Susan Lau

Cocaine Use in the Infertile Male Population: A Marker for Conditions Resulting in Subfertility.

Introduction: We sought to evaluate the incidence and effect of cocaine use in the infertile male population. Materials and Methods: Men presenting for fertility evaluation reporting cocaine usage were identified via prospectively collected database. Data were analyzed for usage patterns, reproductive history, associated drug use and medical conditions, hormonal and semen parameters. Results: Thirty-eight out of 4,400 (0.9%) men reported cocaine use. Most used cocaine every 3 months or less. Compared with non-cocaine using men, cocaine users reported more recreational drug use (89 vs. 9.2%), marijuana use (78.9 vs. 11.4%), chlamydia (10.5 vs. 3%), herpes (7.9 vs. 2.5%), and tobacco use (55.3 vs. 19.5%). After excluding men with causes for azoospermia, the mean semen parameters for cocaine users were: volume 2.47 ± 1.02 ml; concentration 53.55 ± 84.04 × 106/ml; motility 15.72 ± 12.26%; total motile sperm count 76.67 ± 180.30 × 106. Conclusions: Few (< 1%) men in our infertile population reported the use of cocaine, and the frequency of use was low. Given the low use rates and limitations of reporting bias, it is difficult to determine the direct effect of cocaine use on male fertility. However, while infrequent cocaine use seems to have limited impact on semen parameters, men reporting cocaine use represent a different cohort of men than the overall infertile population, with higher rates of concurrent substance abuse, tobacco use and infections, all of which may negatively impact their fertility. Reported cocaine users should be screened for concurrent drug use and infections.

OnabotulinumtoxinA (Botox) nerve blocks provide durable pain relief for men with chronic scrotal pain: a pilot open-label trial.

INTRODUCTION Chronic scrotal pain (CSP) is a common, often debilitating, condition affecting approximately 4.75% of men. While nerve blocks using local anesthetics usually provide temporary pain relief, there are no publications on the use of longer acting nerve blocks to provide more durable pain relief for men with CSP. AIM The aim of this study was to determine if onabotulinumtoxinA (Botox) cord blocks provide durable pain relief for men with CSP. METHODS In this pilot open-label study, men with CSP who had failed medical management but experienced temporary pain relief from a standard cord block underwent a cord block with 100U Botox. MAIN OUTCOME MEASURES The outcomes measured were changes 1, 3, and 6 months post-Botox injection in (i) a 10-point visual analog scale (VAS) pain score; (ii) scrotal tenderness on a three-point scale as rated by physical examination; and (iii) the Chronic Epididymitis Symptom Index (CESI) to measure the severity and impact of scrotal pain on men. Paired t-tests were used to compare groups. RESULTS Eighteen patients with CSP seen between April and September 2013 had Botox injected as a cord block. At the 1-month follow-up, pain reduction was reported by 72% of patients (mean VAS score: 7.36 vs. 5.61, P < 0.003), while by physical examination 44 and 34% of the men had either complete or partial resolution of scrotal tenderness. In addition, there was also a significant reduction in CESI scores (22.19 vs. 19.25, P < 0.04). At 3 months, 56% had both sustained pain reduction and reduced tenderness based on the VAS score (mean: 7.36 vs. 6.02, P < 0.05) and physical exam. The CESI score continued to be significantly lower. Unfortunately, by 6 months, most men had a return to their baseline levels of pain and tenderness. CONCLUSIONS Our pilot study found that Botox cord blocks provide pain reduction for 3 months or more for most men with CSP.

Nomograms for predicting changes in semen parameters in infertile men after varicocele repair.

OBJECTIVE To formulate nomograms based on pre-repair characteristics to predict improvements in semen parameters after varicocele repair. DESIGN Model using multivariable linear regression based on prospectively collected database, with performance was quantified by concordance correlation coefficient and Pearson correlation coefficient after internal validation with bootstrapping. SETTING A male infertility specialty clinic. PATIENT(S) Men presenting for fertility evaluation from 2003-2012 having varicocele repair. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Semen parameters before and after varicocele repair. RESULT(S) Men undergoing varicocele repair (surgical or embolization) were identified via a prospectively collected database. The relationship of pre-repair semen and clinical characteristics to improvements in semen parameters was modeled using multivariable linear regression, then the model performance was quantified by concordance correlation coefficient and Pearson correlation coefficient after internal validation with bootstrapping. A total of 376 men who had undergone varicocele repair had data available for analysis. After varicocelectomy, the total motile count (TMC) varied depending on the initial left varicocele grade, ejaculate volume, sperm concentration, and motility. The final sperm concentration depended on the initial left varicocele grade, sperm concentration, and motility. The postvaricocelectomy sperm motility varied depending on the patients age, left varicocele grade, sperm motility, morphology, and TMC. The final percentage of normal forms depended on the prevaricocelectomy sperm morphology, age, right varicocele grade, normal morphology, and TMC. Nomograms using prevaricocelectomy semen parameters and clinical features were developed to predict postvaricocelectomy TMC, sperm concentration, motility, and morphology. The concordance correlation coefficients were 0.45, 0.47, 0.65, and 0.36, respectively. CONCLUSION(S) Clinical factors provide substantial ability to predict postvaricocele repair semen parameters. These nomograms may be used by clinicians to predict postvaricocele repair semen parameters.

