Surgical or radiological treatment for varicoceles in subfertile men

Background Varicoceles are associated with male subfertility; however, the mechanisms by which varicoceles affect fertility have yet to be satisfactorily explained. Several treatment options exist, including surgical or radiological treatment, however the safest and most efficient treatment remains unclear.

To evaluate the effectiveness and safety of surgical and radiological treatment of varicoceles on live birth rate, adverse events, pregnancy rate, varicocele recurrence, and quality of life amongst couples where the adult male has a varicocele, and the female partner of childbearing age has no fertility problems. Search methods We searched the following databases on 4 April 2020: the Cochrane Gynaecology and Fertility Group Specialised Register, CENTRAL, MEDLINE, Embase, PsycINFO, and CINAHL. We also searched the trial registries and reference lists of articles. Selection criteria We included randomised controlled trials (RCTs) if they were relevant to the clinical question posed and compared different forms of surgical ligation, different forms of radiological treatments, surgical treatment compared to radiological treatment, or one of these aforementioned treatment forms compared to non‐surgical methods, delayed treatment, or no treatment. We extracted data if the studies reported on live birth, adverse events, pregnancy, varicocele recurrence, and quality of life. Data collection and analysis Screening of abstracts and full‐text publications, alongside data extraction and 'Risk of bias' assessment, were done dually using the Covidence software. When we had sufficient data, we calculated random‐effects (Mantel‐Haenszel) meta‐analyses; otherwise, we reported results narratively. We used the I2 statistic to analyse statistical heterogeneity. We planned to use funnel plots to assess publication bias in meta‐analyses with at least 10 included studies. We dually rated the risk of bias of studies using the Cochrane 'Risk of bias' tool, and the certainty of evidence for each outcome using the GRADE approach. Main results We identified 1897 citations after de‐duplicating the search results. We excluded 1773 during title and abstract screening. From the 113 new full texts assessed in addition to the 10 studies (11 references) included in the previous version of this review, we included 38 new studies, resulting in a total of 48 studies (59 references) in the review providing data for 5384 participants. Two studies (three references) are ongoing studies and two studies are awaiting classification. Treatment versus non‐surgical, non‐radiological, delayed, or no treatment Two studies comparing surgical or radiological treatment versus no treatment reported on live birth with differing directions of effect. As a result, we are uncertain whether surgical or radiological treatment improves live birth rates when compared to no treatment (risk ratio (RR) 2.27, 95% confidence interval (CI) 0.19 to 26.93; 2 RCTs, N = 204; I2 = 74%, very low‐certainty evidence). Treatment may improve pregnancy rates compared to delayed or no treatment (RR 1.55, 95% CI 1.06 to 2.26; 13 RCTs, N = 1193; I2 = 65%, low‐certainty evidence). This suggests that couples with no or delayed treatment have a 21% chance of pregnancy, whilst the pregnancy rate after surgical or radiological treatment is between 22% and 48%. We identified no evidence on adverse events, varicocele recurrence, or quality of life for this comparison. Surgical versus radiological treatment We are uncertain about the effect of surgical versus radiological treatment on live birth and on the following adverse events: hydrocele formation, pain, epididymitis, haematoma, and suture granuloma. We are uncertain about the effect of surgical versus radiological treatment on pregnancy rate (RR 1.13, 95% CI 0.75 to 1.70; 5 RCTs, N = 456, low‐certainty evidence) and varicocele recurrence (RR 1.31, 95% CI 0.82 to 2.08; 3 RCTs, N = 380, low‐certainty evidence). We identified no evidence on quality of life for this comparison. Surgery versus other surgical treatment We identified 19 studies comparing microscopic subinguinal surgical treatment to any other surgical treatment. Microscopic subinguinal surgical treatment probably improves pregnancy rates slightly compared to other surgical treatments (RR 1.18, 95% CI 1.02 to 1.36; 12 RCTs, N = 1473, moderate‐certainty evidence). This suggests that couples with microscopic subinguinal surgical treatment have a 10% to 14% chance of pregnancy after treatment, whilst the pregnancy rate in couples after other surgical treatments is 10%. This procedure also probably reduces the risk of varicocele recurrence (RR 0.48, 95% CI 0.29, 0.79; 14 RCTs, N = 1565, moderate‐certainty evidence). This suggests that 0.4% to 1.1% of men undergoing microscopic subinguinal surgical treatment experience recurrent varicocele, whilst 1.4% of men undergoing other surgical treatments do. Results for the following adverse events were inconclusive: hydrocele formation, haematoma, abdominal distension, testicular atrophy, wound infection, scrotal pain, and oedema. We identified no evidence on live birth or quality of life for this comparison. Nine studies compared open inguinal surgical treatment to retroperitoneal surgical treatment. Due to small sample sizes and methodological limitations, we identified neither treatment type as superior or inferior to the other regarding adverse events, pregnancy rates, or varicocele recurrence. We identified no evidence on live birth or quality of life for this comparison. Radiological versus other radiological treatment One study compared two types of radiological treatment (sclerotherapy versus embolisation) and reported 13% varicocele recurrence in both groups. Due to the broad confidence interval, no valid conclusion could be drawn (RR 1.00, 95% CI 0.16 to 6.20; 1 RCT, N = 30, very low‐certainty evidence). We identified no evidence on live birth, adverse events, pregnancy, or quality of life for this comparison. Authors' conclusions Based on the limited evidence, it remains uncertain whether any treatment (surgical or radiological) compared to no treatment in subfertile men may be of benefit on live birth rates; however, treatment may improve the chances for pregnancy. The evidence was also insufficient to determine whether surgical treatment was superior to radiological treatment. However, microscopic subinguinal surgical treatment probably improves pregnancy rates and reduces the risk of varicocele recurrence compared to other surgical treatments. High‐quality, head‐to‐head comparative RCTs focusing on live birth rate and also assessing adverse events and quality of life are warranted. Plain language summary Surgery or radiological treatment for varicoceles in subfertile men

A varicocele is a dilatation (enlargement) of the veins along the spermatic cord (the cord suspending the testis) in the scrotum. Dilatation occurs when valves within the veins along the spermatic cord fail and allow retrograde blood flow, causing a backup of blood. Surgical treatment involves the closing off of the vessels, typically with sutures or clips. Radiological treatment involves both embolisation, in which the vessel is blocked with small particles, or sclerotherapy, where an agent is administered that damages the vessels, causing them to shrink. The mechanisms by which varicoceles might affect fertility, or the mechanisms by which surgical or radiological treatment of varicoceles might restore fertility, have not yet been explained. Review question We reviewed the evidence for the effect of varicocele treatment on live birth, adverse events, pregnancy rate, varicocele recurrence, and quality of life in subfertile couples where the male has a varicocele, and the female partner of childbearing age has no fertility problems. Study characteristics We found 48 randomised controlled trials (a type of study in which people are assigned to one of two or more treatment groups using a random method) comparing treatment versus no treatment or versus a different treatment method in a total of 5384 men. The evidence is current to April 2020. Key results We are uncertain whether surgical or radiological treatment improves live birth rates when compared to no