Amateur vs Professional Users of the YO Home Sperm Test: An Assessment of Usability.

OBJECTIVE: To assess the accuracy of the YO home sperm test by real-world/amateur users. METHODS: This multisite study investigated whether amateur users could use the FDA-cleared YO Home Sperm Test to obtain accurate motile sperm concentration (MSC) results when compared to trained laboratory technicians. The qualitative MSC results of amateur and professional YO users were compared to each other as well as to the results of an established automated sperm quality analyzer (SQA-V) above and below a 6 m/mL MSC cut-off. RESULTS: This was a blinded, prospective study of 316 amateur users and 3 professional laboratory technicians across 3 study sites. Amateur vs Professional YO users demonstrated an accuracy of >97%. Qualitative results of amateurs and professionals vs SQA-V results showed a >95.7% accuracy. CONCLUSION: Amateur users with no prior training were able to follow the YO test directions to receive highly accurate qualitative motile sperm concentration (MSC) results. The YO test is user-friendly and can be used as an effective initial home screening tool to gain preliminary insight into the fertility status of the male in a real-world setting. Furthermore, the YO test results correlated with those obtained by the FDA-cleared SQA-V laboratory analyzer, confirming that the YO test delivers accurate MSC results in the hands of amateur users.

Male Reproduction in Spinal Muscular Atrophy (SMA) and the Potential Impact of Oral Survival of Motor Neuron 2 (SMN2) Pre-mRNA Splicing Modifiers.

Spinal muscular atrophy (SMA) is a neuromuscular disease caused by deletions or mutations in the survival of motor neuron 1 (SMN1) gene resulting in reduced levels of SMN protein. SMN protein is produced by cells throughout the body, and evidence suggests that low SMN protein can have systemic implications, including in male reproductive organs. However, a paucity of research exists on this important topic. This article will discuss findings from non-clinical studies on the role of SMN in the male reproductive system; additionally, real-world observational reports of individuals with SMA will be examined. Furthermore, we will review the non-clinical reproductive findings of risdiplam, a small-molecule SMN2 splicing modifier approved for the treatment of SMA, which has widespread distribution in both the central nervous system and peripheral organs. Specifically, the available non-clinical evidence of the effect of risdiplam on male reproductive organs and spermatogenesis is examined. Lastly, the article will highlight available capabilities to assess male fertility as well as the advanced reproductive technologies utilized to treat male infertility. This article demonstrates the need for further research to better understand the impacts of SMA on male fertility and reproduction.

Multicentric, prospective observational data show sperm capacitation predicts male fertility, and cohort comparison reveals a high prevalence of impaired capacitation in men questioning their fertility.

RESEARCH QUESTIONS: Can a previously defined relationship between sperm capacitation and the probability of a man generating pregnancy within three cycles, prospectively predict male fertility in diverse clinical settings? A second study asked, what is the prevalence of impaired sperm fertilizing ability in men questioning their fertility (MQF), and does this relate to traditional semen analysis metrics? DESIGN: In the multicentric, prospective observational study, data (n = 128; six clinics) were analysed to test a published relationship between the percentage of fertilization-competent, capacitated spermatozoa (Cap-Score) and probability of generating pregnancy (PGP) within three cycles of intrauterine insemination. Logistic regression of total pregnancy outcomes (n = 252) assessed fit. In the cohort comparison, Cap-Scores of MQF (n = 2155; 22 clinics) were compared with those of 76 fertile men. RESULTS: New outcomes (n = 128) were rank-ordered by Cap-Score and divided into quintiles (25-26 per group); chi-squared testing revealed no difference between predicted and observed pregnancies (P = 0.809). Total outcomes (n = 252; 128 new + 124 previous) were pooled and the model recalculated, yielding an improved fit (P < 0.001). Applying the Akaike information criterion found that the optimal model used Cap-Score alone. Cap-Scores were performed on 2155 men (with semen analysis data available for 1948). To compare fertilizing ability, men were binned by PGP (≤19%, 20-29%, 30-39%, 40-49%, 50-59%, ≥60%). Distributions of PGP and the corresponding Cap-Scores were significantly lower in MQF versus fertile men (P < 0.001). Notably, 64% of MQF with normal volume, concentration and motility (757/1183) had PGP of 39% or less (Cap-Scores ≤31), versus 25% of fertile men. CONCLUSIONS: Sperm capacitation prospectively predicted male fertility. Impaired capacitation affects many MQF with normal semen analysis results, informing diagnosis versus idiopathic infertility.

