Open non‐microsurgical,laparoscopic or open microsurgical varicocelectomy for male infertility: a meta‐analysis of randomized controlled trials

Study Type – Therapy (systematic review) Level of Evidence 1a What's known on the subject? and What does the study add? There are several surgical techniques for the treatment of varicocele in infertile men, including open non‐microsurgical, laparoscopic and microsurgical varicocelectomy. It is currently unclear, however, which is the most beneficial method for patients. The present meta‐analysis found that microsurgical varicocelectomy is the most effective and least morbid method among the three varicocelectomy techniques for treating varicocele in infertile men.

OBJECTIVE

• ? To compare various techniques of open non‐microsurgical, laparoscopic or microsurgical varicocelectomy procedures to describe the best method for treating varicocele in infertile men.

PATIENTS AND METHODS

• ? We searched PubMed, Embase, the Cochrane Library, the Institute for Scientific Information (ISI) – Science Citation Index and the Chinese Biomedicine Literature Database up to June 2011. Only randomized controlled trials (RCTs) were included in the present study.
• ? The outcome measures assessed were pregnancy rate (primary), the incidence of recurrent varicocele, time to return to work, the incidence of postoperative hydrocele and operation duration (secondary).
• ? Two authors independently assessed the study quality and extracted data. All data were analysed using Review Manager (version 5.0).

RESULTS

• ? The present study included four randomized controlled trials comprising 1,015 patients in total.
• ? At the follow‐up endpoints, patients who had undergone microsurgery showed a significant advantage over those who had undergone open varicocelectomy in terms of pregnancy rate (odds ratio [OR]= 1.63, 95% confidence interval [CI]: 1.19–2.23].
• ? There was no significant difference between laparoscopic and open varicocelectomy (OR = 1.11, 95% CI: 0.65–1.88) or between microsurgery and laparoscopic varicocelectomy (OR = 1.37, 95% CI: 0.84–2.24).
• ? The incidences of recurrent varicocele and postoperative hydrocele were significantly lower after microsurgery than after laparoscopic or open varicocelectomy.
• ? The time to return to work after microsurgery and laparoscopic varicocelectomy was significantly shorter than that after open varicocelectomy.
• ? The operation duration of microsurgical varicocelectomy was longer than that of laparoscopic or open varicocelectomy.

CONCLUSIONS

• ? Current evidence indicates that microsurgical varicocelectomy is the most effective and least morbid method among the three varicocelectomy techniques for treating varicocele in infertile men.
• ? More high‐quality, multicentre, long‐term RCTs are required to verify the findings.

     

Efficacy of varicocelectomy in the treatment of hypogonadism in subfertile males with clinical varicocele: A meta‐analysis

To reassess the efficacy of varicocelectomy in the treatment of hypogonadism in subfertile males, we carried out a meta‐analysis of clinical trials and retrospective studies that compared the pre‐operative and postoperative serum testosterone. We searched Embase and PubMed (1980 to May 2016) for studies. Eight studies and 712 patients were included. The combined analysis of seven studies discovered that the mean serum testosterone of patients post‐operation improved by 34.3 ng/dl (95% CI: 22.57–46.04, p < .00001, I² = 0.0%) compared with their pre‐operative levels. In subgroup analysis, testosterone improvements in the hypogonadal treated subgroup were more significant (improved by 123 ng/dl, 95% CI: 114.61–131.35, p < .00001, I² = 37%) than in the eugonadals, or the untreated controls. In an analysis of surgery versus untreated control (three studies included), results showed that mean testosterone among hypogonadals increased by 105.65 ng/dl (95% CI: 77.99–133.32), favouring varicocelectomy, as the differences were significant (p < .00001), However, there were insignificant differences in eugonadals (p = .36). In conclusion, varicocelectomy significantly improved testosterone in hypogonadal men with subfertility. Active surgical treatment of varicocele might have a benefit of maintaining healthy androgen levels in subfertile men.     

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).     

