Male Infertility Following Spinal Cord Injury

ABSTRACT

Ejaculatory dysfunction and poor semen quality are responsible for male infertility following spinal cord injury (SCI). Techniques which have been used to obtain semen include intrathecal neostigmine, subcutaneous physostigmine, direct aspiration of sperm from the vas deferens, vibratory stimulation and electroejaculation. Vibratory stimulation and electroejaculation are most widely used in the United States and have a 50–90% success rate at obtaining semen. Poor semen quality following SCI has been attributed to stasis of semen, testicular hyperthermia, urinary tract infections, sperm contact with urine, possible changes in the hypothalamic-pituitary axis, chronic use of various medications and possible sperm antibodies. The Outlook for having a child following SCI continues to improve with advancements in obtaining and processing sperm and assisted reproductive technologies.     

Semen Quality of Spinal Cord Injured Men is Better When Obtained by Vibratory Stimulation Versus Electroejaculation

Purpose

Most spinal cord injured men require assisted ejaculation procedures to obtain semen, and the majority can achieve this result by vibratory stimulation or electroejaculation. We determined if semen obtained by vibratory stimulation differed in quality from that obtained by electroejaculation.

Materials and Methods

Between subjects and within subjects designs were used. Of 77 spinal cord injured men 23 underwent vibratory stimulation only, 44 electroejaculation only and 10 both procedures. Antegrade, retrograde and total ejaculates were analyzed in each subject for total sperm count, percent motile sperm and percent sperm with rapid linear motion.

Results

With vibratory stimulation compared to electroejaculation the percent motile sperm and percent sperm with rapid linear motion were significantly greater, whereas total sperm count was similar, in the antegrade specimens and total ejaculates. This finding was true for different groups of subjects as well as within a group of the same subjects.

Conclusions

Semen obtained by vibratory stimulation is of better quality than that obtained by electroejaculation. In medical practices that include assisted ejaculation of spinal cord injured men, we recommend obtaining a specimen by vibratory stimulation. If that method fails electroejaculation should be performed.     

Electroejaculation Versus Vibratory Stimulation in Spinal Cord Injured Men: Sperm Quality and Patient Preference

Purpose

We compared semen quality and patient preference between penile vibratory stimulation and electroejaculation in spinal cord injured men.

Materials and Methods

We treated 11 spinal cord injured men with penile vibratory stimulation and electroejaculation in random order. End points examined were semen analysis, sperm functional assessment, and patient pain scores (1 to 10) and preferred procedure. Differences between the procedures were determined with the paired Student t test.

Results

There was no difference in antegrade sperm count but penile vibratory stimulation specimens had greater motility (26.0 versus 10.7%), viability (25.2 versus 9.7%) and motile sperm count (185.0 x 10⁶ versus 97.0 x 10⁶). The retrograde sperm count was greater (but not significant) in electroejaculation patients. The total (antegrade plus retrograde) and motile sperm counts were not different. There was no difference in immunobead test (all negative), cervical mucus penetration or sperm penetration assay, although the percent hamster egg penetration approached significance (53.7% for penile vibratory stimulation versus 22.1% for electroejaculation, p = 0.06). There was no difference in the peak blood pressures and no complications were noted. Pain scores were significantly greater for electroejaculation compared to penile vibratory stimulation (5.2 versus 1.7, respectively). All patients preferred penile vibratory stimulation.

Conclusions

There was a slight advantage in sperm quality and a high patient preference in favor of penile vibratory stimulation. Penile vibratory stimulation should be attempted first to induce ejaculation in spinal cord injured men, with electroejaculation reserved for failures.     