Paternal contribution to embryonic competence.

INTRODUCTION: The effect of paternal characteristics on embryo development and the outcome of preimplantation genetic testing for aneuploidy have not been extensively explored. This study investigates the association of sperm parameters, insemination, and extraction techniques, with the rate of embryo aneuploidy. This study sought to evaluate the association between male factor infertility and embryo aneuploidy. MATERIAL AND METHODS: Patients underwent in vitro fertilization using intracytoplasmic sperm injection, with preimplantation genetic testing for aneuploidy. Patients were divided into four groups by sperm parameters: Group A: oligozoospermia (sperm concentration <10 million, morphology > 4%); Group B: teratozoospermia (sperm concentration >10 million, morphology <4%); Group C: oligozoospermia and teratozoospermia (sperm concentration <10 million, morphology <4%); Group D: controls. Additionally, couples were divided into three categories by days of abstinence: Group A: <2; Group B: 2-7; and Group C: >7. RESULTS: A total of 4108 in vitro fertilization cycles with preimplantation genetic testing for aneuploidy were analyzed. After controlling for parental age and follicle count, the rate of embryo aneuploidy was not affected by duration of abstinence, sperm parameters, or the source of the sperm sample. CONCLUSIONS: Numerous factors related to sperm source and quality were evaluated, and a minimal influence on the rate of embryo aneuploidy was observed.

Male Oxidative Stress Infertility (MOSI): Proposed Terminology and Clinical Practice Guidelines for Management of Idiopathic Male Infertility.

Despite advances in the field of male reproductive health, idiopathic male infertility, in which a man has altered semen characteristics without an identifiable cause and there is no female factor infertility, remains a challenging condition to diagnose and manage. Increasing evidence suggests that oxidative stress (OS) plays an independent role in the etiology of male infertility, with 30% to 80% of infertile men having elevated seminal reactive oxygen species levels. OS can negatively affect fertility via a number of pathways, including interference with capacitation and possible damage to sperm membrane and DNA, which may impair the sperm's potential to fertilize an egg and develop into a healthy embryo. Adequate evaluation of male reproductive potential should therefore include an assessment of sperm OS. We propose the term Male Oxidative Stress Infertility, or MOSI, as a novel descriptor for infertile men with abnormal semen characteristics and OS, including many patients who were previously classified as having idiopathic male infertility. Oxidation-reduction potential (ORP) can be a useful clinical biomarker for the classification of MOSI, as it takes into account the levels of both oxidants and reductants (antioxidants). Current treatment protocols for OS, including the use of antioxidants, are not evidence-based and have the potential for complications and increased healthcare-related expenditures. Utilizing an easy, reproducible, and cost-effective test to measure ORP may provide a more targeted, reliable approach for administering antioxidant therapy while minimizing the risk of antioxidant overdose. With the increasing awareness and understanding of MOSI as a distinct male infertility diagnosis, future research endeavors can facilitate the development of evidence-based treatments that target its underlying cause.

Prophylactic sildenafil citrate improves select aspects of sexual function in men treated with radiotherapy for prostate cancer.