treatment. Treatment may improve pregnancy rates compared to delayed or no treatment. The evidence suggests that couples with no or delayed treatment have a 21% chance of pregnancy, whilst the pregnancy rate after surgical or radiological treatment is between 22% and 48%. Data were lacking on adverse events, varicocele recurrence, and quality of life. We are uncertain about the effect of surgical versus radiological treatment on live birth, pregnancy rate, varicocele recurrence, and the adverse event hydrocele formation. Data were lacking on quality of life for this comparison. Microscopic subinguinal surgical treatment probably improves pregnancy rates slightly compared to other surgical treatments. This suggests that couples with microscopic subinguinal surgical treatment have a 10% to 14% chance of pregnancy after treatment, whilst the pregnancy rate in couples after other surgical treatments is 10%. This procedure also probably reduces the risk of varicocele recurrence. This suggests that 0.4% to 1.1% of men undergoing microscopic subinguinal surgical treatment experience recurrent varicocele, whilst 1.4% of men undergoing other surgical treatments do. Results on adverse events were inconclusive. Data were lacking on live birth and quality of life. We are uncertain about the effects of open inguinal surgical treatment versus retroperitoneal surgical treatment on adverse events, pregnancy rates, or varicocele recurrence. Data were lacking on live birth and quality of life. We are uncertain about the effects of radiological treatment (sclerotherapy versus embolisation) on varicocele recurrence. Data were lacking on live birth, adverse events, pregnancy, and quality of life. Certainty of the evidence Our findings were inconclusive, as the certainty of the available evidence ranged from moderate to very low depending on outcome. More research is needed with live birth or pregnancy rate as the primary outcome. Summary of findings Summary of findings 1. Varicocele treatment compared to non‐surgical, delayed, or no treatment for varicoceles in subfertile men. | Varicocele treatment compared to non‐surgical, delayed, or no treatment for varicoceles in subfertile men | ||||| | Patient or population: Varicoceles in subfertile men Setting: Clinical Intervention: Varicocele treatment Comparison: Non‐surgical, non‐radiological, delayed, or no treatment | ||||| | Outcomes | Anticipated absolute effects* (95% CI) | Relative effect (95% CI) | № of participants (studies) | Certainty of the evidence (GRADE) | | | Risk with non‐surgical, delayed, or no treatment | Risk with varicocele treatment | |||| | Live birth | Whilst one study demonstrated higher live birth rates in participants who had varicocelectomy treatment (RR 6.50, 95% CI 2.40 to 17.63, N = 136) (Ghanaie 2012), the other study reported a decreased number (Grasso 2000), but with a very broad confidence interval including both a large reduction and a large increase of live birth in the varicocelectomy treatment group (RR 0.50, 95% CI 0.05 to 5.26, N = 68). Both studies compared surgical treatment to no treatment (observation). | RR 2.27 (0.19 to 26.93) | 204 (2 RCTs) | ⊕⊝⊝⊝ VERY LOW 1 2 3 | | | Adverse events | No evidence identified. | |||| | Pregnancy | 210 per 1000 | 326 per 1000 (223 to 476) | RR 1.55 (1.06 to 2.26) | 1193 (13 RCTs) | ⊕⊕⊝⊝ LOW 1 4 | | Varicocele recurrence | No evidence identified. | |||| | Quality of life | No evidence identified. | |||| | *The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; RCT: randomised controlled trial; RR: risk ratio | ||||| | GRADE Working Group grades of evidence High certainty: We are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: We are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: Our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect. Very low certainty: We have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect. | 1We downgraded one level for risk of bias due to unclear allocation concealment and lack of blinding. 2We downgraded one level for inconsistency because the effect estimates of the two studies were inconsistent: one indicated a beneficial effect of treatment, the other a negative effect, although with a wide CI. 3We downgraded one level for imprecision because the optimal information size was not reached, and both studies had a wide CI. 4We downgraded one level for inconsistency due to heterogeneity: I2 = 65%. Summary of findings 2. Surgical treatment compared to radiological treatment for varicoceles in subfertile men. | Surgical treatment compared to radiological treatment for varicoceles in subfertile men | ||||| | Patient or population: Varicoceles in subfertile men Setting: Clinical Intervention: Surgical treatment Comparison: Radiological treatment | ||||| | Outcomes | Anticipated absolute effects* (95% CI) | Relative effect (95% CI) | № of participants (studies) | Certainty of the evidence (GRADE) | | | Risk with radiological treatment | Risk with surgical treatment | |||| | Live birth | 110 per 1000 | 164 per 1000 (73 to 371) | RR 1.49 (0.66 to 3.37) | 155 (1 RCT) | ⊕⊝⊝⊝ VERY LOW 1 2 | | Adverse event: hydrocele formation | 21 per 1000 | 87 per 1000 (11 to 696) | RR 4.24 (0.53 to 33.76) | 284 (3 RCTs) | ⊕⊝⊝⊝ VERY LOW 1 2 3 | | Pregnancy | 236 per 1000 | 266 per 1000 (177 to 401) | RR 1.13 (0.75 to 1.70) | 456 (5 RCTs) | ⊕⊕⊝⊝ LOW 1 4 | | Varicocele recurrence | 179 per 1000 | 235 per 1000 (147 to 373) | RR 1.31 (0.82 to 2.8) | 380 (3 RCTs) | ⊕⊕⊝⊝ LOW 1 4 | | Quality of life | No evidence identified. | |||| | *The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; RCT: randomised controlled trial; RR: risk ratio | ||||| | GRADE Working Group grades of evidence High certainty: We are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: We are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: Our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect. Very low certainty: We have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect. | 1We downgraded one level for risk of bias due to unclear allocation concealment and lack of blinding. 2We downgraded two levels for imprecision because the optimal information size was not reached, and the CI was very wide including both a large beneficial and a large harmful effect. 3We downgraded one level for inconsistency due to heterogeneity: I2 = 60%. 4We downgraded one level for imprecision because the CI was wide and included both a beneficial effect for surgical as well as for radiological treatment. Summary of findings 3. Surgical treatment compared to other surgical treatment for varicoceles in subfertile men. | Surgical treatment compared to other surgical treatment for varicoceles in subfertile men | ||||| | Patient or population: Varicoceles in subfertile men Setting: Clinical Intervention: (1) Microscopic subinguinal surgical treatment or (2) open inguinal surgical treatment Comparison: (1) Any other surgical treatment or (2) retroperitoneal surgical treatment | ||||| | Outcomes | Anticipated absolute effects* (95% CI) | Relative effect (95% CI) | № of participants (studies) | Certainty of the evidence (GRADE) | | | Risk with surgical treatment | Risk with other surgical treatment | |||| | Live birth | No evidence identified. | |||| | Adverse events | Microscopic subinguinal surgical treatment vs any other surgical treatment | |||| | Single studies reported adverse events: hydrocele formation, testicular atrophy, haematoma, pain, wound infection, oedema, and abdominal distention; however, no meta‐analyses were possible, and results were inconclusive. | ‐ | 890 (7 RCTs) | ⊕⊝⊝⊝ VERY LOW 1 2 | || | Open inguinal surgical treatment vs retroperitoneal surgical treatment | ||||| | Single studies reported adverse events: hydrocele formation, testicular atrophy, haematoma, pain, wound infection, oedema, epididymitis, epididymo‐orchitis, pneumoscrotum, subcutaneous emphysema, inferior epigastric bleeding, persistence of dilated veins, and wound erythema; however, no meta‐analyses were possible, and results were inconclusive. | ‐ | 1273 (9 RCTs) | ⊕⊝⊝⊝ VERY LOW 1 2 | || | Pregnancy | Microscopic subinguinal surgical treatment vs any other surgical treatment | |||| | Risk with subinguinal surgical treatment: 359 per 1000 | Risk with other surgical treatment: 304 per 1000 (264 to 868) | RR 1.18 (1.02 to 1.36) | 1473 (12 RCTs) | ⊕⊕⊕⊝ MODERATE 1 | | | Open inguinal surgical treatment vs retroperitoneal surgical treatment | ||||| | Risk with open inguinal surgical treatment: 263 per 1000 | Risk with retroperitoneal surgical treatment: 258 per 1000 (114 to 442) | RR 1.02 (0.82 to 1.27) | 889 (5 RCTs) | ⊕⊕⊝⊝ LOW 1 3 | | | Varicocele recurrence | Microscopic subinguinal surgical treatment vs any other surgical treatment | |||| | Risk with subinguinal surgical treatment: 45 per 1000 | Risk with other surgical treatment: 93 per 1000 (78 to 840) | RR 0.48 (0.29 to 0.79) | 1565 (14 RCTs) | ⊕⊕⊕⊝ MODERATE 1 | | | Open inguinal surgical treatment vs retroperitoneal surgical treatment | ||||| | Risk with open inguinal surgical treatment: 116 per 1000 | Risk with retroperitoneal surgical treatment: 112 per 1000 (62 to 552) | RR 1.03 (0.43 to 2.46) | 1063 (8 RCTs) | ⊕⊝⊝⊝ VERY LOW 1 3 4 | | | Quality of life | No evidence identified. | |||| | *The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; RCT: randomised controlled trial; RR: risk ratio | ||||| | GRADE Working Group grades of evidence High certainty: We are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: We are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: Our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect. Very low certainty: We have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect. | 1We downgraded one level for high risk of bias due to unclear randomisation/allocation concealment and lack of blinding. 2We downgraded two levels for imprecision because the studies had a small sample size, optimal information size was not reached, and results were inconclusive. 3We downgraded one level for imprecision because the confidence interval included both a large reduction and large increase of risk in the intervention group. 4We downgraded one level for inconsistency because the I2 was high (71%). Summary of findings 4. Radiological treatment compared to radiological treatment for varicoceles in subfertile men. | Radiological treatment compared to radiological treatment for varicoceles in subfertile men | ||||| | Patient or population: Varicoceles in subfertile men Setting: Clinical Intervention: Radiological treatment Comparison: Radiological treatment | ||||| | Outcomes | Anticipated absolute effects* (95% CI) | Relative effect (95% CI) | № of participants (studies) | Certainty of the evidence (GRADE) | | | Risk with radiological treatment | Risk with radiological treatment | |||| | Live birth | No evidence identified. | |||| | Adverse events | No evidence identified. | |||| | Pregnancy | No evidence identified. | |||| | Varicocele recurrence | Study population | RR 1.00 (0.16 to 6.20) | 30 (1 RCT) | ⊕⊝⊝⊝ VERY LOW 1 2 | | | 133 per 1000 | 133 per 1000 (21 to 827) | |||| | Quality of life | No evidence identified. | |||| | *The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; RCT: randomised controlled trial; RR: risk ratio | ||||| | GRADE Working Group grades of evidence High certainty: We are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: We are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: Our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect. Very low certainty: We have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect. | 1We downgraded one level for high risk of bias due to lack of blinding and unclear risk of bias in all other domains. 2We downgraded two levels for imprecision because the optimal information size was not reached, and the confidence interval was very wide.

Description of the condition A varicocele results from the dilation and distention of the internal spermatic vein and pampiniform venous plexus within the spermatic cord in the scrotum. Most varicoceles are left‐sided due to the anatomy of the testicular drainage system, accounting for 85% to 90% of cases, with only 1% being right‐sided, and up to 30% being bilateral (Chiba 2016a; Jarow 2001; Skoog 1997; WHO 1991). Clinical diagnosis is accomplished primarily through physical examination in either adolescents presenting for a routine medical check‐up or adults evaluating their fertility status. Men are visually examined in both supine and standing positions, physically palpated, and perform a Valsalva manoeuvre, which involves attempting exhalation against a closed airway, that further distinguishes the dilation of the pampiniform plexus. Ultrasonography is also used as a tool to diagnose subclinical varicocele and to assess any discrepancies in testicular volume between the left and right testicle which could call for intervention (Chiba 2016a). Adolescent and adult varicoceles are graded following the World Health Organization (WHO) scale: WHO 0: only demonstrable by technical diagnostic methods; WHO I: only palpable/visible during Valsalva manoeuvre; WHO II: palpable when in upright position at room temperature; WHO III: visible when in upright position at room temperature (WHO 1991). The mechanism through which varicoceles impair male fertility remains uncertain. However, impaired blood drainage from the testis leading to increased venous pressure, oxidative stress, imbalances of testosterone, and an elevated testicular temperature in the seminiferous tubules have been proposed to have deleterious effects on spermatogenesis, semen quality, hormone production by Leydig cells, and the function of Sertoli cells (Chiba 2016a; Chiba 2016b; Ding 2012; Duran 2002; Jarow 2001; Kupis 2015; Lewis 2010; Skoog 1997; WHO 1991). Variation in testicular temperature is considered to have the most negative impact on spermatogenesis, which, in combination with oxidative stress and increased levels of reactive oxygen species, can induce apoptosis in spermatozoa. A genetic link may contribute to these aforementioned factors, as decreased levels of heat shock proteins, polymorphisms in the glutathione S transferase and nitric oxide synthase genes, and non‐physiological alterations in the genes and proteins of BCL2 associated X, apoptosis regulator (BAX) and BCL2 apoptosis regulator (BCL2), have been associated with varicocele patients (Hassanin 2018). However, despite these findings, no theory can explain the exact effect of varicoceles on infertility, highlighting the complexity of the condition and the importance of assessing couple fertility status, varicocele grade, and semen quality on a case‐by‐case basis when selecting an appropriate varicocele treatment method that will best impact fertility (Jensen 2017). Many physicians accept occlusion of the spermatic vein as the treatment of choice for this condition. Although many techniques exist, due to the lower complication rates, microsurgical varicocelectomy, and particularly microscopic subinguinal varicocelectomy, has been proposed as the gold‐standard technique (Masterson 2019; Nieschlag 1993; Tatem 2017). However, evidence explaining the mechanisms by which varicocelectomy might restore fertility is lacking. Furthermore, the existence of a causal relationship between the specific distension of the pampiniform plexus (a network of many small veins found in the human male spermatic cord) and fertility impairment has been questioned. The treatment of varicoceles with the aim of increasing male fertility has been performed since 1952. Various techniques were developed in the following decades, and varicocele treatment has since been recognised as a means of helping treat male infertility (Marte 2018). In 1978 and 1992, assisted reproductive technologies (ARTs), namely in vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI), were successfully introduced as additional measures to potentially increase fertility in subfertile couples. IVF may be undergone with additional hormonal ovarian stimulation and involves the fertilisation of ova by spermatozoa in culture media and later implantation of zygotes into the uterus. ICSI is an additional technique where, instead of thousands of spermatozoa being left to fertilise the ova, one single spermatozoon is directly injected into the ovum to ensure fertilisation (CDC 2017). Due to the direct path to pregnancy that IVF and ICSI offer subfertile couples, these methods have been more intensely pursued and researched in the last few decades. Although this has resulted in a lack of recent evidence on the treatment of