|
Research |
||
Expert Consultation On Vasectomy EffectivenessCo-Sponsored by Family Health International & EngenderHealth (formerly AVSC International) |
|
||
Summary of Discussions and RecommendationsDavid C. Sokal, MD, EditorIntroduction and Meeting ObjectivesThis meeting was convened by Family Health International and EngenderHealth in order to present and discuss recent research findings on the effectiveness of currently used vasectomy techniques with experts in the field.1 The meeting included time for the presentation of some very recent and preliminary, unpublished findings, and for discussion of the significance of the findings. See Appendix A for a complete list of meeting participants and Appendix B for the agenda. The objectives for the meeting were:
Session 1: Current Status Of VasectomyPrevalence of occlusion techniques, vasectomy follow-up protocols and compliance with follow-up presented by Amy E. Pollack, MD, MPH, President, EngenderHealth -- The prevalence of commonly used occlusion techniques and follow-up procedures was described. It was noted that most surgeons in the US do not use ligation and excision alone. Between 1991 and 1995, practice in the US changed. In 1995, more surgeons were using cautery or clips and fewer were using only ligation and excision. The use of ligation and excision was reported by about 18% of surgeons in 1995. About 50% of surgeons use fascial interposition in addition to whatever occlusion technique is used. Many surgeons use a combination of methods, e.g. clips plus cautery. In developing countries, ligation and excision with sutures is considered to be the most commonly used procedure by far, but systematically collected data are unavailable. Regarding follow-up testing after vasectomy in developed countries, compliance with postvasectomy follow-up is surprisingly low, with anywhere from 5-45% of men not returning for any follow-up at all. Based on a number of studies anywhere from 15-97% of men do not comply with the follow-up protocol recommended by their provider. Again, data from developing countries are lacking, but very commonly semen analysis is just not available. The conclusions were that (1) there is no widely accepted standard method of vas occlusion, (2) follow-up protocols vary widely, and (3) compliance with follow-up protocols is low. Addendum regarding clip use: (1) The percent of procedures reported with clips alone in the U.S. in 1995 was about 9%.2 (2) Based on a comparison presented during the conference (see below, Session 2, Labrecque), vas occlusion with clips may be similar in some ways to ligation and excision. (3) It was noted during later discussions that some surgeons apply clips or sutures in addition to cauterizing the vas. Theoretically, this might actually be counterproductive if a suture or clip were put on too tightly on top of or proximal to the cauterized portion of the vas. In such a case, some or all of the cauterized end might be sloughed off, potentially facilitating recanalization -- similar to what might occur with ligation and excision. Vas occlusion techniques -- an illustrated overview presented by Michel Labrecque, MD, PhD, Professeur Titulaire, Departement de Medecine familiale, Universite Laval, Quebec -- One clinician's overview was given of the various occlusion techniques that are or have been used for vas occlusion and separation during a vasectomy procedure. Given the various techniques used in different combinations, it was estimated that there are at least 28 different possible surgical occlusion methods. Based on a tabulation of published but mostly uncontrolled studies, one clinician's opinion was given on the relative superiority of various techniques. It was noted that most of the studies were case series by individual surgeons and very few of the studies were methodologically rigorous. Keeping in mind the limitations of the data, in the following listing the underlined techniques appeared to have better success when compared to the alternatives: excision of more than 4 cm vs. less than 3 cm; three or four clips rather than just two; cautery vs ligation and excision; the use of fascial interposition to bury the abdominal end vs the testicular end; and with less evidence, perhaps open-ended vs closed-ended. In conclusion, the clinician's preferred technique is an no-scalpel vasectomy (NSV) approach with cautery plus fascial interposition as the occlusion method, without excision of a segment of the vas. Evidence-based review of failure rates and semen characteristics post-vasectomy presented by Mark A. Barone, DVM, MS, Research Program Manager, EngenderHealth -- It was noted that there are very few studies that provide Level 1 evidence (i.e. results from well-designed randomized controlled trials) with respect to the relative effectiveness of different vas occlusion methods. Most published studies have been reports by individual surgeons on their own series of patients and thus have serious limitations in terms of making an evidence based decision. The situation is similar with regards to time and number of ejaculations to azoospermia after vasectomy. The major conclusions were (1) good data are lacking to support the use of any one occlusion method; (2) long term studies of failure are lacking; and (3) there is little published data on sperm function post-vasectomy or on the relationship between persistent sperm and pregnancy. Semen parameters in vasectomy research -- what do they mean? Semen analysis in practice -- what really matters? presented