CHAPTER 11 Trauma to the urinary tract 544 Torsion of the testis and testicular appendages De \201 nition A testicular torsion is a t wist of the spermatic cord, resulting in strangu- lation of the blood supply to the testis and epididymis. Testicular torsion occurs most frequently between the ages of 10 \200\22330 (peak incidence 13 \200\22315y of age), but any age group may be affected. History and examination Sudden onset of severe pain in the hemiscrotum, sometimes waking th e patient from sleep. It may radiate to the groin, loin, or epigastrium (re- \202 ecting its origin from the dorsal abdominal wall of the embryo and its nerve supply from T10/11). There is sometimes a history of minor trauma to the testis. Some patients report previous e pisodes with spontaneous resolution of the pain (suggesting previous torsion with spontaneo us de- torsion). The patient may have a slight fever. The testis is usually slightly swolle n and very tender to touch. It may be high riding (lying at a higher than normal position i n the testis) and may be in a horizontal position due to twisting of the cord. The cremaste ric re \202 ex is usually, but not always, absent (positive Rabinowitz \200\231s sign). Th e cremasteric re \202 ex may normally be elicited by stroking the \201 nger along inside of the thigh, which results in upwards movement of the ipsilateral testis. Elevation of th e involved testi- cle does not ameliorate the symptoms (negative Prehn \200\231s sign). Differential diagnosis and investigations Epididymo-orchitis, torsion of a testicular appen dage, and causes of \202 ank pain with radiation into the groin and testis (e.g. a ureter ic stone). Color Doppler USS (reduced arterial blood \202 ow in the testicular artery) an d radionuclide scanning (decreased radioisotope uptake) can be used to di- agnose testicula r torsion, but in many hospitals, these tests are not readily available and the diagnosis i s based on symptoms and signs. Surgical management Scrotal exploration should be undertaken as a matter of urgency. Delay in relieving the twisted testis results in permanent ischaemic damage to the testis, causin g atrophy, loss of hormone and sperm production, and as the testis undergoes necrosis and t he blood \200\223testis barrier breaks down, an autoimmune reaction against the contralater al testis (sympathetic or- chidopathia). Fix BOTH testes since the bell-clapper abnormality , which predisposes to torsion, can occur bilaterally. Torsion of testicular appendages The appendix testis (hydatid of Morgagni \200\224a remnant of the M llerian duct) and the appendix epididymis (a remnant of a cranial mesonephric tu - bule of the Wolf \201 an duct) can undergo torsion, causing pain that mimicks a testicul ar torsion. At scrotal exploration, they are easily removed with scissors or a diathermy pr obe. PARAPHIMOSIS 545 Paraphimosis De \201 nition and presentation This is where the foreskin is retracted from over the glans of the penis, becomes oedematous, and cannot then be pulled back over the gl ans into its normal anatomical position. It occurs most commonly in teenagers or young men and also in elderly men (who have had the foreskin retracted during catheterization, but wh ere it has not been returned to its normal position). Paraphimosis is usually painful. The foreskin is oedematous and a small area of ulceration of the foreskin may have developed. Treatment The \200\230iced glove \200\231 method: apply topical lignocaine gel to the glan s and fore- skin for 5min. Place ice and water in a rubber glove and tie a knot in the cuff of the glove to prevent the contents from pouring out. Invaginate the penis into the thumb of the glove. This may reduce the swelling and allow reduction of the foreskin. Granulated sugar: placed in a condom or glove and applied over the end of the penis has bee n used to reduce the oedema by osmosis. The Dundee technique:1 give the patient a broad-spectrum antibiotic such as 500mg of cipro \202 oxacin by mouth. Apply a ring block to the base of the penis using a 26 G needle and 10 \200\22320mL of 0.5% plain bupivacaine (children usually require general anesthesia). Cl ean the skin of the foreskin and the glans with cleaning solution. Using a 25 G needle, mak e approximately 20 punctures into the oedematous foreskin. Squeeze the oedema \202 uid ou t of the foreskin and return to its normal position. Approximately one-third of patients su bsequently require elective circumcision for an underlying phimosis. If this fails, the traditional surgical treatment is a dorsal slit under general anesthetic or ring block. A longitudinal incision is made in the tight band of constricting tissue an d the foreskin pulled back over the glans. Close the incision transversely to lengthen the circumference of the foreskin and prevent recurrences. 