Examining Male Infertility

C O Examining Male Infertility N T I N U Susanne Quallich I N G n increasing number of Problems of male infertility can seem like minor issues within the couples seek evaluation larger realm of urology. But many male infertility diagnoses can be and treatment for infer- successfully treated, allowing the couple to conceive naturally or E tility, especially as more with minimal medical assistance. Some patients presenting with male D Acouples delay childbearing in infertility can have more significant disease. Treatments for male U order to establish their careers. A infertility will continue to progress, and as an increasing number of male factor alone is the cause of couples seek infertility services, the need to provide basic informa- C infertility in up to 20% of infer- tion grows as well. A tile couples and a contributing factor in another 30% to 40% of T all couples presenting for infertil- reproductive technologies. influence on overall male develop- I ity evaluations (American It is common to recommend ment and growth. Spermatogenesis O Urological Association [AUA] & an infertility evaluation in couples is driven by testosterone production N American Society for Reproduc- with a history of unprotected in the Leydig cells of the testes. tive Medicine (ASRM), 2001a; intercourse for at least 12 months Under the influence of luteinizing ASRM, 2004). Problems with without a pregnancy and with hormone (LH) and follicle-stimulat- infertility affect approximately 6.1 attempts to time intercourse with ing hormone (FSH), which are million people in the United ovulation, although this length of released from the anterior pituitary, States, or roughly 10% of the time can be shortened as the the testes begin to produce sperm in reproductive-age population. For female partner’s age increases to a four-step process of development: these couples, a lack of success over age 35 or if the couple is wor- spermatogonia, spermatocyte, sper- with conception is not just an ried about their fertility status. matid, spermatozoon. This cycle inconvenience but rather a disease This guideline is relevant even if takes roughly 74 days to complete, of their reproductive system(s). the couple has previously had with an additional 12 days for final Understanding the basics of male children together. A couple can maturation as the sperm traverse infertility is an important part of present with a history of little dif- the length of the epididymis providing complete urologic care ficulty achieving a first pregnancy, (Sigman, Lipshultz, & Howards, to male patients. and yet be unsuccessful in estab- 1997). The duration of this cycle There are causes of male infer- lishing a second pregnancy (sec- is important, as any changes in tility that are treatable, either ondary infertility). There are other the semen analysis following through medical or surgical man- reasons to consider an evaluation, medical or surgical intervention agement, and causes that can be such as female infertility issues, will not be reflected for at least 3 corrected, or improved, to the including age greater than 35, or a months. point where the couple is able to history of male risk factors for This process is governed by a conceive naturally or to take infertility, such as cryptorchidism negative feedback loop, with advantage of less-costly assisted or a history of cancer treatment. A testosterone acting as the primary screening evaluation for the cou- negative feedback component ple should include a reproductive that slows LH and FSH secretion. Susanne Quallich, APRN, BC, NP- history and at least two semen Inhibin, released during sper- C, CUNP, is a Nurse Practitioner, analyses at a laboratory that is matogenesis, also specifically Division of Andrology and qualified to perform the testing. inhibits activity or down-regu- Microsurgery, Michigan Urology lates FSH. This feedback system Center, University of Michigan Health Development of Sperm can be overridden by the admin- System, Ann Arbor, MI; and an Males do not begin to pro- istration of exogenous testos- Urologic Nursing Editorial Board duce sperm until puberty, when terone, or medications such as Member. testosterone begins to exert its luteinizing hormone-releasing

UROLOGIC NURSING / August 2006 / Volume 26 Number 4 277 C hormone antagonists, both of ronmental toxins, either through cally if there is a history of a O which stop the body’s own pro- occupation or hobbies. These vasectomy. duction of testosterone (and halt include excessive heat, radiation, Sexual history. The history N spermatogenesis as well). heavy metals, and glycol ethers or should include the overall pat- T other organic solvents. tern of sexual activity during the I History Medical history. The evalua- period of time the couple has General history and review of tion should then proceed to a his- been trying to conceive, specifi- N systems. The general history of a tory of any condition that would cally in relation to ovulation. U male patient during an infertility potentially affect erectile func- This includes questions regard- I evaluation begins with the duration, the testes, or the hormonal ing the use of ovulation-predic- tion of the attempts at pregnancy status of the patient (including tor kits or ovulation-promoting N or reason for the evaluation (such such things as cryptorchidism, medications such as clomiphene G as to establish if spermatogenesis epispadias, mumps, orchitis, dia- citrate, a nonsteroidal anti-estro- has returned after chemotherapy). betes, hypothyroidism, varico- genic. The optimal window for E It includes many questions cele, or pituitary malfunction). It pregnancy occurs in the 6 days regarding the reproductive status will also include a review of addi- before ovulation, with day 6 D of his partner, including her age, tional medical conditions for being the actual day of ovulation U the duration of the couple’s which the patient is being fol- (Wilcox, Weinberg, & Baird, C attempts at pregnancy, if they lowed, including any condition 1995). Simply adjusting the tim- have had children or a positive that would require radiotherapy ing of intercourse can result in a A pregnancy test together, and the or chemotherapy. Any history of significantly increased chance T results of any semen analyses treatment for malignancy, regard- for pregnancy. I prior to the current encounter. less of site, should be document- Both partners should be The history addresses whether or ed. Diabetes, chronic obstructive asked about a history of sexually O not either partner has conceived pulmonary disease, sleep apnea, transmitted infections. Each N with another partner, and should renal insufficiency, hemachro- patient should be queried regard- include previous evaluation and matosis, and hepatic insufficiency ing erectile function, ejaculation, treatment for male or female fac- are known possible contributors to and libido; these issues can be tor infertility in the past. Not male subfertility (Burrows, superimposed onto fertility con- every male patient is accompa- Schrepferman, & Lipshultz, cerns. Erectile difficulties may be nied by his partner, but this infor- 2002). Infertility in the male can, accompanied by a history of mation should be collected as in fact, be a hallmark symptom declining erectile function, usual- completely as possible. for other medical conditions in ly insidious and progressive, and The male general history an apparently healthy adult male. may span the course of several includes a discussion of any Surgical history. The surgical years (as is a common scenario recent (within the last 6 months) history during the male infertility with diabetic patients). Alter- systemic illness, particularly if it visit focuses on any history of GU natively, the patient may provide was a febrile illness, and any surgeries at any point during the a history of relatively rapid or recent weight gain or loss. The life of the male undergoing evalu- recent onset of a decline to erec- patient should be asked if there ation. These include such diverse tile function, such as may be asso- are any complaints specific to the procedures such as orchidopexy; ciated with the history of recently genitourinary (GU) structures. Y-V plasty to the bladder neck; starting new medication or the This may reveal complaints of a inguinal hernia repair as infant, stress of the fertility evaluation. dull ache or fullness to the scro- small child, or adult; epispadias The history should include sever- tum, or pain on one side that does or hypospadias repair; prostate al points specific to the patient’s not radiate. The review of sys- surgery; bladder reconstructions; sexual functioning: the precise tems will specifically include bladder surgeries; or testicular nature of the dysfunction (for fevers, colds, sinus infections, surgeries. The surgical history example, whether the problem is anosmia (loss or impairment of should ask about procedures attaining or sustaining an erec- the sense of smell), peripheral which impair retroperitoneal tion, insufficient rigidity, difficul- field visual problems, breast pain sympathetic nerve function, such ty with penetration); the presence or secretions, and scrotal pain. It as retroperitoneal lymph node or absence of nocturnal and should establish that puberty dissection (RPLND). The patient morning erections and their qual- started in the early or middle should be asked specifically ity; and any treatments (pharma- teens to confirm normal physio- about previous treatment for tes- cologic and nonpharmacologic) logic male development. ticular or GU malignancies, either that the patient has tried. The general history includes with surgery or radiation. The If the patient complains of any potential exposure to envi- patient should be asked specifi- low libido, he may also describe