by Charles H. Muller, , PhD, HCLD, Director, Male Fertility Laboratory Univ. of Washington School of Medicine and Susan Rothman, PhD, HCLD, President, Fertility Solutions, Inc. --Various semen parameters were described in relation to post-vasectomy semen analysis. The various methods used for semen analysis and their limitations were presented. It was noted that the usual clinical practice of semen analysis after vasectomy varies widely in quality even in well-resourced settings. In the US, the CLIA (Clinical Laboratory Improvement Act ) regulations apply to semen analysis, and semen analysis is considered to be of moderate to high complexity depending on the parameters being measured, so quality control and proficiency testing are needed. In research studies, the degree of proficiency testing and quality control needed must be established as a function of the endpoints being measured. Session 2: Recent Vasectomy ResearchHistorical perspective on cautery research presented by Ronald D. Reynolds, MD, New Richmond Family Practice, New Richmond, OH -- As background to the discussions, the development of the cautery method by Dr. Stan Schmidt was described.3 Schmidt first reported his cautery method in 1966. His initial report was followed by several others describing his success with the use of cautery and fascial interposition. He theorized that when ligatures were used, necrosis of the vas due to ischemia occurred, leading to open vas ends and increased likelihood of failure. Cautery created a solid scar to seal the vas. Schmidt also developed a thermal cautery device, with co-inventor Bill Sturgeon, specifically designed to make cautery feasible in low-resource settings. Schmidt also did a small study comparing electrical versus thermal cautery and concluded that thermal cautery might lead to fewer cases with vasitis nodosa / spermatic granuloma. Labrecque Study: Effectiveness and complications associated with two vasectomy techniques presented by Michel Labrecque, MD, PhD, Professeur Titulaire, Departement de médecine familiale, Université Laval, Quebec -- The two methods compared in this study were: (1) use of a clip on each end of the cut vas with excision of 1-2 cm; and (2) use of cautery on the abdominal end, with fascial interposition to separate the abdominal end from the testicular end, leaving the testicular end open. Approximately 3,768 men were eligible and 2,472 were found to have been fully compliant with the recommended follow-up. Failure rates were 8.7% for men who received clips but only 0.3% for men who had cautery, a highly significant finding, both statistically and clinically. Median time since vasectomy was 2.9 and 1.4 years in the clip and cautery groups, respectively. Most failures were identified early in the follow-up period, and a similar difference between the two techniques was seen at the first post-vasectomy semen sample. In fact, the use of clips was discontinued by Labrecque based on a clinical impression of lower efficacy, well before this formal analysis. In terms of complications, there were slightly more surgical complications with the cautery method, 1.6% versus 0.5% (p=0.005). Both methods had a similar incidence of non-infectious pain, 4.1% vs. 3.5% (p=0.34) for the cautery and clip methods respectively, i.e. there was no advantage to leaving the testicular end open compared to closing both ends with clips. Experience with cautery from the Elliot Smith Clinic presented by Edward Streeter, BM, BCh, MRCS, Clinic Surgeon, Elliot Smith Clinic, Oxford, UK -- Surgeons at the Elliot Smith Clinic use a very simple cautery technique: excision of approximately 2 cm of vas and cautery of both ends. Fascial interposition is not done. While there is evidence from the clinic data showing a learning curve, the overall failure rates with this simple occlusion method have been very low. In 1984, the clinic reported a failure rate of 0.28% among 12,300 vasectomies, and in 2001, a failure rate of 0.02% among 4,765 subsequent vasectomies. Failures were identified during routine post-vasectomy testing, i.e. not by active long-term follow-up. Time to azoospermia after simple ligation and excision: Results from an FHI / EngenderHealth / IMSS study in Mexico City presented by Mark A. Barone, DVM, MS, Research Program Manager, EngenderHealth -- This study followed 217 men with semen analyses on a bi-weekly basis up to 24 weeks. The original goal of the study was to determine whether simplified vasectomy follow-up guidelines could be developed for settings where semen analysis is unavailable or impractical. The vasectomy technique used was NSV with ligation and excision, without fascial interposition. The results showed a surprisingly high recanalization rate, with 28 men (13%) still having 3 million sperm per ml or more at 24 weeks. An analysis of only the vasectomy successes indicated that there is a great variability in onset of azoospermia in terms of both time and number of ejaculations following vasectomy when simple ligation and excision are used. Based on these results, it does not seem possible to develop simplified guidelines for when men can rely on their vasectomy for contraception -- when simple ligation and excision are used -- based solely on the time or number of ejaculations after vasectomy. Ligation and excision with versus without fascial interposition: Interim data from a randomized clinical trial presented by David C. Sokal, MD, Associate Medical Director, FHI --See addendum below.