1 Reynard JM, Barua JM (1999) Reduction of paraphimosis the simple way \200\224the Dundee t ech- nique. BJU Int 83: 859 \200\22360. CHAPTER 11 Trauma to the urinary tract 546 Malignant ureteric obstruction Locally advanced prostate cancer, bladder or ureteric cancer may cause unilateral or bilateral ureteric obstruction. Locally advanced non-urologi- cal malignancies can also obstruct the ureters (e.g. cervical cancer, rectal cancer, lymphoma). Unilateral obstruction: is often asymptomatic; an incidental USS \201 nding that require s no speci \201 c treatment in the presence of a normal contralat- eral kidney. Occasional ly, loin pain and systemic symptoms may develop due to infection of the obstructed upper ur inary tract. In this circum- stance, drainage by nephrostomy or stenting is required. Bilat eral ureteric obstruction: is a urological emergency. The patient presents either with symp toms and signs of renal failure or anuric without a palpable bladder. A mass will probably be palpable on rectal examina- tion. Investigations: renal USS will demonstrate bilateral h ydronephrosis and an empty bladder; CT-KUB will con \201 rm the presence of dilated ure- t ers down to a mass at the bladder base. Immediate treatment of bilateral ureteric obstruction After treating any life-threatening h yperkalaemia, options include bilateral percutaneous nephrostomy or ureteric stenting. A cl otting screen is re- quired prior to nephrostomy insertion. Insertion of retrograde ureteri c stents in this setting is usually unsuccessful because tumor involving the trigone obscur es the location of the ureteric ori \201 ces. More successful is antegrade ureteric stenti ng following nephrostomy insertion, both of which are performed under sedo-analgesia. The f ull-length double-J silicone or polyurethane ureteric stents require periodic (4 \200\2236 monthly) changes to prevent calci \201 cation or blockage. In the case of prostate cancer, hormone therapy should be commenced, if not previously used; even in patients with androge n-independent disease, high-dose parenteral oestrogens may relieve ureteric obstruction. Long-term treatment of bilateral ureteric obstruction Longer term treatment options include urinary diversion by formation of ileal conduit, ureteric reimplantation, insertion of sho rt \200\230permanent \200\231 me- tallic ureteric stents, or ureteric replacement with iso lated ileal segments or prosthetic graft material. Such procedures are often complicated an d inappropriate in these patients with poor prognosis. This page intentionally left blank CHAPTER 11 Trauma to the urinary tract 548 Metastatic spinal cord and cauda equina compression Metastatic spinal cord compression (MSC C) This is an oncological emergency; failure to diagnose and treat promptly can lead to per manent paraplegia and autonomic dysfunction. It is de \201 ned as spinal cord or cauda equ ina compression by direct pressure and/or induction of vertebral collapse or instability by metastatic spread or direct extension of malignancy that threatens or causes neurological disability1. Ninety- \201 ve percent of patients will complain of back or nerve root pain and have a po sitive bone scan. Five percent of patients do not exhibit these features because their dise ase is paravertebral. The majority of uro- logical cases of MSCC are due to prostate cancer . Patients with back or nerve root pain should be examined neurologically and evaluated rad io- logically. Pain, sometimes worsened by straining or coughing, usually pre- cedes clinic al cord compression by 4 months. Clinical features include sensory changes and muscle weak ness in the lower limbs; 50% of patients present unable to stand or walk. Only two-thirds o f patients presenting as such will recover any function within one month. If cord compression is suspected, the patient should be nursed \202 at with neutral spine alignment (including \200\230log rolling \200\231 or turning beds, with use of a slipper pan for toilet) until bony and neurological stability are ensured and cautious remobilisati on may begin. Every acute UK NHS Cancer Center should have access to a MSCC coordinator who should be informed. The investigation of choice is emergency spinal MRI. STIR and sagittal T2-weighted sequences will reveal the bone deposits and level (multiple in 20% of cases) o f the soft-tissue cord compression. If MRI is not possible, CT scan or myelography should b e considered. Initial treatment is with high-dose intravenous corticosteroids, for example dexamethasone 16mg followed by 4mg 6-hourly for 2 \200\2233 weeks. Analgesics and bisphosphonates are adm inistered for pain relief. Within 24 hours, de \201 nitive treatment is with fractionated radiotherapy or neurosurgical decompression. Surgery to achieve decompression and spinal st ability is considered preferable if there is pathological fracture, unknown tissue diagnosi s or a history of previous radiotherapy. Subsequently, care should include pressure sore an