EAU GUIDELINES POCKET EDITION 1

CONTENTS: ERECTILE DYSFUNCTION MANAGEMENT of URINARY and MALE GENITAL TRACT 3 EAU POCKET GUIDELINES POCKET EDITION 1 Introduction . All EAU members will automatically . All EAU members oweb.nl .ur Introduction of convenient pocket size books This is one of a series comprised version of several EAU a 3) offering (currently avai- based on the currently texts are guidelines. These short texts and can servelable extended guidelines as a quick refe- guide for medical professionals. rence to con- to be of paramount importance The EAU considers it new data texts and introduce tinuously update its guidelines can be viewed online at and the latest versions http://www receive a printed version. receive Office EAU Healthcare Board 2003 March

Introduction EAU POCKET GUIDELINES POCKET EDITION 1 EDITION POCKET GUIDELINES POCKET EAU 2 5 GUIDELINES ON INFERTILITY Infertility (viral) Orchitis torsion Testicular Cytotoxic therapy (chemotherapy) Radiotherapy Y deletions) syndrome, Genetic causes (Klinefelter’s syndrome Kallmann’s syndrome Prader-Willy (adenoma, ) Pituitary gland disorders Congenital absence of the / cysts Müllerian prostatic Epididymal obstructions (infections, congenital) surgery or scrotal After groin Endocrine disorders Obstructions of the male genital tract Sperm antibodies illness stress, Medication, environment, Varicocele disorders Sexual problems/ejaculation Idiopathic 2 Diagnosis 2.1 Introduction of a number focus on must male of The diagnosis testicular and epididy- such as varicocele, disorders, prevalent anom- of the genital tract, and obstructions mal abnormalities, Simultaneous 1). (Table and alies of even if abnor- is preferable, of the female partner assessment in the male. found malities are of 1: The main cause Table insufficiency Testicular

Duration of infertility Primary or secondary infertility Results of analysis status of the female partner Age and fertility About 25% of couples do not achieve within 1 do not achieve pregnancy About 25% of couples

GUIDELINES FOR THE INVESTIGATION FOR GUIDELINES AND TREATMENT OF MALE INFERTILITY MALE OF TREATMENT AND Infertility Surgery, Assisted reproduction) Surgery, diagnosis is mandatory to initiate appropriate therapy (Drugs, therapy diagnosis is mandatory to initiate appropriate applies to all males diagnosed with reduced sperm quality. A quality. sperm applies to all males diagnosed with reduced with fertility problems for urogenital abnormalities. This for urogenital problems with fertility As a urogenital expert, the urologist should examine any male the urologist expert, As a urogenital The main factors influencing the prognosis in infertility are: in infertility the prognosis The main factors influencing 1.2 Prognostic factors 1.2 Prognostic tility and less than 5% remain unwillingly childless. remain tility and less than 5% ing couple to achieve pregnancy in one year” (WHO, 1995). pregnancy ing couple to achieve for infer- Of these couples, 15% seek medical treatment year. “Infertility is the inability of a sexually active, non-contracept- is the inability “Infertility 1. INTRODUCTION 1.1 Definition on Male Infertility. G. Dohle and the members of the guidelines working party guidelines working the members of the G. Dohle and GUIDELINES ON INFERTILITY ON GUIDELINES 4 7 GUIDELINES ON INFERTILITY Infertility Congenital - Klinefelter’s syndrome (sometimes accompa- (sometimes syndrome Congenital - Klinefelter’s in enzyme defects nied by gynaecomastia), anorchia, synthesis and cryptorchididsm androgen , and - after orchitis, Acquired cytotoxic therapy spermatozoa) and teratozoospermia (< 14% normal forms). normal 14% (< teratozoospermia and spermatozoa) as simultaneously occur pathologies three often, all Quite In extreme syndrome. (OAT) oligo-asteno-teratozoospermia just as (< 1 million spermatozoa/ml), syndrome cases of OAT incidence of obstruc- is an increased there with , genetic abnormalities. male genital tract and tion of the 2.3 Hormonal investigation men in infertile prevalent more malfunctions are Endocrine still quite uncommon. but are than in the general population, be limited to determining follicle- can Hormonal screening (FSH), luteinizing hormone (LH) and stimulating hormone diagnosed with azoospermia or levels. In men testosterone to distinguish between obstruc- it is important OAT, extreme causes. A criterion with reasonable tive and non-obstructive is a normal FSH with bilater- value for obstruction predictive with a 29% of men volume. However, ally a normal testicular have defective . normal FSH appear to FSH/LH) hypogonadism (elevated 2.3.1 Hypergonadotrophic elevated with an Primary testicular developmental disorder sper- of is an isolated failure of gonadotrophins production a disruption of the matogenesis and generally not caused by endocrine system. Causes may be: * 50% with progressive motility or motility 50% with progressive 2.0 ml 20 million/ml 40 million/ejaculate and form 14% of normal shape ≥ within 60 25% with rapid motility ≥ ≥ ≥ ≥ particles < 10% spermatozoa with adherent particles minutes after ejaculation **

