Azoospermia and maturation arrest: malfunction of valves in erect poster of humans leads to hypoxia in sperm production site

Maturation arrest (MA) of spermatogenesis is diagnosed on histology as interruption of spermatogenesis before the final stage without impairment of Sertoli or Leydig cells. It is considered a condition of irreversible or absolute infertility. Varicocele, which represents impairment in the testicular venous drainage system, has been shown to be a bilateral disease. Malfunction of the valves increase the hydrostatic pressure in the testicular venous system that exceeds the pressure in the arterial system leading to hypoxia in the testicular microcirculation and in the seminiferous tubules, the sperm production site. Sperm production deteriorates, and ultimately progresses to azoospermia. Our prediction was that MA, if genetic factors are excluded, is the final stage of long standing hypoxia. This would indicate that MA is not always an independent disease entity, but may represent progressive process of deterioration of the testicular parenchyma beyond azoospermia. By histology and electron microscopy, our prediction confirmed, at least partially, that MA is associated with degenerative ischaemic changes in the seminiferous tubules. Adequate treatment of bilateral varicocele by microsurgery or super-selective sclerotherapy of the internal spermatic veins including associated network of venous bypasses, vertically oriented, may resume the flow of oxygenated blood. If irreversible damages did not occur and ischaemia is not too long standing, limited sperm production may be restored, at least partially.     

Azoospermia in two brothers with Kartagener syndrome:a family history and diagnosis

0This article describes 2 infertile brothers of asoospermia equally associated with co-existing sinusitis,bronchiectasis,and situs inversus and their family history.These two cases were diagnosed as Kartagener syndrome(KS).The patients were not offspring of kin marriages but their family members with scattered bronchi-pulmouary infections were discovered.No one manifests azoospermia,dextrocardia or situs inversus in the paternal family ex-cept two cases reported.No abnormalities were found in their mother-side family.KS should be differentiated from Young's syndrome,cystic fibrosis(CF),and other diseases such as Kallmann's syndrome in male infertility clinic.     

Reversal of benign prostate hyperplasia by selective occlusion of impaired venous drainage in the male reproductive system: novel mechanism, new treatment

The prostate is an androgen-regulated exocrine gland producing over 30% of the noncellular components of the semen and promoting optimal conditions for survival and motility of sperm in the vagina. Benign prostate hyperplasia (BPH) is the most common benign neoplasm in men. Its aetiology is not clear, and therefore, current medical treatments are directed towards the symptoms. Though testosterone is known to be the promoter of prostate cell proliferation, no causal relation between serum testosterone levels and BPH has been found. In this study, we propose a novel and tested pathophysiological mechanism for the evolution of BPH and suggest a tested and effective treatment. We found that in all BPH patients, the one-way valves in the vertically oriented internal spermatic veins are destroyed (clinically manifested as varicocele), causing elevated hydrostatic pressure, some 6-fold greater than normal, in the venous drainage of the male reproductive system. The elevated pressure propagates to all interconnected vessels leading to a unique biological phenomenon: venous blood flows retrograde from the higher pressure in the testicular venous drainage system to the low pressure in the prostatic drainage system directly to the prostate (law of communicating vessels). We have found that free testosterone levels in this blood are markedly elevated, with a concentration of some 130-fold above serum level. Consequently, the prostate is exposed to: (i) increased venous pressure that causes hypertrophy; (ii) elevated concentration of free testosterone causing hyperplasia. We have treated 28 BPH patients using a technique that restores normal pressure in the venous drainage in the male reproductive system. The back-pressure and the back-flow of blood from the testicular to the prostate drainage system were eliminated and, consequently, a rapid reduction in prostate volume and a regression of prostate symptoms took place.     

