Idiopathic secondary azoospermia occurrence in men with oligospermia over time.

PURPOSE: To investigate the occurrence of idiopathic secondary azoospermia (ISA) in men with oligospermia over time and identify risk factors for ISA in this population. METHODS: This was a retrospective cohort study conducted in a university-affiliated male infertility clinic. A total of 1056 oligospermic men (concentration < 15 million/ml (M/ml) and no azoospermia) with at least two SA done between 2000 and 2019 were included. The primary outcome was the occurrence of ISA by oligospermia severity. RESULTS: In the entire cohort, 31 patients (2.9%) eventually became azoospermic with time. The ≤ 1 M/ml extremely severe oligospermia (ESO) group (283 patients) had significantly higher rates of ISA in each time period compared to the 1-5 M/ml severe oligospermia (SO) (310 patients) and 5-15 M/ml mild oligospermia (MO) (463 patients) groups (p < 0.05 for all comparisons), with rates of 21.1% in the ESO, 4.8% in the SO, and 0% in the MO group (p = 0.02) after 3-5 years, reaching 32% after 5 years in the ESO group compared to no cases in the other two groups (p = 0.006). Parameters shown to predict ISA were initial concentration < 1 M/ml (OR 22.12, p < 0.001) and time interval of > 3 and 5 years (OR 4.83 and 6.84, p = 0.009 and < 0.001, respectively), whereas testosterone levels were negatively associated with ISA (OR 0.88, p = 0.03). CONCLUSIONS: Men with ≤ 1 M/ml, especially those with low testosterone levels, have a dramatically increased chance of becoming azoospermic with time. Therefore, sperm banking should be recommended in these cases. Men with a sperm concentration above 1 M/ml have low chances of becoming azoospermic, even after 3 or more years.

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.

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.

Testosterone Deficiency: A Review and Comparison of Current Guidelines.

BACKGROUND: There is much controversy regarding the appropriate evaluation and management of testosterone deficiency (TD). AIM: To compare current guidelines on the evaluation and management of TD to provide clarity for patients and clinicians, as well as to highlight areas of controversy. METHODS: A literature search of MEDLINE, Embase, Cochrane Library, and various association websites was performed to identify guidelines for TD. OUTCOMES: Key aspects in the approach were compared, with a focus on the biochemical definition (cutoff) for low testosterone (T), principles of management, and recommendations for testosterone therapy (TTh) in special patient populations. RESULTS: Guidelines from the Canadian Medical Association Journal, American Urological Association, European Association of Urology, Endocrine Society, International Society for Sexual Medicine, and British Society for Sexual Medicine were included for review. Recommendations were generally consistent across guidelines. Key differences include the biochemical cutoff for low T, and recommendations for patients with low to normal T, prostate cancer, or cardiovascular disease. We highlight several case scenarios in which management differs depending on the guideline adopted. CLINICAL IMPLICATIONS: Although general diagnostic and management principles are in agreement across the guidelines, notable differences may impact patient diagnosis and eligibility for TTh. STRENGTHS & LIMITATIONS: Only guidelines written in English were included. The quality of the included guidelines was not evaluated, but this was beyond the scope of this review. CONCLUSION: We highlight the limitations of relying exclusively on guidelines in managing patients with TD. Kwong JCC, Krakowsky Y, Grober E. Testosterone Deficiency: A Review and Comparison of Current Guidelines. J Sex Med 2019;16:812-820.

Peyronie's disease and testosterone deficiency: Is there a link?

