Varicocele sclerotherapy improves serum inhibin B levels and seminal parameters

The usefulness of treating varicocele in order to improve fertility is still a matter of debate. The aim of this study was to evaluate variations in seminal parameters and inhibin B concentrations in a group of males affected by varicocele and treated by percutaneous retrograde sclerotherapy in comparison with a group of patients who did not undergo varicocele treatment. Thirty-eight patients with left varicocele underwent spermatic vein phlebography and percutaneous retrograde sclerotherapy with hydroxy-polyaethoxy-dodecanol. Serum inhibin B, follicle-stimulating hormone (FSH), testosterone levels and seminal parameters (sperm concentration, motility and morphology) were performed before and 6 months after sclerotherapy. Forty patients with left varicocele who did not undergo sclerotherapy were studied as controls. A significant increase (p < 0.01) in serum inhibin B levels and a significant decrease (p < 0.05) in FSH levels were observed 6 months after treatment. Semen analysis showed a significant improvement in sperm concentration (p < 0.05) and progressive motility (p < 0.01) after treatment. In control group no significant variations in hormonal and seminal parameters were observed 6 months after the basal examination. Six months after the basal evaluation, inhibin B levels were significantly higher in treated subjects than in controls (p < 0.05) whereas FSH levels were significantly lower (p < 0.05). Sperm concentration and progressive motility were significantly increased (p < 0.05 and p < 0.001, respectively) in treated subjects in comparison with controls. In conclusion, varicocele sclerotherapy improves inhibin B levels and seminal parameters, confirming the positive effect of this treatment on spermatogenesis and Sertoli cell function.     

Intracytoplasmic sperm injection as a complement to gonadotrophin treatment in infertile men with hypogonadotrophic hypogonadism

In this study we sought to determine whether intracytoplasmic sperm injection (ICSI) could improve the efficacy of treatment with gonadotrophins in gonadotrophin-deficient men in terms of pregnancy. A series of six adult men (aged 26-47 years) with hypogonadotrophic hypogonadism (HH) is reported: four men with prepubertal isolated idiopathic HH (IIHH) and two adult-onset HH, as part of hypopituitarism secondary to surgical treatment of a pituitary tumour. All were azoospermic. To restore spermatogenesis, all received hormonal treatment with intramuscular human menopausal gonadotrophins (HMG) and human chorionic gonadotrophin (HCG) for 2 to 23 months. High basal serum inhibin B was predictive of rapid and complete recovery of spermatogenesis. In the two adult-onset HH, a natural pregnancy was achieved within 3 months. The four men with IIHH underwent ICSI because of poor sperm quality. ICSI using fresh or frozen-thawed ejaculated spermatozoa was performed after 6-23 months of gonadotrophin treatment. ICSI provided good clinical results in terms of fertilization and embryo quality, and resulted in three pregnancies that ended in three term deliveries. In men with oligozoospermia related to prepubertal IIHH, ICSI shortens the hormonal treatment and enhances the chances of pregnancy.     

Obesity leads to higher risk of sperm DNA damage in infertile patients

There has been a growing interest over the past few years in the impact of male nutrition on fertility. Infertility has been linked to male overweight or obesity, and conventional semen parameter values seem to be altered in case of high body mass index （BMI）. A few studies assessing the impact of BMI on sperm DNA integrity have been published, but they did not lead to a strong consensus. Our objective was to explore further the relationship between sperm DNA integrity and BMI, through a 3-year multicentre study. Three hundred and thirty male partners in subfertile couples were included. Using the terminal uridine nick-end labelling （TUNEL） assay, we observed an increased rate of sDerm DNA damage in obese men （odds ratio （95% confidence interval）： 2.5 （1.2-5.1））.     

Sperm aneuploidy in infertile male patients: a systematic review of the literature

Males with abnormal karyotypes and subgroups of fertile and infertile males with normal karyotypes may be at risk of producing unbalanced or aneuploid spermatozoa. Biological, clinical, environmental and other factors may also cause additional sperm aneuploidy. However, increased risk of sperm aneuploidy is directly related to chromosomally abnormal embryo production and hence to poor reproductive potential. This systemic literature review focuses on the identification of these males because this is an essential step in the context of assisted reproduction. This research may allow for a more personalised and, hence, more accurate estimation of the risk involved in each case, which in turn will aid genetic counselling for affected couples and help with informed decision‐making.     