Intracytoplasmic sperm injection in the treatment of male infertility due to obstructive or non-obstructive azoospermia

<正> Objective:To evaluate the effects of intracytoplasmic sperm injection (ICSI) ontreatment of infertility due to obstructive and non-obstructive azoospermia.Methods:A retrospective analysis of fertilization,cleavage,embryo implantationand pregnancy rates was done in 158 ICSI cycles including 112 obstructive azoospermiaand 46 non-obstructive azoospermia.Ovarian hyperstimulation and ICSI procedureswere performed by conventional protocol.The sperm was collected by percutaneous epi-didymal sperm aspiration (PESA) or testicular sperm extraction (TESE).Results:The fertilization rate (73.1% vs.67.0%),cleavage rate (88.6% vs.86.3%),embryo implantation rate (20.7% vs.11.4%),clinical pregnancy rate per trans-fer cycle (35.7% vs.19.6%) were obtained for obstructive and non-obstructiveazoospermia,respectively.Conclusion:The results revealed that in the cases of obstructive azoospermia,ferti-lization rate,embryo implantation rate and clinical pregnancy rate were significantlyhigher than those of non-obstructive azoospermia.But there was no significant differ-ence of the cleavage rate between two groups.     

Use of Raman spectroscopy to identify active spermatogenesis and Sertoli‐cell‐only tubules in mice

Microdissection testicular sperm extraction (micro‐TESE) has become the first line therapy to harvest spermatozoa for men with nonobstructive azoospermia. However, the pitfall is that the selection of seminiferous tubules depends on subjective assessment of the colour and size of tubules, which cannot guarantee successful retrieval of spermatozoa. The aim of this study was to determine whether Raman spectroscopy (RS) could distinguish tubules with spermatogenesis from Sertoli‐cell‐only (SCO) tubules, and potentially serve as a useful tool to improve sperm retrieval rates. Fourteen male adult mice were divided into two groups: SCO group received a single intraperitoneal injection of busulfan (40 mg per kg body weight), and the control group received a placebo dose of 0.9% saline solution. Mice were sacrificed after 4 weeks, and the testicular tissue was assessed by RS and then confirmed with histopathology. The results indicated that tubules with spermatogenesis had intensified Raman peaks at 748, 1124, 1309, 1446 and 1658 cm^?1 compared to SCO tubules, except a decreased peak at 1582 cm^?1. RS was able to distinguish the two groups with a sensitivity of 91.2% and specificity of 82.9%. In conclusion, RS may serve as a useful diagnostic tool prior to sperm retrieval.     

Genomic integrity of the Y chromosome sequence‐tagged‐sites in infertile and Down syndrome Jordanian males

The long arm of the Y chromosome contains nonoverlapping regions termed azoospermia factor (AZF) with great influence on male fertility. Microdeletions at these regions minimise the males' ability to father offsprings. In this preliminary study, we attempted to screen the presence or absence of twenty Y chromosome's sequence‐tagged sites (STS) associated with fertility in infertile and Down syndrome (DS) males. Genomic DNA from 35 fertile, 74 infertile and 22 karyotyped DS males was extracted and amplified in multiplex polymerase chain reaction (PCR) containing 20 primer pairs that amplify Y‐specific STS that cover functional regions associated with AZF and spermatogenesis‐related genes. Our results indicated the integrity of the Y chromosome at the 20 fertility markers for both the fertile and Down syndrome males. However, the results of the infertile males showed the presence of microdeletions at these Y‐specific STS. Three samples showed Y chromosome microdeletion when blood and seminal fluid genomic DNA were assayed, while two samples showed microdeletion only when seminal fluid genomic DNA was assayed. The current study demonstrated that the molecular genetic aspect of infertility should be given proper attention when dealing with infertility cases. Furthermore, our results indicate the importance of genetic counselling in managing infertility cases.     

