Varicocelectomy in men with varicocele-associated infertility: a narrative review of semen quality and reproductive outcomes

Introduction

Infertility affects roughly 8–12% of couples worldwide. Male factors contribute to about half of these cases (1). A varicocele is an abnormal enlargement of the pampiniform venous plexus, the network responsible for testicular blood drainage. While often painless, this condition holds major clinical weight. It is the leading cause of abnormal semen parameters—such as low sperm count, poor motility, and altered morphology (2)—and stands as the most common surgically reversible cause of male infertility. Clinicians observe varicoceles in up to 40% of men evaluated for infertility and in about 15% of the general male population (3).

Current international guidelines base diagnosis and grading on the couple’s medical history combined with a physical exam. The standard grading scale includes four levels: subclinical (detectable only by ultrasound), grade I (palpable during the Valsalva maneuver), grade II (palpable at rest), and grade III (visible through the scrotal skin) (4). According to the European Association of Urology (EAU) guidelines, when a physical examination is inconclusive, scrotal Doppler ultrasound is indicated. A clinically significant varicocele is radiologically defined by a maximum venous diameter exceeding 3 mm in the upright position, coupled with venous reflux lasting longer than two seconds during the Valsalva maneuver (5).

The exact mechanisms disrupting sperm production, structure, and function remain partially unclear, though researchers point to several primary drivers. These include the overproduction of reactive oxygen species (ROS), sperm DNA fragmentation (SDF), elevated scrotal temperatures, and depleted antioxidant reserves. Together, these factors impair spermatogenesis, degrade both sperm quantity and quality, and sometimes trigger testicular pain (6).

Treatment options for infertile men range from open surgery and laparoscopy to radiological embolization (7). Medical consensus supports varicocelectomy as an effective intervention to improve fertility outcomes (8). Recent systematic reviews and meta-analyses have provided valuable quantitative data, consistently confirming that surgical repair improves both semen parameters and male fertility (9-12). For instance, a comprehensive analysis by Xiao et al. demonstrated an overall surgical efficacy rate of approximately 63% regarding semen improvement following varicocelectomy (12). Surgeons utilize several techniques, such as open retroperitoneal or inguinal ligation, laparoscopy, and microsurgical inguinal or subinguinal approaches (13). Most urologists prefer microsurgical varicocelectomy. It carries a lower risk of complications and recurrences while offering strong potential for semen parameter recovery (14).

While existing meta-analyses provide valuable statistical data, they focus strictly on numbers which often results in missing the broader clinical picture, how initial improvements in semen quality lead to final pregnancy outcomes.

Traditional systematic reviews often include only very specific groups of patients, which limits the number of studies analyzed and provides a narrower view of the clinical situation. Given these limitations, we chose a narrative review format. Unlike previous reviews that primarily summarize standard semen parameters, the analytical framework of this narrative review is built upon bridging the clinical outcomes of diverse surgical approaches with microscopic and molecular advancements. This approach allows us to include a wider range of evidence and combine surgical outcomes, molecular mechanisms, and current clinical guidelines into one comprehensive overview.

Furthermore, to provide a complete comparison of surgical methods, this review also evaluates safety endpoints and morbidity, focusing on varicocele recurrence, postoperative hydrocele formation, testicular atrophy, and chronic pain.

Taking the above into consideration, the aim of this review is to narratively synthesize the current medical literature to answer how contemporary varicocele treatments improve conventional and molecular semen parameters, impact overall reproductive success, and how different surgical methods compare in terms of both their therapeutic efficacy and their comprehensive safety profiles. We present this article in accordance with the Narrative Review reporting checklist (available at https://tau.amegroups.com/article/view/10.21037/tau-2026-0189/rc).

Methods

Search strategy

A comprehensive literature search was conducted across the PubMed and Embase databases to identify relevant clinical studies evaluating the impact of varicocelectomy on male fertility. The search algorithm utilized the following keywords and Boolean operators: “(varicocelectomy) AND (semen parameters OR sperm quality OR semen analysis) AND varicocele” (Table 1).

To ensure the clinical relevance of our core findings, the time range was restricted to publications released from January 2010 to April 2026. The cutoff year of 2010 was deliberately chosen for two primary reasons: firstly, to align with the publication of the 5th edition of the World Health Organization (WHO) manual for the examination and processing of human semen, and secondly, to reflect the contemporary era of refined microsurgical and laparoscopic techniques.

While this study is structured as a narrative review to provide a broad clinical perspective, we adopted a methodical search approach for the primary clinical trials to minimize selection bias. Furthermore, to provide a comprehensive theoretical background, deeper understanding of the topic and clinical context, additional literature was included. These supplementary papers were identified using similar keywords but without applying the strict inclusion filters. Additionally, a manual search of the reference lists of the initially included articles was performed to ensure no highly relevant contextual papers were missed.

Eligibility criteria

To ensure the included studies were comparable, inclusion and exclusion criteria were applied:

Inclusion criteria were: (I) English-language clinical trials published since 2010; (II) adult male patients diagnosed with clinical varicoceles who underwent surgical varicocelectomy; and (III) availability of quantitative postoperative efficacy data (such as conventional semen parameters, pregnancy/live birth rates, or specific surgical complications) suitable for comparison.