d venous thromboembolism prophylaxis meas- ures. Bladder and bowel dysfunction may also occ ur, requiring catheteri- sation, stool softeners. Rehabilitation and community support will also be required. Cauda equina compression The adult spinal cord tapers below L2 vertebral level into the con us med- ullaris. The cauda equina consists of the nerve roots of all spinal cord seg- ments below L2, as they run in the subarachnoid space to their exit levels in the lower lumbar a nd sacral spines. METASTATIC SPINAL CORD AND CAUDA EQUINA COMPRESSION 549 Pathophysiology: the cauda equina may be compressed by central interver- tebral disc prolap se (1 \200\22315% of cases), spinal stenosis, or by a benign or malignant tumor within the lower lumbar or sacral vertebral canal. Symptoms: the diagnosis should be considered in any female or young male presenting with di f \201 culty voiding or in urinary retention. There may be back pain. Signs: palpable bladder, loss of perianal (S2-4) and lateral foot sensation (S1-2), reduced anal tone; priapism. Investigations: MRI lumbosacral spine; urodynamic studies reveal a nor- mally-compliant but are \202 exic bladder. Treatment: intermittent self-catheterisation, neurosurgery. 1 UK NICE (2008) Clinical guideline 75 \200\223 Metastatic spinal cord compression. This page intentionally left blank 551 Chapter 12 Infertility Male reproductive physiology 552 Etiology and evaluation of male infertility 554 Investigat ion of male infertility 556 Oligozoospermia and azoospermia 560 Varicocele 562 Treatment op tions for male infertility 564 CHAPTER 12 Infertility 552 Male reproductive physiology Hypothalamic \200\223pituitary \200\223testicular axis The hyp othalamus secretes luteinizing hormone-releasing hormone (LHRH), also known as gonadotrophi n-releasing hormone (GnRH). This causes the pulsatile release of anterior pituitary gonadot rophins called follicle-stim- ulating hormone (FSH) and luteinizing hormone (LH), which act on the testis. FSH stimulates the seminiferous tubules to secrete inhibin and produce sper m; LH acts on Leydig cells to produce testosterone (Fig. 12.1). Testosterone is secreted by the interstitial Leydig cells, which lie adjacent to the semini ferous tubules in the testis. It promotes the development of the male reproductive system a nd secondary sexual characteristics. Steroidogenesis is stimulated by a cAMP \200\223protei n kinase C mechanism which converts cholesterol to pregnenolone. Further steps in the biosy nthesis pathway produce intermediary substances (dehydroepiandrosterone and androstenedione ) prior to producing testosterone. In blood, 60% of testo- sterone is attached to sex hormo ne-binding globulin (SHBG), 38% bound to albumin and 2% is free. At androgen-responsive tar get tissues, testo- sterone is converted into a potent androgen, dihydrotestosterone (DHT), by intracellular 5A-reductase (see b p. 672; Fig. 16.7). Spermatogenesis Seminiferous tubu les are lined with Sertoli cells, which surround developing germ cells (spermatogonia) and provide nutrients and stimulating factors as well as secreting androgen-binding factor and inhibin (Fig. 12.2). Primordial germ cells divide to form primary spermato- cytes. These un dergo a \201 rst meiotic division to create secondary sperma- tocytes (46 chromosomes), f ollowed by a second meiotic division to form spermatids (23 chromosomes). Finally, these di fferentiate into spermato- zoa. This process takes 72 days. The non-motile spermatozoa leav e the seminiferous tubules and pass to the epididymis for storage and matura- tion (until e jaculation). Spermatozoa that are not released are reabsorbed by phagocytosis. Mature sperm has a head, middle piece and tail (Fig. 12.3). The head is composed of a nucle us covered by an acrosome cap containing vesicles \201 lled with lytic enzymes. The middl e piece contains mitochondria and contractile \201 laments which extend into the tail to aid motility. After depo- sition at the cervix, sperm penetrate cervical mucus and travel t hrough the uterus to the site of fertilization in the Fallopian tube, during which time the y undergo functional maturation (capacitation). Sperm start to penetrate the oocyte and bin d to the zona pellucida. The activation phase is initiated (by ZP3), triggering hyperactiva ted motility and the acrosomal reaction which leads to enzyme release, penetration into the cytoplasm of the oocyte, fusion, and fertilization. MALE REPRODUCTIVE PHYSIOLOGY 553 \200\223ve HYPOTHALAMUS LHRH \200\223ve ANTERIOR PITUITARY GLAND \200\223ve LH FSH TESTIS Interstitial cells (Leydig cells) Seminiferous tubules (Sertoli cells) Testosterone Sperm Inhibin Fig. 12.1 Hypothalamic \200\223pituitary \200\223testicular axis. Lumen Spermatozoa Spermatid 2 spermatocyte Sertoli cell 1 spermatocyte Spermatogonia Basal lamina Fig. 12.2 Spermatogenesis in the seminiferous tubules of the testis. Head: Plasma