The higher risk for sperm DNA damage in infertile men (original) (raw)
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Increased sperm nuclear DNA damage in normozoospermic infertile men: a prospective study
Fertility and Sterility, 2002
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)] (Pϭ.02), but not significantly different from infertile men with abnormal sperm parameters [28 (18, 41)] (Pϭ.27).
Fertility and Sterility, 2001
To evaluate two different assays of human sperm DNA integrity, DNA denaturation (DD) and DNA fragmentation (DF), and to correlate these with standard semen parameters. Design: Prospective, observational study. Setting: University infertility clinic. Patient(s): Forty consecutive semen samples from 33 nonazoospermic men presenting for infertility evaluation and 7 fertile men presenting for vasectomy. Intervention(s): Assessment of sperm concentration, motility, morphology, DD and DF. Main Outcome Measure(s): Sperm DD and DF in fertile and infertile men.
Journal of Assisted Reproduction and Genetics, 2014
Background Sperm DNA damage is common in infertile men and is associated with poor semen parameters but the impact of an isolated sperm abnormality on sperm DNA damage has not been studied. Objective To evaluate sperm DNA damage in a large cohort of infertile men with isolated sperm defects. Design, setting and participants Retrospective study of 1084 consecutive, non-azoospermic infertile men with an isolated sperm defect: isolated oligozoospermia (iOligo), isolated asthenozoospermia (iAstheno) or isolated teratozoospermia (iTerato). Outcome measurements and statistical analysis We examined and compared clinical parameters, conventional semen parameters and %sperm DNA fragmentation (%SDF, assessed by flow cytometry-based Terminal deoxynucleotidyl transferase-mediated dUTP Nick End-Labeling assay) in the three groups of men. Results and limitations The mean (±SD) %SDF was significantly higher in the iAstheno compared to the iOligo and iTerato groups (25.0±14.0 vs. 19.2±11.6 and 20.7±12.1 %, respectively, P<0.0001). Similarly, the proportion of men with high %SDF (>30 %) was significantly higher in the iAstheno compared to the iOligo and iTerato groups (31 % vs. 18 % and 19 %, respectively, P<0.0001). In the group of 713 men with iAstheno, %SDF was positively correlated with paternal age (r=0.20, P<0.0001) and inversely correlated with %progressive motility (r=−0.18, P<0.0001). In the subset of 218 men with iTerato, %SDF was also positively correlated with paternal age (r=0.15, P=0.018) and inversely correlated with %progressive motility (r=−0.26, P=0.0001). Conclusions In this large cohort of infertile men with isolated sperm abnormalities, we have found that the sperm DNA fragmentation level is highest in the men with sperm motility defects and that 31 % of these men have high levels of sperm DNA fragmentation. The data indicate that poor motility is the sperm parameter abnormality most closely related to sperm DNA damage.
Etiologies of sperm DNA damage and its impact on male infertility
Andrologia, 2020
Infertility is defined as the inability to conceive after 12 months of regular, unprotected intercourse (Sabanegh & Agarwal, 2010). Although 60%-75% of couples conceive within 6 months, and 90% within 12 months (Spira, 1986), approximately 48.5 million couples worldwide are considered infertile within this definition (Agarwal et al., 2019; Sharlip et al., 2002). Male factor infertility affects up to 50% of couple infertility and is solely responsible for 20% of overall infertility (Thonneau et al., 1991). In recent decades, the incidence of male factor infertility has increased (Turner et al., 2020; Zandieh et al., 2018). Semen analysis is considered as the cornerstone of the male fertility evaluation. This analysis provides information into the possible extent and severity of infertility problems, and aids in diagnosis and clinical management. Based on several population studies, the World Health Organization (WHO) provided updated sampling and laboratory guidelines with clinical thresholds to evaluate male reproductive potential through semen analysis (Mayorga-Torres, Camargo, Cadavid, du Plessis, & Cardona Maya, 2017). However, there remain several limitations associated with the conventional semen analysis in the assessment of male infertility (Majzoub, Agarwal, & Esteves, 2019). These limitations have led to the development of advanced sperm function and seminal fluid quality assessments, such as oxidative stress and sperm DNA fragmentation (SDF), that may better guide diagnostics, management and the prediction of male fertility outcomes (Esteves, Sharma, Gosálvez, & Agarwal, 2014). Spermatozoa are highly differentiated cells, which are made up of a head, mid piece and tail. The head of the spermatozoa contains the haploid genome that is transmitted into the oocyte after successful fertilization. The integrity and composition of the sperm DNA is different from that of somatic cells and critical for its fusion with the maternal genome (Conwell, Vilfan, & Hud, 2003). Adequate sperm DNA integrity is critical for successful fertilization, embryo development, implantation and establishment of pregnancy as it contributes towards 50% of the embryonic genome (Baskaran et al., 2019; Braude, Bolton, & Moore, 1988). Sperm DNA integrity is therefore considered as an important marker of fertility potential of spermatozoa (Cho & Agarwal, 2018).