278 UROLOGIC NURSING / August 2006 / Volume 26 Number 4 moodiness, loss of interest in his Table 1. C usual activities, a decline in erec- Common Medications with an Effect on Sperm Function O tile function, fatigue, and even complaints of diminished muscle Medication Effect N bulk. It should be established if Spironolactone Decreases spermatogenesis T these complaints are new or long- I standing. Calcium channel blockers Decreases fertilization capacity If there are issues with ejacu- N lation, the patient may have com- Anti-androgens Decreases spermatogenesis U plaints of cloudy urine after ejac- Nitrofurantoin (high doses) Decreases spermatogenesis I ulation, decreased volume of ejaculate, hematospermia, diffi- Cimetidine Decreases spermatogenesis N culty with bowel movements, G anejaculation, oligospermia (low Cyclosporine Decreases spermatogenesis sperm count), or azoospermia (no Colchicine Decreases fertilization capacity E sperm in ejaculate) with a low- volume ejaculate on semen analy- Erythromycin Decreases sperm density/motility D sis. The patient may have com- U Source: Adapted from Brugh, Matschke, & Lipshultz, 2003. plaints of pain on ejaculation, C usually of relatively recent onset, and it may localize to a specific A scrotal structure. These com- azoospermic or with persistently result in possible impairment to T plaints can be the result of a vari- decreased counts. The patient erectile function. I ety of surgical procedures, pro- must also be asked about the Family history. The family gressive neurologic disease, or ingestion of nutraceuticals and history should include a discus- O pre-existing treatment with cer- other over-the counter medica- sion of testicular or other GU N tain antidepressants (see the arti- tions, certain steroid hormones, malignancies and specifically any cle, “Premature Ejaculation” else- or other harmful substances that cancer history, prostate or blad- where in this issue for a more may contribute to semen analysis der problems in other family detailed description of ejacula- derangements as well. members (including female relation issues). Social history. Cigarette tives with bladder conditions). It The couple must also be asked smoking, excessive alcohol con- is helpful to include a history of about the used of lubricants: saliva, sumption, and consistent mari- maternal medication/drug use K-Y® jelly, surgilube, and hand juana use are all known to be while pregnant with patient, if lotions are known to impair sperm gonadotoxins (Burrows et al., this information is known. The motility (Burrows et al., 2002). 2002). A careful history of the use patient should be queried regard- Medication history. A careful of these agents and other illicit ing siblings or extended family medication history is a mandato- drug use must be part of the com- members who may have had fer- ry component of the initial evalu- plete male infertility evaluation. tility problems or diagnoses that ation of male-factor infertility. Cigarette smoking has been are genetic in nature (such as cys- Prescription drugs can affect implicated as leading to changes tic fibrosis). sperm count, motility, and mor- in morphology, sperm produc- Female partner history. The phology, and the dose and duration, and motility while chronic history of the patient’s partner tion of use should be document- alcohol use contributes to femi- should include details of any pre- ed. Common antibiotics can tem- nization, erectile dysfunction, and vious pregnancies (including porarily contribute to a decline in hypogonadism (Nudell, Monoski miscarriages or elective termina- the semen analysis quality; calci- & Lipshultz, 2002). Marijuana use tions), menstrual cycle length, um channel blockers and can decrease sperm morphology whether she is undergoing evalu- spironolactone can contribute to over time (Nudell et al., 2002). ation for fertility issues, and any a decreased fertilization capacity Simply eliminating these agents medical or surgical management and a decline in spermatogenesis can improve semen parameters in that has been necessary. It is also respectively (Brugh, Matschke, & the absence of other physical find- helpful to include comments Lipshultz, 2003) (see Table 1). ings. regarding the expected next step Anabolic steroid use can result in Patients should be asked in her management (if known) if a profound decline in sperm about recreational activities, as the male evaluation is negative. counts that may not recover with some activities, such as long-dis- the cessation of the exogenous tance cycling, may put pressure Physical Examination steroid, leaving the patient on the perineal area and may If this is a complaint in a man

