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.

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.

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.

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].

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.

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.

Sperm Genomic Integrity by TUNEL Varies throughout the Male Genital Tract.

PURPOSE: We assessed sperm chromatin fragmentation at different levels of the male genital tract. MATERIALS AND METHODS: Ejaculated specimens from consenting male partners were screened for sperm chromatin fragmentation by TUNEL (terminal deoxynucleotidyl deoxyuridine triphosphate nick end labeling). Men with intracytoplasmic sperm injection failure and high ejaculated sperm chromatin fragmentation underwent surgery to retrieve spermatozoa from different levels of the male genital tract, which were then reassessed for sperm chromatin fragmentation. Approximately 500 or more spermatozoa were assessed per patient with a 15% threshold. Intracytoplasmic sperm injection results of cycles using spermatozoa from different levels of the male genital tract were compared. RESULTS: Topographical assessment of the male genital tract showed a mean ± SD of 20.4% ± 10% sperm chromatin fragmentation in the vas deferens, 15.8% ± 8% in the epididymis and 11.4% ± 6% in the testis. All values were lower than in ejaculated controls (mean 32.9% ± 20%, p <0.05). A total of 25 couples who underwent intracytoplasmic sperm injection with surgically retrieved spermatozoa had lower sperm chromatin fragmentation (p <0.001), and higher implantation, clinical pregnancy and delivery rates (p <0.01). A total of 45 couples with a history of intracytoplasmic sperm injection failure with ejaculate performed elsewhere were treated solely with surgically retrieved spermatozoa at our center. Compared to historical cycles, surgically retrieved spermatozoa had a lower fertilization rate (65%, p <0.05) but enhanced rates of implantation (19.1%), clinical pregnancy (40.0%) and delivery (34.3%) (each p <0.01). CONCLUSIONS: To our knowledge we report for the first time that sperm chromatin fragmentation increases progressively from the testicle to the epididymis and the vas deferens, and is highest in the ejaculate. Men with high ejaculated sperm chromatin fragmentation can benefit from using surgically retrieved sperm for in vitro fertilization and/or intracytoplasmic sperm injection.

A long-term clinical trial on the efficacy and safety profile of doxofylline in Asthma: The LESDA study.

Doxofylline, an oral methylxanthine with bronchodilator and anti-inflammatory activities, offers a promising alternative to theophylline due to its superior efficacy/safety profile. No long-term studies on the efficacy and safety of doxofylline are currently available in asthma. The aim of the Long-term clinical trial on the Efficacy and Safety profile of Doxofylline in Asthma (LESDA) study was to investigate the safety and efficacy profile of doxofylline administered for one year in asthmatic patients. LESDA was a multicenter, open-label, Phase III, clinical trial in which adult asthmatic patients received the same treatment (oral doxofylline 400 mg t.i.d.) for one year. Efficacy was assessed through periodic pulmonary function tests and by having the subjects keep monthly records of asthma events rates and use of salbutamol as rescue medication. The rate of adverse events (AEs) was recorded during the study. Three-hundred nine patients were screened and allocated in the study. Doxofylline significantly improved the change from baseline in forced expiratory volume in 1 s (FEV1) (+16.90 ± 1.81%, P < 0.001 vs. baseline). Doxofylline also significantly improved the rate of asthma events (events/day: -0.57 ± 0.18, P < 0.05 vs. baseline) and the use of salbutamol as rescue medication (puffs/day: -1.48 ± 0.25, P < 0.01 vs. baseline). The most common AEs were nausea (14.56%), headache (14.24%), insomnia (10.68%), and dyspepsia (10.03%). There were neither serious AEs nor deaths during or shortly after the study. Concluding, doxofylline is effective and well tolerated when administered chronically in asthmatic patients.

The Kinetics of Sperm Return and Late Failure Following Vasovasostomy or Vasoepididymostomy: A Systematic Review.

