Changes in Semen Analysis over Time: A Temporal Trend Analysis of 20 Years of Subfertile Non-Azoospermic Men.

PURPOSE: To examine trends of population-level semen quality over a 20-year period. MATERIALS AND METHODS: We performed a retrospective review of data from the andrology lab of a high volume tertiary hospital. All men with semen samples between 2000 and 2019 were included and men with azoospermia were excluded. Semen parameters were reported using the World Health Organization (WHO) 4th edition. The primary outcome of interest was changes in semen parameters over time. Generalized least squares (GLS) with restricted cubic splines were used to estimate average-monthly measurements, adjusting for age and abstinence period. Contrasts of the estimated averages based on GLS between the first and last months of collection were calculated. RESULTS: A total of 8,990 semen samples from subfertile non-azoospermic men were included in our study. Semen volume decreased over time and estimate average at the beginning and end were statistically different (p<0.001). Similarly sperm morphology decreased over time, with a statistically significant difference between estimated averages from start to finish (p<0.001). Semen pH appeared to be increasing over time, but this difference was not significant over time (p=0.060). Sperm concentration and count displayed an increase around 2003 to 2005, but otherwise remained fairly constant over time (p=0.100 and p=0.054, respectively). Sperm motility appeared to decrease over time (p<0.001). CONCLUSIONS: In a large sample of patients presenting to a single institution for fertility assessment, some aspects of semen quality declined across more than two decades. An understanding of the etiologies and driving forces of changing semen parameters over time is warranted.

The contemporary role of varicocele repair: why operate when in-vitro fertilization results are so good?

PURPOSE OF REVIEW: A male factor is either the primary cause or is contributory in at least half of all couples with infertility. Currently, many male factor problems may be disregarded, as reproductive technology has advanced so much that in-vitro fertilization (IVF)/Intracytoplasmic sperm injection (ICSI) allows the use of even a single sperm to achieve pregnancy. RECENT FINDINGS: Varicocele is the most commonly diagnosed correctable cause. Microsurgical repair is considered the gold standard for repair. Research has shown that varicocele repair can impact the outcome of reproductive management and upgrade male infertility from adoption or donor sperm only to IVF/ICSI and microTESE, or IVF/ICSI with ejaculated sperm, or from IVF/ICSI to intrauterine insemination (IUI) or often naturally conceived. SUMMARY: Varicocele diagnosis and repair is an essential part of infertility evaluation. Not only does it potentially impact antiretroviral therapy choices, but it can also increase testosterone levels benefiting long-term male health.

Validation of the SMH Equations for the Estimation of the Total Body Water Volume in Hemodialysis Patients.

Background: Online dialysis clearance monitors typically provide an accurate value for Kt. A value for V (total body water [TBW]) is required to calculate Kt/V, the measure of the adequacy of the delivered dialysis in hemodialysis (HD) patients. Using bioimpedance spectroscopy (BIS), we previously developed 2 sex-specific equations for the estimation of the TBW, which we have chosen to name the St Michael's Hospital (SMH) equations. Objective: The objective of this study was to validate the SMH equations in a second distinct population of patients. Design: Cross-sectional study. Setting: Single center hemodialysis unit at St Michael's Hospital, a tertiary care teaching hospital, in Toronto, Canada. Patients: Eighty-one adult HD patients who had been receiving conventional maintenance HD for at least 3 months. Measurements: Anthropometric measurements including weight, height, and waist circumference were collected. TBW was measured by BIS using the Body Composition Monitor (Fresenius Medical Care, Bad Homburg, Germany). Methods: The Bland-Altman method to calculate the bias and limits of agreement and the difference plot analysis were used to evaluate the difference between the BIS-TBW and the TBW derived from our equations (SMH equation) in this validation cohort. Results: The TBW values based on our equations had a high correlation with BIS-TBW (correlation coefficients = 0.93, P values < .01, bias = 1.8 [95% CI: 1-2.6] liter). Application of SMH equations closely predicted Kt/V, based on BIS value, in all categories of waist circumference. Limitations: Small sample size, single-center, not including peritoneal dialysis patients. A larger and more heterogeneous sample with more patients at the extremes of body mass index would allow for more detailed sub-group analyses in different races and different anthropometric categories to better understand the performance of these equations in discrete sub-groups of patients. Conclusions: In maintenance HD patients, our previously derived equations to estimate the TBW using weight and waist circumference appear to be valid in a distinct patient population. Given the centrality of TBW to the calculation of small molecule clearance, the SMH equations may enhance the measurement of dialysis adequacy and inform practice.