varicoceles for subfertility, the disadvantages associated with ARTs, particularly the high costs, higher maternal and foetal complications, multiple‐gestation pregnancies, ovarian hyperstimulation, and increased birth defects, are notable reasons for why varicocele treatment remains a comparable treatment method (Pandey 2012; Pathak 2016; Revelli 2011). Furthermore, despite male infertility being linked to an increased risk of cancer and other health problems, the overall health of these men is typically disregarded in an attempt to create a viable pregnancy (Eisenberg 2015a; Eisenberg 2015b; Kolettis 2001; Walsh 2009; Walsh 2010). This is also demonstrated in major increases in rates of ICSI despite the availability of specific therapies, such as varicocelectomy, to treat the male aspect of infertility (Boulet 2015). ICSI pregnancies have also been reported to have a 1.5‐ to 4‐fold increase in genetic disorders, intellectual disabilities, and birth defects compared to IVF pregnancies (Amor 2008; Bonduelle 2002; Davies 2012; Gjerris 2008; Sandin 2013; Zhu 2006). Varicocelectomy thus provides an option to treat both the underlying male subfertility and associated health issues whilst aiming to produce a viable pregnancy and healthy baby. Due to the disadvantages, health risks, and costs associated with ARTs, the potential ability of varicocele treatment to both improve male infertility and underlying health problems and increase spontaneous pregnancies without the use of ARTs poses considerable benefits whilst addressing the same goals (Pathak 2016). Varicocele treatment thus presents a treatment option for couples who are unwilling or unable to undergo ARTs or who wish to undergo them whilst addressing the male health aspect. Emerging studies have also begun combining ARTs with varicocele repair, which may further increase pregnancy rates alongside improving male health. This review does not consider the use of ARTs with varicocele treatment, as these methods have different indications. ARTs present an option for treating subfertility mainly in the female partner, apart from the combination treatment with ICSI for the male partner, whilst varicocele treatment is an option if the male alone is subfertile. Nevertheless, studies combining ARTs and varicocele treatment, and studies comparing these methods directly, would be of interest for future research. Description of the intervention Surgical treatment Varicocelectomy refers to the surgical repair of a clinical varicocele which is palpable during physical examination. Several surgical techniques described and reviewed in the literature are used in clinical practice for the correction of varicoceles (Cassidy 2012; Choi 2013; Kupis 2015). Subinguinal varicocelectomy involves a 2‐centimetre traverse incision by the external inguinal ring to approach and deliver the spermatic cord and testis. As this surgical treatment generally uses a microscope, it is often referred to as microscopic subinguinal varicocelectomy. It is viewed as a highly difficult procedure, as there is a higher risk of damaging the arteries; nevertheless, it exposes the spermatic cord without requiring the dissection of abdominal muscles or fascia, resulting in fewer postoperative complications with lower hydrocele formation and reduced varicocele recurrences, thus rendering it the gold standard in this regard (Binsaleh 2007; Hou 2015; Tatem 2017). As microscopic subinguinal varicocelectomy is currently considered the gold standard and was performed in many surgical comparison studies, we chose it to be the main focus of a comparison due to its relevancy to clinical practice. Retroperitoneal varicocelectomy, also referred to as suprainguinal, highest entry point, Palomo, high ligation, or abdominal varicocelectomy, refers to an open varicocelectomy procedure and involves a medial inferior incision to the ipsilateral anterior superior iliac spine through the external and internal oblique fascia, after which the vein in question is ligated. This technique does not allow for the saving of the lymphatics, resulting in a high rate of postoperative hydrocele formation (Chan 2011). Further, the testicular artery and its periarterial network of fine veins may be ligated, leading to a lower recurrence rate, but a destruction of the testicular artery as well (Kass 1992). Laparoscopicvaricocelectomy is a subsection of retroperitoneal varicocelectomy, however involves laparoscopic cameras for a more precise dissection of arteries and internal spermatic veins (Chiba 2016a). Inguinal varicocelectomy involves an incision over the inguinal canal, allowing for elevation of the spermatic cord and vessels for dissection and ligation with sutures or clips. The procedure can be performed conventionally open with or without a microscope. In conventional non‐magnified open inguinal varicocelectomy, also referred to as the Ivanissevich technique, the internal spermatic veins are ligated, which results in a lower rate of varicocele recurrence compared to the retroperitoneal technique (Tatem 2017). With the microsurgical technique, which involves the use of a microscope, the lymphatics can be spared, and the incidence of postoperative hydrocele formation is significantly reduced compared to the retroperitoneal or conventional technique. Radiological treatment Radiological interventions are also performed to treat varicoceles. These comprise varicocele embolisation, which is a frequently used technique that involves the blocking of one or more blood vessels or abnormal vascular channels using either a coil or a balloon, and may include the selective catheterisation and embolisation of the gonadal veins (Cassidy 2012). Depending on the location of the varicocele, different types of embolisation may be performed, including bilateral embolisation, unilateral left‐sided embolisation, and unilateral right‐sided embolisation (Cassidy 2012). Another radiological intervention is sclerotherapy, in which the spermatic vein is ligated after administration of a sclerosing agent, which causes damage to the endothelial cells of the intima of the vessels, causing them to shrink (Tauber 2006). The following two radiological treatment categories comprised the radiological treatment group: Antegrade and retrograde embolisation Antegrade and retrograde sclerotherapy For the comparison of any surgical or radiological treatment with a control intervention, we included non‐surgical methods (treatment with counselling and with clomiphene citrate), delayed treatment, and no treatment as control methods. How the intervention might work The mechanism through which varicoceles impair male fertility remains uncertain. However, impaired blood drainage from the testis leading to increased venous pressure, oxidative stress, imbalances of testosterone, and an elevated testicular temperature in the seminiferous tubules have been proposed to have deleterious effects on spermatogenesis, semen quality, hormone production by Leydig cells, and the function of Sertoli cells. (Chiba 2016a; Chiba 2016b; Ding 2012; Duran 2002; Jarow 2001; Kupis 2015; Lewis 2010; Skoog 1997; WHO 1991). Through either the ligation of or blocking off the dilated veins, the aforementioned techniques strive to reverse these negative effects back to their physiological norm with the aim of restoring fertility. Varicocele treatment has thus been investigated and performed for several decades as a means of potentially improving fertility. Why it is important to do this review Varicoceles are present in 15% of the normal male population and up to 40% of men with infertility. Varicoceles are now recognised as the single most surgically correctable cause of male infertility (Ding 2012). There are a variety of surgical and radiological techniques with different advantages and disadvantages for the correction of clinical varicoceles. To date, there have been numerous recommendations for the ‘gold standard’ approach for correcting clinically diagnosed varicoceles amongst infertile males. From a clinical perspective, it is essential to establish which of these surgical or radiological methods yield the best results in terms of improving fertility outcomes, such as live birth rate and pregnancy, amongst couples unable to conceive due to male factor infertility.