Characteristics and Etiologies of Chronic Scrotal Pain: A Common but Poorly Understood Condition

Chronic scrotal pain (CSP) is a common and debilitating condition, but the underlying characteristics and etiology of CSP are poorly understood. The objective of this study is to identify the characteristic and etiologies of CSP. Men presenting for management of CSP completed a standardized questionnaire and underwent a complete physical examination. From Feb 2014 to Sep 2015, a total of 131 men (mean age 43) with CSP were studied. The CSP was of long duration (mean of 4.7 ± 5.95 years) and dramatically affected mens lives, with adverse effects on normal activities (71.%), ability to work (51.90%), and sexual functioning (61.8%). 50.4% felt depressed on most days, and 67.17% felt either unhappy or terrible with their present condition. Physical examination revealed that the epididymis was the most common tender area found in 70/131 men (53.43%), though a musculoskeletal source for the pain was found in 9.9%. Neuropathic changes were found in 30%. For close to half of the men (43.5%) we were unable to identify any potential cause for the CSP. This study characterizes the dramatic impact that CSP has on the lives of men, while providing an understanding of the common etiologies.

Chronic scrotal pain may lead to reduced sexual function and interest, while sexual activity may worsen chronic scrotal pain: “double jeopardy”

Background While it is recognized that chronic pain may adversely impact sexual function and activity in men and we also recognize that sexual activity may worsen the pain for men with chronic scrotal pain (CSP), the effect on sexual functioning and conversely the impact of sex on CSP has not previously been documented. Methods Retrospective analysis of a prospectively collected database. Results From Feb 2014 to Sep 2015, a total of 128 men presenting for assessment of CSP completed all or parts of a standardized questionnaire. Overall 60% (69/116) of the men felt that the CSP had kept them either a “lot” or “some” of the time from sexual activity and 64% (27/43) had evidence of decreased erectile performance. Those with more severe pain (analog pain scores 7–10/10) had more significant sexual dysfunction than those with less severe pain, with 54% (45/83) vs. 0% (0/33, P<0.01: Fisher’s exact test) noting that the pain kept them from sexual activity “a lot” and 70% (23/33) vs. 40% (4/10, P<0.01) noting sexual dysfunction. Diminished libido was also common in the men [43% (55/128)] as were the symptoms of testosterone deficiency [76% (97/128)]. Conversely, sexual activity often exacerbated the pain, with 37% (47/128) finding that ejaculation aggravated their pain and another 38% (48/128) patients found sexual activity aggravated their pain. Conclusions Men with severe CSP have significantly reduced sexual function and interest compared to men with moderate or minor levels of pain. The majority of men with CSP who were sexually active were faced with worsening pain with sex and ejaculation. Clinicians should be aware of the twin risks of sexual dysfunction occurring in men with CSP and sexual activity worsening the severity of the CSP.

MP19-11 THE EFFECT OF ETHNICITY AND RACE ON SEMEN ANALYSIS AND HORMONES IN THE INFERTILE PATIENT

METHODS Study Design and Setting: • Population based, prospectively collected retrospective study using patient survey and laboratory data (2008-2017) • All men who presented a single tertiary institution for male infertility work-up Questionnaire: • Self-reported questionnaire to collect data on: •Demographics & clinical history Ethnicities: • Caucasian • Native-Canadian • African-Canadian • Hispanic • Asian • Middle Eastern • Indo-Canadian Semen Parameters: • Assessed using 2010 World Health Organization Criteria • Recorded parameters included •Volume •Count •Morphology •Motility •Vitality Hormone Levels • Total Testosterone (nmol/L) • FSH levels (mIU/ml) Statistical Analysis: • Reported medians (IQR) and frequencies (count) for demographics • Linear regression for ethnicity and hormonal profiles • Multivariate logistic regression for ethnicity and semen parameters OBJECTIVE • To determine if race and ethnicity have any impact on semen analysis or baseline hormonal profiles for men with infertility