PURPOSE: Vasovasostomy and vasoepididymostomy are technically challenging microsurgical reconstructive procedures necessary for men with obstructive azoospermia at the level of the vas deferens or epididymis. Patency rates following vasovasostomy or vasoepididymostomy have been widely described in the literature. However, few reports have discussed the timing of sperm return to the ejaculate after reconstruction as well as the proportion of men in whom late failure develops following vasovasostomy or vasoepididymostomy. Therefore, the objective of this article was to review the rates and predictors associated with late failure and the timing of sperm returning to the ejaculate after vasovasostomy and vasoepididymostomy. MATERIALS AND METHODS: A literature search was performed using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines via the PubMed®/MEDLINE® database. We included relevant articles published in English in peer reviewed journals from 1960 to 2017 which reported outcomes regarding time to patency, time to late failure or the late failure rate after vasovasostomy or vasoepididymostomy. Macroscopic reconstructions were excluded from study. RESULTS: A total of 24 articles were included in the review. Mean time to patency after vasovasostomy and vasoepididymostomy ranged from 1.7 to 4.3 and 2.8 to 6.6 months, respectively. The late failure rate after microsurgical vasovasostomy and vasoepididymostomy ranged from 0% to 12% and 1% to 50%, respectively. Mean time to late failure after vasovasostomy and vasoepididymostomy ranged from 9.7 to 13.6 and 6 to 14.2 months, respectively. There was significant heterogeneity in the available data, limiting comparisons between series. CONCLUSIONS: Sperm returns to the ejaculate sooner in men who undergo vasovasostomy compared to vasoepididymostomy. Late failures are heterogeneously defined in the literature but they occur at a rate that is not insignificant. Thus, clinicians should discuss considerations for sperm cryopreservation.

Left ventricular strain analysis using cardiac magnetic resonance imaging in patients undergoing in-centre nocturnal haemodialysis.

AIM: Intensified haemodialysis is associated with regression of left ventricular (LV) mass. Compared to LV ejection fraction, LV strain allows more direct assessment of LV function. We sought to assess the impact of in-centre nocturnal haemodialysis (INHD) on global LV strain (radial, circumferential, and longitudinal) and torsion by cardiac MRI (CMR). METHODS: In this prospective, two-centre cohort study, 37 participants on conventional haemodialysis (CHD, 3-4 h/session for three sessions/week) converted to INHD (7-8 h/session for three sessions/week) and 30 participants continued CHD. Participants underwent CMR using a standardized protocol and had biomarker measurements at baseline and 52 weeks. RESULTS: Among the 55 participants (mean age 55; 40% women) with complete CMR data, those who converted to INHD had a significant improvement in their global circumferential strain (GCS, P = 0.025), while those continuing CHD did not have any significant changes in LV strain. When the two groups were compared, there was significant improvement in torsion. LV strains were significantly correlated with each other, but not with troponin I, C-reactive protein, or brain natriuretic protein (NT-proBNP), except for global longitudinal strain (GLS) with troponin I (P = 0.001) and NT-proBNP (P = 0.038). CONCLUSION: Conversion to INHD was associated with significant improvement in GCS over one year of study, although comparisons with the CHD group were not significant. There was also a significant decrease in torsion in the INHD group compared with CHD. Improvement in LV regional function would support the notion that INHD has favourable effects on both LV structure and function.

Spermatogenesis in humans and its affecting factors.

Spermatogenesis is an extraordinary complex process. The differentiation of spermatogonia into spermatozoa requires the participation of several cell types, hormones, paracrine factors, genes and epigenetic regulators. Recent researches in animals and humans have furthered our understanding of the male gamete differentiation, and led to clinical tools for the better management of male infertility. There is still much to be learned about this intricate process. In this review, the critical steps of human spermatogenesis are discussed together with its main affecting factors.

Association between conversion to in-center nocturnal hemodialysis and right ventricular remodeling.

