Conventional semen analysis and advanced sperm function tests in diagnosis and management of varicocele

Clinical varicoceles are a common cause of male infertility and affect sperm parameters as measured in a conventional semen analysis. Varicocelectomy has been shown in prospective studies to improve semen parameters in men with a clinical varicocele. Clinical varicoceles are also a well-known source of oxidative stress which may affect the quality of spermatozoa. Spermatozoa are particularly susceptible to oxidative stress due to a limited capacity for DNA repair. The susceptibility of spermatozoa to oxidative stress is modulated by a balance between ROS and antioxidants, which can be quantified by various laboratory assays. Varicocelectomy has been consistently shown to reduce both ROS and sperm DNA fragmentation, and various assays should be utilised in the diagnosis and treatment of infertile men with a clinical varicocele.     

显微外科曲张精索静脉结扎术治疗精索静脉曲张(附94例报告)

目的:探讨显微外科曲张精索静脉结扎术治疗精索静脉曲张的临床效果。方法:回顾分析2008年8月至2011年2月显微外科术治疗94例精索静脉曲张患者的临床资料。94例中,主要因睾丸坠胀不适、疼痛等症状就诊者36例;主要因不育或少弱精子症就诊者58例。经腹股沟途径或外环口下途径行显微外科曲张精索静脉结扎术,术后1、3、6个月随访相关并发症及精液参数改善等情况。结果:获得随访6个月至2年的患者88例,失访6例。术前主要以睾丸坠胀不适、疼痛等症状就诊获得随访的32例患者,术后症状消失者21例(65.6%),减轻6例(18.8%),无改善5例(15.6%)。获得随访的56例不育或少弱精子症者术前精子浓度及活力为[(a+b)%]为(8.26±1.68)×106/ml、(5.25±1.09)%,术后3个月及6个月分别为(15.47±3.21)×106/ml、(18.39±4.05)×106/ml和(13.34±5.16)%、(17.23±4.69)%,均较术前显著改善(P均<0.01)。结论:显微外科曲张精索静脉结扎术治疗精索静脉曲张可有效改善睾丸疼痛、坠胀不适等症状,并提高精子浓度和活力。     

The impact of age on fertility rate in patients who underwent microsurgical varicocelectomy

Impacts of a subinguinal microsurgical varicocelectomy on the sperm parameters and fertility rates were investigated in three different ages according to their age at the time of the varicocelectomy: Group 1 was ≤20 years old, Group 2 was 21–30 years old, and Group 3 was ≥31 years old. The patients were also classified both preoperatively and post‐operatively according to the total motile sperm count (TMSC) into the following categories: invitro fertilisation, intrauterine insemination and naturally fertile. The proportion of patients who upgraded to a higher TMSC category level was calculated, and natural fertility rates were recorded. The mean infertility duration was statistically longer in Group 3, compared to Group 1 and 2. The mean TMSCs and normal sperm morphology rates increased in all groups. The mean post‐operative natural fertility rates were similar. The highest rate of TMSC upgrade was observed in Grade 3 varicocele patients under 20 years of age, compared to other grades of varicocele in patients older than 20 years. A microsurgical subinguinal varicocele repair, which is an effective treatment modality reduces the need for any type of ART, has an important impact on the TMSC increase in patients, particularly in the younger population.     

Prediction of reproductive function recovery after microsurgical varicocelectomy in men from infertile couples: Clinical and laboratory predictors

The objective was to reveal predictors for fertility recovery after varicocelectomy in subfertile men. This retrospective study recruited 93 men with clinical varicocele and pathozoospermia who underwent microsurgical varicocelectomy. Stepwise discriminant analysis was performed to identify predictors of spontaneous pregnancy (SP) after surgery. ‘Clinically significant improvement’ (CSI) following varicocelectomy was defined as an increase in total progressively motile sperm count (TPMSC) by at least 12.5 million (calculated from WHO-2010 reference values). 52% of patients showed CSI, and 28% reported SP after surgery. Patients who reported SP (group II), compared to that remained infertile (group I), were younger (27.3 ± 2.9 versus 30.2 ± 4.2 years; p < .01), had less infertility period (24.1 ± 14.0 versus 44.4 ± 32.9 months; p < .05) and had initially higher TPMSC (median (25% −75%) = 34 (11–67) versus 9.5 (0–33) mln; p < .05). The stepwise discriminant analysis showed that male age (coefficient value = −0.157), total sperm motility (0.024) and postoperative increase in TPMSC (0.010) were the significant predictors of SP. The predictive ability, sensitivity and specificity of the discriminant function were 84%, 87%, 76% respectively. This algorithm can be recommended after varicocelectomy in decision-making on natural conception or the ART protocols usage.     