membrane Acrosomal cap Tail: End piece Nucleus Middle piece: Proximal centriole Mitochrondria Microtubules Tail: Principal piece Fig. 12.3 Spermatozoa. CHAPTER 12 Infertility 554 Etiology and evaluation of male infertility De \201 nition of subfertility Failure of conc eption after at least 12 months of regular unprotected intercourse. The chance of a normal couple conceiving is estimated at 20 \200\22325% per month, 75% by 6 months, and 90% at 1y. Epidemiology Up to 50% of infertility is due to male factors. An estimated 14 \200\22325% o f couples may be affected at some point in their reproductive years. Twenty- \201 ve perce nt of subfertile couples will have oligozoospermia and 10% azoospermia. Azoospermia exists in 1% of the male population. Pathophysiology Failed fertilization of the normal ovum due to defective sperm develop- men t, function, or inadequate numbers. There may be abnormalities of morphology (teratozoosper mia, <4% normal forms), motility (astheno- zoospermia, <40% motile sperm), low sperm number s (oligozoospermia, <15 x 106 per mL), or absent sperm (azoospermia). Abnormal epididymal f unction may result in defective spermatozoa maturation or transportation or induce cell dea th. Etiology of male factor infertility - - - - Idiopathic (25%). (present in 740%). Varicocele Undescended testes . Functional sperm disor ders: immunological infertility (antisperm antibodies); head or tail defects; Kartagener \200\231s syndrome (immotile cilia); dyskinetic cilia syndrome. Erectile dysfunction. Ejacu latory problems: volume ejaculate. Testicular injury: testicular torsion; trauma; radiother apy. Endocrine disorders: de \201 ciency causing hypogonadism); Prader \200\223Willi syndr ome . (hypogonadism, short stature, hyperphagia, obesity); pituitary gland adenoma, radiati on, or infection. Hormone excess: androgen (adrenal tumor, congenital adrenal hyperplasia, anabolic steroids); excess oestrogens. Genetic disorders: azoospermia, i FSH/LH and d testo sterone; XX male and XYY syndromes. Deletions in the azoospermic factor (AZF) gene on the Y chromosome are associated with abnormal spermatogenesis, which can be inherited by male of fspring. Microdeletions of region AZFa has associations with Sertoli cell only syndrome; AZ Fb with maturation arrest and AZFc with azoospermia/severe oligozoospermia. retrograde ejaculation causes absent or low orchitis (post-pubertal bilateral mumps orchitis); Kallmann \200\231s syndrome (isolated gonadotrophin excess prolactin (pituitary tumor); excess including Klinefelter \200\231s syndrome (47XXY) with etiology AND EVALUATION OF MALE INFERTILITY 555 Male genital tract obstruction: congenital absence of vas deferens; agenesis of seminal ves icles/Wolf \201 an duct abnormalities; epididymal obstruction or infection; M llerian pro static cysts; inguinoscrotal or pelvic surgery. Systemic disease: Drugs: smoking. Environme ntal factors: Infection: trachomatis can attach to and penetrate sperm; Ureaplasma urealyti cum reduces sperm motility. HIV infection, previous prostatitis, and bilateral epididymitis reduce semen quality. renal failure; liver cirrhosis; cystic \201 brosis. chemotherapy; steroids; alcohol; marijuana; sulphasalazine; pesticides; heavy metals; hot baths. genital tract infections are found in 10 \200\22320%. Chlamydia History - Sexual and reproductive: of intercourse; use of vaginal lubricants (adversely affects sperm function); previous successful conceptions; previous birth control; erectile or ejaculator y dysfunction. Partner \200\231s history: subfertility; medical history. Developmental: gyn aecomastia. Medical and surgical: detailed assessment for risk factors \200\224recent febri le illness; post-pubertal mumps orchitis; varicocele; testicular torsion, orchidopexy, trau ma or tumor; sexually transmitted infections; UTI; genitourinary and pelvic surgery; radiot herapy; respiratory diseases associated with ciliary dysfunction; diabetes. Drug and enviro nmental: previous chemotherapy; exposure to substances which impair spermatogenesis or erec tile function; alcohol consumption; smoking habits; hot baths. Family history: duration of problem; frequency and timing age; previous pregnancies; previous investigation for age at puberty; history of undescended testes; hypogonadism; undescended testes. Examination Perform a full assessment of all systems, with attention to general appear- anc e (evidence of secondary sexual development; signs of hypogonadism; gynaecomastia). Urogeni tal examination should include assessment of the penis (phimosis, hypospadias, chordee); th e presence of testes; meas- urement of testicular consistency, tenderness and volume with a Prader orchidometer (normal >20mL \200\224varies with race); palpate epididymis (ten- dern ess, swelling) and spermatic cord (vas deferens present or absent; varicocele); DRE of pros tate. Of note, the patient \200\231s partner