Seminal vesicle aspiration in spinal cord injured men: insight into poor sperm quality

PURPOSE: In men with spinal cord injury poor quality semen is seen when performing electroejaculation and penile vibratory stimulation. We determined whether sperm stasis within the seminal vesicles is a potential cause of this problem. MATERIALS AND METHODS: Seminal vesicle aspiration was performed immediately before electroejaculation or penile vibratory stimulation in men with aspermia secondary to spinal cord injury. Sperm count and quality of seminal vesicle aspiration and subsequent ejaculation were compared with historical ejaculated counts, ultrasound findings and patient characteristics. RESULTS: Mean total number of right plus left seminal vesicle sperm plus or minus standard deviation was 511 +/- 960 x 10(6). Mean total number of sperm obtained by seminal vesicle plus electroejaculation or penile vibratory stimulation was 918 +/- 1,261 x 10(6). Average motility and viability of the seminal vesicle aspirated sperm were 1.3 and 3.2%, respectively. Average motility of the ejaculated sperm was 26.4% after seminal vesicle aspiration versus 16.3% in previous ejaculation induction procedures performed in the same patients. Seminal vesicle aspirated sperm represented 66% of the total number of sperm obtained during the session and was equal to 49% of the sperm obtained at previous electroejaculation or penile vibratory stimulation sessions. The period of abstinence correlated only with ejaculate count (simple regression p = 0.009). No other clinical characteristics had any effect on sperm count or quality. CONCLUSIONS: Large numbers of poor quality sperm are present within the seminal vesicles of spinal cord injured men and these sperm comprise a large portion of the specimens collected by electroejaculation or penile vibratory stimulation. This phenomenon is independent of the period of abstinence, implicating disordered storage of sperm due to spinal cord injury rather than infrequent ejaculation. The large number of senescent sperm within the seminal vesicles appears to be a primary cause of poor sperm quality in spinal cord injured men.     

Effects of spinal cord injury on semen parameters

OBJECTIVE/BACKGROUND: Neurogenic reproductive dysfunction in men with spinal cord injury (SCI) is common and the result of a combination of impotence, ejaculatory failure, and abnormal semen characteristics. It is well established that the semen quality of men with SCI is poor and that changes are seen as early as 2 weeks after injury. The distinguishing characters of poor quality are abnormal sperm motility and viability. In the majority of the men with SCI, the sperm count is not abnormal. We elaborate on the effects of the SCI on semen parameters that may contribute to poor motility and poor viability. METHODS: Review. DESIGN: PubMed and MEDLINE databases were searched using the following key words: spinal cord injuries, fertility, sexual dysfunction, and spermatogenesis. All literature was reviewed by the team of authors according to the various stages of sperm development and transport in the male reproductive cycle. FINDINGS: The cause of asthenozoospermia appears to be multifactorial. CONCLUSION: Current literature does not support the preeminence of a single factor relating to neurogenic reproductive dysfunction in men with SCI. After SCI, there is ample evidence of disturbance of sperm production, maturation and storage, and transport due to an abnormal neuroendocrine milieu. Semen quality seems to be primarily affected by changes to the seminal plasma constituents, type of bladder management, and the neurogenic impairment to the ejaculatory function. Further focused and structured studies are required.     

Treatment of anejaculation with electroejaculation.

Male infertility caused by anejaculation is common after spinal cord injury (SCI) and following retroperitoneal lymph node dissection (RPLND) for testicular cancer. Other conditions sometimes associated with neurogenic ejaculation loss are diabetes mellitus, multiple sclerosis, extensive pelvic surgery and adult myelodysplasia. Primary absence of ejaculation also has been described. Few treatment options exist for these patients, if they wish to father a child. With electroejaculation (EEJ), or the low-current stimulation of the ejaculatory organs via a rectal probe, emission of semen can be initiated in these men. In non-SCI-patients EEJ requires general anaesthesia. The collected semen is washed and the motile sperm fraction isolated before artificial insemination (AI) of the partner. At the University of Michigan 198 men have been treated between 1986 and December 1991. An ejaculate could be obtained from nearly all patients. A major obstacle to success is the severe asthenozoospermia and the poor functional quality of the obtained sperm samples. This can be caused by the EEJ-technique itself, as well as by the long anejaculatory status. A semen sample with at least 10 million progressively motile sperm cells, useful for AI, was obtained in 75% of the SCI men and in 87% of the men following RPLND. In the couples wishing insemination, 49 pregnancies were induced, accounting for an overall pregnancy rate of 35% per couple. Thirty five healthy babies have been born. Only three complications were encountered. At Hannover Medical School only few patients have been stimulated to date. We could obtain an adequate sperm sample for AI from all of them. No complications were seen. As the first couple has just entered the phase of AI with husband sperm, an analysis of these results would be premature. Electroejaculation combined with artificial insemination is an efficient and safe treatment of male infertility due to neurogenic anejaculation.     