Frequency and severity of chronic scrotal pain in Canadian men presenting to urologists for infertility investigations

Background Chronic scrotal pain (CSP) may be debilitating in men presenting for treatment for CSP, but we have little information on the frequency and severity of CSP in the men who do not seek care for the CSP. Our objective was to identify the frequency and characteristics of CSP in a population of men presenting for reasons other than CSP to a urology clinic. Methods Men presenting to a urology clinic for investigation of male infertility (INF) completed a standardized CSP questionnaires if they self-reported having CSP. This prospectively collected database was then retrospectively analyzed. Results Forty-five of 1,203 (3.7%) of INF patients (mean age 35: range, 24–59), reported having CSP (INF/CSP). Our comparison group was 131 men presenting for investigation of CSP [mean age 43¡À12 (SD) years with a mean duration of CSP of 4.7¡À5.95 years]. On average, men with INF/CSP had less severe and frequent pain than those with CSP, with significantly less pain during “bad” pain episodes (5.2¡À2.2 vs. 7.4¡À2.1, VAS score 0–10, P<0.0001 Student’s t-test), less frequent “bad” pain episodes (23%¡À21% vs. 42%¡À30% of the time, P<0.0001 Student’s t-test) and lower proportion of men who reported having severe pain (VAS score 7–10/10) (4/45 vs. 46/131, P<0.001, chi-squared test). Both groups reported a negative impact of the pain on quality of life (QOL), with 60% and 86% of men with INF/CSP and CSP alone reporting that they would feel ‘mostly dissatisfied’, ‘unhappy’, or ‘terrible’ if they had to continue life with their present scrotal pain symptoms. Conclusions Clinicians should be aware that CSP is common among men presenting for conditions other than CSP and that even if the pain levels are not “severe”, the chronic pain often has a significant negative impact on QOL.

PD13-04 RESULTS OF A NORTH AMERICAN SURVEY ON THE CHARACTERISTICS OF MEN BEING ASSESSED IN MALE INFERTILITY CLINICS: THE ANDROLOGY RESEARCH CONSORTIUM

INTRODUCTION AND OBJECTIVES: The influence of parental demographics on fertility and birth outcomes is a topic of great interest to both epidemiologists and the lay public. Given logistics and certainty of exposures, data on all births in the US is often reported at the maternal level. While paternal characteristics are also known to influence birth outcomes, generational trends of paternal characteristics of child births within the United States have been poorly characterized. We sought to summarize the demographics of fathers in the US over the past 4 decades as well as describe the patterns of missing paternal data on birth certificates. METHODS: We evaluated 158,621,397 U.S. births spanning from 1973 to 2015 using data from the National Vital Statistics System of the Centers for Disease Control. Paternal, maternal and infant characteristics were analyzed and paternal ages of all births and first births were presented over time along with the mean difference in age between parents. Characteristics of births with known and unknown paternity were also compared. RESULTS: There has been a significant increase in mean paternal age among whites, blacks and asians over the past 40 years. In 1973, the mean paternal age for all births was 27.6, and 24.6 for first births, rising to 31.4 and 29.1, respectively, in 2015. Paternal age increased for all races combined and each race individually. However, interracial differences in mean age were apparent with asians > whites > blacks. The mean age difference between parents was similar over the past 40 years. In 1973, the mean parental age difference was 2.8 years’2.7 years for whites, 3.2 years for blacks and 4.2 years for asians. In 2015, the mean overall difference was 2.5 years with the difference between asian fathers and their partners decreasing the most to 3.2 years. Of all the recorded births in 1973, 91.3% had knowledge of paternal identity. This fell to 85.5% of fathers identified in 1991 and resides at 88.4% in 2015. Over the past decade, mothers younger than 20 years had the lowest proportion of reported paternal identity at 67.7% with black mothers under 20 at 50.4%. Overall, births without paternal identity were more likely associated with young, black mothers who reported less weight gain during pregnancy, and lower birth weight children. CONCLUSIONS: Overall, paternal age is rising in the US in parallel with maternal age, a trend encompassing all races. The proportion of missing paternal data is also increasing in recent years. Given the association between paternal factors and birth characteristics, further understanding of these trends is necessary.