Exclusion criteria were: (I) animal or in vitro studies; (II) cohorts managed conservatively or via non-surgical interventions; (III) lack of relevant pre- and post-operative clinical outcome data; (IV) restricted access to the full text; (V) non-English publications; (VI) studies that did not focus solely on the surgical procedure itself (e.g., those involving postoperative supplementation).

Study selection and data extraction

The initial database search yielded a total of 2,005 results (711 in PubMed; 1,294 in Embase). Limiting the publication date to 2010 onwards reduced the pool to 1,573 records. Restricting the publication type strictly to clinical trials left 77 potentially relevant articles. After applying the language filter (English only), 71 full-text articles (48 from PubMed; 23 from Embase) were assessed for eligibility.

Quality assessment

We assessed the quality of the included studies by focusing on key methodological aspects. Since this is a narrative review, we did not use formal scoring systems or software, opting instead for a qualitative evaluation of the evidence. We looked at study designs [prioritizing randomized controlled trials (RCTs) and prospective trials], follow-up durations, and the clarity of outcome reporting. We prioritized studies with complete postoperative data, actively minimizing the inclusion of those with obvious selection bias. While a formal risk-of-bias tool was not used, this qualitative approach allowed us to identify the most reliable evidence available and provided a better context for the results than a purely numerical appraisal.

Ultimately, 24 core clinical trials met all inclusion criteria and were incorporated into the final synthesis. This number refers to the primary trials used to evaluate direct surgical outcomes. We also cited additional supporting literature throughout the manuscript to build a solid theoretical background and discuss broader clinical contexts, which explains the larger number of total references in our final bibliography.

Results

Key findings

Table 2 provides a summary of the 24 main publications included in this review. To ensure optimal clarity and comparability, the table details the first author and year of publication, country of origin, study design, number of participants, key results, and main conclusions. This table provides a concise comparative overview of the included studies and helps illustrate how evidence on surgical management has evolved over time.

Impact of the procedure on basic semen parameters

Basic semen parameters are the primary clinical indicators of surgical efficacy. To ensure clarity, these results are summarized in Table 3.

The analysis of the compiled studies indicates that the surgical treatment of varicoceles leads to a statistically significant improvement in key semen parameters, particularly sperm concentration and motility. The best therapeutic outcomes were achieved using microsurgical techniques, which demonstrated superiority over laparoscopic and open methods, especially regarding improvements in morphology and efficacy in cases of severe oligozoospermia. Positive changes in the spermogram can be observed as early as 3 months post-procedure and are sustained throughout long-term, 12-month follow-up.

Impact of varicocelectomy on molecular and metabolic parameters of semen

Nuclear chromatin condensation

One of the significant processes determining the quality of the male gamete is nuclear chromatin condensation. It involves the replacement of histones with protamines, which ensures the tight packaging of DNA (39).

Disruptions of this mechanism can lead to the formation of immature spermatozoa with a reduced fertilization capacity. To evaluate this phenomenon, aniline blue staining is utilized, among other methods, which allows for the identification of immature spermatozoa containing retained histones (39).

Sadek et al. demonstrated that chromatin quality undergoes significant improvement following the procedure (16). The total stained score of spermatozoa, indicative of abnormal condensation, decreased from an average of 65.15%±20.97% preoperatively to 51.9%±15.2% at the 3rd month post-procedure. Simultaneously, a statistically significant increase in the percentage of spermatozoa with normal condensation (unstained sperms) was recorded, from 54.3%±11.04% to 62.3%±9.9%. It should be noted that the dynamics of this improvement depended on the stage of the disease. In the group with grade II varicocele, the reduction in the percentage of stained heads from 65.27%±17.60% to 54.0%±16.92% did not achieve statistical significance (P=0.084). Conversely, at the grade III stage, the improvement was statistically significant, with the percentage of stained heads decreasing from 61.77%±16.89% to 49.33%±13.32% (P=0.043).

DNA fragmentation

SDF, defined as the percentage of spermatozoa with denatured DNA, constitutes a significant parameter that may contribute to male subfertility (40). The DNA fragmentation rate (SDF), determined using the DNA Fragmentation Index (DFI), is a parameter more frequently elevated in the group of men with fertility disorders compared to the control group (41).

A study conducted by Fathi et al. demonstrated a significant improvement in this parameter, observing a decrease in SDF from 34.93%±5.56% preoperatively to 25.75%±5.15% at the 6th month post-procedure (P<0.001) (30). For comparison, in the control (observation) group, this level changed only slightly, decreasing from 35.33%±6.12% to 31.26%±5.34%.

Kavoussi et al. observed a similar effect, noting a pronounced reduction in DNA fragmentation—a decrease in SDF from 32.39% to 18.36% (95% CI for the difference: −18.07 to −9.99; P=0.001) (31). It is also worth noting that these parameters improved even in groups exposed to additional oxidative stress (OS), e.g., in smokers, where SDF dropped from 30.8% to 16.5% despite the continuation of the addiction.

In another study comparing bilateral to unilateral surgery (with subclinical right-sided lesions), Sun et al. demonstrated that a significant decrease in DNA fragmentation occurs in both cases: from 21.6%±7.1% to 11.8%±6.0% in the bilateral group, and from 23.0%±8.1% to 12.1%±6.8% in the unilateral group (17). In contrast to general parameters (count, motility), where bilateral surgery was superior, in terms of DNA protection, both methods were equally effective, and the differences between the groups were statistically insignificant.

