Comparison of three methods of penile vibratory stimulation for semen retrieval in men with spinal cord injury.

STUDY DESIGN: Prospective, three-way crossover design. OBJECTIVE: Penile vibratory stimulation (PVS) is recommended as the first line of treatment for semen retrieval in anejaculatory men with spinal cord injury (SCI). This study compared ejaculatory success rates and patient preference for three methods of PVS within the same group of men with SCI. SETTING: Major medical university. METHODS: Fifteen men with SCI each received three methods of PVS. Method 1 (M1): applying one FertiCare Personal device to the dorsum or frenulum of the glans penis; Method 2 (M2): 'sandwiching' the glans penis between two FertiCare devices; Method 3 (M3): sandwiching the glans penis between the two vibrating surfaces of the Viberect-X3 device. The order of M1, M2 and M3 was varied to control for sequencing effects. Following each PVS trial, subjects rated their experience on a questionnaire with scaled responses. RESULTS: Ejaculation success rates were high for each method; however, ejaculation latency was significantly longer with M3 compared with M1 or M2. In survey questions about patient preference, there were no significant differences between M1 and M2. In contrast, M3 was rated lower than M1 and M2 in patient preference. Semen collection may be more difficult with the Viberect device. CONCLUSIONS: On the basis of these findings, we recommend attempting PVS with one FertiCare device. If that fails, use two FertiCare devices. Although the Viberect-X3 was preferred less by patients, it had similar efficacy as the Ferticare vibrator(s) and may be suitable for home use by some patients.

Neutralization of ASC improves sperm motility in men with spinal cord injury.

STUDY QUESTION: Does neutralization of apoptosis-associated speck-like protein containing a caspase activation and recruitment domain (ASC) improve sperm motility in men with spinal cord injury (SCI)? SUMMARY ANSWER: Neutralization of ASC improves sperm motility in men with SCI. WHAT IS KNOWN ALREADY: Semen of men with SCI contains normal sperm concentrations but abnormally low sperm motility. Inflammatory cytokines, activated via the inflammasome complex, are contributory. A key component of the inflammasome is ASC. STUDY DESIGN, SIZE, DURATION: This prospective study included semen samples collected from 32 men with SCI. PARTICIPANTS/MATERIALS, SETTING, METHODS: At a major university medical center, untreated semen was compared with semen treated with anti-ASC polyclonal antibody. Semen treated with IgG was used as a control. MAIN RESULTS AND THE ROLE OF CHANCE: Addition of anti-ASC polyclonal antibody to semen significantly increased mean sperm motility from 11.5% (95% CI, 6.3-16.7) to 18.3% (95% CI, 11.8-24.8). Improvements were most pronounced in the subgroup whose starting motility ranged between 6 and 40%. In this subgroup, the mean sperm motility improved from 13.3% (95% CI, 9.3-17.3) to 23.9% (95% CI, 14.7-23.0). Sperm motility did not improve after treatment with IgG. LIMITATIONS, REASONS FOR CAUTION: This study is limited by the small sample size as this is a rare population. WIDER IMPLICATIONS OF THE FINDINGS: Blockade of the inflammasome via treatment with anti-ASC improved sperm motility in men with SCI. In doing so, this treatment significantly increased their total motile sperm count. This is the first study to demonstrate that interference with the inflammasome improves sperm motility in men with SCI. This treatment has potential as a therapeutic intervention. STUDY FUNDING/COMPETING INTERESTS: This study was funded by the Craig H. Neilsen Foundation, Grant # 224598, the University of Miami Miller School of Medicine and the Miami Project to Cure Paralysis, Miami, FL, USA. R.W.K. and J.P.d.R.V. hold a patent for the treatment of inflammation after central nervous system injury using antibodies against inflammasome proteins. The other authors have no conflicts of interest to declare.

Safety and efficacy of a new device for inducing ejaculation in men with spinal cord injuries.