PURPOSE: We studied adjuvant daily sildenafil citrate during and after radiotherapy for prostate cancer for erectile function preservation. MATERIALS AND METHODS: We performed a randomized, prospective trial of 279 patients with localized prostate cancer treated with radiotherapy who received sildenafil citrate (50 mg daily) or placebo (2:1 randomization). Medication/placebo was initiated 3 days before treatment and continued daily for 6 months. Before therapy and 3, 6, 9, 12, 18 and 24 months after radiotherapy patients completed the IIEF questionnaire, including the erectile function domain, the I-PSS questionnaire and the RAND SF-36®. All IIEF domains were scored. RESULTS: At 12 months erectile function scores were better for sildenafil citrate than placebo (p = 0.018), 73% of patients on sildenafil citrate vs 50% on placebo had mild/no erectile dysfunction (p = 0.024) and the sildenafil citrate arm had superior overall satisfaction (p = 0.027) and IIEF total scores (p = 0.043). At 24 months erectile function and IIEF scores were no longer significantly better for sildenafil citrate (p = 0.172 and 0.09, respectively) and yet overall satisfaction scores were higher (p = 0.033). Sexual desire scores in patients who received sildenafil citrate were higher at 24 months although they had completed drug therapy 18 months previously (p = 0.049). At 24 months 81.6% of patients on sildenafil citrate and 56.0% of those on placebo achieved functional erection with or without erectile dysfunction medication (p = 0.045). CONCLUSIONS: Daily sildenafil citrate during and after radiotherapy for prostate cancer was associated with improved overall sexual function compared with placebo for various sexual function domains. To our knowledge this is the largest randomized, prospective, controlled trial to show the usefulness of a phosphodiesterase-5 inhibitor as a rehabilitation strategy in patients with prostate cancer who received radiation therapy.

The treatment of hypogonadism in men of reproductive age.

OBJECTIVE: To review the mechanisms of T replacement therapy's inhibition of spermatogenesis and current therapeutic approaches in reproductive aged men. DESIGN: Review of published literature. SETTING: PubMed search from 1990-2012. PATIENT(S): PubMed search from 1990-2012. INTERVENTION(S): A literature review was performed. MAIN OUTCOME MEASURE(S): Semen analysis and pregnancy outcomes, time to recovery of spermatogenesis, serum and intratesticular T levels. RESULT(S): Exogenous T suppresses intratesticular T production, which is an absolute prerequisite for normal spermatogenesis. Therapies that protect the testis involve hCG therapy or selective estrogen receptor (ER) modulators, but may also include low-dose hCG with exogenous T. Off-label use of selective ER modulators, such as clomiphene citrate (CC), are effective for maintaining T production long term and offer the convenience of representing a safe, oral therapy. At present, routine use of aromatase inhibitors is not recommended based on a lack of long-term data. CONCLUSION(S): Exogenous T supplementation decreases sperm production. Studies of hormonal contraception indicate that most men have a return of normal sperm production within 1 year after discontinuation. Clomiphene citrate is a safe and effective therapy for men who desire to maintain future potential fertility. Although less frequently used in the general population, hCG therapy with or without T supplementation represents an alternative treatment.

Acceptability and preliminary feasibility of an internet/CD-ROM-based education and decision program for early-stage prostate cancer patients: randomized pilot study.