The aforementioned studies and their results allow for the conclusion that varicocelectomy effectively reduces sperm DNA damage, which contributes to increased fertility.

OS and oxidation-reduction potential (sORP)

OS has been recognized as one of the leading etiological factors in male infertility. The source of OS in semen is the excessive production of ROS (42). Disruptions in integrity and sperm DNA damage induced by OS demonstrate an association with abnormal embryonic development, the occurrence of miscarriages, and infertility (43).

A study by Kavoussi et al. demonstrated that preoperatively, the mean level of sORP was 3.56 mV/10⁶ sperm/mL (31). At 3 months post-procedure, this value decreased significantly to 1.29 mV/10⁶ sperm/mL (P=0.001). Statistical analysis revealed that the 95% confidence interval for the reduction of OS ranges from 0.75 to 3.78 mV, proving that varicocelectomy can effectively restore the oxidative balance within the testicular environment.

Metabolic profile

Although metabolomics finds application in the diagnostics of male infertility, there has been a lack of studies to date utilizing this technique to assess changes in semen parameters following a microsurgical procedure (44). In light of the above, Zhang et al. attempted to elucidate the mechanisms underlying the improvement of semen quality following microsurgical varicocelectomy at the metabolic level (29). It was found that varicoceles disrupt sperm metabolism, and surgery effectively reverses these alterations, leading to the upregulation of glycerophospholipid and sphingolipid pathways. The regeneration of cell membrane components explains the clinically observed improvement in morphology (an increase in the percentage of normal forms from 2.00% to 3.98%) and the reduction in sperm apoptosis (a decrease in DFI from 19.33% to 14.16%). Additionally, a statistically significant increase in the level of the dipeptidase 3 (DPEP3) enzyme post-procedure was identified (P<0.05), which constitutes molecular confirmation of the restoration of normal biochemical testicular functions and metabolic homeostasis.

Impact of varicocelectomy on the spontaneous pregnancy rate, live birth rate, and the risk of miscarriages

The ultimate goal of treating male infertility associated with varicoceles is achieving pregnancy and the birth of a healthy child. The analysis of the studies included in the review provides evidence that surgical intervention increases the chances of both natural conception and carrying a pregnancy to term.

Effectiveness of surgical treatment compared to observation

In an RCT involving 145 patients, Abdel-Meguid et al. demonstrated that one year after microsurgical subinguinal varicocelectomy (MSV), the spontaneous pregnancy rate was 32.9%, whereas in the observation-only group, it reached merely 13.9% (P=0.01) (18). Consequently, the probability of achieving pregnancy was more than three times higher [odds ratio (OR) =3.04].

Factors determining success: technique, extent of the procedure, and patient characteristics

The type of surgical technique significantly affects fertility, as Abdel-Maguid and Othman demonstrated that MSV is more effective than non-magnified subinguinal varicocelectomy (NMSV) (19). After 12 months of observation, the pregnancy rates in the microsurgical and conventional surgery groups were 37.8% and 21.2%, respectively (P=0.021). Regarding the comparison between microsurgical and laparoscopic techniques, a higher pregnancy rate (40.5%) is achieved with the microsurgical technique compared to the laparoscopic one (29.7%), which is confirmed by a Polish study by Bryniarski et al. from 2017 (22). In a study by Fayez et al., the one-year pregnancy rates for open, scrotal, and subinguinal sclerotherapy were 20%, 13.73%, and 12.24%, respectively, but these differences are not statistically significant (28). In a prospective RCT conducted in 2023 in Nigeria, Okeke et al. compared the pregnancy rates among partners of patients who underwent loupe-assisted subinguinal varicocelectomy (LASV) and open subinguinal varicocelectomy without magnification (OSV) after a six-month follow-up period (20). Their results indicate an identical pregnancy rate of 4.3% among both patients whose partners underwent LASV and OSV. It should be noted that these results are not statistically significant due to the short observation period.

The extent of the surgery is also significant—in patients presenting with clinical left-sided varicoceles and subclinical right-sided varicoceles, performing a bilateral varicocelectomy results in an almost twofold increase in the pregnancy rate compared to a procedure limited only to the left spermatic cord. This is corroborated by the results of a study by Sun et al. (42% for bilateral and 26% for unilateral varicocelectomy in patients with bilateral varicoceles, P=0.002) (17).

In the age groups of ≤30 and >30 years, the spontaneous pregnancy rates among women whose partners underwent varicocelectomy were 51.1% for the younger group and 44.7% for the older group, respectively; however, with a 90% probability, these differences are not statistically significant [Yazdani et al. 2015 (25)].

The microsurgical varicocelectomy procedure, even in patients with severe oligozoospermia, provides the possibility of achieving natural pregnancy—Vu Tan et al. demonstrated that it resulted in pregnancy in 48% of partners of men with an ejaculate sperm concentration of <5 million/mL within the first 6 months post-procedure, and in 52% within the subsequent six months (15). The results described in this study suggest that this procedure can effectively replace assisted reproductive technologies, even in patients with a very low baseline sperm count in the ejaculate.

A pilot study by Fathi et al. involved 85 infertile men with normal semen parameters but high DNA fragmentation (30). Twelve months after microsurgical varicocelectomy, spontaneous pregnancy was achieved in 62.2% of couples where the men underwent the procedure, whereas it was achieved in only 30% of the control group (P=0.009).