STUDY DESIGN: Prospective case series. OBJECTIVES: Male infertility is a common sequela of spinal cord injury (SCI). Fatherhood is a goal in this group of young patients; however, most are anejaculatory. Penile vibratory stimulation is recommended as the first line of treatment for this condition. Our study evaluated the safety and efficacy of a new device designed to induce ejaculation in these patients. SETTING: The Miami Project to Cure Paralysis, Miami, FL, USA. METHODS: The Viberect-X3 (Reflexonic, Frederick, MD, USA) was applied to 30 consecutive anejaculatory men with SCI whose level of injury was T10 and rostral. RESULTS: The ejaculatory success was 77% (23/30). No adverse events occurred, and there were no malfunctions of the device. CONCLUSION: In this first report on the efficacy of the Viberect-X3 for treatment of anejaculation in men with SCI, we conclude that the device is safe and effective for inducing ejaculation in men with SCI. Recommendation of the Viberect-X3 versus other devices intended for this purpose should not be made until randomized controlled trials are performed.

Semen quality in ejaculates produced by masturbation in men with spinal cord injury.

STUDY DESIGN: Retrospective study. OBJECTIVES: Most men with spinal cord injury are anejaculatory. Much has been reported about their semen quality collected by penile vibratory stimulation and electroejaculation (EEJ). What is not well-described is the nature of semen quality in SCI patients who can ejaculate by masturbation. This study was performed to understand the degree to which their semen quality differed from that of anejaculatory SCI patients versus that of healthy non-SCI control subjects. SETTING: University of Miami. METHODS: Retrospective chart review of Male Fertility Research Program participants from 1991 to 2011. RESULTS: Of 528 SCI subjects, 444 met inclusion criteria of completing an algorithm in which ejaculation occurred by masturbation (n=43), PVS (n=243), or EEJ (n=158). Sperm motility was higher in the SCI-masturbation group (36.9%) than the PVS group (25.9%, P<0.001) or EEJ group (15.0%, P<0.001), but lower compared with a control group of 61 non-SCI healthy men who collected their semen by masturbation (58.0%, P<0.001). The SCI-masturbation group had similar antegrade sperm concentration (83.3×10(6) cc(-1)) as the PVS group (77.4×10(6) cc(-1)) and control group (82.0×10(6) cc(-1)), but higher than the EEJ group (49.8×10(6) cc(-1), P<0.001). The SCI-masturbation group had significantly more men with incomplete injuries (84%) than the PVS group (54%, P<0.01) or EEJ group (41%, P<0.001). CONCLUSION: This is the first report focusing on semen quality obtained by masturbation in men with SCI. Sperm motility was higher in men with SCI who could, versus could not, ejaculate by masturbation. Completeness of injury may contribute to this difference.

Anejaculatory infertility due to multiple sclerosis.

There are few reports of pregnancy outcomes in couples with anejaculatory infertility secondary to multiple sclerosis and no longitudinal reports of semen quality in this population. We report our experience with one such case. The couple achieved two live births from spermatozoa obtained with electroejaculation: the first by intrauterine insemination and the second by in vitro fertilisation with intracytoplasmic sperm injection of donor oocytes. Linear regression analysis showed no progressive decline in semen parameters across 26 semen retrievals performed over 7.7 years. Years of disease do not appear to cause progressive decline in semen quality.

The choice of assisted ejaculation method is relevant for the diagnosis of azoospermia in men with spinal cord injuries.

STUDY DESIGN: Retrospective analysis of research data collected over >18 years at our center. OBJECTIVES: Examine results of repeated semen retrievals in men with spinal cord injury (SCI) who were initially found to be azoospermic. SETTING: Major university medical center. METHODS: Three different groups were analyzed in this study. Group 1 (n = 15) consisted of patients who were found to be azoospermic after the first ejaculation obtained by penile vibratory stimulation (PVS) and who had subsequent ejaculates obtained by PVS. Group 2 (n = 8) consisted of patients who were found to be azoospermic after the first ejaculation obtained by PVS and who had subsequent ejaculates obtained by electroejaculation (EEJ). Group 3 (n = 18) consisted of patients who were found to be azoospermic after the first ejaculation obtained by EEJ and who had subsequent ejaculates obtained by EEJ. RESULTS: In group 1 (PVS-PVS), the second ejaculate contained sperm in none of the 15 patients. In group 2 (PVS-EEJ), the second ejaculate contained sperm in three of eight patients. In group 3 (EEJ-EEJ), the second EEJ resulted in semen with sperm in 6 of 18 patients. In the 388 study subjects, the overall prevalence of azoospermia was 7.0%. CONCLUSION: In a study of a large group of subjects with SCI, the vast majority had normal sperm concentrations. In the minority who were azoospermic on their first ejaculate, and who were past the acute phase of injury, obtaining a second ejaculate by EEJ versus PVS may be a reasonable step before proceeding to surgical sperm retrieval.