Effect of microsurgical repair of the varicocele on testicular function in adolescence and adulthood

OBJECTIVE: Many reports on varicoceles suggest improved spermatic findings and increased pregnancy rates after correction of these lesions. Early repair during adolescence has been advocated, since clinically apparent varicoceles may affect testicular volume and sperm production in the future. We examined the efficacy of microsurgical varicocelectomy, and aimed to establish predictive parameters useful for ascertaining whether varicocele repair provides any benefits in adolescents and adults. METHODS: We carried out microsurgical varicocelectomy on nine boys and 19 men. In adolescents, catch-up growth of the testis, expressed by pre- and postoperative ratios of left and/or right testicular volume, grade and serum level of follicle-stimulating hormone (FSH) were evaluated. In adults, the ratio of sperm concentration improvement, grade, testicular volume, preoperative sperm concentration and serum FSH level were evaluated. All subjects were followed for 12 months. RESULTS: Catch-up growth was seen in 62.5% of boys. FSH level was significantly lower in boys with catch-up growth than in boys without catch-up growth. Improved sperm concentration was seen in 73.6% of adults. FSH level was significantly lower in adults with improved sperm concentration than in patients without improved sperm concentration. No correlations were seen between other parameters and catch-up growth in adolescents, or sperm concentration improvement in adults. CONCLUSIONS: Microsurgical varicocelectomy as a treatment for varicoceles with low FSH might be effective and the relevant predictive parameter for testicular development and function after surgery might be serum FSH level in both adults and adolescents.     

Specialized sperm function tests in varicocele and the future of andrology laboratory

Varicocele is a common medical condition entangled with many controversies. Though it is highly prevalent in men with infertility, still it marks its presence in males who do have normal fertility. Determining which patients are negatively affected by varicocele would enable clinicians to better select those men who benefitted the most from surgery. Since conventional semen analysis has been limited in its ability to evaluate the negative effects of varicocele on fertility, a multitude of specialized laboratory tests have emerged. In this review, we examine the role and significance of specialized sperm function tests with regards to varicocele. Among the various tests, analysis of sperm DNA fragmentation and measurements of oxidative stress markers provide an independent measure of fertility in men with varicocele. These diagnostic modalities have both diagnostic and prognostic information complementary to, but distinct from conventional sperm parameters. Test results can guide management and aid in monitoring intervention outcomes. Proteomics, metabolomics, and genomics are areas; though still developing, holding promise to revolutionize our understanding of reproductive physiology, including varicocele.     

Effect of varicocelectomy on sperm functional characteristics and DNA methylation

In individuals with varicocele, DNA is damaged due to high level of oxidative stress, and varicocelectomy can overcome this effect. Damaged DNA is less liable to DNA methylation, and antioxidant therapy appears to have the potential to reduce sperm oxidative stress and DNA damage and thereby maintain DNA methylation, while effect of varicocelectomy on DNA methylation patterns has remained unclear. In the light of these considerations, we aimed to examine the effect of varicocelectomy on sperm DNA methylation and functional characteristics. Fifty‐two men with left‐sided varicocele (grade II &III) were included. Sperm parameters, DNA fragmentation, protamine deficiency, oxidative stress and global DNA methylation were evaluated before and 3 months after surgery. Our data show that sperm concentration, percentages of spermatozoon with abnormal morphology, DNA fragmentation, protamine deficiency and oxidative stress significantly improved after surgery. Percentage of sperm motility, global DNA methylation and intensity of DNA methylation also improved after surgery, although the differences were not significant when compared with before surgery. Categorisation of individuals to subgroups revealed that improvement of DNA methylation appears to take place in oligozoospermic individuals, which are more severely affected by state of varicocele. However, this is a preliminary study, and further studies are required to solidify this conclusion.     

Long-term effects of microsurgical varicocelectomy on pain and sperm parameters in clinical varicocele patients with scrotal pain complaints

We aimed to investigate the long-term effects of microsurgical varicocelectomy on pain improvement and sperm parameters in patients with varicocele-related pain. A total of 72 patients who had undergone microsurgical subinguinal varicocelectomy because of varicocele with scrotal pain between 2004 and 2009 were included in the study. The patients were grouped according to the presence or absence of pain following surgical treatment. The patients expressing a decrease in frequency and severity of pain or minimal fullness sense were included in the pain-positive group. The mean follow-up period was 54.4 ± 18.06 months. There was left-sided varicocele in 80.3% of patients, while 19.7% had bilateral varicocele. In our study, complete success rate (Visual Analog Scale: 0-1) was found to be 79.2% (57/72), while failure (complete and partial failure) rate was 20.8% (15/72), and a significant difference was found (P < 0.05). Microsurgical subinguinal varicocelectomy is a reliable approach for clinically varicocele patients with scrotal pain complaints. Regardless of the type of pain, varicocelectomy significantly decreases pain. The success of the treatment is not related to the degree of varicocele.     

