Alan W. Shindel

Treatment of stress urinary incontinence with adipose tissue-derived stem cells.

BACKGROUND AIMS Effective treatment for stress urinary incontinence (SUI) is lacking. This study investigated whether transplantation of adipose tissue-derived stem cells (ADSC) can treat SUI in a rat model. METHODS Rats were induced to develop SUI by postpartum vaginal balloon dilation and bilateral ovariectomy. ADSC were isolated from the peri-ovary fat, examined for stem cell properties, and labeled with thymidine analog BrdU or EdU. Ten rats received urethral injection of saline as a control. Twelve rats received urethral injection of EdU-labeled ADSC and six rats received intravenous injection of BrdU-labeled ADSC through the tail vein. Four weeks later, urinary voiding function was assessed by conscious cystometry. The rats were then killed and their urethras harvested for tracking of ADSC and quantification of elastin, collagen and smooth muscle contents. RESULTS Cystometric analysis showed that eight out 10 rats in the control group had abnormal voiding, whereas four of 12 (33.3%) and two of six (33.3%) rats in the urethra-ADSC and tail vein-ADSC groups, respectively, had abnormal voiding. Histologic analysis showed that the ADSC-treated groups had significantly higher elastin content than the control group and, within the ADSC-treated groups, rats with normal voiding pattern also had significantly higher elastin content than rats with voiding dysfunction. ADSC-treated normal-voiding rats had significantly higher smooth muscle content than control or ADSC-treated rats with voiding dysfunction. CONCLUSIONS Transplantation of ADSC via urethral or intravenous injection is effective in the treatment and/or prevention of SUI in a pre-clinical setting.

Prevalence and Predictors of Sexual Problems, Relationship Stress, and Depression in Female Partners of Infertile Couples

INTRODUCTION Infertility has been associated with anxiety, stress, and sexual problems in both men and women. AIM To assess quality of life, sexual health, and depression in the female partner of infertile couples. METHODS Couples presenting for the evaluation of infertility at two tertiary care medical centers were invited to participate in a survey study. MAIN OUTCOME MEASURES Female partners completed the Female Sexual Function Index (FSFI) and a modified Self-Esteem and Relationship (SEAR) Questionnaire. Male partners completed the SEAR and the International Index of Erectile Function (IIEF). Both partners completed the Center for Epidemiological Studies Depression Scale (CES-D) for depression and the Short Form-36 (SF-36) for general quality of life. Demographic, fertility, and comorbidity information was recorded. RESULTS One hundred and twenty-one couples constitute the study population. Mean female and male age was 32 +/- 5 and 35 +/- 7 years, respectively. Most (92%) couples were married. Mean duration of relationship and marriage were 6.4 +/- 3.9 and 3.8 +/- 3.2 years, respectively. Mean duration of attempted conception was 24 +/- 24 months. On CES-D, 19% of women had moderate and 13% had severe depression. Women reported significantly worse SF-36 Mental Health subscale scores (mean = 47.8, P < 0.05) compared with normative values. The mean total FSFI score was 28 +/- 7 (maximum score of 36), with 26% of the women scoring below 26.55, an established cut-off for high risk of female sexual dysfunction. FSFI scores had a modest positive correlation with male IIEF scores (r = 0.37, P < 0.01), and there was a trend toward a negative correlation with female CES-D scores (r = -0.16, P < 0.06). These relationships were maintained on multivariate analysis. CONCLUSIONS Depression and sexual dysfunction are prevalent in female partners of infertile couples. Female sexual function is positively correlated with male partner sexual function in this population.

An Update of the International Society of Sexual Medicine's Guidelines for the Diagnosis and Treatment of Premature Ejaculation (PE)

INTRODUCTION In 2009, the International Society for Sexual Medicine (ISSM) convened a select panel of experts to develop an evidence-based set of guidelines for patients suffering from lifelong premature ejaculation (PE). That document reviewed definitions, etiology, impact on the patient and partner, assessment, and pharmacological, psychological, and combined treatments. It concluded by recognizing the continually evolving nature of clinical research and recommended a subsequent guideline review and revision every fourth year. Consistent with that recommendation, the ISSM organized a second multidisciplinary panel of experts in April 2013, which met for 2 days in Bangalore, India. This manuscript updates the previous guidelines and reports on the recommendations of the panel of experts. AIM The aim of this study was to develop clearly worded, practical, evidenced-based recommendations for the diagnosis and treatment of PE for family practice clinicians as well as sexual medicine experts. METHOD A comprehensive literature review was performed. RESULTS This article contains the report of the second ISSM PE Guidelines Committee. It offers a new unified definition of PE and updates the previous treatment recommendations. Brief assessment procedures are delineated, and validated diagnostic and treatment questionnaires are reviewed. Finally, the best practices treatment recommendations are presented to guide clinicians, both familiar and unfamiliar with PE, in facilitating treatment of their patients. CONCLUSION Development of guidelines is an evolutionary process that continually reviews data and incorporates the best new research. We expect that ongoing research will lead to a more complete understanding of the pathophysiology as well as new efficacious and safe treatments for this sexual dysfunction. We again recommend that these guidelines be reevaluated and updated by the ISSM in 4 years.

