Evaluation and Management of Testosterone Deficiency: AUA Guideline.

Clostridium perfringens enterotoxin fragment removes specific claudins from tight junction strands : Evidence for direct involvement of claudins in tight junction barrier

Background Infertility affects ∼7% of all men. Despite much progress, mainly in genetics, its etiology remains obscure in ∼50% of cases. To fill this gap, imaging of the male genital tract (MGT) has progressively expanded, providing useful information in the assessment of MGT abnormalities. Methods A critical, systematic review of the available literature was performed using Medline, with no restrictions regarding date of publication (i.e. from inception date until March 2014), along with analysis of previous reports in color Doppler ultrasound (CDUS) atlas textbooks. Normal anatomy and sonographic characteristics of the MGT have also been summarized. Results Testicular volume (TV) is tightly associated with both sperm and hormonal parameters. Ultrasound (US) offers a greater accuracy in TV measurement than Prader orchidometer (PO). However US- and PO-derived TV are closely related, making PO-derived TV informative enough in the work-up of the infertile man in everyday clinical practice. US-derived TV might play an independent role in specific clinical conditions (i.e. large hydrocele, inguinal testis, enlarged epididymis). Scrotal US may detect signs of testicular dysgenesis, often related to an impaired spermatogenesis and to a higher risk of malignancy, or testicular lesions suggestive of malignancy. A decreased testis vascularization is characteristic of testicular torsion, whereas hyperemia is often observed in epididymo-orchitis or in some malignant conditions (i.e. lymphoma, leukemia). The impact of varicocele detection and surgical correction on sperm parameters/fatherhood is debated. At present, the clinical management of varicocele is mainly based on physical examination. However, CDUS is useful in assessing venous reflux, when palpation is unreliable and/or in detecting recurrence/persistence after surgery. Epididymis head and/or tail dilation is suggestive of MGT obstruction or inflammation and both are related, along with echo-texture abnormalities, to impaired sperm parameters. Scrotal and transrectal US (TRUS) are useful in detecting congenital uni- or bilateral absence of vas deferens (CBAVD), which may be associated with epididymis, seminal vesicles (SV) or kidney abnormalities/agenesis. TRUS plays a key role in assessing obstructive azoospermia and detecting distal CBAVD or anomalies related to ejaculatory ducts obstruction, such as ejaculatory duct abnormalities, prostate median cysts or SV enlargement/emptying impairment. TRUS findings lead to operational decision-making, such as testicular sperm extraction in the case of CBAVD, cyst aspiration in the case of a large prostatic median cyst, and surgical treatment if ejaculatory duct abnormalities are observed. TRUS may reveal prostate volume reduction (suggestive of hypogonadism) or enlargement, which can be related to aging or even metabolic abnormalities. Finally, TRUS may reveal prostate and SV echo-texture abnormalities suggestive of inflammation or SV stasis. Conclusions MGT-CDUS is a useful tool in detecting abnormalities related to impaired male reproductive health. However, it suffers from a lack of standardization and often produces subjective/vague diagnoses. To fill this gap, the European Academy of Andrology has promoted an ongoing multicenter study aimed at defining the MGT-CDUS characteristics of healthy, fertile men.

/pdf/ultrasound-of-the-male-genital-tract-in-relation-to-male-dfws5tha7g.pdf

Ultrasound of the male genital tract in relation to male reproductive health

Varicocele has been associated with reduced male reproductive potential. With the advances in biomolecular techniques, it has been possible to better understand the mechanisms involved in testicular damage provoked by varicocele. Current evidence suggests the central role of reactive oxygen species (ROS) and the resultant oxidative stress (OS) in the pathogenesis of varicocele-associated male subfertility although the mechanisms have not yet been fully described and it is likely to be multifactorial. Excessive ROS is associated with sperm DNA fragmentation, which may mediate the clinical manifestation of poor sperm function and fertilization outcome related to varicocele. Testing of ROS/OS and DNA fragmentation has the potential to provide additional diagnostic and prognostic information compared to conventional semen analysis and may guide therapeutic management strategies in individual patient.

Novel insights into the pathophysiology of varicocele and its association with reactive oxygen species and sperm DNA fragmentation.