Evaluation of clinical effects of microsurgical subinguinal varicocelectomy with and without testicular delivery

The aim of this study was to access whether microsurgical subinguinal varicocelectomy (MSV) with testicular delivery has a better therapeutic effect than MSV without testicular delivery, including semen quality, serum testosterone (T) level and International Index of Erectile Function (IIEF)-5 score in infertility male patients with varicocele. In this prospective study, 181 patients were included and they chose the treatment by themselves. A total of 114 patients who received MSV without testicular delivery (TD) and 67 patients who received MSV with TD were followed-up 6 months after the operation. Semen parameters, serum T level and IIEF-5 scores were recorded before and 6 months after the operation. Results showed that MSV with or without TD could improve semen quality, serum T level and IIEF-5 score. For semen quality 6 months after the operation, there was no significant difference between patients received MSV with or without TD. But in patients with varicocele of grade III, MSV without testicular delivery improved the sperm concentration and motility more. And patients received MSV without TD have a higher T level 6 months after the operation, especially in patients ≤27 years. MSV with TD is not superior to that without, but this should be verified in more samples and a better designed randomised controlled study in the future.     

Age is a significant predictor of early and late improvement in semen parameters after microsurgical varicocele repair

Accumulating evidence indicates that varicocele repair improves sperm quality. However, longitudinal changes in sperm parameters and predictors of improved semen characteristics after surgery have not been fully investigated. We retrospectively reviewed data from 100 men who underwent microsurgical subinguinal varicocele repair at a single centre. Follow‐up semen examinations were carried out at 3, 6 and 12 months post‐operatively. Logistic regression was used to identify predictors of early (3 months) and late (≥6 months) improvement in semen parameters after varicocele repair. At 3 months post‐operatively, 76.1% of the patients had improved total motile sperm counts, which continued to improve significantly up to 12 months post‐operatively (p = .016). When comparing changes in semen parameters between younger (<37 years) and older (≥37 years) men, post‐operative improvements in sperm concentration and motility were greater among younger men. Multivariate analysis showed that younger age was associated with early (p = .043) and late (p = .010) post‐operative improvement in total motile sperm count. Our findings indicate that early varicocele repair improved semen parameters after surgery.     

Impact of varicocelectomy on premature ejaculation in varicocele patients

In a prospective manner, we studied the effect of varicocelectomy on premature ejaculation and testicular hormonal function in patients with varicocele. Microsurgical subinguinal varicocelectomy was carried out in 73 patients with clinical varicocele associated with premature ejaculation (group 1) and compared with 56 patients without operative intervention (group 2; control). The primary efficacy variable was the mean change in the Premature Ejaculation Diagnostic Tool. The changes in International Index of Erectile Function questionnaire, total serum testosterone and testicular size were also assessed. In group 1, the Premature Ejaculation Diagnostic Tool decreased significantly after varicocelectomy, from 15.56 to 11.37 (P < 0.001), indicating improvement of premature ejaculation. Thirty patients (41.1%) showed improvement of premature ejaculation compared to 5.3% in the control group (P < 0.001). In group I, but not in group II, testosterone levels and International Index of Erectile Function values increased significantly when compared with pre‐operative values (P < 0.001 and 0.040 respectively). Testicular size increased after varicocelectomy, but this increase was nonsignificant till the end of study (P = 0.054). We concluded that varicocelectomy is clearly related to improvement of premature ejaculation and testicular hormonal function in varicocele patients.     

Predictors of varicocele-associated pain and its impact on semen parameters following microsurgical repair

Our study aimed to assess for predictors of varicocele-associated pain and whether it predicts semen parameters after microsurgical varicocelectomy. We assessed all men diagnosed with a varicocele by two surgeons from 2017 to 2020, excluding those who did not undergo surgical treatment. Patients were stratified based on the presence of pain at clinical assessment, and these groups were compared. Logistic regression models were utilised to assess for predictors of pain. A total of 313 men were included, with relatively similar proportions completed by both surgeons (48.2% and 51.8%). A total of 98 (31.3%) had typical varicocele-associated pain at the time of assessment. The pain group was younger than the no pain group (30.5 versus. 35.0, respectively, p < .01), and those with pain had greater varicocele grades (p = .008). Although not statistically different, there was a greater portion of left-sided only varicoceles in the pain group (p = .09). No significant differences were demonstrated between sperm concentration, motility, volume or morphology pre-operatively, or post-operatively between groups. Younger age and varicocele grade were predictive of varicocele-associated pain. In conclusion, almost 1/3 of men presented with varicocele-associated pain. Pain does not predict response to varicocelectomy, but these men tend to be younger, and have higher grade varicoceles.     

