Chlamydial infection and male infertility: an epidemiological study

Chlamydia-positive genitourinary infections are common causes of male and female infertility. Semen abnormalities are often associated with Chlamydia infections. A large population of male patients, admitted to our clinic for genitourinary infection, were examined for genitourinary pathogens, including Chlamydia, and for semen abnormalities. There were higher abnormalities semen in Chlamydia-infected patients than either non-Chlamydia-infected or healthy controls. Chlamydia therapy by antimicrobial agents improved semen characteristics. Chlamydia infection contributes to seminal fluid abnormalities and probably to male infertility. A search for chlamydial infection is warranted whenever semen abnormalities are noted. An antimicrobial therapy improves semen quality when effective in eradicating Chlamydia.     

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.     

Chlamydial infections in urology

Chlamydia trachomatis is the most frequent cause for sexually transmitted diseases in European countries. The organism has an intracellular habitat with a very specific life cycle. A variety of diagnostic tests have been developed with different sensitivity and specificity. Interpretation of these tests can sometimes be difficult. Diseases caused by C. trachomatis in men comprise urethritis, prostatitis, epididymitis, infertility and reactive arthritis. Especially in prostatitis, the exact role of C. trachomatis is still under debate for the technical difficulties localizing the pathogen to the prostate. For treatment, only some antibiotics are effective because of the intracellular habitat of the pathogen. Prevention of infection comprises treatment and screening efforts.     

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。     

Beta-endorphin and male infertility

Beta-endorphin (beta-ED) levels were evaluated in blood and seminal plasma of men with infertility due to varicocele, obstructive and nonobstructive azoospermia, and idiopathic oligoasthenospermia. The relation of this opiate to serum levels of gonadotropins, prolactin, testosterone, androstenedione, and dehydroepiandrosterone sulfate has also been investigated. beta-ED levels in seminal plasma were significantly higher than in blood plasma (p less than 0.001) in all persons studied. No statistically significant differences were found for beta-ED concentrations in semen or blood among any of the infertility situations studied. Nor were significant correlations observed between the concentration of this opiate and that of gonadotropins, prolactin, and androgens. The measurement of beta-ED in semen has little value in the differential diagnosis of male infertility. Nonetheless, its presence in high levels in semen must have some unknown function. Possibly, it comes from the various sites of the male reproductive tract, since no significant differences were found between obstructive and nonobstructive azoospermias.     

Lycopene and male infertility

Excessive amounts of reactive oxygen species （ROS） cause a state of oxidative stress, which result in sperm membrane lipid peroxidation, DNA damage and apoptosis, leading to decreased sperm viability and motility. Elevated levels of ROS are a major cause of idiopathic male factor infertility, which is an increasingly common problem today. Lycopene, the most potent singlet oxygen quencher of all carotenoids, is a possible treatment option for male infertility because of its antioxidant properties. By reacting with and neutralizing free radicals, lycopene could reduce the incidence of oxidative stress and thus, lessen the damage that would otherwise be inflicted on spermatozoa. It is postulated that lycopene may have other beneficial effects via nonoxidative mechanisms in the testis, such as gap junction communication, modulation of gene expression, regulation of the cell cycle and immunoenhancement. Various lycopene supplementation studies conducted on both humans and animals have shown promising results in alleviating male infertility--lipid peroxidation and DNA damage were decreased, while sperm count and viability, and general immunity were increased. Improvement of these parameters indicates a reduction in oxidative stress, and thus the spermatozoa is less vulnerable to oxidative damage, which increases the chances of a normal sperm fertilizing the egg. Human trials have reported improvement in sperm parameters and pregnancy rates with supplementation of 4-8 mg of lycopene daily for 3-12 months. However, further detailed and extensive research is still required to determine the dosage and the usefulness of lycopene as a treatment for male infertility.     

Immunology and male infertility.

This article has attempted to review evidence that suggests that immune factors may be operative in a small but significant number of infertile men. Although our current understanding of the possible processes by which autosensitization to previously sequestered reproductive antigens occurs is incomplete, there are laboratory assays presently available that give an indication, but do not prove, that immune factors may be contributing to the infertile state. Continued research is needed to develop new assays and more purified sperm antigens, which might enhance our knowledge of the underlying immunoreproductive changes. Until these are available, the following procedures should be considered when investigating a patient with infertility of suspected immune origin. The patient's history should be taken, and a physical examination should be performed. A complete blood count, urinalysis, and complete semen analysis and culture should be taken. Next, in vivo cervical tests (Sims-Huhner) are performed, followed by sperm antibody assessment (serum, semen) and perhaps in vitro cervical mucus sperm assays (especially the crossed hostility test). After the tests have been completed, the following possibe treatments exist: 1. Treatment of underlying infections 2. Correction of obstructions 3. Corticosteroid (or testosterone?) therapy 4. Washed sperm insemination 5. First portion of fresh ejaculate insemination 6. Artificial insemination with homologous donor 7. Adoption.     

