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Lesson 22 Volume 27 Vasectomy
Learning Objective: At the conclusion of this continuing medical education activity, the participant will be familiar with the different aspects of vasectomy from its history to its future, surgical technique, outcomes and complications.
Howard H. Kim, M.D.
Disclosures: Nothing to disclose
and Peter N. Schlegel, M.D., F.A.C.S.
Disclosures: Intarcia Therapeutics, Inc.: Consultant/Advisor; Theralogix, Inc.: Board member/Officer/Trustee
Department of Urology and Cornell Institute for Reproductive Medicine The New York Weill Cornell Medical Center and The Population Council Rockefeller University New York, New York
Supported by the Frederick J. and Theresa Dow Wallace Fund of the New York Community Trust.
This self-study continuing medical education activity is designed to provide urologists, Board candidates and/or residents affordable and convenient access to the most recent developments and techniques in urology. The American Urological Association (AUA) is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians. The AUA takes responsibility for the content, quality and scientific integrity of this CME activity.
Credit Designation Statement: The American Urological Association designates this educational activity for a maximum of 1.0 AMA PRA Category 1 Credit™. Each physician should only claim credit commensurate with the extent of their participation in the activity. AUA Disclosure Policy: As a provider accredited by the ACCME, the AUA must insure balance, independence, objectivity and scientific rigor in all its activities. All faculty participating in an educational activity provided by the AUA are required to disclose to the audience any relevant financial relationships with any commercial interest to the provider. The intent of this disclosure is not to prevent faculty with relevant financial relationships from serving as faculty, but rather to provide members
of the audience with information on which they can make their own judgments. The program planners must resolve any conflicts of interest prior to the commencement of the educational activity. It remains for the audience to determine if the faculty’s relationships may influence the educational content with regard to exposition or conclusion. When unlabeled or unapproved uses of drugs or devices are discussed, these are also indicated. Unlabled/Unapproved Uses: It is the policy of the AUA to require the disclosure of all references to unlabeled or unapproved uses of drugs or devices prior to the presentation of educational content. Please consult the prescribing information for full disclosure of approved uses. Publication date: August 2008 Expiration date: August 2011
© 2008 American Urological Association, Education and Research Inc., Linthicum, MD
KEY WORDS: vasectomy; history; surgical procedures, operative; complications
Vasectomy is one of the most cost-effective methods of contraception, resulting in a 5-year savings of $13,899 and prevention of about 4.2 pregnancies per person.1 With its proven safety and efficacy, vasectomy enjoys a benign, even esteemed reputation today, which belies its inauspicious beginnings and turbulent history throughout much of the previous century. HISTORY Perhaps as a prelude to vasectomy, Dr. Ewing Mears experimented with ‘‘physiological castration’’ by ligation of the spermatic cord in 1890.2 In 1897 the first American report of a vasectomy performed in a human was published by Dr. A. J. Ochsner of Chicago.2 The procedure was performed as therapy for severe prostatic hypertrophy. In 1893 White reported prostatic atrophy in castrated dogs, an idea he came upon when considering the analogous shrinkage of uterine fibromyomas with oophorectomy.3 Ochsner guessed (incorrectly) that vasectomy would similarly result in involution of prostatic tissue.2 However when vasectomized patients experienced no impairment of sexual function, Ochsner supported the application of the procedure to eugenics to eliminate paternal contributions to societal undesirables such as ‘‘habitual criminals, imbeciles, perverts, paupers, morons, epileptics and degenerates.’’2, 4, 5 Several prominent surgeons including Drs. G. Frank Lydston and William Belfield also favored eugenic sterilization.6 A complex drama of eugenic, punitive and therapeutic applications of vasectomy ensued at the dawn of the 20th century.7 Dr. Harry C. Sharp of the Indiana State Reformatory in Jeffersonville was a prominent force in promoting vasectomy in the medical and prison reform communities, leading to Indiana’s 1907 state law authorizing compulsory sterilization of those considered unfit to reproduce by a panel of physicians.7 Sharp believed excessive testicular secretions were unhealthy and originally intended vasectomy as a treatment for masturbation.7 He emphasized the health benefits of vasectomy, and eugenic benefits were almost an afterthought.7 He obscured the punitive aspects of vasectomy by emphasizing the similar benefits to castration without the unpleasant side effects.7 A total of 28 other states eventually followed Indiana’s example with eugenic laws permitting involuntary sterilization of the insane and feeble-minded, of which 12 states also allowed for punitive sterilization of criminals.6 Although many of the statutes were challenged and overturned, more than 6000 people were sterilized in the U.S. between 1909 and 1924. Eugenic sterilization peaked in the 1930s before finally waning in the 1960s.6
Rejuvenation was a less nefarious but equally dubious application of vasectomy in the early 20th century. Hormone replacement therapy began in 1889 with Dr. Charles-Edouard ´ quard’s treatment of the frailty of old age with Brown-Se subcutaneous injections of an aqueous testicular extract from dogs and guinea pigs,8 which laid the groundwork for ‘‘rejuvenation.’’ Dr. Eugen Steinach, director of the Physiological Section of the Institute of Experimental Biology in Vienna, observed that rats castrated before puberty were sexually underdeveloped, similar to the near-infantile sexual state of old age.8 He hypothesized that rejuvenation of the aged can mirror the successful treatment of castrates with gonadal implants. He thought that destruction of sperm producing cells of the testes with vasectomy might induce proliferation of hormone producing cells and subsequent physical and mental revitalization.8 Dr. Robert Lichtenstern performed the first rejuvenation surgery in 1918.9 Even at the peak of Steinach’s prominence, his technique was controversial10 and it eventually disappeared from use with the isolation and synthesis of testosterone in 1935.9 EPIDEMIOLOGY United States. In 2002 an estimated 526,501 vasectomies were performed in the U.S., which converts to a rate of about 10 vasectomies for every 1000 men 25 to 49 years old.11 This rate remained unchanged from the initial surveys conducted in 1991 and 1995.12, 13 In a 2002 survey of contraceptive use based on the Behavioral Risk Factor Surveillance System by the Division of Reproductive Health, National Center for Chronic Disease Prevention and Health Promotion at the Centers for Disease Control and Prevention, women reported a median prevalence of birth control use of 84%.14 Vasectomy use ranged from a low of 2% in the District of Columbia to a high of 23% in Idaho. In the data reported by men vasectomy ranked as the most common contraceptive method in 17 states, with an overall range of use from 5% in the U.S. Virgin Islands to 31% in Oregon. The different rates of contraceptive use as reported by women and men are attributed to the slightly different age groups surveyed (18 to 44 years for women and 18 to 59 years for men) and the possibility that sexual partners may not have discussed method of birth control with each other. Overall 7% to 10% of married American couples select vasectomy for contraception, making it the most common urological procedure in North America.15 Men who undergo vasectomy in the United States tend to be non-Hispanic whites, well educated, married or cohabitating, relatively affluent and have private health insurance.16 Other nations. The choice of vasectomy for contraception varies by age, socioeconomic status and geography among other factors. A 1992 review identified vasectomy as a major