should also undergo full screening and assessment fo r infertility by a gynecologist, in either a separate consulta- tion or in a joint clinic. CHAPTER 12 Infertility 556 Investigation of male infertility Basic investigations Semen analysis: 2 \200\2233 specimen s over several weeks, collected after 2 \200\2237 days of sexual abstinence. Deliver specim ens to the laboratory with- in 1h (ideally keeping the specimen warm in a shirt or trouser pocket). Ejaculate volume, liquefaction time, and pH are noted (Table 12.1). Microscopy tec hniques measure sperm concentration, total numbers, morphology, and motility (Table 12.2). The mixed agglutination reaction (MAR) test is used to detect antisperm antibodies (useful for asthenozoo- spermia which can be associated with immunological infertility). The pres- ence of leucocytes (>1 x 106/mL in semen) suggests infection and cultures should be request ed. Low or absent ejaculate volume may suggest abnor- mality of seminal vesicles, ejaculato ry duct obstruction, hypogonadism, or retrograde ejaculation. Hormone measurement: serum FSH, LH and testosterone (Table 12.3). In cases of isolated low testosterone level, it is recommended to test early morning and free testosterone levels. R aised prolactin is associated with sexual dysfunction and may indicate pituitary disease. Special investigations Karyotype: 5 \200\22310% of azoospermic patients have Klinefelter \200\231s syndrome. Y chromosome microdeletion assay: to assess AZF \200\224regions a, b, and c. - - a: microdeletion predicts no spermatogenesis. AZF c: commonest molecular cause of male infe rtility (13% of non- AZF obstructive azoospermics and 6% of oligozoospermics). Around 70% w ill have sperm on testis biopsy. Post-orgasmic urine analysis: the presence of >10 \200\22315 sperm per high pow- ered \201 eld con \201 rms the diagnosis of retrograde ejaculation. Imaging Scrotal USS: is used to assess for testicular abnormalities and detection of varicocele. Transrectal USS: is indicated for low ejaculate volumes, to investigate seminal vesicle obs truction (>1.5cm width) or absence and ejaculatory duct obstruction (>2.3mm). Vasography: the vas deferens is punctured at the level of the scrotum and injected with con trast. A normal test shows the passage of contrast along the vas deferens, seminal vesicles , ejaculatory duct, and into the bladder, which rules out obstruction. Venography: used to diagnose and guide embolization treatment of varicocele. INVESTIGATION OF MALE INFERTILITY 557 Testicular biopsy Performed for azoospermic patients to help differentiate between ob- stru ctive and non-obstructive causes. Simultanous sperm retrieval can be carried out (testicula r sperm extraction, TESE) for use in intracytoplasmic sperm injection (ICSI) treatment, eit her at the time or at a later date (following freezing and storage). The degree of spermato genesis can be histologically scored (this is the Johnsen score; Table 12.4). Only mature s permatozoa (score 8 or above) can be used for fertility treatment. Table 12.1 WHO semen analysis characteristics Semen analysis parameter Lower reference limit (95% CI) Serum volume 1.5mL (1.4 \200\2231.7) pH (cid:116)7.2 39 x 106 per ejaculate (33 \200\22346) Total sperm count 15 x 106 per mL (12 \200\22316) Sperm concentration Motility 40% progressive + non-progressive (38 \200\22340) 32% progressive motility (31 \200\22334) Forward progression >grade 2 Sperm morphology 4% normal forms (3 \200\2234) Vitality 58% live spermatozoa (55 \200\22363) Time to liquefy 5 \200\22325min <1 x 106 WBC per mL White blood cells (WBC) MAR-test (for antisperm antibody) <50% motile spermatozoa with bound particles Zinc (cid:116)2.4 mol per ejaculate Semen fructose (cid:116)13 mol per ejaculate Adapted from World Health Organization (WHO) 2010 lower reference limits (5th centile and t heir 95% CI) for semen characteristics Table 12.2 Grading of sperm motility Grade Type of sperm motility 0 No motility 1 Sluggish; no progressive movement 2 Slow, meandering forward progression 3 Moving in a straight line with moderate speed 4 Moving in a straight line at high speed CHAPTER 12 Infertility 558 Table 12.3 Clinical diagnosis on hormone assay FSH i LH Testosterone Diagnosis Normal Normal Seminiferous tubule damage (defective spermatogenesis) Normal Normal Normal Normal or bilateral genital tract obstruction i i Normal/d d Testicular failure d d Hypogonadotrophism FSH = follicle-stimulating hormone; LH = luteinizing hormone. Table 12.4 The Johnsen Score. Histological analysis of testicular biopsy1 10 Complete spermatogenesis, many spermatozoa 9 Many spermatozoa, disorganized germinal epithelium 8 Few spermatozoa (<5 \200\22310) 7 No spermatozoa but many spermatids 6 No spermatozoa and few spermatids (<5 \200\22310) 5 No spermatozoa or spermatids, but many spermatocytes 4 Few spermatocytes (<5), no spermatozoa or spermatids 3 Spermatogonia are