精索静脉曲张所致不育的免疫学研究

目的研究精索静脉曲张(VC)所致不育与抗精子抗体(AsAb)的关系。方法240例男性不育患者分为VC组和对照组,行精液常规和AsAb检测。结果VC组AsAb阳性率为37.9%,对照组阳性率为25%,两组间有显著性差异(P<0.05);VC组中AsAb阳性率与临床分级密切相关(P<0.005),与精子密度亦明显相关(P<0.01)。结论免疫因素可能是导致VC不育的原因之一。     

Surgical techniques for the management of male infertility

Evaluation and surgical treatment of male infertility has evolved and expanded, now leading to more precise diagnoses and tailored treatments with diminished morbidity and greater success. Surgeries for male infertility are divided into four major categories: (i) diagnostic surgery; (ii) surgery to improve sperm production; (iii) surgery to improve sperm delivery; and (iv) surgery to retrieve sperm for use with in vitro fertilization and intracytoplasmic sperm injection (IVF-ICSI). While today we are more successful than ever in treating male infertility, pregnancy is still not always achieved likely due to factors that remain poorly understood. Clinicians treating infertility should advocate for couple-based therapy, and require that both partners have a thorough evaluation and an informed discussion before undergoing specific surgical therapies.     

男性不育伴精索静脉曲张患者的心理状况调查

目的:探索男性不育伴精索静脉曲张患者的精神心理症状的发生情况及其与不育的关系。方法:采用14项症状的医院焦虑抑郁量表(HAD量表)对110例不育伴精索静脉曲张患者进行精神心理因素的评估,分析各相关因素与患者精神心理因素的相关性,筛选鉴别男性不育伴精索静脉曲张患者发生焦虑抑郁症状的危险因素,并与61例已婚生育健康男性作为对照组进行比较分析。对106例不育伴精索静脉曲张患者的精神心理症状进行多因素分析。结果:男性不育伴精索静脉曲张患者和已经生育的健康对照者焦虑症状发生率分别为61.32%和13.79%,抑郁症状发生率分别为37.73%和6.90%,不育伴精索静脉曲张组的焦虑和抑郁症状发生率显著高于已育健康对照组(P<0.05)。Logistic回归分析结果显示,不育患者发生焦虑抑郁的主要危险因素是就诊次数和睾丸病变程度。结论:男性不育伴精索静脉曲张患者合并有明显精神心理症状,值得关注。患者中多次就诊及睾丸病变程度严重者更容易发生焦虑抑郁。     

精索静脉曲张与男性不育

精索静脉曲张(VC)是导致男性不育的最常见原因之一,手术是治疗VC的主要方法。近来,关于VC导致不育的病理机制研究较多,尤其是细胞分子机制的研究进展较快,主要包括生精细胞凋亡异常和氧化应激。同时,对于VC手术指征和各种术式优劣性的认识也渐趋统一。本文介绍VC导致不育的细胞分子机制及临床治疗决策的研究进展。     

Y chromosome microdeletions and varicocele as aetiological factors of male infertility: A cross‐sectional study

The pathogenic mechanisms by which varicocele disrupt spermatogenesis are not clearly understood. Over 30% of male infertility cases resulting from spermatogenic problems are associated with genetic abnormalities, and Y chromosome microdeletions are the second most frequent genetic cause. Here, we aimed to evaluate the frequency of Y chromosome microdeletion in infertile men with varicocele. A cross‐sectional study comprising 51 infertile men with varicocele presenting spermatogenesis failures was performed. Y chromosome microdeletion research was made using polymerase chain reaction. Of the 51 men with infertility and varicocele, 35.3% (18/51) had nonobstructive azoospermia and 64.7% had severe oligozoospermia. Y chromosome microdeletion was found in two cases (3.9%): one patient had nonobstructive azoospermia and complete microdeletion of the AZFb and AZFc regions, and another patient had severe oligozoospermia and complete microdeletion of the AZFc region. Although in recent years, a genetic aetiology related to Y chromosome microdeletions has become a major cause of infertility in males with spermatogenesis failures, in this study, the varicocele was the clinical cause of seminal abnormalities that could lead to infertility, suggesting that both varicocele and Y chromosome microdeletion aetiologies can present, alone or combined, as factors of male infertility.     