-- As a follow-up to the Mexico City study just described previously, FHI and EngenderHealth began a multicenter trial to evaluate the value of fascial interposition when done with simple ligation and excision. The interim results of the trial were reviewed by a data monitoring committee, and it was decided that the study should continue. Given the speed of recruitment and 34 week follow-up, final results of the study were not expected until 2003. While the results of the interim analysis by group are confidential, the pooled data appeared roughly similar to the study in Mexico City. It was suggested that it would be prudent to begin additional research on other occlusion methods, even before the results of this trial are available. The presentation also included a discussion of the pathophysiology of recanalization after vasectomy. See addendum below. Addendum: Following further review of the interim analysis data, the recruitment of new participants was halted. An age by treatment interaction had made interpretation of the interim analysis results more difficult than expected. Based on the interim time-to-azoospermia life table analysis, the beneficial effect of Fascial Interposition (FI) was limited to younger men. Among men < 35, 91% of men in the FI group reached azoospermia by 34 weeks compared to 76% of men in the non-FI group (p< 0.0001). No benefit from FI was seen for older men (p=0.61). Using an alternate definition of success, less than 100,000 sperm/ml rather than azoospermia, 92-93% of men in the FI group reached success, while in the non-FI group, 77% of men < 35 years (p< 0.0001) and 86% of men ¡Ý35 years reached success (p=0.096). A limitation of this study is that it looks at semen analysis data rather than pregnancy rates, and the relation between sperm counts after vasectomy and the risk of pregnancy is not well understood. Follow-up will continue for men who are already enrolled. The final analysis will be done after these men have finished their follow-up visits. Note: P-values in this addendum are one-sided. Persistent sperm and post-vasectomy pregnancies in Nepal presented by Hanif Nazerali, MPH, Senior Research Associate, FHI -- Data were presented from a retrospective follow-up study of a sample of 1052 men who were interviewed 1 to 4 years after vasectomy in Nepal. 924 men provided evaluable semen samples. Prevalence of persistent sperm in semen following vasectomy (typically suture ligation and excision of 1-2 cm) was 2.3% (95% CI 1.1-3.6%) overall, increasing slightly with years elapsed since vasectomy. 23 men had persistent sperm with counts of 500,000 per ml or higher, and 32 men reported pregnancies, including 7 early pregnancies conceived within three months of vasectomy. A total of 42 men had persistent sperm and/or a reported pregnancy. The life-table pregnancy rate at 36 months was 4.2 per 100 men (95% conf. int.: 3.2 - 5.2). Pregnancies were more common in younger wives. While the study was not expected to evaluate surgical techniques, some data were gathered on this issue, and there was a lower failure among men whose surgeon reported using a "foldback" technique. It was concluded that counseling on vasectomy should include careful explanation of failure and possibility of spousal pregnancy. In addition, a more effective vas occlusion technique and/or improved access to semen testing are needed in order to reduce the risk of pregnancy. Post-vasectomy pregnancies in China presented by Charles Chen, PhD, Demographer, CDC, Atlanta -- An analysis of a National Demographic and Family Planning Survey from China in 1988 showed surprisingly high rates of spousal pregnancy after vasectomy. The sample included 29,075 women whose husbands had had vasectomies. While pregnancy rates after female sterilization were comparable to US rates, pregnancy rates after vasectomy were 2.8 per 100 after 1 year, increasing to 9.4 per 100 after 10 years. Pregnancy rates were higher for younger women, and for spouses of men whose vasectomies had been done in settings such as mobile clinics or rural hospitals. While data were not gathered on the vasectomy methods used, it is likely that most vasectomies were performed using simple ligation and excision. CREST Cohort: Pregnancies after Male or Female Sterilization presented by Caroline Costello, MPH, Health Care Analyst, CDC, Atlanta -- The U.S. Collaborative Review of Sterilization (CREST) study found a higher than expected 10 year cumulative probability of pregnancy among women undergoing tubal sterilization of 18.5 per 1000 procedures (95% confidence interval; 15.1-21.8). A group of 573 women whose husbands had vasectomies served as the CREST controls. They were followed-up for five years by telephone interviews. Ten pregnancies were identified, including six true vasectomy failures, 3 luteal phase pregnancies, and one of unknown status. Of the six vasectomy failures, three were early failures, i.e. possible user failures, that were conceived within 12 weeks of vasectomy. The three others were conceived within two years of vasectomy. The cumulative probability of pregnancy among wives of men undergoing vasectomy was 9.2 per 1000 procedures at 1 year and 18.7 per 1000 procedures at 2 years and then remained constant through 5 years postvasectomy. Limitations of this study include: small population size, no information on vasectomy method, no standard information on semen analysis, and the assumption that the pregnancies were attributable to vasectomy failure. Session 3: Implications of Recent Vasectomy Research