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BACKGROUND: Infertility is caused by heterogeneous risks, but most of them are unexplained. The sperm DNA Fragmentation Index (DFI) was increasingly acknowledged as a parameter for the evaluation of male infertility. This study aimed to investigate the association between sperm DFI and laboratory and clinical outcomes in a population with unexplained infertility. METHODS: The clinical data of an infertile population was collected for the selection of reproductive patients with unexplained infertility. The authors classified the patients with normal sperm parameters in a control group (DFI < 25%) and an observation group (DFI ≥ 25%) and compared the difference in basal characteristics, laboratory, and clinical outcomes between the two groups. The authors conducted a correlation analysis to examine the relationship between DFI and the number of D3 good-quality embryos, as well as the clinical pregnancy rate and live birth rate. A total of 176 cases were enrolled in the retrospective study. RESULTS: The observation group (n = 88) showed advanced male age, lower sperm concentration, progressive motility, and morphology assessment than the control group. In addition, lower No. of D3 good-quality embryos, clinical pregnancy rate, and the live birth rate were shown in the observation group. A negative correlation between the DFI and No. of D3 good-quality embryos (rs = -0.347, p < 0.001) or live birth rate (rs = -0.185, p = 0.028) was shown. CONCLUSIONS: Sperm DFI was a good indicator for the prediction of D3 good-quality embryos in unexplained infertility couples, but it did not provide sufficient information regarding clinical pregnancy outcome but live pregnancy outcome.

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BACKGROUND: Sperm deoxyribonucleic acid (DNA) fragmentation is commonly encountered in spermatozoa, and the oocyte assumes responsibility for repairing sperm DNA fragmentation during the oocyte-embryo transition. OBJECTIVES: This study aimed to investigate whether the effect of sperm DNA fragmentation on intracytoplasmic sperm injection outcomes depends on the incidence of oocyte dimorphisms. MATERIALS AND METHODS: For the present cohort, 2942 fertilized oocytes from 525 patients submitted to intracytoplasmic sperm injection cycles were assessed. The present study was conducted in a private in vitro fertilization center affiliated to a university from June 2016 to July 2019. Semen samples were divided into the following two groups depending on the sperm DNA fragmentation index: a low fragmentation index group (<30% sperm DNA fragmentation, n = 1468) and a high fragmentation index group (≥30% sperm DNA fragmentation, n = 486). In addition, mature oocytes were examined before sperm injection, and intracytoplasmic and extracytoplasmic defects were recorded. The effect of the sperm DNA fragmentation index on laboratory and clinical intracytoplasmic sperm injection outcomes (depending on the presence of oocyte defects) was evaluated. RESULTS: Significant increases in the rates of fertilization, high-quality embryo, implantation, and pregnancy were noted for cycles with <30% sperm DNA fragmentation than cycles with ≥30% sperm DNA fragmentation (regardless of the presence of oocyte dimorphisms). The presence of dimorphisms significantly impacted laboratory and clinical outcomes. The lowest fertilization and high-quality embryo rates were observed when a high sperm DNA fragmentation index was associated with the presence of dark cytoplasm, vacuoles, resistant membrane, and non-resistant membrane. The lowest implantation and pregnancy rates were observed when a high sperm DNA fragmentation index was associated with the presence of vacuoles, defective perivitelline space, and fragmented polar body. The effect of sperm DNA fragmentation on miscarriage rates was significantly influenced by the presence of centrally located cytoplasmic granulation, a defective perivitelline space and non-resistant membrane. CONCLUSION: A high sperm DNA fragmentation index increases the likelihood of miscarriage in intracytoplasmic sperm injection cycles, an effect that may potentially be magnified by the presence of oocyte dysmorphisms.

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Several studies show reductions in some seminal parameters in aged men and describe them as a consequence of many age-dependent changes in male organisms. This study aims to evaluate the impact of age on seminal parameters, particularly the DNA fragmentation index (DFI), and outcomes after in vitro fertilization (IVF) cycles. This is a retrospective study that includes 367 patients who underwent sperm chromatin structure assay testing between 2016 and 2021. The participants were split into three groups according to age: < 35 years (younger group, n = 63), 35-45 years (intermediate group, n = 227), and ≥ 45 years (older group, n = 77). The mean DFI (%) was compared. Among all patients, 255 received IVF cycles after DFI evaluation. For these patients, the sperm concentration, motility, and volume, as well as the fertilization rate, mean oocyte age, and good-quality blastocyst formation rate, were analyzed. One-way ANOVA was applied. The older group showed a significantly higher sperm than did the younger group (28.6% vs. 20.8% p = 0.0135). Despite not presenting a significant difference, the DFI level tends to be inversely related to good-quality blastocyst formation since the oocyte age was similar between the groups (32.0 v.s 33.6 vs. 32.3 years, respectively, p = 0.1183). Among aged men, the sperm DFI level is increased but other seminal parameters are not modified. Considering that men with a high sperm DFI can present some degree of infertility due to high sperm chromatin damage, male age should also be considered a limiting factor of IVF.