Can inhibin-B predict the outcome of microsurgical epididymal sperm aspiration in patients with suspected primary obstructive azoospermia？

Aim： To evaluate whether inhibin-B can predict the outcome of a microsurgical epidymal sperm aspiration （MESA） procedure in patients with suspected primary obstructive azoospermia （OA） and if inhibin-B can replace testicular biopsy in the diagnostic work-up of these patients. Methods： Inhibin-B levels and testicular biopsy scores were related to the outcome of MESA in 43 patients with suspected primary OA. MESA was considered to be successful when epididymal sperm could be identified during the procedure. Results： Spermatozoa were present in the epididymal aspirate in 28 out of the 43 patients （65%）. lnhibin-B values were not significantly different in patients with successful or unsuccessful MESA. The modified Johnsen score, however, was significantly lower in patients with unsuccessful MESA （P = 0.003）. A rete testis obstruction or epididymal malfunctioning was found in 15% of patients with suspected primary OA, reflected by unsuccessful MESA despite normal inhibin-B levels and normal testicular histology. Conclusion： Inhibin-B cannot replace testicular biopsy as a diagnostic tool in the work-up of patients with suspected primary OA. Testicular biopsy is useful in identifying patients with spermatogenic arrest, who might have normal inhibin-B values.     

Impact of varicocelectomy on urine dopamine value in patients with premature ejaculation and varicocele

Dopamine is an important regulator of male sexual function and behaviour. Decreased levels of this substance have been observed in blood and seminal plasma of infertile men. Hence, this study was carried out to determine the impact of varicocelectomy on 24‐hr urine dopamine values in patients with both premature ejaculation (PE) and varicocele. In this prospective study, 55 consecutive patients with premature ejaculation and grade 2 or 3 varicocele were enrolled. The urine dopamine level was measured in a 24‐hr sample by HPLC method in a single laboratory centre. Two samples were gathered from each patient, one before and the other 1 month after varicocelectomy. The mean initial and final 24‐hr urine dopamine levels were 259.6 ± 86.3 and 602.9 ± 88.4 micrograms, respectively, showing statistically significant increase (p = .0001), while there was no statistically significant difference between urine volume and creatinine. However, the change in intravaginal ejaculation latency time value was not statistically significant at this short time visit. According to our findings, varicocelectomy results in a significant increase in 24‐hr urine dopamine levels in patients with premature ejaculation and varicocele. However, the effect of this change on premature ejaculation in the long term has yet to be determined.     

Effect of microsurgical varicocelectomy on fertility outcome and treatment plans of patients with severe oligozoospermia: An original report and meta-analysis

Varicocele ligation has been proven to restore semen parameters and improve pregnancy rates in men with clinical disease. However, its effect in men with severe oligozoospermia (SO) is less clearly elucidated. This original report and meta-analysis examined the impact of subinguinal microsurgical varicocelectomy on semen parameters and fertility outcomes of men with SO. A retrospective chart review of 85 patients was conducted on patients with SO who underwent microsurgical subinguinal varicocelectomy. A literature search was carried out according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A total of 8 studies investigating the effects of varicocele ligation in men with SO were included for the meta-analysis. The original study reported significant improvements in semen parameters following surgery. 78 patients had a pre-operative TMSC < 5 million. Following surgery, 9 (11.5%) patients had a total motile sperm count (TMSC) between 5 and 9 million, while 14 (17.9%) patients had a TMSC > 9 million. Furthermore, the meta-analysis demonstrated a statistically significant increase in sperm count, total motility and TMSC following surgery. The reported natural pregnancy rate was 27.5%. Varicocelectomy does present as an important treatment option for SO patients because improvements in TMSC can broaden their fertility treatment options.     