FindingsImproving access and acceptability of post-vasectomy semen testing (facilitated discussion) presented by Susan Rothman, PhD, HCLD, CLC, President, Fertility Solutions, Inc. and Charles Muller, PhD, HCLD, Director, Male Fertility Laboratory -- The major points made in the discussion were the following: Semen testing is currently unavailable for clients in most developing countries. Even at most developed country clinics, many men do not return for the recommended number of semen tests. The challenge is to provide simplified on-site testing or perhaps home testing that does not require a microscope or other medical equipment. There are at least two kits that are being marketed or developed which could provide several relatively simple chemical or antibody based testing of semen samples, one by John Herr at the University of Virginia, and the second, the VasMarq, which was evaluated in the Nepal study.4 While relatively easy to use, both of these products require some training. The ideal product would be as simple to use as a urine dipstick and would cost about 10 cents or less. If such a product were available, men might be able to take one or two home with them and test their semen on their own. However, such a product is not likely to be available in the foreseeable future. Currently, semen analysis relies on microscopy. Semen can also be preserved and shipped to an off-site lab for analysis, as was done in the Nepal study. Addendum: Jeff Spieler and David Sokal have been in touch with John Herr and will explore the possibility of further collaboration on his "dipstick" method, which can be calibrated to detect less than 50,000 sperm per mL. What to tell men about vasectomy effectiveness during counseling (facilitated discussion) presented by John M. Pile, MPH, Senior Director, EngenderHealth (Carmela Cordero, MD, Senior Director, EngenderHealth, was to have given this presentation but was unable to be present.) -- Current informed consent and counseling practice was reviewed. It was noted that the major emphasis was on the permanence of the method, and little information was presented on failure rates other than to tell clients that vasectomy is highly effective. It was noted that even if one wanted to present more details on failure rates, it would be difficult as failure rates may differ by vasectomy method, the surgeon's experience and the age of the female partner. Rather than trying to arrive at a particular number for the failure rate, it was suggested that there needed to be more emphasis on the possibility -- although rare -- that a pregnancy could occur following vasectomy, in order to protect the woman from being blamed should she become pregnant. For example a man could be given some written information for his wife about the possibility of vasectomy failure, and he could be counseled that if his wife were to get pregnant, he should return for a free repeat vasectomy. It was suggested that whenever possible, both partners should receive counseling before the procedure. Planning for dissemination of findings (facilitated discussion) presented by Elizabeth Robinson, MS, Associate Director, FHI and Herbert B. Peterson, MD, Medical Officer, Dept. of Reproductive Health and Research, WHO, Geneva -- This session discussed the advisability of some sort of consensus statement. For example a consensus statement could be published as a commentary along with the publication of several vasectomy articles in a special issue of a journal. Given current knowledge, the statement might make a general recommendation that practitioners switch to cautery as a method of vas occlusion rather than suture ligation. However, the experts did not agree that a consensus statement was appropriate at this time. It was noted that there is no "level 1" evidence that would justify a general consensus statement of that type. On the other hand, it was suggested that the current data should be rapidly but carefully disseminated in order to alert practitioners to the higher than expected failure rate of simple ligation and excision, but at the same time avoiding alarmist media interpretations about the risk of pregnancy after vasectomy. In addition, it was noted that a formal consensus statement would be extremely time consuming to prepare and would probably slow down the dissemination of the current findings, since numerous institutions would have to review and approve such a consensus statement. It was noted that the current findings were quite analogous to CDC's CREST findings in relation to female sterilization. In both cases, rather than 99.9 % effectiveness in the first year of use, it looks like the method might be only 98 - 99% effective when certain vasectomy techniques are used in a young population. Despite the recent findings, vasectomy remains a highly effective method. It was suggested that a consensus statement would be more appropriate at a later time when there was evidence from trials with more generalizable data, i.e. from multiple surgeons using different techniques under similar conditions. Session 4: Future ResearchFHI/EngenderHealth research strategies presented by Laneta Dorflinger, PhD, Vice President, Clinical Research, FHI -- An "ideal" vasectomy method was described as needing a robust technique that would provide high efficacy in diverse environments when used by different surgeons. It should be effective as quickly as possible if not immediately and should have a low rate of side effects. In addition it should be low-cost, requiring minimal