Genetic evaluation of male infertility

Men with severe oligospermia (<5 million sperm/mL ejaculate fluid) or azoospermia should receive genetic testing to clarify etiology of male infertility prior to treatment. Categorization by obstructive azoospermia (OA) or non-obstructive azoospermia (NOA) is critical since genetic testing differs for the former with normal testicular function, testicular volume (~20 mL), and follicle-stimulating hormone (FSH) (1-8 IU/mL) when compared to the latter with small, soft testes and increased FSH. History and physician examination along with laboratory testing (following appropriate genetic counseling) is critical to accurate selection of genetic testing appropriate for azoospermia due to primary testicular failure as compared with congenital hypogonadotropic hypogonadism (HH). Genetic testing options include cystic fibrosis transmembrane conductance regulator (CFTR) testing for men with congenital absence of the vas, while karyotype, Y chromosome microdeletions (YCMD), and other specific genetic tests may be warranted depending on the clinical context of severe oligospermia or NOA. The results of genetic testing guide management options. The most recent techniques for genetic analysis, including sperm microRNA (miRNA) and epigenetics, are forming the foundation for future genetic diagnosis and therapeutic targets in male infertility.     

Severe oligospermia associated with a unique balanced reciprocal translocation t(6;12)(q23;q24.3): male infertility related to t(6;12)

The prevalence of chromosome abnormalities is increased in infertile men, the incidence of a chromosomal factor being estimated to be about 8%. We report two brothers, a 38-year-old man with 10 years' primary infertility and severe oligospermia, but otherwise healthy, and a 35-year-old man with primary infertility and a history of mumps during puberty. Semen and karyotype analysis, and investigation of Y-chromosome microdeletions were performed. An apparently unique reciprocal translocation t(6;12)(q23;q24.3) was found in both infertile brothers. Semen analyses showed severe oligospermia. No Y-chromosome microdeletions were found. These two cases support the relationship between both environmental and chromosomal abnormalities, combined or separated, with male infertility. Investigation of genetic alterations in infertile males has to be performed prior to performing any assisted reproduction technique.     

Genetic causes of male infertility

Summary.  Male infertility has often been ascribed to infections, immunologic factors, chemical insults or malformations. About 10% of infertile males have severe defects in sperm production. Lately, research has focused on possible genetic aetiologies. In this review genetic causes of male infertility are discussed. For pragmatic reasons three groups have been defined. In the first group, disorders of sexual differentiation associated with male infertility are considered. In the second group, male infertility is discussed in a context of some genetic diseases. In the third group, genetic causes for isolated defects of sperm production and function are reported.     

男性不育209例病因分析

本文报告了对２０９例男性不育患者进行遗传学、生殖内分泌、感染性疾病和抗精子免疫等４种导致不育病因研究的结果。并对４种主要病因检测的意义、睾丸不同发育状况与不同类型染色体异常的生殖激素水平变化的特点、解脲支原体感染与抗精子抗体产生的关系以及其它相关问题进行了分析。     

Anabolic steroids and male infertility: a comprehensive review

What’s known on the subject? and What does the study add? The negative impact of AAS abuse on male fertility is well known by urologists. The secondary hypogonadotropic hypogonadism is often highlighted when AAS and fertility are being discussed. On the other hand, the patterns of use, mechanisms of action and direct effects over the testicle are usually overseen. The present study reviews the vast formal and “underground” culture of AAS, as well as their overall implications. Specific considerations about their impact on the male reproductive system are made, with special attention to the recent data on direct damage to the testicle. To our knowledge this kind of overview is absolutely unique, offering a distinguished set of information to the day‐by‐day urologists. For several decades, testosterone and its synthetic derivatives have been used with anabolic and androgenic purposes. Initially, these substances were restricted to professional bodybuilders, becoming gradually more popular among recreational power athletes. Currently, as many as 3 million anabolic‐androgenic steroids (AAS) users have been reported in the United States, and considering its increasing prevalence, it has become an issue of major concern. Infertility is defined as the failure to achieve a successful pregnancy after 12 months or more of regular unprotected intercourse, with male factor being present in up to 50% of all infertile couples. Several conditions may be related to male infertility. Substance abuse, including AAS, is commonly associated to transient or persistent impairment on male reproductive function, through different pathways. Herein, a brief overview on AAS, specially oriented to urologists, is offered. Steroids biochemistry, patterns of use, physiological and clinical issues are enlightened. A further review about fertility outcomes among male AAS abusers is also presented, including the classic reports on transient axial inhibition, and the more recent experimental reports on structural and genetic sperm damage.     

