Evaluation of nuclear DNA damage in spermatozoa from infertile men with varicocele

OBJECTIVE: To examine levels of sperm DNA damage and oxidative stress (OS) in infertile men with varicocele. DESIGN: Prospective controlled study. SETTING: Male infertility clinic, Glickman Urological Institute, Cleveland Clinic Foundation, Cleveland, Ohio. PATIENT(S): Thirty-one infertility patients and 16 fertile controls. INTERVENTION(S): Sperm DNA fragmentation index (DFI), levels of seminal reactive oxygen species (ROS), and total antioxidant capacity (TAC) were assessed using the sperm chromatin structure assay, chemiluminescence assay, and enhanced chemiluminescence assay, respectively. ROS-TAC score was calculated as a measure of OS. MAIN OUTCOME MEASURE(S): Median (interquartile range) DFI and ROS-TAC scores. RESULT(S): Sixteen of the 31 patients had left varicocele [grade I (n = 3), grade II (n = 10), and grade III(n = 3)], and the remaining 15 had normal genital examination. Patients with varicoceles had significantly higher percent DFI than controls (25%, range: 20%-35%; vs. 15%, range: 10%-22%). Patients with varicoceles had significantly lower ROS-TAC scores (21, range: 9.5-31) than the infertile patients with normal genital examination (34, range: 28-42) or the controls (40.3, range: 38-44). CONCLUSION(S): Infertile men with varicoceles showed significantly increased spermatozoal DNA damage that appears to be related to high levels of OS in semen.     

Improvement in the fertility rate after placement of microsurgical shunts in men with recurrent varicocele

OBJECTIVE: To evaluate the effectiveness of microsurgical shunts for secondary varicocele repair after ligation-like procedures, focusing on long-term functional outcomes. DESIGN: Long-term survey (mean follow-up, 8.5 years) of infertile men after secondary microsurgical reconstructive varicocelectomy. SETTING: University-based medical center. PATIENT(S): Thirty-four infertile men (group A, <30 years of age; and group B, >30 years) with recurrent palpable varicocele after varicocelectomy, according to Ivanissevich (n = 28), or after angiographic vein occlusion (n = 6). Ten patients presented bilateral recurrence. INTERVENTION(S): Microsurgical shunts between spermatic vein and inferior epigastric vein. MAIN OUTCOME MEASURE(S): Sperm count, pregnancy rate, and ultrasound evaluation of varicosity. RESULT(S): Complete disappearance of varicosity was achieved in 97.06% of patients, while in 2.94%, a consistent reduction in size was observed. In patients with severe infertility, a significant postoperative increase in seminal parameters was observed. Pregnancy rates were 43.75% in group A and 22.22% in group B. CONCLUSION(S): Microsurgical drainage in patients with recurrent varicocele after ligation-like procedures was shown to be an effective minimally invasive treatment, with immediate hemodynamic recovery of testicular venous outflow and excellent long-term results in patients with left or bilateral recurrences.     

Oral antioxidant treatment partly improves integrity of human sperm DNA in infertile grade I varicocele patients

Infertile males with varicocele have the highest percentage of sperm cells with damaged DNA, compared to other infertile groups. Antioxidant treatment is known to enhance the integrity of sperm DNA; however, there are no data on the effects in varicocele patients. We thus investigated the potential benefits of antioxidant treatment specifically in grade I varicocele males. Twenty infertile patients with grade I varicocele were given multivitamins (1500 mg L-Carnitine, 60 mg vitamin C, 20 mg coenzyme Q10, 10 mg vitamin E, 200 μg vitamin B9, 1 μg vitamin B12, 10 mg zinc, 50 μg selenium) daily for three months. Semen parameters including total sperm count, concentration, progressive motility, vitality, and morphology were determined before and after treatment. In addition, sperm DNA fragmentation and the amount of highly degraded sperm cells were analyzed by Sperm Chromatin Dispersion. After treatment, patients showed an average relative reduction of 22.1% in sperm DNA fragmentation (p = 0.02) and had 31.3% fewer highly degraded sperm cells (p = 0.07). Total numbers of sperm cells were increased (p = 0.04), but other semen parameters were unaffected. These data suggest that sperm DNA integrity in grade I varicocele patients may be improved by oral antioxidant treatment.     

Clinical data for 185 infertile Iranian men with Y-chromosome microdeletion

Abstract summary

Detection of Y-chromosome microdeletion is useful to obtain reliable genetic information for assisted reproductive techniques, thus avoiding unnecessary treatment and vertical transmission of genetic defects.

Purposes

This research was conducted over a six-year period to analyze clinical data, somatic cytogenetic abnormalities, and types of microdeletions in men with fertility disorders in Iran.

Methods and Patients

A total of 3654 infertile men were included in this study. Semen samples were analyzed according to standard methods. Conventional chromosomal karyotyping was used to analyze chromosome abnormalities. Polymerase chain reaction (PCR) amplification using nine specific sequence-tagged sites (STS) was used to detect AZF microdeletions.

