Abstract
Patients with azoospermia show a prevalence of varicocele of 10.9% and a 14.8% contribution to male infertility. Patients with azoospermia are thought to produce high-quality semen following varicocele treatment. Advising varicocelectomy prior to sperm retrieval in a reproductive program is still debated. This study reviewed the impact of varicocele repair on male infertility using several factors. A literature search was conducted using Scopus, PubMed, Embase, the Wiley Online Library, and Cochrane databases. Sperm concentration, sperm progression, overall sperm motility, sperm morphology, and follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels were also compared. Outcomes were compared between those who received treatment for varicocele and those who did not. The data from the pooled analysis were presented as standardized mean difference (SMD) along with a 95% confidence interval (CI). Heterogeneity was evaluated using I2. Additionally, we conducted analyses for publication bias, sensitivity, and subgroup analysis as appropriate. Nine studies were included after screening relevant literature. Statistical analysis revealed a significant improvement in sperm concentration (SMD: 1.81, 95% CI: 0.84–2.77, P < 0.001), progressive sperm motility (SMD: 4.28, 95% CI: 2.34–6.22, P < 0.001), and sperm morphology (SMD: 3.59, 95% CI: 2.27–4.92, P < 0.001). Total sperm motility showed no significant difference following varicocele repair (SMD: 0.81, 95% CI: −0.61–2.22, P = 0.26). No significant differences were seen in serum FSH (SMD: 0.01, 95% CI: −0.16–0.19, P = 0.87) and LH (SMD: 0.19, 95% CI: −0.01–0.40, P = 0.07) levels as well. This study supports varicocele repair in infertile men with clinical varicocele, as reflected by the improvement in sperm parameters after varicocelectomy compared with no treatment. There were no significant improvements in serum FSH and LH levels.
Keywords: male infertility, spermatozoa quality, varicocele
INTRODUCTION
Infertility is a widespread problem that affects approximately 16.7% of couples worldwide. Male factor infertility accounts for almost half of all infertility cases, and a significant cause of male infertility is azoospermia, which is defined as the absence of sperm in the semen.1 There are two types of azoospermia: obstructive and nonobstructive. Obstructive azoospermia occurs due to an obstruction in the reproductive tract preventing the passage of sperm, whereas nonobstructive azoospermia occurs due to a lack of sperm production or maturation.2
Varicocele is a condition characterized by the dilation of the veins within the scrotum, leading to a build-up of blood and increased pressure in the testicles.3 It is a common cause of azoospermia, as it is prevalent in 10.9% of azoospermia patients and contributes to 14.8% of male infertility.4 The pathophysiology of varicocele-induced infertility is thought to be caused by increased testicular temperature, hypoxia, oxidative stress, and hormonal changes. These factors would impair spermatogenesis and reduce the sperm quality.3 One of the preferred management strategies to alleviate this problem is varicocele repair, which is a surgical procedure aimed at correcting abnormalities in the veins of the scrotum.3 The most common method for varicocele repair is varicocelectomy, in which the affected veins are ligated or removed. The main goal of varicocele repair is to improve sperm parameters and increase the chances of natural conception.5
The efficacy of varicocele repair in improving sperm parameters in infertile men with oligospermia is well established.5 However, the efficacy of varicocele repair in men with azoospermia remains unclear. A systematic review and meta-analysis of studies investigating the outcome of varicocele repair in nonobstructive azoospermia men found that although varicocele repair significantly increased the sperm retrieval rate, there was no significant improvement in clinical pregnancy and live birth rates.6
To understand the impact of varicocele repair on fertility, this study aimed to investigate its impact on sperm parameters in infertile azoospermia men. To this end, we conducted a systematic review and meta-analysis according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.
