Intra-individual changes in sperm parameters and total motile count with time among infertile men.

BACKGROUND: Paternal age association with sperm parameters has been previously studied, demonstrating a decrease in semen volume, sperm motility, and sperm morphology, but not in sperm concentration. However, scarce data exists on the individual intra-personal changes in semen parameters with time. STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To evaluate the changes in semen parameters and total motile count of infertile men over time. MATERIALS AND METHODS: In this retrospective cohort study, infertile men without known risk factors for sperm quality deterioration and at least two semen analyses done > 3 months apart, between 2005 and 2021, were evaluated. Allocation to groups was according to time between first and last semen analyses - 3-12 months, 1-3 years, 3-5 years, and > 5 years. Basic characteristics and first and last semen analyses were compared. The primary outcome was the change in sperm parameters and the secondary outcome was the occurrence of a total motile count < 5 million in men with an initial total motile count > 10 million. RESULTS: A total of 2018 men were included in the study. The median age at first semen analyses was 36.2 (interquartile range: 32.8-40.1) years and the median time between semen analyses was 323 days (range 90-5810 days). The overall trend demonstrated an increase in concentration in the 3-12 months and the 1-3 years groups, whereas volume, motility, and morphology remained similar in these time groups. Semen analyses done more than 5 years apart showed decreased volume (p < 0.05), motility (p < 0.05) morphology (p < 0.05), and steady sperm concentration. Significant declines in TMCs were found over time (p < 0.001), with 18% and 22% of infertile men with an initial total motile count > 10 million dropping to < 5 million after 3 and 5 years, respectively. The factors independently predictive of total motile count < 5 M in the last semen analyses in men with an initial total motile count of > 10 M in a multivariate logistic regression model were baseline volume (odds ratio 0.80, p = 0.03), baseline total motile count (odds ratio 0.98, p = 0.01) and time between semen analyses - 3-5 years (odds ratio 3.79, p < 0.001) and > 5 years (odds ratio 3.49, p = 0.04) DISCUSSION: Our study demonstrates, at the individual level, that while improvement in sperm concentration is observed in the first year and between 1 and 3 years, possibly due to fertility treatments, fertility-related counseling, and lifestyle changes, semen parameters decline with time over 3 years in individuals. Of significance, close to 22% of men with an initial total motile count > 10 million (a range where spontaneous pregnancy is attainable) declined to < 5 million (a range usually indicating a need for in-vitro fertilization/intracytoplasmic sperm injection) over 5 years. This data could contribute to individualized family planning for infertile men regarding the mode and timing of conception and the need for sperm banking, in order to minimize the need for future fertility treatments.

Temporal Trends in Semen Quality, Hormone Levels, and Substance Use Among Infertile Men in Pre- and Post-Cannabis Legalization Eras in Canada.

Background: The Cannabis Act (Bill C-45) was enacted in 2018, to legalize and regulate the use, production, and sale of nonmedical cannabis in Canada. While public health and safety implications of cannabis legalization have yet to be elucidated, the wide availability of cannabis necessitates health care providers to be knowledgeable about therapeutic potential and side effects of use. This study aimed to examine the temporal trends over two decades and the impact of the Cannabis Act in Canada, implemented in October 2018, on substance use, semen parameters, and testosterone levels of infertile men. Methods: We conducted a retrospective cohort study from a prospectively maintained database of a single infertility clinic. Demographic, fertility, and substance use history were correlated with semen and hormone assessments. Temporal trends in cannabis use and semen quality between 2001 and 2021 were investigated and compared between pre-cannabis legalization eras (PRCL) and post-cannabis legalization eras (POCL). Results: Our cohort included 11,630 patients (9411 PRCL and 2230 POCL). Cannabis use increased by 8.4% per year (p<0.001), while alcohol and tobacco consumption declined (0.8% and 1.5% per year, p<0.05 and p=0.004, respectively). Similar trends were noticed in the POCL, with higher rates of cannabis use (22.4% vs. 12.9%, p<0.001) and decreased tobacco and alcohol intake (15.2% vs. 17.7%, p=0.005 and 50.5% vs. 55.2%, p<0.001, respectively) compared to the PRCL group. Semen concentration was lower in the POCL group (24.8±44.8 vs. 28.7±48.3 million/mL, p=0.03). Testosterone did not differ between the cohorts. Comparison between cannabis users (n=1715) and nonusers (n=9924) demonstrated a slight increase in sperm motility (25.9%±15.3% vs. 23.9%±15.0%, p=0.002) and decreased sperm concentration among users (27.6±53.5 vs. 23.9±15.0 million/mL, p=0.03). Conclusion: A nearly 10% rise in cannabis use in the POCL era was observed among men being investigated for infertility. Our data suggest cannabis use may be associated with an increase in testosterone, slightly improved sperm motility, and decreased sperm concentration.