Spermatozoa protein alterations in infertile men with bilateral varicocele

Among infertile men, a diagnosis of unilateral varicocele is made in 90% of varicocele cases and bilateral in the remaining varicocele cases. However, there are reports of under-diagnosis of bilateral varicocele among infertile men and that its prevalence is greater than 10%. In this prospective study, we aimed to examine the differentially expressed proteins (DEP) extracted from spermatozoa cells of patients with bilateral varicocele and fertile donors. Subjects consisted of 17 men diagnosed with bilateral varicocele and 10 proven fertile men as healthy controls. Using the LTQ-orbitrap elite hybrid mass spectrometry system, proteomic analysis was done on pooled samples from 3 patients with bilateral varicocele and 5 fertile men. From these samples, 73 DEP were identified of which 58 proteins were differentially expressed, with 7 proteins unique to the bilateral varicocele group and 8 proteins to the fertile control group. Majority of the DEPs were observed to be associated with metabolic processes, stress responses, oxidoreductase activity, enzyme regulation, and immune system processes. Seven DEP were involved in sperm function such as capacitation, motility, and sperm-zona binding. Proteins TEKT3 and TCP11 were validated by Western blot analysis and may serve as potential biomarkers for bilateral varicocele. In this study, we have demonstrated for the first time the presence of DEP and identified proteins with distinct reproductive functions which are altered in infertile men with bilateral varicocele. Functional proteomic profiling provides insight into the mechanistic implications of bilateral varicocele-associated male infertility.     

热休克蛋白在男性不育中的研究进展

热休克蛋白是一类生物进化上高度保守的伴侣蛋白分子,具有多种生物学功能,包括作为分子伴侣、细胞保护、抗凋亡和免疫调节等。近年来研究发现,多种热休克蛋白参与精子发生、精子获能及受精等一系列活动,与男性生殖过程密切相关。因此,进一步研究热休克蛋白在男性不育中的具体机制及作用,可能为男性不育提供新的治疗途径。本文重点对热休克蛋白在男性不育中的研究进展作一综述。     

The cost-effectiveness of treatment for varicocele related infertility

PURPOSE: We compared the cost-effectiveness of 4 treatment strategies for varicocele related infertility from the perspective of the health care payor and patient. MATERIALS AND METHODS: Cost-effectiveness analysis was performed by studying 4 treatment strategies, namely observation, surgical varicocelectomy followed by in vitro fertilization (IVF) if unsuccessful, gonadotropin stimulated intrauterine insemination (IUI) followed by IVF if unsuccessful, and immediate IVF. The main outcome measure was incremental cost per live delivery of any number of newborns. RESULTS: Immediate IVF cost more per live delivery and was less effective than varicocelectomy/IVF or IUI/IVF. When electing the latter 2 procedures, the preferred approach depended on the choice of perspective. From the health care payor viewpoint each additional birth that resulted from choosing varicocelectomy/IVF over observation cost $52,152, while each additional birth that occurred by electing IUI/IVF over varicocelectomy/IVF cost $561,423. From the patient perspective, while varicocelectomy/IVF resulted in improved outcomes over observation, a rational decision maker would always be willing to pay the slightly higher cost of IUI/IVF (incremental cost per live birth versus observation $27,371) for the added benefit in effectiveness if they were initially willing to invest in varicocelectomy/IVF (incremental cost per live birth versus observation $27,618). CONCLUSIONS: The optimal choice of treatment for varicocele related infertility depends strongly on the decision maker perspective. Regardless of perspective the most technologically advanced treatment, that is immediate IVF, is never favored. The findings of this study should be used to counsel infertile patients with varicocele that immediate IVF is not cost-effective.     

An update on the role of medical treatment including antioxidant therapy in varicocele

Varicocele-associated male infertility has classically been managed using surgery or assisted reproductive techniques. With increasing evidence of oxidative stress as a pathophysiological factor in varicocele-associated infertility, medical therapy especially antioxidants might become a treatment option with lower risks. We reviewed the existing literature on the role of various medical agents in the management of male infertility attributed to varicoceles. Medical therapy is typically evaluated in three different situations such as (a) comparison of two drugs or one drug with placebo, (b) comparison of drugs versus surgery, and (c) comparison of drugs as adjuvant therapy with surgery versus drug therapy alone. Due to heterogeneity of data and lack of well-conducted studies, there is insufficient data to recommend routine use of medical therapy for men with varicocele-associated infertility and surgery remains the treatment of choice. Pregnancy and live birth rates are usually not reported in most studies and mere improvement in sperm parameters or antioxidant capacity is insufficient to support its routine use. Antioxidant therapy is a potential option due to its theoretical benefit, data from preclinical studies, and lack of major side effects. Adjuvant therapy with antioxidants after surgical repair of varicocele may improve the outcome and is a potential area for further research.     