ABBREVIATIONS: BMD (bone mineral density), FSH (follicle-stimulating hormone), GnRH (gonadotropin releasing hormone), LH (luteinizing hormone), PVPS (post-vasectomy pain syndrome), PVSA (post-vasectomy semen analysis)
contraceptive method in only 6 Western countries (Australia, Canada, Great Britain, the Netherlands, New Zealand and United States) and 3 Eastern countries (China, India and South Korea).17, 18 More than 55,000 vasectomies are performed in Canada yearly.15 The average annual incidence of vasectomy from 1992 to 1999 for men 20 to 64 years old in the United Kingdom was 4.48 per 1000 person years.19 The prevalence of sterilization in UK men was 17% in 1990,19 and in New Zealand the overall prevalence of vasectomy is 44%, adjusted to the age distribution of all New Zealand men 40 to 74 years old.18 About 42 million couples worldwide use vasectomy as the method of contraception, of whom 32 million reside in China and India.17, 20 In contrast, few vasectomies are performed in France as a result of the 19th century Napoleonic Code which prohibits vasectomy as a form of self-mutilation.21 SURGICAL TECHNIQUE Several vasectomy techniques are performed today, including those using the standard anesthetic cord blocks. Many of these methods yield good results but we favor a no-scalpel, no-needle approach modified from the Chinese technique initially developed by Li et al in 1974.22 Preparation. Perioperative anti-inflammatory treatment with 200 mg celecoxib orally twice a day started the night before the procedure may help to prevent postoperative pain. This medication can be given for an additional 4 to 7 days postoperatively since it does not increase bleeding risk. The patient may also be given 10 mg diazepam orally or sublingually about 15 minutes before the start of the procedure. In the procedure room he reclines in the supine position and the scrotum is shaved. The penis is kept out of the surgical field using gentle cephalad traction with a rubber band wrapped around the corona and clipped to the patient’s gown at the level of the umbilicus. Before scrubbing and gloving, a finger cot may be placed on the left middle finger to protect it during the delivery of anesthesia using a needleless delivery device. Once gloved, the surgeon preps the anesthetic delivery site with an alcohol pad. ´ is identified, and the nonAnesthesia. The median raphe dominant hand is used to palpate the vas deferens. The index finger and thumb form a C configuration and the vas deferens is pressed between this C and the middle finger. When standing on the patient’s right side, the right-handed surgeon faces the patient’s head when grasping the right vas deferens and the patient’s feet when grasping the left vas deferens. Each vas is brought up against the skin to the same spot at the ´ , about 2 cm below the base of the penis. The median raphe MadaJet XL Medical, Urology (Mada, Inc., Carlstadt, New Jersey) is used to deliver the anesthetic cocktail, which is a 1-to-1 mix of 2% plain lidocaine and 0.5% plain bupivacaine. Each high pressure spray delivers about 0.1 cc of the anesthetic solution.23 About 3 sprays are delivered to each vas deferens, being careful to deliver the anesthetic against the finger
cot to avoid inadvertent injection into the surgeon’s finger. The surgeon removes the gloves and finger cot, and then puts on a gown and fresh gloves for the procedure. The surgical field is prepped with betadine solution and draped in the usual fashion. Alternatively, local infiltration of 1% xylocaine to the skin may be performed with a 1.5-inch 25 gauge or longer needle advanced along the vas deferens to provide a cord block. Other surgeons have used a ‘‘blind’’ cord block at the level of the upper scrotum that appears to have a slightly higher risk of cord hematoma. Vasal access. Once the vas deferens is brought up to the ´ using the 3 finger grasp, a ringskin of the median raphe tipped clamp is used to secure the vas through the skin. One blade of the fine curved mosquito hemostat is used to puncture the skin and the vas deferens until the lumen is reached. The puncture hole is enlarged to about 4 mm by placing both blades of the mosquito hemostat into the hole and gently stretching the skin by opening the blades transversely across the vas deferens. The vas deferens is again speared with 1 blade of the mosquito hemostat and the tip of the instrument is rotated up toward the ceiling. This motion delivers the vas deferens out of the scrotum and into the operative field. The ring-tipped clamp is reapplied for better purchase around the vas deferens. Tissue adherent to the vasal sheath is cleared away with the mosquito hemostat using the same spreading motion of its blades, and the vasal sheath is further cleared of adventitia. It is important to achieve a segment of vasal sheath completely free from adherent tissue. Blunt dissection can be used to push away associated blood vessels. Alternatively, in a modification of the no-scalpel vasectomy a percutaneous vasectomy omits the initial grasping of the vas deferens through the scrotal skin with the ring-tipped clamp.24 Instead, the mosquito hemostat is used to first puncture the scrotal skin and to spread tissue overlaying the vas deferens. Once the vas deferens is exposed, it is grasped with the ring-tipped clamp and pulled out of the scrotum for further dissection. Vasal occlusion. A reusable Hi Temp Cautery device (Advanced Meditech International, Inc., Flushing, New York) is used for the occlusion. The vas deferens is hemi-transected with the cautery, exposing the lumen. The tip of the device is inserted into each end of the vas deferens and both openings are cauterized. Care should be taken to avoid full-thickness cautery of the vas deferens to prevent necrosis. Cautery is done just to obliterate the luminal lining. A small segment of vas deferens is excised for pathological evaluation. The distal cut end of the vas deferens (toward the testis) is closed with a small surgical clip. The proximal end is pushed (telescoped) down into the vasal sheath and a small surgical clip can be placed on the sheath overlying the vasal end. This move separates the 2 ends of the vas deferens into different planes or compartments, reducing the risk of recanalization. Care must be taken to avoid including any spermatic cord nerves in the clip during this process of fascial interposition,