无精子症因子缺失与男性不育相关性研究进展

Y染色体上含有与男性性腺发育和精子发生及分化密切相关的基因。无精子症因子(AZF)是位于Y染色体长臂远端的精子发生调控基因,它的缺失会导致精子发生障碍进而引发男性不育。目前大多数人将AZF分为AZFa、AZFb、AZFc三个区域,也有人认为AZFb和AZFc之间应该增加一个新的区域并命名为AZFd。不同分区的缺失会引起不同的表型。其中,AZFc缺失作为目前最常见的缺失类型被广泛的研究。AZFc缺失包括了AZFc全缺失和AZFc部分缺失,AZFc部分缺失主要为gr/gr缺失和b2/b3缺失。gr/gr缺失在某些地区或人种中引起男性生精障碍的作用已经被证实,b2/b3缺失对生精障碍的影响目前尚无定论,但是它在单倍群N中的普遍分布这一现象也引发了人们的深入思考。本文对AZF不同区域尤其是AZFc区的基本结构、候选基因、缺失情况以及与精子发生的关系作一综述,旨在为临床产前诊断及男性不育治疗提供理论依据。     

阴囊温度升高与男性不育的关系

对２２例生育者、４４例精索静脉曲张（ＶＣ）患者、１７例特发性无精子症（ＩＡ）患者行远红外阴囊测温。并对无精子者行睾丸活检。结果发现：（１）ＶＣ患者阴囊温度显著高于生育者（Ｐ＜０．００１）而低于ＩＡ（Ｐ＜０．００１）。（２）ＶＣ精液正常者阴囊温度与生育者无差异而显著低于ＶＣ精液异常者（Ｐ＜０．０１）。（３）ＩＡ与ＶＣ合并无精子症阴囊温度无显著差异。（４）阴囊温度升高使生精细胞减少，精子成熟障碍，特别是Ｓｅｒｔｏｌｉ细胞变性明显。认为ＶＣ、ＩＡ患者均存在阴囊温度升高，且温度愈高，睾丸生精功能愈差。Ｓｅｒｔｏｌｉ细胞变性是睾丸生精障碍原因之一。阴囊温度调节失调可能是阴囊温度升高的直接原因。     

性染色体与男性不育

男性不育是个全球化的问题,其包括遗传原因在内的影响因素众多。对男性而言,X染色体和Y染色体均为单个拷贝。Y染色体因为包含了许多精子发生和性腺发育的关键基因,因而成为研究的热点。Y染色体微缺失是男性精子发生障碍最常见的原因之一。Y染色体长臂的无精子症因子(AZF)区是Y染色体微缺失的好发区域。目前明确定位于AZF区域与精子发生相关的编码蛋白基因有14个,但由于通常的AZF缺失为多基因的联合缺失,因而AZF区域的特定基因在精子发生中的作用还不是很清楚。哺乳动物X染色体在精子发生中的作用因其富集着许多精子发生过程中生殖细胞特异表达基因而受到重视,如AR、USP26、TAF7L、TEX11、KAL1、AKAP4和NXF2等基因。在男性,由于X染色体为半合子状态,X连锁基因通常承受着特别的进化压力,X染色体连锁的单拷贝基因突变不会象常染色体那样被1个正常的等位基因所掩盖掉。尽管许多关于X染色体与精子发生关系的研究已经进行,但X染色体与男性不育的关系仍然还不清楚,还有待更进一步研究。     

AZF与男性不育研究进展

AZF微缺失的发生率在1%～55%之间不等。AZF基因缺失与严重的生精功能障碍密切相关,是最常见的导致严重少弱精子症和无精子症的分子遗传学因素。对AZF及其相关基因的研究,可从分子水平阐明精子发生障碍的机制,对男性不育症的诊断、治疗及预后判断具有非常重要的意义。本文综述了AZF基因结构和功能特点,及其与男性不育、隐睾、精索静脉曲张、Klinefelter综合征、精原细胞瘤、习惯性流产等之间的关系。     

神经肽催产素与男性不育关系的研究

目的:分析特发性男性不育患者催产素(oxytocin,OT)水平及其受体的表达。方法:选取特发性少精子症(oligozoospermia group,OG)(含无精子)、弱精子症(asthenozoospermia group,AG)及少精子合并弱精子症(oligoasthenozoospermia group,OAG)男性不育患者共65例,年龄20～45岁;对照组(control group,CG)选取有自然生育史的健康男性志愿者20例(精液参数正常),年龄20～45岁。检测各组血清黄体生成素(luteinizing hormone,LH)、卵泡刺激素(follicle-stimulating hormone,FSH)、睾酮(testosterone,T)及OT含量,进一步通过检测催产素受体启动子功能序列(oxytocin receptor promotor fuctional sequence,OTRP)、催产素受体羧基端部分mRNA序列(OTRmR-NA)以及OTR蛋白构象、组成来分析OTR表达情况。OTR蛋白印迹分析结果经灰度软件处理后转化为计数资料;统计方法采用单因素方差分析。结果:①男性生殖内分泌激素含量分析:OT:各病例组均高于CG[(79.30±3.83)pg/ml],具有统计学意义(F0.05/2(2,82)=8.29,P<0.001);LH:AG[(4.26±0.31)IU/L]及OAG[(4.55±0.40)IU/L]均低于OG[(6.77±0.57)IU/L]和CG[(7.19±0.50)IU/L](F0.05/2(2,82)=11.64,P<0.01);FSH:AG[(5.02±0.39)IU/L]低于CG[(8.91±0.91)IU/L]、OG[(11.86±1.76)IU/L]及OAG[(8.82±1.03)IU/L](F0.05/2(2,82)=7.22,P<0.01);T:各组间无统计学差异(F0.05/2(2,82)=0.42,P=0.739)。②OTR基因转录分析:OTR启动子功能序列和OTR成熟mRNA序列未发现明显的变异。③OTR构象分析:人OTR以单体和寡聚体同时存在,以寡聚体为主,常见为四聚体和六聚体;AG(0.41±0.03)和OAG(0.13±0.01)的单体明显多于OG(0.05±0.004)和CG(0.05±0.003)(F0.05/2(2,82)=115.50,P<0.01);AG中20%病例存在寡聚体明显减少现象。结论:男性不育患者血清OT含量及OTR表达的差异提示OT与男性不育间存在一定的联系,OTR单体表达升高及寡聚体表达降低为进一步探索OT与男性不育间的关系提供了新的方向。     