Predictors of success in electroejaculation of spinal cord injured men

Rectal probe electroejaculation was attempted in 48 spinal cord injury men and greater than 10 million sperm were obtained in 71%. Patient age and interval since injury had no effect on outcome. The best performance was seen in thoracic paraplegics and in those using intermittent catheterization for bladder management. Indwelling urethral catheters and high pressure reflex voiding had a negative impact on electroejaculation results.     

Abdominal electrical stimulation rescues failures to penile vibratory stimulation in men with spinal cord injury: a report of two cases

Most men with spinal cord injury are anejaculatory. To retrieve their semen for insemination, the procedure of penile vibratory stimulation is recommended over electroejaculation. Some men with spinal cord injury, however, cannot ejaculate with penile vibratory stimulation. We present 2 cases in which a simple, over-the-counter abdominal muscle stimulator rescued failures to penile vibratory stimulation. Use of this safe, easy, and inexpensive method may prevent some patients from undergoing more expensive, more invasive sperm retrieval methods such as electroejaculation or surgical sperm retrieval from the testis or epididymis.     

Testis biopsy findings in the spinal cord injured patient

PURPOSE: Azoospermia after electroejaculation in spinal cord injured men may be due to testicular failure or obstruction. These men can initiate pregnancy with assisted reproductive techniques, such as intracytoplasmic sperm injection, but only if sperm are present in the testis biopsy. We analyzed the histopathology of testis biopsies from spinal cord injured men and assessed whether patient factors were predictive of testis biopsy pathology. MATERIALS AND METHODS: A total of 50 paraplegic men undergoing testis biopsy were divided into 2 groups based on normal or abnormal testis histopathology. Patient age, post-injury years, level of lesion, hormonal status and semen analysis results were compared. RESULTS: Spermatogenesis was normal in 28 of the 50 patients. Hypospermatogenesis was exhibited in 15, maturation arrest at the spermatid stage in 6 and maturation arrest at the spermatocyte stage in 1 of the 22 abnormal cases. Nevertheless, mature sperm were identified in 43 of 50 biopsies (normal spermatogenesis and hypospermatogenesis). Men with normal spermatogenesis had better forward progression of sperm and a higher testosterone-to-luteinizing hormone ratio. Otherwise, there was no statistically significant correlation between study variables and testis biopsy results. No factors were predictive of testis biopsy histopathology. CONCLUSIONS: The documentation of mature sperm in 43 of 50 biopsies from spinal cord injured patients suggests that a high rate of sperm retrieval is possible using testicular sperm extraction if sperm cannot be retrieved from the ejaculate. With intracytoplasmic sperm injection techniques the majority of spinal cord injured men retain fertility potential, even if azoospermic following electroejaculation.     

PREDICTORS OF NECROSPERMIA IN MEN WITH SPINAL CORD INJURY

Purpose

We identify predictors of the lowest yield of dead sperm in ejaculates of men with spinal cord injury.

Materials and Methods

The percentages of dead immotile sperm and dead total sperm were compared in 141 spinal cord injured and 52 normal men. Predictors of necrospermia investigated in spinal cord injured men included specimen collection by vibratory stimulation versus electroejaculation, residence of sperm in antegrade versus retrograde specimens and level of injury.

Results

Spinal cord injured subjects had a significantly higher percentage of dead sperm in the immotile fraction and total specimen than control subjects. The percentage of dead sperm was lower in antegrade versus retrograde specimens and in specimens produced by vibratory stimulation versus electroejaculation. There was no difference in the percentage of dead sperm by level of injury.

Conclusions

Of the parameters evaluated only method and type of specimen collection were predictive of the degree of necrospermia in men with spinal cord injury. Level of injury was not predictive. The ratio of dead-to-live immotile sperm in spinal cord injured men was double that in normal men, indicating a pathological mechanism for sperm cell death.     

Antisperm antibodies in seminal plasma of spinal cord-injured men.