a potential cause of post-vasectomy pain. For this reason, some surgeons avoid fascial interposition despite its benefit of marginally improving the effectiveness of vasectomy. After careful inspection for hemostasis, the vas deferens is returned to its native position in the scrotum. The same process is repeated for the contralateral vas deferens through the same opening. Once the procedure is completed, the opening is pinched for a few minutes for hemostasis while the betadine is wiped away from the skin. A scrotal supporter with fluff type dressing is applied along with an ice pack. No antibiotics are required, and acetaminophen or celecoxib is sufficient for postoperative pain management. COMPLICATIONS Early. Vasectomies are often performed in the office setting using local anesthesia and in general have low acute complication rates. Early complications of vasectomy include hematoma and infection, with an average reported incidence of about 2% and 3.4%, respectively.25 Long term. Chronic testicular pain or the post-vasectomy pain syndrome is one of the most vexing postoperative complications of vasectomy. Patients can present with orchalgia, pain with intercourse and/or ejaculation, pain with physical exertion and tender or full epididymides.26 In a retrospective survey of 396 patients 27.2% complained of postoperative testicular pain.27 Fortunately, 82% of the patients experienced only transient pain, while 19% had pain for more than 3 months, or a 5% overall incidence of chronic testicular pain in this study group. Troublesome pain resulting in a request for vasectomy reversal appears to occur after fewer than 1 in 1000 vasectomy procedures but some complaints are more common. Leslie et al reported a much higher incidence of chronic pain, 14.7% at 7 months after vasectomy.28 Finally, Manikandan et al reported the incidence of chronic scrotal pain at 1 and 10 years after vasectomy to be 16.8% and 13.8%, respectively.29 The pathophysiology of PVPS is incompletely understood. Because reversal surgery can successfully treat this symptom in some patients and pain can be associated with ejaculation, congestion of the obstructed vas deferens and epididymis has been hypothesized as the etiology.30 In their review of PVPS Christiansen and Sandlow indicated that anatomical derangement following vasectomy results in opposing forces with intercourse and ejaculation. Smooth muscle cells of the efferent ducts and initial segment of the epididymis push fluid into the epididymal tail while contraction of the vas deferens results in retrograde flow of fluid into the caudal epididymis.31 Myers et al reported pain relief after vasectomy reversal in 24 of 32 patients (75%) and in 3 of 32 (9.4%) after a second reversal procedure.32 Denervation of the spermatic cord is another therapeutic strategy, with 1 group reporting 13 of 17 (76.5%) complete and 4 of 17 (23.5%) partial responses.27
Sperm granulomas have been implicated in exacerbation and amelioration of PVPS. Sperm granulomas form in 4% to 60% of closed ended vasectomies.26, 31-36 Shapiro and Silber theorized that the presence of a sperm granuloma at the vasectomy site would prevent epididymal pressure buildup, perforation and the formation of an epididymal sperm granuloma, reducing the likelihood for pain.34 However, Schmidt reported that the sperm granuloma itself was a painful lesion in 40% of cases.33 OUTCOMES Level I evidence indicates that the no-scalpel method is generally preferred over the conventional technique for fewer complications but it appears more difficult for physicians to learn. In a Cochrane database review Cook et al evaluated 2 randomized controlled trials comparing the scalpel and no-scalpel incisions for vasectomy.37 Although no difference in effectiveness was found between the 2 techniques, the authors noted that the no-scalpel approach resulted in less bleeding, hematoma, infection and pain, as well as shorter operative times. The same group compared vasectomy occlusion techniques.38 Of the 6 randomized controlled trials conclusions could not be drawn about trials using vas occlusion clips or vas irrigation. Fascial interposition was noted to reduce surgical failure. Failure rate. In a survey of 586 U.S. urologists about 1 pregnancy was reported per 1000 vasectomies, with 51% of pregnancies occurring during the immediate post-vasectomy period.39 In another review of 5331 vasectomies performed by 1 physician during 24 years with at least 2 postoperative semen tests there were 97 failures of all types, with 32 (0.60%) early overt failures, 4 (0.08%) late overt failures (at least 4 years after the second semen test) and 61 (1.14%) technical failures involving the persistence of small numbers of spermatozoa.40 Of the 97 failures 4 were attributed to missed vasa deferentia and the remaining to recanalization. The U.S. Collaborative Review of Sterilization prospective cohort study reported a 9.4 (95% CI 1.2-17.5) cumulative probability of failure per 1000 procedures 1 year after vasectomy and an 11.3 (95% CI 2.3-20.3) cumulative probability at years 2, 3 and 5.41 Post-vasectomy semen analysis. Follow-up after vasectomy typically involves semen analyses to document azoospermia, although routines vary according to individual practices. There is considerable discord as to how many semen analyses are necessary and at what intervals they should be performed. Studies have demonstrated variable time and number of ejaculations required to achieve azoospermia.42 In a review of 56 studies Griffin et al reported a median achievement of azoospermia of greater than 80% after 3 months and 20 ejaculations, with 1.4% of patients demonstrating persistent nonmotile sperm.43 They recommend a protocol involving 1 semen analysis after 3 months and 20 ejaculations, and patients with positive samples can be followed with periodic
testing until azoospermia is achieved. Men with a persistently low number of nonmotile sperm can be given cautious assurance of success. The British Andrology Society guidelines put forth the following recommendations for assessment of post-vasectomy semen analysis: ‘‘Initial assessment should take place at 16 weeks post vasectomy and after the patient has produced at least 24 ejaculates; if no sperm are seen on direct microscopy of freshly produced specimen, a centrifuged specimen examination for the presence of motile and nonmotile spermatozoa should follow; clearance should be given after 2 sperm free ejaculates; and in cases of persistent identification of nonmotile spermatozoa, the patient should be advised regarding the cessation of other contraceptive precautions.’’44 The finding of motile sperm on the first PVSA is not uncommon and should be followed with additional PVSA before considering a repeat vasectomy. In a descriptive study of 5460 patients Labrecque et al reported that 347 (6.4%) had motile sperm in the initial PVSA.45 Of 309 of these men with motile sperm selected for additional analyses 174 (56.3%, 95% CI 59.7-61.7) had delayed vasectomy success. Many practitioners will accept a semen sample with rare nonmotile sperm as evidence of initial success after vasectomy, allowing couples to stop contraception, with the proviso that a repeat semen analysis is required. In practice most men do not follow full guidelines that are recommended for followup semen analyses after vasectomy. An AUA consensus panel is expected to produce recommendations for