Low inhibin B levels alone are not a reliable marker of dysfunctional spermatogenesis in childhood cancer survivors

Hormone and semen analyses were carried out to examine the diagnostic value of hormones and hormone combinations as markers of spermatogenesis in male patients who had received oncological treatment in childhood. Hormone analyses from 73 participants and spermiograms from 42 participants were evaluated. Spearman's correlation coefficients and measures of diagnostic accuracy were calculated for the hormone and semen analysis values. Inhibin B levels of <80 ml/ml, follicle-stimulating hormone (FSH) levels of >10 IU l(-1) and a combination of the two parameters showed positive predictive values for azoospermia of 0.423, 0.6154 and 0.6667 respectively. While 32% of the 73 participants showed a combination of abnormal inhibin B and FSH values, which strongly indicates impaired spermatogenesis, 31% of the 42 spermiogram results revealed azoospermia. The hormone and semen analyses showed that approximately one-third of the participants had fertility impairment. Inhibin B alone thus does not reflect spermatogenesis as well as inhibin B in combination with FSH in patients who have undergone cancer treatment in childhood. Both parameters should therefore be evaluated in paediatric cancer follow-up programmes to allow better identification of treatment regimens that cause persistent azoospermia in male childhood cancer survivors.     

Leptin and reproductive dysfunction in obese men

Infertility is somewhat more prevalent in men who are obese. They are also reported to have low sperm concentration, higher fraction of spermatozoa that look morphologically abnormal, higher DNA fragmentation index and evidence of oxidative stress. The precise cause for this remains uncertain. Leptin levels in serum and percentage body fat correlate positively, and obese men therefore usually have elevated serum leptin levels. Although leptin is important for normal reproductive function, but when present in excess, leptin could seriously affect reproductive function in men. Reports on the findings of sperm parameters in obese men, particularly those who are subfertile or infertile, seem to be similar to those reported from studies on normal-weight rats treated with leptin. Collectively, the observations reported in human and experimental animal studies point to leptin as a possible link between infertility and obesity. Herein, we review some findings on sperm function in obese subfertile or infertile men and those from animal studies following leptin treatment, and discuss the possible link between leptin and reproductive dysfunction in obese men. The large amounts of leptin secreted by the adipose tissue and its higher circulating levels could indeed be responsible for the higher prevalence of infertility in obese men.     

男性不育患者精子形态学分析与生殖激素关系的研究

目的:研究男性不育患者精子形态与生殖激素的关系,探讨畸形精子症的发病机制。方法:研究对象为90例男性不育患者,年龄25～40岁,利用Prader睾丸计评估患者睾丸容积,根据世界卫生标准进行精液常规分析,利用化学发光法测定血清生殖激素和性激素结合球蛋白(SHBG)浓度,计算得出游离睾酮和生物活性睾酮的浓度。结果:90例男性不育患者精子浓度均在正常范围,根据精子形态分析结果分为3个研究组,即组1(正常形态精子<4%)、组2(正常形态精子≥4%且<10%)和组3(正常形态精子≥10%),每组30例。3组之间年龄没有统计学差异(P>0.05);左侧睾丸容积分别为(14.27±3.65)ml,(16.90±3.57)ml和(14.57±3.57)ml,P组1,2=0.006,P组1,3=0.741和P组2,3=0.014;右侧睾丸容积分别为(14.60±3.70)ml,(16.60±3.35)ml和(14.67±3.54)ml,P=0.05;血清泌乳素(PRL)、卵泡刺激素(FSH)、黄体生成素(LH)、雌二醇(E2)、总睾酮(TT)和SH-BG在3组之间均没有统计学差异(P>0.05);血清游离睾酮(FT)水平分别为(0.25±0.07)nmol/L,(0.29±0.07)nmol/L和(0.31±0.13)nmol/L,P组1,2=0.086,P组1,3=0.010和P组2,3=0.364;生物活性睾酮(Bio-T)水平分别为(5.81±1.58)nmol/L,(6.78±1.55)nmol/L和(7.29±3.02)nmol/L,P组1,2=0.086,P组1,3=0.010和P组2,3=0.364。另外,正常形态精子百分率与血清FT、Bio-T水平之间均存在正相关(P<0.05)。结论:男性不育患者血清FT和Bio-T水平越高,则正常形态精子百分率越高,提示FT和Bio-T可能参与畸形精子症发病过程。     