Results

Out of the 3654 patients who were analyzed, AZF region microdeletions were detected in 185 cases (5.06 %). Karyotype analysis was available for 157 men and among them abnormal karyotypes were found in 51 cases (32.48 %). One hundred and forty-seven cases with Yq microdeletions suffered from azoospermia and 38 from severe oligozoospermia. Our data show that the most frequent microdeletions were in the AZFc region, followed by the AZFb + c + d, AZFb + c, AZFb, AZFa, and AZF a + c regions.

Conclusion

The study has confirmed that the detection of microdeletions in the AZF region is significant from a diagnostic viewpoint. It is also useful to obtain reliable genetic information from infertile men to determine the etiology of the deletions, and to avoid unnecessary treatments and vertical transmission of genetic defects.     

Semen profile, testicular volume, and hormonal levels in infertile patients with varicoceles compared with fertile men with and without varicoceles

OBJECTIVE: To assess semen analysis, testicular volume, and hormone levels in fertile and infertile patients with varicoceles and fertile men without varicoceles. DESIGN: Retrospective study. SETTING: Academic medical center. PATIENT(S): Patients were divided into three groups: fertile men with varicoceles (n = 79), infertile men with varicoceles (n = 71), and fertile men without varicoceles (n = 217). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Levels of LH, FSH, and total T and testicular volume in fertile and infertile men with varicoceles and fertile controls without varicoceles. RESULT(S): LH (IU/L) and T (ng/dl) levels were not statistically different across the three groups. FSH levels were significantly higher in infertile men with varicoceles (7.8 +/- 7.6 IU/L) than in the fertile men with varicoceles (3.5 +/- 2.1 IU/L) or in fertile men without varicoceles (3.5 +/- 1.9 IU/L). The right testicle was smaller in infertile patients with varicoceles (18.7 +/- 8.3 cm(3)) than in fertile men with varicoceles (25.2 +/- 13 cm(3)) or in fertile men without varicoceles (24.9 +/- 10.7 cm(3)). In addition, the left testicle was smaller in infertile men with varioceles (17.6 +/- 8.9 cm(3)) than in fertile men with varicoceles (21.6 +/- 7.8 cm(3)) or in fertile men without varicoceles (23.4 +/- 8.3 cm(3)). Sperm concentration was lower in infertile men with varicoceles (33.7 +/- 23.3 x 10(6)/mL) than in fertile men with varicoceles (101.8 +/- 76.6 x 10(6)/mL) or in fertile men without varicoceles (111.8 +/- 74.2 x 10(6)/mL). In addition, sperm motility was lower in infertile men with varicoceles (37.2% +/- 23.9%) than in fertile men with varicoceles (53.9% +/- 17.4%) or fertile men without varicoceles (58.9% +/- 15.8%). CONCLUSION(S): Infertile patients with varicoceles have higher levels of FSH, smaller testes, and lower sperm concentration and motility compared with controls with or without varicoceles. No statistical differences were seen in the variables evaluated among the fertile men with incidental varicoceles detected at physical examination and those without varicoceles.     

男性继发不育患者临床特点分析

目的调查二胎生育男性不育症患者的基本临床特点。方法选取北京协和医院和北京市仁和医院男科门诊就诊的男性不育患者410例,其中一胎不育患者(A组)264例,二胎不育患者(B组)146例,采用门诊问卷收集患者的一般信息和精液分析数据,并采用勃起功能国际问卷5(IIEF-5)调查患者的勃起功能状况。结果在调查的410例男性不育患者中,A组、B组患者的年龄分别是(31.3±5.4)岁和(39.5±4.8)岁(P0.01);合并一种以上慢性疾病(糖尿病、高血压、前列腺疾病)的发生率分别是14.8%(39/264)和24.7%(36/146)(P0.05);每月性交次数分别为(9.7±1.2)次和(6.5±1.4)次(P0.01);勃起功能障碍(ED)的发生率分别为50.8%(134/264)和70.5%(103/146)(P0.01),其中B组不育者的重度ED发生率为10.3%,明显高于A组不育者的1.1%(P0.01);A组的精子浓度[(39.7±10.6)×10~6/m L]高于B组[(34.6±8.5)×10~6/m L](P0.01),但A组的精子总数[(114.3±33.4)×10~6]少于B组[(150.4±41.1)×10~6](P0.01);A组的a级精子活力12.6%±5.5%高于B组的8.5%±3.2%(P0.01),两者在前向运动精子(a+b)及精子总活动(a+b+c)率方面没有统计学差异。结论二胎生育男性不育患者具有年龄大、合并慢性疾病多、性交次数少、易发生E D、精子质量尚可的特点,临床诊疗工作要给予必要的关注和进行相应的调整。     

Increased sperm nuclear DNA damage in normozoospermic infertile men: a prospective study

