Despite advances in the field of male reproductive health, idiopathic male infertility, in which a man has altered semen characteristics without an identifiable cause and there is no female factor infertility, remains a challenging condition to diagnose and manage. Increasing evidence suggests that oxidative stress (OS) plays an independent role in the etiology of male infertility, with 30% to 80% of infertile men having elevated seminal reactive oxygen species levels. OS can negatively affect fertility via a number of pathways, including interference with capacitation and possible damage to sperm membrane and DNA, which may impair the sperm's potential to fertilize an egg and develop into a healthy embryo. Adequate evaluation of male reproductive potential should therefore include an assessment of sperm OS. We propose the term Male Oxidative Stress Infertility, or MOSI, as a novel descriptor for infertile men with abnormal semen characteristics and OS, including many patients who were previously classified as having idiopathic male infertility. Oxidation-reduction potential (ORP) can be a useful clinical biomarker for the classification of MOSI, as it takes into account the levels of both oxidants and reductants (antioxidants). Current treatment protocols for OS, including the use of antioxidants, are not evidence-based and have the potential for complications and increased healthcare-related expenditures. Utilizing an easy, reproducible, and cost-effective test to measure ORP may provide a more targeted, reliable approach for administering antioxidant therapy while minimizing the risk of antioxidant overdose. With the increasing awareness and understanding of MOSI as a distinct male infertility diagnosis, future research endeavors can facilitate the development of evidence-based treatments that target its underlying cause.
Sperm DNA integrity is crucial for fertilization and development of healthy offspring. The spermatozoon undergoes extensive molecular remodeling of its nucleus during later phases of spermatogenesis, which imparts compaction and protects the genetic content. Testicular (defective maturation and abortive apoptosis) and post-testicular (oxidative stress) mechanisms are implicated in the etiology of sperm DNA fragmentation (SDF), which affects both natural and assisted reproduction. Several clinical and environmental factors are known to negatively impact sperm DNA integrity. An increasing number of reports emphasizes the direct relationship between sperm DNA damage and male infertility. Currently, several assays are available to assess sperm DNA damage, however, routine assessment of SDF in clinical practice is not recommended by professional organizations. This article provides an overview of SDF types, origin and comparative analysis of various SDF assays while primarily focusing on the clinical indications of SDF testing. Importantly, we report four clinical cases where SDF testing had played a significant role in improving fertility outcome. In light of these clinical case reports and recent scientific evidence, this review provides expert recommendations on SDF testing and examines the advantages and drawbacks of the clinical utility of SDF testing using Strength-Weaknesses-Opportunities-Threats (SWOT) analysis.
Purpose:We present final 5-year outcomes of the multicenter randomized sham-controlled trial of a water vapor therapy (Rezūm™) for treatment of moderate to severe lower urinary tract symptoms due to benign prostatic hyperplasia.Materials and Methods:A total of 197 subjects >50 years of age with International Prostate Symptom Score ≥13, maximum flow rate ≤15 ml/second and prostate volume 30 to 80 cc were randomized and followed for 5 years. From the control arm of 61 subjects, a subset of 53 subjects requalified and after 3 months received treatment as part of the crossover group and were also followed for 5 years. The total number of vapor treatments to each lobe of the prostate was determined by length of prostatic urethra and included middle lobe treatment per physician discretion.Results:Significant improvement of lower urinary tract symptoms was observed at <3 months post-thermal therapy, remaining durable through 5 years in the treatment group (International Prostate Symptom Score reduced 48%, quality of life increased 45%, maximum flow rate improved 44%, Benign Prostatic Hyperplasia Impact Index decreased 48%). Surgical re-treatment rate was 4.4% with no reports of device or procedure related sexual dysfunction or sustained de novo erectile dysfunction. Results within the crossover group were similar through 5 years.Conclusions:Minimally invasive treatment with water vapor thermal therapy provides significant and durable symptom relief as well as flow rate improvements through 5 years, with low surgical re-treatment rates and without impacting sexual function. It is a versatile therapy, providing successful treatment to obstructive lateral and middle lobes.