Association of seminal angiotensinogen with sperm motility and morphology in male infertility

Many researchers have shown that renin–angiotensin system (RAS) is involved in various important aspects of male reproduction. In this study, we assessed whether abnormal levels of seminal angiotensinogen (AGT) may be associated with semen parameters in infertile males. A total of 115 male patients were recruited, and semen parameters, seminal AGT and the electrolytes including K⁺, Na⁺, Cl^?, P and Ca were evaluated. According to the World Health Organization (WHO) 2010 criteria, the patients were divided into two groups: G1 group with normal semen parameters (n = 42) and G2 group with subnormal semen parameters (n = 73). The level of seminal AGT was significantly higher in G2 group compared with G1 group. Moreover, the level of AGT was negatively correlated with the percentage of total motility (r = ?.322, p = .000), progressive motility (PR) (r = ?.339, p = .000) and morphologically normal forms (r = ?.263, p = .004). This study suggests that elevated seminal AGT level is associated with increased risk of asthenospermia and teratozoospermia.     

Low total normal motile count values are associated with increased sperm disomy and diploidy rates in infertile patients

This study was undertaken to evaluate the possibility of identifying men at increased risk of sperm aneuploidy and diploidy on the bases of specific cut-off values of the total normal motile count (TNMC). Twenty-seven consecutive, unselected male patients referred to our Unit were studied: 11 patients with normal sperm parameters (group A) suffering from unexplained infertility and 16 infertile patients with abnormal sperm parameters (group B). Disomy rates for chromosomes 1, 4, 8, 12, 18, X and Y were ascertained for each patient by means of triple and double fluorescence in situ hybridization (FISH) experiments. Both univariate and multivariate statistical analyses by principal component analysis (PCA) were performed for comparisons between sperm aneuploidy rates and semen quality (TNMC). TNMC scores in the two groups were significantly different (23.5 x 10(6) and 1.52 x 10(6), in groups A and B, respectively, p = 0.00002). In general, higher sperm disomy rates were noted for all chromosomes in group B compared with group A. Statistical significance was observed for disomy 1, total disomy rate (3.36% vs. 1.38%), and diploidy (0.49% vs. 0.19%) (p < 0.01). For disomy 4 and 8, differences resulted close to significance. PCA clearly showed how independent variables were inter-related. Infertile men with TNMC < 2 x 10(6) (male factor) were found to be at increased risk for sperm aneuploidy and diploidy. Multivariate analysis by PCA resulted as a useful method to visualize the information of the data sets on a bi-dimensional plot considering all the patients and all the variables at the same time.     

不育男性精浆抗心磷脂抗体的检测与意义

应用间接ＥＬＩＳＡ法检测男性不育病人精浆的抗心磷脂抗体（ＡＣＡ），并对其与精子密度、精浆抗精子抗体及血清ＡＣＡ的关系进行了研究。结果表明，不孕、流产组精浆ＡＣＡ总检出率分别为２０．０％和１２．５％，前者较对照组显著增高（Ｐ＜０．０５），ＡＣＡ阳性率有随精子数的减少而逐渐上升趋势，但无统计学意义。精浆中ＡＣＡ与ＡｓＡｂ及与血清ＡＣＡ无关联性。     

Effect of psychological stress on fertility hormones and seminal quality in male partners of infertile couples