OBJECTIVE: To evaluate levels of sperm nuclear DNA damage in infertile men with normal and abnormal standard semen parameters. DESIGN: Prospective study. SETTING: Male infertility clinic. PATIENT(S): Ninety-two men seeking infertility treatment and 16 fertile volunteers. INTERVENTION(S): Standard semen analysis was performed according to the World Health Organization guidelines. MAIN OUTCOME MEASURE(S): Sperm DNA damage was assessed by sperm chromatin structure assay and the results expressed as %DFI. RESULT(S): Of the 92 patients, 21 (23%) had normal standard sperm parameters (concentration, motility, and normal sperm forms), while 71 (77%) had an abnormality in one or more of these parameters. The %DFI [median (25th and 75th percentiles)] in infertile men with normal sperm parameters [23 (15, 32)] was significantly higher than fertile donors [15 (11, 20)] (P=.02), but not significantly different from infertile men with abnormal sperm parameters [28 (18, 41)] (P=.27). CONCLUSION(S): The results of this study indicate that a significant increase in SCSA-defined DNA damage can be found in sperm from infertile men with normal standard sperm parameters. Therefore, sperm DNA damage analysis may reveal a hidden abnormality of sperm DNA in infertile men classified as idiopathic based on apparently normal standard sperm parameters.     

Seminal insulin-like growth factor-I may be involved in the pathophysiology of infertility among patients with clinical varicocele

Varicocele, the most common cause of male infertility, is defined as abnormal dilation of the pampiniform plexus. Although different mechanisms have been proposed to explain the pathophysiology of infertility caused by varicocele, it is still open to debate. Previous studies have demonstrated the effect of insulin-like growth factor-I (IGF-I) on semen quality in animals and humans, but there are no studies on the probable role of seminal IGF-I in the pathophysiology of infertility among patients with clinical varicocele. We therefore aimed to examine the seminal IGF-I concentration in 49 patients with varicocele and primary infertility before and after varicocelectomy and compare the results with those of 50 healthy fertile men (in the control group). Mean seminal IGF-I level of patients before varicocelectomy (93.7 ± 67.2 ng/mL) was significantly different (P < 0.001) from that following varicocelectomy (58 ± 35.1 ng/mL) and from that of the controls (57.6 ± 22.1 ng/mL). However, mean seminal IGF-I levels of patients after varicocelectomy and the controls were not significantly different. Seminal IGF-I level was not correlated with grade and side of varicocele, and semen quality. We conclude that locally secreted IGF-I in the semen may be involved in the pathophysiology of infertility in patients with varicocele or semen.     

Genetic analysis of three polymorphic sites of the luteinizing hormone beta-subunit gene in infertile Korean men with nonobstructive azoospermia

OBJECTIVE: To investigate the genetic background of nonobstructive male factor infertility. DESIGN: Clinical and controlled study. PATIENT(S): Ninety-five nonobstructive male infertile patients (75 with azoospermia, 18 with oligoasthenoteratozoospermia, and two with oligozoospermia) and 200 healthy fertile control men. INTERVENTION(S): Patients were investigated for genetic background including karyotype, Yq chromosome deletion, and three polymorphisms of the LH beta-subunit gene (Trp8Arg, Ile15Thr, and Gly102Ser). MAIN OUTCOME MEASURE(S): To determine three polymorphisms of the LH beta-subunit gene. RESULT(S): An abnormal karyotype was found in 11 of the 75 patients with azoospermia and one of the 18 patients with oligoasthenoteratozoospermia. Eleven (12%) had one or more deleted sites at 13 loci on Yq. The Gly102Ser variant of the LH beta-subunit gene was not detected at all. The frequency of double Trp8Arg and Ile15Thr heterozygotes was similar between the fertile (14.5%, n = 200) and infertile (12.6%, n = 95) groups, with the exception of one homozygous mutation (Arg8 and Thr15) from patient with azoospermia. CONCLUSION(S): Three variants of the LH beta-subunit gene (Trp8Arg, Ile15Thr, and Gly102Ser) may not be associated with male factor infertility. We found one homozygous Arg8 and Thr15 mutation in a patient with azoospermia with normal hormone levels (FSH, LH, PRL, T), a normal karyotype, and no Yq microdeletions.     

精索静脉曲张不育患者术后未育者精子穿卵率的远期观察

目的 :对精索静脉曲张不育患者术后未育者的精子穿卵率作远期观察。方法 :1双侧经髂窝或经腹腔镜精索静脉高位结扎术 ;2人精子去透明带地鼠卵穿透试验 (SPA)。结果 :2 9例精索静脉曲张不育患者 ,术后 1 .5～ 2年随访仍未育 ,作 SPA,与术前 SPA穿卵率对比 ,精索静脉曲张 °组 (n=1 7)有 7例改善了穿卵率 ,精索静脉曲张 °组 (n=1 2 )有 2例改善了穿卵率。但两组穿卵率的升高幅度不大。结论 :精索静脉曲张不育患者术后较长时间仍未育者 ,虽部份患者的精子穿卵率已有改善 ,但穿卵率的增加程度不高。术前精索静脉曲张严重的患者 ,术后可能难以提高穿卵率。应建立 SPA对患者术后精子受精能力作评估 ,以及时调整治疗措施。     

Sperm chromosomal aneuploidy and DNA integrity of infertile men with anejaculation

Purpose  

To explore sperm chromosomal aneuploidy, sperm membrane and DNA integrity in infertile patients with anejaculation.