Guidelines on Male Infertility

52. Berger RE. Epididymitis. In: Holmes KK, Mardh PA, Sparling PF et al. (eds). Sexually TransmittedDiseases. New York: McGraw-Hill, 1984, pp. 650-662.53. Weidner W, Schiefer HG, Garbe C. Acute nongonococcal epididymitis. Aetiological and therapeuticaspects. Drugs 1987;34 (Suppl 1):111-117.http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db;=PubMed&list;_uids=3481311&do;pt=Abstract54. Nilsson S, Obrant KO, Persson PS. Changes in the testis parenchyma caused by acute non-specificepididymitis. Fertil Steril 1968;19:748-757.http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db;=PubMed&list;_uids=5676481&do;pt=Abstract55. Osegbe DN. Testicular function after unilateral bacterial epididymo-orchitis. Eur Urol 1991;19(3):204-208.http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db;=PubMed&list;_uids=1855525&do;pt=Abstract56. Weidner W, Krause W, Ludwig M. Relevance of male accessory gland infection for subsequent fertilitywith special focus on prostatitis. Hum Reprod Update 1999;5(5):421-432.http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db;=PubMed&list;_uids=10582781&d;opt=Abstract57. Ludwig G, Haselberger J. [Epididymitis and fertility. Treatment results in acute unspecific epididymitis.]Fortschr Med 1977;95(7):397-399. [German]http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db;=PubMed&list;_uids=849851&dopt;=Abstract58. Haidl G. Macrophages in semen are indicative of chronic epididymal infection. Arch Androl1990;25(1):5-11.http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db;=PubMed&list;_uids=2389992&do;pt=Abstract59. Cooper TG, Weidner W, Nieschlag E. The influence of inflammation of the human genital tract onsecretion of the seminal markers alpha-glucosidase, glycerophosphocholine, carnitine, fructose andcitric acid. Int J Androl 1990;13(5):329-336.http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db;=PubMed&list;_uids=2283178&do;pt=Abstract60. Robinson AJ, Grant JB, Spencer RC, Potter C, Kinghorn GR. Acute epididymitis: why patient andconsort must be investigated. Br J Urol 1990;66(6):642-645.http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db;=PubMed&list;_uids=2265337&do;pt=Abstract61. Schneede P, Tenke P, Hofstetter AG. Urinary Tract Infection Working Group of the Health Care Office ofthe European Association of Urology. Sexually transmitted diseases (STDs) a synoptic overview forurologists. Eur Urol 2003;44(1):1-7.http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db;=PubMed&list;_uids=12814668&d;opt=Abstract62. Schaeffer AJ, Weidner W, Barbalias GA, Botto H, Bjerklung-Johansen TE, Hochreiter WW, Krieger JN,Lobel B, Naber KG, Nickel JC, Potts JM, Tenke P, Hart C. Summary consensus statement: diagnosisand management of chronic prostatitis/chronic pelvic pain syndrome. Eur Urol 2003;(Suppl 2):1-4.63. Alexander RB, Propert KJ, Schaeffer AJ, Landis JR, Nickel JC, O’Leary MP, Pontari MA, McNaughton-Collins M, Shoskes DA, Comiter CV, Datta NS, Fowler JE Jr, Nadler RB, Zeitlin SI, Knauss JS, Wang Y,Kusek JW, Nyberg LM Jr, Litwin MS; Chronic Prostatitis Collaborative Research Network.Ciprofloxacin or tamsulosin in men with chronic prostatitis/chronic pelvic pain syndrome: arandomized, double-blind trial. Ann Intern Med 2004;141(8):581-589.http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd;=Retrieve&dopt;=AbstractPlus&list;_uids=15492337&query;_hl=215&itool;=pubmed_docsum64. Nickel JC, Narayan P, McKay J, Doyle C. Treatment of chronic prostatitis/chronic pelvic pain syndromewith tamsulosin: a randomized double blind trial. J Urol 2004;171(4):1594-1597.http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd;=Retrieve&dopt;=AbstractPlus&list;_uids=15017228&query;_hl=218&itool;=pubmed_docsum 56UPDATE MARCH 2007 12. GERM CELL MALIGNANCIES ANDTESTICULAR MICROCALCIFICATIONS 12.1 Germ cell malignancies and male infertility Testicular germ cell cancer (TGCC) is the most common malignancy in Caucasian males aged between 15 and40 years and affects about 1% of subfertile males. The lifetime risk of TGCC varies between ethnic groups andfrom country to country. The highest annual incidence occurs in Caucasians, varying from 10 per 100,000 in,for example, Denmark and Norway to 2 per 100,000 