INTRODUCTION: Peyronie's disease (PD) and testosterone deficiency (TD) impact men at the same stage of life and can ultimately contribute to erectile dysfunction. There is speculation that low levels of testosterone (T) may predispose men to penile fibrosis; however, there is no published, up-to-date review summarizing the current evidence. Therefore, we conducted a narrative review of the literature exploring the relationship between PD and TD. METHODS: A comprehensive systematic search of existing literature of five online databases from June 1990 to June 2018 examining the relationship between PD and TD was conducted. The Cochrane risk-of-bias tool for randomized trials and the risk-of-bias assessment tool for cohort studies were used to evaluate the quality of studies. RESULTS: Six studies were identified (n = 675). Overall, five studies supported the link between PD and TD by demonstrating relationships in PD patients with low total T, free T, bioavailable T, greater penile curvature, and plaque development. However, one study demonstrated no connection between the conditions. The literature is restricted by small studies with methodological flaws. CONCLUSION: There are a number of mechanisms to support the link between TD and PD. The literature on the topic is limited by small studies which are overall conflicting. The findings of this work suggest the need for larger, prospective studies to clarify the role of TD in the development, evaluation, and treatment of PD. Establishing such a relationship could change management of PD as a diagnosis of PD may encourage clinicians to evaluate a patient's testosterone levels.

Prevalence and Management of Incidental Small Testicular Masses Discovered on Ultrasonographic Evaluation of Male Infertility.

PURPOSE: We report the safety of surveillance of small testicular masses incidentally discovered during evaluation of male infertility. MATERIALS AND METHODS: We retrospectively reviewed a prospectively collected database to identify patients with male infertility found to have incidental small testicular masses (hypoechoic lesions less than 10 mm) on scrotal ultrasound. The men were offered close surveillance with interval imaging and office followup. Patient and imaging characteristics were collected to compare the surveillance and surgical groups with additional comparisons between benign and malignant pathologies to elucidate predictors of underlying malignancy. RESULTS: Of 4,088 men in whom scrotal ultrasound was completed for male infertility evaluation 120 (2.9%) were found to have a subcentimeter testicular mass. Average followup was 1.30 years (range 0.1 to 16.9). A total of 18 men (15%) proceeded to extirpative surgery while 102 remained on surveillance at last followup. In those with at least 1 month of followup the mean lesion growth rate was -0.01 mm per year. Reasons for surgery included testicular exploration for infertility, mass growth, positive tumor markers, history of testis cancer, concerning imaging characteristics and patient choice. Six of the 18 men who underwent surgery were found to have malignancy, which was seminoma in all. All malignant lesions were greater than 5 mm on initial imaging and demonstrated vascularity, although size and vascularity were not significantly different from those of benign lesions on final pathology findings. No patients demonstrated advanced or recurrent disease. CONCLUSIONS: Small testicular masses are not uncommon, especially in the infertile male population. Most of these masses do not show significant growth during long-term evaluation and can be safely surveilled with close followup.

Basic Laparoscopic Skills Assessment Study: Validation and Standard Setting among Canadian Urology Trainees.

PURPOSE: As urology training programs move to a competency based medical education model, iterative assessments with objective standards will be required. To develop a valid set of technical skills standards we initiated a national skills assessment study focusing initially on laparoscopic skills. MATERIALS AND METHODS: Between February 2014 and March 2016 the basic laparoscopic skill of Canadian urology trainees and attending urologists was assessed using 4 standardized tasks from the AUA (American Urological Association) BLUS (Basic Laparoscopic Urological Surgery) curriculum, including peg transfer, pattern cutting, suturing and knot tying, and vascular clip applying. All performances were video recorded and assessed using 3 methods, including time and error based scoring, expert global rating scores and C-SATS (Crowd-Sourced Assessments of Technical Skill Global Rating Scale), a novel, crowd sourced assessment platform. Different methods of standard setting were used to develop pass-fail cut points. RESULTS: Six attending urologists and 99 trainees completed testing. Reported laparoscopic experience and training level correlated with performance (p <0.01). Attending urologists were significantly better than trainees (p <0.05), demonstrating construct validity evidence for the 4 AUA BLUS tasks. The C-SATS method of assessment correlated well with the traditional methods of time and error based scoring, and the global rating scale. We were able to use relative and absolute standard setting methods to define pass-fail cut points for all 4 AUA BLUS tasks. CONCLUSIONS: The 4 AUA BLUS tasks demonstrated good construct validity evidence for use in assessing basic laparoscopic skill. Performance scores using the novel C-SATS platform correlated well with traditional time-consuming methods of assessment. Various standard setting methods were used to develop pass-fail cut points for educators to use when making formative and summative assessments of basic laparoscopic skill.