The present study evaluated the effect of psychological stress on male fertility hormones and seminal quality in male partner of infertile couples. Seventy male partners of infertile couples were evaluated for level of psychological stress using Hospital Anxiety and Depression Score (HADS) questionnaire, serum total testosterone, luteinising hormone (LH) and follicle‐stimulating hormone (FSH) by electrochemiluminescence assay and serum GnRH by ELISA. Seminal analysis was performed as per WHO guideline. Nineteen (27%) of them had HADS anxiety and depression score ≥8 (abnormal HADS score). The persons having abnormal HADS had lower serum total testosterone, higher serum FSH and LH than those of persons having normal HADS. Serum total testosterone correlated negatively with HADS, but LH and FSH correlated positively. There was no change in GnRH with the change in stress or testosterone levels. Sperm count, motility and morphologically normal spermatozoa were lower in persons having abnormal HADS. Sperm count correlated positively with total testosterone and negatively with FSH and LH. Abnormal sperm motility and morphology were related to lower testosterone and higher LH and FSH levels. Psychological stress primarily lowers serum total testosterone level with secondary rise in serum LH and FSH levels altering seminal quality. Stress management is warranted for male infertility cases.     

Leptin concentrations in semen are correlated with serum leptin and elevated in hypergonadotrophic hypogonadism

Leptin seems to play a role in both food intake and energy balance as well as in the regulation of reproductive features. In order to investigate the regulation of testicular functions by leptin we analysed leptin concentrations in the semen of men with different andrological diseases. It was demonstrated that semen leptin concentrations were inversely correlated with serum testosterone levels and directly with serum leptin concentrations. Furthermore, semen leptin concentrations display only a fraction of serum leptin levels. Semen leptin levels of patients with azoospermia due to hypergonadotrophic hypogonadism, associated with increased follicle-stimulating hormone levels and of high-grade oligozoospermia, were significantly elevated (1.19 +/- 0.46 and 1.09 +/- 0.54 microg l(-1), respectively), while semen levels of leptin in patients with obstructive azoospermia (0.54 +/- 0.41 microg l(-1)) and low-grade oligozoospermia (0.54 +/- 0.34 microg ml(-1)) were comparable with those of normozoospermic men (0.21 +/- 0.21 microg l(-1)). Our data suggest that dysfunction of testicular epithelia as found in hypergonadotrophic hypogonadism and high-grade oligozoospermia with decreased testosterone levels causes elevated spermal leptin concentrations. However, the correlation of semen with serum leptin concentrations indicates that leptin is not actively transported but rather leaks through the blood-testis barrier.     

Seminal parameters of chronic male genital inflammation are associated with disturbed sperm DNA integrity

Definition of chronic male genital tract inflammation and its impact on male infertility is still a matter of debate. In particular, DNA integrity has been reported to be disturbed in subfertile men. Thus, the aim of this study was to investigate an association of DNA integrity to altered standard semen parameters as well as inflammatory parameters such as peroxidase‐positive cells, macrophages and seminal interleukin‐6 concentration. Macrophages were detected by CD18/HLA‐Dr staining, and DNA integrity was analysed by acridine orange staining using flow cytometry. Interleukin‐6 was detected by ELISA. Normal DNA integrity showed a significant correlation to sperm number and progressive motility. Moreover, a significant inverse correlation of DNA integrity to Interleukin‐6 and macrophages could be demonstrated. Further on, seminal interleukin‐6 also significantly correlated to macrophages. No association has been observed between the number of peroxidase‐positive cells and normal DNA integrity. As disturbed DNA integrity has been reported to negatively influence spermatozoon–egg interaction and even fertilisation rates following ICSI, and as early miscarriages have been associated with sperm DNA damage, it should be screened very carefully for male genital tract inflammations in couples undergoing infertility treatment. Measuring Interleukin‐6 seems superior to assessment of the number of leucocytes alone and additional assessment of DNA integrity into the diagnostic work‐up should be considered.     