Biologic variability of sperm DNA denaturation in infertile men
Urology, 2001
Objectives. To examine sperm DNA denaturation (DD) in fertile and infertile men and assess the variability of conventional semen parameters and sperm DD in repeated semen samples from infertile men. Methods. Twenty-one consecutive nonazoospermic, infertile men each submitted two semen samples, 2 to 6 weeks apart. We examined semen samples from consecutive fertile men (n ϭ 10) presenting for vasectomy as controls. Standard semen parameters (World Health Organization criteria) and sperm chromatin structure (evaluated by flow cytometry analysis of acridine orange-treated spermatozoa and expressed as the percentage of spermatozoa with denatured DNA) were monitored. Results. Fertile men had a significantly higher sperm concentration and percentage of sperm motility and a significantly lower percentage of sperm with DD than did infertile men (36 Ϯ 5.2 ϫ 10 6 /mL versus 12.5 Ϯ 2.2 ϫ 10 6 /mL, 60.0% Ϯ 5.2% versus 30.1% Ϯ 4.1%, and 8.9% Ϯ 1.9% versus 20.3% Ϯ 2.5%, respectively, P Ͻ0.05). The sperm concentration, sperm motility, and percentage of spermatozoa with DD were not significantly different between the first and second semen samples from the infertile men. Sperm DD showed the lowest average within-subject coefficient of variation (SD/mean), followed by motility and concentration (coefficient of variation 21%, 24%, and 35%, respectively). Conclusions. Our data demonstrate that infertile men have significantly higher sperm DD compared with fertile men and that sperm DD exhibits a low coefficient of variation (ϳ20%) on repeated assessment. These data suggest that sperm DD has a relatively low degree of biologic variability. UROLOGY 58: 258-261, 2001. © 2001,
Sperm DNA fragmentation: threshold value in male fertility
Human Reproduction, 2005
BACKGROUND: The extent of sperm DNA fragmentation, which can be measured by the TUNEL assay, is one of the determinants of male fertility. However, the clinical application of this test to in-vivo situations is difficult owing to the absence of a statistically validated threshold value. METHODS: The aim of this study was to compare the results of TUNEL assay applied to semen samples from men of proven fertility (n = 47) and patients from an infertile population (n = 66), in order to establish a discriminating threshold value. RESULTS: Infertile patients had a higher mean level of DNA fragmentation than men of proven fertility (40.9 ± 14.3% versus 13.1 ± 7.3%, respectively; P < 0.001). The area under the receiver operating characteristics curve was 0.93 for 20% sperm DNA fragmentation. The calculated threshold value for TUNEL assay to distinguish between fertile controls and infertile men was 20%. At this threshold, specificity was 89.4 [95% confidence interval (CI) 83.7-95.1] and sensitivity was 96.9% (95% CI 93.8-100). The positive and negative predictive values of the 20% sperm DNA fragmentation threshold were high: 92.8% (95% CI 87.9-97.5) and 95.5% (95% CI 91.6-99.3), respectively. CONCLUSION: This study demonstrates that sperm DNA fragmentation, as measured by TUNEL assay, is a highly valuable indicator of male fertility.