Improved sperm DNA fragmentation levels in infertile men following very short abstinence of 3-4 hours.

Background: Limited data exists on possible approaches to improve sperm DNA fragmentation index (DFI) when no identifiable cause is found. The effect of short abstinence on sperm parameters has been extensively studied, but rarely reported on the effect on DFI in infertile men. In this study, we aimed to determine whether a second ejaculate provided after very short abstinence demonstrates lower DFI rates in infertile men. Methods: This prospective cohort study was conducted at Mount Sinai Hospital, Toronto, Canada, a tertiary university affiliated hospital. All men having DFI testing in addition to the standard semen analysis were identified via a prospectively collected database. Infertile men were instructed to provide two semen samples 3-4 hours apart (the first sample was given after 2-5 days of abstinence) to test the effect on DFI levels. Data analysis was performed for the comparison of the change in sperm parameters and DFI between samples and between men with DFI above and under 30%. Results: A total of 52 men provided double ejaculates 3-4 hours apart. In the entire group, DFI decreased from 38.9%±21.4% to 35.1%±21.6% in the second sample (P<0.001). Semen volume was lower on the second sample (2.3±1.4 vs. 1.5±0.9 mL, P<0.001), while the remaining parameters did not change. Forty out of 52 patients (76.9%) had improved DFI (average of 6.0±4.0 percentage points). Change in DFI varied with 22/52 (42.3%) and 7/52 (13.5%) of patients found to have decreases in DFI >5% and >10% in the second ejaculate, respectively. For men with DFI of 30-40%, 64% (7/11) of DFIs reduced to the under 30% range. First DFI value was the only parameter associated with DFI decrease to under 30% in multivariate models [odds ratio (OR), 0.62; 95% confidence interval (CI): 0.39-0.98; P=0.04]. Conclusions: This study identified significant improvements in DFI in infertile men providing a second sample after 3-4 hours. Controlled trials are needed to determine if reproductive outcomes are improved using a second ejaculate for infertile men with high initial sperm DFI values.

Intra-individual changes in sperm DNA fragmentation levels over short and long time periods.

PURPOSE: We aimed to examine the longitudinal, intra-personal changes in DNA fragmentation index (DFI) over time. METHODS: Men who performed at least two DFI measurements (using sperm chromatin structure assay (SCSA) between 2003 and 2019 were included in this study and allocated to groups by time between DFI tests: < 1 year, 1-3 years, 3-5 years, and > 5 years. An analysis of DFI change over time according to age groups was additionally performed. Regression models were developed to predict changes in DFI with time. RESULTS: Overall, 225 patients had two or more DFI measurements done at least a month apart (mean of 586.7± 710.0 days). The < 1 year (n = 124) and 1-3 years (n = 68) groups demonstrated decreased DFI levels, while an increase in DFI was shown in 3-5 years (n = 21) and more than 5 years (n = 12) groups - 7.1 ± 14.9%, - 4.5 ± 13.4%, + 3.2 ± 8.4%, and + 10.8 ± 18.0%, respectively, p < 0.001). This trend was similarly shown in age subgroups of under 40 years and 40-50 years at baseline DFI. Linear regression models showed that the factors predictive of DFI increase are baseline DFI and > 3 years between DFI tests. CONCLUSION: This study shows that DFI, in men being investigated for infertility, initially decreases in the first 3 years of follow-up, and then increases over time with the highest increase occurring after 5 years interval (an average increase of 10.8%). Testing infertile men's DFI levels at first evaluation may contribute to personalized consult regarding future reproductive outcomes.