MAR = Mixed antiglobulin reaction Assessment according to Kruger and Menkfeld criteria. to Kruger and Assessment according Motility million spermatozoa/ml), astenozoospermia (< 50% motile million spermatozoa/ml), astenozoospermia It is important to distinguish between oligozoospermia (< 20 It is important Infertility tests are further andrological tests necessary. andrological further tests are should suffice. Only if the results are abnormal in at least two are Only if the results should suffice. If values are normal according to WHO criteria, one test to WHO criteria, normal according If values are Frequency semen analyses Frequency ** * Immunobaed test < 20% spermatozoa with adherent Morphology Leucocytes < 1 million/ml Total no. of spermatozoa Total pHSperm concentration 7.0-8.0 desirable. criteria to the 1992 WHO sis according Volume standardization of the complete laboratory work-up is highly the complete laboratory of standardization 2: Overview for semen analy- of standard values Table basis of important decisions concerning appropriate treatment, appropriate decisions concerning basis of important abnormalities (Table 2). Since semen analysis still forms the still forms analysis semen 2). Since (Table abnormalities Andrological examination is indicated if semen analysis shows analysis if semen is indicated examination Andrological 2.2 Semen analysis Semen 2.2 MAR-test GUIDELINES ON INFERTILITY ON GUIDELINES 6 9 GUIDELINES ON INFERTILITY Infertility In cases of azoospermia or severe OAT, deletions in the OAT, In cases of azoospermia or severe In men presenting with extremely poor quality semen, poor quality with extremely In men presenting Chromosomal abnormalities are more common in men with more are abnormalities Chromosomal azoospermic factor (AZF) region of the Y chromosome can of the Y chromosome azoospermic factor (AZF) region Y deletions is of occur and testing is advised. The prevalence Identifying of patients. 5%) in this group considerable (around passed on to sons a Y deletion means that the defect will be who will then also be infertile chromosome translocations and deletions can be found, which translocations and deletions can be chromosome and abortion and which may cause habitual may be hereditary It is recommended congenital malformations in the offspring. with < 1 in all men presenting that karyotyping is performed for ICSI. candidates million spermatozoa/ml and who are extreme OAT and with azoospermia. The most common sex and with OAT extreme (47 XXY), syndrome is Klinefelter’s abnormality chromosome 10% of men diagnosed with azoospermia. around which affects is characterized by gynaecomastia and syndrome Klinefelter’s a eunuchoid Occasionally, hypogonadism. hypergonadotrophic and sometimes psychological disorders. phenotype is found with tubular sclerosis. and present very small Both are with levels decrease testosterone 60% of all patients, In around replacement. androgen age requiring used to be described as idiopathic male infertility will, in fact, in will, infertility male idiopathic as be described to used and history family an extensive By taking genetic origin. have a disorders of these a number analysis, out karyotype carrying but also yield a diagnosis, This will not only can be detected. be The latter may genetic counselling. allow for appropriate sperm of intracytoplasmic with the advent very important the and possibly disorder because the fertility injection (ICSI), to the off- transferred defect may be genetic corresponding spring.