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Intracytoplasmic sperm injection (ICSI) using surgically retrieved spermatozoa outside the classic context of azoospermia has been increasingly used to overcome infertility. The primary indications include high levels of sperm DNA damage in ejaculated spermatozoa and severe oligozoospermia or cryptozoospermia, particularly in couples with ICSI failure for no apparent reason. Current evidence suggests that surgically retrieved spermatozoa for ICSI in the above context improves  outcomes, mainly concerning pregnancy and miscarriage rates. The reasons are not fully understood but may be related to the lower levels of DNA damage in spermatozoa retrieved from the testis compared with ejaculated counterparts. These findings are consistent with the notion that excessive sperm DNA damage  can be a limiting factor responsible for the failure to conceive. Using testicular in preference of low-quality ejaculated spermatozoa bypasses post-testicular sperm DNA damage caused primarily by oxidative stress, thus increasing the likelihood of oocyte fertilization by genomically intact spermatozoa. Despite the overall favorable results, data remain limited, and mainly concern males with confirmed sperm DNA damage in the ejaculate. Additionally, information regarding the health of ICSI offspring resulting from the use of surgically retrieved spermatoa of non-azoospermic males is still lacking. Efforts should be made to improve the male partner's reproductive health for safer ICSI utilization. A comprehensive andrological evaluation aiming to identify and treat the underlying male infertility factor contributing to sperm DNA damage is essential for achieving this goal.

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OBJECTIVE: Despite higher sperm DNA fragmentation may affect intracytoplasmic sperm injection (ICSI) outcomes, sperm selection protocols do not evaluate this parameter. Therefore, sperm's head birefringence has been suggested as an adjuvant of seminal processing to select viable sperm for couples with severe male factor. Considering men with normal seminal parameters may also curse with DNA fragmentation, the aim of this study was to evaluate the impact of sperm selection by birefringence on ICSI outcomes in couples with different infertility factors compared to those submitted to conventional sperm selection. METHODS: In this case-control study, medical records from 181 couples who underwent ICSI from January 2018 to August 2020 (107 from the Conventional and 74 from the Birefringence group) were included in the study. Clinical characteristics and ICSI outcomes were compared between the groups using Student's t test or Chi-square test (p<0.05) and a multivariate logistic regression model was applied regarding clinical pregnancy. RESULTS: Despite the Birefringence group showed higher female age (p=0.01), lower seminal sperm concentration (p<0.01) and higher sperm DNA fragmentation (p<0.01), those patients cursed with both higher cleavage rate (p=0.04), clinical pregnancy rate per transfer (p=0.03) and clinical pregnancy rate per initiated cycle (p=0.02). The logistic regression showed a positive group effect on clinical pregnancy. CONCLUSIONS: The findings suggest a positive clinical impact of this cheap and easily reproducible adjuvant technique on ICSI outcomes in couples with different infertility factors. If confirmed by further methodologically appropriate studies, the sperm's head birefringence could be considered to improve the reproductive chances of those patients.

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Abstract Background Infertility is caused by heterogeneous risks, but most of them are unexplained. The sperm DNA Fragmentation Index (DFI) was increasingly acknowledged as a parameter for the evaluation of male infertility. This study aimed to investigate the association between sperm DFI and laboratory and clinical outcomes in a population with unexplained infertility. Methods The clinical data of an infertile population was collected for the selection of reproductive patients with unexplained infertility. The authors classified the patients with normal sperm parameters in a control group (DFI < 25%) and an observation group (DFI ≥ 25%) and compared the difference in basal characteristics, laboratory, and clinical outcomes between the two groups. The authors conducted a correlation analysis to examine the relationship between DFI and the number of D3 good-quality embryos, as well as the clinical pregnancy rate and live birth rate. A total of 176 cases were enrolled in the retrospective study. Results The observation group (n = 88) showed advanced male age, lower sperm concentration, progressive motility, and morphology assessment than the control group. In addition, lower No. of D3 good-quality embryos, clinical pregnancy rate, and the live birth rate were shown in the observation group. A negative correlation between the DFI and No. of D3 good-quality embryos (rs = -0.347, p < 0.001) or live birth rate (rs = -0.185, p = 0.028) was shown. Conclusions Sperm DFI was a good indicator for the prediction of D3 good-quality embryos in unexplained infertility couples, but it did not provide sufficient information regarding clinical pregnancy outcome but live pregnancy outcome.