the only germ cells 2 Sertoli cells only 1 No cells in tubules 1 in human testes. Normal values and results in 335 hypogonadal males. Hormones 1:2 \200 \22325. Johnsen S (1970) Testicular biopsy score count \200\224a method for registration of spermat ogenesis This page intentionally left blank CHAPTER 12 Infertility 560 Oligozoospermia and azoospermia Oligozoospermia De \201 ned as a sperm concentration of <1 5 million per mL of ejaculate. Etiology: varicocele; idiopathic; androgen de \201 ciency. It is identi \201 ed in 760% o f patients presenting with testicular cancer or lymphoma. Associated disorders: Often assoc iated with abnormalities of morphology and motility. The combined disorder is called oligoa sthenoteratozoo- spermia (OAT) syndrome. Common causes of OAT include varicocele, undescend ed testes, idiopathic; drug and toxin exposure, febrile illness. Investigations - Semen analysis: hormone investigation (FSH and testosterone) and genetic analysis. Severe o ligozoospermia is associated with seminiferous tubular failure, small soft testes, and i FS H. Hormone assays: hyperprolactinaemia can adversely affect spermatogenesis. Scrotal sperm counts <5 \200\22310 million/mL (severe form) require also include prolactin levels if testosterone is low as USS: to identify a varicocele. Treatment: Lifestyle advice and modi \201 cation of risk factors. Correct the underlying c ause (i.e. varicocele repair or embolization may improve tes- tosterone and sperm productio n and parameters). Idiopathic cases may respond to empirical medical therapy (clomiphene) o r require assisted reproductive techniques (ART) (see b p. 565). Azoospermia De \201 ned as an absence of sperm in the ejaculate. Etiology Obstructive causes - Vas deferens obstruction: deferens (CBAVD),1 post-surgery, or post-vasectomy. Epididymal ob struction: agenesis. Ejaculatory duct obstruction: M llerian cyst. congenital bilateral absence of vas idiopathic, post-infective or post-surgery, post-infective, post-surgery, congenital, Non-obstructive causes - hypogonadotrophism (Kallmann \200\231s syndrome, Hormonal abnormality: pituitary tumor). Abnormalities of spermatogenesis: (60% of non-obstr uctive azoospermia). Others are secondary to testicular torsion or trauma, viral orchitis o r idiopathic, chromosomal anomalies (i.e. Klinefelter \200\231s syndrome). commonest cause is idiopathic OLIGOZOOSPERMIA AND AZOOSPERMIA 561 Investigations - Hormone assay: (i.e. reduced spermatogenesis presents with i FSH associated with d inhibin) . Normal FSH with normal testes indicates increased likelihood of obstruction. Semen analys is: reduced volume, acidic ejaculate without spermatozoa, or fructose. karyotyping to ident ify Klinefelter \200\231s syndrome Chromosomal analysis: in patients presenting with azoosp ermia, small soft testes, gynaecomastia, d FSH/LH and d testosterone. Y chromosome microdel etion assay (see b p. 556). Transrectal ejaculatory duct obstruction. Exclude cystic \201 brosis in patients with vas deferens defects. Renal tract agenesis. Vasogram: Testicular b iopsy: to help distinguish between obstructed and non- obstructed cases where the etiology is not clear clinically and for sperm retrieval (for therapeutic use). raised FSH suggestive of non-obstructive cause ejaculatory duct obstruction is associated with a USS: assesses absence or blockage of vas deferens and USS: for CBAVD as it is associated with unilateral renal to assess for vas deferens obstruction. Management Treatment will depend on the underlying etiology (see also b p. 554). Obstructiv e etiology - Bilateral absence or agenesis of vas deferens: * ART are required. Options include percutan eous epididymal sperm aspiration (PESA), microsurgical epididymal sperm aspiration (MESA), or testicular exploration and sperm extraction (TESE). Obstructive cause with normal testis : epididymis is identi \201 ed, vasoepididymostomy can be performed. A vaso-vasosotomy can be performed in the case of previous vasectomy with good results and there is a trend to o ffer simultanous TESE, particularly if there has been a long interval since the vasectomy. If reconstruction is not possible, TESE alone may be needed. if an isolated obstruction of the Non-obstructive etiology - Primary testicular failure with testicular atrophy: testicular exploration and sperm extrac tion (micro-TESE) with ICSI and in vitro fertilization (IVF). Consider arti \201 cial inse mination using donor (AID) if this fails Primary testicular failure with normal testis: IVF ; AID. microsurgical TESE with ICSI and Congenital bilateral absence of vas deferens (CBAVD) is associated with mutations in the cy stic \201 brosis transmembrane conductance regulator gene. Most of these patients are not candidates for reconstruction as they have a defect in sperm transportation from mid-epidi dymis to seminal vesicles. CHAPTER 12 Infertility 562 Varicocele De \201 nition