Impact of varicocelectomy on the risk of miscarriages

The surgical procedure also effectively prevents pregnancy loss, which is confirmed by a randomized clinical trial conducted by Mansour Ghanaie et al., which included couples experiencing recurrent first-trimester miscarriages (26). The study enrolled 136 women with recurrent miscarriages. Their partners had normal semen quality parameters and clinically confirmed varicoceles. Each of the men was assigned to one of two numerically equal groups, where they either underwent a varicocelectomy or were subjected to expectant management. Miscarriage occurred in only 13.3% of couples where the men underwent bilateral varicocelectomy, whereas it occurred in a striking 69.2% of partners of men treated expectantly (P=0.001).

Impact of varicocelectomy on live birth rates

As live birth is the ultimate goal of varicocele treatment, a structured summary of live birth rates reported in the selected comparative studies is presented in Table 4.

Comparative analysis of surgical techniques in varicocele treatment

Comparison of microsurgical techniques [MSV, microsurgical retroperitoneal varicocelectomy (MRV)] and conventional/laparoscopic techniques (NMSV, OSV, Palomo, LSV)

In their study comparing MSV with the open technique without magnification (NMSV), Abdel-Maguid and Othman demonstrated a statistically significant superiority of the microsurgical method (19). The authors observed that one year post-procedure, an increase in sperm count of at least 50% occurred in 42.7% of patients in the MSV group, whereas in the NMSV group, such an improvement was recorded in only 23.7% of the subjects (P<0.05). Similarly, a significant increase in sperm motility was noted in 67.1% of patients in the microsurgical group compared to 33.8% in the conventional group (P<0.05). This translated to a higher pregnancy rate (37.8% vs. 21.2%; P<0.05) and a significantly more favorable safety profile. In the MSV group, no recurrences were recorded (0% vs. 11.3% in NMSV; P<0.05), and the rate of hydrocele was substantially lower (1.2% vs. 8.7%; P<0.05).

The advantages of the microsurgical approach are also corroborated by the studies of Pajovic et al., who compared three techniques: microsurgical (MSV), laparoscopic [laparoscopic subinguinal varicocelectomy (LSV)], and open (Palomo method) (21). Their analysis revealed that the greatest mean increase in progressive motility (+11.91 percentage points) and sperm count (+8.95 million/mL) occurred following the microsurgical procedure. For comparison, in the laparoscopic technique (LSV), the mean increase in progressive motility was +4.47 percentage points, and in sperm count, +8.11 million/mL. In the open technique (Palomo), an increase in motility of +6.25 percentage points and the smallest improvement in sperm count (+2.60 million/mL) were recorded. The differences in semen parameters between the MSV group and the others were statistically significant (P<0.05). Furthermore, in terms of complications, the MSV technique was distinguished by the complete absence of hydrocele (0%) and the lowest recurrence rate (2.85%). By comparison, in the laparoscopic group (LSV), 8.5% hydroceles and 14.2% recurrences were recorded, while after the Palomo procedure, these complications occurred in 5.2% and 17.1% of patients, respectively.

Interesting data is provided by a study by Bryniarski et al., who directly compared the laparoscopic technique with the microsurgical one by monitoring semen parameters at the 3rd, 6th, and 12th months post-procedure (22). The authors observed an improvement in all semen parameters in both groups at all time points compared to baseline values. It should be noted that at the 3rd month, the differences between the two methods were not yet statistically significant, which changed over time. Already after 6 months, the median percentage of spermatozoa with normal morphology was significantly higher in the microsurgical group (9% vs. 6.7%; P=0.01). After 12 months, these differences deepened, demonstrating a significant superiority of microsurgery in terms of both the median progressive motility (34.5% vs. 29.9%; P=0.03) and morphology (9.4% vs. 6.8%; P=0.01).

However, for several other clinical and seminal variables—including pregnancy rates—the differences between the groups did not reach statistical significance (P>0.05). Significant differences returned in the analysis of surgical complications: in the laparoscopic group, 13.5% cases of hydrocele were recorded, whereas this complication did not occur in patients operated on microsurgically (P=0.02).

In conclusion, microsurgical techniques offer better outcomes in terms of semen parameters and a lower risk of complications compared to laparoscopic and open methods.

Significance of the extent of surgery: bilateral versus unilateral approach

In the presence of subclinical lesions on the contralateral side, the decision regarding the extent of the procedure may seem ambiguous. An attempt to resolve this dilemma was undertaken by Sun et al., who verified whether bilateral intervention provides additional benefits (17). One year post-procedure, the researchers observed that the bilateral approach resulted in a significantly greater increase in sperm concentration (+19.00 vs. +11.1 million/mL; P=0.041) and a better improvement in progressive motility (an increase of 17% vs. 11.7%; P=0.041) compared to the unilateral procedure. The key conclusion from this study is the fact that the spontaneous pregnancy rate was significantly higher following bilateral varicocelectomy (42.5%) than after unilateral varicocelectomy (26.0%; P=0.002), which suggests a higher therapeutic efficacy of a broader extent of intervention.

