wellbeing.

Reference list: Excluded studies 1. Late failure of vasectomy. Lancet. 1985;1(8432):794-795.

2. Vasectomy: operative procedures and sterility tests not standardized. Family Planning Perspectives. 1979;11(2):122-126.

3. Alderman PM. Vasectomy for voluntary male sterilisation. Lancet. 1968;2(7578):1137-1138.

4. Babayan R and Krane R. Vasectomy: what are community standards? Urology. 1986;27:328-330.

5. Bergsma J. Vasectomy: a two-tier follow-up. Journal of Community Psychology. 1977;5(2):171-174.

6. Berthelsen JG. After vasectomy. A follow-up study. Ugeskrift for Laeger. 1975;137(34):1947-1950.

7. Boyce JM. Sperm-counts after vasectomy. Lancet. 1973;1(7801):492.

8. Cornes JS. Sperm-counts after vasectomy. Lancet. 1973;1(7805):721.

9. Cranston D, Ashwin P, Turner E, Mckenzie I, Guillebaud J. Temporary reappearance of sperm 12 and 24 months after vasectomy clearance. British Journal of Urology. 1997;79 Supplement 4:20.

10. Cruickshank B, Eidus L, Barkin M. Regeneration of vas deferens after vasectomy. Urology. 1987;30(2):137-142.

11. Devine CJ, Jr. Sperm granuloma following vasectomy. Fertility & Sterility. 1978;29(4):470-473.

46

Reference list: Excluded studies (continued)

12. Dodds DJ. Reanastomosis of the vas deferens. Journal of the American Medical Association. 1972;220:1498.

13. Edwards IS. Follow up after vasectomy. Medical Journal of Australia. 1973;2(3):132-135.

14. Egelund B, Hansen GL, Larsen P, Rasmussen HB, Wermuth L. A follow-up study of 302 vasetomized men living in the County of Fyn. Ugeskrift for Laeger. 1980;142(30):1950-1953.

15. Gandotra VK, Joseph G, Mohan D, Ramachandran K. A follow up study of 200 cases of vasectomy. Indian Journal of Medical Research. 1978;68:620-630.

16. Gatenbeck L and Dahlgren SE. Spontaneous recanalisation after vasectomy: A survey. Lakartidningen. 1985;82(37):3064-3065.

17. Goldacre MJ, Clarke JA, Heasman MA, Vessey MP. Follow-up of vasectomy using medical record linkage. American Journal of Epidemiology. 1978;108(3):176-180.

18. Goldstein M. Vasectomy failure using an open-ended technique. Fertility & Sterility. 1983;40(5):699-700.

19. Hancock P and McLaughlin E. British Andrology Society guidelines for the assessment of post vasectomy semen samples. Journal of Clinical Pathology. 2002;55(11):812-816.

20. Haws JM, Morgan GT, Pollack AE, Koonin LM, Magnani RJ, Gargiullo PM. Clinical aspects of vasectomies performed in the United States in 1995. Urology. 1998;52(4):685-691.

21. Hellsten S and Andersson M. Vasectomy--a follow-up study of 53 patients after surgery. Nordisk Medicin. 1985;100(3):84-85.

22. Hole R. Vasectomy procedures and fertility. Lancet. 1994;344(8919):415-415.

23. Jackson LN and Avant P. Vasectomy: a follow-up of two thousand men. Journal of the Royal College of General Practitioners. 1982;32(236):172-173.

24. Jina RP and Kumar V. Recanalisation of vas. Journal of the Indian Medical Association. 1979;72(2):30-32.

25. Kaplan KA and Huether CA. A clinical study of vasectomy failure and recanalization. Journal of Urology. 1975;113(1):71-74.

26. Kropman RF. Surgical techniques and spermatozoa. Nederlands Tijdschrift voor Urologie. 1999;7(3):81-82.

27. Lindsay KS, Floyd I, Swan R. Classification of azoospermic samples. [Letter]. Lancet. 1995;345(8965):1642.

28. Makler A, Zaidise I, Paldi E, Brandes J. Factors affecting sperm motility: in vitro change in motility with time after ejaculation. Fertility & Sterility. 1979;31:147-154.

29. Mellin HE, Bauer HW, Rattenhuber U. Failure following fertility vasectomy. Medizinische Welt. 1980;31(47):1723-1724.

30. Moss WM. Vasectomy failure after use of an open-ended technique. Fertility & Sterility. 1985;43(4):667-668.

47

Reference list: Excluded studies (continued)

31. Mumford SD, Davis JE, Freund M. Considerations in selecting a postvasectomy semen examination regimen. International Urology & Nephrology. 1982;14(3):293-306.

32. Nelson CM and Bunge RG. Semen analysis: evidence for changing parameters of male fertility potential. Fertility & Sterility. 1974;25(6):503-507.

33. Reimann-Hunziker R and Reimann-Hunziker G. Eigene erfahrungen an uber 1000 vaseklomeirten der letzten 20 jahre. Praeventivmed. 1962;7:537-546.

34. Ronquist G, Stegmayr B, Niklasson F. Sperm motility and interactions among seminal uridine, xanthine, urate, and ATPase in fertile and infertile men. Archives of Andrology. 1985;15(1):21-27.

35. Saksena DN. Follow-up study of rural vasectomy acceptors in Uttar Pradesh. Studies in Family Planning. 1974;5(2):50-53.

36. Schloss WA. Letter: Checking success of vasectomy. JAMA. 1975;232(4):347.

37. Schulhof MG and Marshall S. How is postvasectomy sterility confirmed? Journal of the American Medical Association. 1973;224(4):537.

38. Schmidt SS. Prevention of failure in vasectomy. Journal of Urology. 1973;109(2):296-297.

39. Schmidt SS. Vasectomy failure and open-ended vasectomy. Fertility & Sterility. 1985;44(4):557-558.

40. Sivardeen KA and Budhoo M. Post vasectomy analysis: call for a uniform evidence-based protocol. Ann R Coll Surg Engl. 2001;83(3):177-179.

41. Smucker DR, Mayhew HE, Nordlund DJ, Hahn WK, Jr., Palmer KE. Postvasectomy semen analysis: why patients don't follow-up.[comment]. Journal of the American Board of Family Practice. 1991;4(1):5-9.

42. Sobrero AJ and Kohli KL. Vasectomized men: follow-up results at one year. Studies in Family Planning. 1974;5(2):54-57.

43. Wethelund J and Nielsen KW. Vasectomy. A 5-year follow-up study of 120 patients after vasectomy with immediate sterility. Ugeskrift for Laeger. 1985;147(14):1195-1196.

44. Whitby RM, Brown IG, Seeney NC. Vasectomy: follow up of 831 cases. Medical Journal of Australia. 1975;1(6):164-167.

48

APPENDIX C – USE OF DATA

49

Appendix C – Use of Data The following papers were used in those sections of the review where relevant data could be extracted, as outlined in section 3.3.3. Results presented graphically in review: Compliance:

1. Compliance vs. number of tests (figure 1) 2. Compliance at first and second tests (figure 2) 3. Compliance vs. time of first test (figure 3) 4. Compliance vs. time of last test (figure 4)

Outcomes of vasectomy: 5. Total reaching azoospermia when tests based on time or number of

ejaculations (table 10) 6. Percent reaching azoospermia vs. time of first test (figure 5) 7. Percent reaching azoospermia vs. number of ejaculations (figure 6) 8. Percent reaching azoospermia at first and second tests (figure 7) 9. Percent reaching azoospermia vs. number of ejaculations (figure 8) 10. Loss of sperm motility (figure 9) 11. Sperm reappearance (figure 10)

Results Presented Compliance Outcomes of vasectomy 1 2 3 4 5 6 7 8 9 10 11 Alderman 1989 Arango et al 1993 Badrakumar et al 2000 Bedford & Zelikovsky 1979 Belker et al 1990 Black 2002 Bradshaw et al 2001 Burnight et al 1975 Chan et al 1997 DeKnijff et al 1997 Edwards 1993 Eisner et al 2001 Elliot-Smith Clinic Esho & Cass 1978 Foley et al 1998 Freund & Davis 1969 Jackson et al 1970 Jouannet & David 1978 Lee & Paterson 2001 Lehtonen & Juusela 1973 Lehtonen 1975 Leungwattanakij et al 2001 Lewis et al 1984

Continued overleaf…

50

Appendix C – Use of data (continued) Results Presented Compliance Outcomes of vasectomy 1 2 3 4 5 6 7 8 9 10 11 Luke et al 1979 Maatman et al 1997 Marshall & Lyon 1972 Milne et al 1986 Poddar & Roy 1976 Rageth & Leibundgut 1984 Rees 1973 Richardson et al 1984 Santiso et al 1981 Scholmeijer 1975 Schraibman 1973 Smith 1996 Surabote 1989 Sivanesaratnam 1985 Smith et al 1998 Staff of Margaret Pyke 1973 Surabote 1989 Tailly et al 1984 Temmerman et al 1986 Thompson et al 1991 Van Vugt et al 1985

51

APPENDIX D – METHODOLOGICAL ASSESSMENT

AND DATA EXTRACTION TABLES

52

Appendix D – Methodological Assessment and Data Extraction Tables Appendix D.1: Comparative studies

Authors Intervention Study Design Study Population Inclusion/Exclusion Criteria Badrakumar et al.. 2000

Location UK Pinderfields and Pontefract Hospitals NHS Trust, Wakefield, West Yorkshire

Vasectomy Location: Not stated Anaesthesia: Local Incisional technique: Scalpel method Vas occlusion: Not stated Flushing: Not stated Post-vasectomy testing protocol Timing:

1) In group 1, analysis after 4 months postoperatively. If sperm present, monthly tests conducted until negative. 2) In group 2, samples requested after 3 and 4 months. If

sperm present, monthly tests conducted until negative. Number of tests: Variable (1 or 2 initially and then monthly if positive). Definition of sterility: Absence of spermatozoa (motility not assessed). Definition of failure: Presence of sperm.

Comparative study of PVSA test protocol. Level of Evidence: III-2 Follow-up: At least 7 months Lost to Follow-up: In group 1, 151 (16%) withdrew initially. Then, an additional six (0.6%) men withdrew at various times. Three (0.3%) failed to provide a 2nd sample, one (0.1%) a 3rd and two (0.2%) a 4th. In group 2, 66 (5%) withdrew initially, then an additional 101 (7%) withdrew without providing a 2nd sample. An additional patient (0.07%) withdrew after providing the 2nd sample and failed to follow up his positive test. Study Period: October 1995 to at least September 1996. Operator Details: All vasectomies carried out by consultant urologists.

Vasectomised men Sample Size: 1321 (961 in group 1, 360 in group 2) Mean Age: Not stated

Not stated.

53

Authors Intervention Study Design Study Population Inclusion/Exclusion Criteria Smith et al. 1998

Location UK Pyrah Department of Urology, St James’s University Hospital, Leeds; Stobhill General Hospital, Glasgow; Glasgow Royal Infirmary.

Vasectomy Location: St James’s University Hospital (hospital A) and Glasgow Royal Infirmary (hospital B). Anaesthesia: Not stated Incisional technique: Not stated Vas occlusion: Not stated Flushing: Not stated Post-vasectomy testing protocol Timing:

1) At hospital A, 1st semen analysis conducted at 3 months post-vasectomy, a second test performed a mean of 12.5 days after 1st test (range 7-28).

2) At hospital B, 1st and 2nd tests were performed at 6 months. 3) After consultation with 52 patients of hospital A, the

protocol of hospital A was changed to that of hospital B with tests performed at 6 months.

Number of tests: 2 Definition of sterility: Azoospermia Definition of failure: A positive semen analysis was reported if motile or nonmotile spermatozoa were identified.

Comparative study (retrospective comparison using chart review) Level of Evidence: III-3 Follow-up: at least 8 months Lost to Follow-up: Hosp A (part 1): 58 (24%) Hosp A (part 2): 18 (21%) Hosp B: 24 (24%) Study Period: Not stated Operator Details: Not stated

Vasectomy patients in two hospitals. Sample Size: Hospital A (part 1): 245 Hospital A (part 2): 87 Hospital B: 100 Mean Age: Not stated

Not stated.

54

Appendix D.2: Case series and reports

Authors Intervention Study Design Study Population Inclusion/Exclusion Criteria Alderman 1988; Alderman 1989

Location CANADA Lions Gate Hospital, North Vancouver

Vasectomy Location: In office or in hospital Anaesthesia: General or local Incisional technique: Central incision Vas occlusion: Free ends tied with absorbable suture Flushing: None Post-vasectomy testing protocol Timing: Started 3 months postoperatively Number of tests: Monthly until 2 consecutive tests were negative Definition of sterility:

1) Only presence or absence of sperm in specimen (motility ignored)

2) Later motility considered to define different categories of failure

Definition of failure: 1) Early failure – sig. no’s of spermatozoa or more than one

motile sperm per high powered field (>100x106/L). Early failure within approx. 12 months.

2) Late failure – sperm in any number or condition after success of vasectomy already proved. Late failure is any time after proof of success.

3) Overt failure – continuous presence of significant numbers of sperm or any active sperm later than 4 months after vasectomy

4) Technical failure – nonsignificant numbers of sperm present one year after vasectomy or later (<100x106/L)

Case series Level of Evidence: IV Follow-up: At least 8.6 years Lost to Follow-up: Not stated. Study Period: Nov 1 1962 – June 30 1986 Operator Details: single operator (family physician) practice restricted to vasectomy and related research

Vasectomised men with at least two semen tests Sample Size: 5331 (of 8879 consecutive vasectomy patients) Mean Age: Not stated. NOTE: The 1988 paper discusses the 91 failures of the 5331 patients who provided at least 2 samples. The 1989 paper discusses the sperm disappearance in 5233 patients who continued with testing until success/failure was confirmed.

Only patients who had either at least 2 PVSA tests (n = 5331) or until success/failure of vasectomy confirmed by PVSA (n=5233).

55

Authors Intervention Study Design Study Population Inclusion/Exclusion Criteria Arango et al. 1993 SPANISH LANGUAGE

Location SPAIN Department of Urology, University Hospital, University of Barcelona, Barcelona.

Vasectomy Location: Hospital Anaesthesia: Not stated Incisional technique: Not stated Vas occlusion: Each of the cut end tied by catgut ligature but segment of the vas neither resected nor coagulated Flushing: Not stated Post-vasectomy testing protocol Timing: Started at 3 months post-vasectomy and then every 2 months until negative Number of tests: 1 (unless positive, then more) Definition of sterility: Azoospermia Definition of failure: Presence of sperm

Case series Level of Evidence: IV Follow-up: 8 months Lost to Follow-up: 62 (20%) failed to provide any samples, 11 (4%) failed to provide 2nd sample, 3 (1%) failed to provide 3rd sample. Study Period: June 1989 to April 1991 Operator Details: Not stated

Vasectomised men Sample Size: 313 Mean Age: 38.3 (range 23-56)

Not stated.

56

Authors Intervention Study Design Study Population Inclusion/Exclusion Criteria Bedford and Zelikovsky 1979

Location USA Department of Obstetrics and Gynecology, Cornell University Medical College, New York, New York; Margaret Sanger Center, Planned Parenthood of New York City, New York; Department of Urology, New York University School of Medicine, New York, New York.

Vasectomy Location: Margaret Sanger Center, New York, USA Anaesthesia: Local Incisional technique: 1cm incision Vas occlusion: Both cut portions ligated with a 00 chromic catgut suture, terminal end was folded, and the fold itself ligated. Flushing: Not stated. Post-vasectomy testing protocol Timing: 1st test within 3 weeks (preoperatively),2nd test 6 – 19 days (postoperatively). Number of tests: 2 (1 before and 1 after) Definition of sterility: Not applicable Definition of failure: Fertile range of motile spermatozoa/ejaculate: >35 x 106

Lab protocol: Sperm were always examined within 3 hours of collection and storage at a room temperature of 23-24 degrees C, before evaluation the semen was stirred then two drops were placed on a slide and scanned systematically under phase-contrast microscopy by one investigator for presence of motility Motility: any independent movement of spermatazoon including progressive motility

Case series Level of Evidence: IV Follow-up: 19 days Lost to Follow-up: None Study Period: Not stated Operator Details: Vasectomies performed by G. Zelikovsky, urologist in charge, Margaret Sanger Center

Fertile men undergoing vasectomy who provided both pre- and post-vasectomy semen analyses. Sample Size: 82 Mean Age: Not stated

Not stated.