Contexte: En général, les versions en ligne des moniteurs de clairance de la dialyse fournissent une valeur de Kt précise. Une valeur de V (ECT = eau corporelle totale) est nécessaire pour calculer le Kt/V, soit la mesure de l'adéquation de la dialyse chez les patients sous hémodialyse (HD). Grâce à la spectroscopie de bio-impédance (BIS), nous avons précédemment développé deux équations spécifiques au sexe qui permettent d'estimer l'ECT, les « équations du St Michael's Hospital ¼ (équations SMH). Objectif: Valider les équations SMH dans une deuxième population distincte de patients. Conception: Étude transversale. Cadre: L'unité d'hémodialyse du St Michael's Hospital, un hôpital universitaire de soins tertiaires de Toronto (Canada). Sujets: 81 patients adultes suivant des traitements d'HD de maintien conventionnelle depuis au moins 3 mois. Mesures: Des mesures anthropométriques, soit le poids, la taille et le tour de taille, ont été recueillies. L'ECT a été mesurée par BIS (ECT-BIS) à l'aide d'un moniteur de composition corporelle, le Body Composition Monitor TM de Fresenius Medical Care (Bad Homburg, Allemagne). Méthodologie: La méthode Bland-Altman a été utilisée pour calculer le biais et les limites d'agrément. L'analyse des courbes de différence a servi à évaluer la différence entre l'ECT-BIS et l'ECT dérivée de nos équations (équations SMH) dans la cohorte de validation. Résultats: Les valeurs d'ECT obtenues par les équations se sont avérées très étroitement corrélées aux valeurs obtenues par bio-impédance (coefficient de corrélation: 0,93; valeurs de p < 0,01; biais = 1,8 litres [IC 95 %: 1-2,6]). L'application des équations SMH a prédit précisément le Kt/V, sur la base de la valeur par BIS, dans toutes les catégories de tour de taille. Limites: Échantillon de petite taille provenant d'un seul centre et n'incluant pas les patients sous dialyse péritonéale. Un échantillon plus vaste et plus hétérogène, avec davantage de patients dont l'IMC se situe aux extrêmes de la courbe, permettrait une analyse plus détaillée de sous-groupes provenant de différentes ethnies et présentant différentes catégories anthropométriques; ceci permettrait de valider la performance des équations SMH dans des sous-groupes distincts de patients. Conclusion: Dans une population de patients sous HD de maintien, nos équations précédemment dérivées, qui permettent d'estimer l'ECT à partir du poids et du tour de taille, semblent valides. Compte tenu de l'importance de l'ECT dans le calcul de la clairance des petites molécules, les équations SMH pourraient améliorer la mesure de l'adéquation de la dialyse et éclairer la pratique.

ShangRing versus Mogen clamp for early infant male circumcision in eastern sub-Saharan Africa: a multicentre, non-inferiority, adaptive, randomised controlled trial.

BACKGROUND: Use of medical devices represents a unique opportunity to facilitate scale-up of early infant male circumcision (EIMC) across sub-Saharan Africa. The ShangRing, a circumcision device prequalified by WHO, is approved for use in adults and adolescents and requires topical anaesthesia only. We aimed to investigate the safety and efficacy of the ShangRing versus the Mogen clamp for EIMC in infants across eastern sub-Saharan Africa. METHODS: In this multicentre, non-inferiority, open-label, randomised controlled trial, we enrolled healthy male infants (aged <60 days), with a gestational age of at least 37 weeks and a birthweight of at least 2·5 kg, from 11 community and referral centres in Kenya, Tanzania, and Uganda. Infants were randomly assigned (1:1) by a computer-generated text message service to undergo EIMC by either the ShangRing or the Mogen clamp. The primary endpoint was safety, defined as the number and severity of adverse events (AEs), analysed in the intention-to-treat population (all infants who underwent an EIMC procedure) with a non-inferiority margin of 2% for the difference in moderate and severe AEs. This trial is registered with Clinical. TRIALS: gov, NCT03338699, and is complete. FINDINGS: Between Sept 17, 2018, and Dec 20, 2019, a total of 1420 infants were assessed for eligibility, of whom 1378 (97·0%) were enrolled. 689 (50·0%) infants were randomly assigned to undergo EIMC by ShangRing and 689 (50·0%) by Mogen clamp. 43 (6·2%) adverse events were observed in the ShangRing group and 61 (8·9%) in the Mogen clamp group (p=0·078). The most common treatment-related AE was intraoperative pain (Neonatal Infant Pain Scale score ≥5), with 19 (2·8%) events in the ShangRing and 23 (3·3%) in the Mogel clamp group. Rates of moderate and severe AEs were similar between both groups (29 [4·2%] in the ShangRing group vs 30 [4·4%] in the Mogen clamp group; difference -0·1%; one-sided 95% CI upper limit of 1·7%; p=0·89). No treatment-related deaths were reported. INTERPRETATION: Use of the ShangRing device for EIMC showed safety, achieved high caregiver satisfaction, and did not differ from the Mogen clamp in other key measures. The ShangRing could be used by health systems and international organisations to further scale up EIMC across sub-Saharan Africa. FUNDING: Bill & Melinda Gates Foundation.