The role of optical magnification and alternative methods

In addition to full microsurgery, intermediate techniques are also employed in clinical practice. Okeke et al. analyzed the efficacy of LASV compared to the open method without magnification (OSV) (20). Although the differences in the improvement of semen parameters between the groups did not reach statistical significance, the key difference lay in complications, which occurred exclusively in the OSV group (in 30.4% of patients). In this group, the following were recorded: scrotal hematoma in 1 patient (4.3%), testicular atrophy in 2 patients (8.7%), hydrocele in 2 patients (8.7%), and varicocele recurrence in 2 patients (8.7%). In the group operated on with the use of loupes (LASV), no complications were recorded.

Conversely, Fayez et al. compared the classic open technique (Ivanissevich) with two methods of antegrade sclerotherapy: scrotal (Tauber) and subinguinal (28). Although the increase in sperm count was greatest following open surgery (achieving a significant advantage over the Tauber method at the 9th and 12th months of follow-up), subinguinal sclerotherapy stood out with the best safety profile. Despite recording some adverse events (including cases of mild fever in 4.1% or pain in 2%), it was distinguished by a zero percent rate of hydrocele and hematoma (0%). By comparison, in the Ivanissevich group, hydrocele occurred in 5.5% of patients (n=3), and hematoma also in 5.5% (n=3). In the Tauber group, hematoma occurred in 9.8% of the subjects (n=5). These results suggest that subinguinal sclerotherapy may be an attractive alternative to traditional open methods due to the minimization of the risk of severe complications.

Comparison of surgical access routes

The choice of the optimal access route (inguinal, subinguinal, retroperitoneal) affects treatment outcomes, although primarily in terms of safety rather than efficacy.

Zhang et al. compared the microsurgical variants: retroperitoneal (MRV) and subinguinal (MSV) (27). Both methods yielded a significant improvement in semen parameters relative to baseline values (P<0.01). One year post-procedure, the mean concentration in both groups was comparable (approx. 27 million/mL), as was sperm motility (approx. 40%), and a direct comparison revealed no statistically significant differences (P>0.05). The key differences pertained to surgical complications (P<0.01). No complications were recorded in the MRV group (0%), whereas they were frequent in the MSV group: scrotal edema occurred in 42.1% of patients, spermatic cord congestion in 57.9%, and testicular congestion in 31.6%.

In the context of microsurgical techniques, Pan et al. compared the inguinal [microsurgical inguinal varicocelectomy (MIV)] and subinguinal (MSV) approaches (24). Here, too, both methods proved equally clinically effective—after one year, no significant differences were demonstrated in the spontaneous pregnancy rate or the degree of improvement in semen parameters (P>0.05). A significant difference was noted, in postoperative comfort. Patients operated on via the inguinal approach required analgesics significantly more often on the first postoperative day (57.6% vs. 37.5%; P<0.05), which is associated with the necessity of incising the external oblique muscle aponeurosis in the MIV technique. This suggests that with similar efficacy, the subinguinal approach is associated with less pain.

Conversely, the analysis by Sun et al. encompassed classic techniques: open inguinal, retroperitoneal, and laparoscopic (23). All three methods confirmed their efficacy, yielding an increase in sperm concentration (by an average of 11–13 million/mL) and motility (by 12–16 percentage points), with the differences in the degree of improvement between the techniques not being statistically significant (P>0.05). Significant differences were observed in the recurrence rates. The laparoscopic technique was associated with the lowest risk (1.96%), whereas this rate was higher in open methods: 11.76% for retroperitoneal access and 13.73% for inguinal access (a significant difference in favor of laparoscopy). No postoperative hydrocele or testicular atrophy was recorded in any of the studied groups.

Safety profile and postoperative complications of varicocelectomy techniques

The selection of a surgical approach has a direct impact on the patient’s risk of postoperative complications. MSV clearly stands out regarding its safety profile. While numerous studies reported zero incidence of hydrocele or recurrence for MSV, open and laparoscopic techniques showed recurrence rates as high as 17.14%. Additionally, other adverse events, such as testicular atrophy, scrotal edema, and hematoma, often occurred with greater frequency in those groups. A detailed breakdown of postoperative complications across the analyzed studies is presented in Table 5.

Discussion

Varicocelectomy is widely recognized as the most effective method of treating infertility-associated varicoceles (2,12). Various surgical techniques are employed in clinical practice, which include: classic methods of open vein ligation and sclerotherapy, as well as methods utilizing optical magnification, such as laparoscopy and microsurgery (18,23). An analysis of the available literature indicates that the application of almost any of these techniques translates into an improvement in semen parameters (15,19,21-23,28). The most pronounced increase is typically recorded in terms of sperm concentration and motility. Conversely, the impact on their morphology is sometimes less favorable or requires a longer observation period (15,17,25,27,29,31). However, when selecting the optimal therapeutic pathway, it is essential to consider not only the efficacy itself in improving semen parameters but also the safety profile and the risk of postoperative complications, which differ depending on the method (19,20-22,28).

Analysis of the gathered clinical evidence indicates that the choice of surgical approach has a direct impact on the patient’s safety profile. MSV clearly emerges as the gold standard with the highest degree of safety, as corroborated by numerous studies demonstrating zero incidence of hydrocele and a complete lack of recurrence.

A key point of controversy in the literature is the significant heterogeneity of outcomes regarding hydrocele formation, which results from lymphatic vessel injury. In studies utilizing laparoscopic techniques (LSV) or classic open approaches (Palomo, OSV), this rate ranges from 5.2% to as high as 28.6%. Such high rates, as reported by Okeke et al. (20) and Pajovic et al. (21), contrast sharply with MSV outcomes, where this complication is frequently not recorded at all (15,18,22,37).