in Finland and the Baltic countries. It is generally acceptedthat seminomas and non-seminomas are always preceded by CIS, and that CIS will eventually progress to aninvasive cancer if not treated (1,2).The most convincing evidence for a general decline in male reproductive health in humans is theincrease in testicular cancer noted over the recent past in several Western countries (3). The incidence oftesticular cancer has increased in almost all countries which have reliable cancer registers – at least in theCaucasian population (4). It has also been observed that both cryptorchidism and hypospadias are associatedwith an increased risk of testicular cancer, based on the observation that men with cryptorchidism and/orhypospadias are overrepresented among patients with testicular cancer.Dysgenic testes have an increased risk of developing testicular cancer in adulthood. These cancersseem to arise from premalignant gonocytes or CIS cells (5). Testicular microlithiasis can be associated withboth germ cell tumours and CIS of the testis. 12.2 Testicular germ cell cancer and reproductive function.Men with TGCT have decreased semen quality, even prior to a cancer diagnosis (6). Orchidectomy implies arisk of azoospermia in these men, with sperm found in the ejaculate before the tumour-bearing testis has beenremoved. Semen cryopreservation prior to orchidectomy should therefore be considered (see section 14Semen cryopreservation). Treatment of TGCT may imply an additional impairment of semen quality (7).As well as spermatogenic failure, TGCT patients have Leydig cell dysfunction, even in the contralateraltestis (8). The risk of hypogonadism may therefore be increased in men treated for TGCT. Obtainingpretreatment levels of testosterone, SHBG, LH and oestradiol, may help in disclosing post-treatmenthypogonadism. Long-term follow up of TGCT men with low normal androgen levels should be considered asthey may be at risk for developing hypogonadism due to age-related decrease in testosterone production (9). 12.3 Testicular microlithiasisMicrocalcifications inside the testicular parenchyma can be found in 0.6-9% of men referred for testicularultrasound (10-13). Although the true incidence in the general population is unknown, it is probably a rarecondition. However, ultrasound findings of testicular microlithiasis are common in men with germ cell tumours,cryptorchidism, testicular dysgenesis, male infertility, testicular torsion and atrophy, Klinefelter’s syndrome,hypogonadism, male pseudohermaphroditism, varicocele, epididymal cysts, pulmonary microlithiasis and non-Hodgkin’s lymphoma. The incidence seems to be higher with high-frequency ultrasound machines (14).The relationship between testicular microlithiasis (TM) and infertility is unclear. It probably relates todysgenesis of the testis, with degenerate cells being sloughed inside an obstructed seminiferous tubule andfailure of the Sertoli cells to phagocytose the debris. Subsequently, calcification occurs.Testicular microcalcification is a condition found in testis at risk for malignant development. Thereported incidence of TM in men with germ cell malignancy is 6-46% (15-17), and it has therefore beensuggested that TM should be considered premalignant. However, it remains to be established whether TM ispresent before development of invasive TGCT, and whether TM might be an indicator for the preinvasive stageof TGCTs, known as carcinoma in situ (CIS). Testicular biopsies of men with TM have found a higher prevalenceof CIS, especially in men with bilateral microlithiasis (18). On the other hand, TM is found most often in menwith a benign testicular condition and the microcalcifications itself are not malignant.Further investigation of the association between TM and CIS would require testicular biopsies to becarried out in large series of men without signs of a TGCT. Available data, however, indicate that a finding of TMin high-risk patients (e.g. patients referred due to infertility and/or cryptorchidism) warrants follow up byrepeated ultrasound and/or testicular biopsy for detection of CIS. UPDATE MARCH 200757 12.4 RECOMMENDATIONS • It is recommended that either a testicular biopsy or a follow-up scrotal ultrasound should beperformed in men with TM and a history of male infertility, cryptorchidism or testicular cancer and inmen with atrophic testis to rule out CIS of the testis (17,18) (grade B recommendation).