低位显微外科与腹腔镜两种精索静脉结扎术治疗精索静脉曲张性不育疗效比较

目的 比较低位显微外科与腹腔镜精索静脉结扎术治疗精索静脉曲张性不育患者的疗效.方法 40例精索静脉曲张性不育患者,随机分为两组,低位显微外科精索静脉结扎术组(A组,20例)和腹腔镜精索静脉结扎术组(B组,20例),比较术前、术后第1、6、12月的精液质量,并且追踪术后2年内配偶临床妊娠结果.结果 两组术后精子密度、精子总数和(a+b)级精子数均较术前有显著提高(P<0.05),但组内术后第1、6、12月的精液质量各主要参数间对比,无统计学差异(P>0.05).组间术前、术后第1、6、12月精液质量各主要参数进行对比,无统计学差异(P>0.05).术后随访2年配偶临床妊娠A组为13例(65%),B组为12例(60%).结论 低位显微外科精索静脉结扎术对精索静脉曲张(VC)伴有男性不育患者是一种经济、简单、有效、便于推广的手术治疗方式.     

Proteomic signatures of infertile men with clinical varicocele and their validation studies reveal mitochondrial dysfunction leading to infertility

To study the major differences in the distribution of spermatozoa proteins in infertile men with varicocele by comparative proteomics and validation of their level of expression. The study-specific estimates for each varicocele outcome were combined to identify the proteins involved in varicocele-associated infertility in men irrespective of stage and laterality of their clinical varicocele. Expression levels of 5 key proteins (PKAR1A, AK7, CCT6B, HSPA2, and ODF2) involved in stress response and sperm function including molecular chaperones were validated by Western blotting. Ninety-nine proteins were differentially expressed in the varicocele group. Over 87% of the DEP involved in major energy metabolism and key sperm functions were underexpressed in the varicocele group. Key protein functions affected in the varicocele group were spermatogenesis, sperm motility, and mitochondrial dysfunction, which were further validated by Western blotting, corroborating the proteomics analysis. Varicocele is essentially a state of energy deprivation, hypoxia, and hyperthermia due to impaired blood supply, which is corroborated by down-regulation of lipid metabolism, mitochondrial electron transport chain, and Krebs cycle enzymes. To corroborate the proteomic analysis, expression of the 5 identified proteins of interest was validated by Western blotting. This study contributes toward establishing a biomarker “fingerprint” to assess sperm quality on the basis of molecular parameters.     

转流术与断流术治疗精索静脉曲张症的疗效评价

目的　为评价精索静脉转流术与结扎术二种手术方法对治疗精索静脉曲张引起男性不育的疗效。方法　于术后一年中分别随访 82例病人 ,接受转流者 47例 ,结扎者 35例。结果　 (1)术后病人症状、精子质量均得到显著改善 ,但是 ,两组间无明显差异 (P >0 .0 5 )。 (2 ) 15例有症状者术后缓解 ,47例转流受术者无一复发 ,35例结扎受术者 2例复发 ,占 5 .7%。两者精子质量改善者共 47例 ,占 5 8.5 3% ,妊娠及分娩 2 5例 ,占 30 .5 %。 (3)术后 3月 ,精子活力提高明显好于精子质量的其它参数 ,而在术后半月中 ,精子活力的提高转流者 2 7例 ,结扎者仅 7例。结论　精索内静脉转流术仍是部分精索静脉曲张不育症者治疗的较好手段     

不育男性双侧Ⅰ度精索静脉曲张对睾丸体积和生殖激素水平的影响

目的 评价不育男性双侧I度精索静脉曲张对睾丸体积和生殖激素水平的影响.方法 185例不育男性双侧I度精索静脉曲张(A组)和149例正常生育男性(B组),比较其睾丸体积、卵泡刺激素(FSH)、黄体生成素(LH)和睾酮(T)水平.结果 A组患者两侧睾丸体积均小于B组,但睾丸体积绝对差异和睾丸体积相对差异与B组比较,无统计学意义.A组患者血清FSH水平高于B组,而LH、T与B组相比,差异无统计学意义.结论 不育男性双侧I度精索静脉曲张可导致患者双侧睾丸体积减小,血清FSH水平升高.     