The likely cause of this discrepancy is the lack of optical magnification in conventional methods, which precludes the precise differentiation of lymphatic vessels from venous structures. This is confirmed by a study by Guo et al. (35), where the implementation of laparoscopic Doppler ultrasound [laparoscopic Doppler ultrasound-assisted laparoscopic varicocelectomy (LDU-LV)] within laparoscopic techniques allowed for a reduction in hydrocele incidence from 10.7% to 1.4%. This suggests that the primary determinant of success is the precision of structural identification rather than the surgical access route itself.

Outcome heterogeneity is also evident in the durability of the surgical effect. While MSV is characterized by a minimal risk of recurrence, in techniques such as the Tauber or Ivanissevich methods, Fayez et al. (28) describe recurrence rates of 17.65% and 10.91%, respectively. The most concerning data originate from studies on laparoscopy and the Palomo method conducted by Pajovic et al. (21), where recurrence rates were recorded as high as 14.2% and 17.14%.

Such disparities may result from the maturity of the evidence base—smaller cohort studies, such as Vu Tan et al. (15) (N=25), more frequently report an absence of complications, which may not fully reflect the actual clinical risk in the general population. Conversely, larger case series, such as Almekaty et al. (37) (N=302), provide more robust evidence in favor of MSV, demonstrating a negligible incidence of complications (0.66% hydrocele with no recurrences).

The introduction of intraoperative Doppler and auxiliary techniques represents a direct response to the identified gaps in the precision of classical microsurgery. Data from Zhang et al. (27) confirm that Doppler allows for arterial identification in 95% of patients, which is critical in preventing the most severe complication—testicular atrophy. Without such precision, atrophy can affect up to 28.6% of cases in traditional procedures without magnification (OSV), as seen in the study by Okeke et al. (20). However, intraoperative Doppler is not utilized in all centers. Alternatively, Bryniarski et al. (22) apply a few drops of papaverine topically to induce vasodilation and visualize arterial pulsation. Yet, it must be remembered that intensive manipulation during dissection may still induce vascular spasm, hindering this visualization. To improve the vessel identification process, Shebl et al. (46) investigated the efficacy of combining intraoperative Doppler examination with the hydrodissection technique. This method involves the direct injection of saline into the spermatic cord in order to separate the individual vessels from one another. Only after such isolation are the arteries washed with warm, diluted papaverine. The researchers demonstrated that the use of Doppler ultrasound assisted by hydrodissection allows for the preservation of a greater number of testicular arteries compared to the use of Doppler alone (an average of 2.42–2.6 vs. 1.47–1.63 preserved arteries; P<0.001). Additionally, the combined technique translated into better semen parameters, resulting in a statistically significant increase in sperm motility.

Despite this progress, literature analysis reveals significant gaps. While the focus remains on semen parameters and anatomical complications, rarer events, such as genitofemoral nerve injury reported by Park et al. (34) at a frequency of 5.3% in the laparoendoscopic single-site surgery (LESS) technique, or chronic orchialgia described by Fayez et al. (28) in 9.8% of patients following sclerotherapy, are reported inconsistently. This indicates a need for the standardization of reporting protocols for non-surgical complications, which have a significant impact on the patient’s postoperative quality of life.

An important aspect influencing the final treatment outcome is also the extent of the surgery (17,23). Sun et al. (17) noted that although patients with unilateral and bilateral varicoceles benefit from the procedure, the improvement in sperm concentration was significantly greater in the group operated on bilaterally (even with a subclinical right varicocele). In turn, Yazdani et al. (25) demonstrated that age does not disqualify a patient from benefiting from the procedure, as the improvement in semen quality was significant in both the younger (<30 years of age) and older groups of men.

The clinical efficacy of the described surgical techniques is reflected not only in the basic seminogram but also in the improvement of molecular parameters associated with the integrity of sperm genetic material.

One of the semen parameters that improves following the procedure is nuclear chromatin condensation. Sadek et al. (16) demonstrated that varicocele removal leads to a decrease in the percentage of spermatozoa with abnormal chromatin condensation in the cell nucleus. Importantly, this effect is significantly correlated with disease severity; in the analyzed material, patients with grade III varicocele derived the greatest benefit from the procedure.

Varicoceles are associated with increased OS, which may result in damage to the genetic material in spermatozoa. Excessive DNA strand breaks, referred to as SDF, are commonly found in the ejaculates of men with varicoceles and fertility issues (40,41). In the material analyzed in this paper, extensive comparative data specifically concern the impact of the procedure on the SDF parameter. It should be noted that among the papers included in this review, those evaluating SDF (Fathi, Kavoussi, Sun) were based on the microsurgical technique. A comparative analysis of the aforementioned papers allows for the observation of a noticeable reduction in DNA fragmentation in each of these studies, while the degree of improvement in this parameter varies and depends on the profile of the studied patient group; Fathi et al. (30), by examining patients with a specific phenotype (normal semen parameters, high SDF, clinically palpable varicoceles), achieved a strong therapeutic effect. Similar high efficacy was demonstrated by Sun et al. (17), regardless of whether the surgery was unilateral or bilateral. The strongest evidence for the efficacy of varicocelectomy in terms of improving SDF, is provided by the study by Kavoussi et al. (31). These authors studied a group of patients with laboratory-confirmed high OS. They observed the greatest reduction in DNA damage post-procedure among the authors of the aforementioned papers.