The relationship between sperm viability and DNA fragmentation rates.

BACKGROUND: In humans, sperm DNA fragmentation rates have been correlated with sperm viability rates. Reduced sperm viability is associated with high sperm DNA fragmentation, while conversely high sperm viability is associated with low rates of sperm DNA fragmentation. Both elevated DNA fragmentation rates and poor viability are correlated with impaired male fertility, with a DNA fragmentation rate of >30% indicating subfertility. We postulated that in some men, the sperm viability assay could predict the sperm DNA fragmentation rates. This in turn could reduce the need for sperm DNA fragmentation assay testing, simplifying the infertility investigation and saving money for infertile couples. METHODS: All men having semen analyses with both viability and DNA fragmentation testing were identified via a prospectively collected database. Viability was measured by eosin-nigrosin assay. DNA fragmentation was measured using the sperm chromosome structure assay. The relationship between DNA fragmentation and viability was assessed using Pearson's correlation coefficient. RESULTS: From 2008-2013, 3049 semen analyses had both viability and DNA fragmentation testing. A strong inverse relationship was seen between sperm viability and DNA fragmentation rates, with r=-0.83. If viability was ≤50% (n=301) then DNA fragmentation was ≥ 30% for 95% of the samples. If viability was ≥75% (n=1736), then the DNA fragmentation was ≤30% for 95% of the patients. Sperm viability correlates strongly with DNA fragmentation rates. CONCLUSIONS: In men with high levels of sperm viability≥75%, or low levels of sperm viability≤ 30%, DFI testing may be not be routinely necessary. Given that DNA fragmentation testing is substantially more expensive than vitality testing, this may represent a valuable cost-saving measure for couples undergoing a fertility evaluation.

Accuracy of testosterone concentrations in compounded testosterone products.

OBJECTIVE: This study aims to evaluate the accuracy of the testosterone concentrations within testosterone gels and creams manufactured by compounding pharmacies. METHODS: Ten compounding pharmacies within Toronto area were included. Pharmacies were blinded as to the nature of the study. A standardized prescription for 50 mg of compounded testosterone gel/cream applied once daily was presented to each pharmacy. Two independently compounded batches were analyzed from each pharmacy 1 month apart. Testosterone concentrations in a 5-g sachet of Androgel® 1% (Abbott) and 5-g tube of Testim®1% (Auxilium) were evaluated as controls. Samples were analyzed independently and in a blinded fashion by the Laboratory Medicine Program at the University Health Network. Measurement of testosterone concentration was performed using a modified liquid chromatography tandem mass spectrometry validated for serum testosterone. RESULTS: Compounded formulations included seven gels and three creams with a volume/daily dose ranging from 0.2 mL to 1.25 mL. Product cost ranged from $57.32 to $160.71 for a 30-day supply. There was significant variability both within and between pharmacies with respect to the measured concentration of testosterone in the compounded products. In contrast, the concentration of testosterone within Androgel and Testim was consistent and accurate. Collectively, only 50% (batch 1) and 30% (batch 2) of the compounding pharmacies provided a product with a testosterone concentration within ± 20% of the prescribed dose. Two pharmacies compounded products with >20% of the prescribed dose. One pharmacy compounded a product with essentially no testosterone. CONCLUSIONS: Testosterone concentrations in compounded testosterone products can be variable and potentially compromise the efficacy and safety of treatment.

Testosterone therapy at the time of vasectomy reversal: Impact on intraoperative decision-making and interpretation of postoperative outcomes.