UROLOGIC NURSING / August 2006 / Volume 26 Number 4 279 C with no other recognized medical marily on the genitalia (see Table evaluated include the penis, scro- O conditions, a full physical exami- 3), with consideration for the tum, testes, epididymis, spermat- nation is necessary. Examination overall body habitus. For a ic cord and vas deferens, prostate, N of the male patient is best done in detailed discussion of the com- seminal vesicles, and Cowper’s T a warm room, in an attempt to plete male physical examination, gland; however, not all are easily I avoid any exaggeration of the cre- refer to the physical assessment palpated. master reflex (see Table 2). The article that appears elsewhere in The patient should be exam- N examination should focus pri- this issue. The structures that are ined for age-appropriate develop- U ment of male secondary sex characteristics, gynecomastia, or hir- I Table 2. sutism. He should be evaluated Special Maneuvers for the Male Infertility Examination N for lesions or scarring to the G abdomen or groin (as patients Maneuver Description may inadvertently neglect to E Cremasteric Brushing or touching the skin of the scrotum in a down- mention surgery that happened reflex ward direction will result in the prompt elevation of the in their remote past), any discol- D testicle on the same side. This reaction can be aggravated oration to the scrotum, asymme- U by a cool room; the reflex may be engaged prior to any try of the testicles, and the loca- C contact with examiner. tion and size of the opening of the penile meatus. Physical examina- A Valsalva Performed with patient standing, and in warm room; having maneuver to patient perform Valsalva will reverse flow into the pampini- tion could reveal regression of T evaluate for form plexus and result in palpable distention of the vessels secondary sexual characteristics I varicocele (“bag of worms” if varicocele of sufficient size). such as hair loss and possible loss of muscle bulk. Patients using O Source: Quallich, 2005. N Table 3. Physical Findings and Their Relationship to Male Infertility

Visible Male Reproductive Normal Findings on Abnormalities Relevant to Structure Inspection/Palpation Infertility Evaluation Penis Soft and pliable along length of shaft. Meatus not midline or central to glans – Meatus midline, central to glans. hypospadias, epispadias. Foreskin should retract and draw forward easily.

Scrotum Sac of skin partially covered with hair. Unilateral, uncomfortable swelling of the scrotum – varicocele. Testes Two testes, freely movable within scrotum; Mass associated with testicle – tumor, should be nontender. spermatocele. Palpate between thumb and 1st two fingers of Solitary testis – maldescent of testicle or the hand. previous surgical removal. Firm, smooth, rubbery consistency. Small, soft testicle(s) – Klinefelter’s syn- Average 6 cm x 4 cm in size, symmetrical. drome, history of infection, late orchi- Right testicle may be slightly anterior to left. dopexy, atrophy due to long-standing Separate from epididymis. varicocele. Epididymis Soft ridge of tissue longitudinally posterior to Cystic or nodular – spermatocele, previ- testicle. ous infection, history of vasectomy. Separate from testicle. Large and/or fluctuant – spermatocele. Localized pain – epididymitis. Vas deferens and Soft, rubbery consistency. Absence of vas bilaterally or unilaterally spermatic cord Trace vas deferens from epididymis to inguinal – cystic fibrosis/CF variant. canal. Sperm granuloma – s/p vasectomy. Smooth along entire length. Congested veins unilaterally or bilaterally – varicocele. Beading/nodularity of the cord – possible obstruction of epididymis.

Source: Adapted from Quallich, 2005.

280 UROLOGIC NURSING / August 2006 / Volume 26 Number 4 anabolic steroids may also have Table 4. C skeletal muscle hypertrophy, Semen Parameters O acne, gynecomastia, and striae; there may be some noticeable tes- Semen Parameters Normal Values N ticular atrophy on examination. Morphology (strict criteria) > 15% normal forms T Palpation is the most impor- I tant component of the physical Motility > 50% examination when assessing for N male factor infertility. Because Sperm concentration > 20 million U the tone of the tunica dartos mus- Volume 2.0 ml - 5.0 ml I cle will determine the size of the N scrotum, the examination should Source: Adapted from Rowe, Comhaire, Hargreave, & Mahmoud, 2000. be performed in a warm room G whenever possible. In a cool environment the tunica dartos E muscle will cause the scrotum to Semen Analysis and specimens, with 3 days absti- contract. The scrotum must be Laboratory Evaluation nence, a minimum of 3 weeks D carefully and thoroughly palpat- The semen analysis yields a apart. It is common for patients to U ed, and the presence of all scrotal tremendous amount of informa- repeat their semen analysis every C structures should be confirmed, tion as to the potential causes of 3 months after starting any treat- along with their size and consis- male infertility. The primary val- ment, due to the length of time it A tency. Masses may arise from the ues that are evaluated are the vol- takes sperm to mature. The T surface of the testicle, adjacent to ume of the ejaculate, sperm motil- results of the semen analysis can I or separate from the testes. There ity, total sperm count, and sperm indicate any additional testing may be evidence of epididymal morphology (shape) (see Table 4). that might be useful. O induration on physical examina- Patients should receive notifica- There are several additional N tion. The patient may have a tes- tion in advance that they will tests that can be performed on a ticle that is palpable in the need to provide a semen sample semen sample, including a sperm inguinal canal and can be tender after a period of abstinence of 2 to penetration assay, peroxidase on examination, that cannot be 5 days. This sample is collected staining, direct immunobead test- manipulated down into the scro- through masturbation, and must ing, and computer-aided semen tum, or that cannot be palpated at be collected into a container that analysis. The clinical usefulness all. Physical examination may is not toxic to sperm, or by using a of specialized sperm testing show complete absence of the vas special condom designed for remains controversial, however. deferens unilaterally or bilateral- semen collection (latex condoms An endocrine evaluation can ly, or a palpable gap in the vas alter sperm viability, especially if yield a great deal of information deferens. The complete physical they are lubricated). Patients (see Table 5), and may be ordered examination should also include should be discouraged from if there is any suspicion of a digital rectal examination when attempting to collect a sample endocrinopathy or evidence of there are ejaculatory complaints. through intercourse as coitus oligospermia. This will include A varicocele can be exagger- interruptus is not a recommend- total testosterone, free testos- ated during physical examination ed, or reliable, means for sample terone, LH, FSH, and prolactin by asking the patient to perform collection (AUA & ASRM, 2001b). levels; estradiol level may be the Valsalva maneuver while The ideal circumstances for spec- included if the patient has a high standing; any distention of the imen collection are in close prox- body mass index. pampiniform plexus should dis- imity to the laboratory to prevent If the semen analysis shows appear when the patient lies any delay in processing. If the severe oligospermia or azoosper- down. If the varicocele is bulky sample is collected at home it mia and/or the physical examina- enough, there may be resulting should arrive to the lab within 60 tion yields abnormalities as far as scrotal swelling that is noticeable minutes to ensure the accuracy of testicular size or the male’s over- to the patient, along with a bluish the results. all physical development, then discoloration beneath the scrotal When determining a course karyotype analysis and Y-chro- skin. A long-standing varicocele of treatment, it is common to mosome microdeletion testing may cause testicular atrophy. If require serial analyses to avoid are also indicated. the varicocele is large, it may be any spurious results, ideally with visible during inspection (“bag of the same period of abstinence Potentially Reversible Causes worms”). each time. For instance, patients Of Male Infertility could be scheduled for three Varicocele. A varicocele is a

