Infertility in spinal-cord injured male

STERILITY-FERTILIT

INFERTILITY

SHANE

IN SPINAL-CORD

M. VER VOORT,

INJURED MALE

M.D.

From the Departments of Physical Medicine and Rehabilitation, Baylor College of Medicine, Houston, Texas

ABSTRACT-Sterility in spinal-cord injured (XI) men is believed to be caused by ejaculatory dysfunction, genital ductal blockage secondary to infection, and/or impaired spermatogenesis. Semen from SCI men demonstrates diminished numbers of motile, morphologically normal sperm. Testicular biopsies demonstrate impaired spermatogenesis. Leydig and Sertoli cells appear to be normal. Endocrine evaluations reveal normal testosterone levels with an adequate Leydig cell reserve. Luteinixing hormone (LD) and follicle-stimulating hormone (FSH) levels are normal or high with normal or exaggerated stimulation responses. Acute depressions in testosterone, FSH, and LH levels can be seen following SCI, most markedly in quadriplegics. A normal hypothalamic-pituitary-testicular axis is implied by these findings, indicating a primary hypogonadism. Causes of impaired spermatogenesis may include local testicular temperature elevations, nondrainage of the reproductive tract, antisperm antibodies, and recurrent genitourinary infections. Treatment of infertility involves removal of these offending factors, and research is needed to correlate the imvaired swermatogenesis with these factors.

Sterility in spinal-cord injured (SCI) men may arise from several factors. These include failure of ejaculation secondary to neuromuscular dysfunction, obstruction of the genital passages secondary to infections of the lower urinary tract, and failure of spermatogenesis.’ Techniques of ejaculatory stimulation have increased the incidence of ejaculation to as much as 63 per cent.2 The incidence of fertility in SC1 men, however, is reportedly only O-5 per cent3 Only a few pregnancies using artificial insemination with semen obtained by stimulation techniques have been reported.2+7 The findings of several investigators who have examined semen, testicular biopsy specimens, and the hypothalamic-pituitary-testes axis (Fig. 1) in SC1 men were initially reviewed and conclusions were drawn regarding these findings. The primary causes of impaired spermatogenesis as well as areas of needed research are discussed.

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Semen of SC1 Men There is a paucity of literature about the semen of SC1 men. Few SC1 men ejaculate spontaneously; hence, most data are obtained from SC1 men who ejaculated via chemical or electrical methods. Brindley2 reports that of 166 antegrade ejaculates obtained by electroejaculation (EE) from 36 SC1 men, only one in ten forms the coagulum that is normally seen in fertile semen specimens. David, Ohry, and Rozin4 obtained ejaculates using EE from 4 men with upper motor lesions, 3 of whom had incomplete lesions. They were unable to draw any conclusions from measuring seminal fructose, inositol, acid phosphatase, and carnitine because of the small number of specimens. A low value of carnitine seen in one specimen suggests that further information might be obtained by examining seminal parameters in greater detail.

2

157

HYPOTHALAMIC - PITUITARY - TESTICULAR AXIS HIGHER BRAIN

piyyq

LHRH

HYPOTHALAMUS 41

I I4

Peripheral Tissues

TESTES Seminiferous Tubule *-. lnhibiis secretion and/or formation h Facilitates secretion and/or formation I& Movement FIGURE 1. Hypothalamic-pituitary-testicular axis. Hypothalamus secretes luteinizing hormone-releasing hormone (LH-RH), which in turn stimulates release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) from anterior pituitary. LH and FSH exert negative feedback effects on release of LH-RH. Higher brain influences also alter release of LH-RH. LH and FSH are released episodically, with parallel elevations producing signijicant variations in plasma levels. FSH, however, demonstrates more constant levels because its metabolic clearance rate is lower than LH. Luteinizing hormone stimulates release of testosterone from Leydig cells and testosterone, in turn, exerts a negative feedback on LH release. Testosterone is converted by peripheral tissues to estradiol, which exerts negative feedback on FSH and LH release. FSH triggers production and release of androgen binding protein (ABP) by Sertoli cells. Released into luminal fluid ojseminijerous tubules, ABP binds testosterone, thus maintaining high levels of testosterone needed for spermatogenesiz. Inhibin, released by Sertoli cells, exerts selective negative feedback effect or release of FSH.