• It is important to encourage and educate these patients about self-examination, since this may resultin early detection of germ cell tumours.• In case of suspicious findings on physical examination or ultrasound in patients with TM andassociated lesions, a surgical exploration with testicular biopsy or orchidectomy should beconsidered.• Testicular biopsy, follow-up scrotal ultrasound or the routine use of biochemical tumour markers,abdominal and pelvic computed tomography scanning does not seem to be justified for men withisolated TM without associated risk factors (male infertility, cryptorchidism, testicular cancer, atrophictestis) (11) (grade B recommendation).• Men with TGCT are at increased risk of developing hypogonadism, which should be considered infollow up of these patients (9) (grade B recommendation). 12.5 REFERENCES1. Skakkebaek NE. Carcinoma in situ of the testis: frequency and relationship to invasive germ celltumours in infertile men. Histopathology 1978;2(3):157-170.http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd;=Retrieve&dopt;=AbstractPlus&list;_uids=27442&query;_hl=225&itool;=pubmed_docsum2. von der Maase H, Rorth M, Walbom-Jorgensen S, Sorensen BL, Christophersen IS, Hald T, JacobsenGK, Berthelsen JG, Skakkebaek NE. Carcinoma in situ of contralateral testis in patients with testiculargerm cell cancer: study of 27 cases in 500 patients. Br Med J 1986;293(6559):1398-401.http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd;=Retrieve&dopt;=AbstractPlus&list;_uids=3026550&query;_hl=230&itool;=pubmed_docsum3. Jacobsen R, Bostofte E, Engholm G, Hansen J, Olsen JH, Skakkebaek NE, Moller H. Risk of testicularcancer in men with abnormal semen characteristics: cohort study. BMJ 2000;321(7264):789-792.http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd;=Retrieve&dopt;=AbstractPlus&list;_uids=11009515&query;_hl=232&itool;=pubmed_docsum4. Huyghe E, Matsuda T, Thonneau P. Increasing incidence of testicular cancer worldwide: a review. JUrol 2003;170(1):5-11.http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db;=PubMed&list;_uids=12796635&d;opt=Abstract5. Giwercman A, Muller J, Skakkebaek NE. Carcinoma in situ of the undescended testis. Semin Urol1988;6(2):110-119.http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db;=PubMed&list;_uids=2903524&do;pt=Abstract6. Petersen PM, Skakkebaek NE, Vistisen K, Rorth M, Giwercman A. Semen quality and reproductivehormones before orchiectomy in men with testicular cancer. J Clin Oncol 1999;17(3):941-947.http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd;=Retrieve&dopt;=AbstractPlus&list;_uids=10071288&query;_hl=237&itool;=pubmed_docsum7. Eberhard J, Stahl O, Giwercman Y, Cwikiel M, Cavallin-Stahl E, Lundin KB, Flodgren P, Giwercman A.Impact of therapy and androgen receptor polymorphism on sperm concentration in men treated fortesticular germ cell cancer: a longitudinal study. Hum Reprod 2004;19(6):1418-1425.http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd;=Retrieve&dopt;=AbstractPlus&list;_uids=15105386&query;_hl=240&itool;=pubmed_docsum8. Willemse PH, Sleijfer DT, Sluiter WJ, Schraffordt Koops H, Doorenbos H. Altered Leydig cell function inpatients with testicular cancer: evidence for bilateral testicular defect. Acta Endocrinol (Copenh)1983;102(4):616-624.http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd;=Retrieve&dopt;=AbstractPlus&list;_uids=6133401&query;_hl=242&itool;=pubmed_docsum9. Nord C, Bjoro T, Ellingsen D, Mykletun A, Dahl O, Klepp O, Bremnes RM, Wist E, Fossa SD. Gonadalhormones in long-term survivors 10 years after treatment for unilateral testicular cancer. Eur Urol2003;44(3):322-328.http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd;=Retrieve&dopt;=AbstractPlus&list;_uids=12932930&query;_hl=245&itool;=pubmed_docsum 58UPDATE MARCH 2007 10. Parra BL, Venable DD, Gonzalez E, Eastham JA. Testicular microlithiasis as a predictor of intratubulargerm cell neoplasia. Urology 1996;48(5):797-799.http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db;=PubMed&list;_uids=8911532&do