Uncovering the Association Between Complete AZFc Microduplications and Spermatogenic Ability: The First Reported Series.

Purpose This article aims to report the first series of men with complete AZFc microduplications and their clinical and reproductive characteristics. Methods We sampled 3000 men who presented for reproductive urology evaluation from 2012-2020, of which 104 men underwent high-resolution Y-chromosome microarray testing, and five men were identified to have complete AZFc microduplications. Medical, surgical, and reproductive histories were obtained. Semen and hormonal parameters as well as response to fertility therapies were recorded. Results Five men were identified as having complete AZFc microduplications. The mean age was 33.75 years, representing 0.2% (5/3000) of men presenting for fertility investigation, 4.8% (5/104) of men undergoing microarray testing, and 21% (5/24) of men with AZFc abnormalities. Two of the men had prior undescended testicles and one had several autoimmune processes. The mean follicle-stimulating hormone (FSH) was 5.5 IU/L, luteinizing hormone (LH) 3.6 IU/L, and testosterone 14.56 nmol/L. One man was azoospermic, one man alternated between severe oligospermia and rare non-motile sperm, one had variable parameters, with one semen analysis demonstrating azoospermia and a second demonstrating a total motile sperm count (TMSC) of 4 ×106, one man was persistently oligospermic with TMSCs ranging 3.96-12.6 ×106, and one man initially had severe oligospermia, with a mean TMSC of 1.5 ×106, which increased to 21.7 ×106 after intervention (varicocele embolization, clomiphene citrate). This last man then fathered a spontaneous pregnancy. Conclusion AZFc complete microduplications are a rare cause of spermatogenic failure but not an uncommon form of AZFc abnormality. Clinically, they represent a heterogeneous group, having a variable reproductive potential. Cases should be managed on an individual basis.

How far will they go? Distance and driving times that north American men travel to see a reproductive urologist.

Male factor infertility affects about 50% of infertile couples. However, male factor infertility is largely under-evaluated due to multiple reasons. This study is to determine the time men travel for fertility evaluation, and factors associated with driving longer. Data from the Andrology Research Consortium were analysed. Driving distance and time were calculated by comparing "patient postal code" with "clinic postal code", then stratified into quartiles. Patients with the longest driving times (> 75th percentile [Q4]) were compared with those having shorter driving times. Logistic regression analysis was used to identify factors associated with longer driving times. Sixteen clinics and 3029 men were included. The median driving distance was 18.1 miles, median driving time was 32 min, and Q4 driving time was 49 min. Factors correlated with having Q4 driving time were age > 30 years, native Indian and Caucasian race, body mass index (BMI) > 30 kg/m2 , history of miscarriage, children with previous partner, self-referral, prior vasectomy, and prior marijuana use. On logistic regression, males aged < 30 years were more likely to be in Q4 for driving time versus older males. Blacks and Asians were less likely to travel further than Caucasians. Overweight/obese men, those having children with previous partner, and with prior vasectomy were more likely to be in Q4 travelling time. Factors correlated with longer driving times include younger age, native Indian and Caucasian race, higher BMI, children with prior partner, and prior vasectomy. These may reflect groups that drive long distances for reproductive care. The study provides an opportunity to better access these groups and minimise their barriers to fertility care.

Artificial Intelligence Based Machine Learning Models Predict Sperm Parameter Upgrading after Varicocele Repair: A Multi-Institutional Analysis.