Central to the problem of reproductive rehabilitation of spinal cord-injured men treated by assisted ejaculatory techniques is the consistent observation of deficient semen quality. Most studies have reported asthenospermia despite the presence of normal sperm concentration in most men undergoing these procedures. To date little attention has been given to the incidence and relevance of sperm autoimmunity in this group. In 9 anejaculatory spinal cord-injured men, electroejaculation was performed. Antegrade ejaculates were obtained in 7 men and analyzed. Mean sperm antegrade concentration was 74.4 +/- 113 x 10(6)/mL with a mean motile sperm concentration of 28.6 +/- 54.0 x 10(6)/mL. Enzyme-linked immunosorbent assay (ELISA)-determined antisperm antibody response was positive in the seminal plasma of 5 of 7 patients. Because of the disproportionately high incidence of an immunologic factor in men with neurogenic infertility, sperm autoimmunity should be considered among the important causes underlying their seminal dysfunction.     

Male sexual dysfunction and infertility associated with neurological disorders

Normal sexual and reproductive functions depend largely on neurological mechanisms. Neurological defects in men can cause infertility through erectile dysfunction, ejaculatory dysfunction and semen abnormalities. Among the major conditions contributing to these symptoms are pelvic and retroperitoneal surgery, diabetes, congenital spinal abnormalities, multiple sclerosis and spinal cord injury. Erectile dysfunction can be managed by an increasingly invasive range of treatments including medications, injection therapy and the surgical insertion of a penile implant. Retrograde ejaculation is managed by medications to reverse the condition in mild cases and in bladder harvest of semen after ejaculation in more severe cases. Anejaculation might also be managed by medication in mild cases while assisted ejaculatory techniques including penile vibratory stimulation and electroejaculation are used in more severe cases. If these measures fail, surgical sperm retrieval can be attempted. Ejaculation with penile vibratory stimulation can be done by some spinal cord injured men and their partners at home, followed by in-home insemination if circumstances and sperm quality are adequate. The other options always require assisted reproductive techniques including intrauterine insemination or in vitro fertilization with or without intracytoplasmic sperm injection. The method of choice depends largely on the number of motile sperm in the ejaculate.     

Anejaculation following spinal cord injury does not induce sperm-agglutinating antibodies

Antisperm antibodies were tested for by the MAR-test and the tray agglutination test in 16 men with spinal cord injury. None of these men could ejaculate without artificial methods. Seven men ejaculated externally by vibrator stimulation or electroejaculation, while seven exhibited retrograde ejaculation; in two cases no semen was obtained. Sperm density in the external ejaculations was high (average = 405 x 10(6)/ml), with 10-45% motility. None of these 16 men had antisperm antibodies. This result indicates that anejaculation and sperm retention in men with spinal cord injury, even of 30 years duration, does not result in antisperm antibody formation.     

Semen retrieval in men with spinal cord injury is improved by interrupting current delivery during electroejaculation.

PURPOSE: Based on the findings of a previous study of pressure differentials in the external and internal urinary sphincters during electroejaculation we determined whether semen retrieval in men with spinal cord injury would be improved by interrupting current delivery during electroejaculation. MATERIALS AND METHODS: We tested continuous versus interrupted current delivery in the same group of 12 men with spinal cord injury. Patients underwent a mean of 4 randomly assigned continuous or interrupted trials 4 to 8 weeks apart. Antegrade and retrograde semen parameters were analyzed per trial. Multiple trials of each method per patient were averaged and semen parameters by the continuous and interrupted methods were compared. RESULTS: Interrupted delivery resulted in significantly greater mean antegrade volume versus continuous delivery (2 versus 0.9 cc). In this antegrade fraction mean total sperm count and mean total motile sperm was higher for interrupted (130 million and 35 million) versus continuous (79 million and 26 million, respectively) delivery. The mean retrograde total sperm count was 4-fold higher for continuous (120 million) versus interrupted (29 million) delivery. In the total ejaculate of the combined antegrade and retrograde fractions the mean total sperm count and mean total motile sperm were not significantly different for the 2 methods. CONCLUSIONS: Each method resulted in a similar mean total sperm count and total motile sperm in the total ejaculate but a higher proportion of sperm was found in the antegrade fraction using the interrupted method. We recommend interrupted current delivery as the technique of choice when electroejaculation is performed to obtain sperm for fertilization.     