post-vasectomy follow-up in the next year. Compliance: Proponents for fewer post-vasectomy sperm analyses point to poor overall patient compliance rates after vasectomy. Badrakumar et al assessed compliance rates for 1 and 2 PVSA regimens, and not surprisingly compliance was better for the first requested sample (82% to 84% vs 72%).46 A review of 1892 consecutive patient records revealed that 644 (34%) never returned for follow-up after vasectomy, 1619 (33%) returned for a single PVSA, 1629 (33%) returned for a second PVSA and only 60 (3%) completed instructions for a yearly PVSA.47 Chawla et al reported that 45.6% of 690 patients failed to submit even 1 sample.48 Persistent Nonmotile Sperm: Persistence or reappearance of nonmotile sperm after vasectomy is a management dilemma familiar to many urologists. In 1 study nonmotile sperm was found in 33% of patients 12 weeks after surgery and the mean time to azoospermia was 6.36 months, while reappearance of nonmotile sperm after initial azoospermia was reported in 5 of 65 patients.49 Philp et al reported no pregnancies in 310 men with persistent nonmotile sperm who were given special clearance.50 Two other studies also indicated no pregnancies by 15151 and 20052 men with persistent nonmotile sperm. Lest these reports lull urologists into complacency, there are reports of DNA confirmed paternity in vasectomized men with 2 consecutive azoospermic samples,53, 54 including 1 man whose spun sample demonstrated only a few nonmotile
spermatozoa.55 In a medicolegal review of vasectomy Gingell et al recommended that the patient, not the physician, should make the decision to discontinue contraception in cases of persistent nonmotile sperm.56 Fresh semen samples should be examined to ensure that the sperm are truly nonmotile, as the presence of even 1 motile sperm more than 3 to 6 months after the procedure is an indication for repeat vasectomy. Furthermore, as a procedure vulnerable to litigation, the authors stress the importance of sound surgical technique, clear communication with the patient, and documentation of all aspects of the procedure and encounters, including counseling and consent. Laboratory results should be communicated directly to the patient by the surgeon. OTHER CONSIDERATIONS Despite extensive discussion in the lay press, there are no data to link performance of a vasectomy as a cause for another significant medical disorder. Prostate and testicular cancers. The popularity of vasectomy has been shadowed by studies reporting an association between this procedure and prostate cancer.57, 58 Several physiological alterations after vasectomy are proposed to explain this potential link, including an increase in circulating androgen levels, formation of anti-sperm antibodies, production of local growth factors such as epidermal growth factor and transforming growth factor-alpha, and changes in seminal fluid.59 None of these biological factors has been conclusively demonstrated to support the relationship of vasectomy and prostate cancer. Many studies including several meta-analyses have disputed the link to prostate cancer.59, 60 In 1998 Bernal-Delgado et al performed a meta-analysis of 14 original studies (5 cohort and 9 case control) evaluating the association of vasectomy and prostate cancer.59 Although the overall relative risk was 1.23 (95% CI 1.01-1.49), indicating a slight but statistically significant excess risk of prostate cancer among individuals who had undergone vasectomy, the systematic review demonstrated numerous methodological problems of the constituent studies. Sensitivity analysis indicated the detected effect was influenced strongly by studies more vulnerable to bias (case control and hospital based) and internal validity problems (detection bias and inadequate selection of controls). As a result, the authors concluded no causal association between vasectomy and prostate cancer. Similarly, in their 2002 meta-analysis of 22 studies (5 cohort and 17 case control) Dennis et al noted that men with a prior vasectomy may be at an increased risk of prostate cancer but concluded that the increase may not be causal because of potential bias.60 Several population based studies also revealed no causal relationship between vasectomy and prostate cancer. In a national population based, case control study 923 new cases of prostate cancer from the New Zealand Cancer Registry were compared to 1224 randomly selected controls.61 The relative risk of prostate cancer for men who had a vasectomy
versus those who had not was 0.92 (95% CI 0.75-1.14). The time since vasectomy was also not significant (RR 0.92, 95% CI 0.68-1.23 for greater than or equal to 25 years since vasectomy). In a population based registry data study from Denmark a total of 46 cohort patients were diagnosed with prostate cancer while 46.93 were expected (standardized incidence ratio 0.98, 95% CI 0.7-1.3); time since or age at vasectomy also showed no trend.62 In a study from England Goldacre et al found no elevation of prostate cancer risk after vasectomy (rate ratio 0.74, 95% CI 0.45-1.14).63 The literature is replete with studies looking into the relationship between vasectomy and prostate cancer. The overall trend of these reports points to the general consensus that there is no definitive evidence for causal association between vasectomy and prostate cancer despite a few positive associations. The positive findings are weakened by methodological issues such as detection bias and lack of statistical power among other factors. For example, as vasectomies are often performed by urologists in the United States, undergoing this procedure may increase the likelihood for prostate cancer screening and detection by said provider.64 Some small studies have proposed a link between vasectomy and testicular cancer. Although this potential association has received less media attention than the alleged relationship between vasectomy and prostate cancer, Moller et al performed a large cohort study of more than 73,000 men to explore the possible risk of testicular cancer after vasectomy.65 They found no increased incidence of testicular cancer in vasectomized men compared to the whole Danish population (standardized morbidity ratio 1.01, 95% CI 0.791.28). They also reported that vasectomy does not accelerate the growth or diagnosis of preexisting testicular neoplasms. Autoimmunity. The production of anti-sperm antibodies in men undergoing vasectomy is attributed to granuloma formation, increased permeability of epithelial barriers in the rete testis and epididymis, and transport of phagocytic cells to regional lymph nodes.66 Do the autoimmune effects of vasectomy have an impact on immunological disorders in vasectomized men? To answer this question, Goldacre et al compared a population of men who underwent vasectomy with a reference population to determine the rate ratios for selected immune related diseases before and after vasectomy.67 After a mean follow-up of 13 years, the authors reported no longterm elevation of risk following vasectomy of several immune related diseases including asthma, diabetes mellitus, ankylosing spondylitis, thyrotoxicosis, multiple sclerosis, myasthenia gravis, inflammatory bowel disease, rheumatoid arthritis and testicular atrophy. Cardiovascular disease. As a corollary to autoimmune concerns of vasectomy, another potential sequela of circulating immune complexes derived from anti-sperm antibodies is endothelial injury and inflammation leading to cardiovascular disease. In 1980 Clarkson and Alexander reported more severe and extensive atherosclerosis in rhesus monkeys vasec202