Oxidative stress status and sperm DNA fragmentation in fertile and infertile men

Evidence suggests that disturbing the balance between reactive oxygen species levels and antioxidant contents in seminal plasma leads to oxidative stress resulting in male infertility. This study was carried out to identifying clinical significance of seminal oxidative stress and sperm DNA fragmentation in treatment strategies of male infertility in southwest Iran. Sperm parameters, lipid peroxidation and activity of antioxidant enzymes were assessed in fertile (n = 105) and infertile (n = 112) men. Malondialdehyde (MDA) levels in seminal plasma were found to be higher significantly (p < .001) in patients. Superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities in seminal plasma were significantly (p < .001) lower in infertile men. Significant negative correlations were observed between MDA levels and sperm motility and normal morphology. Spermatozoa with fragmented DNA were higher (p < .001) in infertile men and significantly correlated with MDA levels and SOD and GPx activities. MDA of 4.2 nmol/ml, SOD of 4.89 U/ml and GPx of 329.6 mU/ml were optimum cut‐off limits to discriminate infertile patients from fertile men. The results show the leading role of oxidative stress in aetiology of male infertility in southwest Iran and indicate that evaluation of seminal antioxidant status and DNA integrity can be helpful in men attending infertility clinics during fertility assessment.     

养精胶囊联合锌硒宝对不育患者精子DNA完整性的影响

目的探讨应用养精胶囊联合锌硒宝治疗男性不育对患者精子DNA完整性的影响。方法选择60例合并精子DNA完整性异常[DNA片段化指数(DFI)>10％]的不育患者,随机分为治疗组30例与对照组30例,治疗组口服养精胶囊和锌硒宝,对照组服用维生素E,治疗3个月。分别通过精子染色质结构分析(SCSA)和计算机辅助精液分析(CASA)检测DFI和精液常规参数,并分析治疗前后2组患者各参数的变化。结果治疗前2组精子密度、活力、正常形态百分率和DFI各项参数差异无显著性(P>0．05)。治疗前60例不育患者DFI与精子活力呈显著负相关(r=-0．58,P<0．01),而与精子密度和精子正常形态百分率无显著相关性(P>0．05)。治疗3个月后,治疗组的精子密度、活力、正常形态百分率与治疗前相比差异均有显著性(P<0．05),治疗组的DFI值[(9．4±7．2)％]与治疗前[(22．2±10．3)％]相比显著下降(P<0．01);对照组上述参数与治疗前相比差异均无显著性(P>0．05)。结论养精胶囊联合锌硒宝可显著降低不育患者的精子DFI值,提示应用养精胶囊和锌硒宝治疗男性不育可显著改善患者的精子DNA完整性。     

Relationship between sperm telomere length and sperm quality in infertile men

Telomeres, noncoding and repetitive DNA sequences play a significant function in chromatin integrity. Telomere length is age-dependent in somatic cells, while it increases in sperm cell with age. Therefore, we aimed to assess sperm chromatin, leucocyte and sperm telomere length (LTL, STL) in spermatozoon of 38 infertile and 19 fertile men aged between 20 and 50 years. Protamine deficiency (chromomycin A3 test), DNA fragmentation (TUNEL assay), lipid peroxidation (Bodipy probe) and telomere length (quantitative real-time PCR) were assessed. A significant decrease in mean of sperm concentration and motility and a significant increase in means of sperm abnormal morphology, DNA fragmentation, lipid peroxidation and protamine deficiency were observed in infertile compared with fertile men. In addition, the mean of LTL and STL were significantly shorter in infertile men compared with fertile individuals. We observed significant associations between telomere length with sperm concentration, DNA fragmentation and lipid peroxidation. We hypothesised that increased oxidative stress in spermatozoa of infertile men can result in abnormal packaging of chromatin, damage of DNA and shorter sperm telomere length. Together, these anomalies may account for fertility failure in these individuals.     

Primary male infertility in Kuwait: a cytogenetic and molecular study of 289 infertile Kuwaiti patients