Cytidine 3',5'-monophosphate phosphodiesterase: decreased activity in the regenerating and developing liver.

A decrease in the activity of the enzyme cytidine 3',5'-monophosphate (cyclic CMP) phosphodiesterase was noted in the regenerating liver of young rats as early as 8 hours after partial hepatectomy, with a maximum decrease occurring 12 hours after the surgery. In comparison, in old rats which showed a slower liver growth, the maximum decrease in the activity of cyclic CMP phosphodiesterase was smaller and occurred at a much later time (2 days after surgery). A similar decrease in the enzyme activity was observed in the fetal liver of guinea pigs. These findings suggest that regulation of tissue concentration of cyclic CMP may be crucial for the regeneration and development of the liver.

Male fertility following spinal cord injury: an update.

Spinal cord injury (SCI) occurs most often in young men at the peak of their reproductive health. The majority of men with SCI cannot father children naturally. Three major complications contribute to infertility in men with SCI: erectile dysfunction, ejaculatory dysfunction, and abnormal semen quality. Erectile dysfunction can be managed by regimens available to the general population, including oral administration of phosphodiesterase-5 (PDE-5) inhibitors, intracavernosal injections, vacuum devices, and penile prostheses. Semen may be obtained from anejaculatory men with SCI via the medically assisted ejaculation methods of penile vibratory stimulation (PVS) or electroejaculation (EEJ). Sperm retrieval is also possible via prostate massage or surgical sperm retrieval. Most men with SCI have abnormal semen quality characterized by normal sperm concentrations but abnormally low sperm motility and viability. Accessory gland dysfunction has been proposed as the cause of these abnormalities. Leukocytospermia is evident in most SCI patients. Additionally, elevated concentrations of pro-inflammatory cytokines and elevated concentrations of inflammasome components are found in their semen. Neutralization of these constituents has resulted in improved sperm motility. There is a recent and alarming trend in the management of infertility in couples with SCI male partners. Although many men with SCI have sufficient motile sperm in their ejaculates for attempting intrauterine insemination (IUI) or even intravaginal insemination, surgical sperm retrieval is often introduced as the first and only sperm retrieval method for these couples. Surgical sperm retrieval commits the couple to the most advanced, expensive, and invasive method of assisted conception: in vitro fertilization with intracytoplasmic sperm injection (IVF/ICSI). Couples should be informed of all options, including semen retrieval by PVS or EEJ. Intravaginal insemination or IUI should be considered when indicated.

Alterations in activities of cyclic nucleotide systems and in beta-adrenergic receptor-mediated activation of cyclic AMP-dependent protein kinase during progression and regression of isoproterenol-induced cardiac hypertrophy.

Initial and transient increases in the basal levels of cyclic GMP in the heart were noted prior to cardiac hypertrophy in rats administered isoproterenol. Increased levels of cyclic AMP-phosphodiesterase (in both the soluble and particulate fractions) and stimulatory modulator of cyclic GMP-dependent protein kinase, however, were associated with the progression, or the state, of cardiomegaly, with their levels returning to the control values upon regression of the hypertrophy. The levels of cyclic GMP phosphodiesterase in the soluble fraction were lower, whereas those in the particulate fraction were higher, in the hypertrophied heart than the control. In cardiac hypertrophy, the maximal activity ratio(--cyclic AMP/+cyclic AMP) of cyclic AMP-dependent protein kinase in the incubated minced heart caused by isoproterenol was lower, whereas the concentration of isoproterenol required to increase the activity ratio half-maximally was higher than controls; the reduced responsiveness to the drug, however, was reversed when the hypertrophy regressed. These observations, taken collectively, appear to suggest that the desensitization of the beta-adrenergic mechanism seen in the cardiac hypertrophy produced by repeated administration of isoproterenol is associated with adaptive modifications in certain parameters of the cyclic nucleotide systems.