UROLOGIC NURSING / August 2006 / Volume 26 Number 4 281 C Table 5. O Endocrine Abnormalities Seen with Male Infertility N Condition Testosterone level LH level FSH Level Prolactin T Abnormal spermatogenesis Normal Normal Elevated or normal Normal I Anabolic steroid use Elevated or low Decreased Decreased Normal N (depends on specific U chemical) I Hypogonadotropic hypogonadism Decreased Decreased Decreased Normal N Normal spermatogenesis Normal Normal Normal Normal G Partial androgen resistence Elevated Elevated Normal Normal Testicular failure Decreased or normal Elevated Elevated Normal E D U C palpable or visible dilation of the changes. It is unusual for males to treatment has a high success rate vessels of the pampiniform exhibit a varicocele prior to ado- (AUA & ASRM, 2001c). Both A plexus in the scrotum. It is the lescence, and the majority of surgery and embolization have T reflux of venous blood from the varicoceles are asymptomatic, short recovery periods. The pri- I internal spermatic vein which causing neither pain nor semen mary risks are infection, varico- dilates the pampiniform plexus analysis changes. Adult males cele recurrence, and failure of the O and results in a varicocele. It is with a varicocele and some semen analysis to improve after N estimated that varicoceles may be abnormalities of their semen the procedure. For those patients present in 15% of the male popu- parameters may benefit from who do not show improvement lation, and this number increases treatment for the varicocele as a or show only modest improve- to 40% in men presenting for an way to protect their future fertili- ment over the course of a year, infertility evaluation (AUA & ty and prevent any potential for and in whom the varicocele has ASRM, 2001c). Varicoceles are future decline to their semen not recurred, intrauterine insemi- more common on the left, possi- parameters (Chehval & Purcell, nation (IUI) or in vitro fertiliza- bly due to the greater distance the 1992). tion (IVF) may be advised, internal spermatic vein must tra- A scrotal ultrasound is not depending on the total sperm verse to the left renal vein when necessary to diagnose a varico- count. compared with the distance on cele, but it will confirm the pres- the right. If a varicocele is ence of a varicocele and eliminate Ejaculatory and Sexual painful, there may be a history of other testicular or scrotal patholo- Dysfunction a dull ache, fullness, pain that gy. However, only those varicoce- A secondary goal of the infer- does not radiate, or pulling to the les palpable on physical exami- tility evaluation is to identify any affected side of the scrotum after nation have been documented as underlying health conditions that prolonged standing, exertion, or contributing to male infertility may be contributing to difficul- sitting. Pain from a varicocele is (AUA & ASRM, 2001c). ties with conception. This could rare after prolonged recumbency Treatment of a varicocele is include any conditions that or sleeping. possible either through surgical would contribute to problems A varicocele might be sus- repair or percutaneous emboliza- with ejaculation, such as undiag- pected in the male with tion. Surgical repair can be nosed diabetes, or problems with decreased semen parameters, as achieved with a variety of erection, such as might be caused varicoceles represent a common approaches, including microsur- by a significant smoking history, cause of secondary male infertili- gical, inguinal, or subinguinal. severe hypercholesterolemia, or ty. The etiology of varicoceles Neither embolization nor surgery hypogonadism. A full discussion remains unclear, and there are no has been clearly shown to of the diagnosis and treatment of specific risk factors. The mecha- improve fertility (AUA & ASRM, erectile dysfunction (ED) is nism by which varicoceles alter 2001c). Any offered surgical cor- beyond the scope of this article; the semen analysis is also uncer- rection will be secondary to the however, it is not uncommon for tain, and may be the result of tem- individual surgeon’s experience, men to report some stress-related perature elevation, venous con- while embolization requires in- ED during the course of the infer- gestion, or testicular hormone terventional radiology. Surgical tility evaluation and treatment.