The impaired ejaculatory function of SC1 men precludes random sampling of their semen, In the relatively few specimens examined, most demonstrated decreased numbers of sperm, decreased percentage of motility, and increased number of abnormal forms (Table I). Horne, Paull, and Monroa attempted to correlate the level of lesion with the spermogram, but could find no relationship. Testicular Histology Studies of testicular histology also provide ,useful information about the reproductive tract of the SC1 man. The majority of testicular biopsies were performed by early researchers. Their

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findings must be interpreted cautiously, however, because the subjects of these early experiments probably experienced many medical complications preventable by today’s standards of care. In 1949, Bors et ~1.~ reported their findings in bilateral testicular biopsies from 34 S,CI men. They identified normal testis histology (3 cases), spermatogenic arrest (2)) tubular fibrosis (7), and secondary atrophy of the seminiferous tubules (22 cases). In the majority of these men, urinary 17-Ketosteroids, estrogens, and gonadotropins were also measured. They were unable to correlate these hormonal parameters with the biopsy findings or the level and extent of the cord lesion. In addition, no correlation

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TABLE I.

Studies of semen of SCI men

Series

Number of Subjects

Method of Ejaculat.

Horne et al8

12

3 best:M* 9:EEJ

78

ITN$

1.1-7.1

36

EE

0.2-10.5

3

EE

?

Martin et a1.37 (1983)

5

EE

?

David et al4 (1977)

4

EE

(1948)

Guttman and Walsh35 (1970) Brindley2 (1981) Bensman and Kottke3e (1966)

Volume (ml) ?

0.9-3.0

Total Sperm/ml 2 0.5-100 x 108

<40x

106

14,000 13 x lo5 and 41 x 104 (per cm3 of urine) 5.8, 45 83, 176, 445 x 106 (in urine) 0.5-24 x lo6

Motile Sperm 6: >30 x lo8 (Total motile sperm) lo-60 %

Abnormal Forms (%)

Type of Lesion

?

. .

Varied greatly

Various

(26%

?

Various

0%

?

?

5%, 50%, lo%, 18% 10%

45-65

Thoracic

l-60 %

27-93

. .

*Masturbation. fElectroejaculation. $Intrathecal neostigmine.

was found between the biopsy findings and the incidence of urinary, prostatic or epididymis infections, urinary calculosis, or decubitus ulcers, nor did a later study demonstrate a correlation between biopsy findings and lesion level.‘O In their attempts with EE, Horne et uZ.~examined testicular biopsy specimens in 7 of their 18 subjects. Four men demonstrated spermatogenie arrest, 2 showed normal testis histology, and 1 demonstrated tubular atrophy in 1 testis and normal histology in the other. The investigators believed that a reasonably close correlation between sperm counts and biopsy specimen existed. In 1949, Stemmerman et al.” examined testicular histology in four autopsy specimens and 16 living SC1 men. The autopsy specimens were from men who had been in emaciated nutritional states with multiple medical complications. The living men were in comparatively good health. The autopsy specimens revealed maturation arrest (3) and normal spermatogenesis (1). Results of the biopsies revealed abnormal spermatogenesis in 10 cases ranging from absence of spermatogenic cells to rare spermatids and spermatozoa. The remaining 6 showed normal spermatogenesis. There appeared to be no variation of Leydig cells in normal or abnormal biopsy specimens. Also no relationship was found between biopsy findings

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and epididymitis, .duration or level of lesion, sexual potency, or general systemic features. In two poorly documented articles, Tsuji et ~1.‘~ and Leriche et al. l3 reported on their biopsy findings. Tsuji et ~1.‘~ found 70 per cent of 62 biopsy specimens from 34 hospitalized SC1 men “showed spermatogenesis to be more or less damaged.” The number of men demonstrating these changes was not given. Leriche et al. I3 observed that 50 per cent of their biopsy specimens showed an absence or arrest of spermatogenesis, but did not give the number of biopsies performed. They did claim that of 7 men with cauda equina lesions, all had normal spermatogenesis. It is difficult to draw substantive conclusions from these pieces of information. A lack of a standard method of analysis or comparison to control subjects makes comparison of these studies difficult. The majority of these SC1 men were hospitalized and may have had medical complications seen less frequently today. Nevertheless, neither Bors et uZ.~ nor Stemmerman et al.” were able to correlate the medical condition with the biopsy findings. In addition, theylOJ1 could not correlate the biopsy findings with the level of lesion. Few other authorsr2J3 have attempted these correlations, and those who have did not substantiate their findings. Most testicular biopsy specimens demonstrate

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159

TABLE

Series Mizutani

Hormones Evaluated

N

Subjects Lesion Duration Level

Ages (Yrs.)