Modified cyclic nucleotide systems in Morris hepatoma 3924A favoring expression of cyclic GMP effect.

Modifications in the cyclic nucleotide systems favoring the expression of cyclic GMP effects were found to occur in the transplanted fast-growing Morris hepatoma 3924A. These included: (a) a decreased level of cyclic GMP phosphodiesterase and an increased level of cyclic AMP phosphodiesterase; (b) a disproportionately increased level of cylic GMP-dependent protein kinase relative to that of cyclic AMP-dependent protein kinase; (c) a disproportionately increased level of stimulatory modulator of cyclic AMP-dependent protein kinase relative to that of inhibitory modulator of cyclic AMP-dependent protein kinase; and (d) an increased level of phosphoprotein phosphatase.

Midbrain lesions, dopamine and male sexual behavior.

Destruction of the medial preoptic area (MPOA) eliminates mating in male rats and this region is believed to play a major role in the control of male sexual behavior. Efferents from the MPOA pass through and/or terminate in 4 midbrain regions: the dorsolateral tegmentum (DLT), the central gray, and the A9 and A10 areas. The present study reports the effects of bilateral destruction of each of these midbrain regions on brain catecholamines and sexual behavior in male rats. DLT lesions eliminated mating, reproducing the effect of bilateral preoptic lesions. The sexual activity of males with central gray lesions was accelerated in the sense that the mounting rate for these males was significantly faster than for controls and lesioned males ejaculated more frequently and with shorter latencies than did controls. A9 lesions impaired mating--lesioned males mounted at a slower rate and ejaculated less frequently than controls. Males with A10 lesions took longer to re-initiate mating after an ejaculation than controls, but copulation per se (as reflected in mount rate, ejaculation frequency and latency to ejaculate) was not affected by A10 damage. Brain catecholamine levels were not affected by either DLT or central gray lesions. A9 lesions produced a significant depletion in neostriatal dopamine which was highly correlated with mount latency, mount rate, ejaculation latency and ejaculation frequency. A10 lesions produced a significant depletion of dopamine in the nucleus accumbens and cingulate cortex, but these effects were not significantly correlated with any measure of sexual behavior.

Anesthetic block of the dorsal penile nerve inhibits vibratory-induced ejaculation in men with spinal cord injuries.

OBJECTIVES: [corrected] We investigated which nerve pathways are necessary to achieve ejaculation using penile vibratory stimulation (PVS) in men with spinal cord injury (SCI). METHODS: Eight men with SCI were selected based on the presence of a bulbocavernosus reflex (BCR) and consistent antegrade ejaculation with PVS. Level of injury was cervical (4), upper thoracic (4), and lower thoracic (1). Mean age was 30.4 years (range 22 to 38). Usual responses to PVS included autonomic dysreflexia (4), erection (4), and consistent somatic responses such as abdominal contractions (8). Local anesthesia of the dorsal penile nerves (penile block) was achieved using 1% plain lidocaine injection. Effective penile block was confirmed by loss of the BCR. Two PVS ejaculation trials were performed: one trial during the penile block and one trial when the penile block had worn off. In 4 subjects, the bladder contents were analyzed for retrograde ejaculation. RESULTS: With the penile block, ejaculation was inhibited in 100% of the subjects. None of the bladder washings demonstrated sperm, indicating absence of retrograde ejaculation. None of the subjects exhibited their usual erectile response, somatic responses, or signs of autonomic dysreflexia. After the penile block wore off, PVS induced ejaculation in all subjects. If subjects usually had erection, somatic responses, or signs of autonomic dysreflexia, these also returned. CONCLUSIONS: Our data suggest that ejaculatory response to PVS in SCI men requires the presence of intact dorsal penile nerves.

Seminal reactive oxygen species and sperm motility and morphology in men with spinal cord injury.