282 UROLOGIC NURSING / August 2006 / Volume 26 Number 4 These patients may benefit from a pression, irritability, loss of moti- LH, decreased FSH) can also bene- C prescription for a PDE-5 inhibitor. vation) in addition to complaints fit from treatment with exoge- O Alprostadil (Muse®) is not recom- of lethargy or loss of energy. nous hormones to stimulate their mended since its potential effect Physical examination may system into a more normal pro- N on the ejaculate is not known. demonstrate some regression of file. Their prospects for recovery T Patients who complain of dif- secondary sexual characteristics of spermatogenesis are modest; I ficulty with ejaculation and cli- such as hair loss and possible loss even with treatment it may be a max may be taking psychothera- of muscle bulk. There is no year or more before sperm pro- N peutic agents that block change to penis or prostate size, duction returns. The most pro- U dopamine production and conse- but the testes may be softer in found cases of this are caused by I quently blunt the hypothalamic- consistency and smaller than hypothalamic disorders such as pituitary axis and possibly might be expected from the Kallman’s syndrome. Men diag- N decrease libido. Other psy- patient’s chronologic age. nosed with a form of hypogo- G chotherapeutic agents can decrease Obesity can lead to the arom- nadotropic hypogonadism may vasodilation and decrease the qual- atization of testosterone in fatty still sire genetic offspring, via tes- E ity of erections. Tricyclic antide- tissue to estradiol, leaving less ticular aspiration and IVF and pressants, selective-serotonin reup- testosterone available for mainte- intracytoplasmic sperm injection D take inhibitors, and monoamine nance and virilization functions. (ICSI). U oxidase inhibitors can lead to ED, This will lead to a decline in Obstructive azoospermia. C anejaculation, and decreased sperm production, as the testes Patients who have previously had libido. These patients can have no longer receive an adequate vasectomies suffer from obstruc- A their regimen changed, or may be hormonal signal to produce tive azoospermia. These patients T offered other means of medically sperm. As a result of lowered are usually otherwise healthy, I managing their complaints, such as testosterone, a clinically obese and have normal GU examina- a PDE-5 inhibitor. male may demonstrate evidence tions, with the exception of O Endocrinopathy. Hypogonad- of feminization (such as gyneco- sperm granulomas as a result of N ism represents the only cause of mastia) or regression of secondary the vasectomy, and varying male infertility that can successful- male sexual characteristics on degrees of induration and/or ten- ly be treated with hormone therapy, physical examination. Testo- derness to their epididymis. although the response is largely sterone and free testosterone lev- These patients can be offered a dependent on the length of time els, along with estradiol, LH, and vasectomy reversal as treatment and causes of the hypogonadism. FSH levels will aid in determin- for their infertility, and may be Hypogonadism is failure of the ing the degree to which obesity candidates for a vasovasotomy or testes to produce normal levels of may have upset the patient’s hor- vasoepididymostomy depending testosterone and/or sperm. Pri- monal balance and contributed to on their physical examination mary causes of hypogonadism are alterations to the semen analysis. (AUA & ASRM, 2001b). The commonly due to testicular failure, The most definitive treatment is offered surgical approach will be while secondary causes are due to weight loss, but some patients may based on the individual surgeon’s pituitary or hypothalamic causes, also respond well to treatment with experience. Vasectomy reversals and combined hypogonadism is clomiphene citrate, a synthetic may become less successful as due to the combinations of the nonsteroidal anti-estrogen. the time after the vasectomy decreased pulsatility of the pitu- All forms of hypogonadism increases. A microsurgical vasec- itary gonadotropins coupled with can be confirmed by checking a tomy reversal remains the most the decreased response of the tes- testosterone level; morning val- cost-effective option for fertility ticular Leydig cells. Hypogona- ues are preferred to afternoon restoration after a vasectomy dism is more common in aging blood samples because testos- (Pavlovich & Schlegel, 1997). males who have passed through terone is secreted in the morning. A minority of patients pre- their reproductive stage. This should include total testos- senting for a male infertility eval- Reversible endocrinopathies terone, free testosterone, LH, and uation may have suffered an that directly contribute to male FSH. Estradiol should be ob- inadvertent vasectomy during infertility are unusual (Kolettis, tained if the patient has a higher surgery for another condition, 2003). In the adult male, hypogo- body mass index. Prolactin and a such as a inguinal hernia repair as nadism manifests with changes thyroid profile can also be useful a child or adult. In some cases in sexual function, behavior, in diagnosing secondary causes these patients can be successfully muscle mass, and some loss of in selected cases. reconstructed. secondary sexual characteristics. Men who are diagnosed with Ejaculatory duct obstruction. The patient may also report mood hypogonadotropic hypogonadism Ejaculatory duct obstruction de- and behavioral symptoms (de- (decreased testosterone, decreased scribes a condition in which one, or