INTRODUCTION: During vasectomy reversal (VR), accurate intraoperative microscopic assessment of the vasal fluid for sperm presence and quality is essential in determining the indication for a vasovasostomy (VV) or vasoepididymostomy (VE). The use of testosterone therapy (TT), known to supress spermatogenesis, can potentially interfere with this determination. This initiative evaluated the impact of TT on vasal and epididymal fluid sperm characteristics and intraoperative decision-making among men on TT at the time of VR. METHODS: Of 2622 consecutive VRs performed from 2007-2023, patients actively using TT at the time of VR were identified. Details as to the type, dose, and duration of TT were documented. All patients were counselled regarding the impact of TT on spermatogenesis and encouraged to discontinue TT if possible. During VR, vasal and epididymal fluid (as indicated) was sampled and each aspirate underwent microscopic evaluation for sperm presence and quality, and categorized as: motile sperm/intact-non-motile sperm/sperm parts/no sperm. Rates of sperm presence/absence in the vasal/epididymal fluid, frequency of VV/VE, postoperative patency (presence of motile sperm), and semen parameters were compared among patients on TT vs. clinically matched patients not using TT at the time of VR. RESULTS: Among the 2622 VRs reviewed, 54 men (2%) reported using TT at the time of their VR. Despite its impact on spermatogenesis, intraoperative microscopic analysis of the reproductive fluid (vasal or epididymal) identified the presence of sperm in 95% (51/54) of patients. Testis biopsy confirmed sperm production among three patients with absence of sperm within the vasal or epididymal fluid. Rates of VV or VE did not significantly differ among men using TT at the time of VR compared to nonusers. Postoperative patency rates (TT: 78 % vs. no TT: 93%) and mean total motile sperm counts (TMC) were lower among patients using TT at the time of VR (7.9 vs. 28.3, p=0.02). CONCLUSIONS: Use of TT at the time of VR does not appear to impact rates of intraoperative microscopic identification of sperm within the reproductive fluid or the indication for VV/VE. Postoperative patency rates and total motile sperm counts may be lowered by use of TT. Moreover, the determination to the etiology azoospermia postoperatively (production vs. obstruction) may be clouded by the use of TT during VR.

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.

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.

Preoperative hair removal on the male genitalia: clippers vs. razors.

INTRODUCTION: In an effort to reduce the incidence of postoperative surgical site infections (SSIs), many hospitals have adopted a strict practice of preoperative hair removal using clippers, as opposed to razors. However, the skin of the male genitalia is delicate, elastic with irregular skin folds and may be ill-suited for clippers. AIM: To compare shave quality and the degree of skin trauma using two methods of preoperative hair removal on the scrotal skin: clippers vs. razors. METHODS: Patients undergoing surgery involving the male genitalia requiring preoperative hair removal were randomized to hair removal using clippers or a razor. Immediately following hair removal, a standardized digital photograph was taken of the male genitalia. All digital photos were evaluated in a blinded fashion by groups of urologic surgeons and surgical nurses using a standardized five-point global rating scale. The incidence of SSIs was monitored. MAIN OUTCOME MEASURES: Primary outcomes included blinded global ratings of (i) the completeness of the preoperative hair removal within the surgical field and (ii) degree of skin trauma following hair removal. The incidence of SSIs within 3 months of surgery was monitored throughout the study period. RESULTS: Two hundred fifteen consecutive patients were randomized (107 clipper, 108 razor). Overall, preoperative hair removal on the male genitalia using a razor resulted in significantly less skin trauma (P = 2.5E-10) and a more complete hair removal within the surgical field (P = 0.017) compared with clippers. SSIs were identified in four patients during follow-up (1.8%--two using clippers; two, razors). CONCLUSIONS: Our data suggest that preoperative hair removal on the scrotal skin using a razor results in less skin trauma and improved overall shave quality with no apparent increased risk of SSIs. Based on these findings, surgeons should be permitted their choice of razors or clippers for preoperative preparation of the male genitalia.

Survey of the quality and origins of websites on penile low-intensity shockwave therapy in Canada.