BACKGROUND: Prostate cancer is the most common cancer affecting men in the United States. Management options for localized disease exist, yet an evidence-based criterion standard for treatment still has to emerge. Although 5-year survival rates approach 98%, all treatment options carry the possibility for significant side effects, such as erectile dysfunction and urinary incontinence. It is therefore recommended that patients be actively involved in the treatment decision process. We have developed an Internet/CD-ROM-based multimedia Prostate Interactive Educational System (PIES) to enhance patients' treatment decision making. PIES virtually mirrors a health center to provide patients with information about prostate cancer and its treatment through an intuitive interface, using videos, animations, graphics, and texts. OBJECTIVES: (1) To examine the acceptability and feasibility of the PIES intervention and to report preliminary outcomes of the program in a pilot trial among patients with a new prostate cancer diagnosis, and (2) to explore the potential impact of tailoring PIES treatment information to participants' information-seeking styles on study outcomes. METHODS: Participants (n = 72) were patients with newly diagnosed localized prostate cancer who had not made a treatment decision. Patients were randomly assigned to 3 experimental conditions: (1) control condition (providing information through standard National Cancer Institute brochures; 26%), and PIES (2) with tailoring (43%) and (3) without tailoring to a patient's information-seeking style (31%). Questionnaires were administrated before (t1) and immediately after the intervention (t2). Measurements include evaluation and acceptability of the PIES intervention, monitoring/blunting information-seeking style, psychological distress, and decision-related variables (eg, decisional confidence, feeling informed about prostate cancer and treatment, and treatment preference). RESULTS: The PIES program was well accepted by patients and did not interfere with the clinical routine. About 79% of eligible patients (72/91) completed the pre- and post-PIES intervention assessments. Patients in the PIES groups compared with those in the control condition were significantly more likely to report higher levels of confidence in their treatment choices, higher levels of helpfulness of the information they received in making a treatment decision, and that the information they received was emotionally reassuring. Patients in the PIES groups compared with those in the control condition were significantly less likely to need more information about treatment options, were less anxious about their treatment choices, and thought the information they received was clear (P < .05). Tailoring PIES information to information-seeking style was not related to decision-making variables. CONCLUSIONS: This pilot study confirms that the implementation of PIES within a clinical practice is feasible and acceptable to patients with a recent diagnosis of prostate cancer. PIES improved key decision-making process variables and reduced the emotional impact of a difficult medical decision.

Identification and characterization of repopulating spermatogonial stem cells from the adult human testis.

BACKGROUND: This study was conducted to identify and characterize repopulating spermatogonial stem cells (SSCs) in the adult human testes. METHODS: Testes biopsies from obstructive azoospermic patients and normal segments of human testicular tissue were used. Flow cytometry, real-time PCR and immunohistochemical analysis were performed. Purified human spermatogonia were transplanted into busulfan-treated recipient mouse testes and integrated cells were detected by human nuclear protein antibody co-localized with stem cell and germ cell markers. RESULTS: Testicular biopsies collected from obstructive azoospermic men showed similar morphology and distribution of markers to the normal human testes. Flow cytometry showed distinct populations of stage-specific embryonic antigen-4 (SSEA-4), CD49f and CD90 positive cells in the adult human testes. SSEA-4 (+) cells showed high expression levels of SSC-specific genes and high levels of telomerase activity. Extensive colonization of human cells in the mouse testes indicates the presence of highly enriched populations of SSCs in the SSEA-4 (+) sorted cells. All the HNP (+) cells in the mouse testes were positive for germ cell marker dead box mRNA helicase and only half of them were dimly positive for c-kit. In addition, subpopulations of human spermatogonia that colonized mouse testes were positively stained for CD49f, GPR-125, Nanog and Oct-4 indicating the existence of population of cells among human spermatogonia with SSC and pluripotent characteristics. CONCLUSIONS: This study clearly demonstrates that repopulating human SSCs have phenotypic characteristics of SSEA-4(+), CD49f(+), GPR-125(+)and c-Kit (neg/low). The results have direct implications for enrichment of human spermatogonia for further culture and germ cell differentiation studies.

Medical implications of erectile dysfunction.

Erectile dysfunction (ED) is a common condition in aging men, with a prevalence of 52% in men aged 40 to 70 years. It is frequently associated with several comorbid conditions, including cardiovascular disease, lower urinary tract symptoms, and testosterone deficiency. These conditions often have major consequences on the quality of life of patients and require adequate evaluation by the primary care practitioner. Complaints of ED, therefore, serve as a marker for these conditions and give the practitioner an opportunity to prevent the consequences of a delay in treatment. In this article, the evidence behind these associations is described.

Sex chromosome micromosaicism in infertile men with normal karyotypes.