PURPOSE: Varicocele repair is recommended in the presence of a clinical varicocele together with at least one abnormal semen parameter, and male infertility. Unfortunately, up to 50% of men who meet criteria for repair will not see meaningful benefit in outcomes despite successful treatment. We developed an artificial intelligence (AI) model to predict which men with varicocele will benefit from treatment. MATERIALS AND METHODS: We identified men with infertility, clinical varicocele, and at least one abnormal semen parameter from two large urology centers in North America (Miami and Toronto) between 2006 and 2020. We collected pre and post-operative clinical and hormonal data following treatment. Clinical upgrading was defined as an increase in sperm concentration that would allow a couple to access previously unavailable reproductive options. The tiers used for upgrading were: 1-5 million/mL (ICSI/IVF), 5-15 million/mL (IUI) and >15 million/mL (natural conception). Thus moving from ICSI/IVF to IUI, or from IUI to natural conception, would be considered an upgrade. AI models were trained and tested using R to predict which patients were likely to upgrade after surgery. The model sorted men into categories that defined how likely they were to upgrade after surgery (likely, equivocal, and unlikely). RESULTS: Data from 240 men were included from both centers. A total of 45.6% of men experienced an upgrade in sperm concentration following surgery, 48.1% did not change, and 6.3% downgraded. The data from Miami were used to create a random forest model for predicting upgrade in sperm concentration. On external validation using Toronto data, the model accurately predicted upgrade in 87% of men deemed likely to improve, and in 49% and 36% of men who were equivocal and unlikely to improve, respectively. Overall, the personalized prediction for patients in the validation cohort was accurate (AUC 0.72). CONCLUSIONS: A machine learning model performed well in predicting clinically meaningful post-varicocelectomy sperm parameters using pre-operative hormonal, clinical, and semen analysis data. To our knowledge, this is the first prediction model to show the utility of hormonal data, as well as the first to use machine learning models to predict clinically meaningful upgrading. This model will be published online as a clinical calculator that can be used in the preoperative counseling of patients.

Semen and serum platinum levels in cisplatin-treated survivors of germ cell cancer.

BACKGROUND: Testicular cancer survivors often have impaired gonadal function possibly related to chemotherapy. Platinum is a heavy metal that can be detected at low levels in serum many years after treatment, it is not known whether platinum also persists in semen and if platinum persistence in semen is associated with impaired fertility. METHODS: Adult cisplatin-treated testicular cancer survivors were enrolled. High-Performance Liquid Chromatography-tandem mass spectrometry was used to measure semen and serum platinum levels. Semen quality and DNA Fragmentation Index (DFI) were assessed. RESULTS: From 11/2017 to 12/2019, 38 patients (median age 32 years; range: 19-52) were enrolled. Median cumulative cisplatin dose was 301 mg/m2 (range: 274-404). Platinum levels were higher in semen than in blood (p = 0.03). Semen platinum levels were not significantly associated with time from last cisplatin dosing (r = -0.34; p = 0.09) nor cumulative dose (r = -0.10, p = 0.63). Sperm concentration was correlated with time from last cisplatin dosing (r = 0.58, p < 0.001) but not with semen platinum level (r = -0.15, p = 0.46). DFI was not significantly associated with time from last cisplatin dosing (r = 0.55, p = 0.08) or semen platinum level (r = -0.32, p = 0.33). In four patients with serial semen samples, platinum level decreased and sperm concentration and motility increased over time. CONCLUSIONS: Platinum is detected in semen of testicular cancer survivors at higher levels than matched blood samples. These preliminary findings may have important implications for the reproductive health of survivors of advanced testicular cancer, further study is needed to assess the relationship between platinum persistence in semen and recovery of fertility postchemotherapy.

Evaluation of patient compliance with the use of scrotal cooling devices.

OBJECTIVE: To evaluate the compliance of infertile men with the use of scrotal cooling devices. As a secondary objective, sperm parameters, deoxyribonucleic acid fragmentation, and hormone profiles were examined. DESIGN: This exploratory study on scrotal cooling provided scrotal cooling devices to men with primary infertility and abnormal semen parameters. Feedback on the devices after their use was gathered in the form of a questionnaire, and semen parameters were examined after device use. SETTING: Single center infertility clinic in Toronto, Ontario, Canada. PATIENTS: Patients with primary infertility and abnormal semen parameters were prospectively evaluated before and after scrotal cooling. INTERVENTIONS: One of two scrotal cooling devices (Underdog or Snowballs) was used, on the basis of patient preference. MAIN OUTCOME MEASURES: Questionnaires were completed by patients on compliance with device use and concerns about and recommendations for improving the cooling devices. Baseline deoxyribonucleic acid fragmentation index, sperm parameters, and hormones were measured at the initial visit (t = 0) and at subsequent visits (t = 4-12 weeks). Statistical comparison of values before and after scrotal cooling was performed. RESULTS: Forty patients were enrolled in the study, and the questionnaire was completed by 65.0% (n = 26). Most respondents (76.9%) used scrotal cooling less than the recommended duration. Respondents believed that the devices were uncomfortable (31.5%), impeded work (21.0%), and lost cooling rapidly (14.3%). Significant increases in sperm motility and vitality (from 25.4 % to 29.0% and from 64.8% to 71.7%, respectively) were demonstrated after scrotal cooling. CONCLUSIONS: Most patients were not compliant with the recommended use of the scrotal cooling devices because of issues of comfort, convenience, and concealability. Further work on improving scrotal cooling devices is necessary to enhance their potential as a therapeutic tool for men with abnormal sperm parameters and infertility.