Congenital anomalies - isolated arrest of FSH and LH secre- anomalies - isolated arrest Congenital iso- by anosmia), accompanied syndrome, tion (Kallmann’s idiopathic eunuch), (fertile secretion of LH lated arrest and delayed puberty. hypopituitarism of a more expression - generally as an anomalies Acquired or hypothalamus, of the pituitary gland complex disorder hormone [GnRH] (gonadotrophin-releasing or iatrogenic agonists and anti-androgens)

Infertility A substantial number of andrological fertility disorders, which disorders, fertility A substantial number of andrological 2.5 Genetic evaluation cause obstruction of the genital tract . radicals. Gonorrhoea and trachomatis can also radicals. Gonorrhoea may instigate the production of spermatotoxic free oxygen free of spermatotoxic may instigate the production infection of the prostate or seminal vesicles. Genital infections or seminal vesicles. Genital infection of the prostate obstruction of the ejaculatory ducts caused by a (chronic) obstruction of the ejaculatory ducts caused tion with a small ejaculate volume, this may point to a (partial) tion with a small ejaculate volume, this may semen sample is as yet undetermined. However, in combina- semen sample is as yet undetermined. However, The clinical implications of white blood cells detected in a The clinical implications of white blood infections’ (MAGI) and sexually transmitted diseases (STDs). infections’ (MAGI) and sexually transmitted urine samples, urinary tract infections, ‘male accessory gland urine samples, urinary Indications for microbiological assessment include abnormal Indications for microbiological 2.4 Microbiological assessment 2.4 Microbiological or a computed tomography (CT) scan of the pituitary gland or a computed tomography examination should include magnetic resonance imaging (MRI) magnetic resonance examination should include If hypogonadotrophic hypogonadism is suspected, the medical hypogonadism If hypogonadotrophic itary gland or hypothalamus may occur as a result of: as a result may occur or hypothalamus itary gland Low levels of gonadotrophins due to dysfunction of the pitu- of due to dysfunction of gonadotrophins Low levels 2.3.2 Hypogonadotrophic hypogonadism (deficient FSH/LH) (deficient hypogonadism Hypogonadotrophic 2.3.2 GUIDELINES ON INFERTILITY ON GUIDELINES 8 11 GUIDELINES ON INFERTILITY Infertility Absence of seminiferous tubules (tubular sclerosis) (tubular tubules of seminiferous Absence only syndrome) cell (Sertoli cells only of Sertoli Presence not spermatogenesis, - incomplete arrest Maturation spermatocyte stage beyond the are up to spermatozoa - all cell types Hypospermatogenesis in the number of is a distinct decline but there present, spermatogonia reproducing especially in men testis can be found, in situ of the Carcinoma in the testes and in men with with bilateral microcalcifications tumour. a history of testicular 3. TREATMENT 3.1 Counselling for ‘lifestyle’ factors may be responsible Sometimes certain example, alcohol abuse, use of anabol- poor : for (marathon training, excessive sports extreme ic steroids, through temperature in scrotal and increase sports), strength occupational sauna or hot tub use or thermal underwear, A considerable number of drugs can to heat sources. exposure the spermatogenesis affect 3.2 Medical (hormonal) treatment therapies, such as No studies have confirmed that hormonal chorionic (HMG)/human human menopausal gonadotrophin (clomiphene anti-oestrogens (HCG), androgen, gonadotrophin and inhibitors (bromocriptine) and tamoxifen), prolactin idiopathic rates in men with pregnancy improved steroids, some primarily endocrinological pathologies However, OAT. medically. can be treated