单精子卵胞浆内穿刺术治疗男性不育症的探讨(附23例报告)

目的：探讨单精子卵胞浆内穿刺椁（ＩＣＳＩ）治疗严重粗液异常和梗生无精子症所致不育的疗产。方法;对２３例严重精液异常和梗阻性无精子症患者施行ＩＣＳＩ,妇方行常规超促排卵以获取卵子并选择成熟的终卵细胞,同时采用手淫法、经皮附睾穿刺术（ＰＥＳＡ）和睾丸精子获取术（ＴＥＳＥ）以获得精液、附睾及睾丸精子行ＩＣＳＩ。结果：２３例２３个治疗周期共获卵３３２个,其中３００个成熟卵母细胞进行了ＩＣＳＩ,１９３（６４     

性激素负反馈作用在男性不育诊疗中的应用

下丘脑-垂体-睾丸轴对男性的生殖功能起着关键性作用,下丘脑和垂体共同参与调控睾丸的甾体激素合成与精子发生;复杂的刺激和反馈机制通过神经腺成分来控制激素的合成和分泌。下丘脑和垂体均有大量雄、雌激素的受体,同时受睾酮及其芳香化产物(包括雌激素)的负反馈调节。利用男性生殖内分泌轴系中的负反馈作用,通过给予抗雌激素药物或芳香化酶抑制剂,可减弱睾酮及其芳香化产物的持续负反馈调节作用,增加内源性促性腺激素的分泌,而且还能去除雌激素对生精的副作用,恢复生精或提高精液质量。     

河北省男性不育抽样调查

１９８５年５月～１９９０年７月，在河北省石家庄、唐山、秦皇岛市及１０个地区对３９４７６对育龄夫妇（２０～４０岁）进行了抽样调查，发现不育夫妇有４５３０对，不育率为１１．４７％，其中男性不育患者为１５０２例，占不育症的３３．１５％。结果表明男性不育不是个独立疾病，它是由许多疾病和诸多因素造成的，如生殖器的异常及其炎症、性功能障碍、环境污染、不同的饮食结构都影响着男性的生育功能，其中精索静脉曲张、生殖器官炎症、工业化造成的环境污染更带有普遍性。     

Y染色体基因微缺失在严重少精子症和无精子症中的应用

目的 利用Y染色体基因微缺失的检测来明确少精子症、无精子症患者病因.方法 采用多重聚合酶链反应技术,针对31例严重少精子症和9例无精子症患者与对照组41名已正常生育的男性,进行AZFa、AZFb、AZFc、3个区域共12个序列标签位点(sequence tag site,STS)的微缺失分析.结果 严重少精子症31例中发现Y染色体微缺失6例,无精子症9例中发现Y染色体微缺失3例,而正常对照组41例均未发现Y染色体微缺失.此研究中发现缺失形式有2种,分别是AZFa+AZFb+AZFc区的全缺失和AZFc区的单独缺失.结论 Y染色体微缺失与精子发生障碍导致的不育有一定的联系.     

男性不育的遗传学评估

无精子症或严重少精子症男性(5×10 6/ml)在接受治疗之前应通过遗传学检测确定其不育的真正原因。正确区分梗阻性无精子症(obstructive azoospermia,OA)与非梗阻性无精子症(non-obstructive azoospermia,NOA)至关重要,因为相比于NOA(睾丸体积小、质地柔软、FSH水平升高),OA(正常的睾丸功能、睾丸体积以及FSH水平)的遗传学检测有所不同。在NOA患者人群中,病史回顾、体格检查和实验室检测对于遗传学检测方法的选择是必须的,尤其针对原发性睾丸衰竭或先天性低促性腺激素型性腺功能低下症的NOA患者。遗传学检测包括由于先天性输精管缺如所致OA的囊性纤维化跨膜传导调节因子的检测,和针对严重少精子症或NOA患者的染色体核型分析、Y染色体微缺失等其他特殊检测方法。这些遗传学检测能够帮助判定哪些患者适合药物和/或手术治疗。最新的遗传学分析技术将有助于男性不育的诊断和掌控。     