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OBJECTIVE: To investigate the intraindividual agreement of the sperm chromatin dispersion (SCD) assay results to assess sperm DNA fragmentation (SDF) in men with infertility. DESIGN: Diagnostic test reliability study. SETTING: Andrology laboratories. PATIENT(S): A total of 219 men with infertility. INTERVENTION(S): Sperm DNA fragmentation assessment in two ejaculates of the same subjects within a 3-month interval, using the SCD assay performed and analyzed by the same observers under similar testing conditions. MAIN OUTCOME MEASURE(S): Cohen's κ statistics to assess the degree of agreement between the pairs of results after converting the nominal SCD values into categorical data, that is, normal (<20%), intermediate (21%-29%), and high (≥30%) SDF rates. We also assessed the pairs of results using reliability measures for numerical variables (intraclass correlation coefficient for consistency using the two-way mixed-effects model and Bland-Altman plots). RESULT(S): The degree of agreement in classifying patients according to normal and pathological SDF classes was overall substantial (κ = 0.632; 95% confidence interval [CI], 0.546-0.718). A total of 76.7% of individuals were classified under the same class using paired ejaculates. The agreement rate was highest (approximately 80%) in ejaculates initially classified as either normal or high and lowest (approximately 60%) among those with intermediate SDF levels. The frequency of intermediate SDF ejaculates downgraded to normal or upgrade to high SDF classes in the second test was similar (approximately 20%). The intraclass correlation coefficient was 0.856 (95% CI, 0.812-0.887), and the mean difference between the pairs of observations was 0.80% (95% CI, -0.72 to 2.23), indicating no systematic difference between paired observations. CONCLUSION(S): Our study indicates a substantial intraindividual agreement of paired SCD assay results to classify men with infertility into three SDF categories: normal, intermediate, and high. The reliability of the SCD assay was adequate and exceeded 0.80 using two ejaculates analyzed within a 3-month interval under similar conditions. Although this evidence overall supports a single SCD test for patient classification using predefined SDF thresholds, particularly when the first test shows normal or high SDF levels, one in four men will have discordant values in paired ejaculates. Clinicians should be judicious when using SDF test results in decision-making.

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OBJECTIVE: This study aimed to assess the effects of sperm DNA fragmentation in parents belonging to different age groups. The couples included in the study comprised normozoospermic men and infertile women undergoing conventional IVF. METHODS: The results obtained from 163 conventional IVF cycles were analyzed retrospectively. The couples enrolled in the study included women aged between 30 and 37 years. Sperm DNA fragmentation was studied using the TUNEL assay. The patients were split into four groups based on male age and sperm DNA fragmentation, as follows: Group 1: ≤39 years and TUNEL assay ≤20%; Group 2: ≤39 years and TUNEL assay >20%; Group 3: ≥40 years and TUNEL assay ≤20%; and Group 4: ≥40 years and TUNEL assay >20%. RESULTS: No significant differences were found in semen parameters or fertilization rates between groups. Groups with <20% sperm DNA fragmentation showed significant differences in other parameters, including higher blastocyst formation rate (Group 1: 63% and Group 3: 60% vs. Group 2: 43% and Group 4: 41%, p<0.05) and higher expanded blastocyst formation rate (Group 1: 42% and Group 3: 40% vs. Group 2: 21% and Group 4: 18%, p<0.05). Miscarriage rate was significantly higher in Group 4 (42% and 46% vs. 5%, 25% and 5% in Groups 1, 2 and 3, respectively, p<0.05). CONCLUSIONS: Our results showed lower blastocyst formation rates from IVF when males had high levels of sperm DNA fragmentation. Higher miscarriage rates were also observed in couples with males aged 40+ years. These results reinforce the need to inform couples with male partners aged 40+ years about the potential risks inherent to fertility treatment.