regarding the true effect of varicocele treatment on live birth and pregnancy can only be derived from prospective studies with an unbiased comparison group: randomised controlled trials (RCTs). We therefore aimed to consolidate the evidence from RCTs on surgical and radiological treatment when evaluating the effects of varicocele repair on fertility status. This will permit the development of consistent and clear guidelines on treating varicocele‐related male infertility that can be put into effect worldwide. This review is an update and extension of the 2012 review, which compared any treatment (surgical/radiological) to non‐surgical, non‐radiological, delayed, or no treatment (Kroese 2012). This current review extends the scope of the previous review, and now compares different treatment methods directly with each other. The outcomes investigated were also expanded through the addition of quality of life as an outcome. This extension was made at the request of the Cochrane Gynaecology and Fertility Group to fit the requirements of an upcoming WHO report on the prevention, diagnosis, and treatment of infertility, and to inform their recommendations on varicocele treatment.

To evaluate the effectiveness and safety of surgical and radiological treatment of varicoceles on live birth, adverse events, pregnancy rate, varicocele recurrence, and quality of life amongst couples where the adult male has a varicocele, and the female partner of childbearing age has no fertility problems.

Criteria for considering studies for this review Types of studies Published and unpublished randomised controlled trials (RCTs) were eligible for inclusion. We excluded non‐randomised trials, as they are associated with a high risk of bias. RCTs were eligible if they dealt with the surgical or radiological repair of varicocele amongst infertile couples, and if they contained a control group that received a different surgical repair or radiological treatment to the intervention group, a non‐surgical technique, delayed treatment, or no treatment. We excluded quasi‐randomised studies. Types of participants We included adult men (18 years or older) with a varicocele of any grade with either normal or abnormal semen analysis, who were part of a couple with otherwise unexplained subfertility (female partner of childbearing age with no fertility issues). The American Urological Association (AUA) and the American Society for Reproductive Medicine (ASRM) recommend varicocele treatment when the following conditions are fulfilled: infertile men attempting to conceive, a palpable varicocele, and abnormal semen parameters (Schlegel 2021). The European Association of Urology (EAU) guidelines also recommend treatment in adolescents with ipsilateral reduction in testicular volume (EAU 2018). Following these guidelines, men with a subclinical varicocele and normal semen analysis are not offered varicocele treatment and would be excluded from this review. To give this review a broad scope, we did not exclude men with a subclinical varicocele and normal semen analysis. However, in order to reflect the AUA/ASRM and EAU guidelines, we have presented a subgroup analysis only including men with a clinical varicocele and abnormal semen analysis. We recognise the bias this introduces in the results, as men with normal semen analyses or a subclinical varicocele, or both, are less likely to see improvement in live birth and pregnancy rates to the same extent as men with abnormal semen parameters and a clinical varicocele. Types of interventions We included the following interventions and comparisons. Treatment versus non‐surgical, non‐radiological, delayed, or no treatment Surgical versus radiological treatment Microscopic subinguinal surgical treatment versus other surgical treatment Radiological versus other radiological treatment Types of outcome measures We included studies that met the inclusion criteria described above, regardless of whether they reported on the following outcomes. Primary outcomes Live birth Adverse events Secondary outcomes Pregnancy as defined by trial authors Varicocele recurrence Quality of life (measured with a validated tool, e.g. 36‐item Short Form Health Survey (SF‐36)) Semen quality was specified in the original review as a secondary outcome, but later seemed irrelevant in the presence of more clinically meaningful and patient‐relevant outcomes. It was therefore omitted in the 2012 update of the review, and again when updating and extending the current review. Search methods for identification of studies We searched for all published and unpublished RCTs, without language restriction, and in consultation with the Cochrane Gynaecology and Fertility Group Information Specialist. The Information Specialist consulted the search strategy for previous reviews and adapted it to fit the expanded review by not limiting the search dates as initially planned for the update search. The search was able to capture all of the studies for the 'treatment versus no treatment' comparison, and for the new 'treatment versus treatment' comparison. An update search was run on 4 April 2020. Electronic searches We searched the following electronic databases, trial registers, and websites: The Cochrane Gynaecology and Fertilty Group Specialised Register (ProCite platform), searched 4 April 2020 (Appendix 1); The Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library Issue 4, 2020) via the Cochrane Register of Studies Online (CRSO) (Web platform), searched 4 April 2020 (Appendix 2); MEDLINE (Ovid platform), searched from 1946 to 4 April 2020 (Appendix 3); Embase (Ovid platform), searched from 1980 to 4 April 2020 (Appendix 4); PsycINFO (Ovid platform), searched from 1806 to 4 April 2020 (Appendix 5); CINAHL (EBSCO platform) (Cumulative Index to Nursing and Allied Health Literature), searched 1961 to 4 April 2020 (Appendix 6); Web of Knowledge (Web platform) searched 4 April 2020 (Appendix 7); US National Institutes of Health Ongoing Trials Register ClinicalTrials.gov (Web platform) searched 4 April 2020 (www.clinicaltrials.gov); World Health Organization International Trials Registry Platform (WHO ICTRP) (Web platform) searched 4 April 2020 (www.who.int/trialsearch/Default.aspx). Searching other resources We handsearched the reference lists of included studies and systematic reviews retrieved by the search and contacted experts in the field to obtain additional data. We also handsearched Epistemonikos.org, ISI Web of Science, and OpenGrey for any additional titles that were not included in the previous searches. Data collection and analysis Selection of studies Titles and abstracts retrieved by the search were dually and independently screened, meaning two reviewers independently reviewed each record, by a team of six review authors (EP, CO, SK, BN, GW, NM). We retrieved the full texts for all records deemed potentially relevant, and review authors EP, CO, and SK dually and independently screened these against the eligibility criteria. Any disagreements were resolved by consensus. Title, abstract, and full‐text screening was conducted in Covidence software (Covidence), and tracked in an EndNote X8 database (EndNote ). Studies requiring translation were sent to native speakers, who checked the study for eligibility. The selection process is documented in the PRISMA flow diagram (Moher 2009). Data extraction and management Four review authors (EP, CO, SK, NM) dually and independently extracted data from the eligible studies using a data extraction form in Covidence that was designed by the review authors (Covidence). Any disagreements were resolved by consensus. Data extracted included study characteristics