These conclusions are reflected in large meta-analyses. A comprehensive meta-analysis by Cannarella et al. (9), encompassing the latest clinical reports, shows that varicocelectomy leads to a statistically significant reduction in DNA fragmentation with a mean difference (MD) of −6.92%. Another meta-analysis by Szabó et al. (10) demonstrated that this molecular effect is a dynamic process that progresses over time. These researchers observed that while the improvement is moderate in the early postoperative period, the reduction in SDF reaches as high as 12.39% at the 6th month post-procedure. These results confirm that microsurgical varicocele removal effectively protects sperm DNA, which directly translates into improved fertility.

The mechanism behind this improvement appears to be closely linked to the reduction of OS. The essence of OS is the dominance of ROS over the body’s defense (antioxidant) mechanisms. Metabolic analyses by Zhang et al. (29) indicate that the surgical procedure correlates with an improvement in the metabolic parameters of semen. Furthermore, studies on the static oxidation-reduction potential (sORP) by Kavoussi et al. (31) demonstrated that varicocele removal reduces the level of OS measured by sORP in semen, which is indirectly associated with the reduction of excess ROS that generate OS. This mechanism finds direct confirmation in the previously cited meta-analysis by Cannarella et al. (9). These authors demonstrated that, parallel to the improvement in genome integrity, there is a statistically significant decrease in the concentration of malondialdehyde (MDA)—a key marker of lipid peroxidation—with a MD of −2.39 nmol/mL (P<0.001).

However, the ultimate verifier of the efficacy of male infertility treatment is not merely the improvement of laboratory or molecular parameters, but achieving clinical pregnancy and the birth of a healthy child. The analysis of the collected literature confirms that the biological benefits described earlier translate strongly into reproductive success.

The strongest evidence for the validity of surgical intervention comes from the results of randomized controlled trials. Abdel-Meguid et al. (18) demonstrated that in men with clinical varicoceles, microsurgical varicocelectomy is associated with a significantly higher spontaneous pregnancy rate compared to the group subjected only to observation (32.9% vs. 13.9%). This proves that pregnancies in this group are not the result of chance or natural variability, but a direct consequence of the treatment.

Fathi et al. (30) proved that in a group of men characterized by a specific semen phenotype (normal seminogram, high DNA fragmentation), varicocele removal allowed for natural pregnancy to be achieved in over 62% of couples, which was double the rate of the control group (30%). Notable findings emerge from the observations of Vu Tan et al. (15) regarding patients with severe oligozoospermia. It was demonstrated that even with very low initial parameters, the improvement in semen quality following a microsurgical procedure is sufficient to restore the potential for natural conception, allowing many couples to avoid costly in vitro procedures [in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI)] (37). It should be noted that the aforementioned study included a small group of patients (N=25); therefore, the conclusions drawn from it should be confirmed by the results of studies involving a larger number of participants.

Nevertheless, this potential for natural conception is broadly supported by broader analyses. A review by Richardson et al. (47), comprising 24 studies, indicated that the mean natural birth rate [without assisted reproductive technologies (ART)] for patients after varicocelectomy was 39.5%. Similarly, Ma et al. (48) reported live birth rates of 31.08% via natural conception for those who underwent microsurgical varicocelectomy, compared to 24.00% via intrauterine insemination (IUI) for those who did not undergo the procedure (P<0.05).

Even when natural conception is not achieved, prior varicocele repair significantly enhances the success of ART. Recent meta-analyses confirm that varicocelectomy leads to notably higher live birth rates in patients undergoing IVF or ICSI compared to untreated controls, with ORs indicating a roughly twofold increase in success (OR ranging from 1.76 to 2.18) (11,49).

Therapeutic success does not end with fertilization itself. Mansour Ghanaie et al. (26) shed new light on the relationship between varicoceles and pregnancy maintenance. In their study, which included couples experiencing recurrent pregnancy loss (RPL), the removal of varicoceles in the partner resulted not only in achieving pregnancy but, above all, in an increase in the live birth rate. This is clinical confirmation of the previously discussed mechanisms—repairing sperm DNA damage reduces the risk of lethal embryonic defects. However, a 2025 meta-analysis by Teng et al. (11), encompassing a larger number of studies of varying methodological quality, did not confirm a significant reduction in miscarriages following varicocelectomy, highlighting the lack of standardized outcome reporting and the small number of randomized trials in this field.

It is also important that in patients with a clinical varicocele on one side and a subclinical one on the other, the procedure be performed bilaterally, as this results in higher pregnancy rates compared to a unilateral procedure, suggesting that treating both sides may be significant for optimizing reproductive outcomes in this group of patients (17).

Finally, it is worth emphasizing that the choice of surgical method also determines the chances of reproductive success. A comparative analysis conducted by Abdel-Meguid and Othman (19) demonstrated that microsurgical techniques are characterized by a higher achieved pregnancy rate (37.8%) compared to macroscopic methods (21.2%). Similar results were presented by Bryniarski et al. (22), noting a higher pregnancy rate following microsurgical procedures compared to laparoscopy, which the authors associate with better protection of testicular function and the absence of complications that could secondarily impair spermatogenesis.