Sexual function and quality of life in the male partner of infertile couples: prevalence and correlates of dysfunction.

PURPOSE We prospectively collected data on mental and physical health related quality of life as well as sexual and relationship function in couples presenting for the treatment of infertility. MATERIALS AND METHODS Infertile couples were invited to complete a demographic survey, the Short Form 36 and the Center for Epidemiological Studies Depression Inventory. Male partners completed the International Index of Erectile Function and the Self-Esteem and Relationship Quality scale. Female partners completed the Female Sexual Function Index and a version of the Self-Esteem and Relationship Quality Scale modified for women. Multiple regression analysis was conducted to assess for associations between partner responses. RESULTS A total of 121 couples were enrolled at 2 sites. Male partners reported significantly lower standardized scores on the Mental Health subscale of the Short Form 36 (mean 47.6, p <0.05) compared to normative values. Of the men surveyed 11% and 12% reported moderate or severe depression, respectively. There were 18% who had mild erectile dysfunction and 4% had moderate erectile dysfunction. The mean transformed score for the Self-Esteem and Relationship Quality Scale in our subjects was 29.44 (range 0 to 100). In multivariate analysis white race and partner Female Sexual Function Index score were significant predictors of International Index of Erectile Function Erectile Function Domain scores (p <0.01). Relationship duration and partner Self-Esteem and Relationship Quality Scale scores were significantly associated with male Self-Esteem and Relationship Quality Scale score on multivariate analysis. CONCLUSIONS Depression, erectile dysfunction and sexual relationship problems are prevalent among male partners of infertile couples. Partner sexual function is a significant predictor of male partner sexual function. Relationship duration and female partner assessment of relationship health are predictive of mens assessment of their relationship status.

An evidence-based unified definition of lifelong and acquired premature ejaculation: Report of the second international society for sexual medicine Ad Hoc committee for the definition of premature ejaculation

INTRODUCTION The International Society for Sexual Medicine (ISSM) Ad Hoc Committee for the Definition of Premature Ejaculation developed the first evidence-based definition for lifelong premature ejaculation (PE) in 2007 and concluded that there were insufficient published objective data at that time to develop a definition for acquired PE. AIM The aim of this article is to review and critique the current literature and develop a contemporary, evidence-based definition for acquired PE and/or a unified definition for both lifelong and acquired PE. METHODS In April 2013, the ISSM convened a second Ad Hoc Committee for the Definition of Premature Ejaculation in Bangalore, India. The same evidence-based systematic approach to literature search, retrieval, and evaluation used by the original committee was adopted. RESULTS The committee unanimously agreed that men with lifelong and acquired PE appear to share the dimensions of short ejaculatory latency, reduced or absent perceived ejaculatory control, and the presence of negative personal consequences. Men with acquired PE are older, have higher incidences of erectile dysfunction, comorbid disease, and cardiovascular risk factors, and have a longer intravaginal ejaculation latency time (IELT) as compared with men with lifelong PE. A self-estimated or stopwatch IELT of 3 minutes was identified as a valid IELT cut-off for diagnosing acquired PE. On this basis, the committee agreed on a unified definition of both acquired and lifelong PE as a male sexual dysfunction characterized by (i) ejaculation that always or nearly always occurs prior to or within about 1 minute of vaginal penetration from the first sexual experience (lifelong PE) or a clinically significant and bothersome reduction in latency time, often to about 3 minutes or less (acquired PE); (ii) the inability to delay ejaculation on all or nearly all vaginal penetrations; and (iii) negative personal consequences, such as distress, bother, frustration, and/or the avoidance of sexual intimacy. CONCLUSION The ISSM unified definition of lifelong and acquired PE represents the first evidence-based definition for these conditions. This definition will enable researchers to design methodologically rigorous studies to improve our understanding of acquired PE.