One size does not fit all: variations by ethnicity in demographic characteristics of men seeking fertility treatment across North America.

OBJECTIVE: To compare racial differences in male fertility history and treatment. DESIGN: Retrospective review of prospectively collected data. SETTING: North American reproductive urology centers. PATIENT(S): Males undergoing urologist fertility evaluation. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Demographic and reproductive Andrology Research Consortium data. RESULT(S): The racial breakdown of 6,462 men was: 51% White, 20% Asian/Indo-Canadian/Indo-American, 6% Black, 1% Indian/Native, <1% Native Hawaiian/Other Pacific Islander, and 21% "Other". White males sought evaluation sooner (3.5 ± 4.7 vs. 3.8 ± 4.2 years), had older partners (33.3 ± 4.9 vs. 32.9 ± 5.2 years), and more had undergone vasectomy (8.4% vs. 2.9%) vs. all other races. Black males were older (38.0 ± 8.1 vs. 36.5 ± 7.4 years), sought fertility evaluation later (4.8 ± 5.1 vs. 3.6 ± 4.4 years), fewer had undergone vasectomy (3.3% vs. 5.9%), and fewer had partners who underwent intrauterine insemination (8.2% vs. 12.6%) compared with all other races. Asian/Indo-Canadian/Indo-American patients were younger (36.1 ± 7.2 vs. 36.7 ± 7.6 years), fewer had undergone vasectomy (1.2% vs. 6.9%), and more had partners who underwent intrauterine insemination (14.2% vs. 11.9%). Indian/Native males sought evaluation later (5.1 ± 6.8 vs. 3.6 ± 4.4 years) and more had undergone vasectomy (13.4% vs. 5.7%). CONCLUSION(S): Racial differences exist for males undergoing fertility evaluation by a reproductive urologist. Better understanding of these differences in history in conjunction with societal and biologic factors can guide personalized care, as well as help to better understand and address disparities in access to fertility evaluation and treatment.

The effect of ethnicity on semen analysis and hormones in the infertile patient.

INTRODUCTION: We aimed to study the association of ethnicity on semen parameters and hormones in patients presenting with infertility. METHODS: Data from men presenting for infertility assessment were prospectively collected and retrospectively reviewed. Demographic and clinical history was self-reported. Semen analysis included volume, count, motility, morphology, and vitality. The 2010 World Health Organization cutoffs were used. Baseline total testosterone and follicle-stimulating hormone (FSH) levels were recorded. Ethnicity data was classified as Caucasian, African Canadian, Asian, Indo-Canadian, Native Canadian, Hispanic, and Middle Eastern. All patients with complete data were included and statistical analysis was performed. RESULTS: A total of 9079 patients were reviewed, of which 3956 patients had complete data. Of these, 839 (21.2%) were azoospermic. After adjusting for age, African Canadians (odds ratio [OR] 1.70; 95% confidence interval [CI] 1.28-2.25) and Asians (1.34; 95% CI 1.11-1.62) were more likely to be azoospermic compared to Caucasians. Similarly, African Canadians (OR 1.75; 95% CI 1.33-2.29) were more likely to be oligospermic and Asians (OR 0.82; 95% CI 0.70-0.97) less likely to be oligospermic. Low volume was found in African Canadian (OR 1.42; 95% CI 1.05-1.91), Asians (OR 1.23; 95% CI 1.01-1.51), and Indo-Canadians (OR 1.47; 95% CI 1.01-2.13). Furthermore, Asians (OR 0.73; 95% CI 0.57-0.93) and Hispanics (OR 0.58; 95% CI 034-0.99) were less likely to have asthenospermia. Asians (OR 0.73; 95% CI 0.57-0.94) and Indo-Canadians (OR 0.58; 95% CI 0.35-0.99) were less likely to have teratozospermia. No differences were seen for vitality. No differences were seen for FSH levels, however, Asians (p<0.01) and Indo-Canadians (p<0.01) were more likely to have lower testosterone. CONCLUSIONS: Our study illustrates that variations in semen analyses and hormones exist in men with infertility. This may provide insight into the workup and management for infertile men from different ethnicities.