and outcome data, as follows: method of randomisation; number of men randomised, excluded, and analysed (when reported); whether a single‐centre or multicentre study; whether a parallel or cross‐over design; nature of interventions; participant age (standard deviation), and eligibility criteria. We listed inclusion and exclusion criteria; blinding of treatment (virtually impossible in studies involving surgery); the use of sequential analysis or factorial design; the performance of a power calculation; duration of follow‐up; whether pregnancy was an outcome measure and, if so, how it was confirmed (if reported); and the source of any funding. For females, we recorded age and confirmation of non‐female factor infertility, when applicable. The data were exported from Covidence to RevMan Web (RevMan Web 2019), and presented in the Characteristics of included studies tables. Where studies had multiple publications, the main trial report was used as the reference, and additional details were derived from secondary papers. We corresponded with study investigators for further data on methods or results, or both, as required. In the preparation of the previous review, additional information was obtained from Dr. Nieschlag on the randomisation procedure in his studies (Nieschlag 1993; Nieschlag 1995/1998). Assessment of risk of bias in included studies Four review authors (EP, CO, SK, NM) dually and independently assessed the included studies for risk of bias using the Cochrane 'Risk of bias' assessment tool based on the following domains (Higgins 2021): selection bias (random sequence generation and allocation concealment); performance bias (blinding of participants and personnel); detection bias (blinding of outcome assessors); attrition bias (incomplete outcome data); reporting bias (selective reporting); and other bias. Any disagreements were resolved by discussion. All judgements have been described fully and are presented in the Characteristics of included studies tables. Measures of treatment effect When three or more studies allowed for quantitative analysis, we used the numbers of events in the intervention and comparative groups of each study to calculate the Mantel‐Haenszel risk ratios (RRs) for dichotomous data. We presented 95% confidence intervals (CI) for all outcomes. We used RR as an effect measure as it is easier to interpret for decision makers and clinicians than odds ratios (OR). We reported the study results narratively when insufficient data were available. We planned to pool continuous data using the mean difference (MD) if the outcome was measured employing the same scale across all studies; otherwise, we would use the standardised mean difference (SMD). We planned to compare final measurements instead of mean‐changes from baseline to postintervention. However, none of the included studies reported on the only continuous outcome of quality of life. Unit of analysis issues The primary analysis was per man (from a couple) analysed. We counted multiple live births/pregnancies per man as one live birth/pregnancy. Dealing with missing data We analysed the data on an intention‐to‐treat basis as much as possible (i.e. including all randomised participants in the analysis in the groups to which they had been randomised), and made attempts to obtain missing data from the original investigators. Live birth or pregnancy was assumed not to have occurred in couples without a reported outcome or couples who were lost to follow‐up. For other outcomes, only the available data were analysed. No imputation was undertaken. Assessment of heterogeneity We considered whether the clinical and methodological characteristics of the included studies were sufficiently similar for meta‐analysis to provide a clinically meaningful summary. We assessed statistical heterogeneity using the I2 statistic. An I2 measurement greater than 50% was considered indicative of substantial heterogeneity (Higgins 2021). Assessment of reporting biases Due to the difficulty of detecting and correcting for publication bias and other reporting biases, we aimed to minimise their potential impact by ensuring a comprehensive search for eligible studies and by being alert to duplication of data. There is always the risk of publication bias. If there were 10 or more studies in a primary analysis, we planned to produce a funnel plot to explore the possibility of small‐study effects (a tendency for estimates of the intervention effect to be more beneficial in smaller studies). Data synthesis We analysed data using RevMan Web (RevMan Web 2019), and graded the certainty of evidence using GRADEpro GDT (GRADEpro GDT). Where three or more studies were sufficiently similar in terms of intervention, comparison, and outcome, we combined the data using Mantel‐Haenszel random‐effects model. We did not use fixed‐effect model because based on the variation in delivering surgical and radiological treatment, we could not assume one fixed effect in the included studies. We rated the certainty of the evidence using the GRADE approach, developed by the GRADE Working Group (Schünemann 2013). In the meta‐analysis graphs, an increase in the risks of a particular outcome, which may have been beneficial (e.g. pregnancy/live birth) or detrimental (e.g. adverse events), was displayed to the right of the centre line, and a decrease in the risks of an outcome to the left of the centre line. Subgroup analysis and investigation of heterogeneity Where data were available, we conducted a subgroup analysis with more strictly defined inclusion criteria, as follows: studies that included men with abnormal semen and clinical varicocele, and studies that reported live birth/pregnancy as a primary outcome. We planned that if we detected substantial heterogeneity, we would explore possible explanations for it via subgroup analyses. As such, we analyzed one subgroup concerning men with abnormal semen analysis and clinical varicocele, however didn’t do further subgroup analyses. We planned to take any statistical heterogeneity into account when interpreting the results, especially if there was any variation in the direction of effect. Sensitivity analysis We planned to conduct sensitivity analyses for the primary outcomes to determine whether the conclusions were robust to arbitrary decisions made regarding eligibility and analysis. These analyses included consideration of whether the review conclusions would have differed if eligibility was restricted to studies without high risk of bias. However, due to the lack of blinding, nearly all studies were rated at high risk of bias, therefore we did not conduct this sensitivity analysis. Summary of findings and assessment of the certainty of the evidence Summary of findings tables were generated for the three main comparisons using GRADEpro GDT software and Cochrane methods GRADEpro GDT; Schünemann 2013). This table evaluated the overall certainty of the body of evidence for the review outcomes (live birth, adverse events, pregnancy, varicocele recurrence, quality of life), using GRADE criteria (study limitations (i.e., risk of bias), consistency of effect, imprecision, indirectness and publication bias) for the main review comparisons (surgical treatment or radiological treatment versus another surgical or radiological treatment method, or versus a control method (non‐surgical method, delayed treatment, or no treatment)). Judgements about evidence certainty (high, moderate, low or very low) were made by two review authors (EP, BN) working independently, with disagreements resolved by discussion. Judgements were justified, documented, and incorporated into reporting of results for each outcome.