Age is a significant predictor of early and late improvement in semen parameters after microsurgical varicocele repair

Accumulating evidence indicates that varicocele repair improves sperm quality. However, longitudinal changes in sperm parameters and predictors of improved semen characteristics after surgery have not been fully investigated. We retrospectively reviewed data from 100 men who underwent microsurgical subinguinal varicocele repair at a single centre. Follow‐up semen examinations were carried out at 3, 6 and 12 months post‐operatively. Logistic regression was used to identify predictors of early (3 months) and late (≥6 months) improvement in semen parameters after varicocele repair. At 3 months post‐operatively, 76.1% of the patients had improved total motile sperm counts, which continued to improve significantly up to 12 months post‐operatively (p = .016). When comparing changes in semen parameters between younger (<37 years) and older (≥37 years) men, post‐operative improvements in sperm concentration and motility were greater among younger men. Multivariate analysis showed that younger age was associated with early (p = .043) and late (p = .010) post‐operative improvement in total motile sperm count. Our findings indicate that early varicocele repair improved semen parameters after surgery.     

Assessment of seminal granulysin in infertile men with varicocele

Varicocele has a common association with male infertility, but its exact role is still debated. Apoptosis has been suggested as one of the mechanisms of varicocele‐associated infertility. Granulysin is a molecule that plays a role in apoptosis with no previous study about its role in male infertility. This case‐controlled study aimed to assess seminal plasma granulysin level in infertile patients with varicocele. This study involved 90 men that were allocated into fertile normozoospermic men (n = 20), infertile men without varicocele (n = 30) and infertile men with varicocele (n = 40). These men were subjected to history taking, clinical examination, semen analysis and estimation of seminal granulysin. In general, seminal granulysin level was significantly elevated in infertile men compared with fertile men. Infertile men with varicocele showed significantly higher seminal granulysin compared with infertile men without varicocele, in bilateral varicocele cases and in grade III varicocele. Seminal granulysin level was negatively correlated with sperm concentration, sperm motility, sperm normal forms percentage and testicular volumes. It is concluded that increased seminal granulysin has a negative impact on spermatogenesis in infertile men in general and in infertile men associated with varicocele in particular.     

The role of infections and leukocytes in male infertility

Declining birth rates are one of the problems facing society today. Male counterparts are responsible for about half of the infertility cases, and genitourinary tract infections may play a contributing role in approximately 15% of male infertility cases. Leukocytospermia is an established indicator of infection in the male urogenital tract, although other microorganisms such as bacteria and virus may also be contributors to the etiology of male infertility. The pathophysiology of these infectious agents may be initiated by a local inflammatory reaction resulting in an increase in reactive oxygen species (ROS). This results in testicular injury, thereby affecting sperm morphology, sperm motility, sperm viability and elevation of the seminal leukocyte as a result of the genital tract infection. The infectious and inflammatory changes can result in male infertility. It is proposed that high concentrations of seminal leukocyte and infectious agents may affect sperm function resulting in clumping of motile spermatozoa, decreasing acrosomal functionality and also causing alterations in sperm morphology. However, the literature has poorly clarified the role of infection in male infertility, provoking further debate and research on this topic.     

Cost-effectiveness of varicocele surgery in the era of assisted reproductive technology

The advent of innovative techniques for addressing infertility has made for exciting times in the arena of andrology. The success of microTESE for retrieving sperm has enabled azoospermic men to have the opportunity to father biological children when it was previously impossible. The ability to offer a variety of assisted reproductive techniques that includes intracytoplasmic sperm injection has opened the door for couples with male factor infertility who were otherwise untreatable. With the multitude of options available to infertile couples, however, comes an unsurprising degree of controversy regarding what treatments should be offered and when. Complicating the picture is the question of if and when varicocele repair should be undertaken, and the financial implications of the treatment decisions that are made. The infertile couple with varicocele warrants careful consideration. The overall efficacy of varicocele repair as well as cost-effectiveness of repair compared to immediate microTESE in azoospermic men and assisted reproductive technology in men with suboptimal semen parameters will be reviewed.