Efficacy of antioxidant therapy on sperm quality measurements after varicocelectomy: A systematic review and meta‐analysis

Antioxidants were proved to be efficient to improve the quality of spermatozoa after varicocelectomy. We carried out a systematic review and performed a meta‐analysis to evaluate the efficacy of antioxidant therapy in sperm parameters' quality after varicocelectomy during 3 or 6 months' treatment cycle. During research, randomised controlled trials were searched by MEDLINE, EMBASE and the Cochrane Controlled Trials Register, and necessary parameters were compared between two groups after varicocelectomy. Finally, six studies including 576 patients were included in our meta‐analysis. As for sperm parameters, significant improvements of sperm concentration (p < .0001), sperm motility (p = .03), progressive sperm motility (p < .00001) and sperm morphology (p < .00001) were existed in antioxidant group 3 months after varicocelectomy. With regard to the 6 months' outcomes, sperm parameters were improved as well except sperm motility (p = .72) and progressive sperm motility (p = .57). Referring to pregnancy rate, no significant difference was existed between two groups (p = .36), and the FSH level of antioxidant group was lower than placebo group 3 or 6 months after varicocelectomy (3 months, p = .02; 6 months, p = .03). In conclusion, compared with the placebo, the antioxidant therapy after varicocelectomy can improve the quality of sperm parameters and construct a favourable living condition for spermatozoa by reducing FSH level.     

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.     

Clinical effectiveness of microsurgical subinguinal varicocelectomy with enhanced recovery after surgery for varicocele

BackgroundVaricocele (VC) is one of the most common causes of infertility in men, and microscopic varicocelectomy is currently the major surgical procedure for VC. We assessed the clinical effectiveness of microsurgical subinguinal varicocelectomy (MSV) with enhanced recovery after surgery (ERAS) in the treatment of VC in terms of semen quality improvement rate, pregnancy rate, pain relief rate, recurrence rate, and complication rate after MSV and explored the indications for VC surgery.MethodsIn total, 216 patients undergoing MSV in our center between June 2019 and July 2020 were enrolled in this study. All patients received the surgery under local anesthesia and were admitted and discharged within 24 hours. All patients were followed up for more than 6 months, and the rates of semen quality improvement, pregnancy, pain relief, recurrence, and postoperative complications were recorded. We can evaluate the pain degree of patients through the numerical rating scale (NRS). (I) 0 points for painless; (II) 1–3: mild pain; (III) 4–6: moderate pain; (IV) 7–10 points are severe pain. 0 is the most slightly, indicating comfort, and 10 is the most painful and unbearable.ResultsThe sperm concentration, total sperm count, progressive motility rate, sperm viability, and morphology were significantly improved after the surgery (all P values <0.05). The rate of semen quality improvement was 88.2%, and the semen indicators returned to normal in 26.6% of the patients. Among the patients who were followed up for 1 year, the natural conception rate reached 27.1% and was accompanied by a 95.5% pain relief rate, a 0.5% VC recurrence rate, and a 2.3% postoperative complication rate.We obtained data through laboratory examination of semen DNA fragments index (DFI). Compared with preoperative and postoperative DFI, postoperative DFI was improved, and the pregnancy outcome was improved.ConclusionsMSV under local anesthesia increases the rates of semen quality improvement, pregnancy, and pain relief while lowering the rates of recurrence and postoperative complications. MSV may also help to improve the pregnancy outcomes in patients with VC accompanied by sperm DNA fragmentation or nonobstructive azoospermia, but this should be verified by further investigation.     

Effect of adjuvant drug therapy after varicocelectomy on fertility outcome in males with varicocele‐associated infertility: Systematic review and meta‐analysis

Varicocele is one of the common correctable causes of male infertility. Recent studies have demonstrated varicocelectomy in males with abnormal semen parameters was associated with better fertility outcome, but the effect of adjuvant drug therapy after varicocelectomy on fertility outcome in patients with varicocele‐associated infertility remains undefined. Hence, the present meta‐analysis was performed to assess the efficacy of adjuvant drug therapy after varicocelectomy. The protocol was registered with PROSPERO (No. CRD42018093749). Ten randomised controlled trails containing 533 patients with adjuvant drug therapy after varicocelectomy and 368 patients with no medical treatment after varicocelectomy were included. Our analysis revealed that the improvement in pregnancy rate after adjuvant drug therapy was insignificant. (OR = 1.70, 95%CI = 0.99–2.91), but resulted in significant improvements in sperm concentration (MD = 13.71, 95%CI = 5.80–21.63) and motility (MD = 4.77, 95%CI = 3.98–5.56) at 3 months, sperm DNA integrity (SMD = 3.13, 95%CI = 1.50–4.75) and serum FSH level (MD = ?1.02, 95%CI = ?1.79 to ‐0.24). Therefore, compared to no medical treatment, the adjuvant drug therapy, especially the use of antioxidants seems to be associated with better fertility outcome. However, more evidences with high‐quality studies are necessary to conform its benefits.     