The effect of semen quality of the electrical current and heat generated during rectal probe electroejaculation.

Rectal probe electroejaculation is effective in procuring sperm from spinal cord injured patients with ejaculatory incompetence. The seminal quality in these patients is usually suboptimal and the motility is almost always low. We conducted an in vitro experiment to determine whether the heat and current generated during rectal probe electroejaculation impaired sperm motility or forward progression, or if the poor semen quality is the result of existing testicular dysfunction.     

Antibiotic susceptibility of urogenital microbial profile of infertile men in South‐eastern Nigeria

Male factors are known to contribute significantly to the infertility problem. The urogenital bacteria profile and semen quality were investigated among 160 men attending infertility clinics in South‐eastern Nigeria. Both semen and urine samples were obtained from each subject and analysed according to standard techniques. A total of 16 (10%) had bacterial infection in their semen samples and individuals of older age groups were significantly affected (χ² = 23.18, P < 0.05). Urinary tract infection (UTI) was observed in 30.6% of subjects, with the highest rate occurring among men aged 36–40 years, but the difference was not significant (χ² = 7.62, P > 0.05). A total of 33.8% of the men had semen volume less than 2 ml per ejaculate, 33.8% also recorded total sperm count of <40 × 10⁶ ml^?1, while 36.3% recorded sperm motility <50%. Fifty‐three individuals (33.1%) had suboptimal sperm morphology (<60%), with the men aged 46–50 years old significantly affected (χ² = 13.03, P < 0.05). All the individuals with bacterial infection in semen also had UTI and suboptimal semen parameters. The commonest bacterial isolates were Proteus species, Staphylococcus aureus and Escherichia coli, which were resistant to most of the antibiotics assessed.     

Erectile function and male reproduction in men with spinal cord injury: a review

Spinal cord injury (SCI) in men results in defects in erectile function, ejaculatory process and male reproductive potential. There are alterations in the capacity of men with SCI to achieve reflexogenic, psychogenic and nocturnal erections. The sexual function in different stages after SCI and the types of erections depend mainly on the completeness of the injury and the level of neurological damage. Furthermore, most of the SCI men demonstrate defects concerning the entrance of semen into the posterior urethra and the expulsion of the semen through the penile urethra and the urethral orifice. In addition, SCI men develop defects in the secretory function of the Leydig cells, Sertoli cells and the male accessory genital glands. The overall result is a decreased quality of the semen is recovered either with penile vibratory stimulation (PVS) or with electroejaculation. Nowadays the therapeutic andrological approach of SCI men focuses on achievement of erectile function, recovery of spermatozoa and assisted reproductive technology. The first line of therapy recommended for infertility in SCI men is collection of semen via PVS with concomitant evaluation of total motile sperm yields for assisted conception which may include intravaginal insemination, intrauterine insemination, or in vitro fertilisation/intracytoplasmic sperm injection. Patients failing PVS may be referred for electroejaculation or surgical sperm retrieval.     

Sperm cryopreservation and assisted reproductive technology outcome in patients with spinal cord injury

This study aimed to describe spinal cord injured patients’ semen characteristics before and after cryopreservation, and assisted reproductive technology cycles outcome compared to the infertile population. Data about sperm analysis and assisted reproductive technology (ART) cycles outcomes for 78 men with spinal cord injury referred for sperm cryopreservation between 1998 and 2013 were retrospectively analysed and compared with a reference group consisting of every Intra Cytoplasmic Sperm Injection (ICSI) cycle performed in our in vitro fertilization unit over the 2009–2014 period. Semen was collected by penile vibratory stimulation (PVS), electroejaculation or via testis biopsies. Fresh and frozen semen parameters and ART outcomes with frozen‐thawed sperm were measured. Patients were divided into three groups according to the sperm retrieval methods: 37 electroejaculations, 37 PVSs and four surgical sperm retrievals. Low ejaculate volume was observed in 33% of the patients, and oligozoospermia in 37% of the patients. Specimens from 77 of the patients contained motile sperm and were therefore frozen for future use. There was no statistical difference for any of the fresh semen parameters between all groups. Twenty of them underwent ICSI leading to five live births, while four underwent intrauterine insemination. ART with frozen‐thawed spermatozoa can provide men with SCI with comparable results as in the infertile population.     