INTRODUCTION: The aim of this study was to establish the quality of patient-facing websites advertising low-intensity shockwave therapy (LISWT) for erectile dysfunction (ED) and Peyronie's disease (PD) patients in Canada. METHODS: Canadian websites offering LIWST for ED or PD were identified using online web searches. The characteristics of these websites were reviewed, along with examining the presence of HONCode certification, assigning a brief DISCERN score (a tool designed to evaluate health information online) and readability scores. We also examined the LIWST technology advertised, as well as benefits of LIWST cited by the websites. RESULTS: Twenty-five unique websites linked to 46 clinics were identified and reviewed. Twenty-four percent of websites were run by a urologist. Other specialties offering LISWT included general practitioners, anesthesiologists, naturopaths, nurse practitioners, physiotherapists, and registered massage therapists. Twenty-four percent of the websites advertised the use of a focused shockwave generator. Forty percent of the websites had peer-reviewed references. The average brief DISCERN score was 14 (standard deviation 3.4). There was no association between the physician-or non-physician-led websites and the use of peer-reviewed references, readability scores, the number of clinic locations, or higher brief discern scores. CONCLUSIONS: LISWT is readily advertised online for ED and PD patients in Canada; however, only a minority use a focused shockwave generator. There is a wide diversity of practitioners offering LISWT. Websites offering LISWT are generally of poor quality and do not provide adequate information for patients to make educated treatment decisions.

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.

Analysis of seminal plasma from patients with non-obstructive azoospermia and identification of candidate biomarkers of male infertility.

Infertility affects approximately 15% of couples with equivalent male and female contribution. Absence of sperm in semen, referred to as azoospermia, accounts for 5-20% of male infertility cases and can result from pretesticular azoospermia, non-obstructive azoospermia (NOA), and obstructive azoospermia (OA). The current clinical methods of differentiating NOA cases from OA ones are indeterminate and often require surgical intervention for a conclusive diagnosis. We catalogued 2048 proteins in seminal plasma from men presented with NOA. Using spectral-counting, we compared the NOA proteome to our previously published proteomes of fertile control men and postvasectomy (PV) men and identified proteins at differential abundance levels among these clinical groups. To verify spectral counting ratios for candidate proteins, extracted ion current (XIC) intensities were also used to calculate abundance ratios. The Pearson correlation coefficient between spectral counting and XIC ratios for the Control-NOA and NOA-PV data sets is 0.83 and 0.80, respectively. Proteins that showed inconsistent spectral counting and XIC ratios were removed from analysis. There are 34 proteins elevated in Control relative to NOA, 18 decreased in Control relative to NOA, 59 elevated in NOA relative to PV, and 16 decreased in NOA relative to PV. Many of these proteins have expression in the testis and the epididymis and are linked to fertility. Some of these proteins may be useful as noninvasive biomarkers in discriminating NOA cases from OA.

Vasectomy reversal provides long-term pain relief for men with the post-vasectomy pain syndrome.

PURPOSE: The post-vasectomy pain syndrome is a rare but serious and debilitating complication of vasectomy. For men with the post-vasectomy pain syndrome vasectomy reversal is a surgical option after medical management has failed. However, there is a paucity of data in the literature defining its therapeutic efficacy. In this study we better define the role and effect of vasectomy reversal in the treatment of men with the post-vasectomy pain syndrome. MATERIALS AND METHODS: Three urologists in Toronto, Ontario performed 149 publically funded vasectomy reversals between January 2000 and September 2010. The electronic health records were reviewed and 23 of the 149 (15%) procedures were performed for the post-vasectomy pain syndrome. Of these men who underwent 14 vasovasostomies 13 completed a telephone conducted questionnaire (response rate 56%). Patient demographics, preoperative and postoperative pain scores, and quality of life were retrospectively assessed. RESULTS: Orchialgia occurred a mean ± SD of 19 ± 42.5 months after vasectomy and the men (mean age 43.8 ± 5.2 years) experienced pain for 50.3 ± 34.9 months before vasovasostomy. After vasovasostomy improvement of pain occurred in 93% (13 of 14) and 50% were rendered pain-free with an average improvement in pain intensity scores of 65% (p <0.005). Of the men 15% (2 of 13) had a recurrence of pain to baseline but overall 79% (11 of 14) had a durable positive response. Quality of life was significantly improved after vasovasostomy (p <0.005) and 93% (13 of 14) of the patients said they would undergo the same operation again. CONCLUSIONS: Vasovasostomy is an effective treatment modality for the post-vasectomy pain syndrome, and it can achieve robust and durable long-term improvement in pain intensity and quality of life.

Time for improvement in semen parameters after varicocelectomy.