PATIENTS AND METHODS
Following the aim of this study, the primary outcome of this study is the sperm parameters of azoospermia patients who underwent varicocele repair. These parameters included sperm concentration, progression, total motility, and morphology. The inclusion criterion for the patient group was any infertile man diagnosed with azoospermia (absence of viable or motile sperm in the semen). Meanwhile, the intervention was varicocelectomy, and the comparison included patients diagnosed with varicocele who did not undergo varicocele repair. Any data on hormonal medications taken by the control group would be noted, if mentioned.
Literature search was done in accordance with the PRISMA guidelines. The database search was conducted using five databases: Cochrane, Embase, PubMed, Scopus, and the Wiley Online Library. The keywords used in the search were “varicocele”, “varicocelectomy”, “azoospermia”, “sperm”, and “infertility”. The inclusion criteria for these studies were as follows: (1) comparison between patients who underwent varicocelectomy and those who did not; (2) semen analysis result consisting of at least one of the following: sperm concentration (× 106 ml−1), progression (%), total motility (%), and morphology (%); (3) language used was either English or Bahasa Indonesia; and (4) samples included were diagnosed with nonobstructive azoospermia. The exclusion criteria were as follows: (1) full-text unavailable, (2) review studies, or (3) studies without any null hypothesis analysis. Studies meeting the aforementioned criteria were included in the review.
Data extracted from these studies included descriptive statistics such as study design, intervention group sample size, control group sample size, varicocelectomy type, and timing of postsurgical sperm evaluation. Characteristics such as patient’s age, timing of evaluation, duration of fertility, and sperm recovery were also extracted. Regarding the primary outcome, the data extracted included whether sperm parameters were significantly affected by surgery. The extracted sperm parameters included sperm concentration, sperm progression, sperm total motility, and sperm morphology. The secondary outcome was whether varicocele repair has any significant impact toward serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels.
Statistical analyses were conducted using Review Manager version 5.3 (The Cochrane Collaboration 2014, Medan, Indonesia). The results were analyzed in the form of forest plots using a random-effects analysis model. Statistical significance would be reported using standardized mean difference (SMD) with 95% confidence interval (CI), along with a heterogeneity test using I2 statistics. Subgroup analysis was performed for varicocele grades. Funnel plots were used to determine publication bias. In addition to statistical analysis, quality assessment of each included study was conducted using two different tools: the Cochrane Risk of Bias for randomized controlled trials (RCTs) and the Cambridge Quality Checklists. Sensitivity analyses that included only studies with a low risk of bias and those with comparable confounding factors were performed to enhance the accuracy of our results. P < 0.05 was considered statistically significant.
RESULTS
After careful selection, nine studies7,8,9,10,11,12,13,14,15 were included in the analysis. The detailed process of the literature search is shown in Figure 1 and was conducted in accordance with PRISMA guidelines. Of the nine studies, six were observational and three were RCTs. The outcome measurement of sperm concentration was reported in seven included studies,8,9,10,11,12,13,15 four studies9,10,11,12 included parameters of sperm progression in sperm analysis, four studies7,8,13,15 measured total sperm motility, and eight studies7,8,9,10,11,12,14,15 analyzed the changes in sperm morphology (Table 1).
Figure 1.

The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram for literature search.
Table 1.