OBJECTIVE: To define the prevalence of low-level sex chromosome mosaicism in a cohort of infertile men. DESIGN: Prospective cohort study of infertile men. SETTING: Tertiary university infertility center. PATIENT(S): One hundred one consecutive men who presented with primary infertility for evaluation. INTERVENTION(S): Fluorescent in situ hybridization for X and Y was performed on 200 cells, and if an aberrant sex chromosome complement was noted, 400 cells were counted. For this study, any abnormality in sex chromosome complement was defined as micromosaicism. MAIN OUTCOME MEASURE(S): Low-level sex chromosome mosaicism. RESULT(S): Sixty-seven of these men (67%) had no mosaicism, and 34 men (34%) had micromosaicism. The median percentage of abnormal chromosomes in these men was 2%. The mean age of the men without micromosaicism was lower than for men with micromosaicism (31.1 years vs. 35.2 years). A trend toward higher FSH levels in men with low-level mosaicism was seen. Median sperm density and percent motility were higher in normal men. Percent normal morphology was identical between groups. CONCLUSION(S): We found low-level sex chromosome mosaicism in 34% of infertile men who presented for evaluation. Men with low-level mosaicism were significantly older. Low-level mosaicism may emerge with advancing age and may therefore help to explain the decline in fertility potential seen in older men.

Paternal age and assisted reproductive technology outcome in ovum recipients.

This study suggests that paternal age may be inversely associated with reproductive outcome, as demonstrated by a decline in fertilization, blastocyst formation, implantation and cryopreservation rates with advancing age.

The morphology of extracted testicular sperm correlates with fertilization but not pregnancy rates.

OBJECTIVE: To investigate sperm morphology on the day of fresh testicular sperm extraction (TESE) with intracytoplasmic sperm injection (ICSI), and its effect on fertilization and pregnancy rates, as TESE in conjunction with ICSI results in high fertilization and pregnancy rates in most patients, but to our knowledge only one small study has assessed the morphology of retrieved sperm and found no correlation with the success of fertilization. PATIENTS AND METHODS: In a retrospective database analysis in a large academic centre, 68 men had 75 cycles of TESE combined with ICSI from January 2004 until April 2006. Sperm obtained by TESE was morphologically analysed at high (x 400-600) magnification and used for ICSI on the day of tissue retrieval. Sperm were classified as being either normal, having an amorphous head, having a mid-piece defect or having multiple defects. The calculated percentage of abnormal sperm injected was compared with the normal fertilization rate using Pearson's correlation coefficient, and pregnancy rates between groups were compared using chi-square analysis. RESULTS: Fifteen cycles had all morphologically normal sperm; 21 cycles had 50-99% normal forms and 39 cycles had <50% normal sperm. There was a highly significant correlation between the percentage of normal sperm used for ICSI and fertilization rates (P = 0.007). Overall, 43 clinical pregnancies resulted in this series, i.e. three among the group with all normal sperm injected, 12 in the group with 50-99% normal sperm and 28 in the group with <50% normal forms. There were also 11 pregnancies in cycles that used no normal forms. Pregnancy rates did not differ significantly among the groups (P = 0.08). CONCLUSIONS: TESE with ICSI frequently results in successful pregnancy; normal morphology was highly and significantly associated with successful fertilization, but importantly there were still 10 clinical pregnancies in cycles where only abnormal sperm were used. Sperm morphology after TESE should be assessed at the time of the procedure, and whenever possible, morphologically normal sperm chosen for injection. However, it is reassuring that acceptable fertilization and pregnancy rates are still achievable in cases with no morphologically normal sperm available.

Medical and surgical management male infertility.

Male infertility is the result of a variety of highly treatable conditions. The critical step in treating male infertility is to evaluate properly every male partner of an infertile couple and to generate the proper treatment strategy. There are many medical and surgical options that can help most couples overcome male factor infertility. Male infertility can most easily be broken down into problems of sperm production (testicular dysfunction) and problems of sperm transport (obstruction). When applicable, medical therapies are used as an initial strategy to improve sperm production or as a preliminary therapy to boost production transiently in anticipation of a surgical sperm retrieval attempt. A range of surgical options is available to correct varicoceles, reconstruct the obstructed system, or retrieve sperm for assisted reproduction.

Plasmid-based gene transfer for treatment of erectile dysfunction and overactive bladder: results of a phase I trial.