UROLOGIC NURSING / August 2006 / Volume 26 Number 4 283 C both, of the ducts leading from the Table 6. O seminal vesicles into the prostate Discussion of Clomiphene Citrate become(s) partially or completely (Selective Estrogen Receptor Modulator) N blocked. This results in only pro- T static fluids contributing to the Male Female I ejaculate volume. As a result the Action Functions at level of pituitary: Functions at level of pituitary: semen analysis will show causes increased FSH secretion causes increased FSH secretion N decreased volume, increased acidi- Result Increased testosterone pro- Stimulates ovulation U ty, possible hematospermia, possi- duction, likely increased sperm I ble oligospermia, or azoospermia. production, increased sperm The patient may provide a history count, and concentration N of pain immediately following ejac- G ulation. Digital rectal examination Potential Dizziness Abdominal discomfort adverse Gynecomastia Abnormal uterine bleeding may show some tenderness to the effects Headache Headache E prostate and/or epididymis, and Lightheadedness Ovarian hyperstimulation possible distended seminal vesi- Mental depression syndrome D cles, but the diagnosis is more com- Vision problems (rare) Vasomotor flushes U monly made after a transrectal Visual symptoms C ultrasound. Treatment involves the transurethral resection of the ejacu- A latory ducts. T Chemotherapeutic agents. smoking cessation, cessation of because of its estrogenic effects, I Men who have been treated with recreational drug use, and cessa- there is the potential for alter- chemotherapeutic agents have tion of alcohol intake. Medical ations in libido, gynecomastia, O varying chances of recovering management is often related to weight gain, and headache (see N spermatogenesis, depending on addressing some endocrine Table 6). There have been a vari- the specific agents involved. abnormality; in the case of a spe- ety of uncontrolled studies as to Damage is done directly to the cific hormone deficiency, admin- the effectiveness of clomiphene germinal epithelium and Sertoli istration of the hormone, or a sub- citrate in treating male subfertili- cells that support spermatogene- stance that promotes its produc- ty, but when the outcome is mea- sis. The most gonadotoxic agents tion, can restore the patient to sured as an increase in pregnancy are alkylating agents, antimetabo- normal hormone levels. After a rate, clomiphene citrate fares lit- lites, and vinca alkaloids (Nudell period of time, 6, 9, 12 months or tle better than placebo (Sokol, et al., 2002). Agents such as more, there can be improvements Steiner, Bustillo, Petersen, & methotrexate, cisplatin, and 6- in overall semen parameters Swerdloff, 1988). It will not have mercaptopurine offer better either to normal ranges or such an effect on the male who has a chances of sperm recovery that the couple becomes a candi- normal testosterone level and a (Nudell et al., 2002), but offering date for low-tech interventions. decreased semen analysis. the opportunity to cryopreserve This is true for all attempts at If there is retrograde or low- sperm prior to initiation of treat- hormone replacement except for volume ejaculation, a trial of sym- ment should be considered when- testosterone. The patient who is pathomimetics can be useful. The ever possible. Spermatogenesis given any form of testosterone goal of this therapy is to convert can recover during the 2 to 4 years replacement will suffer a progres- the retrograde ejaculation to ante- after the cessation of treatment; sive decline in the function of the grade or partially antegrade ejacu- progress toward recovery can be testicles, as the exogenous testos- lation; a variety of medications monitored with yearly semen terone is a powerful inhibitor of have been used, with varying samples. the feedback loop that governs degrees of success (Schuster & spermatogenesis and testicular Ohl, 2002). This approach is Male Infertility and Medical testosterone production. To boost more successful with patients Management testosterone levels in the subfer- who suffer a progressive decline Medical management of male tile male, clomiphene citrate in their ejaculatory function, such infertility occurs when a specific (Clomid®), a synthetic nons- as that seen with neurologic dis- contributing factor that is poten- teroidal anti-estrogen is given, ease, than with the abrupt onset tially amenable to attempts at commonly at 25 mg daily. In men, seen as a result of a variety of medical treatment is identified. it blocks feedback inhibition and surgeries, such as radical retropu- This routinely includes the rec- so increases FSH and LH, thus bic prostatectomy. ommendation to remove any increasing testosterone and Use of the supplement L-car- environmental toxins, such as sperm production. In part, nitine, either by itself or in a mix-

284 UROLOGIC NURSING / August 2006 / Volume 26 Number 4 ture of additional substances, has teristics on physical examination seminal vesicles, and ejaculatory C been proposed as a supplement (atrophic [< 2.0 cm] testes, small ducts are generally atrophic or O that can improve overall sperm phallus, diminished body hair, absent. Physical examination motility and the total sperm diminished muscle bulk), and a may show complete absence of N count, and enabling a patient to feminine, or truncal, rather than the vas deferens unilaterally or T avoid invasive procedures such male, fat distribution that often bilaterally, or a palpable gap in I as varicocele repair or testicular includes gynecomastia. Patients the vas deferens. Testosterone biopsy. However, its use remains may be tall, due to a delay in the levels in these patients will be N somewhat unfounded. Although fusion of the epiphyseal plates in normal. Spermatogenesis is usu- U carnitine serves a role in the mat- the long bones. ally normal as well, and so testes I uration of sperm, there have been Clinical suspicion after the size and consistency are normal, no prospective, randomized, dou- physical examination will usual- with the patient describing nor- N ble-blind, placebo-controlled tri- ly lead to a karyotype analysis, mal libido and demonstrating G als to evaluate this supplement’s which will show 47, XXY or a appropriate secondary sexual utility in improving male-factor mosaic pattern such as 46, XY/47, characteristics. It is possible that E infertility (Siddiq & Sigman, XXY, indicating a diagnosis of the patient may have a much 2002). Klinefelter’s syndrome. Serum more rare unilateral absence of D Generally, attempts at med- hormone studies will demon- the vas deferens, which is usually U ical treatments for male infertility strate a decreased or normal associated with Wolffian duct C have been limited by poorly testosterone, decreased free abnormalities and renal malfor- designed research studies, and by testosterone, elevated estradiol, mations. A wide variations in dosage and normal or elevated LH, and ele- The physical examination T duration of therapy, lack of a vated FSH. and history are sufficient to con- I placebo-control arm, and a failure Treatment for infertility in firm a suspicion of CF; the patient to control for the variation seen in the patient with Klinefelter’s can will be sent for karyotype analy- O semen quality with time. take a variety of forms (see Table sis and CF testing. The couple N 7). It is only recently, with the will be sent to a genetics clinic for Irreversible Causes of Male advent of the microTESE (micro- additional counseling and test- Infertility surgical testicular extraction) pro- ing. Males with CF have the Klinefelter’s syndrome. Kline- cedure, that patients diagnosed option to sire genetic offspring felter’s syndrome is the most with Klinefelter’s syndrome were via testicular aspiration and IVF. common abnormality of sexual given the potential to father Anejaculation after a spinal differentiation, and occurs in genetic offspring via microTESE cord injury or surgery. Ap- approximately 1 in 500 live and ICSI (intracytoplasmic sperm proximately 80% of spinal cord births. It is one of the most com- injection). injured (SCI) men will demon- mon causes of primary hypogo- Congenital bilateral absence strate some preservation of their nadism, and is the most common of the vas deferens. Congenital erectile function (Schuster & Ohl, sex chromosome abnormality bilateral absence of the vas defer- 2002). Men with a T9 level injury seen in infertile men. Patients ens is a genetic abnormality that or above can have reflex erections will present with a typical triad of is seen with cystic fibrosis (CF) that do not persist long enough or small, firm testes; gynecomastia; and its multiple variants. If not are reliable for sexual activity. In and elevated urine gonado- previously diagnosed with cystic men who have suffered lower tropins. Variants of Klinefelter’s fibrosis, the patient may have one motor neuron injuries (below T9), may also result in increased of the less-severe CF mutations, erectile activity is absent. height, diabetes mellitus, obesity, and report a history of chronic Ejaculatory function in men and decreased intelligence. The bronchitis that may have required with SCI is a separate challenge. infertility evaluation may be the hospitalization, recurrent respira- Only 5% to 15% of men will have first time the patient has a com- tory infections as a child and ado- any evidence of ejaculation after plete physical examination as an lescent, asthma or an asthma-like their injury (Biering-Sørensen & adult. condition, or even have no symp- Sønksen, 2001) and this repre- During the history, patients toms at all (most common). There sents a major aspect contributing may describe the delayed com- are usually no other physical to infertility. This is complicated pletion of puberty and delayed complaints; but there may be a further by a significant decline in virilization. There are usually few family history of infertility or per- overall sperm quality. Sperm physical complaints associated sistent respiratory illnesses. obtained from men who are with Klinefelter’s syndrome. Males with CF frequently unable to ejaculate demonstrate a There will be a lack of develop- demonstrate malformation of the variety of abnormalities that ment of secondary sexual charac- epididymis. The vas deferens, include significantly decreased