57

Authors Intervention Study Design Study Population Inclusion/Exclusion Criteria Belker et al. 1990

Location USA Departments of Surgery (Division of Urology) and Medicine (Section of Infectious Diseases), University of Louisville, School of Medicine, Louisville, Kentucky.

Vasectomy Location: Not stated. Anaesthesia: Not stated. Incisional technique: Not stated. Vas occlusion: Mucosa of divided vas cauterised. Ligatures not used. 1cm vas resected in most cases. Interposition of spermatic fascia between divided ends performed in all cases. Flushing: None. Post-vasectomy testing protocol Timing: First sample at 4 months post vasectomy. Number of tests: 2 initially, then repeated tests until 2 consecutive azoospermic tests provided. Definition of sterility: Azoospermia in 2 consecutive postvasectomy semen samples. Definition of failure: Presence of sperm (unless special clearance given in some cases where “rare” nonmotile sperm persisted).

Case series (retrospective chart review) Level of Evidence: IV Follow-up: At least 18 months and up to 38 months. Lost to Follow-up: 375 (36%) failed to provide any samples. 84 (8%) failed to provided a second sample. Study Period: February 1982 to December 1986. Operator Details: Not stated.

Patients who had undergone vasectomy between February 1982 to December 1986. Sample Size: 1029 Mean Age: Not stated

9 physicians who had undergone vasectomy were excluded as it was assumed they had conducted the PVSA themselves.

58

Authors Intervention Study Design Study Population Inclusion/Exclusion Criteria Benger et al. 1995

Location UK The Bristol Urological Institute, Southmead Hospital, Westbury-On-Trym, Bristol.

Vasectomy Location: Urology Department, Southmead Hospital. Anaesthesia: Not stated Incisional technique: Not stated Vas occlusion: Not stated Flushing: Not stated Post-vasectomy testing protocol Timing: Not stated Number of tests: Not stated Definition of sterility: Azoospermia Definition of failure: Persistent sperm after vasectomy (no distinction made between motile and nonmotile)

Case series and survey of urologists. Level of Evidence: IV Follow-up: Up to 36 months Survey response rate: 65%. 129 questionnaires not returned + 4 not completed. Study Period: January, 1993 to March 1994 Operator Details: Not stated.

1) Vasectomized men. 2) Consultant urologists in England and Wales. Sample Size: 1) 633 vasectomies and 31 repeat vasectomies. 2) 294 questionnaires sent out to urologists. Mean Age: Not stated.

Not stated.

59

Authors Intervention Study Design Study Population Inclusion/Exclusion Criteria

Black 2002

Location

UK Marie Stopes International, London; Middlesex University, London.

Vasectomy Location: Marie Stopes centres (22 – 26 different centres). Anaesthesia: Local. Incisional technique: 5 – 7mm vertical scrotal incision in an avascular postion. Vas occlusion: Electrocoagulation using a Hyfrecator. Flushing: Not stated. Post-vasectomy testing protocol Timing: Starting at 12 weeks, then at 14 weeks. Number of tests: 2 Definition of sterility: 2 consecutive azoospermic samples. Definition of failure: Presence of spermatozoa. Primary failure – PVSA positive for sperm Secondary failure – reappearance of sperm at “later stage”

Case series.

Level of Evidence: IV Follow-up: At least 14 weeks. Lost to Follow-up: 3309 (7%) Study Period: Vasectomies performed from 1990 to 1999. (2 periods 1990 – 1994 and 1995-1999) Operator Details: Not stated (at least 24 – 30 operating doctors)

Vasectomised men. Sample Size: 45123 Mean Age: Not stated.

Not stated.

60

Authors Intervention Study Design Study Population Inclusion/Exclusion Criteria Bradshaw et al. 2001

Location UK Department of Urology, Chesterfield and North Derbyshire Royal Hospital, Calow, Chesterfield.

Vasectomy Location: A district general hospital (location not stated) Anaesthesia: Not stated Incisional technique: Not stated Vas occlusion: Not stated Flushing: Not stated Post-vasectomy testing protocol Timing: 3 and 4 months post vasectomy. Number of tests: 2 initially, more if not cleared. Definition of sterility: Two consecutive azoospermic specimens. Definition of failure: One microbiologist – no assessment of motility made unless clearly motile sperm present azoospermia – no sperm very scanty sperm (<5/HPF) scanty (5-10/HPF) moderate (10-50/HPF) numerous (>50/HPF)

Case series and survey Level of Evidence: IV Follow-up: median 37 (30 – 42) months. Lost to Follow-up: 34 (14%) initially, then a further 22 (9%) before 2nd specimen. A further 10 (4%) failed to provide further requested specimens. Survey response rate: 100% Study Period: April 1995 to at least October 1997. Operator Details: Not stated

1) Surgeons (urologists and general surgeons) performing vasectomy in a district general hospital. 2) Men undergoing vasectomy between April 1995 and April 1996 in the same hospital. Sample Size: 1) 15 surgeons 2) 240 patients Mean Age: Not stated

Not stated.

61

Authors Intervention Study Design Study Population Inclusion/Exclusion Criteria Burnight et al. 1975

Location THAILAND Carolina Population Centre, Ramathibodi Hospital and Institute for Population and Social Research, Mahidol University, Bangkok.

Vasectomy Location: Ramathibodi Hospital, Bangkok. Anaesthesia: Not stated. Incisional technique: Not stated. Vas occlusion: Not stated. Flushing: Not stated. Post-vasectomy testing protocol Timing: Not stated. Number of tests: Not stated. Definition of sterility: Not stated. Definition of failure: Not stated.

Retrospective study of a case series Level of Evidence: IV Follow-up: At least 2 months. Lost to Follow-up: 107 (37%) did not reply (23 were returned as addressee could not be located). Study Period: Vasectomies performed January 1970 to March 1973. Study conducted May-July 1973. Operator Details: Not stated.

Thai males who had been vasectomised at Ramathibodi Hospital, Bangkok between January 1970 and March 1973. Sample Size: 292 Mean Age: 33.5 (range 21-52)

Not stated.

62

Authors Intervention Study Design Study Population Inclusion/Exclusion Criteria Chan et al. 1997

Location UK Department of Obstetrics and Gynaecology, University of Edinburgh; Edinburgh Healthcare (NHS) Trust.

Vasectomy Location: Edinburgh Healthcare (NHS) Trust Family Planning Clinic. Anaesthesia: Local. Incisional technique: Not stated. Vas occlusion: Ligaclips (67%), hyfrecator (33%) or ligation (0.4%). Flushing: Not stated. Post-vasectomy testing protocol Timing: Started at 12 weeks, then every 4 weeks. Number of tests: 2 initially, more if needed to reach 2 consecutive negative tests. Definition of sterility: 2 consecutive azoospermic samples. Definition of failure: Presence of spermatozoa (motility of sperm was noted but was not used as the sole basis of failure, this due to fact that samples were sent by post and motility analysis therefore unreliable).

Case series. Level of Evidence: IV Follow-up: Up to 70 weeks. Lost to Follow-up: 60 (10%) (34 did not provide any samples, 26 did not fully comply) Study Period: Vasectomies performed Sept 1994 to Aug 1995. Operator Details: Not stated.

Vasectomised men. Sample Size: 574 (consecutive) Mean Age: 35.7 (range 23 – 62).

Not stated.

63

Authors Intervention Study Design Study Population Inclusion/Exclusion Criteria Cornes 1973 Letter

Location UK Pathology Department, Bristol General Hospital, Bristol.

Vasectomy Location: Not stated. Anaesthesia: Not stated. Incisional technique: Not stated. Vas occlusion: Not stated. Flushing: Not stated. Post-vasectomy testing protocol Timing: Not stated. Number of tests: Not stated. Definition of sterility: Not stated. Definition of failure: Not stated.

Letter - case reports. Level of Evidence: IV Follow-up: Not stated. Lost to Follow-up: Not stated. Study Period: Not stated. Operator Details: Not stated.

Post-vasectomy samples where pregnancy had occurred. Sample Size: 5 Mean Age: Not stated.

Not stated.

64

Authors Intervention Study Design Study Population Inclusion/Exclusion Criteria Cortes et al. 1997

Location MEXICO and USA Instituto Mexicano del Seguro Social (IMSS), Mexico City; Family Health International, Research Triangle Park, North Carolina; AVSC International, New York, New York.

Vasectomy Location: A clinic in Mexico City. Anaesthesia: Local. Incisional technique: No scalpel Vas occlusion: Vas ligated in 2 locations 1 cm apart using silk ligatures, segment of vas excised, no fascial interposition used. Flushing: Not stated. Post-vasectomy testing protocol Timing: Started 1 week post-vasectomy. Then weekly up to 16 weeks, then biweekly until azoospermia or to 24 weeks. Number of tests: Varied, but 2 negative required for clearance. Definition of sterility: 2 consecutive negative samples, at least 3 days apart. Definition of failure: User failure: Failures (pregnancy for example) when the patient failed to follow-up vasectomy or have failed to use a back-up contraceptive method before being cleared. Method failure: Presence of motile sperm after previously submitting 2 consecutive azoospermic samples and being cleared (due to recanalisation).

Case series. Level of Evidence: IV Follow-up: 24 weeks Lost to Follow-up: 9 (24%) patients discontinued the study prior to reaching azoospermia or 24 weeks. 3 (8%) of these never returned for follow-up but are included in intention to treat analysis. Study Period: Not stated. Operator Details: Not stated.

Vasectomised men. Sample Size: 38 Mean Age: 30.6 (range, 22-43) years

Admission criteria were that the men had to: 1) agree to give a prevasectomy sample; 2) be currently sexually active; 3) be ≥ 21 years of age; 4) agree to have their vasectomy within 2 weeks of giving acceptable semen sample (sperm count ≥ 20x106/ml); 5) agree to return for follow-up clinic visits; 6) freely consent to participate in the study and sign an Informed Consent Form; 7) and meet clinic eligibility criteria for vasectomy.

65

Authors Intervention Study Design Study Population Inclusion/Exclusion Criteria Davies et al. 1990

Location UK Elliot Smith Clinic, Churchill Hospital, Oxford

Vasectomy Location: Elliot Smith Clinic, Churchill Hospital Anaesthesia: Local Incisional technique: Not stated Vas occlusion: Hyfrecator cautery applied to ends of divided vas (in almost all cases) Flushing: Not stated Post-vasectomy testing protocol Timing: 3 years minimum from clearance Number of tests: 1 (after clearance, does not include initial tests) Definition of sterility: Azoospermia Definition of failure: Not stated

Case series Level of Evidence: IV Follow-up: 3-8 years Lost to Follow-up: 101 (67%) of invited men did not reply or supply specimen. Study Period: vasectomies performed between 1980 and 1985, study done in 1988. Operator Details: Not stated

Vasectomised men with persistently positive semen samples that were given a “special clearance”. This was after 2 consecutive specimens with <10,000/ml at least 7 months since vasectomy. Sample Size: 151 (given special clearance (of 6067 vasectomy patients)) Mean Age: 40 (27 – 66) years

Not stated.

66

Authors Intervention Study Design Study Population Inclusion/Exclusion Criteria DeKnijff et al. 1997

Location NETHERLANDS Department of Urology, University of Maastricht, Maastricht.

Vasectomy Location: Urology Clinic Anaesthesia: Local (lidocaine 1%) Incisional technique: Not stated. Vas occlusion: Both ends ligated with vicryl 1.0 and spermatic fascia interposed. Flushing: Not stated Post-vasectomy testing protocol Timing: 6 and 12 weeks postoperatively (and then repeated until azoospermia, times not stated). Number of tests: 2 initially (study focussed on 2nd test results) Definition of sterility: Azoospermia Definition of failure: Presence of sperm

Case series Level of Evidence: IV Follow-up: Between 12 weeks and 21 months. Lost to Follow-up: 18 (4%) initially. Then 39 (9%) after 1st test. Study Period: April 1, 1993 to at least July 31, 1995. Operator Details: 6 different urologists

Vasectomised men. Sample Size: 413 Mean Age: 38.4 (for men who showed non-motile sperm at 12 weeks). Not sig. different to mean age overall.

Not stated.

67

Authors Intervention Study Design Study Population Inclusion/Exclusion Criteria Denniston 1985

Location USA Population Dynamics, Seattle, Washington

Vasectomy Location: Not stated Anaesthesia: Local, 1% lidicaine Incisional technique: single, high incision Vas occlusion: Vas cut once and cauterised, distil end covered with sheath Flushing: Not stated Post-vasectomy testing protocol Timing: After 15 ejaculations and a minimum of 6 weeks Number of tests: Not stated Definition of sterility: ‘negative’ Definition of failure: Not stated

Case series Level of Evidence: IV Follow-up: Not stated Lost to Follow-up: NA Study Period: 1971 - 1982 Operator Details: Not stated

Men undergoing vasectomy Sample Size: 2500 Age: 80% between 25 and 45 years

Not stated.

68

Authors Intervention Study Design Study Population Inclusion/Exclusion Criteria Edwards 1977

Location AUSTRALIA Cronulla NSW.

Vasectomy Location: Office procedure in a private practice Anaesthesia: Local Incisional technique: Not stated Vas occlusion: Light diathermy of the endothelium of each cut end of the vas without ligation and without excision of any piece of vas. Closure of the sheath over one end of the vas using plain 000 catgut. Initially, lower end of vas was buried (n=255) and in subsequent cases upper end buried (n=245). Flushing: None Post-vasectomy testing protocol Timing: After 10 ejaculations Number of tests: 1 initially, a 2nd one if motile sperm present. Definition of sterility: Azoospermia or only nonmotile sperm present. Definition of failure: Motile sperm in first test required a 2nd test (after approx 3 more weeks). Motile sperm in the 2nd test was taken to indicate recanalization and revasectomy was advised.

Case series Level of Evidence: IV Follow-up: 12 – 15 months Lost to Follow-up: 317 (63%) For survey: 48 failed to reply, 402 failed to provide sample. Study Period: Not stated Operator Details: All vasectomies carried out by I. S. Edwards.

Men who have had a vasectomy and submitted fresh seminal specimens after 10 ejaculations. Sample Size: 183/500 Mean Age: Not stated

Not stated.

69

Authors Intervention Study Design Study Population Inclusion/Exclusion Criteria Edwards 1993

Location AUSTRALIA Cronulla Private Medical Clinic, Cronulla, New South Wales.

Vasectomy Location: Cronulla Private Medical Clinic Anaesthesia: Local Incisional technique: Not stated Vas occlusion: No section of vas excised. Intraluminal cautery without ligatures, sheath closed over prostatic end, testicular end left outside sheath (n=1367). “Open-ended” method where testicular end not sealed (n=1811). Flushing: None Post-vasectomy testing protocol Timing: Protocol changed over time: Initially: After 10 ejaculations Then: 3 weeks postoperatively Finally: 4 weeks postoperatively Number of tests: 1 initially, more if motile or large numbers of nonmotile sperm found. Definition of sterility: No sperm or nonmotile sperm found in a single test. Definition of failure: Motile sperm present.

Case series Level of Evidence: IV Follow-up: 3 weeks to 18 months. Lost to Follow-up: 918 (29%) did not provide sample. Study Period: 1975-1992 Operator Details: I. S. Edwards, M.B., B. S.

Men undergoing vasectomy. Sample Size: 3178 Mean Age: Not stated

Not stated.

70

Authors Intervention Study Design Study Population Inclusion/Exclusion Criteria Edwards and Farlow 1979

Location AUSTRALIA Cronulla, NSW and the Sutherland Hospital, Caringbah, NSW

Vasectomy Location: Not stated Anaesthesia: Local Incisional technique: Not stated Vas occlusion: Light diathermy of each cut end without ligation, sheath closed over one end. Flushing: Not stated Post-vasectomy testing protocol Timing: After at least 10 ejaculations Number of tests: 1 Definition of sterility: Azoospermia or presence of non-motile sperm only Definition of failure: Presence of motile sperm

Case series Level of Evidence: IV Follow-up: 12 to 15 months Lost to Follow-up: 10 (5%) did not reply to letter, 152 (76%) did not supply further specimen Study Period: Not stated Operator Details:

Vasectomised men. Sample Size: 200 (of 461 patients who submitted specimens) Mean Age: Not stated **PROBABLY OVERLAP IN PATIENTS WITH OTHER EDWARDS STUDIES**

Included: men who had initial PVSA negative for motile sperm (non-motile sperm could be present)

71

Authors Intervention Study Design Study Population Inclusion/Exclusion Criteria Eisner et al. 2001 Abstract

Location USA University of Michigan, Ann Arbor, Michigan

Vasectomy Location: Not stated Anaesthesia: Not stated Incisional technique: Not stated Vas occlusion: Not stated Flushing: Not stated Post-vasectomy testing protocol Timing: Started 6 weeks postoperatively Number of tests: Every 6 weeks until 2 consecutive tests were negative. Definition of sterility: Azoospermia Definition of failure: Not stated

Case series Level of Evidence: IV Follow-up: at least 22 weeks Lost to Follow-up: 109 (25%) men (of 443 instructed) never returned. 182 (41%) did not fully comply with instructions (returned for only one test but were included in results). Study Period: Not stated Operator Details: Not stated

Vasectomised men with at least one semen test Sample Size: 443 Mean Age: Not stated

Not stated.