Despite this strong consensus on the overall clinical benefits of varicocelectomy, a closer appraisal of the literature reveals considerable variations in the reported efficacy rates across different trials.

Understanding the sources of this heterogeneity in scientific study results is crucial for properly interpreting their conclusions, especially when dealing with complex issues such as the treatment of infertility associated with varicocele. Analyzing various publications, we quickly observe that discrepancies in outcomes often arise from fundamental differences in study design and execution.

A primary driver of these inconsistent outcomes is patient selection. Eligibility criteria, such as the grade of varicocele, are significantly important—for example, Sadek et al. (16) observed improvements in semen quality only in Grade III varicoceles, but not in Grade II. Patient age also plays a role, with Yazdani et al. (25) indicating a significantly greater increase in sperm concentration in patients under 30 years. Furthermore, baseline semen quality differs widely, ranging from normal morphology with high DNA fragmentation [Fathi et al. (30)] to cases of severe oligozoospermia [Vu Tan et al. (15)].

When analyzing clinical outcomes, a major limitation across the primary literature is the inconsistent evaluation of confounding female partner factors, such as maternal age, tubal patency, and ovarian reserve. As reported by Abdel-Meguid et al. (18) and Mansour Ghanaie et al. (26), these are critical co-determinants of conception that are often used as exclusion criteria, which limits the comparability of studies and can easily confound apparent surgical success rates if not strictly controlled for.

Study methodology and surgical execution represent another area of differences. Various surgical techniques naturally lead to different outcomes [e.g., Sun et al. (23)]. Moreover, surgeon’s experience—often overlooked in analyses—is crucial. As evidenced by Bryniarski et al.’s (22) observations regarding surgeon tenure, and Fayez et al. (28) mentioning the special training required for microsurgery, the consistent superiority and near-zero complication rates of microsurgical techniques may partially reflect the expertise of highly trained specialists in high-volume centers, rather than solely the intrinsic superiority of the technique itself.

Outcome heterogeneity is also a consequence of differences in endpoints and follow-up duration. Many studies focus on surrogate endpoints, such as oxidation-reduction potential [Kavoussi et al. (31)], instead of the true treatment goal, which is pregnancy. Furthermore, follow-up periods that are too short, such as 3 months [Park et al. (34)] or 6 months [Jin et al. (36)], may not reflect the full improvement in semen parameters. This underestimates treatment efficacy compared to studies with longer follow-ups of one year [Abdel-Meguid et al. (18)] or even 10 years [Okeke et al. (20)].

Finally, methodological limitations across primary studies are a major source of bias. Issues such as small sample sizes (15,22), lack of randomization (27,30), and high dropout rates (28) make it difficult to draw definitive conclusions. Furthermore, outcome selection biases such as analyzing only successful cases (15) or excluding patients with varicocele recurrence (25) can lead to an overestimation of success rates. All these factors make comparing and synthesizing the results of studies on varicocele treatment challenging and require a critical evaluation of the methodology of each publication.

Another major limitation of the current literature is the reliance on semen parameters as surrogate endpoints, rather than prioritizing live birth rates. Pregnancy reporting is also highly variable, often failing to differentiate between spontaneous conceptions and those requiring ART. Although we summarized short-term complications in this review, there remains a notable lack of robust long-term safety data. Most trials have follow-up periods that are too short to adequately evaluate late recurrences and long-term testicular function.

Recognizing these limitations is essential when interpreting the available evidence. This review has several strengths, including a comprehensive literature search and a focused synthesis of recent clinical trials. As a narrative review, we did not perform a meta-analysis or use quantitative risk-of-bias scoring tools. Instead, we evaluated the evidence qualitatively to minimize selection bias. Nevertheless, the current literature remains limited by methodological heterogeneity, varying patient phenotypes, and confounding factors such as surgeon expertise. These underlying issues require a cautious interpretation of the outcomes and highlight the need for better-designed future studies.

Conclusions

The current evidence indicates that varicocelectomy is an established treatment for infertile couples whose infertility is caused by varicocele. Across different age groups, there is an improvement in sperm concentration and motility post-surgery. Microsurgery is considered the best surgical approach. When comparing the results of microsurgery with laparoscopy and other traditional approaches, microsurgery results in less recurrence risk while eliminating the risk of hydrocele and arterial damage. The physiological advantages of microsurgical varicocelectomy are the improvement of the testicular microenvironment through the reduction of OS and DNA fragmentation. This results in increased pregnancy rates while reducing miscarriages. In bilateral cases of varicocele, bilateral repair is necessary for optimal results. For many infertile couples, especially those with severe oligozoospermia, this is an alternative way of achieving conception naturally. However, the current literature still has limitations, mostly resulting from methodological heterogeneity and inconsistent reporting. Therefore, future studies should meet several key criteria. First, we need prospective comparative trials that use standard outcome measures for all patients. Second, future studies should routinely and transparently report safety endpoints, such as recurrence rates and hydrocele formation. Third, studies should group patients by their specific characteristics (like exact baseline sperm counts). This would help identify who actually benefits from surgery. Finally, future trials should focus on outcomes that really matter to patients, namely natural pregnancy and live birth rates. Meeting these criteria will ensure reliable data collection, confirm the correlation between surgical repair and fertility improvement, and help determine the optimal surgical technique for future patients.

Acknowledgments

None.

Footnote

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