Microsurgical Management of Male Infertility: Compelling Evidence That Collaboration with Qualified Male Reproductive Urologists Enhances Assisted Reproductive Technology (ART) Outcomes.

A male factor plays a significant role in a couple's reproductive success. Today, advances in reproductive technology, such as intracytoplasmic sperm injection (ICSI), have allowed it to be possible for just a single sperm to fertilize an egg, thus, overcoming many of the traditional barriers to male fertility, such as a low sperm count, impaired motility, and abnormal morphology. Given these advances in reproductive technology, it has been questioned whether a reproductive urologist is needed for the evaluation and treatment of infertile and subfertile men. In this review, we aim to provide compelling evidence that collaboration between reproductive endocrinologists and reproductive urologists is essential for optimizing a couple's fertility outcomes, as well as for improving the health of infertile men and providing cost-effective care.

Microsurgical Excision of a Supernumerary Testis: A Novel Technique to Avoid Iatrogenic Injury to the Adjacent Testis.

INTRODUCTION: In this report, we discuss the evaluation of a patient with chronic scrotal pain found to have a supernumerary testis (SNT), as well as a novel microsurgical approach to safely removing this testis. TECHNICAL CONSIDERATIONS: To avoid any iatrogenic injury to the adjacent testis, we used an operating microscope to visualize the cord structures of both testes and carefully remove the smaller, atrophic, supernumerary testis. The surgery was successfully completed without any intraoperative or postoperative complications. Total operative time was 2 hours. While the patient had not yet attempted to conceive at the time of follow-up, given our careful dissection, we expect him to have normal testicular function and fertility in the future. CONCLUSION: This case demonstrates a novel microsurgical approach to excising a supernumerary testis that avoids injury to the blood supply, epididymis, and vas deferens associated with the normal testis.

Genitourinary Infections Related to Circumcision and the Potential Impact on Male Infertility.

Male circumcision (MC) is one of the oldest surgical procedures still completed today. Medical indications for MC include phimosis, recurrent balanitis, cosmesis, and infection prevention. In this review, we mainly focus on the role of MC in the prevention of human immunodeficiency virus, human papillomavirus, herpes simplex virus, gonorrhea, chlamydia, chancroid, and syphilis, and the subsequent impact of these genitourinary infections on male fertility. Overall, many compelling data support that MC may play an essential role in both genitourinary infection prevention and male fertility.

Effect of varicoceles on spermatogenesis.

Varicoceles are dilated veins within the spermatic cord and a relatively common occurrence in men. Fortunately, the large majority of men are asymptomatic, however, a proportion of men with varicoceles can suffer from infertility and testosterone deficiency. Sperm and testosterone are produced within the testis, and any alteration to the testicular environment can negatively affect the cells responsible for these processes. The negative impact of varicoceles on testicular function occurs mainly due to increased oxidative stress within the testicular parenchyma which is thought to be caused by scrotal hyperthermia, testicular hypoxia, and blood-testis barrier disruption. Management of varicoceles involves ligation or percutaneous embolization of the dilated veins. Repair of varicoceles can improve semen parameters and fertility, along with serum testosterone concentration. In this review, we discuss the pathophysiology of varicoceles, their impact on testicular function, and management.

Impact of testicular delivery and vasal vein ligation on clinical outcomes in men undergoing microsurgical varicocelectomy.