72

Authors Intervention Study Design Study Population Inclusion/Exclusion Criteria Esho et al. 1974 & Esho and Cass 1978

Location USA Department of Urology, St. Paul-Ramsey Hospital, St. Paul, Minnesota University of Minnesota Medical School, St. Paul, Minnesota

Vasectomy Location: Not stated Anaesthesia: Not stated Incisional technique: Not stated Vas occlusion: 1.5cm vas resected. ligation method (n=564): cut ends ligated with 3-0 chromic catgut; or fulguration with fascial sheath interposition method (n=963): cut ends electrofulgurated, distil cut end buried in fascial sheath Flushing: Not stated Post-vasectomy testing protocol Timing: Started 8 weeks post-vasectomy, then at 4 week intervals until negative test supplied Number of tests: 1 (more if required) Definition of sterility: Azoospermia Definition of failure: Presence of sperm

Case series; Comparative study of vasectomy methods, but not of PVSA methods Level of Evidence: IV Follow-up: Up to 36 months Lost to Follow-up: 119/889 (13%) (1974 paper) failed to submit samples; 67/564 (12%) and 143/963 (15%) (1978 paper) failed to provide PVSA samples. Study Period: June 1970 – December 1976 Operator Details: Not stated

Vasectomised men Sample Size: 1974 paper: 889 (a subset of the following patients) 1978 paper: 564 (fascial sheath) 963 (fulguration) Mean Age: Not stated

Not stated.

73

Authors Intervention Study Design Study Population Inclusion/Exclusion Criteria Foley et al. 1998 Letter

Location UK Royal Hampshire County Hospital, Winchester

Vasectomy Location: Not stated Anaesthesia: Not stated Incisional technique: Not stated Vas occlusion: Not stated Flushing: Not stated Post-vasectomy testing protocol Timing: Not stated Number of tests: Not stated Definition of sterility: Not stated Definition of failure: Not stated

Letter Level of Evidence: Not applicable. Follow-up: At least 3 months Lost to Follow-up: Not stated Study Period: Not stated Operator Details: Not stated

Vasectomised men Sample Size: 230 Mean Age: Not stated

Not stated.

74

Authors Intervention Study Design Study Population Inclusion/Exclusion Criteria Freund and Davis 1969

Location USA Laboratory of Reproductive Pharmacology, Departments of Pharmacology and of Obstetrics and Gynaecology and the Department of Urology, New York Medical College, New York

Case series Vasectomy Location: Not stated Anaesthesia: Local Incisional technique: Separate scrotal incisions over each vas deferens Vas occlusion: 1½ - 2 cm vas resected, ends ligated with 00 black silk, sheath of each cut segment closed over that segment Flushing: Not stated Post-vasectomy testing protocol Timing: 1 test preoperatively then starting 1 day postoperatively Number of tests: 1 preoperatively, 10 postoperatively Definition of sterility: Not applicable Definition of failure: Not applicable

Level of Evidence: IV Follow-up: 7 – 37 days (mean, 15 days) Lost to Follow-up: None Study Period: Not stated Operator Details: Not stated

Men undergoing vasectomy Sample Size: 13 men, 143 specimens Mean Age: 42 years (range, 26-58)

Not stated.

75

Authors Intervention Study Design Study Population Inclusion/Exclusion Criteria Goldstein 1983

Location USA Department of Urology, State University of New York, Downstate Medical Center, Brooklyn, New York.

Vasectomy Location: An outpatient clinic. Anaesthesia: Local. Incisional technique: Transverse high scrotal incision. Vas occlusion: 0.5cm segments of vas removed, abdominal side lumina cauterised. Testicular side not cauterised or ligated. Flushing: Not stated. Post-vasectomy testing protocol Timing: Started after 15 ejaculations, post-vasectomy. Number of tests: Varied. Definition of sterility: Azoospermia (presence of nonmotile spermatozoa not mentioned). Definition of failure: Presence of motile spermatozoa.

Case series Level of Evidence: IV Follow-up: At least 5 months. Lost to Follow-up: Not stated. Study Period: Not stated. Operator Details: Not stated.

Men undergoing open-ended vasectomy. Sample Size: 4 Mean Age: Not stated.

Not stated.

76

Authors Intervention Study Design Study Population Inclusion/Exclusion Criteria Haldar et al. 2000

Location UK Elliot-Smith Clinic, Churchill Hospital, Oxford.

Vasectomy Location: Elliot-Smith Clinic Anaesthesia: Local Incisional technique: Not stated Vas occlusion: intraluminal cautery applied to ends of vas after removal of 1-2cm. Flushing: Not stated Post-vasectomy testing protocol Timing: 16 and 18 weeks post-vasectomy Number of tests: 2 Definition of sterility: 2 consecutive azoospermic semen samples at 16 and 18 weeks post-vasectomy. Definition of failure: Early failure: patient not cleared at first semen analysis. Late failure: presence of sperm in ejaculate after initial negative semen analysis.

Prospective study; case series. Level of Evidence: IV Follow-up: 3 years Lost to Follow-up: 850 (38%) between 1 & 2 years. 400 (18%) between 2 & 3 years. Study Period: 1990 - 1993 Operator Details: Clinic surgeons.

Men who had undergone vasectomy and had shown azoospermia in two consecutive samples at 16 and 18 weeks. Sample Size: 2250 Mean Age: Not stated

Men with two consecutive samples showing azoospermia at 16 and 18 weeks postoperatively were included.

77

Authors Intervention Study Design Study Population Inclusion/Exclusion Criteria Jackson et al. 1970

Location UK Family Planning Association, Cardiff; United Cardiff Hospitals; Welsh National School of Medicine.

Vasectomy Location: Cardiff Family Planning Association Clinic Anaesthesia: Local Incisional technique: Either 1 midline or 2 lateral incisions Vas occlusion: 3-4cm vas resected, cut ends doubled back and ligated with catgut (n=230), or ligated with thread (n=100) Flushing: Not stated Post-vasectomy testing protocol Timing: Initially, tests requested at 8, 10 and 12 weeks postoperatively. Later, tests were requested at 12 and 16 weeks. 2 consecutive negative tests one month apart required. Number of tests: 2 (more if required) Definition of sterility: Azoospermia Definition of failure: Presence of sperm

Case series Level of Evidence: IV Follow-up: Up to 38 weeks Lost to Follow-up: 20 (6%) failed to complete testing, 12 (4%) of these submitted no samples Study Period: October 1968 – May 1970 Operator Details: Not stated


130/330 excluded as not enough time had elapsed since vasectomy for clearance.

78

Authors Intervention Study Design Study Population Inclusion/Exclusion Criteria Jina et al. 1977

Location INDIA Department of Surgery, L. L. R. M. Medical College, Meerut.

Vasectomy Location: Not stated Anaesthesia: Not stated Incisional technique: Not stated Vas occlusion: Not stated Flushing: Not stated Post-vasectomy testing protocol Timing: Not stated Number of tests: Not stated Definition of sterility: Not stated Definition of failure: Not stated

Case report Level of Evidence: IV Follow-up: 3 years Lost to Follow-up: NA Study Period: Not stated Operator Details: Not stated

A vasectomised man Sample Size: 1 Age: 30

Not stated.

79

Authors Intervention Study Design Study Population Inclusion/Exclusion Criteria Jouannet and David 1978

Location FRANCE Laboratoire d’Histologie, Centre Hospitalier, Paris

Vasectomy Location: Not stated Anaesthesia: Not stated Incisional technique: Not stated Vas occlusion: Not stated Flushing: Not stated Post-vasectomy testing protocol Timing: Started from 2 to 8 days postoperatively. Number of tests: Every 8 days until 2 consecutive tests showed asthenospermia. Definition of sterility: Asthenospermia Definition of failure: Not applicable

Case series Level of Evidence: IV Follow-up: at least 50 days Lost to Follow-up: Not stated Study Period: Not stated Operator Details: Not stated

Vasectomised men who had at least 2 pre- and post- vasectomy examinations of their semen. Sample Size: 76 Mean Age: Not stated

Not stated.

80

Authors Intervention Study Design Study Population Inclusion/Exclusion Criteria Khan and Cranston 1997

Location UK Department of Urology and Elliot Smith Clinic, Churchill Hospital, Oxford

Vasectomy Location: Elliot Smith Clinic Anaesthesia: Not stated Incisional technique: Not stated Vas occlusion: Not stated Flushing: Not stated Post-vasectomy testing protocol Timing: At 16 and 18 weeks initially, then at approx. 22 months and then again after 12 years. Number of tests: 5 in total Definition of sterility: tests negative for spermatozoa Definition of failure: paternity and tests positive for spermatozoa

Case report Level of Evidence: IV Follow-up: 12 years Lost to Follow-up: Not applicable Study Period: 1983 - 1995 Operator Details: Not stated

A vasectomised man Sample Size: 1 Age: 57

Not stated.

81

Authors Intervention Study Design Study Population Inclusion/Exclusion Criteria Lee and Paterson 2001 Letter

Location UK Department of General Surgery, Birmingham Heartlands and Solihull NHS Trust, Bordesley Green East, Burmingham.

Vasectomy Location: Not stated Anaesthesia: Not stated Incisional technique: Not stated Vas occlusion: Not stated Flushing: Not stated Post-vasectomy testing protocol Timing: After 30 post-vasectomy ejaculations (and then after 50 if 1st test positive) Number of tests: 1 initially, 2 if 1st positive Definition of sterility: Azoospermia Definition of failure: Presence of sperm

Case series Level of Evidence: IV Follow-up: Not stated Lost to Follow-up: None Study Period: Not stated Operator Details: Not stated

Men who had undergone vasectomy. Sample Size: 462 Mean Age: Not stated

Not stated.

82

Authors Intervention Study Design Study Population Inclusion/Exclusion Criteria Lehtonen 1975

Location FINLAND Department of Surgery II, University Central Hospital, Helsinki.

Vasectomy Location: University Central Hospital, Helsinki. Anaesthesia: Local. Incisional technique: Not stated. Vas occlusion: 1-2 cm resected, ends ligated with catgut. Fascial sheath sutured over distil cut end with catgut. Flushing: Not stated. Post-vasectomy testing protocol Timing: 2 weeks and 2 months post-vasectomy, then monthly until 2 negative tests provided. Number of tests: 2 initially, more if required. Definition of sterility: Azoospermia (no mention made of motility). Definition of failure: Presence of spermatozoa.

Case series Level of Evidence: IV Follow-up: Up to 3 months. Lost to Follow-up: None. Study Period: Vasectomies performed January 1, 1972 to December 31, 1973. Operator Details: Not stated.

Men undergoing vasectomy for voluntary sterilisation. Sample Size: 90 Mean Age: Not stated. Range 21 - 50

Not stated.

83

Authors Intervention Study Design Study Population Inclusion/Exclusion Criteria Lehtonen and Juusela 1973

Location FINLAND Department of Surgery II, University Central Hospital, Helsinki

Vasectomy Location: University Central Hospital, Helsinki Anaesthesia: Local Incisional technique: Not stated Vas occlusion: 1-2cm resected, cut ends ligated with catgut. Flushing: Not stated. Post-vasectomy testing protocol Timing: 2 and 4 months Number of tests: 2 Definition of sterility: Not stated Definition of failure: Not stated THIS STUDY IMMEDIATELY PRECEDES LEHTONEN 1975

Case series Level of Evidence: IV Follow-up: At least 18 months Lost to Follow-up: Not stated Study Period: July 1970 to December 1971 Operator Details: Not stated

Men undergoing vasectomy. Sample Size: 94 Mean Age: range, 20-58 years

Not stated.

84

Authors Intervention Study Design Study Population Inclusion/Exclusion Criteria Lewis et al.. 1984

Location USA University of California, School of Medicine, California.

Vasectomy Location: Not stated Anaesthesia: Not stated Incisional technique: Not stated Vas occlusion: Not stated Flushing: Not stated Post-vasectomy testing protocol Timing: 1 (pre-vasectomy, the morning of their scheduled procedure), a second test 3 days post-operatively. Number of tests: 2 (1 before & 1 after) Definition of sterility: Not applicable Definition of failure: Not applicable Lab protocol: Semen samples delivered within 2 hours of collection Volume of specimen measured, visual assessment of motility, sperm concentration determined by haemocytometer. Swimming speed assessed by video recording.

Case series Level of Evidence: IV Follow-up: 3 days Lost to Follow-up: None Study Period: Not stated Operator Details: Not stated

Men undergoing vasectomy and providing a pre-vasectomy semen analysis and a post-vasectomy semen analysis. Sample Size: 9 Mean Age: Not stated

Not stated.

85

Authors Intervention Study Design Study Population Inclusion/Exclusion Criteria Leungwattanakij et al. 2001

Location THAILAND Division of Urology, Department of Surgery, Ramathibodi Hospital, Mahidol University, Bangkok.

Vasectomy Location: Ramathibodi Hospital, Bangkok Anaesthesia: Local. Incisional technique: No scalpel technique. Vas occlusion: 0.5 – 1cm vas resected, proximal end ligated with 3/0 silk thread. Flushing: In irrigated group, an Angiocath 24 gauge needle was inserted into vas lumen, 20 mL of normal saline solution was irrigated manually on both sides. Post-vasectomy testing protocol Timing: 2, 6 & 12 weeks. Number of tests: 3. Definition of sterility: No motile sperm (asthenospermia). Definition of failure: Presence of motile sperm.

Comparative study investigating irrigation vs. no irrigation, but not of different PVSA protocols. Level of Evidence: IV Follow-up: 12 weeks Lost to Follow-up: 9 (15%) from no irrigation group failed to follow up, 5 (8%) from irrigated group failed to follow up. Study Period: Vasectomies performed between July 15 1998 and October 15 1999. Operator Details: Not stated.

Men undergoing vasectomy Sample Size: 62/78 (16 excluded) (31 per group) Mean Age: 36.8 (no irrigation group) 36.0 (irrigated group)

Exclusion criteria included: - inflammation or infection of scrotal sac - abnormality or congenital anomalies of vas deferens - previous sterilizaton - loss to follow-up - assignment allocation error - technical error - aged less than 25 years - less than 2 living children

86

Authors Intervention Study Design Study Population Inclusion/Exclusion Criteria Livingstone 1971

Location CANADA Calgary, Alberta

Vasectomy Location: Not stated Anaesthesia: Local Incisional technique: Not stated Vas occlusion: Not stated Flushing: Not stated Post-vasectomy testing protocol Timing: Not stated Number of tests: 2? Definition of sterility: Not stated Definition of failure: Not stated

Case series Level of Evidence: IV Follow-up: Not stated Lost to Follow-up: Not stated Study Period: Not stated, but over 11 years Operator Details: Not stated

Vasectomised men Sample Size: 3200 Mean Age: 35-40 (range 21-75)

Not stated.

87

Authors Intervention Study Design Study Population Inclusion/Exclusion Criteria Lo et al. 1980

Location US and TAIWAN International Fertility Research Program, Research Triangle Park, North Carolina; Maternal and Child Health Center, Taiwan Area, Taipei.

Vasectomy Location: Not stated. Anaesthesia: Not stated. Incisional technique: Not stated. Vas occlusion: Not stated. Flushing: Not stated. Post-vasectomy testing protocol Timing: Started 28 days post-vasectomy. Number of tests: 5. Definition of sterility: Not stated. Definition of failure: Not stated although pregnancy occurred.

Case report Level of Evidence: IV Follow-up: 374 days Lost to Follow-up: Not applicable. Study Period: Not stated. Operator Details: Not stated.

A patient who underwent a routine vasectomy procedure whose partner subsequently became pregnant. Sample Size: 1 Age: 32

Not stated.