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OBJECTIVE: To evaluate the effect of varicocelectomy on sperm deoxyribonucleic acid fragmentation (SDF) rates in infertile men with clinical varicocele. DESIGN: Systematic review and meta-analysis. SETTING: Not applicable. PATIENT(S): Infertile men with clinical varicocele subjected to varicocelectomy. INTERVENTION(S): Systematic search using PubMed/Medline, EMBASE, Cochrane's central database, Scielo, and Google Scholar to identify relevant studies published from inception until January 2021. We included studies comparing SDF rates before and after varicocelectomy in infertile men with clinical varicocele. MAIN OUTCOME MEASURE(S): The primary outcome was the difference between the SDF rates before and after varicocelectomy. A meta-analysis of weighted data using random-effects models was performed. Results were reported as weighted mean differences (WMD) with 95% confidence intervals (CIs). Subgroup analyses were performed on the basis of the SDF assay, varicocelectomy technique, preoperative SDF levels, varicocele grade, follow-up time, and study design. RESULT(S): Nineteen studies involving 1,070 patients provided SDF data. Varicocelectomy was associated with reduced postoperative SDF rates (WMD -7.23%; 95% CI: -8.86 to -5.59; I2 = 91%). The treatment effect size was moderate (Cohen's d = 0.68; 95% CI: 0.77 to 0.60). The pooled results were consistent for studies using sperm chromatin structure assay, terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling, sperm chromatin dispersion test, and microsurgical varicocele repair. Subgroup analyses showed that the treatment effect was more pronounced in men with elevated vs. normal preoperative SDF levels, but the impact of varicocele grade remained equivocal. Meta-regression analysis demonstrated that SDF decreased after varicocelectomy as a function of preoperative SDF levels (coefficient: 0.23; 95% CI: 0.07 to 0.39). CONCLUSION(S): We concluded that pooled results from studies including infertile men with clinical varicocele indicated that varicocelectomy reduced the SDF rates. The treatment effect was greater in men with elevated (vs. normal) preoperative SDF levels. Further research is required to determine the full clinical implications of SDF reduction for these men.

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This work aimed to establish whether the temperature humidity index (THI) under different intertropical zones affects the retention of cytoplasmic droplets (CDs), sperm function and DNA integrity in boars. With this purpose, two separate studies were devised. In the first one, 49 boars from six farms were collected every 45 days (230 ejaculates). THI were measured daily, and sperm parameters were evaluated. Boars were classified into three groups based on the incidence of ejaculates having more than 25% spermatozoa with CDs: persistent (at least three consecutive ejaculates), moderate (less than three ejaculates) and absent (no ejaculate having ≥25% spermatozoa with CDs). Farms were classified based on THI through cluster analysis into two groups. In the second study, 32 liquid-stored semen samples were classified based on three cluster analysis: low and high incidence of proximal (PCDs), distal (DCDs) CDs and a combination of PCD and DCDs. high THI farms presented significantly (p < .05) higher proportions of boars with moderate and persistent incidence of CD than those with low THI. In study 2, the presence of PCDs was negatively correlated with sperm DNA integrity (r = -0.691; p < .01). However, differences between groups were more apparent when ejaculates were classified based on both PCDs and DCDs than when PCDs or DCDs were considered separately. In conclusion, classification of boars according to the severity and persistence of CDs in boars allows understanding more clearly the dynamics of CD retention and the effects of ambient temperature and relative humidity. Additionally, the joint analysis of both PCDs and DCDs is necessary in routine sperm quality analyses.

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PURPOSE: Metabolic surgery is a recommended treatment for obese patients that results in BMI reduction; however, the observed impact of this therapy on male fertility is inconsistent. This research aimed to study the effects of BMI changes after metabolic surgery on seminal analysis, sex hormonal profile, sperm functional integrity, and the seminal plasma lipid peroxidation levels. MATERIALS AND METHODS: A prospective study was performed in 15 patients for whom metabolic surgery was recommended. The patients were evaluated by the techniques proposed in this study before and after the surgical procedure for 12 months. In each analysis, the male sex hormonal profile, semen analysis, sperm functional integrity, and seminal lipid peroxidation levels were assessed. RESULTS: The surgery resulted in BMI reduction and improvement in seminal characteristics and male sex hormone profile. The semen analysis showed increases in volume, sperm progressive motility, and in sperm morphology and a decrease in immotile sperms. Sperm mitochondrial activity and sperm DNA integrity were improved, and the levels of seminal lipid peroxidation were decreased. The hormonal profile showed lower levels of estradiol and highest levels of luteinizing hormone (LH), sex hormone-binding globulin (SHBG), and testosterone. CONCLUSION: BMI changes resulting from this treatment and its metabolic consequences can be associated with changes in the male fertile potential, leading to an improvement in the seminal quality, male sex hormone profile, sperm functional aspects, and levels of seminal lipid peroxidation, thus decreasing the testicular oxidative stress.