Characteristics of included studies
| Study | Study design | Varicoc- electomy (n) | Control (n) | Type of varicocelectomy | Age (year), mean±s.d. | Grade | Duration of infertility (year), mean±s.d. | Timing of evaluation (month) | Outcome | Sperm recovery | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
|
|
||||||||||||||||
| Spermatozoa concentration | Spermatozoa progression | Total spermatozoa motility | Spermatozoa morphology | FSH | LH | Control, n/total (%) | Varicoc- electomy, n/total (%) | OR (95% CI) | |||||||||
| Çakan et al.7 2008 | Observational (retrospective) | 29 | 23 | Spermatic vein ligation or embolization | Control: 25.4±4.8; treatment: 26.9±5.0 | Grade 1, 2, and 3 (clinical) | Control: 4.7±1.1; treatment: 5.2±1.2 | 12 | No | No | Yes | Yes | Yes | No | 0/23 (0) | 5/29 (17.8) | 10.55 (0.55–201.56) |
| Seo et al.8 2010 | Observational (retrospective) | 25 | 25 | Microsurgical | Control: 32.7±3.5; treatment: 32.1±2.1 | Grade 0 (subclinical) | Not mentioned | 6 | Yes | No | Yes | Yes | No | No | 3/16 (18) | 12/20 (60) | 6.5 (1.39–30.37) |
| Abdel-Meguid et al.9 2011 | RCT | 73 | 72 | Microsurgical | Control: 29.3±5.7; treatment: 28.4±5.7 | Grade 1, 2, and 3 (clinical) | Control: 1.5±0.4; treatment: 1.5±0.4 | 12 | Yes | Yes | No | Yes | No | No | 10/72 (13.8) | 24/73 (33) | 3.04 (1.33–6.95) |
| Ghanem et al.10 2011 | Observational (retrospective) | 59 | 27 | Antegrade scrotal sclerotherapy | Control: 33.6±61.7; treatment: 32.7±61.1 | Grade 1 and 2 (clinical) | Not mentioned | 6 | Yes | Yes | No | Yes | No | No | 0/27 (0) | 9/59 (15) | 10.35 (0.58–184.59) |
| Ghanaie et al.11 2012 | RCT | 68 | 68 | Non- microsurgical | Control: 36.8±4.6; treatment: 36.1±4.2 | Grade 1, 2, and 3 (clinical) | Control: 5.4±2.6; treatment: 5.6±2.8 | 12 | Yes | Yes | No | Yes | Yes | No | 13/68 (19) | 30/68 (44) | 3.34 (1.54–7.22) |
| Gokce et al.12 2013 | Observational (retrospective) | 168 | 138 | Microsurgical | Control: 34.4±4.1; treatment: 34.8±4.3 | Grade 1, 2, and 3 (clinical) | Not mentioned | 3 | Yes | Yes | No | Yes | No | No | 35/138 (25) | 105/168 (62.5) | 1.87 (1.18–2.96) |
| McGarry et al.13 2015 | Observational (retrospective) | 290 | 155 | Microsurgical | Control: 38±6; treatment: 35±4 | Grade 1, 2, and 3 (clinical) | Control: 3.25±2.7; treatment: 2.6±1.5 | 6 | Yes | No | Yes | No | Yes | Yes | 4/16 (25) | 12/23 (52) | 1.82 (0.49–6.68) |
| Ketabchi and Salajegheh14 2018 | RCT | 24 | 28 | Microsurgical | Control: mean 32; treatment: mean 33.4 | Grade 1, 2, and 3 (clinical) | Control: 7.6 (5–11); treatment: 6.5 (3–8) | 6 | No | No | No | Yes | No | No | 12/70 (17) | 30/70 (42) | 3.63 (1.66–7.93) |
| Turgut15 2020 | Observational (retrospective) | 52 | 36 | Microsurgical | Control: 29.6±3.9; treatment: 28.2±4.6 | Grade 1, 2, and 3 (clinical) | Not mentioned | 3 | Yes | No | Yes | Yes | Yes | Yes | 4/36 (11) | 20/52 (38) | 5.00 (1.54–16.27) |
FSH: follicle-stimulating hormone; LH: luteinizing hormone; RCT: randomized controlled trial; s.d.: standard deviation; CI: confidence interval; OR: odds ratio
The quality of the included studies was assessed using the Cochrane Risk of Bias for RCTs,16 and all three RCTs were deemed high-quality studies. The quality of the remaining six observational studies was assessed using the Cambridge Quality Checklist,17 in which two studies7,10 scored 11 out of 15, three studies8,12,13 scored 8–9, and one study15 scored 7 (Table 2). However, there was no established precise threshold for the total score to categorize high-and low-quality observational studies.