OBJECTIVE: To assess the generation of reactive oxygen species and its relation to semen characteristics in men with spinal cord injury. DESIGN: Cross-sectional study. SETTING: Andrology laboratory at a tertiary care facility and research laboratory at a major medical center. PATIENT(S): Men with spinal cord injury and normal men. INTERVENTION(S): Collecting ejaculates from men with spinal cord injury by electroejaculation and vibratory stimulation and from normal men by masturbation. MAIN OUTCOME MEASURE(S): Measurement of reactive oxygen species before and after stimulation with 50 microM N-formyl-methionyl-leucylphenylalanine (FMLP) and 100 nM 12-myristate 13-acetate phorbol ester (PMA), white blood cell (WBC) concentration, sperm motility and morphology, and ejaculation method. RESULT(S): Compared with controls, levels of reactive oxygen species in men with spinal cord injury were significantly higher in unstimulated, f-MLP-stimulated, and PMA-stimulated specimens. The WBC concentration was significantly elevated in patients with spinal cord injury. Sperm motility in men with spinal cord injury was inversely related to the level of reactive oxygen species. The percentage of morphologically normal spermatozoa was significantly lower in men with spinal cord injury. Levels of seminal reactive oxygen species did not differ when comparing specimen type (antegrade versus retrograde) or method of ejaculation in men with spinal cord injury. CONCLUSION(S): Men with spinal cord injury had elevated levels of reactive oxygen species in their semen. Levels of reactive oxygen species were negatively correlated with sperm motility. Levels of reactive oxygen species were independent of the method of ejaculation or the type of specimen.

Scrotal and oral temperatures are not related to semen quality of serum gonadotropin levels in spinal cord-injured men.

Scrotal temperature, oral temperature, and the difference between oral and scrotal temperature were measured in spinal cord-injured subjects (SCI) and non-injured subjects as controls. We statistically correlated these measures to semen quality and serum gonadotropin levels in both groups. No difference was found between SCI and control subjects on any temperature measurement. Mean sperm motility, mean sperm morphology, and mean serum gonadotropin levels were significantly lower in SCI compared to control subjects, but these measures were not correlated to scrotal temperature, oral temperature, or the difference between oral and scrotal temperature in SCI or control subjects. These data indicate that: 1) there is not a generalized scrotal thermoregulatory dysfunction in SCI men; 2) scrotal temperature does not appear to contribute to poor semen quality in SCI men; and 3) elevated gonadotropin levels are not related to elevated scrotal temperatures in SCI men, as has been reported in non-injured, infertile men.

Semen of spinal cord injured men freezes reliably.

The objectives of the present study were to: 1) determine the effect of cryopreservation on the percent and the grade of motility of sperm from spinal cord injured (SCI) men and 2) determine which method of freezing yields the best post-thaw motility in sperm from SCI men. Antegrade semen samples were obtained from 9 SCI subjects and 10 age-matched healthy control subjects. Motility in fresh samples was determined and cryopreservative medium was added to each sample. Aliquots of each sample were frozen according to three methods: 1) liquid nitrogen vapor only (V); 2) vapor for 12 minutes followed by submersion into liquid nitrogen (V+N2); and 3) direct submersion into liquid nitrogen (N2). Samples were frozen for 1 week, then thawed. The post-thaw percent and grade of motility was determined. The mean percent motility of fresh samples for SCI subjects (21.0%) was significantly lower than for control subjects (55.7%). After thawing, the mean percent drop in motility for V, V+N2, and N2 for controls was 65.2%, 73.5%, and 79.4%, respectively, and for SCI subjects, it was 64.7%, 74.5%, and 81.6%, respectively. There was no statistically significant difference between control and SCI subjects by method of freezing. Vapor only as a freezing method was superior to all other methods for retention of sperm motility in both control and SCI subjects. We conclude that the semen of SCI men may be frozen reliably and that their sperm retain motility similar to that of normal men. Vapor only, being the most gentle method used, gives the best recovery of sperm motility in either group.

Brown-colored semen in men with spinal cord injury.