BACKGROUND: Ion Channel Innovations has developed a gene transfer product, hMaxi-K, and has begun clinical trials to investigate the effect of increased expression of Maxi-K channels in the smooth muscle of the penis or bladder in patients with erectile dysfunction and those with overactive bladder. The primary function of K channels is to modulate Ca++ influx through Ca-channels (i.e., L-type, voltage-dependent). The amount of Ca++ that enters the cell through these channels is a major determinant of the free intracellular calcium levels inside the smooth muscle cell, which in turn determines the degree of smooth muscle cell contraction. Increased Maxi-K channel activity is associated with smooth muscle cell relaxation, resulting in, for example, penile erection and detrussor muscle relaxation. A phase I clinical trial that used hMaxi-K has been completed and a similar trial to assess safety of the transfer for overactive bladder is about to begin. OBJECTIVES: To assess the safety and tolerability of escalating hMaxi-K doses by clinical evaluations and laboratory tests, and to measure efficacy objectives by means of the International Index of Erectile Function scale. METHODS: In the erectile dysfunction trial 11 patients with moderate to severe erectile dysfunction were given a single-dose corpus cavernosum injection of hMaxi-K, a "naked" DNA plasmid carrying the human cDNA encoding for the gene for the alpha, or pore-forming, subunit of the human smooth muscle Maxi-K channel, hSlo. Three patients each were given 500, 1000, and 5000 pg and two patients were given 7500 microg doses of hMaxi-K and followed for 24 weeks. Patient responses were validated by partner responses. RESULTS: There were no serious adverse events and no dose-related adverse events attributed to gene transfer for any patient at any dose or study visit. No clinically significant changes from baseline were seen in physical evaluations (general and genitourinary), hematology, chemistry and hormone analyses, or in cardiac events evaluated by repeated electrocardiograms. Importantly, no plasmid was detected in the semen of patients at any time after the injections. Patients given the two highest doses of hMaxi-K had apparent sustained improvements in erectile function as indicated by improved IIEF-EF domain scores over the length of the study. One patient given 5000 microg and one given 7500 microg reported EF category improvements that were highly clinically significant and were also maintained through the 24 weeks of study. CONCLUSIONS: Efficacy conclusions cannot be drawn from results of a phase 1 trial with no control group. However, the promising primary safety outcomes of the study and preliminary indications of effectiveness provide evidence that hMaxi-K gene transfer is a viable approach to the treatment of erectile dysfunction and other smooth muscle diseases with targeted access.

hMaxi-K gene transfer in males with erectile dysfunction: results of the first human trial.

Eleven patients with moderate to severe erectile dysfunction (ED) were given a single-dose corpus cavernosum injection of hMaxi-K, a "naked" DNA plasmid carrying the human cDNA encoding hSlo (for human slow-poke), the gene for the alpha, or pore-forming, subunit of the human smooth muscle Maxi-K channel. Three patients each were given 500, 1000, and 5000 microg, and two patients were given 7500 microg, of hMaxi-K and monitored for 24 weeks. The primary objectives of this phase I study were safety and tolerability of escalating hMaxi-K doses as assessed by clinical evaluations and laboratory tests. Secondary efficacy objectives were measured primarily by use of the International Index of Erectile Function (IIEF) scale. Patient responses were validated by partner responses. There were no serious adverse events and no dose-related adverse events attributed to gene transfer for any patient at any dose or study visit. No clinically significant changes from baseline were seen in physical evaluations (general and genitourinary), hematology, chemistry, and hormone analyses, or in cardiac events evaluated by repeated electrocardiograms. Importantly, no plasmid was detected in the semen of patients at any time after the injections. Patients given the two highest doses of hMaxi-K had apparent sustained improvements in erectile function (EF) as indicated by improved IIEF-EF domain scores over the length of the study. One patient given 5000 microg and one given 7500 microg reported EF category improvements that were highly clinically significant and were also maintained through the 24 weeks of study. Efficacy conclusions cannot be drawn from results of a phase I trial with no control group. However, the promising primary safety outcomes of the study and preliminary indications of effectiveness provide evidence that hMaxi-K gene transfer is a viable approach to the treatment of ED and that further studies investigating the efficacy of hMaxi-K in patients with ED should be performed.