Side effects of intradetrusor botulinum toxin injections on ejaculation and fertility in men with spinal cord injury: preliminary findings

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? The beneficial effect of intradetrusor botulinum toxin (BT) injections on hyperactive bladders in individuals with spinal cord injury is known from the literature, but its potential effect on ejaculation and fertility through diffusion is not. As BT injection paralyses the bladder muscle, it may also paralyse the muscular envelopes of the adjacent reproductive organs and lead to potential negative side effects, which have not been studied yet. This study provides preliminary data on the potential negative side effects of BT injections on semen volume and retrograde ejaculation, as well as some potential beneficial effects on semen quality.

OBJECTIVE

• ? To investigate the effect of botulinum neurotoxin A on ejaculation potential and fertility. Intradetrusor injection of botulinum neurotoxin A is most commonly used nowadays to treat overactive bladder in patients with spinal cord injury (SCI).

PATIENTS AND METHODS

• ? Retrospective analyses were carried out of 11 patients with complete lesions from C5 to T6 who had received botulinum (BT) injections for their overactive bladder and who had undergone ejaculation tests before and after BT treatment.

RESULTS

• ? BT treatment was found effective in improving bladder function in up to 85% of the cases.
• ? While no patients maintained natural ejaculation following their SCI, BT treatment was found to increase the incidence of retrograde ejaculation (vibrostimulation) in 46% of cases and to diminish semen volume in 77% of cases, from an average of 1.8 mL to 1 mL.
• ? Semen quality was slightly improved following BT treatment, sperm mobility increased in 67% of cases, sperm vitality in 50% and semen culture improved in 43%.

CONCLUSIONS

• ? BT treatment has beneficial and detrimental effects on ejaculation function. The detrimental effects involve retrograde ejaculation and reduced semen volume, which are explained by the spread of toxin to the bladder neck, reducing its tonus, and to the smooth muscle sexual accessory organs, reducing the strength of their contraction.
• ? The beneficial effects are explained by the reduced contamination of the semen by urinary infection, which may improve spermatogenesis and subsequent semen quality.
• ? The results are discussed in terms of their clinical implications and advice to patients.

     

Canine model of infertility after spinal cord injury: time course of acute changes in semen quality and spermatogenesis

PURPOSE: We established a canine model of subfertility after spinal cord injury and examined the time course of acute changes in semen quality and spermatogenesis after spinal cord injury. MATERIALS AND METHODS: Seven dogs underwent surgical T7 spinal cord injury. Six dogs were used as controls. Electroejaculation and testicular fine needle aspiration were performed at baseline and twice weekly for 3 weeks after spinal cord injury. Semen quality change was examined by standard semen analysis. Spermatogenesis was assessed by flow cytometry of testicular fine needle aspiration in all dogs as well as by testicular histology at study conclusion in 4 controls and 4 spinal cord injured dogs. RESULTS: No significant changes in spinal cord injured dogs were noted before 3 weeks after injury. From baseline to 3 weeks after injury certain changes were evident in spinal cord injured dogs. Mean antegrade sperm motility decreased from 62.9% to 20.1% (p = 0.008), mean total sperm (antegrade plus retrograde total sperm) decreased from 423 to 294 x 106 which was not statistically significant, and the incidence of testicular haploid cells decreased from 75.6% to 48.3% (p = 0.028). No significant change in any parameter was present in control dogs. The mean number of mature spermatids per cross-sectional tubule on final testicular histology was significantly decreased in spinal cord injured dogs compared with controls (13.6 versus 43.9, p = 0.02). CONCLUSIONS: In the canine model tested the dogs readily survived spinal cord injury, electroejaculation was effective for obtaining ejaculate and fine needle aspiration allowed serial examination of spermatogenesis. Three weeks after spinal cord injury but not before 3 weeks sperm motility and spermatogenesis were significantly decreased. However, at the same point this decrease in spermatogenesis was not yet reflected in the total ejaculated sperm count.