The interesting condition of brown-colored semen has often been observed during assisted ejaculation of men with spinal cord injury (SCI). This condition has not been reported in the literature, and its cause is unknown. To investigate this condition, the present study examined the incidence and quality of brown semen and its relationship to level of SCI, time since SCI, number of successive ejaculations, ejaculation frequency, and ejaculation method in a total of 664 semen specimens from 162 SCI men. In addition, a microscopic evaluation was performed on brown semen specimens from SCI men, not-brown specimens from SCI men, and normally colored specimens from normal men. The results showed that 27% of SCI subjects had brown semen on at least one ejaculation. There was no difference between men producing and men not producing brown semen in age, level of injury, or years postinjury. The duration of an ejaculation, number of successive ejaculations, and frequency of ejaculation were not associated with occurrence of brown semen. Sperm concentration and sperm motility were not significantly different in brown and not-brown specimens. Specimens from subjects who produced brown semen had similar pH but lower volume than specimens from subjects who did not produce brown semen. Brown semen had a thin consistency more often than not-brown semen. Brown specimens contained intact red blood cells (RBCs) and/or heme pigment more often than not-brown specimens; however, one half and one third of the specimens, respectively, contained neither RBCs nor heme pigment. The cause of brown semen is unknown but may relate to seminal-vesicle dysfunction.

Medial preoptic connections with the midbrain tegmentum are essential for male sexual behavior.

The medial preoptic area appears to play a major role in the control of sexual behavior. Efferents from the medial preoptic area course through the medial forebrain bundle to pass through and/or terminate in the dorsolateral and ventral tegmentum of the midbrain. Bilateral lesions of the dorsolateral tegmentum eliminate mating behavior in male rats, reproducing the effect of bilateral medial preoptic lesions. Sexual behavior is also eliminated when a preoptic lesion on one side of the brain is combined with a lesion of the dorsolateral tegmentum on the other side of the brain. In other words, asymmetric brain damage which bilaterally destroys the preoptic connections with the dorsolateral tegmentum eliminates male sexual behavior, and we conclude that the connections between these two regions are essential for copulation.

Male fertility following spinal cord injury: facts and fiction.

Although most spinal cord injuries (SCIs) occur to males of parenting age, myths abound as to whether men can biologically father children after SCI. Following SCI, most men experience impairments in erectile and ejaculatory function. Semen can be obtained from almost all men with SCI through the use of vibratory or electrical stimulation. Their ejaculates often have normal sperm counts but more immotile sperm than found in men without SCI. This condition does not seem to be caused by lifestyle factors (such as elevated scrotal temperature, ejaculation frequency, and method of bladder management) but may be related to factors within the seminal plasma. Sperm from men with SCI may be used in assisted reproductive techniques to attempt biological fatherhood. Health care providers, including physical therapists, should encourage men with SCI seeking biological fatherhood to be evaluated at a center dedicated to assisting men with SCI in this specialty area.

International standards to document remaining autonomic function after spinal cord injury.

STUDY DESIGN: Experts opinions consensus. OBJECTIVE: To develop a common strategy to document remaining autonomic neurologic function following spinal cord injury (SCI). BACKGROUND AND RATIONALE: The impact of a specific SCI on a person's neurologic function is generally described through use of the International Standards for the Neurological Classification of SCI. These standards document the remaining motor and sensory function that a person may have; however, they do not provide information about the status of a person's autonomic function. METHODS: Based on this deficiency, the American Spinal Injury Association (ASIA) and the International Spinal Cord Society (ISCoS) commissioned a group of international experts to develop a common strategy to document the remaining autonomic neurologic function. RESULTS: Four subgroups were commissioned: bladder, bowel, sexual function and general autonomic function. On-line communication was followed by numerous face to face meetings. The information was then presented in a summary format at a course on Measurement in Spinal Cord Injury, held on June 24, 2006. Subsequent to this it was revised online by the committee members, posted on the websites of both ASIA and ISCoS for comment and re-revised through webcasts. Topics include an overview of autonomic anatomy, classification of cardiovascular, respiratory, sudomotor and thermoregulatory function, bladder, bowel and sexual function. CONCLUSION: This document describes a new system to document the impact of SCI on autonomic function. Based upon current knowledge of the neuroanatomy of autonomic function this paper provides a framework with which to communicate the effects of specific spinal cord injuries on cardiovascular, broncho-pulmonary, sudomotor, bladder, bowel and sexual function.