4-167m

57 18-66 X-51

18 UMN 33 LMN

T

50

25 Cervical 6m-21y 18 Thoracic 7 Lumbar Ce-L1 7w-18y

Kikuchi et aZ.ls FSH, LH, (1976) T, Ez, and HCG stim. Morley et aLzl LH-RH stim. (1979) HCG stim.

?

15 21-41

18 19-45 C5-L1 and 70

LH-RH stim. 15 18-66 Hayes et aLz2 LH, FSH, T,PRL X-40.5 (1979) Naftchi et al.23 Acute and 20 19-40 chronic X-25 (1980) changes in LH, FSH, T Cortes-Gallegos FSH, LH, PRL, 10 12-48 et aZ.24(1981) T, DHT, A

10 quads 10 paras

1_3m-30y X-8. ly Varied as per study

Presence of Other Medical Conditions Medication No gynecomastia; otherwise not mentioned ?

?

Gynecomastia (2)

None for prior 10 days No anabolic steroids

?

No gynecomastia; normal renal and hepatic function; no premorbid hypogonadism ? ?

group

C5-L1

l-79m

No endocrine disease and normal renal function and U/A

LH = luteinizing hormone; E D = estradiol; HCG LHRH = luteinizing hormone releasing hormone;

abnormalities in spermatogenesis varying from absence of spermatids to complete tubular fibrosis. The Leydig and Sertoli cells appear to be normal; however, there may be hyperplasia, or a paucity of the Leydig cells.s*eJ3 It may be that light microscopy is inadequate to examine these cells. Hypothalamic-Pituitary-Testes

4w-19y

C5-L2

KEY: T = testosterone; FSH = follicle-stimulating hormone; gonadotropin; PRL = prolactin: DHT = dihvdrotestosterone: iears; qua-& = quadriplegia; paras = paraplkgia.

Axis

Since spermatogenesis is dependent on a functioning and intact hypothalamic-pituitarytesticular axis, several researchers have attempted to evaluate its function in SC1 men. Earlier investigators examined the urinary excretion of hormones.9J4 As blood level measurements of hormones are more precise than urinary level measurement, only the findings of more recent examiners will be reviewed. Testosterone

In 1972, Mizutani et aE.15 examined blood testosterone levels and testicular volume in 51 SC1 men. The population characteristics can be seen in Table II. These measurements were compared with those in control subjects. No significant difference in mean testosterone values was

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evaluations of SCI men

T

et a1.15

(1972) Phelps et aZ.le (1983)

Studies of endocrine

II.

2

= human chorionic m = months, y =

seen between SC1 men and control subjects. The mean testicular volume in SC1 men was lower than the mean volume in control subjects although not significantly. No correlation was found between testosterone levels and level or duration of lesion in SC1 men. In 1983 Phelps et all6 measured the blood levels of testosterone and sex steroid-binding protein and calculated free testosterone levels in 50 SC1 men (Table II). No significant difference in the total blood testosterone levels was seen between the cervical and thoracic groups, and each group’s levels fell within normal adult male limits. When the lumbar and thoracic groups were combined, the total testosterone values were significantly greater than those of the cervical group. No comparison with control subjects was made regarding this finding. However, there was no significant difference in levels of sex steroid-binding protein and calculated free testosterone between the quadriplegic and paraplegic groups. Attempting to evaluate the acute changes in testosterone levels following a cervical SCI, Claus-Walker et a1.l’ divided their data into four periods: (1) onset of injury to eight weeks,

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(2) nine to thirty weeks, (3) nine to eighteen months, and (4) over eighteen months. Stating only that their subjects had complete physiologic cervical cord transections and were without acute medical complications, they obtained blood testosterone levels from 20, 24, 10, and 8 subjects, respectively, for each period. Comparing the testosterone values to controls, they discovered that the quadriplegics had significantly lower testosterone values during all four periods. The testosterone values during periods 3 and 4 in the subjects, however, were significantly higher than those of period 1. They noted that testosterone values below 4 mg/ml were associated with periods of obvious stress (acute urinary tract infection, skin surgery) and postulated that decreased testosterone levels may be related to increased circulatory epinephrine.