PURPOSE: To assess the impact of microsurgical varicocelectomy technique on clinical outcomes. METHODS: Men diagnosed with varicocele between 2017 and 2020 were reviewed. We included men who underwent microsurgical varicocelectomy by two high-volume surgeons who differed in surgical technique: Method (1) testicular delivery with gubernacular vein ligation, and ligation of vasal veins > 2.5 mm; Method (2) no delivery and ligation of dilated vasal veins in cases of recurrence. Post-operative changes for semen parameters, DNA fragmentation, and serum testosterone were evaluated for each technique and compared. RESULTS: 313 patients were included; 162 with Method 1 and 151 with Method 2. The cohorts were of similar age (median 35 years, interquartile range (IQR) 28-43; 34, IQR 28-39, respectively), and BMI (25 kg/m2, IQR 23-27; 25, IQR 23-28, respectively). For Method 1, 84 (51.9%) had bilateral surgery, and 78 (48.1%) had unilateral surgery. For Method 2, 63 (41.7%) had bilateral surgery, and 88 (58.3%) unilateral surgery. In patients with sperm concentration > 5 M/mL, both techniques resulted in an improvement (p < 0.01), but there was no difference between the methods (p = 0.18). Both methods were associated with an improvement in total motile count (p < 0.05) and the amount of DNA fragmentation (p < 0.05), although no differences were apparent between the techniques (p = 0.09, p = 0.81, respectively). Finally, testosterone levels improved with Method 1, but the post-operative difference was not different than Method 2 (p = 0.06). CONCLUSION: Delivery of the testis and ligation of dilated vasal veins compared to not performing those steps do not impact semen parameters, but are associated with improvement in testosterone levels.

Technological Advancements in Male Infertility Microsurgery.

There have been significant advancements in male infertility microsurgery over time, and there continues to be significant promise for new and emerging techniques, technologies, and methodologies. In this review, we discuss the history of male infertility and the evolution of microsurgery, the essential role of education and training in male infertility microsurgery, and new technologies in this space. We also review the potentially important role of artificial intelligence (AI) in male infertility and microsurgery.

Testicular Torsion and Spermatogenesis.

Testicular torsion (TT) is a common urologic emergency that can occur at any age. It is most common in newborns and during puberty. Prompt evaluation and management is required to salvage the testis following an episode of torsion. TT brings about damage to testicular tissue and spermatogenesis through various hypothesized mechanisms; however there is a consensus that the effects of ischemia, ischemia-reperfusion injury, and oxidative stress account for the most destructive effects. Numerous studies have examined the effects of various agents and therapies in limiting the effects of TT on the testis.

Regulation of Human Spermatogenesis.

Human spermatogenesis (HS) is an intricate network of sequential processes responsible for the production of the male gamete, the spermatozoon. These processes take place in the seminiferous tubules (ST) of the testis, which are small tubular structures considered the functional units of the testes. Each human testicle contains approximately 600-1200 STs [1], and are capable of producing up to 275 million spermatozoa per day [2].

Optimal timing for repeat semen analysis during male infertility evaluation.

OBJECTIVE: To assess whether the 4-week time period between semen analyses during the workup of male infertility is optimal and whether two samples are needed. DESIGN: Retrospective study. SETTING: Tertiary hospital. PATIENTS: Men whose semen samples were obtained within 90 days of each other, without known fertility intervention, treatment, and/or azoospermia. INTERVENTIONS: Semen analysis. MAIN OUTCOME MEASURES: Correlation between semen parameters and agreement among consecutive semen analyses. RESULTS: A total of 2,150 semen samples from 1,075 men were included in the analysis. The optimal correlation for volume occurred at weeks 2, 8, and 12 (r = 0.803, r = 0.802, and r = 0.821, respectively). For concentration, the correlation was maximized at weeks 1, 4, and 5 (r = 0.950, r = 0.841, and r = 0.795, respectively). Total sperm count correlated at weeks 1, 2, and 4 (r = 0.929, r = 0.727, and r = 0.808, respectively). Motility was maximally correlated at weeks 1, 10, and 13 (r = 0.711, r = 0.760, and r = 0.708, respectively). Morphology was optimally correlated at weeks 1, 2, and 9 (r = 0.935, r = 0.815, and r = 0.839, respectively). Semen volume was correlated in 55% of men, sperm concentration in 64% of men, sperm motility in 52% of men and sperm morphology 64% of men. CONCLUSIONS: Our data suggest that four weeks may not be the optimal time for repeat semen analysis and that one sample is insufficient to assess any abnormalities in the result of semen analysis. The optimal time between repeat semen analyses should be individualized depending on the results of the initial analysis and additional factors, suggesting the need for future large-scale studies to investigate this trend.

Assessing the clinical value of the Kruger strict morphology criteria over the World Health Organization fourth edition criteria.

