The impact of coexisting sperm DNA fragmentation and seminal oxidative stress on the outcome of varicocelectomy in infertile patients: A prospective controlled study

Abstract

ObjectivesTo study the relationship between sperm DNA fragmentation (SDF) and reactive oxygen species (ROS) levels in infertile patients with varicocele, and to examine the beneficial effect of varicocelectomy and elucidate predictors of improvement after repair.Patients, subjects and methodsWe prospectively studied 60 patients with varicocele and abnormal semen variables who attended the outpatient clinic complaining of infertility for ≥12 months. In all, 25 patients (41.7%) had bilateral varicoceles and 35 (58.3%) had left varicoceles. The DNA fragmentation index (DFI%, percentage of sperm with denatured nuclei), ROS and total non-enzymatic antioxidant capacity (TAC) were measured. Inguinal varicocelectomy was performed in all patients. At 3–6 months postoperatively, all measurements were repeated. A control group, comprised of 20 normozoospermic fertile men, was included. Regression analysis was used to examine predictors of improvement.ResultsThe mean (SD) DFI% in the 60 infertile patients with varicocele was 29.9 (8.3) and 7.56 (2.84)% in the controls; ROS levels were 4.49 (0.9) in patients and 2.62 (0.8) photons/min in controls; and the TAC was 0.97 (0.4) in patients and 1.5 (0.5) mM in controls; with highly significant differences between the patients and controls. The DFI% showed a positive correlation with ROS levels, whilst the total motile sperm count (TMSC) had a significant negative correlation with DFI%, ROS levels and grade of varicocele, whilst there was significant positive correlation with TAC. The grade of varicocele and duration of infertility were related to the presence of higher levels of ROS and increased of DFI%. Postoperatively, improvement (measured as a >50% increase in TMSC) occurred in 40 of 55 (73%) patients available at follow-up, with a significant reduction in the mean (SD) DFI% from 29.49 (8.58) to 18.78 (7.23)%, ROS levels from 4.49 (0.88) to 3.27 (1.3) photons/min (both P < 0.001), and a significant increase in the mean (SD) TAC from 1.01 (0.44) to 2.05 (0.51) mM (P < 0.001). Responders had a shorter infertility duration and lower preoperative DFI% and ROS levels. Regression analysis showed that DFI% is a predictor of improvement after varicocelectomy.ConclusionSDF was shown to have a negative impact on improvement after varicocelectomy. Hence, DFI% could be recommended as a prognostic test in infertile patients with varicocele to help decision-making as regards the necessity and the anticipated outcome of varicocelectomy in patients with infertility.

The higher risk for sperm DNA damage in infertile men

“…Furthermore, the levels of sperm DNA fragmentation were designated based on the following criteria: low SDF level (0-15% sperm cells with fragmented DNA, high fertility potential), moderate SDF level (16-30%, moderate fertility potential) and high SDF level (> 30%, low fertility potential) [7,[10][11][12]. Healthy volunteers and infertile men differed significantly (p < 0.0001) at low levels (57.90% vs 17.03% subjects, respectively) and high levels (5.26% vs 35.17% subjects, respectively) of SDF (Tab.…”

“…Bungum et al [18] showed that in the range of 0-20% sperm DNA fragmentation, the chance of a spontaneous pregnancy was constant, while DNA fragmentation index (DFI) levels > 30-40% resulted in reduced chances close to zero. However, these 2 categories can reasonably be extended to 3, as proposed by Leach et al [7], Abdelbaki et al [10] and Al Omrani et al [12]. In this division, a threshold of 0-15% is considered a high fertility potential, while 16-30% and > 30% are considered moderate and low fertility potentials, respectively.…”

“…In this context, many authors try to find optimal threshold of SDF for assessment of male fertility potential [6][7][8][9]. It is suggested that low SDF level (0-15% sperm cells with DNA fragmentation) corresponds to high fertility potential, moderate SDF level (16-30%) to moderate fertility potential while high SDF level (> 30%) to low fertility potential [7,[10][11][12]. The aim of this study was therefore to determine the extent of SDF and establish a discriminating threshold value of SDF for fertility potential.…”

European Academy of Andrology guideline Management of oligo‐astheno‐teratozoospermia

“…Correlation between varicocoele (uni‐ or bilateral) and OAT is controversial, due to its presence both in adult men with normal semen analysis and men with OAT (World Health Organization, ). Recent meta‐analyses show semen quality improvement following palpable varicocoele repair (Marmar et al ., ), possibly with a higher conception rate after surgery vs. no‐surgery (Agarwal et al ., ; Marmar et al ., ; Abdel‐Meguid et al ., ; Baazeem et al ., ; Kroese et al ., ), and sperm DNA damage decrease (Abdelbaki et al ., ). In addition, varicocelectomy may increase total testosterone level in hypogonadal men with subfertility (Chen et al ., ).…”

Oxidative Stress in Male Infertility: Causes, Effects in Assisted Reproductive Techniques, and Protective Support of Antioxidants

“…The surgical treatment of varicocele has been demonstrated to be an effective method to remove the alterations caused by the affected veins, as blocking blood reflux prevents temperature increases. The effects observed after the recovery from surgery include a decrease in reactive oxygen species and an increase in total antioxidant capacity, which comes from augmenting the levels of antioxidant enzymes and molecules [27,103,104]. As a consequence, DNA damage is reduced after varicocelectomy [105].…”