The use of complementary and alternative fertility treatment in couples seeking fertility care: data from a prospective cohort in the United States

OBJECTIVE To determine the prevalence of complementary and alternative medicine (CAM) use among couples seeking fertility care and to identify the predictors of CAM use in this population. DESIGN Prospective cohort study. SETTING Eight community and academic infertility practices. PATIENT(S) A total of 428 couples presenting for an infertility evaluation. INTERVENTION(S) Interviews and questionnaires. MAIN OUTCOME MEASURE(S) Prevalence of complementary and alternative medicine therapy. RESULT(S) After 18 months of observation, 29% of the couples had utilized a CAM modality for treatment of infertility; 22% had tried acupuncture, 17% herbal therapy, 5% a form of body work, and 1% meditation. An annual household income of > or =

Sexual, marital, and social impact of a man's perceived infertility diagnosis.

200,000 (odds ratio 2.8, relative to couples earning <

Adipose derived stem cells ameliorate hyperlipidemia associated detrusor overactivity in a rat model.

100,000), not achieving a pregnancy (odds ratio 2.3), and a positive attitude toward CAM use at baseline were independently associated with CAM use. CONCLUSION(S) A substantial minority of infertile couples use CAM treatments. CAM was chosen most commonly by wealthier couples, those not achieving a pregnancy, and those with a baseline belief in the effectiveness of CAM treatments.

Erectogenic and Neurotrophic Effects of Icariin, a Purified Extract of Horny Goat Weed (Epimedium spp.) In Vitro and In Vivo

INTRODUCTION Male factor infertility is a relatively common problem. This diagnosis may increase sexual, marital, and relationship strain in male partners of infertile couples. AIM To measure the personal, social, sexual, and marital impacts of a male factor infertility diagnosis among men in couples evaluated for infertility. METHODS Cross-sectional analysis of 357 men in infertile couples from eight academic and community-based fertility clinics. Participants completed written surveys and face-to-face and telephone interviews at study enrollment. This interview queried each participants perception of their infertility etiology to determine the primary study exposure (i.e., male factor only, male and female factors, female factor only, unknown). MAIN OUTCOME MEASURES Personal Impact, Social Impact, Marital Impact, and Sexual Impact scales. RESULTS Among the 357 men, no male factor was reported in 47%, isolated male factor was present in 12%, combined male and female factors were present in 16%, and unexplained infertility was present in 25% of couples. Male factor infertility was independently associated with worse Sexual (mean 39 vs. 30, standard deviation [SD] 2.7, P = 0.004) and Personal (mean 37 vs. 29, SD 3.8, P = 0.04) Impact scores relative to men in couples without male factor infertility. These differences remained statistically significant after controlling for male age, partner age, race, religion, educational level, employment status, prior pregnancy, duration of infertility, and prior paternity. CONCLUSIONS Male partners in couples who perceive isolated male factor infertility have a lower sexual and personal quality of life compared with male partners of couples without perceived male factor infertility. Social strain is highest among couples without a clear etiology for infertility. These findings highlight the clinically significant negative sexual, personal, and social strains of a perceived infertility diagnosis for men.

The future is today: emerging drugs for the treatment of erectile dysfunction

PURPOSE Adipose tissue derived stem cells can differentiate into muscle and neuron-like cells in vitro. We investigate the usefulness of adipose tissue derived stem cells for overactive bladder in obese hyperlipidemic rats. MATERIALS AND METHODS Hyperlipidemia was induced in healthy rats by a high fat diet. The resulting obese hyperlipidemic rats were treated with bladder injection of saline, adipose tissue derived stem cells or tail vein injection of adipose tissue derived stem cells. Bladder function was assessed by 24-hour voiding behavior study and conscious cystometry. Bladder histology was assessed using immunostaining and trichrome staining, followed by image analysis. RESULTS Serum total cholesterol and low density lipoprotein were significantly higher in obese hyperlipidemic rats than in normal rats (p <0.01). The micturition interval was shorter in saline treated obese hyperlipidemic rats than in normal rats, obese hyperlipidemic rats that received adipose tissue derived stem cells via the tail vein and obese hyperlipidemic rats that received adipose tissue derived stem cells by bladder injection (mean +/- SEM 143 +/- 28.7 vs 407 +/- 77.9, 281 +/- 43.9 and 368 +/- 66.7 seconds, respectively, p = 0.0084). Bladder wall smooth muscle content was significantly lower in obese hyperlipidemic rats than in normal animals (p = 0.0061) while there was no significant difference between obese hyperlipidemic groups. Nerve content and blood vessel density were lower in controls than in obese hyperlipidemic rats treated with adipose tissue derived stem cells. CONCLUSIONS Hyperlipidemia is associated with increased urinary frequency, and decreased bladder blood vessel and nerve density in rats. Adipose tissue derived stem cell treatment ameliorates these adverse effects and holds promise as a potential new therapy for overactive bladder.