88

Authors Intervention Study Design Study Population Inclusion/Exclusion Criteria Luke et al. 1979 DANISH LANGUAGE

Location DENMARK Department of Surgery, Sct Elisabeth, Copenhagen

Vasectomy Location: Sct. Elisabeth? Anaesthesia: Local Incisional technique: 1.5cm resection of the vas deferens Vas occlusion: metal clips Flushing: Not stated Post-vasectomy testing protocol Timing: 3 – 4 months Number of tests: 2 Definition of sterility: 2 consecutive azoospermic tests Definition of failure: Presence of sperm

Case series Level of Evidence: IV Follow-up: 6 months Lost to Follow-up: 215 (37%) did not provide samples Study Period: March – December 1977 Operator Details: Not stated

Men undergoing vasectomy Sample Size: 580 Mean Age: Not stated

Not stated.

89

Authors Intervention Study Design Study Population Inclusion/Exclusion Criteria Maatman et al. 1997

Location USA Michigan Urological Clinic, Grand Rapids, Michigan.

Vasectomy Location: Michigan Urological Clinic Anaesthesia: Local Incisional technique: Conventional incisional technique initially and then the ‘no scalpel’ technique. Vas occlusion: 1 cm of vas removed and cautery of all vassal lumina Flushing: None Post-vasectomy testing protocol Timing: After 12 ejaculations Number of tests: 2 initially, more if tests positive, then annually Definition of sterility: 2 consecutive negative semen analyses 1 month apart. Definition of failure: Positive semen analysis – sperm present, negative semen analysis – no sperm seen on multiple fields Written instructions: 2 sets detailing method used for determining sterility + careful oral instruction

Retrospective case series Level of Evidence: IV Follow-up: At least 1 year. Lost to Follow-up: 644 (34%) never supplied any samples. 619 (33%) only provided 1 sample. 629 (33%) provided 2 or more samples but failed to follow up annually. Study Period: 1985-1995 Operator Details: Vasectomies performed by one of two urological surgeons (T.J. Maatman or G.G. Carothers).

Patients undergoing vasectomy. Sample Size: 1892 Mean Age: Not stated

Not stated.

90

Authors Intervention Study Design Study Population Inclusion/Exclusion Criteria Marshall and Lyon 1972

Location USA Division of Urology, University of California School of Medicine, San Francisco, California.

Vasectomy Location: Not stated. Anaesthesia: Not stated. Incisional technique: Not stated. Vas occlusion: Small portions excised, electrocoagulation of the vasa was performed and ligation to severed ends with silk. In some cases, fascial sheath was closed over one end. Flushing: Not stated. Post-vasectomy testing protocol Timing: Started after 4 ejaculations, and repeated after every 4 subsequent ejaculations. Number of tests: 4 minimum Definition of sterility: A minimum of 4 samples tested (reflecting 16 ejaculations) and the last 2 had to be azoospermic. Later, a negative specimen at 2 months post-vasectomy was also required. Definition of failure: Presence of sperm (no mention of motility).

Case series Level of Evidence: IV Follow-up: Up to 6 months Lost to Follow-up: Study Period: Not stated. Operator Details: Not stated.

Men undergoing vasectomy. Sample Size: 200 Mean Age: Not stated, range 25-60 Note: Overlap in patients from other Marshall and Lyon 1972 paper.

Consecutive patients

91

Authors Intervention Study Design Study Population Inclusion/Exclusion Criteria Marshall and Lyon 1972

Location USA Division of Urology, University of California School of Medicine, San Francisco.

Vasectomy Location: Not stated. Anaesthesia: Not stated. Incisional technique: Not stated. Vas occlusion: electrocoagulation of lumina, severed ends then ligated with silk and ends pointed in different directions. Flushing: Not stated. Post-vasectomy testing protocol Timing: Every 4 ejaculations (from 1 week post-vasectomy) Number of tests: Not stated. Definition of sterility: Aspermia (?) Azoospermia? Definition of failure: Presence of sperm

Case report and case series Level of Evidence: IV Follow-up: Up to 26 weeks. Lost to Follow-up: Not stated. Study Period: Not stated. Operator Details: Not stated.

Men undergoing vasectomy. Sample Size: 400 Mean Age: Not stated (range: 24 – 60). Note: Probably some overlap in patients from other Marshall and Lyon 1972 paper.

Not stated.

92

Authors Intervention Study Design Study Population Inclusion/Exclusion Criteria Milne et al. 1986

Location UK Lothian Health Board Family Planning Services, Edinburgh

Vasectomy Location: Edinburgh Family Planning Centre. Anaesthesia: Local. Incisional technique: 1 or 2 incisions depending on surgeon. Vas occlusion: Length of vas removed varied. Dexon or catgut used to occlude vas. Flushing: Not stated. Post-vasectomy testing protocol Timing: Started at 12 weeks post-vasectomy, then 3 weekly. Number of tests: 2 initially, more if needed. Definition of sterility: 2 consecutive negative samples (importance motility not reported in paper). Definition of failure: Presence of sperm.

Case series. Level of Evidence: IV Follow-up: 1 year. Lost to Follow-up: 18 (9%) patients did not submit samples. Study Period: Not stated. Operator Details: 4 different surgeons.

Vasectomised men. Sample Size: 200 (seen consecutively) Mean Age: 34 years (range 24 – 53).

Not stated.

93

Authors Intervention Study Design Study Population Inclusion/Exclusion Criteria O’Brien et al. 1995


Vasectomy Location: Elliot-Smith Clinic Anaesthesia: Local Incisional technique: Not stated. Vas occlusion: intra-luminal diathermy to the vasal stumps Flushing: Not stated Post-vasectomy testing protocol Timing: At 16 and 18 weeks initially, and then after 1 year. Number of tests: 3 Definition of sterility: Azoospermia (confirmed by two successive negative semen analyses). Definition of failure: Presence of sperm

Case series Level of Evidence: IV Follow-up: 1 year Lost to Follow-up: 1 (0.1%) man failed to provide a follow up sample after an initial positive test. Study Period: 1990-1991 Operator Details: Not stated

The first 1000 men providing a semen sample 1 year after undergoing vasectomy at the Elliot-Smith clinic in 1990. Sample Size: 1000 Mean Age: Not stated

Not stated.

94

Authors Intervention Study Design Study Population Inclusion/Exclusion Criteria O’Reilly and Gradwell 2000 Letter

Location UK Stepping Hill Hospital, Stockport.

Vasectomy Location: Not stated. Anaesthesia: Not stated. Incisional technique: Not stated. Vas occlusion: Segment of vas excised, ends doubled back and ligated with linen. Flushing: Not stated. Post-vasectomy testing protocol Timing: Not stated. Number of tests: Not stated. Definition of sterility: Not stated. Definition of failure: Not stated.

Case report Level of Evidence: IV Follow-up: 10 years Lost to Follow-up: Not applicable. Study Period: 1986 - 1996 Operator Details: Not stated.

Vasectomised man. Sample Size: 1 Age: Not stated

Not stated.

95

Authors Intervention Study Design Study Population Inclusion/Exclusion Criteria Philp et al. 1984


Vasectomy Location: Elliot-Smith Clinic. Anaesthesia: Local. Incisional technique: Not stated. Vas occlusion: Up to 1974, vas ligated at both ends, with one or both ends doubled back, usually without fascial interposition (n=4500). After 1974, intraluminal diathermy was conducted (n=12300) with fascial interposition in only a few cases. Flushing: Not stated. Post-vasectomy testing protocol Timing: Started at 4 months and then 1 to 2 weeks later. Number of tests: 2. Definition of sterility: 2 consecutive azoospermic specimens at least 4 months post-vasectomy. Definition of failure: Presence of spermatozoa.

Case series. Level of Evidence: IV Follow-up: Up to 36 months to time of conception. Lost to Follow-up: Not applicable Study Period: Vasectomies performed April 1970 to December 1983. Operator Details: Various

Vasectomized men. Sample Size: 6 (of 16796 vasectomies) Mean Age: Not stated. Note: May be some overlap in patients with other studies from the Elliot-Smith clinic.

Not stated.

96

Authors Intervention Study Design Study Population Inclusion/Exclusion Criteria Poddar and Roy 1976

Location Not stated

Vasectomy Location: Not stated Anaesthesia: Not stated Incisional technique: Not stated Vas occlusion: Half inch of vas resected, lower end of vas folded and both ends ligated with cotton or silk. Flushing: Not stated Post-vasectomy testing protocol Timing: By 2 months Number of tests: 1 (more if positive) Definition of sterility: Azoospermia Definition of failure: Presence of sperm

case series Level of Evidence: IV Follow-up: Up to ~270 days Lost to Follow-up: ~750 (~63%) Study Period: Completed in 1974 Operator Details: Not stated

Vasectomised men Sample Size: ~1200 Mean Age: Not stated

Not stated.

97

Authors Intervention Study Design Study Population Inclusion/Exclusion Criteria Pugh et al. 1969

Location UK Department of Pathology, St Paul’s Hospital, London; The Institute of Urology, London

Vasectomy Location: Not stated Anaesthesia: Not stated Incisional technique: Not stated Vas occlusion: Vas either resected and tied (n=3) or cut and tied (n=4) Flushing: Not stated Post-vasectomy testing protocol Timing: Varied Number of tests: Varied Definition of sterility: Not stated Definition of failure: Persistence of sperm or pregnancy

Case series Level of Evidence: IV Follow-up: At least 18 months Lost to Follow-up: Not stated Study Period: Not stated Operator Details: Not stated


Not stated.

98

Authors Intervention Study Design Study Population Inclusion/Exclusion Criteria Rageth and Leibundgut 1984 GERMAN LANGUAGE Location SWITZERLAND Urologishce Klinik, Kantonsspital, Basel

Vasectomy Location: University Hospital Basel Anaesthesia: Not applicable Incisional technique: Not applicable Vas occlusion: Not applicable Flushing: Not applicable Post-vasectomy testing protocol Timing: Not applicable Number of tests: Not applicable Definition of sterility: Not applicable Definition of failure: Not applicable

Case series Level of Evidence: IV Follow-up: 3 weeks to at least 1 year Lost to Follow-up: 63 (26%) patients failed to provide samples Study Period: Not stated. Operator Details: Not stated.

Vasectomised men Sample Size: 247 Mean Age: Not stated.

Not stated.

99

Authors Intervention Study Design Study Population Inclusion/Exclusion Criteria Rees 1973

Location UK Cardiff Royal Infirmary, Newport Road, Cardiff.

Vasectomy Location: Family Planning Association Clinic in Cardiff. Anaesthesia: Recommended local. Incisional technique: Not stated. Vas occlusion: Recommended double ligation of the vas, keeping ends well apart. Flushing: Not stated. Post-vasectomy testing protocol Timing: 12 and 16 weeks postoperatively. Number of tests: 2. Definition of sterility: Azoospermia Definition of failure: Presence of sperm (motile or nonmotile).

Case series Level of Evidence: IV Follow-up: Up to 60 weeks. Lost to Follow-up: 53 (6%) submitted no specimen, 48 (5%) submitted 1 specimen only, 48 (5%) submitted multiple specimens but were never cleared. Study Period: Not stated. Operator Details: Not stated.

Men undergoing vasectomy at the Cardiff Royal Infirmary. Sample Size: 903 (of 1000 vasectomies performed). Mean Age: Not stated.

93 patients were excluded as their vasectomies were performed too recently to be complete by the time of the survey.

100

Authors Intervention Study Design Study Population Inclusion/Exclusion Criteria Richardson et al. 1984

Location UK M.R.C. Unit of Reproductive Biology, Edinburgh; Family Planning Centre, Edinburgh

Vasectomy Location: Edinburgh Family Planning Centre Anaesthesia: Not stated Incisional technique: Not stated Vas occlusion: Not stated Flushing: Not stated Post-vasectomy testing protocol Timing: 1st test within 4 weeks pre-vasectomy, 2nd test 3-16 days post-vasectomy Number of tests: 2 Definition of sterility: Not applicable Definition of failure: Not applicable

Case series Level of Evidence: IV Follow-up: 3-16 days Lost to Follow-up: None Study Period: Not stated Operator Details: Not stated

Men undergoing vasectomy Sample Size: 47 Pre- and post-vasectomy: n=40 Post-vasectomy only: n=7 Age: range, 23-50

Not stated.

101

Authors Intervention Study Design Study Population Inclusion/Exclusion Criteria Santiso et al. 1981

Location USA Asocación ProBienestar de La Familia (APROFAM), Guatemala City, Guatemala; Tulane University School of Public Health and Tropical Medicine, New Orleans, Louisiana.

Vasectomy Location: APROFAM Surgical Centre in Guatemala Anaesthesia: Not stated. Incisional technique: Not stated. Vas occlusion: Not stated. Flushing: Not stated. Post-vasectomy testing protocol Timing: Approximately 1 month post-vasectomy. Number of tests: 1 Definition of sterility: Not stated. Definition of failure: Not stated.

Case series - Interviews Level of Evidence: IV Follow-up: 1 to 3 years Survey response rate: 500 (57.3%); 372 did not respond. Study Period: Vasectomies performed January 1977 to December 1979. Operator Details: Not stated.

Vasectomised men. Sample Size: 500/ 872 Mean Age: 36

Residence outside Guatemala City Men who had requested that APROFAM not contact them were excluded.

102

Authors Intervention Study Design Study Population Inclusion/Exclusion Criteria Schirren 1984 GERMAN LANGUAGE

Location GERMANY Department for Andrologie, Center for Reproduction Medicine, University Hospital Hamburg Eppendorf

Vasectomy Location: Not stated Anaesthesia: Not stated Incisional technique: Not stated Vas occlusion: Not stated Flushing: Not stated Post-vasectomy testing protocol Timing: Not done Number of tests: Not done Definition of sterility: Not reported Definition of failure: Not reported

Case report Level of Evidence: IV Follow-up: None Lost to Follow-up: Not applicable Study Period: Not applicable Operator Details: Not stated

Vasectomised man Sample Size: 1 Age: 46

Not stated.

103

Authors Intervention Study Design Study Population Inclusion/Exclusion Criteria Scholtmeijer 1975 DUTCH LANGUAGE

Location THE NETHERLANDS Amsterdam

Vasectomy Location: Not stated Anaesthesia: Not stated Incisional technique: Not stated Vas occlusion: 1-1.5cm vas resected, testicular end tied with reabsorbable suture Flushing: Not stated Post-vasectomy testing protocol Timing: 6 weeks and 10 ejaculations Number of tests: Not stated Definition of sterility: Azoospermia Definition of failure: Presence of sperm

case series Level of Evidence: IV Follow-up: 3 years Lost to Follow-up: Not stated. Study Period: Not stated. Operator Details: ?single operator

Men undergoing vasectomy Sample Size: 463 Mean Age: Not stated.

Not stated.

104

Authors Intervention Study Design Study Population Inclusion/Exclusion Criteria Schraibman 1973 LETTER

Location UK The Infirmary, Rochdale, Lancs

Vasectomy Location: Not stated Anaesthesia: General? Incisional technique: Not stated Vas occlusion: 2.5 cm resesected, ends doubled back and double ligated with non-absorbable suture Flushing: Not stated Post-vasectomy testing protocol Timing: 2 tests after 4 months and then monthly until 2 negative tests. Number of tests: 2 (more if required) Definition of sterility: Azoospermia Definition of failure: Presence of sperm

Letter – case series Level of Evidence: IV Follow-up: Up to 15 months Lost to Follow-up: Not stated Study Period: Not stated Operator Details: Not stated


Not stated.

105

Authors Intervention Study Design Study Population Inclusion/Exclusion Criteria Sherlock and Holl-Allen 1984

Location UK Department of Surgery, East Birmingham Hospital, Bordesley Green East, Birmingham.

Vasectomy Location: Not stated. Anaesthesia: Local initially, then general at revasectomy Incisional technique: Not stated. Vas occlusion: Simple ligation with excision of 3 – 6 cm initially, then at revasectomy, at least 3 cm above and below scarred region excised and ends covered with surrounding tissue using catgut purse-string suture. Flushing: Not stated. Post-vasectomy testing protocol Timing: 2 months postvasectomy , then monthly until 2 consecutive negative tests obtained for 1st vasectomy, then monthly for at least 8 months after revasectomy. Number of tests: 2 (more if necessary to reach 2 consecutive negative tests). Definition of sterility: Azoospermia. Definition of failure: Not stated.

Case series Level of Evidence: IV Follow-up: Up to 4 months initially, then at least 8 months after revasectomy. Lost to Follow-up: None Study Period: 1977 - 1983 Operator Details: Various.

Men undergoing repeat vasectomy after proven failure (by pregnancy). Sample Size: 8 Mean Age: 35 (range 30 – 41)

Not stated.