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Varicocele has been extensively described and studied as the most important reversible cause of male infertility. Its impact on semen parameters, pregnancy rates, and assisted reproductive outcomes have been associated with multifactorial aspects, most of them converging to increase of reactive oxygen species (ROS). More recently, sperm DNA fragmentation has gained significant attention and potential clinical use, although the body of evidence still needs further evolution. The associations between sperm DNA damage and a variety of disorders, including varicocele itself, share common pathways to ROS increase. This mini-review discusses different aspects related to the etiology of ROS and its relation to varicocele and potential mechanisms of DNA damage.

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We herein summarise the evidence concerning the impact of sperm DNA fragmentation in various clinical infertility scenarios and the advances on sperm DNA fragmentation tests. The collected evidence was used to formulate 41 recommendations. Of these, 13 recommendations concern technical aspects of sperm DNA fragmentation testing, including pre-analytical information, clinical thresholds and interpretation of results. The remaining 28 recommendations relate to indications for sperm DNA fragmentation testing and clinical management. Clinical scenarios like varicocele, unexplained infertility, idiopathic infertility, recurrent pregnancy loss, intrauterine insemination, in vitro fertilisation/intracytoplasmic sperm injection, fertility counselling for men with infertility risk factors and sperm cryopreservation have been contemplated. The bulk evidence supporting the recommendations has increased in recent years, but it is still of moderate to low quality. This guideline provides clinicians with advice on best practices in sperm DNA fragmentation testing. Also, recommendations are provided on possible management strategies to overcome infertility related to sperm DNA fragmentation, based on the best available evidence. Lastly, we identified gaps in knowledge and opportunities for research and elaborated a list of recommendations to stimulate further investigation.

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PURPOSE: Growing evidence in the literature suggests that obesity is capable of altering reproductive hormone levels and male fertility. Effects on classic semen parameters and sperm DNA fragmentation (SDF), however, have not been properly established. Additionally, the impact of bariatric surgery (BS) on those parameters is still controversial. MATERIALS AND METHODS: In Phase 1, 42 patients with obesity and 32 fertile controls were submitted to reproductive hormone evaluation, semen analysis, and SDF testing. In Phase 2, patients with obesity were submitted to BS or clinical follow-up and were invited to 6-month revaluation. RESULTS: Phase 1: Men with obesity have higher levels of estradiol, LH, and FSH and lower levels of total testosterone (TT) when compared with eutrophic fertile men. Additionally, they present worse semen parameters, with reduction in ejaculated volume and sperm concentration, worse sperm motility and morphology, and higher SDF. Phase 2: 32 patients returned to revaluation. Eighteen were submitted to BS (group S) and 14 were not submitted to any specific therapeutic regimen (group NS). In group S, TT more than doubled after surgery (294.5 to 604 ng/dL, p < 0.0001). Worsening of sperm concentration and total ejaculated sperm count were also noticed, and 2 patients became azoospermic after BS. SDF, however, improved after the procedure. No changes in the variables studied were observed in non-operated patients. CONCLUSION: In this prospective study, we have found that BS results in improvements in reproductive hormone levels and SDF after 6-month follow-up. Sperm concentration, however, reduced after the procedure.