病毒感染与男性不育关系的研究进展

近年来研究发现病毒感染与不孕不育存在一定的联系,人类免疫缺陷病毒、乙肝病毒等感染不仅损伤生殖系统的功能、影响生育能力,而且也能够通过性接触传播而导致不育,病毒的遗传物质可通过干扰精卵正常受精或影响胚胎的正常着床导致不孕。在男性不育方面,病毒主要通过损伤睾丸功能和影响精子浓度、活力、形态以及DNA完整性使精子质量降低,影响正常精卵结合,进而导致男性生育能力下降甚至不育。本文就相关病毒感染与男性不育的关系做一综述。     

Outcome of gonadotropin therapy for male hypogonadotropic hypogonadism at university affiliated male infertility centers: a 30-year retrospective study

PURPOSE: Hypogonadotropic hypogonadism (HH) is an uncommon cause of male infertility. Even specialized centers see small numbers of patients and have little experience in restoring fertility in these patients. To explore the phenotypic heterogeneity and treatment outcome of HH, we summarized our 30-year experience. MATERIALS AND METHODS: Medical charts of 36 male patients (age range 11 to 42 years) with HH (81% primary, 19% secondary) treated at university affiliated male infertility centers were reviewed. Pubic hair stage, genital stage, testicular volume (TV), sexual function and sperm production were determined before and after human chorionic gonadotropin/human menopausal gonadotropin (hCG/hMG) treatment. Differences were analyzed statistically. RESULTS: The population was stratified according to initial TV into a small testis subset (TV less than 4 ml in 23) and a large testis subset (TV 4 ml or greater in 13). Comparison of these 2 subsets revealed significant differences in the incidence of cryptorchidism (39% vs 8%) and Kallmann's syndrome (22% vs 0%), pubic hair stage (1.3 +/- 0.5 vs 3.5 +/- 1.4), genital stage (1.2 +/- 0.4 vs 3.9 +/- 0.9) and TV (1.6 +/- 0.9 vs 7.5 +/- 3.5 ml). Long-term administration of hCG/hMG for 12 to 240 months (average 56 +/- 11) resulted in sperm production in only 36% of the small testis subjects but in 71% of the large testis subjects. CONCLUSIONS: Initial TV values provide insight into phenotypic variables such as time of onset and severity in patients with primary or secondary HH, and may predict sperm output in response to hCG/hMG therapy.     

Efficacy of Aescuven forte on male infertility with varicocele

Objective:To explore the effectiveness of Aescuven forte in treatment of male infertility with varicocde.Methods:One hundred and forty-three male patients with infertility with vsricocele were randomly divided into medication group,control group and surgery group.Among them,seventy-four patients in medication group took Aescuven forte(0.3g,2/day)for 2-3 months combined with other medicine availing for semen quality.Semen was analyzed and the diameter of vena spermatica interns was measured with ultrasound before and after the treatment.Forty-one patients in control group only took the same medicine availing for semen quality.Twenty-eight patients in surgery group accepted varicocelectomy and took the same medicine availing for semen quality after the operation.Results:After the operation or medication,the improving rates for the sperm density in medication group,con-trol group and surgery group were 53.2%,39.0%,and 67.9% respectively.The significant difference existed be-tween control group and surgery group(P<0.05).The improving rates for the sperm motility in the three groups were 51.6%,46.3%,and 71.4% respectively.The significant difference existed between control group and surgery group(P<0.05).After Aescuven forte treatment,the effective retracting rates for the 108 sides varicocele in 74 patients in medication group reached 43.5%.The effective retracting rates for varicoeele in mild,moderate and se-vere varicocele group defined by the diameter of the vessel were 39.2%,60.7%,and 16.7% respectively.The im-proving rate in moderate varicocele group was much higher than that in the other two group.(P<0.05)Conclusion:Aescuven forte combined with other medicine can improve semen quality in male infertility with vari-cocele.It can retract the vein to some degree in some patients with varicocele,especially for the patients with middle degree varicocele.It could be a therapeutic choice for male infertility with varicocele.     