Description of studies

of the search Our search identified 1897 references after de‐duplication. We excluded 1773 citations during title and abstract screening. We assessed 113 new full texts for eligibility in addition to the 10 studies (11 references) included in the previous version of this review, and included a total of 48 studies (59 references) reporting on a total of 5384 men. Two studies (three references) are ongoing studies, and two studies are awaiting classification. The PRISMA flow diagram documents the study selection in this review (Figure 1). Reasons for excluding studies at the full‐text level are provided in Characteristics of excluded studies. Overall, 16 studies (1753 men) compared surgical or radiological treatment versus non‐surgical, non‐radiological, delayed, or no treatment (Abdel‐Meguid 2011a; Bo 1996; Breznik 1993; De Rose 2003; Dohle 2010; Ghanaie 2012; Grasso 2000; Hargreave 1996; Ketabchi 2018a; Ketabchi 2018b; Krause 2002; Madgar 1995; Nieschlag 1995/1998; Nilsson 1979; Unal 2001; Yamamoto 1996), and 33 studies (4070 men) compared different varicocele treatments with each other (Al Kandari 2007; Al Said 2008; Barbalias 1998; Barry 2012; Bryniarski 2016; Cayan 2000; Chaudhary 2000; Chen 1996; Fang 2013; Fayez 2010; Gao 2015; Gao 2017; Gontero 2005; Meng 2017; Min 2011; Nieschlag 1993; Nieschlag 1995/1998; Niu 2017; Pan 2013; Pocek 1999; Pu 2014; Punekar 1999; Qi 2009; Ren 2015; Sautter 2002; Song 2012; Su 2017; Sun 2012; Telkar 2012; Yang 2017; Yavetz 1992; Zhang 2015a; Zheng 2012). Included studies Study design and setting All 48 included studies were parallel RCTs. Forty‐six were single‐centre trials (Abdel‐Meguid 2011a; Al Kandari 2007; Al Said 2008; Barbalias 1998; Barry 2012; Bo 1996; Breznik 1993; Bryniarski 2016; Cayan 2000; Chaudhary 2000; Chen 1996; De Rose 2003; Dohle 2010; Fang 2013; Fayez 2010; Gao 2015; Gao 2017; Ghanaie 2012; Gontero 2005; Grasso 2000; Ketabchi 2018a; Ketabchi 2018b; Madgar 1995; Meng 2017; Min 2011; Nieschlag 1993; Nieschlag 1995/1998; Nilsson 1979; Niu 2017; Pan 2013; Pocek 1999; Pu 2014; Punekar 1999; Qi 2009; Ren 2015; Sautter 2002; Song 2012; Su 2017; Sun 2012; Telkar 2012; Unal 2001; Yamamoto 1996; Yang 2017; Yavetz 1992; Zhang 2015a; Zheng 2012), and two were multicentre trials (Hargreave 1996; Krause 2002). The studies were conducted in China, Egypt, Germany, Greece, the Netherlands, India, Iran, Israel, Italy, Kuwait, Pakistan, Poland, Saudi Arabia, Slovenia, Sweden, Switzerland, and Turkey. Study designs and settings are described for each treatment comparison below and in the Characteristics of included studies tables. Participants This review contains data for a total of 5384 men with an average age of 20 to 38 years from 48 studies. All men were from couples with otherwise unexplained subfertility. Twenty‐two studies reported men with clinical varicocele (Al Kandari 2007; Al Said 2008; Barbalias 1998; Bryniarski 2016; Dohle 2010; Fang 2013; Fayez 2010; Ketabchi 2018a; Krause 2002; Madgar 1995; Meng 2017; Min 2011; Nieschlag 1993; Nieschlag 1995/1998; Nilsson 1979; Niu 2017; Pan 2013; Pocek 1999; Punekar 1999; Ren 2015; Telkar 2012; Yavetz 1992). Three studies included men with subclinical varicocele only (Grasso 2000; Unal 2001; Yamamoto 1996). Eleven studies included men with clinical and subclinical varicocele (Abdel‐Meguid 2011a; Barry 2012; Breznik 1993; Cayan 2000; Chaudhary 2000; Gao 2017; Ghanaie 2012; Ketabchi 2018b; Pu 2014; Sautter 2002; Yang 2017). Twelve studies did not mention the varicocele grade (Bo 1996; Chen 1996; De Rose 2003; Gao 2015; Gontero 2005; Hargreave 1996; Qi 2009; Song 2012; Su 2017; Sun 2012; Zhang 2015a; Zheng 2012). Seven studies excluded azoospermia (Abdel‐Meguid 2011a; Breznik 1993; Dohle 2010; Ketabchi 2018b; Krause 2002; Nilsson 1979; Yavetz 1992). One study excluded men with teratozoospermia (Ketabchi 2018a); one study excluded men with sperm counts of fewer than 5 million per millilitre (Madgar 1995), and one study excluded men with sperm counts of fewer than 2 million per millilitre, with or without less than 10% progressive motility (Krause 2002). Fifteen studies only included couples with infertility persisting longer than one year (Abdel‐Meguid 2011a; Bryniarski 2016; Cayan 2000; Dohle 2010; Fayez 2010; Gao 2017; Grasso 2000; Krause 2002; Madgar 1995; Nieschlag 1993; Nieschlag 1995/1998; Pan 2013; Unal 2001; Yamamoto 1996; Yang 2017). One study included participants with infertility persisting at least two years (Nilsson 1979). Thirty‐two studies did not mention the duration of infertility (Al Kandari 2007; Al Said 2008; Barbalias 1998; Barry 2012; Bo 1996; Breznik 1993; Chaudhary 2000; Chen 1996; De Rose 2003; Fang 2013; Gao 2015; Ghanaie 2012; Gontero 2005; Hargreave 1996; Ketabchi 2018a; Ketabchi 2018b; Meng 2017; Min 2011; Niu 2017; Pocek 1999; Pu 2014; Punekar 1999; Qi 2009; Ren 2015; Sautter 2002; Song 2012; Su 2017; Sun 2012; Telkar 2012; Yavetz 1992; Zhang 2015a; Zheng 2012). Fifteen studies mentioned no obvious causes of female infertility (Abdel‐Meguid 2011a; Barbalias 1998; Breznik 1993; Bryniarski 2016; Cayan 2000; Dohle 2010; Hargreave 1996; Madgar 1995; Nieschlag 1993; Nieschlag 1995/1998; Nilsson 1979; Pan 2013; Yamamoto 1996; Yang 2017; Yavetz 1992); one study included couples with treatable female infertility (Krause 2002); two studies excluded couples with females aged over 35 years (Ketabchi 2018a; Ketabchi 2018b); one study excluded couples with females aged over 40 years (Ghanaie 2012); and 29 studies did not mention female infertility (Al Kandari 2007; Al Said 2008; Barry 2012; Bo 1996; Chaudhary 2000; Chen 1996; De Rose 2003; Fang 2013; Fayez 2010; Gao 2015; Gao 2017; Gontero 2005; Grasso 2000; Meng 2017; Min 2011; Niu 2017; Pocek 1999; Pu 2014; Punekar 1999; Qi 2009; Ren 2015; Sautter 2002; Song 2012; Su 2017; Sun 2012; Telkar 2012; Unal 2001; Zhang 2015a; Zheng 2012). Interventions We identified 16 studies comparing surgical or radiological treatment versus non‐surgical, non‐radiological, delayed, or no treatment (Abdel‐Meguid 2011a; Bo 1996; Breznik 1993; De Rose 2003; Dohle 2010; Ghanaie 2012; Grasso 2000; Hargreave 1996; Ketabchi 2018a; Ketabchi 2018b; Krause 2002; Madgar 1995; Nieschlag 1995/1998; Nilsson 1979; Unal 2001; Yamamoto 1996); seven studies comparing surgical versus radiological treatment (Barbalias 1998; Chen 1996; Fayez 2010; Nieschlag 1993; Nieschlag 1995/1998; Sautter 2002; Yavetz 1992); 19 studies comparing microscopic subinguinal surgical treatment versus other surgical treatment (Al Kandari 2007; Al Said 2008; Bryniarski 2016; Fang 2013; Gao 2015; Gao 2017; Gontero 2005; Meng 2017; Min 2011; Pan 2013; Pu 2014; Punekar 1999; Qi 2009; Ren 2015; Song 2012; Su 2017; Yang 2017; Zhang 2015a; Zheng 2012); nine studies comparing open inguinal surgical treatment versus retroperitoneal surgical treatment (Barbalias 1998; Barry 2012; Cayan 2000; Chaudhary 2000; Fang 2013; Pu 2014; Su 2017; Sun 2012; Telkar 2012); one