Transrectal ultrasonography (TRUS) is indicated in men Transrectal When performing ICSI with surgically-retrieved sperm, surgically-retrieved with ICSI performing When

genital tract. Pathological classifications are: between testicular insufficiency and obstruction of the male between testicular insufficiency and normal FSH levels. The biopsy is aimed at differentiating and normal FSH levels. The biopsy is aimed or extreme OAT in the presence of a normal testicular volume in the presence OAT or extreme Indications for performing a testicular biopsy are azoospermia a testicular biopsy are Indications for performing 2.7 Testicular biopsy 2.7 Testicular or stenosis of the ejaculatory ducts. tion of the ejaculatory ducts caused by a midline prostatic cyst prostatic tion of the ejaculatory ducts caused by a midline with a low volume of ejaculate (< 1.5 ml) to exclude obstruc- with a low volume of ejaculate (< 1.5 ml) a history of cryptorchism. around 5% of infertile males, especially patients diagnosed with 5% of infertile around fications, a potentially premalignant condition, are detected in condition, are premalignant fications, a potentially can be found in 0.5% of infertile men and testicular microcalci- of infertile can be found in 0.5% varicocele in around 30% of infertile males. Testicular tumours males. Testicular of infertile 30% varicocele in around defects. Colour Doppler ultrasound of the scrotum can detect a ultrasound of the scrotum defects. Colour Doppler Ultrasonography is a useful tool for locating intrascrotal Ultrasonography is 2.6 Ultrasonography counselling is recommended in these cases. counselling is recommended there is a 25% chance of a child with CF or CBAVD. Genetic a child with CF or CBAVD. is a 25% chance of there rier of a CFTR-mutation, depending on the mutation involved, depending rier of a CFTR-mutation, two CFTR-gene mutations. In cases where the partner is a car- is a the partner where mutations. In cases two CFTR-gene all males diagnosed with CBAVD also test positive for one or also test with CBAVD all males diagnosed fibrosis (CF), this gene is also associated with CBAVD; 85% of with CBAVD; gene is also associated (CF), this fibrosis membrane regulator (CFTR) gene. Apart from causing cystic from Apart (CFTR) gene. regulator membrane should be checked for mutations in the cystic fibrosis trans- in the cystic fibrosis checked for mutations should be deferens (CBAVD), both the male and the female partners the female male and both the (CBAVD), deferens based on a diagnosis of congenital bilateral absence of the vas of the absence bilateral of congenital on a diagnosis based Infertility GUIDELINES ON INFERTILITY ON GUIDELINES 10 13 GUIDELINES ON INFERTILITY Infertility undertake this procedure. Considering its limited effect on effect its limited Considering procedure. this undertake epididy- to combine advisable it is rates (20-30%), pregnancy aspiration sperm epididymal microsurgical with movasostomy the harvested spermatozoa for ICSI. cryopreserve (MESA), and include congenital for epididymovasostomy The indications the of the epididymis, in at the level obstructions and acquired (testicular biopsy) spermatogenesis of a normal presence 3.3.3 or either macroscopically be performed can Vasovasostomy in improving effective the latter is more though microscopically, is likelihood of initiating pregnancy rates. The pregnancy to the obstruction interval and becomes inversely proportional the factors are prognostic Important less than 50% after 8 years. antibodies, the quality of the semen development of antisperm have 20% of men who age. In approximately and the partner’s sperm quality deteriorates to the a vasovasostomy, undergone within 1 year. or extreme level of azoospermia a prevent autoantibodies frequently Poor sperm quality and is indicated. and assisted reproduction spontaneous pregnancy 3.3.4 MESA when reconstruc- MESA in combination with ICSI is indicated cannot be per- epididymovasostomy) tion (vasovasostomy, would be percuta- formed or is unsuccessful. An alternative (PESA). the caput epididymis neous aspiration of sperm from spermatozoa, does not produce If a MESA or PESA procedure with testicular sperm a testicular biopsy can be performed extraction (TESE) to be used for ICSI. g, increased if necessary to if necessary g, increased µ g, every 90 minutes. If insufficient response, HCG response, minutes. If insufficient g, every 90 µ

10-20 i.m. twice weekly HMG 150 IE (FSH) 1500 IE and - dopamine agonists Hyperprolactinaemia Low testosterone - testosterone substitution is indicated; is substitution - testosterone testosterone Low has a values physiological normal exceeding substitution on the spermatogenesis effect negative - pulsatile GnRH, i.v or hypogonadism Hypogonadotrophic dose is 5 starting sc; the usual