A Randomized, Double-Blind, Controlled Trial Shows that Onabotulinum Toxin A Nerve Blocks do Not Provide Improved Pain Control in Men with Chronic Scrotal Pain.

PURPOSE: The use of onabotulinum toxin A to chemically denervate the testis has been studied as a minimally invasive therapy to treat chronic scrotal pain. To our knowledge no randomized, controlled trials of onabotulinum toxin A for chronic scrotal pain management have been reported to date. MATERIALS AND METHODS: In this double-blind, randomized, controlled trial men with chronic scrotal pain who achieved at least temporary pain relief following a cord block with local anesthesia were randomly assigned to a block using local anesthesia alone vs local anesthesia plus 200 IU onabotulinum toxin A. Standardized assessments of pain levels using a visual analogue score, disease impact, quality of life and mood were performed 1, 2, 3, 4, 12 and 18 weeks after injection. The study primary outcome was the change in the visual analogue score at 1 month. After study completion the men in the control group were given the option to receive onabotulinum toxin A as part of an open label trial. RESULTS: Of 64 men with a mean ± SD age of 45.9 ± 11 years and a mean 5.7 ± 5.7-year history of pain 32 received local anesthesia plus onabotulinum toxin A and 32 received local anesthesia alone. There was no statistically significant difference in any measured outcome when comparing those who received onabotulinum toxin A to controls. Nine of the 13 men (69.2%) in the open label trial achieved an improvement in the visual analogue score (mean group score 6.1 ± 1.66 to 4.5 ± 2.36, Student t-test p=0.022) with a reduction in persistent pain at 3 months in 6 of the 9 (66.7%). CONCLUSIONS: This randomized, double-blind, controlled trial showed no superiority of onabotulinum toxin A plus local anesthesia over local anesthesia alone for pain control in men with chronic scrotal pain. Interestingly, significant pain improvement was noted in our open label onabotulinum toxin A trial, suggesting a potential placebo effect.

Reproductive endocrinologists are the gatekeepers for male infertility care in North America: results of a North American survey on the referral patterns and characteristics of men presenting to male infertility specialists for infertility investigations.

OBJECTIVE: To characterize the referral patterns and characteristics of men presenting for infertility evaluation using data obtained from the Andrology Research Consortium. DESIGN: Standardized male infertility questionnaire. SETTING: Male infertility centers. PATIENT(S): Men presenting for fertility evaluation. INTERVENTION(S): Not applicable. MAIN OUTCOME MEASURE(S): Demographic, infertility history, and referral data. RESULT(S): The questionnaires were completed by 4,287 men, with a mean male age of 40 years ± 7.4 years and female partners age of 37 years ± 4.9 years. Most were Caucasian (54%) with other races being less commonly represented (Asian 18.6%, and African American 5.5%). The majority (59.7%) were referred by a reproductive gynecologist, 19.4% were referred by their primary care physician, 4.2% were self-referred, and 621 (14.5%) were referred by "other." Before the male infertility investigation, 12.1% of couples had undergone intrauterine insemination, and 4.9% of couples had undergone in vitro fertilization (up to six cycles). Among the male participants, 0.9% reported using finasteride (5α-reductase inhibitor) at a dose used for androgenic alopecia, and 1.6% reported exogenous testosterone use. CONCLUSION(S): This broad North American patient survey shows that reproductive gynecologists are the de facto gateway for most male infertility referrals, with most men being assessed in the male infertility service being referred by reproductive endocrinologists. Some of the couples with apparent male factor infertility are treated with assisted reproductive technologies before a male factor investigation. The survey also identified potentially reversible causes for the male infertility including lifestyle factors such as testosterone and 5α-reductase inhibitor use.