PURPOSE: While there are a number of studies documenting a positive effect of varicocelectomy on semen parameters, the length of time required following varicocelectomy for semen quality to improve is not well established. Therefore, in this study we identified the changes with time in semen parameters after varicocelectomy. MATERIALS AND METHODS: The records and database of 304 patients who underwent varicocele repair for subfertility were reviewed retrospectively. All men had at least 2 preoperative semen analyses as well as semen testing at 3 and 6 months postoperatively. RESULTS: For the 100 patients who met the study inclusion criteria mean sperm counts increased significantly by 3 and 6 months after varicocelectomy (by 53% and 38% by 3 and 6 months, p = 0.0003 and 0.001, respectively). By 3 and 6 months the combined groups had a mean 2.5 and 1.5-fold higher total motile count compared to the preoperative total motile count, respectively. There was no further improvement in semen parameters in those men followed for more than 6 months. There were no statistically significant differences in the improvement in semen volume, motility, count or total motile count comparing the results at 3, 6 and more than 9 months postoperatively. CONCLUSIONS: Sperm parameters improve by 3 months after varicocele repair and then do not improve further. This finding should allow physicians to decide quickly if varicocelectomy has been effective and, then, if required, plan on the use of other therapies to manage the couples' infertility.

Predictors of success after bilateral epididymovasostomy performed during vasectomy reversal: A multi-institutional analysis.

INTRODUCTION: Vasectomy reversal (VR) represents an excellent option for paternity in men who desire to expand their family following vasectomy. Traditional VR via vasovasostomy has a success rate upwards of 90% but when sperm or sperm parts are not present in vasal fluid, epididymovasostomy (EV) must be performed instead. Our objective was to determine which factors influence success after bilateral EV. METHODS: A prospectively maintained database with data from the U.S. and Canada was used to identify men who underwent bilateral EV at time of VR. Success was defined as motile sperm in any postoperative semen analyses. Multivariable logistic regression was used to identify predictors of success. RESULTS: A total of 200 men had at least one postoperative semen analysis, and 171 men were included in the analysis. Average age was 44.7 years, with average followup of seven months. Median time elapsed between vasectomy and EV was 15 years (interquartile range [IQR] 10-18). Overall success rate was 50%. Despite the study being adequately powered, factors such as years since vasectomy (odds ratio [OR] 1.01, confidence interval [CI] 0.95-1.06), age (OR 0.96, CI 0.91-1.01), intraoperative presence of motile sperm (OR 0.81, CI 0.41-1.62), and epidydimal fluid characteristics did not predict success. CONCLUSIONS: Bilateral EV at time of VR is successful in 50% of cases in a multi-institutional, North American cohort. Microsurgeons can be reassured that neither time elapsed nor epididymal fluid characteristics negatively impact success rates as long as sperm or sperm parts are present. Surgeons performing VR should be comfortable and prepared to perform EV if indicated.

Proteomic analysis of seminal plasma from normal volunteers and post-vasectomy patients identifies over 2000 proteins and candidate biomarkers of the urogenital system.

Seminal plasma is a fluid that originates from the testis, epididymis,prostate, and seminal vesicles, and hence, proteomic studies may identify potential markers of infertility and other diseases of the genito-urinary tract. We profiled the proteomes of pooled seminal plasma from fertile Control and post-vasectomy (PV) men. PV seminal plasma samples are void of proteins originating from the testis and the epididymis due to ligation of the vas deferens, and hence, comparative analysis of Control and PV data sets allows for identification of proteins originating from these tissues. Utilizing offline MudPIT and high-resolution mass spectrometry, we were able to identify over 2000 proteins in Control and PV pools each and over 2300 proteins all together. With semiquantitative analysis using spectral counting, we catalogued 32 proteins unique to Control, 49 at lower abundance in PV, 3 unique to PV, and 25 at higher abundance in PV. We believe that proteins unique to Control or at lower abundance in PV have their origin in the testis and the epididymis. Public databases have confirmed that many of these proteins originate from the testis and epididymis and are linked to the reproductive tract. These proteins may serve as candidate biomarkers for future studies of infertility and urogenital diseases.