tomized for 9 to 14 years and fed a non-atherogenic diet compared to controls.68 However, this finding has been disputed by several human and animal studies. One such study was performed by Manson et al in 1999 as part of the U.S. Physicians’ Health Study.69 Of 22,071 participating U.S. male physicians 4546 reported having undergone vasectomy including 1159 who had undergone the procedure at least 15 years before study entry. With 258,892 person years of follow-up, the reported multivariate relative risk of total myocardial infarction was 0.94 (95% CI 0.77-1.14) for men with compared to men without vasectomy. Risk estimates for fatal and nonfatal events were not significantly different for the 2 groups. A study of men participating in the Atherosclerosis Risk in Communities Study also revealed no evident association between vasectomy and atherosclerosis.70 Urolithiasis. To explore the reported increase in renal stone frequency and disturbance of mineral and hormone homeostasis after vasectomy, Schreiber and Schwille compared 14 vasectomized rats to 12 sham surgery controls.71 At 7 months after surgery serum magnesium was decreased (p=0.014) and phosphaturia was increased (p=0.025) in the vasectomy group. Vasectomy resulted in significant accumulation of phosphorus, calcium and magnesium in renal papillae. Furthermore, calcium phosphate stones were found in 2 of the vasectomized rats. The authors theorized that vasectomy may result in disturbance of magnesium, calcium and phosphorus homeostasis at the level of the kidney, and induce mild hypomagnesemia and marked hyperphosphaturia in the presence of normal parathyroid function. Some human data are also available, although they do not adequately consider socioeconomic variables that predispose men to choose vasectomy and the risk of urolithiasis. As an offshoot of the U.S. Coronary Artery Surgery Study, data on urological disease in 11,205 men were collected, and the age adjusted relative risk for calculi in vasectomized men was 1.67 (p <0.001).72 Osteoporosis. Based on the evidence of various immunological and histological changes of the testis and alterations to the hypothamalo-pituitary axis after vasectomy, Byrne et al investigated the influence of vasectomy on bone mineral density and predisposition to osteoporosis.73 Specifically, changes in the release of LH and FSH have been observed after vasectomy,74 which may reflect a decrease in negative feedback at the level of the hypothalamus and pituitary as a consequence of decreased gonadal activity.75 From these data Byrne et al hypothesized that BMD may be altered in patients who underwent vasectomy.73 However, when the authors compared the BMD of 25 vasectomized men with age matched controls, no statistically significant differences were detected. Psychological effects. Given the sensitive nature of sterilization procedures and reproductive health, numerous studies and reviews have been published on the psychological effects of vasectomy. Vasectomy has been found to have a range of effects on psychological health from beneficial to detri-
mental. In a questionnaire analysis of psychological correlates of vasectomy Sandlow et al reported that anxiety about vasectomy was driven mainly by fear of pain and of the unknown and, although concerns about the finality of the procedure was not a major concern, there was confusion about the reversibility of the procedure.76 The authors recommended adequate pre-vasectomy counseling to counter these fears and misconceptions. Another group used a biographical questionnaire to determine whether vasectomy had effects on marriage such as sexual and marital satisfaction, communication and frequency of sexual intercourse.77 The authors did not detect a significant difference in these parameters before and after vasectomy. In contrast, Maschhoff et al reported that certain indices of marital stability improved after vasectomy, notably sexual frequency and the initiation of intercourse by the female.78 Sexual effects. Although an anatomical etiology of erectile dysfunction following vasectomy does not exist, Buchholz et al scrutinized the psychosexual aspects of post-vasectomy erectile dysfunction.79 Of the patients who attributed erectile dysfunction to a previous vasectomy a significant 22% had been urged into the decision to undergo a vasectomy by their female partners, and many of these patients believed there was a relationship between the erectile dysfunction and vasectomy. Although erectile dysfunction is not a widespread problem following vasectomy, psychological studies provide insight into potential non-organic consequences of the procedure. Reversal surgery. Since up to 6% of men undergoing vasectomy eventually seek reversal surgery, Potts et al evaluated patient characteristics that may predict this change of heart.80 Among age at time of vasectomy, religion, occupation, wife employment status, number of marriages, number of children, reason for reversal and number of years between vasectomy and reversal, younger age at time of surgery and a wife who worked outside the home were associated with increased vasectomy reversal. In a related study of vasectomy regret from the partner’s perspective Jamieson et al found the cumulative probability of a woman expressing regret within 5 years after her husband’s vasectomy was 6.1% (95% CI 3.6-8.6), which is comparable to the 7.0% (95% CI 5.8-8.1) 5-year cumulative probability of regret among women after tubal sterilization.81 Women who had substantial conflict with their husbands before the surgery were more likely to request vasectomy reversal compared to women who did not report conflict (rate ratio 25.3, 95% CI 2.9-217.2).81 FUTURE Surgical contraception. Variations of the Standard Vasectomy: Numerous variations on a theme have emerged on the vasectomy procedure, ranging from slight alterations of occlusion techniques to implementation of new devices and
technology. An example of occlusion technique modification is use of an implantable ligation device called the Vasclip.82 The overall procedure is similar to the standard vasectomy but instead of sectioning and cauterizing the vas deferens, a small biocompatible polymer lock is placed. Percutaneous injection of polyurethane elastomer plugs is another alternative occlusion method used in China.83 With this no-incision method, the vas deferens is secured and anesthetized, and a 6 gauge needle is used to deliver the polymer into the lumen. In a series of 12,000 men Zhao reported an azoospermia rate of 98% at 1, 2 and 3 years, and a complication rate of 0.47% (84% local infection, 16% local hematoma).83 Furthermore, of 86 men who had the plugs removed 51 achieved pregnancy. Another novel application of technology for vasal occlusion is the use of high intensity focused ultrasound ablation. Roberts et al applied this technique in a canine model using a high intensity focused ultrasound transducer which was incorporated into a handheld clip.84 The authors aim is to use current technology for benign prostatic hyperplasia and renal tumor ablation for a rapid non-invasive alternative to vasectomy. Laparoscopy: As with many areas of urological surgery, laparoscopy may play a significant albeit limited role as a vasectomy technique, and several cases have been reported in the literature.85-89 Specifically, men undergoing a laparoscopic hernia repair who desire vasectomy may benefit from a concurrent laparoscopic vasectomy and avoid a separate scrotal incision. One group hypothesized that another potential benefit to the laparoscopic approach is fewer symptomatic post-vasectomy sperm granulomas.85 Schmidt postulated that pain associated with a sperm granuloma may be secondary to entrapment of nerves within the granuloma.33 As the vas deferens diverges from the cord structures at the internal ring, Kakitelashvili et al note that granuloma pain may be less likely with the laparoscopic approach.85 However, difficulty of future reversal surgery is a major disadvantage to this approach. Obviously, laparoscopy is a far more invasive procedure, requiring general anesthesia, than the standard scrotal procedure. Medical contraception. Reversibility is a key benefit of medical and pharmacological contraception. To date, male, non-barrier contraceptive options have been limited to vasectomy and inadequate non-surgical methods such as withdrawal and periodic abstinence.90 Potential developments in male contraception include hormonal suppression of testosterone and vaccines to immobilize sperm.91 Vaccines: Many sperm proteins are being considered as potential targets for anti-sperm vaccines,91 including a human sperm antigen called SP-10, which has been called a primary vaccine candidate by the WHO’s Taskforce on Contraceptive Vaccines.92 Vaccines against sperm acrosome, midpiece and tail cause sperm clumping and also prevent penetration of the zona pellucida.91 Animal trials have demonstrated persistent
immunity for about 1 year.91, 93-95 Immunization against another spermatozoal antigen, PH-20, resulted in reversible infertility in male guinea pigs lasting about 1 year.96 Immunization can be directed against other targets along the endocrine axis such as FSH, LH and GnRH. However, potential problems with immunotherapy such as induction of autoimmunity and variable responses in individual patients make it a less attractive male contraceptive option.97 Hormonal Contraception: In the reproductive endocrine axis pulsatile GnRH secretion from the hypothalamus triggers the release of LH and FSH from the anterior pituitary. Leydig and Sertoli cells in the testis are dependent on LH and FSH for testosterone production and spermatogenesis. Hormonal contraception inhibits spermatogenesis by the negative feedback effect of exogenous testosterone. Different regimens have been tested, including various formulations of testosterone and GnRH analogues, and combination therapy with progestins and antiandrogens.90 In a Cochrane database review Grimes et al evaluated 30 randomized trials of male hormonal contraception with azoospermia as the primary outcome measure.98 Various regimens were included and results varied widely. Although the data were insufficient to evaluate pregnancy rates and side effects, the authors concluded that several trials of male hormonal contraception demonstrated promising efficacy for inducing azoospermia. Potential adverse effects of exogenous testosterone such as acne and weight gain depend on the formulation and dose. More significant and long-term consequences to the cardiovascular system, bone and prostate are difficult to determine with available short-term studies.97 Non-endocrine Contraception: Several non-endocrine male contraceptives are being investigated, including Eppin (epididymal protease inhibitor), calcium channel blockers, londamine derivates, triptolide and N-butyldeoxynojirimycin.90 Non-hormonal agents have the potential advantages of rapid action and sparing of non-reproductive androgen dependent function.97 Eppin, a protein specific to the testis and epididymis, is an illustrative example of a non-hormonal post-testicular male contraceptive target. Eppin originates from Sertoli cells and epididymal epithelial cells, and coats the surface of ejaculated human spermatozoa.99 Eppin interacts with semenogelin and forms a part of the ejaculate coagulum,100 and also has strong antibacterial activity.101 In 2004 O’Rand et al immunized 9 male Macaca monkeys with Eppin, of which 7 (78%) developed high titers and infertility.102 In addition, 5 of the 7 monkeys (71%) recovered fertility with cessation of immunization therapy. The authors speculated that infertility resulted from the interference of Eppin interaction with semenogelin and the sperm surface by antibodies. Potential targets for male medical contraception abound but are limited not only by conventional criteria such as efficacy, safety and cost, but by personal and sociopolitical attitudes. With the exception of vasectomy and barrier meth204
ods such as condoms, contraception traditionally has focused on women, perhaps because contraceptive failure has greater consequences for women.97 Would women trust men not to forget a dose? And would men willingly take on this responsibility? In surveys 44% to 83% of men103 and 71% to 90% of women104 indicated their willingness to use male medical contraception. Implementation of male medical contraception represents a paradigm shift that faces many challenges. Even with increasing interest and research in male medical contraception, years will pass before its clinical fruition. In the meantime vasectomy remains one of the safest and most cost-effective contraceptive options. REFERENCES Trussell J, Leveque JA, Koenig JD et al: The economic value of contraception: a comparison of 15 methods. Am J Public Health 1995; 85: 494. Reilly PR: Involuntary sterilization in the United States: a surgical solution. Q Rev Biol 1987; 62: 153. White JW: II. The present position of the surgery of the hypertrophied prostate. Ann Surg 1893; 18: 152. Ochsner AJ: Surgical treatment of habitual criminals. JAMA 1899; 53: 867. Ochsner AJ: The surgical treatment of habitual criminals, imbeciles, perverts, paupers, morons, epileptics, and degenerates. Ann Surg 1925; 82: 321. Drake MJ, Mills IW and Cranston D: On the chequered history of vasectomy. BJU Int 1999; 84: 475. Gugliotta A: ‘‘Dr. Sharp with his little knife’’: therapeutic and punitive origins of eugenic vasectomy—Indiana, 1892-1921. J Hist Med Allied Sci 1998; 53: 371. Sengoopta C: ‘Dr Steinach coming to make old young!’: sex glands, vasectomy and the quest for rejuvenation in the roaring twenties. Endeavour 2003; 27: 122. Wolfers D and Wolfers H: Vasectomania. Fam Plann Perspect 1973; 5: 196. Kahn A: Regaining lost youth: the controversial and colorful beginnings of hormone replacement therapy in aging. J Gerontol A Biol Sci Med Sci 2005; 60: 142. Barone MA, Hutchinson PL, Johnson CH et al: Vasectomy in the United States, 2002. J Urol 2006; 176: 232. Marquette CM, Koonin LM, Antarsh L et al: Vasectomy in the United States, 1991. Am J Public Health 1995; 85: 644. Haws JM, Morgan GT, Pollack AE et al: Clinical aspects of vasectomies performed in the United States in 1995. Urology 1998; 52: 685. Bensyl DM, Iuliano DA, Carter M et al: Contraceptive use—United States and territories, Behavioral Risk Factor Surveillance System, 2002. MMWR Surveill Summ 2005; 54: 1. Monoski MA, Li PS, Baum N et al: No-scalpel, noneedle vasectomy. Urology 2006; 68: 9.