Pressure flow pattern of varicocele veins and its correlation with testicular blood flow and semen parameters

The pressure pattern in varicocele veins of infertile patients and its correlation with semen quality and testicular blood flow was determined. Consecutive patients at andro‐urology clinic of a teaching hospital undergoing microsurgical varicocelectomy were included. Their semen quality and testicular blood flow were determined. Peak systolic velocity (PSV) and resistive index (RI) of subcapsular and intraparenchymal branches of testicular artery were noted by colour Doppler ultrasonography. During surgery before ligation of varicocele veins, intravenous pressures of internal spermatic (ISV) and external spermatic (ESV) veins were determined at baseline and after Valsalva manoeuvre. Thirty patients, 20–45 years old, were evaluated. Baseline pressure for maximum dilated ISV (A), less dilated ISV (B) and ESV was 15.93 ± 6.34, 12.38 ± 4.60 and 12.92 ± 5.65 mm. Hg, respectively, which increased after Valsalva by 104.4%, 116.2% and 38.22% respectively. Correlation (r = ?.71; p < .05) was appreciated between percentage increase in pressure of ISV B with PSV of intraparenchymal testicular arteries and progressive motility (r = ?.759; p < .05), nonprogressive motility (r = ?.738; p < .05) and morphology (r = ?.653; p = .07) of spermatozoa. In conclusion, ISV develops higher pressure on Valsalva as compared to ESV and has correlation with semen quality and testicular blood flow.     

Critical appraisal of conventional semen analysis in the context of varicocele

Varicocele is present in approximately 15% of men, and, although it is the most commonly diagnosed cause of male infertility, nearly two-thirds of men with varicoceles remain fertile. It was decided to make use of the current evidence obtained from the previous meta-analyses between 2004 and 2015 as well as available articles covering this field, preferably randomized controlled articles dealing with the topic of semen analysis before and after repair. Two important meta-analyses were discussed as well as other articles dealing with the topic of semen analysis before and after varicocelectomy. The evidence suggests that all semen parameters improve after varicocele repair. Based on the available evidence, it is clear that there is a benefit in treating men with a palpable varicocele. One can expect that all semen parameters will improve within 3 months after repair.     

Bilateral is superior to unilateral varicocelectomy in infertile men with bilateral varicocele: Systematic review and meta‐analysis

To investigate whether bilateral surgery can bring more benefits to infertile patients with bilateral varicocele than unilateral surgery. A search of PubMed, Web of Science, EMBASE and the Cochrane Library on 13 January 2019 was conducted to identify studies published in English that used varicocelectomy. The protocol of the present meta‐analysis was pre‐published on PROSPERO (registration number CRD42019093894). Primary outcomes were spontaneous pregnancy rates. A total of eleven articles were finally enrolled in, with a total of 1,743 patients. Spontaneous pregnancy rate was higher in patient with bilateral varicocelectomy than unilateral varicocelectomy with an odds ratio (OR) of 1.89 (95% CI 1.52–2.35; I² = 0%; p < .00001). The results indicated bilateral is superior than unilateral varicocelectomy concerning sperm concentration (SMD: 2.88 × 10⁶/ml; 95% CI: 1.06, 4.70; I² = 93%), sperm motility (SMD: 5.08; 95% CI: 2.65, 7.50; I² = 0%), progression of sperm motility (SMD: 6.48; 95% CI: 5.16, 7.81; I² = 0%) and sperm morphology (SMD: 2.38%; 95% CI: 0.72, 4.03; I² = 94%) between bilateral and unilateral varicocelectomy. Bilateral varicocelectomy may be superior to unilateral in regard to spontaneous pregnancy rate and sperm motility for infertile male with bilateral varicocele (both left clinical and right subclinical varicocele and bilateral clinical varicocele).     

Comparison between microsurgical varicocelectomy with and without testicular delivery for treatment of varicocele: A systematic review and meta‐analysis

The present study was conducted to assess the semen parameters, complications and clinical effect of microsurgical varicocelectomy with testicular delivery (TD) for treatment of varicocele. Relevant studies were collected and reviewed systemically from PubMed, Medline, Embase, Web of Science, China National Knowledge Infrastructure databases and the Cochrane Library and a meta‐analysis was performed. Relative ratio (RR), standardised mean difference (SMD) and their 95% confidence intervals (CIs) were adopted to estimate the outcome measures. Eight articles and a total of 1,139 subjects including 487 patients with TD in microsurgical varicocelectomy and 652 patients without TD were enrolled in this meta‐analysis. The pooled RR indicated that microsurgical varicocelectomy with TD increased the incidence of orchiepididymitis (RR = 4.36, 95% CI = 1.12–16.99, p = 0.034) and scrotal oedema (RR = 4.25, 95% CI = 2.40–7.54, p = 0.000) than microsurgical varicocelectomy without TD postoperatively. In conclusion, compared to microsurgical varicocelectomy without TD, TD to further ligate the gubernacular veins in microsurgical varicocelectomy results in a higher incidence of orchiepididymitis and scrotal oedema and take longer operation time. However, TD may not have any beneficial influences on semen parameters, serum testosterone, varicocele occurrence, wound infection and natural conception.