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BACKGROUND: Sperm chromatin integrity is essential for normal embryo development and pregnancy outcome. Sperm DNA fragmentation (SDF) testing constitutes a diagnostic tool to measure the proportion of spermatozoa with damaged chromatin in the ejaculate. SDF is associated with potentially treatable conditions, including varicocele, male accessory gland infections, inadequate lifestyle, and gonadotoxin exposure, thus prompting their treatment as a means of improving sperm DNA quality and the reproductive outcomes. OBJECTIVE: To provide an up-to-date review of the role of clinical and surgical interventions on SDF values in subfertile men. MATERIALS AND METHODS: An extensive search of studies examining the relationship between male infertility conditions associated with SDF was performed using PubMed and MEDLINE, with a focus on interventional therapy. The start date for the search was not defined, whereas the end date was March 2019. Randomized and non-randomized controlled trials, observational studies, systematic and narrative reviews, and case series were evaluated. RESULTS: Treating the underlying male infertility factor seems a promising way to alleviate SDF and to increase the likelihood of achieving natural and assisted conception, but data remain limited. The best evidence relates to varicocele repair and hormonal therapy with the follicle-stimulating hormone. Antioxidant therapy and lifestyle changes might alleviate oxidative sperm markers and decrease SDF but their effects on pregnancy outcomes are still unclear. Among men with high SDF undergoing assisted reproductive technology, the use of testicular spermatozoa in preference over ejaculated spermatozoa for intracytoplasmic sperm injection (ICSI) has been shown to improve pregnancy rates possibly owing to the better sperm chromatin quality in testicular spermatozoa than in ejaculated spermatozoa. CONCLUSION: Current evidence supports interventional therapy as a means to alleviate sperm DNA damage. Identification of the conditions associated with SDF remains important to enable treatment to potentially improve pregnancy outcomes but given the limited data further research is needed to determine the exact role of specific interventional therapy for subfertile men with impaired sperm chromatin.

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INTRODUCTION: This study aimed to look into possible correlations between male age and different sperm parameters derived from semen analysis and sperm deoxyribonucleic acid (DNA) fragmentation. METHODS: This retrospective descriptive study included 2681 male patients who underwent semen analysis at Clínica Las Condes (CLC), Santiago, Chile, between January 2014 and May 2017; correlations between age and sperm parameters were analyzed. RESULTS: Males above the age of 50 were significantly more likely to present anomalies in semen volume, sperm concentration, and sperm DNA fragmentation; males aged 41+ years were more likely to have lower sperm concentration levels; males aged 31+ years were more likely to have decreased sperm motility; when concentration was constant, more volume and motility anomalies were seen as age increased; when volume was kept constant, more motility and concentration anomalies were seen as age increased; and when motility was constant, normal semen volumes decreased as age increased. CONCLUSION: Our study showed that male age significantly affects sperm parameters that might have an impact on male fertility.

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Sperm retrieval combined with intracytoplasmic sperm injection (ICSI) is the treatment of choice for couples with untreatable azoospermia-related infertility. However, an increasing body of evidence has been mounting, suggesting that ICSI with testicular sperm instead of ejaculated sperm (when both are available) increases pregnancy outcomes in some specific scenarios. This has led to the exploration of extended indications for sperm retrieval. This review summarizes the current literature concerning sperm retrieval and ICSI for non-azoospermic men with elevated sperm DNA fragmentation, oligozoospermia, and cryptozoospermia.

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Excessive oxidation and antioxidant imbalance resulting from several conditions may cause sperm DNA damage, which, in turn, affect male fertility, both natural and assisted. Sperm DNA damage transferred to the embryo might also affect the health of offspring. Several conditions associated with excessive oxidative stress are modifiable by the use of specific treatments, lifestyle changes, and averting exposure to environmental/occupational toxicants. Here, we discuss the strategies to reduce sperm DNA damage with a focus on clinical and surgical interventions.

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Varicocele pathophysiology is related to increased oxidative stress, which might result in loss sperm DNA integrity as well as in genomic instability. Sperm telomere shortening and loss of global DNA methylation are the main features of genomic instability, leading to cell senescence and death, whereas sperm DNA fragmentation (SDF) characterizes the loss of chromatin integrity. We hypothesize that sperm genomic stability and DNA integrity is reduced in infertile men with moderate and large-sized varicoceles, thus being candidate markers of sperm quality in varicocele-related infertility. Here, we assessed the sperm global DNA methylation, telomere length, and SDF in men with and without clinically palpable varicoceles. While the rates of SDF and telomere length were not statistically different between varicocele patients and controls, global sperm DNA methylation seems to be lower in men with varicocele (49.7% ± 20.7%) than controls (64.7% ± 17.1%). A negative correlation between SDF and sperm motility and a positive correlation between sperm morphology and telomere length were observed. Our results suggest that varicocele may result in genomic instability, in particular, global DNA hypomethylation. However, a large sample size may confirm these findings. The understanding of the molecular mechanisms involved in the pathophysiology of varicocele-related infertility may help to better select candidates for varicocele repair.

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