Background: In-center nocturnal hemodialysis (INHD) is associated with favorable left ventricular (LV) remodeling. Although right ventricular (RV) structure and function carry prognostic significance, the impact of dialysis intensification on RV is unknown. Our objectives were to evaluate changes in RV mass index (MI), end-diastolic volume index (EDVI), end-systolic volume index (ESVI) and ejection fraction (EF) after conversion to INHD and their relationship with LV remodeling. Methods: Of 67 conventional hemodialysis (CHD, 4 h/session, three times/week) patients, 30 continued on CHD and 37 converted to INHD (7-8 h/session, three times/week). Cardiac magnetic resonance imaging was performed at baseline and 1 year using a standardized protocol; an experienced and blinded reader performed RV measurements. Results: At 1 year there were significant reductions in RVMI {-2.1 g/m2 [95% confidence interval (CI) -3.8 to - 0.4], P = 0.017}, RVEDVI [-9.5 mL/m2 (95% CI - 16.3 to - 2.6), P = 0.008] and RVESVI [-6.2 mL/m2 (95% CI - 10.9 to - 1.6), P = 0.011] in the INHD group; no significant changes were observed in the CHD group. Between-group comparisons showed significantly greater reduction of RVESVI [-7.9 mL/m2 (95% CI - 14.9 to - 0.9), P = 0.03] in the INHD group, a nonsignificant trend toward greater reduction in RVEDVI and no significant difference in RVMI and RVEF changes. There was significant correlation between LV and RV in terms of changes in mass index (MI) (r = 0.46), EDVI (r = 0.73), ESVI (r = 0.7) and EF (r = 0.38) over 1 year (all P < 0.01). Conclusions: Conversion to INHD was associated with a significant reduction of RVESVI. Temporal changes in RV mass, volume and function paralleled those of LV. Our findings support the need for larger, longer-term studies to confirm favorable RV remodeling and determine its impact on clinical outcomes.

Impact of doxofylline compared to theophylline in asthma: A pooled analysis of functional and clinical outcomes from two multicentre, double-blind, randomized studies (DOROTHEO 1 and DOROTHEO 2).

This pooled analysis of double-blind, randomized, placebo-controlled trials aimed to investigate the impact of DOxofylline compaRed tO THEOphylline (DOROTHEO 1 and DOROTHEO 2 studies) on functional and clinical outcomes in asthma. Asthmatic patients ≥16 years of age with forced expiratory volume in 1 s (FEV1) ≥50% and <80% and with ≥15% post-bronchodilator increase in FEV1 were randomized in a 1:1:1:1 ratio in DOROTHEO 1 to receive doxofylline 200 mg, doxofylline 400 mg, theophylline 250 mg, or placebo; in DOROTHEO 2 patients were randomized in a 1:1:1 ratio to receive doxofylline 400 mg, theophylline 250 mg, or placebo. All double-blind treatments were taken orally with immediate release formulations and three times daily. Data evaluating the effect of doxofylline 400 mg, theophylline 250 mg and placebo on FEV1, asthma events rate, use of salbutamol as rescue medication and adverse events (AEs) were pooled from both studies. The pooled-analysis of 483 patients demonstrated that both doxofylline 400 mg and theophylline 250 mg significantly increased FEV1, reduced the rate of asthma events and use of salbutamol to relieve asthma symptoms compared to placebo (p < 0.01). No significant differences were detected between doxofylline 400 mg and theophylline 250 mg. Doxofylline 400 mg did not significantly (p > 0.05) increase the risk of AEs compared to placebo, conversely in patients treated with theophylline 250 mg the risk of AEs was significantly (p < 0.05) greater than in those that received placebo. We conclude that doxofylline seems to offer a promising alternative to theophylline with a superior efficacy/safety profile in the management of patients with asthma.

Frailty and the Quality of Life in Hemodialysis Patients: The Importance of Waist Circumference.

OBJECTIVE: Frailty among the end-stage renal disease (ESRD) population is highly prevalent and has been associated with mortality. Little is known about the relation of different aspects of body composition, a modifiable risk factor, with the risk of frailty in ESRD population. DESIGN AND METHODS: One hundred and fifty-one patients including 85 men and 66 women, aged ≥18 years with ESRD who had been receiving conventional maintenance hemodialysis (HD) for at least 3 months were included. Body fat and muscle mass from both bioimpedance spectroscopy and skin-fold thickness and waist circumference as a surrogate of abdominal obesity were measured. Frailty was defined based on Fried's criteria. Health-related quality of life was collected using the RAND version of the Kidney Disease Quality of Life (KDQOL-36) Survey. RESULTS: We performed single and multiple predictor logistic regression analyses to determine factors associated with frailty. After adjustment for age, sex, and comorbidities, fat mass (both by bioimpedance spectroscopy and anthropometry) and waist circumference, but not muscle mass remained the main predictors of frailty. The odds ratio of frailty in the third tertile compared with the first was 4.97 (1.70-14.55) and 3.84 (1.39-10.61) for fat mass and waist circumference, respectively (P for trends for both <.05). The scores of physical health and kidney disease effect component of quality of life were lower in frail compared with nonfrail patients (40.7 ± 9.2 vs. 33.7 ± 10.2, P < .01 and 66.8 ± 22.4 vs. 51.6 ± 25.7, P < .05 for physical health and effects of disease, respectively). CONCLUSIONS: Frailty, which is associated with poor outcomes in chronic HD patients, is common and predicted by fat mass and waist circumference but not by body mass index and muscle mass. Interventions to modify abdominal obesity, reflected by waist circumference, could potentially lower the incidence of frailty and hence improve the quality of life in the HD population.