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37. Cook LA, Pun A, van Vliet H et al: Scalpel versus noscalpel incision for vasectomy. Cochrane Database Syst Rev 2007; CD004112. 38. Cook LA, Van Vliet H, Lopez LM et al: Vasectomy occlusion techniques for male sterilization. Cochrane Database Syst Rev 2007; CD003991. 39. Deneux-Tharaux C, Kahn E, Nazerali H et al: Pregnancy rates after vasectomy: a survey of US urologists. Contraception 2004; 69: 401. 40. Alderman PM: The lurking sperm. A review of failures in 8879 vasectomies performed by one physician. JAMA 1988; 259: 3142. 41. Jamieson DJ, Costello C, Trussell J et al: The risk of pregnancy after vasectomy. Obstet Gynecol 2004; 103: 848. 42. Barone MA, Nazerali H, Cortes M et al: A prospective study of time and number of ejaculations to azoospermia after vasectomy by ligation and excision. J Urol 2003; 170: 892. 43. Griffin T, Tooher R, Nowakowski K et al: How little is enough? The evidence for post-vasectomy testing. J Urol 2005; 174: 29. 44. Hancock P and McLaughlin E: British Andrology Society guidelines for the assessment of post vasectomy semen samples (2002). J Clin Pathol 2002; 55: 812. 45. Labrecque M, St-Hilaire K and Turcot L: Delayed vasectomy success in men with a first postvasectomy semen analysis showing motile sperm. Fertil Steril 2005; 83: 1435. 46. Badrakumar C, Gogoi NK and Sundaram SK: Semen analysis after vasectomy: when and how many? BJU Int 2000; 86: 479. 47. Maatman TJ, Aldrin L and Carothers GG: Patient noncompliance after vasectomy. Fertil Steril 1997; 68: 552. 48. Chawla A, Bowles B and Zini A: Vasectomy followup: clinical significance of rare nonmotile sperm in postoperative semen analysis. Urology 2004; 64: 1212. 49. De Knijff DW, Vrijhof HJ, Arends J et al: Persistence or reappearance of nonmotile sperm after vasectomy: does it have clinical consequences? Fertil Steril 1997; 67: 332. 50. Philp T, Guillebaud J and Budd D: Complications of vasectomy: review of 16,000 patients. Br J Urol 1984; 56: 745. 51. Davies AH, Sharp RJ, Cranston D et al: The long-term outcome following ‘‘special clearance’’ after vasectomy. Br J Urol 1990; 66: 2. 52. Edwards IS and Farlow JL: Non-motile sperms persisting after vasectomy: do they matter? Br Med J 1979; 1: 87. 53. Smith JC, Cranston D, O’Brien T et al: Fatherhood without apparent spermatozoa after vasectomy. Lancet 1994; 344: 30. 54. Khan MA and Cranston D: Recanalization of the vas following vasectomy. Br J Urol 1997; 79: 484.
55. Thomson JA, Lincoln PJ and Mortimer P: Paternity by a seemingly infertile vasectomised man. BMJ 1993; 307: 299. 56. Gingell C, Crosby D and Carroll R: Review of the complications and medicolegal implications of vasectomy. Postgrad Med J 2001; 77: 656. 57. Giovannucci E, Ascherio A, Rimm EB et al: A prospective cohort study of vasectomy and prostate cancer in US men. JAMA 1993; 269: 8. 58. Giovannucci E, Tosteson TD, Speizer FE et al: A retrospective cohort study of vasectomy and prostate cancer in US men. JAMA 1993; 269: 878. 59. Bernal-Delgado E, Latour-Perez J, Pradas-Arnal F et al: The association between vasectomy and prostate cancer: a systematic review of the literature. Fertil Steril 1998; 70: 191. 60. Dennis LK, Dawson DV and Resnick MI: Vasectomy and the risk of prostate cancer: a meta-analysis examining vasectomy status, age at vasectomy, and time since vasectomy. Prostate Cancer Prostatic Dis 2002; 5: 193. 61. Cox B, Sneyd MJ, Paul C et al: Vasectomy and risk of prostate cancer. JAMA 2002; 287: 3110. 62. Lynge E: Prostate cancer is not increased in men with vasectomy in Denmark. J Urol 2002; 168: 488. 63. Goldacre MJ, Wotton CJ, Seagroatt V et al: Cancer and cardiovascular disease after vasectomy: an epidemiological database study. Fertil Steril 2005; 84: 1438. 64. Peterson HB and Howards SS: Vasectomy and prostate cancer: the evidence to date. Fertil Steril 1998; 70: 201. 65. Moller H, Knudsen LB and Lynge E: Risk of testicular cancer after vasectomy: cohort study of over 73,000 men. BMJ 1994; 309: 295. 66. Anderson DJ and Alexander NJ: Consequences of autoimmunity to sperm antigens in vasectomized men. Clin Obstet Gynaecol 1979; 6: 425. 67. Goldacre MJ, Wotton CJ, Seagroatt V et al: Immunerelated disease before and after vasectomy: an epidemiological database study. Hum Reprod 2007; 22: 1273. 68. Clarkson TB and Alexander NJ: Long-term vasectomy: effects on the occurrence and extent of atherosclerosis in rhesus monkeys. J Clin Invest 1980; 65: 15. 69. Manson JE, Ridker PM, Spelsberg A et al: Vasectomy and subsequent cardiovascular disease in US physicians. Contraception 1999; 59: 181. 70. Coady SA, Sharrett AR, Zheng ZJ et al: Vasectomy, inflammation, atherosclerosis and long-term followup for cardiovascular diseases: no associations in the atherosclerosis risk in communities study. J Urol 2002; 167: 204. 71. Schreiber M and Schwille PO: Vasectomy in the rat-effects on mineral metabolism, with emphasis on renal tissue minerals and occurrence of urinary stones. J Urol 1995; 153: 1284.