Abbreviations & AcronymsObjectives: To present an overview of our surgical experience in the management of growing teratoma syndrome. Methods: A retrospective analysis of all patients undergoing post-chemotherapy retroperitoneal lymphadenectomy between November 2005 and February 2012 revealed 15 patients who met the criteria for growing teratoma syndrome. Their clinical data, imaging characteristics, and surgical and oncological outcomes were reviewed. Results:The median age at diagnosis was 23 years. Primary testis tumors included nonseminomatous germ cell tumor in 12 of 15 patients, seminoma in two of 15 patients and hemorrhagic mass in one patient. Mature teratoma was present in just six (40%) of the orchiectomy specimens. All patients received preoperative chemotherapy. On imaging, the median size of the largest retroperitoneal mass was 7 cm (range 3.9-24.5 cm). The median rate of linear growth was 0.5 cm/month (range 0.03-2.9), and the increase in volume was 9.2 cm 3 /month. All tumors were found to have cystic and necrotic components. Median operative time was 6.2 h (range 4.2-15.2 h). Estimated blood loss was 600 mL (range 100-7000 mL), and median length of stay was 5 days (range 3-19 days). Four patients required resection of non-retroperitoneal growing teratoma masses after post-chemotherapy retroperitoneal lymphadenectomy to achieve tumor-free status. There were two minor (Clavien I-II) and two major postoperative complications (Clavien ≥III). All patients are alive and disease free with a median duration of follow-up of 8 months (range 1-64 months). Conclusions: Growing teratoma syndrome tumors vary in their growth rate, but they all appear to have cystic features with necrosis elements on radiographic evaluation. Aggressive surgical excision is associated with excellent outcomes.
Erectile dysfunction (ED) is a prevalent and pertinent condition in the chronic kidney disease (CKD) population. It has a multifactorial etiology, including disruptions of the hypothalamic-pituitarygonadal axis, the endothelial paracrine signaling system, calcium and vitamin D homeostasis, along with several other factors. Efficacy of treatment of ED in the CKD population is comparable to non-CKD patients across multiple modalities, including PDE5 inhibitors, vacuum erectile devices, intracavernosal injections and penile prostheses. Renal transplant improves the contributing comorbid conditions that lead to ED in CKD patients; thus rates of ED are improved post-transplant. It is important to note that there is a small percentage of patients with persistent ED after renal transplantation.
BackgroundChronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is often associated with pelvic floor muscle spasm. While pelvic floor physical therapy (PFPT) is effective, some men are unable to resolve their symptoms and have residual trigger points (TPs). TP injection has been used for treatment in several neuromuscular pain syndromes. The objective of this study was to examine the efficacy and side effects of TP injection in men with CP/CPPS and pelvic floor spasm refractory to PT.MethodsUsing an IRB approved Men’s Health Registry we reviewed the records of all men with a diagnosis of CP/CPPS who received at least 1 TP injection. Patients were phenotyped with UPOINT (all had the “T” domain for tenderness of muscle) and symptoms measured with the NIH Chronic Prostatitis Symptom Index (CPSI). Response was measured by a 5-point Global Response Assessment (GRA) and change in CPSI (paired t-test). For pelvic TPs, a pudendal block was done in lithotomy position and then each TP was identified transrectally by palpation. A nerve block needle was passed through the perineum into the TP confirmed by palpation. Between 0.5–1 cc was injected into each TP of a local anesthetic mixture (30:70 of 2% lidocaine and 0.25% bupivacaine). For anterior TPs, an ultrasound guided ilioinguinal block was done first and then each TP injected by direct palpation through the abdominal skin. Men were offered up to three sets of injections separated by 6 weeks each.ResultsWe identified 37 patients who had a total of 68 procedures. Three men had no follow-up after their first injection and were included for side effects but not included for outcome. The indication was failure to progress on PT in 33, recurrent symptoms in 1 and refusal to do PT in 3. Mean age was 43.7 years (range 21–70 years) and median UPOINT domains was 3 (range 1–5). Initial CPSI was pain 13.7±3.4, urinary 5.3±2.2, quality of life 9.8±2.1 and total 28.8±6.0. 16 men had 1 injection, 11 had 2 and 10 had 3. All had pelvic TPs injected and 9 also had anterior TPs. By GRA, 12 had significant improvement (35.3%), 10 had some improvement (29.4%), 11 had no change (32.3%) and 1 was worse (2.9%). Mean CPSI dropped from 28.8±6.0 to 21.8±7.2 (P<0.0001). 18 men had a drop of 6 or more points in CPSI (53%). Of note, none of 3 men who were noncompliant with PT had benefit. 3 men had temporary numbness in the lateral thigh after the injection (4.4%) and 1 had difficulty weight bearing on 1 leg for about 30 minutes.ConclusionsTP injection in CP/CPPS patients as an adjunct to PT is well tolerated and leads to symptom improvement in about half. Durability and long term results are yet to be determined.