Table 2.
Quality assessment of included studies using Cochrane Risk of Bias for randomized controlled trial16 and Cambridge Quality Checklist17
| Study | Cochrane Risk of Bias for RCT16 | Cambridge Quality Checklist17 | |||
|---|---|---|---|---|---|
|
| |||||
| Correlates score (0–5) | Risk factor score (1–3) | Causal risk factor score (1–7) | Total score (2–15) | ||
| Çakan et al.7 2008 | Low quality | 3 | 2 | 6 | 11 |
| Seo et al.8 2010 | Low quality | 0 | 2 | 6 | 8 |
| Abdel-Meguid et al.9 2011 | High quality | - | - | - | - |
| Ghanem et al.10 2011 | Low quality | 2 | 3 | 6 | 11 |
| Ghanaie et al.11 2012 | High quality | - | - | - | - |
| Gokce et al.12 2013 | Low quality | 1 | 2 | 6 | 9 |
| McGarry et al.13 2015 | Low quality | 3 | 2 | 4 | 9 |
| Ketabchi and Salajegheh14 2018 | High quality | - | - | - | - |
| Turgut15 2020 | Low quality | 1 | 2 | 4 | 7 |
RCT: randomized controlled trial; -: not available.
Sperm concentration
Seven studies comprising a total of 1170 participants (692 participants who underwent varicocelectomy vs 478 controls) analyzed the sperm concentration parameters.8,9,10,11,12,13,15 These studies demonstrated substantial heterogeneity as shown by the I2 = 98%. The random-effects analysis model utilized showed a significant increase in sperm concentration in favor of varicocelectomy (SMD: 1.81, 95% CI: 0.84–2.77, P < 0.001; Figure 2a). Funnel plots were symmetrical, suggesting no publication bias.
Figure 2.
Forest plot and funnel plot of the spermatozoa parameters analysis in infertile participants with varicocele who underwent varicocelectomy compared to control (no treatment). (a) Spermatozoa concentration analysis. (b) Spermatozoa progression analysis. (c) Spermatozoa motility analysis. (d) Spermatozoa morphology analysis. s.d.: standard deviation; CI: confidence interval; IV: inverse variance; SMD: standardized mean difference; s.e.: standard error.
Sperm progression
Among the included studies, four studies9,10,11,12 assessed the effect of varicocelectomy on sperm progression as a parameter of sperm motility. Statistical analysis using a random-effects model was conducted on 368 participants who underwent varicocelectomy vs 305 controls indicated substantial heterogeneity (I2 = 99%). All the included studies concluded that the procedure significantly enhanced sperm progression, similar to the results of an RCT by Ghanaie et al.11 Additionally, the pooled analysis also indicates significant improvement in progressive sperm motility after varicocele repair (SMD: 4.28, 95% CI: 2.34–6.22, P < 0.001; Figure 2b). Funnel plots were symmetrical, suggesting no publication bias.
Total sperm motility
Statistical analysis using the random-effects model of four studies7,8,13,15 with a sample size of 634 participants (395 underwent varicocele repair vs 239 received no treatment) revealed no statistically significant changes with regard to total sperm motility after varicocelectomy (SMD: 0.81, 95% CI: −0.60–2.22, P = 0.26). Of the four studies, only one retrospective study by Seo et al.8 showed no improvement in total sperm motility after varicocelectomy. Two studies showed significant improvement, and one study showed a significant decline in sperm motility. Nevertheless, all studies have shown high interstudy heterogeneity (I2 = 97%; Figure 2c).7,13 Funnel plots were symmetrical; however, seven of the eight included studies were outside the triangle, suggesting a risk of publication bias.