UROLOGIC NURSING / August 2006 / Volume 26 Number 4 285 C Table 7. O Examples of Treatment Options for Male Infertility Diagnoses N Diagnosed Condition Treatment Option A Treatment Option B Treatment Option C T Antisperm antibodies IUI IVF + ICSI Donor insemination + IUI I Cystic fibrosis Testicular sperm extraction Donor insemination + IUI Adoption N with IVF U Diabetes with Trial of sympathomimetic Testicular sperm extraction Donor insemination + IUI anejaculation to promote antegrade with IVF I ejaculation N Failed vasectomy reversal Testicular sperm Donor insemination + IUI Adoption G extraction with IVF Hypergonadotropic Possible hormone Testicular sperm extraction Donor insemination + IUI; E hypogonadism replacement with IVF Adoption D Idiopathic male infertility IUI +/- donor insemination IVF +/- ICSI Adoption U (depends on count) (depends on count) C A Klinefelter’s syndrome MicroTESE and IVF + ICSI Donor insemination + IUI Adoption T Persistent low sperm IUI Donor insemination + IUI IVF count after medical or I surgical treatment O Retrograde ejaculation Trial of sympathomimetic IUI Testicular sperm extraction N to promote antegrade with IVF ejaculation Varicocele Varicocele repair IUI IVF

IUI: Intrauterine insemination IVF: In vitro fertilization ICSI: Intracytoplasmic sperm injection

motility and viability, decreased Anejaculatory men can still and reversal, testis injury or ability to penetrate cervical father their own children; both infection, or cancer; it can also be mucus, and decreased fertilizing penile vibratory stimulation idiopathic. Past attempts at treat- capability. Only 5% of men with (PVS) or electroejaculation (EEJ) ment of this condition with such SCI will be able to initiate a preg- are successful options for specific medications as corticosteroids nancy without some degree of groups of patients and allows the have met with little success. medical intervention (Schuster & possibility for IUI (see Table 8). These particular patients can be Ohl, 2002). Alternatively, anejaculatory men treated with IUI (low success) or Surgical procedures in the have the option to proceed with IVF with ICSI. pelvis or retroperiteneum can result testes aspiration and IVF. Other genetic causes. There are in neurogenic impairment of the Antisperm antibodies (im- other less-commonly seen genetic ejaculatory process by damaging munologic infertility). Some men causes of male infertility that peripheral nerves. This can mani- will demonstrate antisperm anti- include conditions such as fest as an incompetent bladder neck bodies that are associated with Kallman’s syndrome, Y-chromo- and retrograde ejaculation, or total their sperm. These can be anti- some microdeletions, various neu- anejaculation. Men with testis can- bodies that are attached to the romuscular conditions, immotile cer, in particular, are at risk for this head, tail, or all parts of the cilia syndromes, and Kartagener’s type of injury with a RPLND. Men sperm, and their presence syndrome. Depending on sperm who suffer from surgically induced inhibits the fertilizing ability of counts, these patients can be anejaculation will experience the sperm. It is unclear precisely offered sperm aspiration with IVF decreases to their semen quality why these antibodies form, but it or IVF and ICSI. similar to that of men with SCI. can be the result of vasectomy

286 UROLOGIC NURSING / August 2006 / Volume 26 Number 4 Table 8. C Methods of Sperm Retrieval O Assisted N Reproduction Method Indications Procedure Options T I Penile vibratory Anejaculation (inability to Collected in treatment room in clinic; IUI stimulation (PVS) or ejaculate) application of a vibrator to the penis IVF N electroejaculation (EEJ) (PVS) or probe is inserted into the rec- IVF with ICSI U tum, and a current is applied, produc- ing erection and ejaculation (EEJ) I N Retrograde semen Retrograde ejaculation Collected in treatment room in clinic or IUI collection assisted reproductive technologies (ART) IVF G lab; can also be collected after PVS or EEJ

Epididymal sperm Azoospermia; obstructive Done in clinic treatment room under IVF E extraction azoospermia; absence of local anesthesia or operating room with IVF with ICSI D vas deferens general anesthesia U Testicular sperm extraction Azoospermia; obstructive Done in clinic treatment room under IVF C azoospermia; cystic fibrosis local anesthesia or operating room with IVF with ICSI A general anesthesia T Testes biopsy Azoospermia – to Done in clinic treatment room under IVF I diagnose normal or local anesthesia or operating room with IVF with ICSI abnormal sperm general anesthesia O development; also to N retrieve sperm

