Emad Ibrahim

Treatment for Ejaculatory Dysfunction in Men With Spinal Cord Injury: An 18-Year Single Center Experience

PURPOSE In what is to our knowledge the largest study of its kind to date we retrospectively reviewed the records of 3,152 semen retrieval procedures in a total of 500 men with spinal cord injury to make recommendations to the medical field on ejaculatory dysfunction treatment in this specialized patient population. MATERIALS AND METHODS We retrospectively studied data from 1991 to 2009 in the Miami Project to Cure Paralysis male fertility research program at our institution. We assessed the semen retrieval success rate and semen quality. RESULTS Of the 500 men 9% could ejaculate by masturbation. Penile vibratory stimulation was successful in 86% of patients with a T10 or rostral injury level. Electroejaculation was successful in most cases of failed penile vibratory stimulation. Sperm were obtained without surgical sperm retrieval, in 97% of patients completing the treatment algorithm. Total motile sperm counts exceeded 5 million in 63% of cases. CONCLUSIONS Sperm can be easily obtained nonsurgically from most men with spinal cord injury. Sufficient sperm are available for simple insemination procedures. A treatment algorithm based on our experience is presented.

Treatment of infertility in men with spinal cord injury

Most men with spinal cord injury (SCI) are infertile. Erectile dysfunction, ejaculatory dysfunction and semen abnormalities contribute to the problem. Treatments for erectile dysfunction include phosphodiesterase type 5 inhibitors, intracavernous injections of alprostadil, penile prostheses, and vacuum constriction devices. In anejaculatory patients who wish to father children, semen retrieval is necessary. Penile vibratory stimulation is recommended as the first line of treatment. Patients who fail penile vibratory stimulation can be referred for electroejaculation. If this approach is not possible, prostate massage is an alternative. Surgical sperm retrieval should be considered as a last resort when other methods fail. Most men with SCI have a unique semen profile characterized by normal sperm count but abnormally low sperm motility. Scientific investigations indicate that accessory gland dysfunction and abnormal semen constituents contribute to the problem. Despite abnormalities, sperm from men with SCI can successfully induce pregnancy. In selected couples, the simple method of intravaginal insemination is a viable option. Another option is intrauterine insemination. The efficacy of intrauterine insemination increases as the total motile sperm count inseminated increases. In vitro fertilization and intracytoplasmic sperm injection are options in cases of extremely low total motile sperm count. Reproductive outcomes for SCI male factor infertility are similar to outcomes for general male factor infertility.

Pregnancy outcomes by intravaginal and intrauterine insemination in 82 couples with male factor infertility due to spinal cord injuries

OBJECTIVE To report our centers pregnancy rates (PR) by intravaginal insemination (IVI) or intrauterine insemination (IUI) in 82 couples with male partners with spinal cord injuries. DESIGN Retrospective analysis. SETTING Major medical center. PATIENT(S) Male patients with spinal cord injuries and their female partners. INTERVENTION(S) Intravaginal insemination and IUI. MAIN OUTCOME MEASURE(S) Pregnancy and live birth outcomes. RESULT(S) Overall, 31 of the 82 couples (37.8% PR) achieved 39 pregnancies. Sperm were obtained by masturbation, penile vibratory stimulation, or electroejaculation in 4 men (4.9%), 42 men (51.2%), and 36 men (43.9%), respectively. Intravaginal insemination, performed mostly at home by selected couples, was undertaken in 45 couples, 17 of whom (37.8% PR) achieved 20 pregnancies. Intrauterine insemination was performed in 57 couples, 14 of whom (24.6% PR) achieved 19 pregnancies, with a cycle fecundity of 7.9%. Eighteen and 21 live births occurred by IVI and IUI, respectively. CONCLUSION(S) The methods of IVI and IUI are reasonable options for this patient population. These methods warrant consideration before proceeding to assisted reproductive technologies (ART).