Sperm morphology
Eight studies7,8,9,10,11,12,14,15 included normal sperm morphology as an outcome. The compiled population of these studies resulted in a comparison between 467 participants who underwent varicocelectomy and 407 participants who received no treatment (Figure 2d). Statistical analysis revealed a significant improvement in normal sperm morphology (SMD: 3.59, 95% CI: 2.27–4.92, P < 0.001). In addition, a significant heterogeneity between studies was found (I2 = 98%). Studies by Seo et al.,8 Ketabchi and Salajegheh,14 and Turgut15 showed no significant improvement in sperm morphology after varicocele treatment compared with no treatment. The remaining five studies demonstrated a significant increase in normal sperm morphology after the procedure. Funnel plots were symmetrical, suggesting no publication bias.
FSH
Four studies7,11,13,15 analyzed serum FSH levels in patients undergoing varicocele repair and the control group. If pooled, the total population of patients undergoing varicocele repair was 438, compared to 282 participants who underwent no treatment (Figure 3). Statistical analysis suggested no statistically significant difference in FSH levels between the two populations (SMD: 0.01, 95% CI: −0.16–0.19, P = 0.87). However, heterogeneity was still considered low (I2 = 13%). These findings are consistent with the results of the present study, in which none of the included studies showed significant differences. Funnel plots were symmetrical, suggesting no publication bias.
Figure 3.
Forest plot and funnel plot of FSH serum levels in participants receiving varicocelectomy compared to control. FSH: follicle-stimulating hormone; s.d.: standard deviation; CI: confidence interval; IV: inverse variance; SMD: standardized mean difference; s.e.: standard error.
LH
Only two studies13,15 measured serum LH levels in patients who underwent varicocele repair and in the control group. A total of 342 participants were included in the intervention group and 191 participants were in the control group (Figure 4). On forest plot analysis, no statistically significant difference was found with regard to LH levels (SMD: 0.19, 95% CI: −0.01–0.40, P = 0.07). Similar to FSH level analysis, heterogeneity between included studies was low (I2 = 13%). Individually, neither study showed significant differences between the two groups. Funnel plots were symmetrical, suggesting no publication bias.
Figure 4.
Forest plot and funnel plot of LH serum levels in participants receiving varicocelectomy compared to control. LH: luteinizing hormone; s.d.: standard deviation; CI: confidence interval; IV: inverse variance; SMD: standardized mean difference; s.e.: standard error.
Subgroup analysis
A subgroup analysis was performed to address varicocele grading as a confounding factor. Out of the nine included studies, eight articles could be grouped into the clinical grade group (consisting of varicocele grades 1, 2, and 3, which present clinical manifestations) and the subclinical grade group (grade 0 or only visible on testicular Doppler ultrasound), as presented in Table 1. Seo et al.8 (the only study in the subclinical grade group) reported only three outcomes of interest: sperm concentration, motility, and morphology. Interestingly, the analyses of the subclinical subgroups showed no significant difference in sperm concentration (SMD: 0.20, 95% CI: −0.36–0.75; P = 0.44), total motility (SMD: −0.54, 95% CI: −1.10–0.03; P = 0.06), and morphology (SMD: −0.17, 95% CI: −0.72–0.39; P = 0.55). In terms of sperm concentration and morphology, this was in contrast to the results in the clinical subgroups (Figure 2).
Sensitivity analysis
Sensitivity analysis was performed to omit potential confounding variables that might influence the results of the study. After selection of potential confounding variables, we identified 2 variables that affected the differences in results if the involved article was omitted, namely, shorter timing of follow-up and lower score of quality of article or higher risk of bias. One article satisfied both reasons15 and we decided to conduct a sensitivity analysis. There were no significant differences in several outcomes, with only a slight difference in SMD for all outcomes. The forest plot for sensitivity analysis was not shown; however, it is accessible upon request.