MP07-03 IMPROVED SPERM DNA INTEGRITY IN THE SECOND SEMEN SAMPLE FROM MEN PROVIDING DOUBLE EJACULATES

INTRODUCTION AND OBJECTIVES: Non-coding RNAs (ncRNAs) are emerging as important but poorly understood regulators of mRNA transcription and translation. However, common library preparation techniques for RNA sequencing selects for coding mRNAs by the presence of a poly-A tail; thus, by excluding non-PolyA ncRNAs, many biologically significant transcripts may be overlooked by using this method. The objective of this study was to evaluate differences in testicular RNA identification using 2 different methods of library preparation: polyA and ribosomal RNA depletion (RibZero) using Illumina kits. METHODS: Total RNA was extracted from 3 human testis samples and processed using two different methods of library preparations: one based on polyA tags, and the other on depletion of ribosomal RNAs. The cDNA libraries were then sequenced at the same depth and annotated to known published databases. Identified transcripts were divided into two groups based on presence in one of the library preparation methods but not the other. Clinical and biological significance of identified genes was examined using the DAVID. Failure of detection of RibZero-only genes by RNAseq using polyA preparation was then confirmed by analyzing results of RNAseq in 64 testicular samples from normal patients, men with sertoli cell only (SCO), early and late maturation arrest and hypospermatogenesis. RESULTS: 61 genes were detected only using polyA method with no detection in RibZero group (p1⁄40.05): 17 of them belonged to small nuclear RNAs (snRNAs), 12 were snRNAs hosting genes, 3 humanin like proteins, and 3 were miRNA hosting genes: MIR137HG, MIR17HG, MIRLET7DHG. Deletion of MIR17HG leads to Feingold syndrome in humans and animal models. 74 genes were identified exclusively in RibZero group and not identified in the polyA group. The top 4 genes identified exclusively by RibZero were TAS2R50, MAGI1AS, HIST1H3I, HIST1H4K. HIST1H4K was then further analyzed and its expression was highly abundant and specific to pachytene spermatocytes. Important components of the miRNA processing complex: AGO1,2, and 3 were expressed at >2x higher level (p1⁄40.03) in ribosomal RNA library depletion preparation then polyA prep. CONCLUSIONS: PolyA tail RNA enrichment method fails to adequately detect at least 7% of important RNAs in the human testis. Including ribosomal depletion RNA library preparation in addition to polyA tags enrichment is an important step to more comprehensively evaluate ncRNAs and testicular function.

ORIGINAL RESEARCHOnabotulinumtoxinA (Botox) Nerve Blocks Provide Durable Pain Relief for Men with Chronic Scrotal Pain: A Pilot Open‐Label Trial

INTRODUCTION Chronic scrotal pain (CSP) is a common, often debilitating, condition affecting approximately 4.75% of men. While nerve blocks using local anesthetics usually provide temporary pain relief, there are no publications on the use of longer acting nerve blocks to provide more durable pain relief for men with CSP. AIM The aim of this study was to determine if onabotulinumtoxinA (Botox) cord blocks provide durable pain relief for men with CSP. METHODS In this pilot open-label study, men with CSP who had failed medical management but experienced temporary pain relief from a standard cord block underwent a cord block with 100U Botox. MAIN OUTCOME MEASURES The outcomes measured were changes 1, 3, and 6 months post-Botox injection in (i) a 10-point visual analog scale (VAS) pain score; (ii) scrotal tenderness on a three-point scale as rated by physical examination; and (iii) the Chronic Epididymitis Symptom Index (CESI) to measure the severity and impact of scrotal pain on men. Paired t-tests were used to compare groups. RESULTS Eighteen patients with CSP seen between April and September 2013 had Botox injected as a cord block. At the 1-month follow-up, pain reduction was reported by 72% of patients (mean VAS score: 7.36 vs. 5.61, P < 0.003), while by physical examination 44 and 34% of the men had either complete or partial resolution of scrotal tenderness. In addition, there was also a significant reduction in CESI scores (22.19 vs. 19.25, P < 0.04). At 3 months, 56% had both sustained pain reduction and reduced tenderness based on the VAS score (mean: 7.36 vs. 6.02, P < 0.05) and physical exam. The CESI score continued to be significantly lower. Unfortunately, by 6 months, most men had a return to their baseline levels of pain and tenderness. CONCLUSIONS Our pilot study found that Botox cord blocks provide pain reduction for 3 months or more for most men with CSP.