The Impact of Additives on the Phosphorus, Potassium, and Sodium Content of Commonly Consumed Meat, Poultry, and Fish Products Among Patients With Chronic Kidney Disease.

OBJECTIVE: Patients with chronic kidney disease (CKD) are advised to limit their dietary intake of phosphorus and potassium as hyperphosphatemia and hyperkalemia are both associated with an increased risk of mortality. There is uncertainty concerning the actual content of these minerals in the Canadian food supply, as phosphorus and potassium are increasingly being used as food additives. This study aimed to determine the impact of food additives on the chemically analyzed content of phosphorus, potassium, sodium, and protein in commonly consumed meat, poultry, and fish products (MPFs). DESIGN: Foods representing commonly consumed MPF identified by a food frequency questionnaire in dialysis patients were purchased from three major grocery store chains in Canada. MPF with and without phosphorus and potassium additives listed on their ingredient list (n = 76) as well as reference MPF that was additive free (n = 15) were chemically analyzed for phosphorus, potassium, sodium, and protein content according to Association of Analytical Community official methods. RESULTS: Phosphorus, potassium, and sodium additives were present on the ingredient list in 37%, 9%, and 72% of MPF, respectively. Among MPF categories that contained a phosphorus additive, phosphorus content was significantly (P < .05) higher in MPF with phosphorus additives versus MPF without phosphorus additives and MPF reference foods (median [min, max]): (270 [140, 500] mg/100 g) versus (200 [130, 510] mg/100 g) versus (210 [100, 260] mg/100 g), respectively. Among MPF categories containing a potassium additive, foods listing a potassium additive had significantly more (P < .05) potassium than foods that did not list potassium additives and reference foods (900 [750, 1100] mg/100 g) versus (325 [260, 470] mg/100 g) versus (420 [270, 450] mg/100 g). CONCLUSIONS: The use of additives in packaged MPF products as indicated by the ingredient list can significantly contribute to the dietary phosphorus and potassium loads in patients with CKD. Patients with CKD should be educated to avoid MPF foods listing phosphorus and/or potassium additives on the ingredient list, which may lead to improved dietary adherence.

Microsurgically Assisted Inguinal Hernia Repair and Simultaneous Male Fertility Procedures: Rationale, Technique and Outcomes.

PURPOSE: Inguinal herniorrhaphy is the most common general surgical procedure. It is associated with frequent complications such as recurrence in 2.0% to 14.1% of cases with mesh as well as postoperative hematoma in 4.5% of cases, reduced sensation in 0% to 42.8%, chronic postoperative pain in 5.1%, vasal injury in 0.1% to 0.53% and infection in 3% to 6%. Drawing on our experience with the operating microscope for varicocelectomy, vasectomy reversal and repair of iatrogenic vasal obstruction from hernia repair, we applied the operating microscope for inguinal hernia repair. This study describes the rationale, technique and outcomes of microsurgically assisted inguinal hernia repair. MATERIALS AND METHODS: A total of 291 microsurgically assisted inguinal hernia repairs were performed in 253 men by the same urologist (MG). Simultaneous microsurgical varicocelectomy or other testicular procedures were performed in 83% of cases. All were open repairs through an inguinal incision with the vas deferens, ilioinguinal nerve, genital branch of the genitofemoral nerve, and spermatic vasculature identified and preserved. Median followup was 8.6 months. Outcomes were assessed by examination, pain reporting and pathology reports. RESULTS: Chronic postoperative pain, sensory loss, infection, hematoma, vasal injury and recurrence were assessed. The incidence of hematoma was 0.85%. No recurrent hernia, chronic postoperative pain, sensory loss, infection or vasal injury was reported. CONCLUSIONS: Using an operating microscope the complications of inguinal hernia repair, such as vasal obstruction, testicular atrophy, recurrence, infection, hematoma, chronic postoperative pain and loss of sensation, are minimized. Microsurgically assisted hernia repair is a promising technique, especially when performed by a urologist who simultaneously performs microsurgical varicocelectomy or procedures involving spermatic cord structures or the testis.