Microsurgical varicocelectomy for clinical varicocele: A review for potential new indications

Microsurgical varicocelectomy is considered the gold‐standard technique treating varicocele in both adults and adolescents, due to relatively more favourable outcomes and lower post‐operative recurrence and complication rates. Despite of mounting literature on this topic, several aspects are still not well defined. We summarised the most recent literature and presented findings that might extend its indications. Microsurgical varicocelectomy and intracytoplasmic sperm injection are both effective to father a child for infertile men with clinical varicocele even for those with worst condition of spermatozoa, nonobstructive azoospermia, and prior varicocele repair has substantial benefits for couples with a clinical varicocele. Microsurgical subinguinal and inguinal varicocelectomy seem to have comparable effectiveness for adolescents and infertile men with varicoceles. However, the subinguinal approach may have some advantages to deal with painful varicocele. The superior outcomes of bilateral varicocelectomy for patients with clinical left varicocele and concomitant clinical right varicocele are justified, while the benefit is still uncertain for concomitant subclinical right varicocele. Varicocelectomy may have the potential to improve sexual function along with serum testosterone. In conclusion, indications for microsurgical varicocelectomy may be extended by the concomitant right and left clinical varicocele and sexual dysfunction with varicocele.     

Clinical significance of subclinical varicocelectomy in male infertility: systematic review and meta‐analysis

Recent meta‐analysis by the Cochrane collaboration concluded that treatment of varicocele may improve an infertile couple's chance of pregnancy. However, there has been no consensus on the management of subclinical varicocele. Therefore, we determine the impact of varicocele treatment on semen parameters and pregnancy rate in men with subclinical varicocele. The randomised controlled trials that assessed the presence and/or treatment of subclinical varicocele were included for systematic review and meta‐analysis. Random effect model was used to calculate the weighted mean difference of semen parameters and odds ratio of pregnancy rates. Seven trials with 548 participants, 276 in subclinical varicocelectomy and 272 in no‐treatment or clomiphene citrate subjects, were included. Although there was also no statistically significant difference in pregnancy rate (OR 1.29, 95% CI 0.99–1.67), surgical treatment resulted in statistically significant improvements on forward progressive sperm motility (MD 3.94, 95% CI 1.24–6.65). However, the evidence is not enough to allow final conclusions because the quality of included studies is very low and further research is needed.     

Erectile dysfunction and atrial fibrillation: A systematic review and meta‐analysis

Objective

To investigate the pooled incidence or the prevalence of erectile dysfunction, and to assess the risk of erectile dysfunction in patients with atrial fibrillation.

Methods

A systematic review was carried out in the MEDLINE, EMBASE and Cochrane databases from inception through January 2018 to identify: (i) studies that reported the incidence and/or prevalence of erectile dysfunction in atrial fibrillation patients; or (ii) studies that assessed the association between atrial fibrillation and erectile dysfunction. Pooled odds ratios and 95% confidence intervals were calculated using a random effects model.

Results

Five observational studies (27 841 patients) were enrolled. The pooled estimated prevalence of erectile dysfunction in atrial fibrillation patients was 57% (95% confidence interval 50–64, I² = 0). A study showed an incidence of newly diagnosed erectile dysfunction in atrial fibrillation patients of 0.96% during the mean follow‐up duration of 4.67 ± 3.20 years. There was a significant association of atrial fibrillation with an increased risk of erectile dysfunction, with a pooled odds ratio of 1.79 (95% confidence interval 1.44–2.23, I² = 0%). The data on the risk of atrial fibrillation development in patients with erectile dysfunction were limited. A study showed the comparable risk of atrial fibrillation in patients with erectile dysfunction (odds ratio 1.03, 95% confidence interval 0.67–1.5), when compared with those without erectile dysfunction.

Conclusions

The present study suggests a significant association between erectile dysfunction and atrial fibrillation. The overall estimated prevalence of erectile dysfunction among atrial fibrillation patients is 57%. However, despite limited data, the current evidence suggests a low incidence of new erectile dysfunction in atrial fibrillation patients.