Early use of a phosphodiesterase inhibitor after brachytherapy restores and preserves erectile function.

OBJECTIVE: To investigate whether the early use of phosphodiesterase inhibitors (PDEIs) after brachytherapy (BT) is associated with better erectile function, as of men potent before BT 38-70% have erectile dysfunction afterward. PATIENTS AND METHODS: We evaluated a prospectively created database of 2500 patients who had had BT at our institution since 1992. We measured baseline age, cancer stage, Gleason grade, prostate specific antigen (PSA) level at diagnosis, implant type, use of neoadjuvant and adjuvant hormonal suppression therapy, use of external beam radiotherapy in conjunction with interstitial therapy, and follow-up PSA levels. Men were stratified by their use of PDEIs at <1 year (early group) or >1 year after implantation (late group). We excluded all men who did not have baseline Sexual Health Inventory for Men (SHIM) scores and at least one follow-up SHIM score; the latter were obtained at 6-month intervals after BT. Data were analysed using the Mann-Whitney U-test. RESULTS: In all, 210 men met the inclusion criteria; 85 began using PDEIs within a year of BT, and 125 started after a year. The mean time to PDEI use was 191 days in the early and 595 days in the late group. The median age was 62 years in the early and 63 years in the late group (P = 0.02). Baseline Gleason scores did not differ, nor did PSA levels between the groups. Of men in the early group, 48% received neoadjuvant and/or adjuvant hormonal suppression therapy, vs half of men in the late group. Baseline SHIM scores were not significantly different, nor were scores at the first two follow-up assessments, but the scores at 18-36 months after BT were significantly different. CONCLUSION: The early use of PDEIs after BT is associated with a significant improvement in and maintenance of erectile function compared with late use. Men undergoing BT should be encouraged to use PDEIs early after implantation, to preserve erectile function.

The first human trial for gene transfer therapy for the treatment of erectile dysfunction: preliminary results.

OBJECTIVE: To test the safety of a single intracavernous injection of a plasmid vector (hMaxi-K) that expresses the hSlo gene, that encodes the alpha-subunit of the Maxi-K channel, for the treatment of erectile dysfunction (ED). METHODS: Six men, thus far have fulfilled the entry criteria of the protocol and had gene transfer with hMaxi-K. Three received a dose of 500 microg and three received a dose 1000 microg of the gene product, injected intracavernously as naked DNA. Dosing at 5000 microg and higher is planned. RESULTS: The primary end point of the phase I trial is safety. No drug-related adverse events or significant laboratory changes have occurred after the gene transfer. Moreover, there is no evidence of the gene in semen at the one copy per mug total DNA in any of the participants. CONCLUSION: Preliminary results indicate that, in a single dose escalation study, ion channel gene transfer with hMaxi-K can be administered safely to men with ED without adverse events.

Intratesticular mucinous cystadenoma: immunohistochemical comparison with ovarian and colonic tissue.

We report a case of a primary intratesticular mucinous cystadenoma in an asymptomatic 39-year-old man. The mass was found incidentally during a consultation for infertility. Pathologic examination of the orchiectomy specimen revealed a unilocular cyst lined with bland mucinous epithelium and mucinous extravasation, consistent with a diagnosis of mucinous cystadenoma. Foci of bone were also found in association with extensive chronic inflammation. Immunohistochemical stains performed showed immunoreactivity for cytokeratin 7, and nonreactivity for cytokeratin 20, CA125, chromogranin, and synaptophysin. The immunohistochemical staining patterns of the present case are compared with those of known mucinous cystadenomas of the ovary and nonneoplastic colonic mucosa. The histogenesis of this entity is discussed in light of the literature and the immunohistochemical findings in this rare case.