PurposeSperm play an essential role in embryonic genome activation and embryonic progression to blastocyst. In the present work, we focus on development of embryos created as a result of ICSI with testicular or epididymal sperm from azoospermic males and compare this to outcomes from normospermic males. The objective of this study was to determine if sperm origin influences clinical outcomes, the kinetics of embryo development, or the incidence of cleavage anomalies and multinucleation.MethodsA total of 93 consecutive intracytoplasmic sperm injection cycles (ICSI) performed for 83 couples were included in this study. Observations were made on 594 fertilized oocytes cultured in the EmbryoScope using time-lapse microscopy (TLM). Epididymal sperm (n = 29) cycles or surgically retrieved sperm from the testis (TESE; n = 37 cycles) of men with either obstructive (OA) or non-obstructive azoospermia (NOA) were used to inject oocytes. A further 27 ICSI cycles were performed using ejaculated sperm from normospermic males, designated as our control sperm (CS) group. Kinetic data and cycle outcomes were retrospectively analyzed.ResultsThe clinical pregnancy rate was not different between the three groups (TESE 51.4%, PESA 57.7%, and CS 59.3%). A non-significant decrease was observed in both implantation (30.9%) and live birth rate (43%) with TESE as compared to PESA (35.3%, 58%, respectively) and CS groups (45.1%, 56%, respectively). Failure to compact was significantly higher amongst TESE-NOA embryos (35.2%; P < 0.001) as compared to TESE-OA (4%), PESA (9%), and CS (3.8%) embryos. The two points at which TESE-derived embryos (both NOA and OA) behaved most differently from PESA and CS embryos was at cc2 (t3-t2; time to initiation of the second cell cycle) and tSB (time to start of blastulation). A significantly lower percentage of TESE embryos exhibited kinetics typically ascribed to high quality embryos with the greatest developmental potential. Finally, the incidence of direct uneven cleavage (DUC) was observed to be significantly higher after ICSI with sperm retrieved from azoospermic males.ConclusionsTLM allowed a more in depth comparison of paternal influence on embryo morphokinetics and helped to identify specific differences in cell cycle kinetics. TESE-NOA embryos exhibited a higher incidence of compaction failure.
The catalytic reduction of acetophenone in 2-propanol by the organometallic complex [Cp 2 -Mo(µ-OH) 2 MoCp 2 ](OTs) 2 (I) proceeds through a molybdocene hydride intermediate. Activation parameters for the reduction of acetophenone to 1-phenylethyl alcohol in 2-propanol-d 8 are 19 kcal mol -1 and -26 cal mol -1 K -1 for ∆H q and ∆S q , respectively. These parameters suggest 2-propanol and I are involved in a C-H activation step to form a molybdocene monohydride that may be the active species in the hydrogenation catalysis. When the catalysis reaction was performed with (CH 3 ) 2 CHOD as the solvent, 1-deuterio-1-phenylethyl alcohol was almost quantitatively formed. This is consistent with a mechanism where a Cp 2 Mo hydride, formed in the C-H activation of (CH 3 ) 2 CHOD, is converted to the deuteride by the solvent's alcoholic deuteron. The labeling experiment further supports the a molybdocene hydride as the catalytic species.
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