OBJECTIVE: To assess if the newer Kruger strict morphology (WHO5; normal ≥4%) adds any clinical value beyond the criteria of the World Health Organization fourth edition (WHO4; normal ≥14%). DESIGN: Retrospective study. SETTING: Tertiary hospital. PATIENTS: Men without known azoospermia who had semen analysis (SA) collected over a 10-year period of time. INTERVENTIONS: Morphology classification under Kruger WHO5 strict criteria and WHO4 criteria. MAIN OUTCOME MEASURES: Correlation between the WHO5 and WHO4 morphological classifications. RESULTS: A total of 4,510 SAs were identified during the study period. Of these, both Kruger WHO5 and WHO4 morphologies were included in 932 SAs (20.7%) from a total of 691 men. The median age of the men was 37 years (interquartile range, 32.0-43.8 years). The mean (±SD) semen volume, sperm concentration, and motility were 2.6 ± 1.4 mL, 50.0 ± 35.6 × 106/mL, and 53.1% ± 18.6%, respectively. The correlation between the WHO4 and WHO5 morphology assessments was high (Spearman correlation coefficient = 0.94). Only 545 (58.5%) of 932 SAs had abnormal Kruger WHO5 morphology, of which 543 (99.6%) of 545 also had abnormal morphology by the WHO4 criteria. CONCLUSIONS: The Kruger WHO5 and WHO4 morphologic criteria correlate closely. Only two men (0.4%) with an abnormal Kruger morphology had normal WHO4 morphology. Given the limited predictive value of sperm morphology, the additional cost and effort of Kruger criteria may not be warranted in lieu of, or in addition to, the WHO4 classification.

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.

Predictors of varicocele-associated pain and its impact on semen parameters following microsurgical repair.

Our study aimed to assess for predictors of varicocele-associated pain and whether it predicts semen parameters after microsurgical varicocelectomy. We assessed all men diagnosed with a varicocele by two surgeons from 2017 to 2020, excluding those who did not undergo surgical treatment. Patients were stratified based on the presence of pain at clinical assessment, and these groups were compared. Logistic regression models were utilised to assess for predictors of pain. A total of 313 men were included, with relatively similar proportions completed by both surgeons (48.2% and 51.8%). A total of 98 (31.3%) had typical varicocele-associated pain at the time of assessment. The pain group was younger than the no pain group (30.5 versus. 35.0, respectively, p < .01), and those with pain had greater varicocele grades (p = .008). Although not statistically different, there was a greater portion of left-sided only varicoceles in the pain group (p = .09). No significant differences were demonstrated between sperm concentration, motility, volume or morphology pre-operatively, or post-operatively between groups. Younger age and varicocele grade were predictive of varicocele-associated pain. In conclusion, almost 1/3 of men presented with varicocele-associated pain. Pain does not predict response to varicocelectomy, but these men tend to be younger, and have higher grade varicoceles.

Standing Ultrasound Adds Clinical Utility for the Diagnosis of Varicoceles.

PURPOSE: We assessed the role of standing vs supine scrotal ultrasound (SUS) for varicocele assessment by evaluating differences in clinical outcomes. MATERIALS AND METHODS: We retrospectively reviewed men from 2008-2020 diagnosed with varicocele who had documented SUS with both supine and standing assessments with and without Valsalva. Clinical outcomes (semen parameters, TUNEL and serum testosterone [T]) after microsurgical varicocelectomy were compared among men who had varicoceles diagnosed by standing SUS (vein size >2.5 mm, vein size >3.0 mm or reversal of flow) to those who would have been missed on supine SUS only. RESULTS: A total of 349 men underwent varicocelectomy (right: 5 [1.4%]; left: 118 [33.8%]; bilateral: 226 [64.8%]). Disagreement between those with abnormal standing vs normal supine for vein size >2.5 mm was: 56 men (16.1%) on the right and 31 men (8.9%) on the left, for vein size >3.0 mm was: 64 men (18.3%) on the right, and 56 men (16.1%) on the left, and for flow reversal was: 36 (14.0%) on the right and 40 (15.4%) on the left. For those >2.5 mm, only T had significant improvements on the left (p=0.05). For those >3.0 mm significant differences were seen for sperm motility on the right (p=0.04), and TUNEL (p=0.04) and T (p <0.01) on the left. For flow reversal, significant differences were seen for sperm concentration (p <0.01), morphology (p=0.03) and volume (p=0.05) on the right and TUNEL on the left (p=0.02). CONCLUSIONS: Standing SUS identifies a greater number of men who would have been missed using supine SUS only.