Dilatation of veins in the pampiniform plexus of the spermatic c ord. Prevalence Found in 15% of men in the general population, 20 \200\22340% of males present- ing with primary infertility and 45 \200\22380% of men with secondary infertility. Rare pri or to puberty; present in 710% of adolescents. Bilateral or unilat- eral (left side affecte d in 90%). Etiology Incompetent valves in the internal spermatic veins lead to retrograde blood \202 ow, vessel dilatation, and tortuosity of the pampiniform plexus. The left internal spermat ic (testicular) vein enters the left renal vein at right angles and is under a higher press ure than the right vein which enters the vena cava obliquely at a lower level. As a consequ ence, the left side is more likely to develop a varicocele. Pathophysiology Testicular venous drainage is via the pampiniform plexus, a meshwork of vei ns encircling the testicular arteries. This arrangement normally provides a countercurrent heat exchange mechanism which cools arterial blood as it reaches the testis. Varicoceles ad versely affect this mechanism, resulting in elevated scrotal temperatures and consequent de leterious effects on spermatogenesis (9 loss of testicular volume over time). Table 12.5 Varicocele grading system Grade Size De \201 nition 0 Subclinical Detected only on USS 1 Small Palpable only with Valsalva maneuver 2 Moderate Palpable without Valsalva 3 Large Visible through the scrotal skin Presentation The majority are asymptomatic, although large varicoceles may cause pain or a heavy feeling in the scrotal area. Examine, both lying and standing, and ask the patient to perform the Valsalva maneuver (strain down). A varicocele is identi \201 ed as a mass of dilated and tortuous veins above the testicle ( \200\230bag of worms \200\231) which decomp ress on lying supine. Examine for testicular atrophy. Investigation - Scrotal Doppler patient supine). Venography: is the \200\230gold standard \200\231, but is reserved for patients considering embolization or for varicocele recurring after treatment . USS: is diagnostic (venous diameter >3.5mm with VARICOCELE 563 Semen analysis: counts, reduced sperm motility, and abnormal morphology, either alone or in combination (OAT syndrome). varicoceles are associated with low or absent sperm Indications for varicocele repair Adolescents: Pain, bilateral large varicoceles, varicocele in a solitary testis, persistent delayed testicular growth by >20% (as compared with non- affected side). Adults: Varicocele repair improves semen parameters and is recom- mended in the United Stat es.* However, in the UK, the Cochrane review failed to identify any bene \201 t to pregnan cy rates and intervention for infer- tility reasons is not currently recommended by NICE. P atients should be fully counseled on the limitations of varicocele repair for infertility b efore being booked for treatment. Management Embolization: interventional radiological technique where the femoral vein is us ed to access the spermatic veins for venography and embolization (with coils or other scler osing agents), with success rates of 83%. Surgical ligation of spermatic veins - High retroperitoneal (Palomo) approach: made near the anterior superior iliac spine and the internal spermatic veins are ligated at that level. Inguinal (Ivanissevich) approach: the spermatic cord and the external spermatic veins are tied off as they exit the internal ring . Subinguinal (Marmar) approach: accessed and ligated via a small transverse incision below the external ring. With microscopic assistance, this technique is reported to have superio r outcomes to other approaches. Laparoscopic: retroperitoneum. a muscle-splitting incision is the inguinal canal is incised to access external spermatic veins are internal spermatic veins are occluded high in the Surgical complications Varicocele recurrence; hydrocele formation; testicular atrophy, ilio inguinal nerve damage. Surgical outcomes Ninety- \201 ve percent success rate of treating the varicocele; 70% of men have improvement of sperm parameters. Joint Committee of the American Urological Association and the American Society for Reprodu ctive Medicine recommend intervention for a palpable varicocele associated with abnormal se men analysis. CHAPTER 12 Infertility 564 Treatment options for male infertility General: aim to identify and treat reversible causes of subfertility and im- prove semen quality. Advice on modi \201 cation of lifestyle fact ors (i.e. reduce alcohol consumption, avoid hot baths). Medical treatment Antibiotics Treat any positive semen, urine, or urethral cultures with th e appropriate antibiotics. Hormonal - Secondary hypogonadism administration of human chorionic gonadotrophin (HCG) which stimulat es an increase in testosterone and testicular size. If the patient remains azoospermic afte r 6 months of treatment, FSH is added (human recombinant FSH or human