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.

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 men's 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.

Quality of life in men with chronic scrotal pain.

Background: Chronic scrotal pain (CSP) is a common and often debilitating condition found in up to 4.75% of men. There is little written on the impact of CSP on men's lives. Aim: The aim of this study was to understand the impact of CSP on men's lives. Methods: Patients with CSP were prospectively asked to complete a comprehensive questionnaire, including questions on quality of life (QoL), activities, and mood. Results: The mean age of the 131 patients was 43 years. Pain was intermittent, with severe pain episodes (mean pain scores 7.2 ± 2 out of 10) affecting men on average 40% ± 30% of the time. Overall, 88/131 (67.17%) of patients responded that they felt "unhappy" or "terrible" with their present situation. More than 40% of patients complained of depressive symptoms more than half the days of the month. Normal activities were adversely affected, with 68/131 (51.90%) reporting limited ability to work, 93/131 (70.99%) patients reporting decreased physical activity, and 81/131(61.83%) reporting decreased sexual activity. Comparing men with pain levels ≥ 7/10 vs. those with pain levels < 7/10, 47% (41/88) vs. 8.1% (3/37) reported that they felt "terrible," 40% (35/88) vs. 13% (5/38) had depressive feelings more than half the time, and 35% (28/80) vs. 16% (6/38) felt little pleasure doing things (P < 0.01 for all). Conclusion: Our study suggests that QoL, mood, and the ability to perform normal activities are profoundly disturbed in CSP patients and that the pain severity is directly related to QoL.

Contexte: La douleur scrotale chronique est une affection commune et souvent débilitante dont souffrent près de 4,75 % des hommes. Il y a peu d'écrits sur l'impact de la douleur scrotale chronique sur la vie des hommes.But: Comprendre l'impact de la douleur scrotale chronique sur la vie des hommes.Méthodes: On a demandé de manière prospective à des patients souffrant de douleur scrotale chronique de remplir un questionnaire détaillé comprenant des questions sur leur qualité de vie, leurs activités et leur humeur.Résultats: L'âge moyen des 131 patients était de 43 ans. La douleur était intermittente, comportait des épisodes de douleur intense (scores de la douleur moyens 7,2 +/- 2 sur 10) et affectait les hommes 40 % +/- 30 % du temps. Globalement, 88/131 (67,17 %) des patients ont répondu qu'ils se sentaient malheureux ou « horriblement mal ¼ en raison de leur situation actuelle. Plus de 40 % des patients se sont plaints de symptômes de dépression plus de la moitié des jours du mois. Leurs activités habituelles étaient affectées négativement, alors que 68/131 (51,90 %) disaient avoir une capacité de travail limitée, que 93/131 (70,99 %) des patients signalaient une diminution de leur activité physique et que 81/131 (61,83 %) d'entre eux faisaient état d'une diminution de leur activité sexuelle. La comparaison des hommes qui avaient un niveau de douleur ≥ 7/10 à ceux qui avaient un niveau de douleur < 7/10 a révélé que 47 % d'entre eux (41/88) se sentaient « horriblement pas bien ¼ contre 8,1 % (3/37), que 40 % (35/88) avaient des sentiments dépressifs plus de la moitié du temps contre 13 % (5/38) et que 35 % (28/80) ressentaient peu de plaisir à faire les choses contre 16 % (6/38) (p < 0,01 pour tous).Conclusion: Notre étude suggère que la qualité de vie, l'humeur et la capacité à vaquer à ses activités habituelles sont profondément perturbées chez les patients qui souffrent de douleur scrotale chronique et que l'intensité de la douleur est directement liée à la qualité de vie.

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.

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 × 10(6)/ml; motility 15.72 ± 12.26%; total motile sperm count 76.67 ± 180.30 × 10(6). 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 patient's 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.