106

Authors Intervention Study Design Study Population Inclusion/Exclusion Criteria Sivanesaratnam 1985

Location MALAYSIA Department of Obstetrics and Gynaecology, University Hospital, Kuala Lumpur.

Vasectomy Location: University Hospital, Kuala Lumpur. Anaesthesia: Local. Incisional technique: Single incision in the mid-anterior aspect of the scrotum, just lateral to the median raphe. Vas occlusion: Ligation with 2/0 chromic catgut. Fascial interposition Flushing: None. Post-vasectomy testing protocol Timing: Starting after 1 month, then monthly until 3 consecutive negative samples provided. Number of tests: 3 initially. Definition of sterility: Azoospermia. Definition of failure: Presence of sperm (motile or nonmotile).

Retrospective case series Level of Evidence: IV Follow-up: At least 6 months. Lost to Follow-up: Not stated. Study Period: January 1971 to June 1980. Operator Details: Not stated.

Malaysian men who had undergone vasectomy. Sample Size: 916 Mean Age: 96% between 20 and 45 years

Not stated.

107

Authors Intervention Study Design Study Population Inclusion/Exclusion Criteria Smith 1996 Abstract

Location UK Oxford

Vasectomy Location: Not stated. Anaesthesia: Not stated. Incisional technique: Not stated. Vas occlusion: Not stated. Flushing: Not stated. Post-vasectomy testing protocol Timing: Not stated. Number of tests: Not stated. Definition of sterility: Not stated. Definition of failure: Not stated.

Case series Level of Evidence: IV Follow-up: 2 years Lost to Follow-up: 600 (71%) did not reach 2 year follow-up Study Period: Not stated. Operator Details: Not stated.

Men who had undergone vasectomy. Sample Size: 850 (?) Mean Age: Not stated.

Not stated.

108

Authors Intervention Study Design Study Population Inclusion/Exclusion Criteria Spencer and Charlesworth 1976

Location UK Departments of Social Research and Surgery, University of South Manchester.

Vasectomy Location: Manchester Family Planning Association Clinic Anaesthesia: Local Incisional technique: Not stated. Vas occlusion: Not stated. Flushing: Not stated. Post-vasectomy testing protocol Timing: Started 12 weeks post-vasectomy. Number of tests: 2 initially (12 and 16 weeks), then 4-weekly until 2 consecutive negative samples provided. Definition of sterility: Azoospermia. Definition of failure: Not stated.

Case series (retrospective chart review) Level of Evidence: IV Follow-up: At least 16 weeks. Lost to Follow-up: None stated but 1 missing from data. Study Period: Vasectomies performed February 1973 to September 1974. Operator Details: Not stated.

Men who had undergone vasectomy under local anaesthesia at the Manchester Family Planning Association Clinic between February 1973 and September 1974. Sample Size: 831 Mean Age: 34.5 [6.0]

Not stated.

109

Authors Intervention Study Design Study Population Inclusion/Exclusion Criteria Staff of the Margaret Pyke Centre 1973; Marwood and Beral 1979 Location UK Department of Obstetrics and Gynaecology, Guy’s Hospital, London; Department of Epidemiology, London School of Hygiene and Tropical Medicine, London.

Vasectomy Location: Margaret Pyke Centre Anaesthesia: Local Incisional technique: Not stated Vas occlusion: 1 – 4cm resected, ends crushed and ligated with 3-0 black silk Flushing: None Post-vasectomy testing protocol Timing: Started at 12 weeks, then monthly until 2 consecutive negative tests Number of tests: 2 (or more if required) Definition of sterility: Azoospermia Definition of failure: Not stated

Case series Level of Evidence: IV Follow-up: 18 months Lost to Follow-up: 71 (7%) defaulted at some point (1973 study), 12 (2%) lost to follow-up before being cleared (1979 study) Study Period: July 1971 – October 1972 Operator Details: Not stated

Vasectomised men Sample Size: n=1000 (1973 paper) n=624 (1979 paper) Why different? Age: 20-29 years (17%) 30-39 years (54%) over 40 years (29%) (as reported in 1979 paper) THERE IS OVERLAP IN PATIENTS BETWEEN THE TWO STUDIES

Not stated.

110

Authors Intervention Study Design Study Population Inclusion/Exclusion Criteria Surabote 1989

Location THAILAND Division of Urology, Department of Surgery, Lerd Sin Hospital, Bangkok

Vasectomy Location: Lerd Hin Hospital, Bangkok Anaesthesia: Local Incisional technique: 1cm longitudinal incision Vas occlusion: 182 single ligation and 688 double ligation (section resected and cut ends double ligated with non absorbable suture). Flushing: None. Post-vasectomy testing protocol Timing: 12 to 16 weeks. Number of tests: 1 Definition of sterility: Azoospermia. Definition of failure: Presence of sperm

Case series Level of Evidence: IV Follow-up: Up to 18 months Lost to Follow-up: 520 (60%) failed to provide post-vasectomy samples. Study Period: Vasectomies conducted between January 1977 and December 1986 Operator Details: Not stated.

Vasectomised men Sample Size: 870 Mean Age: 39 years

Not stated.

111

Authors Intervention Study Design Study Population Inclusion/Exclusion Criteria Tailly et al. 1984

Location BELGIUM Department of Urology, Catholic University of Leuven, Leuven.

Vasectomy Location: Not stated. Anaesthesia: Local. Incisional technique: 5mm transverse incision. Vas occlusion: Vas resected and both cut ends ligated twice with nonabsorbable braided 2-0 polyester thread. Flushing: None. Post-vasectomy testing protocol Timing: Started 6 to 8 weeks post-vasectomy. Number of tests: 2 (or more until 2 consecutive negative tests). Definition of sterility: Azoospermia Definition of failure: Presence of sperm

Case series Level of Evidence: IV Follow-up: At least 296 days. Lost to Follow-up: 42 (12%) (35 failed to deliver any samples, 7 delivered only 1 sample). Study Period: Vasectomies performed July 1978 to December 1980. Operator Details: Not stated.

Men undergoing vasectomy. Sample Size: 357 Mean Age: 37

Not stated.

112

Authors Intervention Study Design Study Population Inclusion/Exclusion Criteria Temmerman et al. 1986

Location BELGIUM Department of Gynaecology, Andrology and Obstetrics, Adademisch Ziekenhuis, Brussel.

Case series Vasectomy Location: Not stated. Anaesthesia: Local. Incisional technique: Transverse, high scrotal incision. Vas occlusion: Abdominal side lumen of vas cauterised over 10mm and ligated with chromic catgut 00. Testicular side neither cauterised nor ligated. Ends of vas separated into different fascial planes by sealing sheath of vas over proximal end. Flushing: None stated. Post-vasectomy testing protocol Timing: 6 weeks and 6 months post vasectomy. Number of tests: 2. Definition of sterility: Not stated (presence of nonmotile sperm not considered/mentioned). Definition of failure: Presence of motile sperm (presence of nonmotile sperm not considered/mentioned).

Level of Evidence: IV Follow-up: 6 months. Lost to Follow-up: 3 (3%) did not provide any samples. 37 (37%) failed to attend 6 month follow-up. 2 of the 63 attending the follow-up failed to provide semen sample. Study Period: December 1981 to July 1982. Operator Details: All vasectomies performed by same surgeon.

Men undergoing open-ended vasectomy. Sample Size: 100 Mean Age: 35 (range 27 – 61) years

Not stated.

113

Authors Intervention Study Design Study Population Inclusion/Exclusion Criteria Thompson et al. 1991

Location UK Department of Obstetrics and Gynaecology, University of Aberdeen, Aberdeen.

Vasectomy Location: Not stated. Anaesthesia: Not stated. Incisional technique: Not stated. Vas occlusion: Not stated. Flushing: Not stated. Post-vasectomy testing protocol Timing: Started 3 months post-vasectomy. Number of tests: 2 initially, more if tests positive. Definition of sterility: Azoospermia. Definition of failure: Presence of sperm (distinction between motile and nonmotile spermatozoa was not reported).

Case series Level of Evidence: IV Follow-up: At least 40 weeks. Lost to Follow-up: 15 (5%) failed to provide any samples, 25 (9%) provided some samples but were never cleared. Study Period: Vasectomies requested between 1978 and 1981. Operator Details: Not stated.

Vasectomized men. Sample Size: 284 (a random sample of 568 men who underwent vasectomy) for comparative group. Mean Age: Not stated.

1) Resident in Aberdeen City District. 2) Vasectomy for contraceptive purposes only.

114

Authors Intervention Study Design Study Population Inclusion/Exclusion Criteria Thomson et al. 1993

Location UK Department of Haematology, London Hospital Medical College, London. Family Planning Service, Croydon Community Health, Croydon, Surrey.

Vasectomy Location: Not stated Anaesthesia: Not stated Incisional technique: Not stated Vas occlusion: Not stated Flushing: Not stated Post-vasectomy testing protocol Timing: At 12 and 18 weeks initially, then at 2½ years and 5 years Number of tests: 4 in total Definition of sterility: Azoospermia Definition of failure:

1) early failure: presence of spermatozoa 2) later failures: either high levels of active spermatozoa (due

to recanalisation) or “non-significant” numbers of non-motile spermatozoa.

Case report Level of Evidence: IV Follow-up: 5 years Lost to Follow-up: Not applicable Study Period: Dec 1987 - 1992 Operator Details: Not stated.

Vasectomised man Sample Size: 1 Age: Not stated

Not stated.

115

Authors Intervention Study Design Study Population Inclusion/Exclusion Criteria Urquhart-Hay 1975

Location NEW ZEALAND Wellington Hospital, Wellington

Vasectomy Location: Not stated. Anaesthesia: Not stated. Incisional technique: Not stated. Vas occlusion: Not stated. Flushing: Irrigated with 2.5ml 1/1000 solution sterile euflavine Post-vasectomy testing protocol Timing: 2 – 11 days post-vasectomy Number of tests: 1 (that was reported in this paper, standard protocol?) Definition of sterility: Not azoospermia, but exactly what not stated? Definition of failure: Not stated

Case series Level of Evidence: IV Follow-up: 31 to 57 weeks Lost to Follow-up: 1 (3%) Study Period: Not stated Operator Details: Not stated

Vasectomised men Sample Size: 32 (of ?) Mean Age: Not stated THIS STUDY REPORTS THE 32 PATIENTS WHO DECIDED NOT TO WAIT FOR AN AZOOSPERMIC SAMPLE BEFORE ABANDONING ALTERNATIVE CONTRACEPTIVE METHODS.

Patients (n not specified) who chose to wait for azoospermia were excluded.

116

Authors Intervention Study Design Study Population Inclusion/Exclusion Criteria van Vugt et al. 1985 DUTCH LANGUAGE Location THE NETHERLANDS Zeikenhuis Leyenburg, The Hague, Department of Surgery, Urology and Pathology

Vasectomy Location: Hague infirmary Anaesthesia: local Incisional technique: 1-4 cm incision closed with reabsorbable suture Vas occlusion: Both ends tied with non reabsorbable suture Flushing: Not stated. Post-vasectomy testing protocol Timing: after the 10th ejaculation Number of tests: Definition of sterility: O –sterility confirmed – azoospermia or single non-motile sperm, NMZO – sterility not clearly confirmed – non-motile sperm concentration more than 0.1 x 106/ml NO – sterility not confirmed – motile sperm, regardless of number Definition of failure: Not stated.

Retrospective chart review Level of Evidence: IV Follow-up: Up to 48.5 weeks. Lost to Follow-up: 32 (1%) patients did not provide further tests after NMZO result; 5 (0.2%) did not provide further tests after NO result. Study Period: January 1980 – January 1984 Operator Details: Not stated

Men undergoing vasectomy Sample Size: 3150 men, 4406 PVSA tests Mean Age: Not stated

Not stated.

117

Appendix D.3: Data summary table – Post-vasectomy protocols

Definition of sterility / success

Number of required tests Timing of tests

Number of ejaculations

required

Use of histological

testing Definition of failure

Comparative studies

Badrakumar et al. 2000

Azoospermia. Group 1: 1 azoospermic test. Group 2: 2 consecutive azoospermic tests.

Group 1: Single test at 4 months postoperatively, more tests at monthly intervals if required.

Group 2: Tests at 3 and 4 months, then monthly if required.

Smith et al. 1998 Azoospermia. 2 Hosp A: 1st test at 3 months postoperatively, 2nd at 7-28 days later. Hosp B: 2 tests at 6 months postoperatively. Hosp A, part II: 2 tests at 6 months postoperatively.

Hosp A: Histological analysis performed in some cases. Hosp B: Histological confirmation performed in all cases.

Presence of sperm (motile or non-motile).


118

Appendix D.3: Data summary table – Post-vasectomy protocols (continued)




required

Use of histological


Case series

Alderman 1988; Alderman 1989

Azoospermia. 2 consecutive azoospermic tests.

Started 3 months postoperatively, then monthly.

Early failure: sig. no. of sperm or more than 1 motile sperm per HPF (within 12 months) (>100 x 106/L). Late failure: sperm in any number or condition after success of vasectomy proved. Overt failure: continuous presence of sig. no. of sperm or any motile sperm later than 4 months after vasectomy. Technical failure: nonsignificant numbers of sperm present one year after vasectomy or later (<100 x 106/L).

Arango et al. 1993 SPANISH

Azoospermia. 1 (unless positive, then more).

Started at 3 months, then every 2 months until negative.

Belker et al 1990 Azoospermia. Special clearance given in cases where rare non-motile sperm present.

2 consecutive azoospermic tests.

First sample at 4 months.

Benger et al. 1995 Azoospermia. Persistent sperm after vasectomy (no distinction made between motile and non-motile).


119





required

Use of histological


Black 2002 Azoospermia. 2 consecutive azoospermic tests.

12 and 14 weeks. Primary failure: PVSA positive for sperm. Secondary failure: reappearance of sperm at “later stage”.



3 and 4 months postoperatively.

Chan et al 1997 Azoospermia. 2 consecutive azoospermic tests.

12 and 16 weeks. Presence of spermatozoa.

DeKnijff et al. 1997 Azoospemia. 2 tests, with 2nd test azoospermic, more tests if last test not negative.

6 and 12 weeks. Histological confirmation after every vasectomy.

Denniston 1985 Not stated. Not stated. 6 weeks. 15 ejaculations.

Presence of ‘live’ sperm.

Edwards 1977, 1993 Azoospermia or non-motile sperm only.

1 intially, 2 if motile sperm or large numbers of non-motile sperm present.

Protocol changed over time. Initially, time of sample based on no. of ejaculations; in a later period, sample requested at 3 weeks; most recently, sample requested at 4 weeks (regardless of no. ejaculations).

10 (in earlier part of period reported in paper).

Motile sperm in 2nd test was taken to indicate recanalization and revasectomy was advised.

Eisner et al. 2001 Azoospermia. 2 consecutive azoospermic tests.

Started 6 weeks postoperatively, then every 6 weeks.


120





required

Use of histological


Elliot Smith clinic Halder et al. 2000 O’Brien et al. 1995 Philp et al. 1984

Azoospermia. 2 consecutive azoospermic tests, at least 4 months post-vasectomy.

16 and 18 weeks. Early failure: patient not cleared at first semen analysis. Late failure: presence of sperm in ejaculate after initial negative semen analysis.

Esho et al. 1974 and Esho and Cass 1978

Aspermia (azoospermia?).

1 azoospermic test. Started at 8 weeks then every 4 weeks until cleared.

Histological examinations performed.

Jackson et al. 1970 Azoospermia. 2 consecutive azoospermic tests.

Initially, tests required at 8, 10 and 12 weeks. Later, 12 and 16 weeks.

Lee and Paterson 2001

Azoospermia. 1 azoospermic test. 30, then after 50 if first is positive.

Lehtonen and Juusela 1973

Not stated. 2 2 and 4 months. Histological examination in 92/94.

Lehtonen 1975 Did not state whether motile and non-motile sperm were distinguished. ‘Negative’.

2 consecutive negative samples at least 1 month apart.

2 weeks and 2 months. Histological confirmation in all cases.

Leungwattanakij et al. 2001

Asthenospermia.

3 2, 6 and 12 weeks. Presence of motile sperm.


121





required

Use of histological


Maatman et al. 1997 Azoospermia. 2 consecutive azoospermic tests.

12

Marwood and Beral 1979 and Staff of Margaret Pyke Centre 1973


Starts at 12 weeks and then monthly.

Milne et al. 1986 Azoospermia. 2 consecutive negative samples.

12 and 15 weeks. Presence of sperm (motility not reported).

Rees 1973 Aspermia. Azoospermia?

2 consecutive azoospermic samples.