Infertility is one of the major public health problems, affecting 15% of couples who attempt pregnancy; in 50% of these, the male partner is responsible. Chromosomal abnormalities and Y microdeletions in the azoospermia factor (AZF) region are known to be associated with spermatogenetic failure. In the present study, 289 patients with primary male infertility because of spermatogenetic failure were studied in order to highlight the molecular background of male infertility in Kuwait, and to avoid the possibility of transmission of any microdeletions/chromosomal aberrations to offspring via intracytoplasmic sperm injection (ICSI). Of the 289 infertile men, 23 patients (8%) had chromosomal aberration in the form of Klinefelter syndrome/variant (16/23; 69.6%), XYY syndrome (3/23; 13%), XX male syndrome (2/23; 8.7%), 45,X/46X, i(Yp)(1/23; 4.4%) and 45,XY, t(9;22) (1/23;4.4%). Y-chromosome microdeletion in the AZFb and AZFc regions were detected in 7/266 cases (2.6%). Testicular biopsy was carried out in 31 azoospermic patients, of whom five men had Sertoli-cell only syndrome, while 26 patients had spermatogenic arrest. In conclusion, this study showed that the frequency of both chromosomal anomalies and Y microdeletions were found in 10.4% of the infertile men. The potential risk of transmitting these genetic disorders to offspring provides a rationale for screening infertile men prior to ICSI.     

Relationship between seminal ascorbic acid and sperm DNA integrity in infertile men

Ascorbic acid has recently been reported to protect sperm DNA from the damage induced by exogenous oxidative stress in vitro. But, there is no report on seminal ascorbic acid and sperm DNA fragmentation in infertile men. In this study, we asked whether sperm DNA damage correlates with seminal ascorbic acid levels. Sperm DNA fragmentation index (DFI) was analysed in 75 men by flow cytometry after acridine orange staining. We also measured the levels of seminal plasma ascorbic acid and total antioxidant capacity. Abnormal sperm DNA integrity (DFI >or= 30%) was observed in 12% of the patients with normal semen parameters and in 52% of the patients with abnormal semen parameters. There were significant correlations between the level of DFI and conventional semen parameters including sperm count, motility and morphology (r = -0.29, -0.55 and -0.53 respectively; p < 0.05). Seminal ascorbic acid level was significantly lower in the patients with leucospermia than the patient with normal semen parameters. Interestingly, a significantly greater percentage of men with abnormal DFI were observed in the patients with low levels of seminal ascorbic acid compared with those with normal or high levels of ascorbic acid (59% vs. 33%, p < 0.05). Men with insufficient seminal ascorbic acid frequently have sperm DNA damage.     

Semen characteristics and inflammatory mediators in infertile men with different clinical diagnoses

This study was aimed at investigating whether semen characteristics in different clinical diagnoses of infertility are associated with PMN elastase, IL-6, IL-8, IL-1beta and TNFalpha levels detected in seminal plasma. Sixty-eight patients were divided into groups according to their clinical diagnosis: idiopathic infertility (group I), varicocele with infections (group II), varicocele (group III), infections (group IV), controls (group V). Physical examination and scrotal Eco-color Doppler was used to detect the varicocele. Patients with positive bacteriological semen analysis were considered as having an infection of the male reproductive tract. Samples were examined by light microscopy and transmission electron microscopy (TEM). TEM data were quantified with a mathematical formula furnishing a fertility index and the percentage of sperm apoptosis, immaturity and necrosis. PMN elastase/alpha1-PI complex levels were determined by ELISA and IL-6, IL-8, IL-1beta, TNFalpha by Bio-Plex Cytokine assay. Sperm concentration (I-II: p < 0.005; III-IV: p < 0.0001), motility (I-IV: p < 0.0001) and the fertility index (I: p < 0.005; II-IV: p < 0.0001) were significantly lower in the groups vs. controls, whereas sperm pathologies, except for apoptosis, were significantly higher in group I and apoptosis and necrosis were higher in group III. An increase in immaturity (p < 0.005) with a decrease in necrosis (p < 0.005) were observed in group III vs. group IV. Significantly higher levels of inflammatory mediators were detected in groups III and IV vs. controls. Despite a broad relationship among different inflammatory mediators, no correlation was found among them and the semen parameters, including indices from TEM analysis. In conclusion, patients with idiopathic infertility showed altered semen quality and normal levels of inflammatory mediators. Genitourinary infection and varicocele induced an inflammatory effect which could play a detrimental role in spermatogenesis, revealed by a decrease in sperm motility and the fertility index, concomitant with an increase in immaturity mainly in varicocele and necrosis in infection.