Aquaporin-9 immunohistochemistry in varicocele testes as a consequence of hypoxia in the sperm production site

Aquaporin-9 (AQP-9) regulates tissue hydration by promoting transmembrane exchanges of both water and solutes, such as lactate. The latter is a key metabolite of primary spermatocytes and of maturing haploid germ cells (h-GCs). The present investigation was aimed at immunolocalising human AQP-9 in both normal and varicocele testes. Histology and immmunocytochemistry were investigated in archival biopsies from 20 varicocele testes and in eight unaffected ones. AQP-9 immunostaining was performed using a rabbit antibody, and either focal or diffuse cell membrane labelling was recorded. Varicocele testes showed disarranged tubular compartments, with sloughing h-GCs, tissue hyperhydration, spermiogenesis failure and fibrosis. AQP-9 immunohistology of the control testes showed a diffuse cell membrane staining of the primary spermatocytes and h-GCs, without any positive reaction of spermatogonia and Sertoli cells. AQP-9 cell expression in the varicocele testes was focal or lacking in both adluminal and sloughing GCs. AQP-9 expression occurs in normal human testis, at cell membrane of primary spermatocytes and h-GCs, suggesting a possible role of AQP-9 in the water and lactate transport from Sertoli cells to GCs. AQP-9 is focal or lacking in adolescent varicocele testes, and this suggests AQP-9 to be downregulated in such testicular disorder, leading to lactate deprivation with subsequent hypospermatogenesis.     

Effect of the metabolic syndrome on male reproductive function: a case‐controlled pilot study

The metabolic syndrome (MetS) is a constellation of various risk factors. This study aimed to investigate the effect of MetS on testosterone and progesterone, and semen parameters, in a case‐controlled pilot study. Male patients (n = 54) had body mass index, waist‐to‐hip ratio (WHR) and blood pressure recorded. Blood was analysed for HDL cholesterol, triglycerides and glucose. Saliva was assayed for free testosterone and free progesterone. Ejaculates were analysed for volume, sperm concentration, total sperm count, motility, vitality, mitochondrial membrane potential (MMP), DNA fragmentation and leucocyte concentration. Participants were divided into the control group (n = 28) and the MetS group (n = 26). Differences were found between the groups for body mass index, WHR, blood pressure, high‐density lipoprotein (HDL), triglycerides and glucose. The MetS group showed significant reductions in sperm concentration (P = 0.0026), total sperm count (P = 0.0034), total motility (P = 0.0291), sperm vitality (P = 0.002), MMP (P = 0.0039), free testosterone (P = 0.0093) and free progesterone (P = 0.0130), while values for DNA fragmentation increased (P = 0.0287). Results indicate that patients with MetS have compromised sperm parameters in the absence of leucocytospermia. A reduction in free progesterone suggests that steroidogenesis cascades may be compromised. It is hypothesised that a systemic pro‐inflammatory state with oxidative stress associated with MetS may provide a novel explanation.     

Single‐nucleotide polymorphisms in the LRWD1 gene may be a genetic risk factor for Japanese patients with Sertoli cell‐only syndrome

Genetic mechanisms have been implicated as a cause of some cases of male infertility. Recently, ten novel genes involved in human spermatogenesis, including human LRWD1, have been identified by expression microarray analysis of human testictissue. The human LRWD1 protein mediates the origin recognition complex in chromatin, which is critical for the initiation of pre‐replication complex assembly in G1 and chromatin organization in post‐G1 cells. The Lrwd1 gene expression is specific to the testis in mice. Therefore, we hypothesized that mutation or polymorphisms of LRWD1 participate in male infertility, especially azoospermia. To investigate whether LRWD1 gene defects are associated with azoospermia caused by SCOS and meiotic arrest (MA), mutational analysis was performed in 100 and 30 Japanese patients by direct sequencing of the coding regions, respectively. Statistical analysis was performed for patients with SCOS and MA and in 100 healthy control men. No mutations were found in LRWD1; however, three coding single‐nucleotide polymorphisms (SNP1‐SNP3) could be detected in the patients. The genotype and allele frequencies in SNP1 and SNP2 were notably higher in the SCOS group than in the control group (P < 0.05). These results suggest the critical role of LRWD1 in human spermatogenesis.     