Microsurgical testicular Microsurgical method for Surgical procedure with local or gener- IVF with ICSI sperm extraction obtaining sperm from a al anesthesia (MicroTESE) male who does not have sperm in his ejaculate (azoospermia) with severe production problems

Azoospermia: Lack of sperm in the ejaculate IUI: Intrauterine insemination IVF: In vitro fertilization ICSI: Intracytoplasmic sperm injection

Fertility Preservation ation treatment and can serve as a for a variety of male infertility The future of infertility treat- “backup” in the event that sper- diagnoses requires a basic under- ment continues to evolve. This is matogenesis does not rebound standing of male GU anatomy and partly a response to changes in after treatment. But it is also an function, as well as understand- technology as a whole, but is also option for those at risk for expo- ing of the hormonal processes inspired but the increasing sur- sure to toxins or even those being that control spermatogenesis. The vival rates of cancers that affect deployed in the military. The male infertility evaluation often young people during their repro- future may see options for the represents the first time an other- ductive years and the trend for storage of testicular tissue, autol- wise healthy male is faced with couples to delay pregnancy. ogous spermatogonial stem cell the concept that he is somehow There are currently available transplantation, or gene therapies “not normal.” Not only can this options for preservation of fertili- to treat genetic causes of male be an affront to his masculinity, ty for men, primarily sperm cry- infertility. but depending on the larger reli- opreservation; this can be a rea- gious and/or cultural context, sonable option for men planning Conclusions failure to have children can to undergo chemotherapy or radi- The discussion of treatments impact his standing in his com-

UROLOGIC NURSING / August 2006 / Volume 26 Number 4 287 C munity. This can be heightened American Urological Association (AUA) & testicular damage. Fertility & Sterility, by the fact that the outcome is not American Society for Reproductive 57(1), 174-177. O Medicine (ASRM). (2001c). Report on Kolettis, P.N. (2003). Evaluation of the sub- always predictable, even with the varicocele and infertility. Retrieved fertile male. American Family N use of assisted reproductive tech- September 1, 2005, from http://www. Physician, 67(10), 2165-2172. T nologies. As technologies contin- auanet.org/timssnet/products/ Nudell, D.M., Monoski, M.M., & Lipshultz, I ue to progress, there will be new guidelines/main_reports/varicocele L.I. (2002). Common medications and options that become available to infertility.pdf drugs: How they affect male fertility. N American Society for Reproductive Medi- Urologic Clinics of North America, couples whose only options cur- cine (ASRM). (2004). Frequently asked 29(4), 983-992. U rently are donor insemination or questions about infertility. Retrieved Pavlovich, C.P., & Schlegel, P.N. (1997). adoption. • September 17, 2005, from http://www. Fertility options after vasectomy: A I asrm.org/Patients/faqs.html#Q2 cost-effectiveness analysis. Fertility & N References Biering-Sørensen, F., & Sønksen, J. (2001). Sterility, 67(1), 133-141. Sexual function in spinal cord Quallich, S.A. (2005). Male reproductive American Urological Association (AUA) & G lesioned men. Spinal Cord, 39, 455- assessment. In M.J. Goolsby & L. American Society for Reproductive 470. Grubbs (Eds.), The missing step: Medicine (ASRM). (2001a). Report on Brugh, V.M., Matschke, H.M., & Lipshultz, From advanced assessment to differ- optimal evaluation of the infertile E L.I. (2003). Male factor infertility. ential diagnosis. New York: F.A. male. Retrieved September 1, 2005, Endocrinology & Metabolic Clinics of Davis. from http://www.auanet.org/timss- D North America, 32(3), 689-707. Rowe, P.J., Comhaire, F.H., Hargreave, T.B., net/products/guidelines/main_report Burrows, P.J., Schrepferman, C.G., & & Mahmoud, A.M.A. (2000). WHO U s/optimalevaluation.pdf Lipshultz, L.I. (2002). Comprehensive manual for the standardized investi- American Urological Association (AUA) & C office evaluation in the new millenni- gation, diagnosis and management of American Society for Reproductive um. Urologic Clinics of North America, the infertile male. Cambridge, A Medicine (ASRM). (2001b). Report 29(4), 873-894. England: Cambridge University on optimal of the azoospermic male. T Chehval, M.J., & Purcell, M.H. (1992). Press. Retrieved September 1, 2005, from Deterioration of semen parameters Schuster, T.G., & Ohl. D.A. (2002). http://www.auanet.org/timssnet/pro I over time in men with untreated Diagnosis and treatment of ejaculato- ducts/guidelines/main_reports/azoss varicocele: Evidence of progressive ry dysfunction. Urologic Clinics of O permicmale.pdf North America, 29(4), 939-948. N Siddiq, F.M., & Sigman, M. (2002). A new look at the medical management of infertility. Urologic Clinics of North America, 29(4), 949-963. Sigman, M., Lipshultz, L.I., & Howards, S.S. (1997). Evaluation of the subfer- tile male. In L.I. Lipshultz, & S.S. Howards (Eds.), Infertility in the male (3rd ed.) (p. 173). St. Louis: Mosby. Sokol, R.Z., Steiner, B.S., Bustillo, M., Petersen, G., & Swerdloff, R.S. (1988). A controlled comparison of the effi- cacy of clomiphene citrate in male infertility. Fertility & Sterility, 49(5), 865-870. Wilcox, A.J., Weinberg, C.R., & Baird, D.D. (1995). Timing of sexual intercourse in relation to ovulation. Effects on the probability of conception, survival of the pregnancy, and sex of the baby. New England Journal of Medicine, 333(23), 1517-1521.

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