Only urologists with experience in microsurgery should with experience in microsurgery Only urologists 3.3.2. Microsurgery/epididymovasostomy improvement in semen quality in at least 44% of men treated. in semen quality in at least 44% improvement treat varicocele. Successful treatment will lead to a significant varicocele. Successful treatment treat A range of surgical and radiological techniques can be used to A range of surgical studies did show a benefit in favour of treatment with counselling. However smaller series and unpublished with counselling. However smaller series in pregnancy rates when treatment of varicocele was compared of varicocele was rates when treatment in pregnancy prospective randomized trial, however, showed no difference randomized trial, however, prospective the idea that varicocele may be a cause of infertility. A recent infertility. the idea that varicocele may be a cause of of a considerable number of non-randomized studies ‘support’ of a considerable number of non-randomized cocele as a cause of disruption in spermatogenesis. The results cocele as a cause of disruption al need to treat varicocele, but also on the significance of vari- varicocele, al need to treat cal andrology. This controversy is based not only on the actu- This controversy cal andrology. The treatment of varicocele is a controversial subject in clini- is a controversial of varicocele The treatment 3.3.1 Varicocele 3.3. Surgical treatment serious side effects. steroids, although effective, are not recommended because of not recommended are although effective, steroids, In patients with sperm autoantibodies, high-dose cortico- In patients with sperm Infertility GUIDELINES ON INFERTILITY ON GUIDELINES 12 15 GUIDELINES ON INFERTILITY Infertility ejaculation techniques. It is possible to induce ejaculation in ejaculation induce to It is possible techniques. ejaculation the however, injuries, cord with spinal of patients 90% around motile sper- number of with a low often poor quality is semen of assist- results accounts for the disappointing matozoa. This intrauterine insemina- such as techniques, ed reproduction fertilization In-vitro injuries. with spinal cord tion, in patients often required. and ICSI are Infertility guidelines on Male consult the extensive For further information Association to all members of the European (ISBN 90-806179-8-9), available - www.uroweb.org. at their website of Urology prostatic cyst prostatic

Treatment of is basically aimed at retrograde of Treatment In neurological diseases, such as multiple sclerosis, diabetes as multiple sclerosis, diseases, such In neurological injuries spinal cord and mellitus (neuropathy) sympa- bladder neck surgery, surgery, Following prostate node such as lymph surgery, thectomy and retroperitoneal dissections for testicular tumours therapy During antidepressant

Infertility Anejacualtion can be treated by vibrostimulation or electro- by vibrostimulation Anejacualtion can be treated from the urine after orgasm. from removing the cause of the disorder or harvesting spermatozoa the cause of the disorder removing very low (partial retrograde ejaculation). retrograde very low (partial ejaculation should also be suspected if the ejaculate volume is ejaculation should also be suspected if the microscopic assessment of the post-ejaculate urine. Retrograde assessment of the post-ejaculate urine. microscopic diagnosis is based on the medical history and laboratory diagnosis is based on the medical history found. The ejaculation can be Often no cause for retrograde Retrograde ejaculation and anejaculation can occur: ejaculation and Retrograde 4.1 Disorders of ejaculation occasionally, spontaneous pregnancy. spontaneous occasionally, Dysfunction. Erectile latory ducts may lead to an increase in semen quality and, in may lead to an increase latory ducts see EAU Guidelines on of sexual dysfunction, For treatment obstruction by transurethral incision of the cyst or the ejacu- incision by transurethral obstruction 4. SEXUAL DYSFUNCTION or by a cyst in the midline of the prostate. Treatment of the Treatment prostate. in the midline of the or by a cyst by infections of the prostatic and the accessory glands, and the accessory urethra of the prostatic by infections Distal obstructions of the genital tract are commonly caused commonly are genital tract of the obstructions Distal 3.3.4 midline ducts or of ejaculatory incision Transurethral GUIDELINES ON INFERTILITY ON GUIDELINES 14