DISCUSSION
In men with azoospermia with varicocele (4.3%–13.3% of the cases), the role of varicocelectomy has been an interesting issue for debate.18 The potential reversibility of impaired spermatogenesis due to varicocele pathophysiology may serve as a basis for intervention.19,20 A previous study has postulated that varicocelectomy may help male patients with infertility with azoospermia by inducing spermatogenesis and improving the rates of spontaneous pregnancy and sperm retrieval.20 However, the recommendation for varicocelectomy within the current guidelines for patients with azoospermia has not been clearly elucidated, and the supporting evidence is barely consistent.20 Hence, this study aimed to conduct a meta-analysis of the currently published literature focusing on the specific outcomes of sperm parameters and serum levels of FSH and LH postvaricocelectomy of current published studies, specifically in men with azoospermia.
Our meta-analysis reported improvements in three aspects of sperm quality: sperm concentration (SMD: 1.81, P < 0.001), progressive sperm motility (SMD: 4.28, P < 0.001), and sperm morphology (SMD: 3.59, P < 0.001). Only total sperm motility showed no significant difference in improvement following varicocele repair (SMD: 0.81, P = 0.26). Despite no improvements in total motility, several studies included in this review support our hypothesis that higher sperm quality is achieved following varicocele repair. In accordance with the literature, no significant differences in serum FSH (SMD: 0.01, 95% CI: −0.16–0.19, P = 0.87) and LH (SMD: 0.19, 95% CI: −0.01–0.40, P = 0.07) levels were reported after intervention.
Understanding the pathophysiology of varicocele-related infertility is fundamental to elucidating the role of varicocelectomy in azoospermia.19,21 Generally, the major harmful effect of varicoceles is elevated temperatures due to the turbulence of blood flow caused by dilated scrotal veins.19 A higher scrotal temperature more than 2°C is associated with decrease in sperm count and quality, believed to be caused by DNA and protein damage within the nucleus of spermatic tubule cells and/or Leydig from the thermal injury.21,22 Varicocelectomy plays a major role in correcting scrotal temperature by removing dilated scrotal veins.18,23 A more elaborate explanation of how the mechanism occurs and whether the reversibility of spermatogenesis is sustainable requires histopathological and in vivo investigation, something that is currently unavailable.18
A study has reported improvements in the sperm parameters after varicocelectomy in patients with azoospermia.24 The first to note the effect of varicocele repair was reported by Tulloch,24 in which the couple had a spontaneous postvaricocelectomy pregnancy. Following that, many single-arm studies have been conducted to evaluate improvements in sperm parameters after treatment.20,25,26,27,28,29 These studies reported about 21%–56% of motile sperm postvaricocelectomy (indicating sperm recovery) and 0–15% had spontaneous pregnancy. These data are in accordance with the results reported in our included studies where approximately 15%–62.5% sperm recovery was found. As opposed to the one-armed studies, our included controlled studies benefit from a perspective where the possibility of spontaneous return of sperm in the ejaculate of men with azoospermia exists; thus, a control group is necessary to make a comparison with the varicocelectomy/intervention group.30 This is supported by the data found in our study, where approximately 0–19% had spontaneous sperm return upon follow-up without any intervention. It should be noted that none of the studies regarded hormonal medications as one of the inclusion and/or exclusion criteria; thus, no data on hormone/supplement consumption are mentioned within the publication and still serve as a potential confounding factor. A similar meta-analysis was performed on nonobstructive azoospermia postvaricocelectomy and/or embolization by Weedin et al.31 The meta-analysis reported a recovery of sperm density (mean±standard deviation [s.d.]: 1.6 × 106 ± 1.2 × 106 ml−1) and motility (mean ± s.d.: 20.1% ± 18.5%), respectively, which is comparable to our study.31 Another meta-analysis 32 reported an average of 27.3% spermatogenesis rate postsurgery and a mean increased rate of motility of 29% (range: 8%–55%). Similar to our study, their meta-analysis also included more non-RCTs that were small and retrospective. We found only 3 RCTs that are prospective, one with a small number of participants.14 Future prospective RCTs should be conducted with larger numbers of participants.