12 and 16 weeks postoperatively, more if required.


Santiso et al. 1981 Not stated. 1 Approx. 1 month postoperatively.

Schraibman 1973 Letter

Azoospermia. 2 consecutive azoospermic samples.

2 tests after 4 months and then monthly until cleared.

Sherlock and Holl-Alen 1984


Started 2 months postoperatively, then monthly until cleared.

Sivanesaratnam 1985


Started 1 months postoperatively, then monthly until cleared.

Histological confirmation in all cases.


Spencer and Charlesworth 1976


12 and 16 weeks initially, then monthly if required.

Surabote 1989 Azoospermia. 1 azoospermic sample. Between 12 and 16 weeks.


122





required

Use of histological


Tailly et al. 1984 Azoospermia. 2 consecutive azoospermic samples.

Started 6 – 8 weeks postoperatively.

Histological confirmation obtained.

Temmerman et al 1986

Not stated. 2 6 weeks and 6 months postoperatively.

Histological confirmation obtained.

Thompson et al. 1991


Started 3 months postoperatively.

van Vugt et al. 1985 DUTCH

Azoospermia or single (few?) non-motile sperm.

1? After 10 ejaculations.

NMZO-sterility not clearly confirmed (> 0.1 x 106/ml non-motile sperm). NO-sterility not confirmed (motile sperm present).

123

Appendix D.4: Data summary table – Compliance with post-vasectomy testing

Failed to follow-up (no samples provided)

Partial follow-up (some samples provided)

Lost to follow-up (not known whether any

samples given) Total lost to follow up Fully complied with

follow-up protocol

Comparative studies

Badrakumar et al. 2000

Group 1: 151/961 (15.71%) Group 2: 66/360 (18.33%)

Group 1: 6/961 (0.62%) (3 failed to provide 2nd sample, 1 a 3rd, 2 a 4th) Group 2: 36/360 (10%)(35 failed to provide 2nd sample, 1 failed to provide further samples after a positive test)

Group 1: 157/961 (16.34%) Group 2: 102/360 (28.33%)

Group 1: 804/961 (83.66%) Group 2: 258/360 (71.67%)

Smith et al. 1998 Hosp A: 58/245 (23.67%) Hosp A (part 2): 18/87 (20.69%) Hosp B: 24/100 (24%)

Hosp A: not reported Hosp A (part 2): 0/87 (0%) Hosp B: 0/100 (0%)

Hosp A: not clear Hosp A II: 18/87 (20.69%) Hosp B: 24/100 (24%)

Hosp A: not reported Hosp A (part 2): 69/87 (79.31%) Hosp B: 76/100 (76%)

Case series

Arango et al. 1993 SPANISH

62/313 (19.81%) 14/313 (4.47%) (11 failed to provide 2nd sample, 3 failed to provide 3rd sample)

76/313 (24.28%) 237/313 (75.72%)

Belker et al. 1990 375/1029 (36.44%) 84/1029 (8.16%) (failed to provide 2nd sample)

459/1029 (44.61%) 570/1029 (55.39%)

Black 2002 3309/45123 (7.33%) 3309/45123 (7.33%) ?41814/45123 (92.67%)


124

Appendix D.4: Data summary table – Compliance with post-vasectomy testing (continued)





follow-up protocol

Bradshaw et al. 2001 34/240 (14.17%) 32/240 (13.33%) (22 failed to provide 2nd sample, 10 failed to provide further samples)

66/240 (27.5%) 174/240 (86%)

Burnight et al. 1975 141/292 (48.29%) 141/292 (48.29%) ?151/292

Chan et al. 1997 34/574 (5.92%) 26/574 (4.53%) 60/574 (10.45%) 514/574 (89.55%)

Cortes et al. 1997 3/38 (7.89%) 6/38 (15.79%) 9/38 (23.68%) 29/38 (76.32%)

DeKniff et al. 1997 18/413 (4.36%) 39/413 (9.44%) 57/413 (13.80%) 356/413 (86.20%)

Edwards 1977, 1993 918/3178 (28.89%) 918/3178 (28.89%) 2260/3178 (71.11%)

Eisner et al. 2001 109/443 (24.60%) 182/443 (41.08%) returned only 1 sample

291/443 (65.69%) 152/443 (34.31%)

Esho et al. 1974 and Esho and Cass 1978

119/889 (13.39%) 210/1527 (13.75%) (2nd paper)

119/889 (13.39%) 210/1527 (13.75%)

770/889 (86.61%) 1317/1527 (86.25%) (2nd paper)

Goldstein 1983 (was a test of new technique – include here?)

0/4 (0%) 0/4 (0%) 0/4 (0%) 4/4 (100%)

Jackson et al. 1970 * 2 patients missing

12/200 (6.00%) 8/200 (4.00%) 20/200 (10%) 178/200 (89.00%)

Lee and Paterson 2001 (letter)

0/462 (0%) 0/462 (0%) 0/462 (0%) 462/462 (100%)


125






follow-up protocol

Leungwattanakij et al. 2001

14/62 (22.58%) 14/62 (22.58%) 48/62 (77.42%)

Lehtonen 1975 0/90 (0%) 0/90 (0%) 0/90 (0%) 90/90 (100%)

Luke et al. 1979 DANISH

215/580 (37.07%) Partial compliance can not be determined without full translation.

215/580 (37.07%) ?

Maatman et al. 1997 644/1892 (34.04%) 619/1892 (32.72%) 1263/1892 (66.75%) 629/1892 (33.25%)

Marshall and Lyon 1972

0/200 (0%) 0/200 (0%) 0/200 (0%) 200/200 (100%)

Marwood and Beral 1979 and Staff of Margaret Pyke Centre 1973

12/624 (1.92%) 71/1000 (7.10%) 71/1000 (7.1%) 12/624 (1.92%)

929/1000 (92.90%) 612/624 (92.08%)

Milne et al. 1986 18/200 (9.00%) 0/200 (0%) 18/200 (9%) 182/200 (91.00%)

Rageth and Leibundgut 1984 GERMAN

63/247 (25.51%) 63/247 (25.51%) 184/247 (74.49%)

Rees 1973 53/903 (5.87%) 275/903 (30.45%) (48/903 submitted only 1 specimen, 222 submitted multiple specimens but never cleared)

328/903 (36.32%) 575/903 (63.68%)

Santiso et al. 1981 131/500 (26.50%) 131/500 (26.2%) 369/500 (73.80%)


126






follow-up protocol

Surabote 1989 520/870 (59.77%) 520/870 (59.77%) 350/870 (40.23%)

Tailly et al. 1984 35/357 (9.80%) 7/357 (1.96%) (provided only 1 sample)

42/357 (11.76%) 315/357 (88.80%)

Temmerman et al. 1986

3/100 (3.00%) 39/100 (39.00%) (provided only 1 sample)

42/100 (42%) 58/100 (58.00%)

Thompson et al. 1991 15/284 (5.28%) 25/284 (8.80%) (provided some samples but never completed follow-up)

40/284 (14.08%) 244/284 (85.92%)

Urquhart-Hay 1975 1/32 (3.13%) 1/32 (3.13%) 31/32 (96.88%)

van Vugt et al 1985 DUTCH

37/3150 (1.17%) (32 failed to provide sample after NMZO result, 5 failed to provide sample after NO result)

37/3150 (1.17%) ?

127

Appendix D.5: Data summary table – Outcomes of vasectomy Badrakumar et al.

2000 Smith et al. 1998 Alderman 1988; Alderman 1999 Arango et al. 1993 Belker et al. 1990 Benger et al. 1995

Level of Evidence III-2

Level of Evidence III-3 Level of Evidence IV Level of Evidence IV Level of Evidence IV Level of Evidence IV

n=1321 (group 1: 961, group 2:

360)

n=432 (Hosp A: 245,

Hosp A part 2: 87, Hosp B: 100

n=5233 / n=5331 (of 8879) n=313 n=1029 n=633

FU at least 7 months FU at least 8 months FU at least 8.6 years FU 8 months FU 18 to 38 months FU up to 36 months SPANISH Azoospermia reached (total) Group 1: 804/810

(99.3%) Group 2: 287/294

(97.6%)

Hosp A: at least 151/245* (61.6%)

Hosp A part 2: 69/69 (100%)

Hosp B: 76/76 (100%)

At least 5077/5233† (97%)

At least 3/5331 (0.1%)

236/237 (99.6%) 644/654 (98.5%)

Azoospermia reached at 1st test Group 1: 783/810 (96.7%)

(4 months) Group 2: 287/294

(97.6%) (3 months)

Hosp A: 151/187 (80.7%)

Hosp A part 2: 62/69 (89.9%)

Hosp B: 66/76 (86.8%)

4197/5233 (80.2%) (98 days post op,

median) 3/5331 (0.06%)

210/237 (88.5%) (3 months)


* It is not clear how many patients failed to submit a 2nd sample at hospital A. Hence the number of azoospermic patients can not be derived. † Probable that there is overlap in patients between these 2 papers. Denominators represent pool of patients each value comes from.

128

Appendix D.5: Data summary table – Outcomes of vasectomy (continued) Badrakumar et al.


Azoospermia reached at 2nd test 18/237 (7.6%) (5 months)

Azoospermia reached at another test

(including after long term persistence of sperm)

Group 1: 21/810 (2.6%)

(within 7 months)

Hosp A part 2: 7/69 (10.1%)

(all negative by 8 months)

Hosp B: 10/76 (13.2%) (time not reported)

3/8879 (0.03%) (after intermittent

presence of sperm with last appearance

ranging from 297 – 448 days postop.).

2/8879 (0.02%) (1 had normal no’s

sperm at 90 and 260 days, azoospermic

after 5 years. Other had 2nd neg test at 252

days).

8/237 (3.4%) (4 at 7 months, 4 at 8

months)

644/654 (98.5%) (timing not stated

except for 2 patients who had persistent non

motile sperm, consecutive

azoospermic samples at 11 and 29 months

and 13 and 14 months) 1/654 (0.2%)

(after long term persistence of non-

motile sperm, azoospermia reached at 32 and 38 months)

Azoospermia reached in 2 consecutive tests

Group 2: 255/259 (98.5%)

(of those who provided 2 samples)

At least 5077/5233 (97%)

560/654 (85.5%)

Time period in which Azoospermia reached

Azoospermia reached at 0 – 6 weeks



129




Group 1: 783/810 (96.7%)

(4 months) Group 2: 287/294

(3 months)

Hosp A: 151/187 (80.7%)

(3 months)

210/237 (88.6%) (3 months)


4060/5233 (77.6%)

(cumulative)

18/237 (7.6%) (5 months)

Azoospermia reached at 25 or more weeks

Group 1: 21/810 (2.6%)

(4 – 7 months)

Hosp A part 2: 69/69 (100%)

(6 – 8 months) Hosp B: 76/76 (100%)

(6 months (66/76) (86.8%) or more (10/76) (13.2%))

4/8879 (0.05%) (as above)

8/237 (3.4%) (4 at 7 months, 4 at 8

months)

Persistent sperm (azoospermia delayed or never reached)


130



Persistent motile sperm 1/432 (0.2%)

(6 months) What hospital this

occurred at is not clear in the paper. Patient is probably included in

data below.

Persistent non-motile sperm 59/5331 (1.1%) 10/654 (1.5%)

(2 given repeat vas. (listed below); 1

special clearance (rare non-motile sperm at 12½ months, 1 per 100 HPFs at 16 ½ months, none at 20 months, 1 per 100

HPFs at 26 months and azoospermia at 32 and

38 months); 6 had occasional non-motile

sperm per HPF 4-6 months after

vasectomy; 2 had rare non-motile sperm 8

and 10 months postop. but were eventually

azoospermic)


131



Persistent sperm (motility not stated)

Group 1: 21/810 (2.6%)

(cleared within 7 months)

Hosp A: 4/187 (2.1%) (at 6 months, 1 required further

exploration) Hosp A part 2: 7/69

(10.1%) (at 6 months, all

cleared by 8 months) Hosp B: 10/76 (13.2%)

(at 6 months, all eventually cleared)

29/5331 (0.5%) 1/237 (0.4%) (at 8 months)

27/633 (4.3%) (> 1 in 5 HPFs – 5; 1 in 5 to 20 HPFs – 7; 1 in 50 to 100 HPFs –

15)

Permanent reappearance of sperm (if not stated otherwise in paper)

Reappearance of non-motile sperm after azoospermia

188/5223 (3.6%) (at 2nd test)

2/5331 (0.04%) (3 and 9 years after

clearance)

Reappearance of motile sperm after azoospermia

4/5331 (0.08%) (4.5 – 8.6 yrs after

clearance)


132



Reappearance of motile sperm after presence of non-motile sperm

Reappearance of sperm after azoospermia (motility not stated)

Hosp A: 10/187 (5.3%)

(of 151 patients with initial negative sample;

4 of these patients were positive at 6 months but only 1 required further

exploration; it is not clear how many of

these were eventually azoospermic, if ever)

3/5331 (0.06%) 1/8879 (0.01%)

(1 month after 2nd neg test at 252 days)

Temporary reappearance of sperm

Intermittent presence of sperm 14/8879 (0.2%) (1 provided 2 consec.

neg. samples twice with reappearance after each time).

Reappearance of sperm (motility not stated)

Group 2: 4/259 (1.5%) (of the patients

providing 2nd sample at 4 months, 3 had 2

subsequent samples negative)


133






Pregnancy 5/5331 (0.1%) 2/1029 (0.2%)

(1 at 29 months, 1 at 67 months (never

submitted samples for PVSA but showed

motile sperm at time of pregnancy))

Repeat vasectomy performed 2/1029 (0.2%) 31/633 (4.9%)


134

Appendix D.5: Data summary table – Outcomes of vasectomy (continued)

Black 2002 Bradshaw et al. 2001 Burnight et al. 1975 Chan et al. 1997 Cortes et al. 1997 Davies et al. 1990

Level of Evidence IV Level of Evidence IV Level of Evidence IV Level of Evidence IV Level of Evidence IV Level of Evidence IV n=45123 n=240 n=292 n=574

n=480 (2nd part) n=38 n=151* of 6067

FU at least 14 weeks FU 30 – 42 months FU at least 2 months FU up to 70 weeks FU 24 weeks FU 3 – 8 years Azoospermia reached (total). 196/206 (95.1%) 510/574 (88.9%)

476/480† (99.2%) At least 26/38 (68.4%) 49/50 (98%)

Azoospermia reached at 1st test 154/206 (74.8%) (3 months)

444/514 (86.4%) (~12 weeks)

431/480 (89.8%)

(12-16 weeks)

Azoospermia reached at 2nd test 37/480 (7.7%)

Azoospermia reached at another test (including after long term persistence

of sperm)

42/206 (20.4%) (timing not clear)

66/514 (12.8%)

22/480 (4.6%)

At least 25/38 (65.8%) (median 10 weeks;

median no. ejaculations 25-30)

1/38 (2.6%) (7 months)

49/50 (98%) (3 – 8 years after

vasectomy)


† The authors took a sub-sample of 480 patients from the total pool of 574. These patients had complied with the protocol and had submitted their 1st sample by 16 weeks (no more than 4 weeks late). These patients are shown in the table with the denominator of 480. *151 men given “special clearance”. 50 supplied a specimen 3-8 years postoperatively.