Genetics of Male Infertility.

While 7 % of the men are infertile, currently, a genetic etiology is identified in less than 25 % of those men, and 30 % of the infertile men lack a definitive diagnosis, falling in the "idiopathic infertility" category. Advances in genetics and epigenetics have led to several proposed mechanisms for male infertility. These advances may result in new diagnostic tools, treatment approaches, and better counseling with regard to treatment options and prognosis. In this review, we focus on clinical aspects of male infertility and the role of genetics in elucidating etiologies and the potential of treatments.

A case report of unusually long lag time between immunotactoid glomerulopathy (itg) diagnosis and diffuse large B-cell lymphoma (DLBCL) development.

BACKGROUND: Immunotactoid glomerulopathy (ITG) is a rare cause of proteinuria characterized by organized microtubular deposits in the glomerulus. ITG has been associated with underlying lymphoproliferative disorders and any renal impairment may be reversible with treatment of the concomitant hematologic malignancy. This case is the first reported in literature where diffuse large B cell lymphoma developed two years following the initial ITG diagnosis. CASE PRESENTATION: A 55-year-old woman with a history of well-controlled diabetes mellitus and thalassemia trait presented with proteinuria (830 mg/day) in 2010. Initially, she was managed with renin-angiotensin-aldosterone-system blockade. In 2012, the proteinuria worsened (4.3 g/day) and a renal biopsy showed immunotactoid glomerulopathy (Fig. 1). Despite extensive work up, no lymphoproliferative disorder was initially found. In January 2014, the patient presented with a soft-palate mass found on biopsy to be diffuse large B-cell lymphoma. She received 6 cycles of R-CHOP, 4 cycles of high dose methotrexate chemotherapy for CNS prophylaxis and 30 Gy of Intensity Modulated Radiation Therapy. Follow-up revealed complete remission of diffuse large B-cell lymphoma and resolution of proteinuria from the ITG. CONCLUSION: As we recognize that patients with ITG may develop hematopoietic neoplasms, close long-term monitoring is important. Moreover, treatment of the lymphoproliferative disorder can allow for complete remission of ITG.

Intensive hemodialysis associates with improved pregnancy outcomes: a Canadian and United States cohort comparison.

Pregnancy is rare in women with ESRD and when it occurs, it is often accompanied by significant maternal and fetal morbidity and even mortality. Preliminary data from the Toronto Nocturnal Hemodialysis Program suggested that increased clearance of uremic toxins by intensified hemodialysis improves pregnancy outcomes, but small numbers and the absence of a comparator group limited widespread applicability of these findings. We compared pregnancy outcomes from 22 pregnancies in the Toronto Pregnancy and Kidney Disease Clinic and Registry (2000-2013) with outcomes from 70 pregnancies in the American Registry for Pregnancy in Dialysis Patients (1990-2011). The primary outcome was the live birth rate and secondary outcomes included gestational age and birth weight. The live birth rate in the Canadian cohort (86.4%) was significantly higher than the rate in the American cohort (61.4%; P=0.03). Among patients with established ESRD, the median duration of pregnancy in the more intensively dialyzed Toronto cohort was 36 weeks (interquartile range, 32-37) compared with 27 weeks (interquartile range, 21-35) in the American cohort (P=0.002). Furthermore, a dose response between dialysis intensity and pregnancy outcomes emerged, with live birth rates of 48% in women dialyzed ≤20 hours per week and 85% in women dialyzed >36 hours per week (P=0.02), with a longer gestational age and greater infant birth weight for women dialyzed more intensively. Pregnancy complications were few and manageable. We conclude that pregnancy may be safe and feasible in women with ESRD receiving intensive hemodialysis.