217例男性不育症精子顶体酶检测与分析

目的　研究人精子顶体酶与男性不育之间的关系。　方法　 2 1 7例不育男性 ,年龄 2 4～ 43岁 ,根据精液常规检查结果分为不育 A、B两组 ;46例生育男性为对照组。手淫留取精液标本 ,常规洗涤后孵育 ,采用固定明胶底膜法检测精子顶体酶。　结果　正常生育组的精子顶体酶活性阳性率为 86.5% ,酶活性亮区直径为 42 .9μm。不育 A组酶活性阳性率为 57.0 % ,酶活性亮区直径为 3 8.5μm。不育 B组酶活性阳性率为3 5.2 % ,酶活性亮区直径为 2 7.5μm。经统计学处理 ,生育组与不育组之间精子顶体酶阳性率差异有显著性 ( P<0 .0 1 )。　结论　顶体酶阳性率和活力低下是男性不育的一个重要原因 ,精子顶体酶是受精过程中的关键酶     

Teucrium polium attenuates carbon tetrachloride‐induced toxicity in the male reproductive system of rats

The aim of this study was to investigate the protective effects of Teucrium polium (T. polium) on carbon tetrachloride (CCl₄)‐induced male reproductive system damage. The effects of T. polium and vitamin C (Vit C) on sperm parameters, gonadotrophin and testosterone levels, oxidative status and testis tissue structure were assessed in CCl₄‐treated male rats. CCl₄ caused significant alteration of sperm parameters in epididymal and testicular tissues, a decrease in hormone levels, and a decrease in antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) in testicular tissues. A noteworthy increase in malondialdehyde (MDA) level was induced in CCl₄‐treated rats with some histopathological damages on the testes compared with control group. Remarkable ameliorations were observed with respect to all the previous parameters, following the administration of CCl₄ with T. polium, and with vitamin C used as a positive control, when compared with CCl₄ alone. Teucrium polium extracts showed good antioxidant performance, suggesting its protective effect against chemically induced reprotoxicity.     

Treatment of infertility due to anejaculation in the male with electroejaculation and intracytoplasmic sperm injection

PURPOSE: We tested the hypothesis that spinal cord injury and/or anejaculation affects the outcome of intracytoplasmic sperm injection (ICSI). MATERIALS AND METHODS: From November 1993 to October 1998 we obtained and prospectively reviewed data on 34 ICSI cycles using electroejaculated sperm, 620 male factor infertility ICSI cycles using normal ejaculated sperm and 120 cases of obstructive azoospermia, in which microsurgical epididymal aspiration and testicular sperm extraction-ICSI were done in 93 and 27, respectively. RESULTS: A total of 34 ICSI cycles were performed in 17 couples with male infertility due to anejaculation secondary to spinal cord injury in 10 patients and retroperitoneal lymph node dissection in 5, and idiopathic in 2. In all 17 couples at least 3 previous intrauterine insemination cycles had failed. After electroejaculation 11 men had oligozoospermia and 6 normal sperm density. Median sperm retrieval volume plus or minus standard deviation was 1.9 +/- 1.9 ml., median sperm concentration 70.7 +/- 60.2 x 106 sperm per ml., median motility 10.7% +/- 10.8% and median forward progression 2.3 +/- 0.5 (scale 1 to 4). In the anejaculation group ICSI resulted in a median fertilization of 60% +/- 28%, 15% pregnancies per cycle and 29% pregnancies per couple. In the control group of 620 ICSI cycles from ejaculated specimens obtained from male patients with infertility median fertilization was 58% +/- 26%, and there were 39% pregnancies per cycle and 47% pregnancies per couple. The rate of pregnancies per embryo transfer and per couple was higher in the control than in the electroejaculation-ICSI group (p <0.05). However, there was no statistically significant difference in the fertilization rate. CONCLUSIONS: ICSI or in vitro fertilization is a viable alternative for patients with anejaculation in whom intrauterine insemination failed. While the fertilization rate is similar in these couples, the pregnancy rate is significantly lower than that achieved with ejaculated specimens from patients with severe male factor infertility. ICSI is a viable alternative for a patient with anejaculation in whom intrauterine insemination or in vitro fertilization failed.     