72. Kronmal RA, Alderman E, Krieger JN et al: Vasectomy and urolithiasis. Lancet 1988; 1: 22. 73. Byrne PA, Evans WD and Rajan KT: Does vasectomy predispose to osteoporosis? Br J Urol 1997; 79: 599. 74. Fisch H, Laor E, BarChama N et al: Detection of testicular endocrine abnormalities and their correlation with serum antisperm antibodies in men following vasectomy. J Urol 1989; 141: 1129. 75. Silber SJ: Vasectomy and its microsurgical reversal. Urol Clin North Am 1978; 5: 573. 76. Sandlow JI, Westefeld JS, Maples MR et al: Psychological correlates of vasectomy. Fertil Steril 2001; 75: 544. 77. Hofmeyr DG and Greeff AP: The influence of a vasectomy on the marital relationship and sexual satisfaction of the married man. J Sex Marital Ther 2002; 28: 339. 78. Maschhoff TA, Fanshier WE and Hansen DJ: Vasectomy: its effect upon marital stability. J Sex Res 1976; 12: 295. 79. Buchholz NP, Weuste R, Mattarelli G et al: Post-vasectomy erectile dysfunction. J Psychosom Res 1994; 38: 759. 80. Potts JM, Pasqualotto FF, Nelson D et al: Patient characteristics associated with vasectomy reversal. J Urol 1999; 161: 1835. 81. Jamieson DJ, Kaufman SC, Costello C et al: A comparison of women’s regret after vasectomy versus tubal sterilization. Obstet Gynecol 2002; 99: 1073. 82. Kirby D, Utz WJ and Parks PJ: An implantable ligation device that achieves male sterilization without cutting the vas deferens. Urology 2006; 67: 807. 83. Zhao SC: Vas deferens occlusion by percutaneous injection of polyurethane elastomer plugs: clinical experience and reversibility. Contraception 1990; 41: 453. 84. Roberts WW, Chan DY, Fried NM et al: High intensity focused ultrasound ablation of the vas deferens in a canine model. J Urol 2002; 167: 2613. 85. Kakitelashvili V, Thompson J and Balaji KC: Laparoscopic vasectomy: case report and review of the literature. J Endourol 2002; 16: 105. 86. Smith AI and Polglase AL: Laparoscopic vasectomy. Med J Aust 1993; 158: 358. 87. Mosquera LF and Urban J: Laparoscopic vasectomy. Surg Laparosc Endosc 1994; 4: 461. 88. Patterson R, Temple CL and Mulloy RH: Laparoscopic vasectomy en passant. Can J Surg 1996; 39: 513. 89. Kasirajan K, Govindrajan S, Erzurum VZ et al: Synchronous laparoscopic vasectomy and hernia repair. J Laparoendosc Adv Surg Tech A 1999; 9: 177. 90. Hoesl CE, Saad F, Poppel M et al: Reversible, nonbarrier male contraception: status and prospects. Eur Urol 2005; 48: 712. 91. Reifsnider E: On the horizon: new options for contraception. J Obstet Gynecol Neonatal Nurs 1997; 26: 91.
92. Reddi PP, Castillo JR, Klotz K et al: Production in Escherichia coli, purification and immunogenicity of acrosomal protein SP-10, a candidate contraceptive vaccine. Gene 1994; 147: 189. 93. Alexander NJ: Future contraceptives. Sci Am 1995; 273: 136. 94. Coonrod SA, Westhusin ME, Naz RK: Monoclonal antibody to human fertilization antigen-1 (FA-1) inhibits bovine fertilization in vitro: application in immunocontraception. Biol Reprod 1994; 51: 14. 95. Naz RK and Wolf DP: Antibodies to sperm-specific human FA-1 inhibit in vitro fertilization in rhesus monkeys: development of a simian model for testing of antiFA-1 contraceptive vaccine. J Reprod Immunol 1994; 27: 111. 96. Primakoff P, Woolman-Gamer L, Tung KS et al: Reversible contraceptive effect of PH-20 immunization in male guinea pigs. Biol Reprod 1997; 56: 1142. 97. Anderson RA and Baird DT: Male contraception. Endocr Rev 2002; 23: 735. 98. Grimes DA, Lopez LM, Gallo MF et al: Steroid hormones for contraception in men. Cochrane Database Syst Rev 2007; CD004316.
99. Wang Z, Widgren EE, Richardson RT et al: Characterization of an eppin protein complex from human semen and spermatozoa. Biol Reprod 2007; 77: 476. 100. O’Rand MG, Widgren EE, Wang Z et al: Eppin: an effective target for male contraception. Mol Cell Endocrinol 2006; 250: 157. 101. Yenugu S, Richardson RT, Sivashanmugam P et al: Antimicrobial activity of human EPPIN, an androgenregulated, sperm-bound protein with a whey acidic protein motif. Biol Reprod 2004; 71: 1484. 102. O’Rand MG, Widgren EE, Sivashanmugam P et al: Reversible immunocontraception in male monkeys immunized with eppin. Science 2004; 306: 1189. 103. Martin CW, Anderson RA, Cheng L et al: Potential impact of hormonal male contraception: cross-cultural implications for development of novel preparations. Hum Reprod 2000; 15: 637. 104. Glasier AF, Anakwe R, Everington D et al: Would women trust their partners to use a male pill? Hum Reprod 2000; 15: 646.
Study Questions Volume 27 Lesson 22
1. Which of the following interventions during vasectomy have been shown to decrease failure (recanalization) rates? a. Vas occlusion clips b. Polyurethane elastomer plugs c. Fascial interposition d. Vas irrigation e. High intensity focused ultrasound ablation 2. In the British Andrology Society guidelines for post-vasectomy semen analysis the initial assessment should take place how many weeks after surgery? a. 8 b. 10 c. 12 d. 14 e. 16 3. In an animal study vasectomized rats demonstrated a. Hyperphosphaturia b. Hypocitraturia c. Hypercalciuria d. Hypermagnesemia e. Hypercalcemia 4. What percent of vasectomized patients eventually seek reversal surgery? a. 0-2 b. 3-6 c. 7-10 d. 11-14 e. 15-20 5. Which of the following is not a potential male medical contraceptive? a. Testosterone b. Progestin c. Triptolide d. Pyrazolidine derivates e. Londamine derivatest
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