In the first attempt to evaluate plasma gonadotropins in SC1 men, Kikuchi et al.‘* measured plasma FSH, LH, testosterone, and estradiol (E,) in 15 SC1 men and the response of testosterone to exogenous human chorionic gonadotropin (HCG) in 5 SC1 men (Table I). These values were compared with those of agematched control subjects. In their abstract they state that normal basal levels of these hormones were found in 14 of the 15 men. In the text, however, they give results for only 6 of the 15 men. Five of 5 men tested demonstrated a normal testosterone response to HCG. One man showed elevated basal levels of LH and FSH with normal levels of testosterone and Ez. The discrepancy between information in the text and the abstract faults this otherwise well-controlled study. Normal basal levels of FSH, LH, and testosterone may be seen even in the presence of impaired spermatogenesis. A more sensitive test of testicular damage is the measurement of the response of FSH and LH to exogenous LHRH.1g.20 Morley et al. in 1979,21 reported on the gonadotropin response to LH-RH in 18 men with paraplegia, 17 secondary to trauma, and 1 with tuberculosis (Table II). Testicular biopsies were performed on 7 men and testosterone responsiveness to HCG was measured in 8 men. Morley et al. 21 discovered impaired spermatogenesis with normal Leydig cells in three of seven biopsies. Normal basal testosterone levels were seen in all 18 men and testosterone responsiveness to HCG was normal in the 8 men

tested, 2 of whom had abnormal findings on biopsies. Five of the 18 men demonstrated exaggerated LH and FSH responses to LH-RH stimulation, and 13 had normal responses. Hayes et a1.22 used the LH-RH stimulation test in 13 SC1 men and 2 men with paraplegia secondary to a tumor (Table II). Basal FSH, LH, testosterone and prolactin (PRL) levels, and FSH and LH response to LH-RH was determined. They discovered elevated basal FSH and LH in 8 and 9, respectively. The response of FSH and LH to LH-RH was elevated in 14 and 9 men, respectively, Normal PRL and testosterone levels were seen in 15 and 12 men, respectively, with 3 showing slightly subnormal testosterone values. Specific values were not provided for each subject; therefore, no correlations could be made. This study demonstrated only that in these 15 paraplegic men, most or all had normal basal testosterone and PRL levels and most demonstrated exaggerated LH and/or FSH kinetics. Naftchi et al. in 1980,23 evaluated the acute and chronic changes in FSH, LH and testosterone in SC1 men. In 10 paraplegics and 10 quadriplegics plasma FSH, LH, and testosterone levels were determined weekly for four months beginning one week post injury (Table II). These values also were determined once in 10 ycung chronic (1 to 6 years post injury) paraplegic and 10 chronic quadriplegic subjects. Comparing the findings to age-matched controls they discovered significantly lower testosterone values for six weeks post injury in paraplegics and for the entire four months post injury in quadriplegics. The mean testosterone values in chronic paraplegics and quadriplegics were within normal limits. Serum FSH and LH values were significantly lower for two weeks post injury in paraplegics and for three and sixteen weeks post injury, respectively, in quadriplegics. Average serum FSH and LH values in chronic paraplegics and average FSH values in chronic quadriplegics was below that of controls. One acute paraplegic was excluded from the analysis since his FSH and LH levels were three times above controls with a low testosterone. In 1981 Cortes-Gallegos et aZ.24 attempted to correlate FSH, LH, PRL, testosterone, dihydrotestosterone (DHT), and androstenedione (A) values in 10 complete SC1 men with the duration of lesion (Table II). Two subjects who had not achieved sexual maturation were excluded from the analysis. They discovered a