Randomized Multicenter Phase II Trial Comparing Two Schedules of Etirinotecan Pegol (NKTR-102) in Women With Recurrent Platinum-Resistant/Refractory Epithelial Ovarian Cancer

PURPOSE Etirinotecan pegol (NKTR-102) is a unique, long-acting topoisomerase-I inhibitor with prolonged systemic exposure to SN38 (7-ethyl-10-hydroxycamptothecin), the active metabolite of irinotecan. This randomized phase II trial investigated two dosing schedules of etirinotecan pegol in patients with platinum-resistant/refractory ovarian carcinoma. PATIENTS AND METHODS A total of 71 eligible patients were randomly assigned to receive etirinotecan pegol 145 mg/m(2) every 14 or 21 days until progression or unacceptable adverse events (AEs). The primary end point was objective response rate (ORR) by RECIST (version 1.0). Secondary end points included response by Gynecologic Cancer Intergroup criteria, duration of ORR, progression-free survival (PFS), and overall survival (OS). RESULTS The overall confirmed ORR was 20% (95% CI, 10% to 30%): 20% for once every 14 days, and 19% for once every 21 days. Median response duration was 4.1 months for once every 14 days and 4.0 months for once every 21 days. Median PFS for every 14 and every 21 days was 4.1 and 5.3 months, respectively, and median OS was 10.0 and 11.7 months, respectively. Etirinotecan pegol was well tolerated, with the most common grade 3 to 4 AEs being dehydration (24%) and diarrhea (23%). Diarrhea, dehydration, nausea, and neutropenia were less frequent with the schedule of once every 21 days than with that of once every 14 days. CONCLUSION Both schedules of etirinotecan pegol showed activity in patients with heavily pretreated ovarian cancer, with encouraging ORR and PFS rates. The schedule of once every 21 days was better tolerated and had slightly longer PFS and OS rates. The treatment schedule of etirinotecan pegol 145 mg/m(2) once every 21 days was selected for the expanded phase II study and is preferred for future phase III studies. These findings provide support to directly compare etirinotecan pegol versus one of the approved drugs (eg, pegylated liposomal doxorubicin or topotecan) in platinum-resistant ovarian cancer.

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.

Semen Quality Remains Stable During the Chronic Phase of Spinal Cord Injury: A Longitudinal Study

PURPOSE In a longitudinal study we examined changes in semen quality with time during the chronic phase of spinal cord injury. MATERIALS AND METHODS Included in this study were 87 men with spinal cord injury who underwent 2 or more semen retrieval procedures with a minimum of 3 years between the first and last procedures. Patients were selected from our database of 500 with spinal cord injury who were volunteers enrolled in the Male Fertility Research Program of the Miami Project to Cure Paralysis from January 1, 1991 through April 31, 2009. Semen was collected by masturbation, penile vibratory stimulation or electroejaculation. Semen analysis was done according to WHO criteria. We used a statistical generalized linear mixed model to analyze changes in sperm concentration, total sperm count, total motile sperm count and sperm motility with time. RESULTS Mean patient age was 30.1 years (range 16 to 48) and mean time after injury at the initial sperm retrieval procedure was 7.1 years (range 1 to 26). Sperm concentration decreased slightly with time but all other parameters were unchanged, including total sperm count, indicating a stable, null pattern in measures with time. CONCLUSIONS Semen quality does not show clinically significant progressive changes during years after injury in men with spinal cord injury. This information is relevant for urologists who counsel these patients on family planning. Also, routine sperm freezing for fertility preservation is not indicated in this patient population.