A comparison of long‐term outcomes of portal versus systemic venous drainage in pancreatic transplantation: a systematic review and meta‐analysis

Pancreas transplantation venous effluent can be drained via the portal vein or the systemic circulation; however, no recommendation exists for the ideal technique. A systematic review of the literature from 1989 through 2014 using PubMed, CINHAL, and Cochrane Library for portal versus systemic venous drainage was undertaken. Only studies on humans and published in English were considered. Measures of glycemic control and total cholesterol were synthesized for meta‐analysis utilizing random‐effects models. Of 166 articles retrieved, 15 articles were included for meta‐analysis. Patient and graft survival were comparable in a large database study as well as in the only randomized control study. No differences in complications were seen when exocrine drainage was enteric for the systemic venous group. Fasting insulin (?34.13 pmol/mL, p < 0.001) was significantly lower within the portal drained group; however, fasting blood glucose levels (?3.4 mg/dL, p = 0.32) and hemoglobin A1C levels (mean difference 0.124%, p = 0.25) were comparable. Total cholesterol levels (?3.62 mg/dL, p = 0.447), as well as other measures of lipids, showed no difference. Based on this systematic review and meta‐analysis, there is no evidence of differences in outcomes or metabolic control in patients undergoing pancreatic transplant with portal venous drainage compared to the systemic venous drainage.     

男性不育的辅助生殖技术处理:潜在风险与思考

辅助生殖技术是上世纪末出现的治疗男性不育的重要手段,它在男性不育的治疗中有着不可替代的作用,但有关男性不育的辅助生殖技术处理也存在潜在风险,在男性不育的诊疗中如何规避这些潜在风险值得男性生殖健康领域的工作者思考。本文对辅助生殖技术潜在风险进行总结,同时,为提高男性不育的治疗效果,尽量减少辅助生殖技术带来的风险,提出了包括患者的评估、健康教育以及治疗等男性不育规范化处理方面的一些建议,并强调病因处理和抗氧化治疗在男性不育治疗中的重要作用。     

Fifteen-year trend in the use of male reproductive surgery: analysis of the healthcare cost and utilization project data

Study Type – Utilization analysis (cost of care)Level of Evidence 2b What’s known on the subject? and What does the study add? Prior to this work, there were no systematic studies determining the national trends in the utilization of reproductive surgery in males. The role of reproductive surgery as it pertains to the treatment of infertility has become less clear given the increasing use of assisted reproductive technologies with intracytoplasmic sperm injection. The current study showed that the number of male reproductive surgeries has declined during the period between 1988 and 2002.

OBJECTIVE

? To determine trends in male reproductive surgeries.

MATERIALS AND METHODS

? A database analysis was performed using the Healthcare Cost and Utilization Project databases from 1988, 1992 and 1998–2002. SAS statistical software was used to estimate the total numbers of reproductive surgeries and their variances for each year.

RESULTS

? The number of male reproductive surgeries has declined during the period of study, both in the inpatient and outpatient arenas. The number of procedures with a diagnosis of infertility has also declined.

CONCLUSION

? The number of male reproductive surgeries has declined from 1988 to 2002.     