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significant linear correlation between time elapsed after trauma and testosterone and DHT levels. FSH and LH levels were markedly elevated in all 8 men while A and PRL levels were within normal limits. No correlation with duration of lesion was seen with these levels. Analysis of Endocrine

Findings

A critical evaluation of these studies reveals a marked heterogeneity of population samples and sophistication of experimental design. Table II indicates that the subject population was generally well described except a few failed to state completeness of lesion.8x15J8,21No study described a random selection method and not all SC1 syndromes were secondary to trauma. Little to no mention of the concurrent medical status of the subjects was made in these studies. Only Kikuchi et aZ.ls attempted to control for the effects of medications on his subjects while the majority did not even mention patients’ medications. In the analysis of the data, not all examiners utilized a control group, and the majority obtained only a single sample of blood for analysis. This latter fact could significantly affect LH evaluations because of its varying pulsatile release. Finally, only in two studies did they attempt to correlate hormonal findings with a testicular biopsy.g,21 Despite these differences, some generalizations can be made when these studies are analyzed as a group: (1) plasma testosterone levels are normal in a large majority of SC1 men, but there may be acute depressions following SC1 trauma, most notably in quadriplegics; there appears to be a linear correlation between time elapsed after trauma and testosterone and DHT levels; (2) response of testosterone to HCG is adequate; (3) SC1 men have normal E2, A, and PRL levels; (4) normal or elevated basal FSH levels with a possible acute depression following SC1 exist; (5) normal or elevated basal LH levels with possible acute depression following SC1 and possible chronic depression in quadriplegics exist; and (6) responsiveness of LH and FSH to LH-RH is normal or exaggerated. These generalizations suggest several conclusions. Normal or elevated basal LH and FSH levels and their normal or exaggerated responsiveness to LH-RH indicate a functioning hypothalamic-pituitary axis in SC1 men. Normal testosterone levels and its adequate response to HCG indicate functioning Leydig cells with an adequate Leydig cell reserve. Elevated LH basal levels and/or hyper-responsiveness to LH-

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RH may indicate some mild Leydig cell dysfunction in some SC1 men. The elevated basal FSH levels and/or FSH hyper-responsiveness to LH-RH in many SC1 men demonstrate that the brunt of testicular damage is on the seminiferous tubules. This is confirmed by biopsy findings. The acute hormonal depressions may reflect a stress-induced state. After examining acute testosterone changes in quadriplegics, ClausWalker et aZ.17 concluded that alteration in steady state hormonal secretion is not a direct result of the quadriplegia, but instead, of the original nervous system trauma and the lifestyle changes that result. The work of Naftchi et aZ.23 implies that these stresses are more profound in quadriplegics compared with paraplegics and hence the more prolonged reduction in testosterone FSH, and LH values in the former. Exogenous stress affects LH-RH release25 and therefore could diminish the output of FSH and LH. Sufficient evidence exists suggesting that infertility in SC1 men is a result of primary testicular damage, most of which occurs to the seminiferous tubules and hence spermatogenesis. Acutely following spinal cord injury, however, physical and psychologic stressors might depress the hypothalamic-pituitary-testicular axis and secondarily alter spermatogenesis. Primary Causes of Impaired Spermatogenesis Stemmerman et al.” believed that the possible factors for tubular degeneration could be classified into three categories: systemic, neurogenie, and 1oca1.25-2g Systemic Spinal cord injury may be associated with malnutrition, anemia, chronic infectious processes, and secondary parenchymatous changes such as atrophic pyelonephritis and amyloid disease which are, when associated with marked debility, commonly associated with testicular atrophy.’ The febrile state, stress, anxiety, and emotional tension may temporarily depress sperm production.25 Two research groupseJ1 found no correlation between testicular biopsy abnormalities and general systemic factors such as nutrition, renal infection or calculosis, decubitus ulcers, or other sources of infection. It is, therefore, unlikely that these factors are a direct cause of impaired spermatogenesis, but they may be contributory.