135

Appendix D.5: Data summary table – Outcomes of vasectomy (continued) Black 2002 Bradshaw et al. 2001 Burnight et al. 1975 Chan et al. 1997 Cortes et al. 1997 Davies et al. 1990


168/206 (81.6%) 510/514 (99.2%)

476/480 (99.2%)

25/38 (65.8%)



Azoospermia reached at 7 – 12 weeks 444/514 (86.4%) (~12 weeks)

25/38 (65.8%) (median 10 weeks)


154/206 (74.8%) (3 months)

431/480 (89.8%) (12-16 weeks)



1 /38 (2.6%)(7 months)

49/50 (98%)



(submitted 2 samples, failure diagnosed at 15

weeks; repeat vasectomy)

1/480 (0.2%) (same patient)

2/38 (5.3%)


136


Persistent non-motile sperm 1 /38 (2.6%)

(eventually azoospermic at 7

months)

1/50 (2%)

Persistent sperm (motility not stated) 16/206 (7.8%)

(4 eventually given “special clearance”)




1 /38 (2.6%)(38x106/ml; 5 months post-vasectomy; led to

pregnancy)




137



Intermittent presence of sperm 1/514 (0.2%) (motile sperm;

submitted 9 samples, was azoospermic at 16

weeks (2nd sample), 38, 45 and 66 weeks;

repeat vasectomy)

1/480 (0.2%) (same patient)



15/184 (8.2%) (8 eventually

produced 2 consec. neg. samples; 4 given special clearance; 3 failed to follow up)

2/514 (0.4%) (submitted 5 and 6

samples, were azoospermic at 3rd and

2nd samples respectively; repeat

vasectomies)

2/480 (0.4%) (same patients)



138



Pregnancy 15/45123 (0.03%)

(13/15 had been given clearance; details not given on time since

vasectomies)

1/292 (0.3%) 2/38 (5.3%) (1 was azoospermic at

2, 3 & 4 weeks, pregnancy occurred 5

months; other pregnancy occurred 1

month post-vasectomy, patient had

discontinued study early while motile sperm still present)

Repeat vasectomy performed 267/45123 (0.6%)

(details not given on time since

vasectomies)

2/240 (0.8%) (only 1 patient

actually received the 2nd vasectomy, the

other declined)

4/574 (7.7%) (failures diagnosed at

15, 26, 44 and 70 weeks after vasectomy)

4/480 (0.8%)

(same patients)


139


DeKnijff et al 1997 Denniston 1985 Edwards 1977 Edwards 1993 Edwards and Farlow 1979 Eisner et al. 2001

Level of Evidence IV Level of Evidence IV Level of Evidence IV Level of Evidence IV Level of Evidence IV Level of Evidence IV n=413 N=2500 n=183

(of 500 vas. patients) n=3178 n=461 n=443

FU 12 weeks to 21 months FU not stated FU 12 – 15 months FU 3 weeks to 18

months FU 12 to 15 months FU at least 22 weeks

Azoospermia reached (total). 349/395 (88.4%) 92/183 (50.3%) 1016/3178 (32%) 331/334 (99.1%)

Azoospermia reached at 1st test 91/183 (49.7%) (after 10 ejaculations,

no time limit)

1016/3178 (32%) (95 at 3 weeks, 194 at 4 weeks, 333 at 5-6 weeks, 303 at 7-14 weeks, 91 at >14

weeks)

249/334 (74.6%) (6 weeks)

Azoospermia reached at 2nd test 262/395 (66.3%) (at 12 weeks)

27/334 (8.1%) (10 weeks)


of sperm)

87/91 (95.6%) (after 3–21 months)

1/183 (0.5%) (at 7 weeks, after

having motile sperm at 4 weeks)

x/33 with motile sperm eventually

became azoospermic

55/334 (16.5%) (14-22 weeks)


53/65 (81.5%) (still azoospermic

when provided sample after letter)

At least 141/334 (42.2%)



140

Appendix D.5: Data summary table – Outcomes of vasectomy (continued) DeKnijff et al 1997 Denniston 1985 Edwards 1977 Edwards 1993 Edwards and Farlow

1979 Eisner et al. 2001

Azoospermia reached at 0 – 6 weeks 622/3178 (19.6%) 249/334 (74.6%)

Azoospermia reached at 7 – 12 weeks 262/395 (66.3%)

62/183 (33.9%) (0-8 weeks)

29/183 (15.8%) (more than 8 weeks

after vasectomy)

303/3178 (9.5%) (7-14 weeks)

27/334 (8.1%)


91/3178 (2.9%) (>14 weeks)

52/334 (15.6%)


3/ 334 (0.9%)


87/91 (95.6%) (after 3–21 months)



(early recanalization) 5/2500 (0.2%) (5 – 50 motile

sperm/high power field)

4/183 (2.2%) (at 4-6 weeks, 3/4 had

non-motile or no sperm 2-3 weeks later)

33/3178 (1%) (16 at 3 weeks, 7 at 4

weeks, 8 at 5-6 weeks, 2 at 7-14 weeks;

in most ¸1x106/ml, ≤ 5% motility;

longest time motile sperm found was 9

weeks; all eventually

azoospermic or non-motile)


141



Persistent non-motile sperm 91/395 (23%) (87 reached azoospermia

eventually – listed above)

7/65 (10.8%)

(still had non-motile sperm when further

samples provided after letter)

79/183 (43.2%) (<1x106/ml) 4/183 (2.2%)

(1x106 to 5x106) 2/183 (1.1%)

(≥ 5x106)

2/183 (0.5%) (at 7 and 8 weeks,

after showing motile sperm at 4 and 5

weeks)

11/98 (11.2%) (12-15 months after

vasectomy. Not stated if these are

reappearances or patients with non-motile sperm from

start).

1207/3178 (38%) (213 at 3 weeks, 333 at 4 weeks, 420 at 5-6

weeks, 220 at 7-14 weeks, 21 at 14

weeks; range 1/HPF –

33x106/ml, most < 1x105)

x/33 with motile sperm eventually

became non-motile

200/461 (43.4%) (44/200 < 4 weeks, 97/200 4-8 weeks, 59/200 > 8 weeks)



142





5/65 (51.1%) (these px provided

samples 12 (2 px), 18, 20 and 22 months after vasectomy)





Intermittent presence of sperm






143



Pregnancy 1/395 (0.3%)

(patient was one of those with early recanalization -

unprotected intercourse before 12

weeks)

1/2500 (0.04%) (7 months)

2/3178 (0.06%) 0/461 (0%)

Repeat vasectomy performed 4/395 (1%) 1/183 (0.5%)


144

Appendix D.5: Data summary table – Outcomes of vasectomy (continued) Esho et al. 1974 and

Esho and Cass 1978 Jackson et al. Lee and Paterson 2001

Lehtonen and Juusela 1973 Lehtonen 1975 Livingstone 1971

Level of Evidence IV Level of Evidence IV Level of Evidence IV Level of Evidence IV Level of Evidence IV Level of Evidence IV n=889; n=1527 n=200 n=462 n=94 n=90 n=3200 FU up to 36 months FU up to 38 weeks FU not stated FU at least 18

months FU up to 3 months FU not stated

Azoospermia reached (total). 764/770 (99.2%)

1311/1317* (99.5%) 172/200 (86%) 462/462 (100%) 89/90 (99%) 2/4† (50%)

Azoospermia reached at 1st test 658/770 (85.5%) (8 weeks)

1092/1317 (82.9%)

(2 months)

152/200 (76%) (12 weeks)

457/462 (99%) (after 30

ejaculations)

6/90 (6.7%) (2 weeks)

Azoospermia reached at 2nd test 63/770 (8.2%) (12 weeks)

155/1317 (11.8%)

(3 months)

? 5/462 (1.1%) (after 50

ejaculations)

43/90 (47.8%) (2 months)


* There is overlap in patients between the 2 studies but different outcomes were measured. Denominator demonstrates what paper those patients come from. † This paper only reports the 4 failures from the 3200 vasectomies.

145




Azoospermia reached at another test (including after long term persistence of

sperm)

43/770 (5.6%) (17 at 16 weeks, 19

at 4-6 months, 7 at 6-12 months)

64/1317 (4.9%)

(33 at 4 months, 21 at 4-6 months, 10 at

6-12 months)

20/200 (10%) 40/90 (44.4%) (3 months)

Azoospermia reached in 2 consecutive tests 663/770? (86.1%)

1311/1317? (99.5%)

172/200 (86%)


Azoospermia reached at 0 – 6 weeks 6/90 (6.7%)

Azoospermia reached at 7 – 12 weeks 658/770 (85.5%) (8 weeks)

1092/1317 (82.9%)

(2 months)

43/90 (47.8%)


146




Azoospermia reached at 13 – 18 weeks 80/770 (10.4%) (63 at 12 weeks, 17

at 16 weeks)

188/1317 (14.3%) (155 at 3 months, 33

at 4 months)

40/90 (44.4%)


Azoospermia reached at 25 or more weeks 26/770 (3.4%) (19 at 4-6 months, 7

at 6-12 months)

31/1317 (2.4%) (21 at 4-6 months, 10

at 6-12 months)



(1 up to 22 months, 1 up to 7 months, 1 up

to 10 months)

5/94* (5.3%) (all with

oligospermia or normospermia)

Persistent non-motile sperm 1/770 (0.1%)

(up to 12 months)


* This study only reports the 5 patients who underwent repeat vasectomy.

147





(sperm present up to 6 months)

6/1317 (0.5%)

6/200 (3%) (3/200 up to 38

weeks)

2/4 (50%)




2/770 (0.3%) (azoospermia at 2

and 9 months, motile sperm at 13-14 and

9-11 months respectively)

1 /90 (1.1%)(at 2 months)


2/770 (0.3%) (motile sperm noted

at 3 months, in 1 patient motility

ceased at 7 months)


3/215 (1.4%) (after 1 year;

215/770 supplied samples)

2/4 (50%) (1 occurred 2 months after negative PVSA,

1 occurred after 2 negative PVSA)


148










Pregnancy 1/4 (25%)

Repeat vasectomy performed 7/770 (0.9%) and

2/770 (0.3%) “awaiting” repeat

vasectomy (repeats performed at 6 (2), 7, 8, 11, 14 and

16 months)

5/94 (5.3%) (1 at 6 months, 4 at

12 months; all eventually

azoospermic)

At least 2/4 (50%)


149


Luke et al. 1979 Maatman et al. 1997 Marshall and Lyon 1972

Marwood and Beral 1979 and Staff of

Margaret Pyke Centre 1973

Milne et al. 1986 O’Brien et al. 1995 Halder et al. 2000

Level of Evidence IV Level of Evidence IV Level of Evidence IV Level of Evidence IV Level of Evidence IV Level of Evidence IV n=580 n=1892 n=200; n=400 n=624; n=1000*

n=200 n=2250 FU 6 months FU at least 1 year FU up to 6 months FU 18 months FU 1 year FU 3 years DANISH Azoospermia reached (total). 312/365 (85.5%) 1295/1892 (68.4%) 200/200 (100%)

(5 days to 6 months) 179/182 (98.4%) 2250/2250 (100%)

(criteria for inclusion) Azoospermia reached at 1st test 312/365 (85.5%)

(16 at 1-2 months, 271 at 3-4 months, 24 at 5-

6 months, 1 at 6 months)

†

21/200 (10.5%) (after 4 ejaculations)

2250/2250 (100%) (16 weeks; criteria for

inclusion)

Azoospermia reached at 2nd test 48/200 (24%) (after 8 ejaculations)


* Overlap in patients between these two studies, denominator shows which subset of patients is being referred to. † Accurate figures could not be determined for azoospermia, attempted contact with authors for clarification was not successful.

150







of sperm)

129/200 (64.5%) (after 12 to more than

24 ejaculations)

615/929 (66.2%) (within 6 months)

300/624 (48.1%) (within 6 months) 249/624 (39.9%)

(within 12 months) 53/624 (8.5%)

(within 18 months) 9/624 (1.4%)

(after 18 months)

92/182 (50.5%) (14-17 weeks)

52/182 (28.6%) (18-21 weeks)

21/182 (11.5%) (22-26 weeks) 8/182 (4.4%) (27-39 weeks) 6/182 (3.3%) (40-52 weeks)


At least 174/182 (95.6%)

2250/2250 (100%) (criteria for inclusion)





92/182 (50.5%) 2250/2250 (100%) (criteria for inclusion)


52/182 (28.6%) (18-21 weeks)


35/182 (19.2%) (22-52 weeks)


151







Persistent motile sperm 2/200 (1%) 7/929 (0.8%)

(at 3 or more months)


(at 6-18 months)


(3 at 1-2 months, 45 at 3-4 months, 4 at 5-6

months, 1 at 6 months)

8/182 (4.4%) (offered repeat

vasectomy)






152







15/2250 (0.7%) (1 year after vasect.)

4/1400 (0.3%) (2 years after vasect.)

1/1000 (0.1%) (3 years after vasect.) (samples of 14 men were neg. 1 month

later, no statement of which patients).

(O’Brien reported that 6/2250 (0.3%) were positive after 1 year,

5/6 (83.3%) negative 1 month later).





153







1/400 (0.3%) (5 weeks post-

vasectomy; return to azoospermia 7 weeks

post-vasectomy)


7/400 (1.8%) 2/929 (0.2%) (after 12 and 17

months)


Pregnancy 6/1892 (0.3%)

Repeat vasectomy performed 21/1892 (1.1%) 6/929 (0.6%)

1/624 (0.2%)

5/182 (2.7%) (a further 3 declined

offer of repeat)

1/2250 (0.04%)


154


Philp et al. 1984 Poddar and Roy 1976 Pugh et al. 1969 Rageth and Leibundgut 1984 Rees 1973 Santiso et al. 1981

Level of Evidence IV Level of Evidence IV Level of Evidence IV Level of Evidence IV Level of Evidence IV Level of Evidence IV n=6 of 16796 n=1200 n=7 n=247 n=903 n=500 FU up to 36 months FU up to ~270 days FU at least 18 months FU 3 weeks – 1 year FU up to 60 weeks Fu 1 – 3 years GERMAN Azoospermia reached (total). 6/6 (100%) 375/450 (83.3%) 2/7 (28.6%)*

184/184 (100%) At least 802/850

(94.4%) 362/369 (98.1%)

Azoospermia reached at 1st test Prob. 4/6 (66.7%) (4 months)

(maybe 5/6 (83.3%); 4-4.5 months)

At least 623/850 (73.3%)

(12 weeks)

Azoospermia reached at 2nd test


of sperm)

Prob. 2/6 (33.3%) (4.5 – 5.5 months)

(maybe 1/6 (16.7%))

375/450 (83.3%) (whether they were 1st, 2nd or 3rd tests was not

reported)

2/7 (28.6%) (not sure what test, 1 at 2 months, other at

10 and 12 weeks)

At least 179/850 (21.1%)

362/369 (98.1%) (1 or 2 months)


6/6 (100%) 754/850 (88.7%)


Azoospermia reached at 0 – 6 weeks 4/450 (0.9%) 99/184 (53.8%) (3-8 weeks)

Azoospermia reached at 7 – 12 weeks 5/6 (83.3%) 193/450 (42.9%) (4.5 – 13 weeks)

2/7 (28.6%) 45/184 (24.5%) (2-3 months)

At least 623/850 (73.3%)


* This paper only reports 7 cases where patients underwent repeat vasectomy (does not say what pool of patients these 7 come from).

155




1/6 (16.7%) 54/450 (12%) 35/184 (19%) (4-12 months)


51/450 (11.3%) (17 – 25.5 weeks)


73/450 (16.2%) 5/184 (2.7%) (more than 1 year)



(6 & 13 weeks)

Persistent non-motile sperm


(time of last test from 0 – 270+ days)

4/7 (57.1%) (motility not stated but prob. motile; 1 at 4 & 12 weeks, 1 at 3 & 4

months, 1 at 3 months and 1 at 5 months)

179/850 (21.1%) (multiple tests required before

clearance)

48/850 (5.6%) (timing not stated;

samples ranged from many sperm (motility

not stated) to azoospermic (no’s. of

azoospermic not given))


156




6/6 (100%) (from 16796 vasectomies)


5/6 (83.3%)




2/7 (28.6%) (1 at 10 months and 1 at 3 months, both after pregnancy confirmed)





157







(1 at 1 month, 2 at 10 months, these 2 after

azoospermia)

9/500 (1.8%) (5 within 1 year, 1 in 2nd year, 3 in 3rd year

or more)

Repeat vasectomy performed 3/1200 (0.3%) 7/7 (100%)

(3, 5, 6, 9, 10, 16 & 18 months after 1st

vasectomy)


158


Scholmeijer 1975 Schraibman 1973 Sherlock and Holl-Allen 1984 Sivanesaratnam 1985 Smith 1996 Surabote 1989

Level of Evidence IV Level of Evidence IV Level of Evidence IV Level of Evidence IV Level of Evidence IV Level of Evidence IV n=463 n=223 n=8 n=916 n=850; n=250*

n=870

FU 3 years FU up to 15 months FU up to 4 months initially, then up to approx. 6½ years.

FU at least 6 months FU 2 years FU up to 18 months

DUTCH Azoospermia reached (total). 463/463 (100%) 223/223 (100%) 8/8† (100%) 912/916 (99.6%) 350/350 (100%)

Azoospermia reached at 1st test ~380/463 (82.1%) (within 6 weeks or

after 10 ejaculations)

203/223 (91%) 6/8 (75%) (2 months)

595/916 (65%) (1 month)

344/350 (98.3%) (12-16 weeks)

Azoospermia reached at 2nd test 2/8 (25%) (3 months)

174/916 (19%) (2 months)


of sperm)

83/463 (17.9%) (24 weeks)

17/223 (7.6%) (after 8 months)

3/223 (1.3%) (at 12, 14 & 15

months)

143/916 (15.6%) (40 at 3 months, 67 at

4 months, 19 at 5 months, 17 at 6

months)

6/350 (1.7%) (6, 7, 8, 9, 12 & 18

months)


223/223 (100%) 8/8 (100%)


Azoospermia reached at 0 – 6 weeks 380/463 (82.1%) 595/916 (65%) (1 month)


* These data are from an abstract. Pool of patients these subsets come from is not clear. † This paper reports eight cases of recanalization. It does not state the size of the pool of vasectomy patients these cases come from.