Involvement of the inflammasome in abnormal semen quality of men with spinal cord injury

OBJECTIVE To study the mechanism leading to elevated semen cytokines in men with spinal cord injury (SCI) and to understand if inflammasome pathways are involved in this process. To investigate inflammasome components and end-product cytokines in semen of SCI and control subjects. DESIGN Prospective study. SETTING Major university medical center. PATIENT(S) Men with and without SCI (n = 28 per group). INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Seminal plasma concentrations of caspase-1, interleukin (IL) 1β, and IL-18 were quantified by ELISA. Caspase-1 in sperm fractions and apoptosis-associated speck-like protein containing a caspase activation and recruitment domain (ASC) in seminal plasma and sperm fractions were identified by Western blot. Localization of proteins in sperm was accomplished by immunocytochemistry. RESULT(S) ASC, caspase-1, IL-1β, and IL-18 concentrations were elevated in the seminal plasma of SCI subjects compared with control subjects. ASC and caspase-1 were elevated in sperm cells of SCI subjects. Immunocytochemistry revealed that ASC was located in the acrosome, equatorial segment, and midpiece, and caspase-1 in the midpiece. CONCLUSION(S) This study provides the first evidence of ASC in human semen and demonstrates the involvement of inflammasome proteins in semen of men with SCI. These findings suggest an immunologic basis for abnormal semen quality in men with SCI.

Advances in the management of infertility in men with spinal cord injury

Couples with a spinal cord injured male partner require assisted ejaculation techniques to collect semen that can then be further used in various assisted reproductive technology methods to achieve a pregnancy. The majority of men sustaining a spinal cord injury regardless of the cause or the level of injury cannot ejaculate during sexual intercourse. Only a small minority can ejaculate by masturbation. Penile vibratory stimulation and electroejaculation are the two most common methods used to retrieve sperm. Other techniques such as prostatic massage and the adjunct application of other medications can be used, but the results are inconsistent. Surgical sperm retrieval should be considered as a last resort if all other methods fail. Special attention must be paid to patients with T6 and rostral levels of injury due to the risk of autonomic dysreflexia resulting from stimulation below the level of injury. Bladder preparation should be performed before stimulation if retrograde ejaculation is anticipated. Erectile dysfunction is ubiquitous in the spinal cord injured population but is usually easily managed and does not pose a barrier to semen retrieval in these men. Semen analysis parameters of men with spinal cord injury are unique for this population regardless of the method of retrieval, generally presenting as normal sperm concentration but abnormally low sperm motility and viability. When sperm retrieval is desired in this population, emphasis should be placed on initially trying the simple methods of penile vibratory stimulation or electroejaculation before resorting to more advanced and invasive surgical procedures.

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.

A Minority of Men With Spinal Cord Injury Have Normal Semen Quality—Can We Learn From Them? A Case-control Study

OBJECTIVES To determine factors that may help predict normal semen quality in this unique population of male patients, we examined our large database of men with spinal cord injury (SCI). Most men with SCI have abnormal semen quality; however, a small minority retain normal semen parameters. METHODS A retrospective analysis was performed on semen retrieval procedures administered between 1991 and 2009 in 500 men with SCI. From those men, we selected subjects who underwent at least 1 penile vibratory stimulation, electroejaculation, or masturbation procedure resulting in antegrade ejaculation (n = 400). Cases were defined as men who, according to World Health Organization criteria, had normal semen volume, sperm concentration, sperm motility. Control subjects (CR) were defined as all remaining subjects. Risk factors for normal semen parameters were evaluated by conditional logistic regression analysis. RESULTS Of the 400 subjects evaluated, only 30 had normal semen parameters. These 30 CS subjects were matched to 120 CR subjects. Analysis of risk factors revealed that incomplete lesion of the spinal cord (ASIA B to D) was significantly associated with the presence of normal sperm parameters (odds ratio 2.6 [95% confidence interval 1.1-6.1], P = .028). CS subjects were also more likely to be able to collect their samples via masturbation (odds ratio 2.7 [95% confidence interval 1.1-7.1], P = .037). Other risk factors evaluated were not predictive of normal semen parameters. CONCLUSIONS This retrospective, case-control study, performed on a large group of subjects, showed that completeness of SCI is an important risk factor influencing semen quality.