Chromosomal disorders and male infertility

Infertility in humans is surprisingly common occurring in approximately 15% of the population wishing to start a family. Despite this, the molecular and genetic factors underlying the cause of infertility remain largely undiscovered. Nevertheless, more and more genetic factors associated with infertility are being identified. This review will focus on our current understanding of the chromosomal basis of male infertility specifically: chromosomal aneuploidy, structural and numerical karyotype abnormalities and Y chromosomal microdeletions. Chromosomal aneuploidy is the leading cause of pregnancy loss and developmental disabilities in humans. Aneuploidy is predominantly maternal in origin, but concerns have been raised regarding the safety of intracytoplasmic sperm injection as infertile men have significantly higher levels of sperm aneuploidy compared to their fertile counterparts. Males with numerical or structural karyotype abnormalities are also at an increased risk of producing aneuploid sperm. Our current understanding of how sperm aneuploidy translates to embryo aneuploidy will be reviewed, as well as the application of preimplantation genetic diagnosis (PGD) in such cases. Clinical recommendations where possible will be made, as well as discussion of the use of emerging array technology in PGD and its potential applications in male infertility.     

Testicular cancer and male infertility

PURPOSE OF REVIEW: Testicular cancer and infertility affect a similar age group of patients and have common biologic, epidemiologic, and environmental backgrounds. In this review, we provide current literature on links between infertility and testicular cancer, and new developments in the management of testicular cancer aimed at improving quality of life in men with testicular cancer. RECENT FINDINGS: In-utero environmental exposure to endocrine disruptors modulates the genetically determined fate of primitive gonad and results in testicular dysgenesis syndrome, which may result in infertility and testicular cancer. Excellent response of testicular cancer to radiation and chemotherapy results in over 90% of survival and quality of life--fertility and sexual function--is of significant concern to patients and clinicians. The testicular-sparing management of testicular masses emerges as a sound alternative to radical orchiectomy and allows for preservation of spermatogenesis and hormonal function, and at the same time achieving similar survival rates. Secondary malignancies, pulmonary, and cardiovascular complications are recognized as late complications of treatment for testicular cancer. SUMMARY: Better understanding of common mechanisms involved in infertility and testicular cancer, and scientifically driven evidence-based treatment options should improve quality of life in young men faced with this potentially life-threatening disease.     

Chlamydia infections and tubal infertility

This is a screening study for chlamydial infections (1153 patients females). In the number of 272 cases (23.59%) chlamydial infection was confirmed by ELISA blood tests. We purpose to determine the risk factors for tubal infertility, because Chlamydia trachomatis (CT) is the most important cause of pelvic inflammatory disease (PID) and permanent tubal damage. High correlations (correlation coefficient-"r") of chlamydial infection with hygienic level (r=0.51), avoided use of condoms (r=0.58) or number of abortions (r=0.65) were noticed. Results with primary prevention through sexual education have been disappointing, so is necessary preventing or limiting sequelae of chlamydial infection, such as PID and tubal infertility.     

Diagnosis of male infertility

A detailed medical history and clinical examination are important steps in the diagnosis of male infertility. Tests include semen analysis according to WHO standards, laboratory tests (mainly determination of follicle-stimulating hormone) and scrotal sonography. Invasive diagnostic procedures, such as testicular biopsy or investigation of seminal pathway obstruction, are generally combined with therapeutic sperm retrieval for cryopreservation or microsurgical refertilization.     

Sulphasalazine-induced reversible male infertility

A male patient suffering from ulcerative colitis, presented with primary infertility due to sulphasalazine therapy. Sulphasalazine was discontinued and the patient was treated with a 5-aminosalicylic acid preparation (Salofalk) in the form of an enema. After 3 months, the semen quality was dramatically improved and a successful pregnancy ensued. The sulphapyridine moiety of sulphasalazine seems to be responsible for male infertility and depressed semen quality. The metabolite 5-aminosalicylic acid is proposed as a suitable alternative to sulphasalazine in cases of male infertility.