menopausal gonadotrop hin). Alternatively, pulsatile LHRH can be administered subcutaneously via a minipump (used for treating Kallman \200\231s syndrome). Hyperprolactinaemia: MRI to rule out a pituitary tumor. Antioestrogens increase LHRH which stimulates endogenous gonadotrophin secretion. U sed for idiopathic oligospermia. (pituitary intact): may respond to is treated with dopamine agonists. Arrange an (clomiphene citrate 25mg od): are used empirically to Antioxidants Vitamin E supplements have been shown to improve sperm function and IVF succes s rates; zinc and folic acid may increase sperm concentrations. Erectile and ejaculatory dysfunction Erectile dysfunction may be treated conventionally (or al, intraurethral, intracavernosal drugs; vacuum devices or prostheses). Ejaculatory failur e may respond to sympathomimetic drugs (desipramine) or electroejacula- tion or vibro-ejacu lation (used in SCI), where an electrical stimulus is used to produce ejaculation. It is de livered via a rectal probe to the post-gangli- onic sympathetic nerves that innervate the p rostate and seminal vesicles. Surgical treatment Genital tract obstruction - Epididymal obstruction: anastomosis between the epididymal tubule and vas (vasoepididymosto my). Vas deferens obstruction: ends of the vas (vasovasotomy) and is used for vasectomy rev ersal. Highest success rates for \201 nding viable sperm occur in the \201 rst 8y post- vasectomy (80 \200\22390%); overall pregnancy rates are 750%. Patency rates are better tha n pregnancy rates; success rates drop to 30% if >15y post-vasectomy.1 Ejaculatory duct obst ruction: ejaculatory ducts (TURED). Varicocele: surgical ligation. can be overcome by microsurgical is treated by microsurgical reanastomosis of requires transurethral resection of the can be treated by embolization or open or laparoscopic TREATMENT OPTIONS FOR MALE INFERTILITY 565 Assisted reproductive techniques (ART) Sperm extraction: sperm are removed directly from th e epididymis by PESA or MESA. If these methods fail, TESE by conventional biopsy or mi- cro surgical techniques, or aspiration (TESA) may be tried. Sperm undergo cryopreservation unti l required. Later, they are separated from seminal \202 uid by dilution and centrifuge me thods, with further selection of motile sperm and normal forms using Percoll gradient techn iques. Assisted conception - Intrauterine insemination are placed directly into the uterus. IVF : controlled ovarian sti mulation with gonadotrophins produces oocytes which are then retrieved by transvaginal USS- guided needle aspiration. Oocytes and sperm are placed in a petri dish for fertilization to occur. Embryos are incubated and cultured for 2 \200\2233 days and then transferred to the uterine cavity. Pregnancy rates are 20 \200\22330% per cycle. Gamete intrafallopian transf er and deposited into the Fallopian tubes via laparoscopy. Variations include zygote intraf allopian transfer (ZIFT) and tubal embryo transfer (TET). : A single spermatozoa is injecte d directly into the oocyte ICSI cytoplasm (through the intact zona pellucida). The advantag e is that fewer sperm are needed. ICSI is always combined with IVF and the clinical pregnan cy rate is 28 \200\22340% per cycle. (IUI): following ovarian stimulation, sperm (GIFT): oocytes and sperm are mixed 1 Belker AM, Thomas AJ Jr, Fuchs EF, Konnak JW, Sharlip ID (1991) Results of 1,469 microsur gical vasectomy reversals by the Vasovasostomy Study Group. J Urol 145:505 \200\22311. This page intentionally left blank 567 Chapter 13 Sexual health Physiology of erection and ejaculation 568 Erectile dysfunction: evaluation 572 Erectile dy sfunction: treatment 576 Peyronie \200\231s disease 580 Priapism 584 Retrograde ejaculation 588 Premature ejaculation 590 Other disorders of ejaculation and orgasm 592 Late-onset hyp ogonadism (LOH) 594 Hypogonadism and male hormone replacement therapy 596 Urethritis 600 No n-speci \201 c urethritis and urethral syndrome 602 CHAPTER 13 Sexual health 568 Physiology of erection and ejaculation Innervation Autonomic: sympathetic nerves originatin g from T11 \200\223L2 and parasympa- thetic nerves originating from S2 \200\2234 join to fo rm the pelvic plexus. The cav- ernosal nerves are branches of the pelvic plexus (i.e. paras ympathetic) that innervate the penis. Parasympathetic stimulation causes erection; sympa- t hetic activity causes ejaculation and detumescence (loss of erection). Somatic: somatosenso ry (afferent) information travels via the dorsal penile and pudendal nerves and enters the spinal cord at S2 \200\2234. Onuf \200\231s nucleus (segments S2 \200\2234) is the somatic center for efferent (i.e. somato- motor) innervation of the ischiocavernosus and bulbocaver nosus muscles of the penis. Central: medial preoptic area (MPOA) and paraventricular nucleu s (PVN) in the hypothalamus are important centers for sexual function and penile erection.