解脲支原体与男性免疫性不育关系的探讨

本文对１５０例男性不育患者进行了精浆抗精子抗体检测与解脲支原体培养，发现抗精子抗体阳性组解脲支原体检出率为６６．７％，抗精子抗体阴性组解脲支原体检出率为４０．２％，两组之间存在显著性差异（Ｐ＜０．００５）。对抗精子抗体、解脲支原体均为阳性组进行了两种治疗方法的疗效对比，结果表明，使用抗生素组抗体转阴率为７０％，未使用抗生素组抗体转阴率为３６．４％，两组疗效存在显著性差异（Ｐ＜０．０５）。提出解脲支原体可能是导致男性免疫性不育的病因之一。认为积极治疗生殖道感染有助于降低抗体滴度，阻止抗体形成，对免疫性不育的治疗有重要意义。     

不育男性患者前列腺和阴囊的超声检查

目的:评价不育男性患者行前列腺和阴囊Doppler超声检查的临床意义。方法:总结268例不育男性患者前列腺和阴囊的超声资料,并与临床体检进行对比。结果:268例中182前列腺和(或)阴囊异常(67.9%)。其中,前列腺结石14.9%,前列腺囊肿2.2%,附睾囊肿13.1%,睾丸囊肿0.4%,睾丸内微小结石3.4%,睾丸鞘膜积液3.0%,精索静脉曲张24.3%。与触诊比较,精索静脉曲张的的检出率超声是24.3%,触诊是14.5%,差异有统计学意义(P<0.05)。将患者按精液常规分成无精子症、少精子症和精子密度正常等3组,超声异常率依次为80.5%,75.4%和55.6%,各组间差异亦有统计学意义(P<0.05)。结论:超声是诊断不育男性前列腺和(或)阴囊异常的重要手段,与临床触诊相比,其结果更为客观、可信。     

Genetics of hypogonadotropic hypogonadism

Male congenital hypogonadotropic hypogonadism (CHH) is a heterogenous group of genetic disorders that cause impairment in the production or action of gonadotropin releasing hormone (GnRH). These defects result in dysfunction of the hypothalamic-pituitary-gonadal hormone axis, leading to low testosterone levels and impaired fertility. Genetic testing techniques have expanded our knowledge of the underlying mechanisms contributing to CHH including over 30 genes to date implicated in the development of CHH. In some cases, non-reproductive signs or symptoms can give clues as to the putative genetic etiology, but many cases remain undiagnosed with less than 50% identified with a specific gene defect. This leads to many patients labelled as “idiopathic hypogonadotropic hypogonadism”. Medical and family history as well as physical exam and laboratory features can aid in the identification of hypogonadotropic hypogonadism (HH) that is associated with specific medical syndromes or associated with other pituitary hormonal deficiencies. Genetic testing strategies are moving away from the classic practice of testing for only a few of the most commonly affected genes and instead utilizing next generation sequencing techniques that allow testing of numerous potential gene targets simultaneously. Treatment of CHH is dependent on the individual’s desire to preserve fertility and commonly include human chorionic gonadotropin (hCG) and recombinant follicle stimulating hormone (rFSH) to stimulate testosterone production and spermatogenesis. In situations where fertility is not desired, testosterone replacement therapies are widely offered in order to maintain virilization and sexual function.     

男性不育症患者精浆锌与血清生殖激素测定及意义

目的评价精浆锌及血清生殖激素水平测定在不育症诊断及判定睾丸功能损害程度的意义。方法对200例男性不育症患者进行了精浆锌、血清生殖激素(FSH、LH、T、PRL)检测,并结合精液常规检查、睾丸容积测定以及睾丸病理活检进行分析。结果不育症患者精浆锌含量下降、血清生殖激素异常与睾丸间质细胞功能受损、生精上皮不同程度的破坏有明显的关系。结论精浆锌及血清生殖激素的检测,对判定男性不育症患者睾丸损害程度及鉴别睾丸原发性与梗阻性无精子症具有重要的作用。     

Surgical management of male infertility: an update

Male factor infertility is common, affecting 7% of the total population and up to half of couples who are trying to conceive. Various surgical and reconstructive options allow biological paternity depending on the etiology of the male factor issues. This article describes historical treatments and newer approaches, discussing the role for traditional open surgery, microsurgery and robotic surgery, as well as interventional radiologic procedures in the management of male infertility.     

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.