Melatonin therapy adds extra benefit to varicecelectomy in terms of sperm parameters,hormonal profile and total antioxidant capacity: A placebo‐controlled,double‐blind trial

In this study, we aimed at investigating the impact of melatonin supplementation on semen parameters, hormonal profile and total antioxidant capacity after varicocelectomy. Infertile male patients who were diagnosed with varicocele and underwent subinguinal varicocelectomy were included in the study. After performing subinguinal varicocelectomy, the patients were randomised into two groups: 27 receiving melatonin for 3 months and 27 as the placebo‐controlled group receiving placebo for 3 months. The pre‐operative parameters of semen analyses, hormonal profile and seminal oxidative stress status of both groups were compared with those of post‐operative parameters. There were statistically significant improvements in post‐operative parameters of semen analyses (sperm concentration, motility and proportions of normally formed spermatozoa), peripheral blood inhibin B and total antioxidant capacity in melatonin group compared with placebo group. In conclusion, melatonin therapy adds extra benefit to varicecelectomy in terms of sperm parameters, peripheral blood inhibin B and total antioxidant capacity; however, further studies including large number of samples are needed to make a proper decision on melatonin supplementation after varicocelectomy.     

Comparative evaluation of the effects of Withania somnifera with pentoxifylline on the sperm parameters in idiopathic male infertility: A triple‐blind randomised clinical trial

In this triple‐blind randomised clinical trial, we compared the effects of Withania somnifera and pentoxifylline on the sperm parameters in idiopathic male infertility. One hundred infertile male patients were randomly allocated into either W. somnifera or pentoxifylline groups. Patients in the herbal group received six capsules containing 5 g/daily of W. somnifera root, and subjects in the pentoxifylline group received six capsules containing 800 mg/daily of pentoxifylline and placebo for 90 days. Sperm parameters were analysed at the beginning and end of the study. W. somnifera increased mean sperm count (12.5%) and progressive motility (21.42%) and improved sperm morphology (25.56%) compared to the baseline (p = .04, p = .001 and p = .000 respectively). Moreover, pentoxifylline increased mean semen volume (16.46%), progressive motility (25.97%) and improved sperm morphology (13.28%) versus the baseline (p = .02, p = .003 and p = .01 respectively). Intergroup comparison showed no significant differences between the two groups regarding semen volume (p = .11), sperm count (p = .09), morphology (p = .12) and progressive motility (p = .77) after treatment. No major complication was reported in either of the two groups. W. somnifera, a traditional medicine remedy, improves sperms parameters in idiopathic male infertility without causing adverse effects. Therefore, this medication can be considered to be an alternative to pentoxifylline in this regard.     

CAG‐repeat polymorphisms in the polymerase γ gene and male infertility: a meta‐analysis

CAG‐repeat in the polymerase γ (POLG) gene encoding polymerase γ for mitochondria is important to spermatogenesis. Compared with a few researchers who raised alteration of CAG‐repeat‐affected male reproductive ability, others did not find the association between CAG‐repeat polymorphisms and male infertility. Therefore, a comprehensive meta‐analysis is necessary to determine the association; 13 case–control studies were screened out using keywords search. From these studies, characteristics were extracted for conducting meta‐analysis. Odds ratio (OR) and 95% confidence interval (CI) were used to describe the results; the results indicated that CAG‐repeat allele was not a risk factor to male infertility (pooled OR = 1.03, 95% CI: 0.79–1.34, P = 0.828). Four different genetic comparisons also demonstrated a negative result: heterozygote comparison (not 10/10 versus 10/10. Pooled OR = 0.99, 95% CI: 0.77–1.27, P = 0.948), homozygote comparison (not 10/not 10 versus 10/10. Pooled OR = 1.08, 95% CI: 0.56–2.06, P = 0.816), the recessive genetic comparison (not 10/not 10 versus not 10/10 + 10/10. Pooled OR = 1.07, 95% CI: 0.58–1.95, P = 0.829) and the dominant genetic comparison (not 10/not 10 + not 10/10 versus 10/10. Pooled OR = 0.97, 95% CI: 0.72–1.29, P = 0.804); based on current researches, this meta‐analysis demonstrated no apparent association between POLG‐CAG‐repeat and male infertility. Similarly, CAG‐repeat was not a sensitive site to male infertility.