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Neurogenic

The human testicles located in the scrotum are on average 2.2% cooler than the intra-abdominal temperature. 25 Elevated temperatures, either from a febrile state or local elevations, can affect the seminiferous tubules and/or the epididymis, impairing spermatogenesis and/or causing abnormal sperm morphology.28,29 The Leydig cells are unaffected by the temperature changes and continue to produce testosterone. If the temperature is diminished, the maturation arrest of spermatogenesis can be reversed in three weeks. When Bors et al9 examined testicular biopsies in 34 SC1 men in 1949, they believed that the less damaged testes were consistently associated with the lower level injuries. Postulating that disruption of sympathetic fibers resulted in hyperemia and hen’ce hyperthermia of the testes of SC1 men, he used crude sweating tests to evaluate the function of the sympathetic system. Using an arbitrarily measured bar graph to compare level of sweating, level of lesion, and biopsy grade, he concluded “that extent of sweating coincided with the more nearly normal testicular structure found in patients with injuries at or below Tii.” Comarr and Bors’O several years later were unable to confirm these findings in 25 SC1 men. Morales and Hardin in 195826 measured scrotal and subcutaneous thigh and arm temperatures in 29 SC1 men and control subjects using a hypodermic thermistor. They also measured testicular temperatures in 19 of these SC1 men. Pain prevented measurement of testicular temperature in 10 SC1 men and the control subjects. They determined that in the SC1 men, the subcutaneous temperature below the level of lesion remains essentially unaltered as evidenced

by similar thigh and arm measurements. The scrotal temperature was less than that in the thigh in both paraplegics and normal subjects, suggesting no difference in scrotal thermal environment between the groups. Finally, they found testicular temperatures to be slightly higher than the scrotal temperatures of SC1 men; a relationship, they say, that was found in normal men by other researchers. They concluded that scrotal hyperthermia does not develop in paraplegic men. Using a mercury-in-glass thermometer and scrotal invagination technique, Brindley30 determined the deep scrotal temperature, which approximates testicular temperature, in several SC1 men. In 23 apyrexial SC1 men and 13 control subjects, deep scrotal temperatures were measured when the subject had been sitting still, fully clothed for at least twenty minutes in an environmentally controlled room. He discovered that the mean deep scrotal temperature of the SC1 men was significantly greater than that of the control subjects. No correlation between level of lesion and scrotal temperature could be made. In a different group of 21 apyrexial SC1 men and 14 control subjects, the deep scrotal temperatures were measured while the subjects were in bed at night. Brindley30 found that the mean temperature in the paraplegics (35.67 “C) was not significantly different from that of controls (35.55 “C) . Brindley suggests that temperature differences seen in subjects while sitting may be a result of the paraplegic lifestyle instead of neurogenic factors. By using himself as an experimental subject, Brindley demonstrated that walking and running further lower scrotal temperature; therefore, the average daily scrotal temperature of paraplegics is probably greater than observed. Urinary tract infection (UTI) occurs at some point in the life of most SC1 men. Every UT1 in the male is accompanied by infection of the glandular tubules of the prostate and often can lead to epididymitis. 31 The semen of men with evidence of prostatic inflammatory changes often demonstrates lower sperm counts and motility indices than in those men without infection.32 Epididymitis might impair fertility as a result of ductal blockage” or as a result of concomitant inflammatory changes of the testes impairing spermatogenesis.25 Two groups of researchersgJ1 were unable to correlate testicular biopsy findings with the incidence of UTI, prostatitis, or epididymitis. Both admit, however,

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Little evidence exists to claim or disclaim that neurogenic factors play a role in causing testicular atrophy. One researcher offers indirect evidence of a direct neural link between the hypothalamus and the gonads.27 Tsuji et ~1.‘~ believed that a close correlation between the ability to detect gonadal pain and less severe testicular damage on biopsy existed, but their findings did not have statistical validity. Stemmerman et al.” were unable to correlate the level of lesion with testicular damage on biopsy. Using hormonal parameters, several investigatorssJ5,21 were unable to correlate testicular damage with level of lesion.