     

Effect of surgical repair on testosterone production in infertile men with varicocele: a meta-analysis

Objectives: To determine the effect of surgical varicocele repair in improving testicular Leydig cell function as shown by increased testosterone production. Methods: Eligible studies were searched in Medline and the Pubmed database, and cross‐referenced as of 31 May 2011 using the terms “varicocele,”“testosterone” and “surgery.” The database search, quality assessment and data extraction were independently carried out by two reviewers. Only studies including patients with testosterone evaluation before and after surgery were considered for the analysis. A systematic review and meta‐analysis was carried out for continues variables using random effect models. Results: Out of 125 studies, a total of nine were selected, including 814 patients. The combined analysis showed that mean serum testosterone levels after surgical treatment increased by 97.48 ng/dL (95% confidence interval 43.73–151.22, P = 0.0004) compared with preoperative levels. Conclusions: Surgical treatment of varicocele significantly increases testosterone production and improves testicular Leydig cell function.     

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.     

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.     

Serum vitamin D levels and erectile dysfunction: A systematic review and meta‐analysis

Suboptimal levels of serum vitamin D levels have been implied to be associated with cardiovascular diseases and endothelial dysfunction, conditions closely associated with erectile dysfunction (ED). The present systematic review and meta‐analysis was performed to evaluate the vitamin D levels in subjects with ED compared to controls and the 5‐item version of the international index of erectile function (IIEF‐5) score in subjects with vitamin D deficiency compared to those without vitamin D deficiency in order to elucidate the role of vitamin D in the pathogenesis of ED. Studies evaluating the possible association between vitamin D levels and ED were initially screened and thus included following electronic literature search of database Cochrane Library, PUBMED, EMBASE and MEDLINE. Essential article information including outcome measures was extracted from the qualified studies by two independent authors, and STATA 12.0 software was used conducted the meta‐analysis. Subgroup analyses were conducted by vitamin D detection methods and sample size. The standard mean difference (SMD) as well as the 95% confidence intervals (95% CIs) was applied to estimate the outcome measures. A total of seven articles were included in our meta‐analysis with a total of 4,132 subjects. Pooled estimate was in favour of increased vitamin D levels in subjects without ED with a SMD of 3.027 ng/ml, 95%CI 2.290–3.314, p = 0.000. However, subgroup analysis showed an opposite trend, after one study with a sample size over 1,000 that could possibly influence the weight balance was excluded, with a SMD of 0.267, 95%CI ?0.052 to 0.585, p = 0.101. We also identified about 0.320 higher in IIEF‐5 score (95%CI = 0.146–0.494, p = 0.000) in subjects without vitamin D deficiency versus with vitamin D deficiency. Nevertheless, subgroup analysis based on vitamin D detection methods obtained differential results (radioimmunoassay subgroup, SMD(95%CI) = 0.573 (0.275–0.870), p = 0.000; immunoassay subgroup, SMD(95%CI) = 0.189 (?0.025 to 0.404), p = 0.084). In conclusion, results from the present meta‐analysis did not provide a strong relationship between vitamin D and the risk of ED. However, the results should be interpreted with caution and more high quality studies are warranted.     

Platelet indices and erectile dysfunction: A systematic review and meta‐analysis

Elevated platelet levels have been postulated to be associated with cardiovascular diseases, conditions closely linked to erectile dysfunction (ED). The current systematic review and meta‐analysis was performed to assess the platelet indices, which including platelet count (PLT), mean platelet volume (MPV) and platelet distribution width (PDW) in subjects with ED compared to controls in an attempt to clarify the possible role of platelet indices in the pathogenesis of ED. We initially screened the candidate studies observing the possible association between platelet indices and ED following literature search of database Cochrane Library, PubMed, EMBASE and MEDLINE and therefore included the studies based on the pre‐defined inclusion and exclusion criteria. Two independent investigators extracted the related information on article data and outcome measures from the qualified studies, and a meta‐analysis was therefore performed using Stata 12.0 software. Subgroup analyses were conducted by the different ED aetiology obtained from the eligible studies. The standard mean difference (SMD) and the corresponding 95% confidence intervals (95% CIs) were applied to estimate the outcome measures. A total of 14 articles were qualified in our meta‐analysis with a total of 1595 cases and 987 controls included. Pooled estimate was in favour of increased MPV levels in subjects with ED with a SMD of 0.651 fl, 95% CI 0.567–0.735, p = 0.000. Subgroup analysis showed that vasculogenic ED had a higher MPV levels than controls as well (SMD [95% CI] = 1.026 [0.823–1.228], p = 0.000). However, pooled analysis based on PLT and PDW levels has produced inconsistent results and not strong evidence on platelet level and ED correlation. In conclusion, vasculogenic ED patients had a higher MPV level in our study. However, the results need further interpretation with caution and more high‐quality studies are warranted.