equipment or supplies, and it should be simple enough for it to be performed at peripheral levels of the health care system. The lack of multicenter randomized trials was noted. Issues that require study include -- a need to compare cautery with a lower tech method such as the foldback method for efficacy, and the use of open-ended versus closed-ended techniques for side effects. A brief summary of proposed research topics was introduced, and was elaborated by the later speakers. Multicenter RCT of cautery versus another method presented by Belinda Irsula, Senior Clinical Research Associate, FHI -- A brief description was given of a possible study design for a multicenter randomized controlled trial to compare cautery and excision without fascial interposition versus ligation and excision with fascial interposition. Nepal RCT of cautery versus another method presented by Hanif Nazerali, MPH, Senior Research Associate, FHI -- A brief description was given of a possible study design for a randomized controlled trial that could be conducted during a single season of the mobile camp vasectomy program in Nepal. One possible study design would be a randomized controlled trial to compare cautery and excision without fascial interposition versus ligation and excision with the foldback technique. The potential for reuse of disposable cautery tips presented by Glenn Austin, BSID, Senior Technical Officer, PATH, Seattle -- With respect to use in low-resource settings, a major disadvantage of thermal cautery devices is that they are more costly than the ligation and excision method. The retail cost of disposable cautery tips is US$4.00 each. Based on preliminary information from FHI and anecdotal information from clinicians, re-sterilization and re-use appear to be feasible. Re-sterilization and re-use could potentially decrease the cost from US$4.00 per procedure to less than US$1.00. A methodology for the evaluation of cautery tip re-use was presented and briefly discussed. A formal re-use evaluation should be done to define the best sterilization techniques for re-use and develop field guidelines for re-sterilization and re-use. It was noted that PATH has successfully conducted such evaluations for a number of other medical devices. Vas irrigation presented by PRK Reddy, PhD, Senior Research Associate, FHI -- A brief summary of FHI's research on vas irrigation was presented. FHI conducted a survey of U.S. urologists and found that about half of reported pregnancies were attributed to user failures, i.e. intercourse in the first few weeks after vasectomy without the use of effective contraception. These pregnancies could potentially be avoided if vasectomy were effective immediately -- something that would be possible if vas irrigation were used. With laboratory support from CONRAD, FHI has tested several potential agents and has identified a marketed formulation of diltiazem as a good candidate for vas irrigation. Diltiazem is a calcium channel blocker currently used for cardiovascular indications. It is a good candidate for vas irrigation, because (1) it kills sperm rapidly in CONRAD's in-vitro model, and (2) given its approval for intravenous use, there should be no major safety issues for the use of a small dose in the vas. Session 5: Break-out Sessions / Next StepsThe plenary discussion of "Next Steps" was moderated by David C. Sokal, MD, Associate Medical Director, FHI, and Laneta Dorflinger, PhD, Vice President, Clinical Research, FHI Two small groups each discussed two topic areas: (A) Improving Vasectomy Effectiveness (Techniques), and (B) Measuring Effectiveness (Endpoints). They were charged with:
Following presentations by both groups, the recommendations were discussed. The major points of agreement are summarized below:
It was recommended that as soon as possible, FHI and EngenderHealth initiate an observational study of the cautery method to obtain early semen analysis data that would be comparable to the data from the Time to Azoospermia study in Mexico and the current randomized controlled trial (RCT) of fascial interposition, i.e. semen analysis at approximately 2, 4, 6, 10 and 14 weeks, plus later testing as needed. This should be done rapidly, probably using a few existing cautery practitioners who would use their usual technique. It was suggested that if this study shows a clear difference in the frequency of early recanalization compared to the fascial interposition group in the ongoing FHI/EngenderHealth RCT, then this might provide sufficient evidence for programs to begin switching to the use of the cautery technique without requiring an RCT of cautery versus another technique. It was noted that there are some practical concerns about recommending any new procedures for vasectomy. Organizations involved in training and especially in supporting public sector family planning programs may need to begin planning to address those issues. Specifically the major practical issues would relate to training and to the supply and maintenance of special instruments, eg. hand-held cautery units, especially for public sector family planning programs.
Appendix A: list of meeting participantsAppendix B: meeting agendaNote: *In order to view Acrobat format format, you will need a PDF Reader. If you do not have one, you may download a free copy of Adobe Acrobat Reader 4.0 or higher by clicking here. Older versions of Adobe Acrobat may not work on some systems. If you experience problems, please download the most recent version of Acrobat Reader.
|
|||
 |
|||