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that these factors may play subsidiary roles in impairing spermatogenesis. Brindley2 postulated that nondrainage of the male reproductive tract due to prolonged continence of sperm was a contributory factor in the poor quality of semen in paraplegic men. Several researchers have seen improvements in the quantity and quality of spermatozoa in SC1 men after repeated ejaculations, but this is an inconsistent finding.2*5J Francois et al. 5 believed that repeated ejaculations were “bringing about a wakening of the spermatogenesis.” Kuntz33 demonstrated in animal models that obstruction of the vas deferens is followed by degeneration of the testicular germinal epithelium. In up to 70 per cent of vasectomized men, antibodies against sperm have been demonstrated that impair spermatogenesis directly or immobilize mature spermatozoa.34 No attempts to measure antisperm antibody titers in SC1 men have been made. However, in testicular biopsy specimens of 2 SC1 men, Kikuchi et al. l8 demonstrated minimal IgG staining about the seminiferous tubules in one and moderate IgA staining of the spermatogonia in the other. Although one biopsy specimen showed normal spermatogenesis and both were obtained from men with scrotal hydroceles, this study raises the question of autoimmunity as a cause of infertility in SC1 men. Future Research As methods of stimulating ejaculation in SC1 men become more sophisticated, safer, and simpler to use,35-37evaluating the spermatozoa obtained will become easier. Future research should be directed toward identifying the factors responsible for the poor quality semen seen in SC1 men. Using well-controlled studies, attempts are needed to correlate spermatozoa quantity and quality with seminal biochemical parameters, infections of the genitourinary tract, plasma hormone levels, testicular biopsy findings, scrotal temperatures, and antisperm antibody titers. The effects of the initial trauma and stress of SC1 and of repeated ejaculatory stimulations on seminal and hormonal parameters and spermatogenesis also need to be evaluated. Conclusion The semen obtained from SC1 men often show decreased numbers of motile sperm with increased numbers of abnormal forms. Testicu-

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lar biopsy specimens often reveal impaired spermatogenesis of varying severity to be the major abnormality. Ductal blockage secondary to recurrent genitourinary infections also may result in poor quality semen. Hormonal evaluations indicate an intact hypothalamic-pituitarytesticular axis and reflect primary testicular failure, with the most damage occurring to the seminiferous tubules. Primary causes of impaired spermatogenesis can be classified into systemic, neurogenic or local groups. Causes implicated in SC1 infertility include poor nutrition, local testicular temperature elevations, recurrent genitourinary infections, and nondrainage of the reproductive tract. Most of these causes are preventable or may be treatable. A clearer understanding of the pathophysiology of infertility in SC1 men will enable improvement in the presently poor prognosis for fatherhood. 1333 Moursund Avenue Houston, Texas 77030 References 1. Talbot HS: The sexual function in paraplegia, J Urol 73: 91 (1955). 2. Brindley GS: Electroejaculation: its technique, neurological implications and uses, J Neurol Neurosurg Psychiatry 44: 9 (1981). 3. Griffith ER, Tomko MA, and Timms RJ: Sexual function in spinal cord injured patients, a review, Arch Phys Med Rehabi154: 539 (1973). 4. David A, Ohry A, and Rozin R: Spinal cord injuries: male infertility aspects, Paraplegia 15: 11 (1977-78). 5. Francois N, et al: Electroejaculation of a complete paraplegic followed by pregnancy, Paraplegia 16: 248 (1978-79). 6. Spira R: Artificial insemination after intrathecal injection of neostigmine in a paraplegic, Lancet 1: 670 (1956). 7. Thomas RJS, McLeish G, and McDonald IA: Electroejaculation of the paraplegic male followed by pregnancy, Med J Aust 2: 798 (1975). 8. Horne HW, Paul1 DP, and Monro D: Fertility studies in the human male with traumatic injuries of the spinal cord and cauda equina, N Engl J Med 239: 959 (1948). 9. Bors E, Engle ET, Rosenquist RC, and Hollinger VH: Fertility in paraplegii males: a preliminary report of endocrine studies. 1 Clin Endocrinol Metab 10: 381 (1950). 16. Comarr AE, and Bors E: Spermatocystography in patients with spinal cord injury, J Urol 73: 172 (1955). 11. Stemmerman GN, Weiss L, Averbach 0, and Friedman M: A study of the germinal epithelium in male paraplegics, Am J Clin Path01 20: 24 (1950). 12. Tsuji I, Nakajima F, Morimoto J, and Nounaka Y: The sexual function in patients with spinal cord injury, Urol Int 12: 270 (1961). 13. Leriche A, et ~2: Histological and hormonal testicular changes in spinal cord patients, Paraplegia 15: 274 (1977-78). 14. Cook AW, and Lyons HA: Urinary excretion of 17-ketosteroids in tetraplegic and paraplegic patients, US Armed Forces Med J 1: 583 (1950). 15. Mizutani S, Sonoda T, Matsumoto K, and Iwasa K: Plasma testosterone concentration in paraplegic men, J Endocrinol 54: 363 (1972). 16. Phelps 6, et al: Sexual experience and plasma testosterone