159



Azoospermia reached at 7 – 12 weeks 6/8 (75%) 174/916 (19%) (2 months)


203/223 (91%) 2/8 (25%) 107/916 (11.7%) (3 & 4 months)

344/350 (98.3%) (12-16 weeks)


83/463 (17.9%) 19/916 (2.1%) (5 months)


20/203 (9.9%) 17/916 (1.9%) (6 months)

6/350 (1.7%) (6, 7, 8, 9, 12 & 18

months)


Persistent motile sperm






160




8/8 (100%) (2 at 3.5 yrs, 1 at 4

yrs, 1 at 4.5 yrs, 2 at 5 yrs, 1 at 5.5 yrs, 1 at 6

yrs)

4/870 (0.5%) (not clear if these

patients had initially reached azoospermia

or not) Reappearance of motile sperm after

presence of non-motile sperm





6/850 (0.7%) (after 1 year; negative

1 month later) 1/250 (0.4%)

(after 2 years; negative 1 month later)





161



Pregnancy 8/8 (100%) 6/14000 (0.04%)

(where negative samples were obtained

but paternity confirmed through

DNA testing)


(although author suggests these should

have been given special clearance)


162


Tailly et al. 1984 Temmerman et al. 1986 Thompson et al. 1991 van Vugt 1985 Foley et al. 1998 Khan and Cranston

1997 Level of Evidence IV Level of Evidence IV Level of Evidence IV Level of Evidence IV Level of Evidence IV Level of Evidence IV n=357 n=100 n=284 n=3150 n=230 n=1 FU at least 296 days FU 6 months FU up to 3 years FU FU at least 3 months FU 12 years DUTCH LETTER Azoospermia reached (total). 315/322 (97.8%) 97/97 (100%) 244/269 (90.7%)

(not sure of timing) (possibly another

25/284 (8.8%), but these never cleared)

2756/3150 (87.5%) (after 10 ejaculations;

none or few non-motile; not

distinguished)

1/1 (100%)

Azoospermia reached at 1st test 186/322 (57.8) (mean of 67 days)

82/97 (84.5%) (6 weeks)

2756/3150 (87.5%) (after 10 ejaculations;

none or few non-motile; not

distinguished)

1/1 (100%) (16 weeks)

Azoospermia reached at 2nd test 95/322 (29.5%) (mean of 82 days)

15/97 (15.5%) (10 weeks)

329/3150 (10.4%) (289 after non-motile sperm, 40 after motile

sperm)


of sperm)

34/322 (10.6%) (mean of 257 days)

6/3150 (0.2%) (time?)

≈ 207/230 (90%) (at 3 months)


315/322 (97.8%) 244/269 (90.7%) 252/3150 (8%) (although this did not

seem to be part of PVSA protocol)

1/1 (100%)



163



1997 Azoospermia reached at 0 – 6 weeks 82/97 (84.5%)

Azoospermia reached at 7 – 12 weeks 281/322 (87.3%) 15/97 (15.5%)


1/1 (100%)



34/322 (10.6%)



(only had 1 test) 63/3150 (2%)

(present at 1st test, remained from 2 to

48.5 weeks after vasectomy)


(last pos. sample mean 124 days, 1st neg.

sample mean 257 days – all eventually azoospermic)

331/3150 (10.5%) (present at 1st test, remained up to 39

weeks)


(timing not stated, no. of samples not stated)

≈ 23/230 (10%) (at 3 months)


164



1997



7/534 (1.3%) (2nd test; note that some of these may

have already had non-motile sperm present)


2/61 (3.3%) (6 months)

2/534 (0.4%) (2nd test)

(1 eventually azoospermic, 1 revasectomy)



1/1 (100%) (12 years post-

vasectomy)






165



1997 Reappearance of motile sperm after

azoospermia 1/534 (0.2%)

(eventually became azoospermic)



(4 months) 1/1 (100%)

(at 18 months and 12 years post-vasectomy)



166


Lo et al. 1990 O’Reilly and Gradwell 2000 Schirren 1984 Thomson et al. 1993

Level of Evidence IV Level of Evidence IV Level of Evidence IV Level of Evidence IV n=1 n=1 n=1 n=1 FU 374 days FU 10 years FU ? FU 5 years GERMAN Azoospermia reached (total). 1/1 (100%) 1/1 (100%) 1/1? (100%) 1/1 (100%)

Azoospermia reached at 1st test 1/1 (100%) (12 weeks)

Azoospermia reached at 2nd test


of sperm)

1/1 (100%) (3rd test, 13.7 weeks

post-vasectomy)

1/1 (100%) (not stated if

azoospermia was found during PVSA

but samples were negative 10 years later)


1/1 (100%)



Azoospermia reached at 7 – 12 weeks 1/1

Azoospermia reached at 13 – 18 weeks 1/1 (100%)


167






Persistent motile sperm

Persistent non-motile sperm








168







1/1 (100%) (at 31.4 weeks post-

vasectomy, 17.7 weeks after azoospermia

shown; azoospermic again at 53.4 weeks)

1/1 (100%) (at 3 years, after

pregnancy; azoospermia followed

at 5 years post-vasectomy)



Pregnancy 1/1 (100%)

(confirmed 8 weeks post-vasectomy)

1/1 (100%) (10 years post-

vasectomy)

1/1 (100%) 1/1 (100%) (3 years post-vasectomy)

Repeat vasectomy performed

169

Appendix D.6: Patients reaching azoospermia Note: Only studies where number of patients achieving azoospermia was reported are included. % reaching azoospermia were of those patients who provided a specimen. Hence, if only 1 patient required a 2nd specimen and were found to be azoospermic, this is reported as 100%.

TEST 1 ANY OTHER TESTS 2 CONSECUTIVE TESTS

No. patients

(patients who submitted samples)

% azoospermia

(total) (of those providing samples)

% attending % azoospermic

Cumulative lost to

follow up % attending %

azoospermic

Cumulative lost to

follow up

% attending (patients

who submitted ≥ 2 samples)

% azoospermic

Badrakumar et al. 2000 Group 1: 961 Group 2: 360

G1: 804/810 (99.26%) G2: 287/294 (97.62%)

G1: 810/961 (84.26%) G2: 294/360 (81.67%)

G1: 783/810 (96/67%) G2: 287/294 (97.62%)

G1: 151/961 (15.71%) G2: 66/360 (18.33%)

G1: 21/961 (2.19%) G2: not clear

G1: 21/21 (100%) G2: not clear

G1: 157/961 (16.34%) G2: 101/360 (28.06%)

G2: 259/360 (71.94%)

G2: 255/259 (98.46%)

Smith et al. 1998 Hosp A: 245 Hosp AII: 87 Hosp B: 100

Hosp A: 151/187 (80.75%) Hosp AII: 69/69 (100%) Hosp B: 76/76 (100%)

Hosp A: 187/245 (76.33%) Hosp AII: 69/87 (79.31%) Hosp B: 76/100 (76.00%)



Hosp A: not clear Hosp AII: 7/87 (8.05%) Hosp B: 10/100 (10.00%)

Hosp A: not clear Hosp AII: 7/7 (100.00%) Hosp B 10/10 (100.00%)

Hosp A: not clear Hosp AII: 18/87 (20.69%) Hosp B: 24/100 (24.00%)


170

Appendix D.6: Patients reaching azoospermia (continued) TEST 1 ANY OTHER TESTS 2 CONSECUTIVE TESTS

No. patients


% azoospermia



Cumulative lost to


azoospermic

Cumulative lost to

follow up



% azoospermic

Alderman 1988, 1999 5233 4640/5233 (88.67%)

?5233/5233 (?100.00%)

4197/5233 (80.20%)

0/5233 (0%)

1036/5233 (19.80%)

880/1036 (84.94%) 0/5233 (0%) ?5233/5233

(?100.00%) 5077/5233 (97.02%)

Arango et al. 1993 313 236/237 (99.58%)

237/313 (75.72%)

210/237 (88.61%)

76/313 (24.28%)

Test 2: 240/313 (76.68%) Test 3: 237/313 (75.72%)

Test 2: 18/240 (7.50%) Other: 8/237 (3.38%)

76/313 (24.28%)

Belker et al. 1990 1029 645/654 (98.62%) 647/1029

(62.88%) 561/647 (86.71%)

Bradshaw et al. 2001 240 196/206 (95.15%)

206/240 (85.83%)

154/206 (74.76%)

34/240 (14.17%)

184/240 (76.67 or 72.50%) (only 174 persisted until outcome reached%)

42/184 (or 42/174?) (22.83 or 24.14%)

56/240 (23.33 or 27.50%) (another 10 provided at least 3 samples but defaulted before being cleared)

184/240 (76.67%)

168/184 (91.30%)

Chan et al. 1997 574 510/540

(94.44%) 540/574 (94.08%)

444/540 (82.22%)

34/574 (5.29%)

514/574 (89.55%)

66/514 (12.84%)

60/574 (10.45%)

514/574 (89.55%)

510/514 (99.22%)


171


No. patients


% azoospermia



Cumulative lost to


azoospermic

Cumulative lost to

follow up



% azoospermic

DeKnijff et al. 1997 413 349/395

(88.35%)

395/413 (95.64%)*

262/395 (66.33%)

18/413 (4.36%)

91/413 (22.03%)

87/91 (95.60%)

57/413 (13.80%) (+ 3 failures)

not reported although clinic usually requests 2 negative tests

Edwards 1993 3178 1016/2260

(44.96%) 2260/3178 (71.11%)

1016/2260 (44.96%)

918/3178 (28.89%)

33/3178 (1.04%)

33/33 (100%) (some may have had few non-motile sperm)

918/3178 (28.89%) (no more defaulted but only those with motile sperm required to submit more tests)

Eisner et al. 2001 443 331/334 (99.10%)

334/443 (75.40%)

249/334 (74.55%)

109/443 (24.60%)

195/443 (44.02%)

152/195 (77.95%)

248/443 (55.98%)

195/443 (44.02%)

152/195 (77.95%)


* It was not clear if these were results from the first or second test

172


No. patients


% azoospermia



Cumulative lost to


azoospermic

Cumulative lost to

follow up



% azoospermic

Esho and Cass 1978 1527 1311/1317

(99.54%) 1317/1527 (86.25%)

1092/1317 (82.92%)

210/1527 (13.75%)

225/1527 (14.73%)

219/255 (85.88%)

210/1527 (13.75%) (no more defaulted but only those with sperm present were required to supply more specimens (n=255)

Jackson et al. 200 172/186 (92.47%)

186/200 (93.00%)

172/186 (92.47%)

12/200 (6.00%)

The outcomes of the 8 patients who submitted some specimens but were never cleared is not reported.

?/200 (86.00 – 90.00%) (not clear how many patients submitted 2 or more samples, between 172 - 180

172/(172-180) (95.56 – 100.00%)


173


No. patients


% azoospermia



Cumulative lost to


azoospermic

Cumulative lost to

follow up



% azoospermic

Lee and Paterson 2001 462 462/462 (100.00%)

462/462 (100.00%)

457/462 (98.92%) 0/462 (0%)

5/462 (1.08%) (only those with initial positive tests needed to provide further samples)

5/5 (100.00%) 0/462 (0%)

Lehtonen 1975 90 89/90 (98.89%)

90/90 (100.00%) 6/90 (6.67%) 0/90 (0%)

84/90 (93.33%)

83/84 (98.81%) 0/90 (0%) not reported even though is

part of protocol

Luke et al. 1979 580 312/365

(85.48%) 365/580 (62.93%)

312/365 (85.48%)

215/580 (37.07%) ? ? ?

Marshall and Lyon 1972 200 198/200 (99.00%)

200/200 (100.00%)

21/200 (10.50%)

0/200 (0%) 179/200 (89.50%)

177/179 (98.89%)

0/200 (0%) Not reported even though is part of testing protocol for clinic.

Marwood and Beral 1979 624 611/624 (97.92%)

624/624 (100.00%)

Staff of Margaret Pyke Centre 1000 ~750/929 (~80.73%) Not known 929/1000

(92.90%)

~750/929 (80.73%)

71/1000 (7.10%)


174


No. patients


% azoospermia



Cumulative lost to


azoospermic

Cumulative lost to

follow up



% azoospermic

Milne et al. 1986 200 179/182 (98.35%)

182/200 (91.00%)

92/182 (50.55%)

18/200 (9.00%)

90/200 (45.00%)

90/90 (100.00%)

18/200 (9.00%)

182/200 (91.00%)

179/182 (98.35%)

Poddar and Roy 1976 1200 375/450 (83.33%)

450/1200 (37.5%) not reported 750/1200

(62.5%) not reported not reported not reported

Rageth and Leibundgut 1984 GERMAN 247 184/184

(100.00%)

Not known when 1st tests were conducted

182/247 (73.68%)

182/182 (100.00%)

63/247 (25.51%)

Rees 1973 903 At least 802/850 (94.35%)

850/903 (94.13%)

At least 623/850 (73.29%)

53/803 (6.60%)

227/803 (28.27%)

179/227 (78.85%)

101/803 (12.58%) (48 provided multiple specimens but were never cleared, defaulted?)

802/903 (88.82%)

754/802 (94.01%)

Santiso et al. 1981 500 362/369 (98.10%)

369/500 (73.80%)

362/369 (98.10%)

131/500 (26.20%)


175


No. patients


% azoospermia



Cumulative lost to


azoospermic

Cumulative lost to

follow up



% azoospermic

Scholmeijer 1975 DUTCH 463 463/463

(100.00%) 463/463 (100.00%)

~380/463 (~82.07%)

0/463 (0%) 83/463 (17.93%)

83/83 (100.00%) 0/463 (0%)

Schraibman 1973 223 223/223 (100.00%)

223/223 (100.00%)

203/223 (87.12%)

0/223 (0%) 20/223 (8.97%)

20/20 (100.00%)

0/220 (0%) 223/223 (100.00%)

223/223 (100.00%)

Sivanesaratnam 1985 916 912/916 (99.56%)

916/916 (100.00%)

595/916 (64.96%)

0/916 (0%) 321/916 (35.04%)

317/321 (98.75%)

0/916 (0%) 916/916 (100.00%)

?912/916 (?99.56%)

Surabote 1989 870 350/350 (100.00%)

350/870 (40.23%)

344/350 (98.29%)

520/870 (59.77%)

6/870 (0.69%)

6/6 (100%)

520/870 (59.77%)

Tailly et al. 1984 357 315/322 (97.83%)

322/357 (90.20%)

186/322 (57.76%)

35/357 (9.80%)

129/357 (36.13%)

129/129 (100.00%)

42/357 (11.76%)

315/357 (88.24%)

315/315 (100.00%)

Temmerman et al. 1986 100 97/97 (100.00%)

97/100 (97.00%)

82/97 (84.54%)

3/100 (3.00%)

15/100 (15.00%)

15/15 (100.00%)

3/100 (3.00%)


176

177


No. patients


% azoospermia



Cumulative lost to


azoospermic

Cumulative lost to

follow up



% azoospermic

Thompson et al. 1991 284

At least 244/269 (might be up to 269/269) (90.71 – 100.00%)

269/284 (94.72%)

At least 244/269 (not sure of timing or test number; might be up to 269/269) (90.71 – 100.00%)

15/284 (5.28%) 269/284

(94.72%) 244/269 (90.71%)

van Vugt et al 1985 DUTCH 3150 3091/3150

(98.13%) 3150/3150 (100.00%)

2756/3150 (87.49%)

0/3150 (0%)

357/3150 (11.33%) (another 2 defaulted before being cleared)

335/357 (93.84%) (329 at 2nd test, 6 at 3rd test)

37/3150 (1.17%) (did not provide 2nd test, an additional 2 did not provide 3rd test)

534/3150 (16.95%) (was not a requirement to provide another test after a negative result)

525/534 (98.31%)

Foley et al. 1998 LETTER

230 ~207/230 (~90.00%)

?230/230 (?100.00%)

~207/230 (~90.00%)

0/230 (0%) Not stated

asernip s - racs · asernip-s report no. 39 . december 2003. australian safety & efficacy...

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