Background The majority of human embryos created using in vitro fertilisation (IVF) techniques are aneuploid. Comprehensive chromosome screening methods, applicable to single cells biopsied from preimplantation embryos, allow reliable identification and transfer of euploid embryos. Recently, randomised trials using such methods have indicated that aneuploidy screening improves IVF success rates. However, the high cost of testing has restricted the availability of this potentially beneficial strategy. This study aimed to harness next-generation sequencing (NGS) technology, with the intention of lowering the costs of preimplantation aneuploidy screening.

Methods Embryo biopsy, whole genome amplification and semiconductor sequencing.

Results A rapid (<15 h) NGS protocol was developed, with consumable cost only two-thirds that of the most widely used method for embryo aneuploidy detection. Validation involved blinded analysis of 54 cells from cell lines or biopsies from human embryos. Sensitivity and specificity were 100%. The method was applied clinically, assisting in the selection of euploid embryos in two IVF cycles, producing healthy children in both cases. The NGS approach was also able to reveal specified mutations in the nuclear or mitochondrial genomes in parallel with chromosome assessment. Interestingly, elevated mitochondrial DNA content was associated with aneuploidy (p<0.05), a finding suggestive of a link between mitochondria and chromosomal malsegregation.

Conclusions This study demonstrates that NGS provides highly accurate, low-cost diagnosis of aneuploidy in cells from human preimplantation embryos and is rapid enough to allow testing without embryo cryopreservation. The method described also has the potential to shed light on other aspects of embryo genetics of relevance to health and viability.

https://jmg.bmj.com/content/jmedgenet/51/8/553.full.pdf

Clinical utilisation of a rapid low-pass whole genome sequencing technique for the diagnosis of aneuploidy in human embryos prior to implantation

Objectives: To determine the effect of surgical varicocele repair in improving testicular Leydig cell function as shown by increased testosterone production.



Methods:  Eligible studies were searched in Medline and the Pubmed database, and cross-referenced as of 31 May 2011 using the terms “varicocele,”“testosterone” and “surgery.” The database search, quality assessment and data extraction were independently carried out by two reviewers. Only studies including patients with testosterone evaluation before and after surgery were considered for the analysis. A systematic review and meta-analysis was carried out for continues variables using random effect models.



Results:  Out of 125 studies, a total of nine were selected, including 814 patients. The combined analysis showed that mean serum testosterone levels after surgical treatment increased by 97.48 ng/dL (95% confidence interval 43.73–151.22, P = 0.0004) compared with preoperative levels.



Conclusions:  Surgical treatment of varicocele significantly increases testosterone production and improves testicular Leydig cell function.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1442-2042.2011.02890.x

Effect of surgical repair on testosterone production in infertile men with varicocele: a meta-analysis.

Varicocele is currently the most common irregularity identified in males that is associated with impaired spermatogenesis. It primarily presents in the form of decreased sperm count and motility, abnormal morphology, and significantly increased sperm DNA fragmentation. Several studies have shown that surgical repair improves semen parameters and increases the odds of spontaneous pregnancy. However the exact effect of surgical repair treatment remains controversial. Therefore, the aim of our study was to evaluate the effectiveness of microsurgical repair by comparing common semen parameters and sperm DNA fragmentation index (DFI). We evaluated infertile men (n = 19) who underwent microsurgical subinguinal varicocelectomy for treatment of clinical varicocele before and 3 months after surgery. Normozoospermic men (n = 19) were considered as the normal control group. Semen parameters improved significantly after surgery when compared with that before surgery, but still significant differences with the normal control group were observed. In comparison, sperm DNA integrity improved significantly after surgery (percentage DFI decreased from 28.4 ± 15.6% before surgery to 22.4 ± 12.9%, at 3 months post surgery) to similar levels as the normal control group. These results suggest that microsurgical repair may be considered as a treatment option in infertile men with palpable varicocele.

https://www.tandfonline.com/doi/pdf/10.3109/19396368.2012.692431

Makoto Ando

Papers

Effect of surgical repair on testosterone production in infertile men with varicocele: a meta-analysis.

Significant improvement of sperm DNA quality after microsurgical repair of varicocele.

Finasteride-associated male infertility

Effect of Varicocelectomy on Testicular Volume in Children and Adolescents: A Meta-analysis

Novel telementoring system for robot-assisted radical prostatectomy: impact on the learning curve.