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levels in male veterans after spinal cord injury, Arch Phys Med Rehabil 64: 47 (1983). 17. Claus-Walker J, Scurry M, Carter RE, and Campos RJ: Steady state hormonal secretion in traumatic quadraplegia, J Clin Endocrinol Metab 44: 530 (1977). 18. Kikuchi TA, Skowsky WR, El-Toraei I, and Swerdloff R: The pituitary-gonadal axis in spinal cord injury, Fertil Steril 27: 1142 (1976). 19. Gray P, Franken DR, Slabber CF, and Potgeiter GM: A comparison of endocrine function and semen analysis in fertile and subfertile men, Andrologia 13: 260 (1981). 20. Negro-Vilar A, and Lumpkin MD: Inhibin: Central and peripheral effects to regulate follicle-stimulating hormone secretion, in Nemo-Vilar A (Ed): Male Reoroduction and Fertilitv. ,, New York, Raven Press, i98’1. A 21. Morley JE, et al: Testicular function in patients with spinal cord damage, Horm Metab Res 11: 679 (1979). 22. Hayes PJ, et al: Testicular endocrine function in paraplegic men, Clin Endocrinol 11: 549 (1979). 23. Naftchi NE, Viau AT, Sell GH, and Lowman EW: Pituitary-testicular axis dysfunction in spinal cord injury, Arch Phys Med Rehabil 61: 402 (1980). 24. Cortes-Gallegos V, & al: Pituitary-testes relationship in paraplegic men, J Androl 2: 326 (1981). . 25. Amelar RD. and Dubin L: Other factors affecting male infertility, in Amelar RD, Dubin L, and Walsh PC (Eds): Male Infertility, Philadelphia, W.B. Saunders Co, 1977, pp 69-102. 26. Morales PA, and Hardin J: Scrotal and testicular temperature studies in paraplegics, J Urol 79: 972 (1958).

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27. Gerendai I, and Halaoz B: Participation of a pure neuronal mechanism in the control of gonadal functions, Andrologia 13: 275 (1981). 28. Afzelius BA: Why man but not the shrew has a scrotum, in Bierich JR and Giarok A: Cryptorchidism, London, Academy Press, 1979, pp 57-61. 29. Glover TD, and Young DH: Temperature and the production of spermatozoa, Fertil Steril 14: 441 (1963). 30. Brindley GS: Deep scrotal temperature and the effect on it of clothing, air temperature, activity, posture and paraplegia, Br J Urol 54: 49 (1982). 31. Comhaire F: Diagnosis and treatment of male adnexitis in relation to infertility, in Negro-Vilar A (Ed): Male Reproduction and Fertlity, New York, Raven Press, 1981, pp 265-272. 32. Abyholm T, An andrological study of 51 fertile men, Int J Androl 4: 646 (1981). 33. Kuntz A: Degenerative changes in the seminal epithelium and associated hyperplasia of the interstitial tissue in mammalian testis, Endocrinology 5: 190 (1921). 34. Rumke PH: Immunopathological implications of the cryptorchid testes, in Bierich JR, and Giarola A (Eds): op Cit.“8 pp 159-174. 35. Guttman L, and Walsh JJ: Prostigmin assessment test of fertility in spinal man, Paraplegia 9: 39 (1970). 36. Bensman A, and Kottke FJ: Induced emission of sperm utilizing electrical stimulation of the seminal vesicles and vas deferens, Arch Phys Med Rehabil 47: 436 (1966). 37. Martin DE, et al: Initiation of erection and semen release by rectal probe electrostimulation, J Ural 129: 637 (1983).

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