In contrast to our study, a recent meta-analysis evaluated sperm retrieval.32 A notable finding of that study was the relapse of azoospermia and the histopathological evaluation. Long-term follow-up conducted in the study showed that in the three included studies, approximately 20.8% experienced recurrence of azoospermia. The study also noted that from their histopathological findings, there is a higher probability of the successful induction of spermatogenesis in men with late maturation arrest or hypospermatogenesis in comparison with Sertoli cell-only pattern (42.1% or 54.5% compared to 11.3% of pregnancy rate, respectively).32
With regard to FSH and LH levels, an older systematic review and meta-analysis arrived at a conclusion different from our findings.33 They reported a significant difference of FSH (mean difference [MD]: 0.48, 95% CI: 0.19–0.77, P = 0.001) and LH (MD: 0.58, 95% CI: 0.25–0.91, P = 0.0005) levels, where both parameters’ means were significantly lowered by varicocele repair. This was hypothesized to be caused by the restoration of Leydig function. However, the authors were not confident in their conclusions due to the lack of a large-scale multicenter randomized trial. Additionally, despite the statistically significant difference, the clinical significance of such changes is questionable, as the difference in serum levels was only slight, which is similar to our findings.33 The theory that varicoceles may disrupt the hypothalamic–pituitary–gonadal axis due to Leydig cell injury remains debatable. Our study supports the notion that varicocelectomy in varicocele patients with azoospermia should not show any hormonal effects.19
We conducted a subgroup analysis based on the varicocele grade, dividing the patients into subgroups of subclinical and clinical varicoceles. No significant changes were observed. However, we should carefully consider this information, as only one of the included studies investigated subclinical varicoceles. We suggest that future investigations on subclinical varicocele in men with azoospermia should be conducted to draw conclusions.
Our study provides evidence that varicocelectomy improves sperm quality in infertile men with varicoceles. The current meta-analysis had several limitations. First, only a few RCTs were included in the statistical analysis. Second, high interstudy heterogeneity was found in all analyzed sperm parameters, supported by publication bias in a few of the pooled analyses shown by the funnel plot. Third, the meta-analysis included observational studies with low-quality scores, indicating some concern (Table 2). However, we attempted to compensate for this by omitting the study using a sensitivity analysis, and no significant differences were found. Fourth, one of the major limitations of our study was that we did not include an analysis of pregnancy rates and histopathological changes within the studies. Insufficient data were available, making it impossible to determine the pregnancy and live birth rates reported in this study. Insufficient published data on histopathological reports within the included studies were the reason why no histopathological analysis or subgroup analysis could be performed.
This systematic review of controlled studies provides insight that varicocelectomy (microsurgical, nonmicrosurgical, ligation, and sclerotherapy) significantly improves sperm quality, as reflected by significant improvements in sperm parameters (concentration, progressive motility, and normal morphology). However, there were no significant changes toward serum FSH and LH levels. This study compared changes in outcomes after varicocelectomy to control groups that received no treatment for clinical varicocele in infertile male participants. Sperm parameters were analyzed during the same period. Thus, our study provides evidence and may strengthen the currently available evidence to establish further guidelines regarding the management of varicocele in infertile men by favoring varicocelectomy to improve sperm quality.
CONCLUSION
Our study revealed that varicocelectomy, regardless of the specific surgical method used, notably enhanced sperm quality. This improvement is evident through significant enhancements in critical sperm parameters such as sperm concentration, progressive motility, and normal sperm morphology. However, it is important to note that varicocelectomy does not appear to significantly affect the FSH and LH levels in the bloodstream.
AUTHOR CONTRIBUTIONS
RR and SMW conceived and drafted the manuscript. GPS and FFP performed statistical analyses. DDK and MRZT participated in the study design and coordination and helped draft the manuscript. All authors read and approved the final manuscript.
COMPETING INTERESTS
All authors declare no competing interests.
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