study comparing radiological treatment (embolisation) versus radiological treatment (sclerotherapy) (Pocek 1999); and one study comparing microscopic inguinal surgical treatment versus laparoscopic surgical treatment (Niu 2017). Outcomes Three studies reported live birth (Fayez 2010; Ghanaie 2012; Grasso 2000); 28 studies reported pregnancy rate (not further specified) (Abdel‐Meguid 2011a; Al Kandari 2007; Al Said 2008; Bo 1996; Breznik 1993; Bryniarski 2016; Cayan 2000; Chen 1996; De Rose 2003; Dohle 2010; Fang 2013; Fayez 2010; Gao 2017; Hargreave 1996; Ketabchi 2018a; Ketabchi 2018b; Madgar 1995; Nieschlag 1993; Nieschlag 1995/1998; Nilsson 1979; Pan 2013; Punekar 1999; Qi 2009; Song 2012; Su 2017; Unal 2001; Yamamoto 1996; Yavetz 1992); and two studies reported clinical pregnancy (sonographically proven) (Ghanaie 2012; Krause 2002). Twenty‐three studies reported varicocele recurrence (Barbalias 1998; Barry 2012; Cayan 2000; Chaudhary 2000; Fang 2013; Fayez 2010; Gao 2015; Gontero 2005; Meng 2017; Min 2011; Niu 2017; Pan 2013; Pocek 1999; Pu 2014; Punekar 1999; Ren 2015; Song 2012; Su 2017; Sun 2012; Yang 2017; Yavetz 1992; Zhang 2015a; Zheng 2012). Two additional studies reported varicocele occurrence, but reported their events per number of varicoceles instead of per number of men, so the data were not included in the analysis to keep consistent denominators (Al Kandari 2007; Al Said 2008). Regarding adverse events, 14 studies reported hydrocele formation (Barbalias 1998; Barry 2012; Cayan 2000; Chaudhary 2000; Fayez 2010; Nieschlag 1993; Niu 2017; Pan 2013; Pu 2014; Punekar 1999; Ren 2015; Sautter 2002; Song 2012; Telkar 2012). Two additional studies reported hydrocele formation, but reported their events per number of varicoceles instead of per number of men, so the data were not included in the analysis to keep consistent denominators (Al Kandari 2007; Al Said 2008). Five studies reported testicular atrophy (Al Said 2008; Chaudhary 2000; Fang 2013; Min 2011; Punekar 1999), five studies haematoma (Al Kandari 2007; Al Said 2008; Barry 2012; Chaudhary 2000; Sautter 2002), three studies scrotal pain (Al Said 2008; Barry 2012; Sautter 2002), four studies wound infection (Al Said 2008; Barry 2012; Chaudhary 2000; Telkar 2012), two studies oedema (Fang 2013; Min 2011; Su 2017), two studies abdominal distention (Al Kandari 2007; Song 2012), two studies epididymitis (Sautter 2002; Su 2017), one study epididymo‐orchitis (Barry 2012), one study pneumoscrotum (Barry 2012), one study subcutaneous emphysema (Barry 2012), one study inferior epigastric bleeding (Barry 2012), one study persistence of dilated veins (Chaudhary 2000), one study wound erythema (Telkar 2012), and one study suture granuloma (Sautter 2002). No study reported on quality of life. Studies included in this review but not included in quantitative evidence syntheses Two studies are included and classified as 'awaiting classification' (Cavallini 2003; Feng 2017). We contacted the authors to see if they reported on some outcomes of interest, but have not yet received a response. Two other studies were not integrated in the quantitative treatment versus non‐surgical, non‐radiological, delayed, or no treatment comparison as they reported conflicting data. We reported these narratively instead (De Rose 2003; Hargreave 1996). One study was not integrated in a quantitative comparison and was reported narratively instead, as it reported on microscopic inguinal surgical treatment, but we chose to focus on microscopic subinguinal surgical treatment, which is regarded as the gold standard and more clinically relevant (Niu 2017). Excluded studies We excluded 65 of 113 references assessed at the full‐text level. Reasons for exclusion are described in detail in the Characteristics of excluded studies table. Ongoing studies Two studies comparing microscopic subinguinal versus laparoscopic treatment met the eligibility criteria but were still ongoing at the time this review was completed. Both are still labelled as "recruiting". The primary completion date of the study from Poland is July 2019 (NCT02722187), and from China is January 2017 (NCT02695199). We contacted both authors for preliminary data but did not receive a response. Risk of bias in included studies The 'Risk of bias' assessment is illustrated per domain as well as per study in Figure 2 and Figure 3. Detailed 'Risk of bias' assessments are summarised in the Characteristics of included studies tables. One trial used a randomised postponement‐of‐treatment design (Madgar 1995), and only data from the period before treatment in the controls have been included in the present review. Only the corresponding data (from the first 12 months following varicocelectomy) were used for the immediate intervention group of this study. Another study recruited women who were unable to conceive first and then targeted their partners (Ghanaie 2012). Six papers included men with normal semen analyses or subclinical varicocele, or both, which introduces bias in the results (Breznik 1993; Grasso 2000; Nilsson 1979; Sautter 2002; Unal 2001; Yamamoto 1996). Men with normal semen analyses and subclinical varicocele are arguably not as negatively affected by their varicocele, and thus less likely than men with abnormal semen parameters or clinical varicocele, or both, to see as much of an improvement in live birth and pregnancy rate. This was visible in the results. Fifteen papers were only available in Chinese and required translation (Chen 1996; Fang 2013; Gao 2015; Gao 2017; Meng 2017; Min 2011; Niu 2017; Pu 2014; Qi 2009; Ren 2015; Song 2012; Su 2017; Yang 2017; Zhang 2015a; Zheng 2012). Data extraction and general understanding for these papers may have been hindered. Allocation Random sequence generation Although the included studies all contained a statement about random allocation, this often remained unclear. Nine studies (11 references) used computer randomisation and were considered to be at low risk of selection bias (Abdel‐Meguid 2011a; Barbalias 1998; Barry 2012; Ketabchi 2018a; Ketabchi 2018b; Krause 2002; Nieschlag 1993; Nieschlag 1995/1998; Yang 2017). Thirty‐nine studies mentioned randomisation, but it was unclear how this was done (Al Kandari 2007; Al Said 2008; Bo 1996; Breznik 1993; Bryniarski 2016; Cayan 2000; Chaudhary 2000; Chen 1996; De Rose 2003; Dohle 2010; Fang 2013; Fayez 2010; Gao 2015; Gao 2017; Ghanaie 2012; Gontero 2005; Grasso 2000; Hargreave 1996; Madgar 1995; Meng 2017; Min 2011; Nilsson 1979; Niu 2017; Pan 2013; Pocek 1999; Pu 2014; Punekar 1999; Qi 2009; Ren 2015; Sautter 2002; Song 2012; Su 2017; Sun 2012; Telkar 2012; Unal 2001; Yamamoto 1996; Yavetz 1992; Zhang 2015a; Zheng 2012); we assessed these studies as at unclear risk of selection bias. Allocation concealment Five studies (six references) described a strategy for concealment of the allocation sequence and were at low risk of selection bias (Abdel‐Meguid 2011a; Fayez 2010; Krause 2002; Nieschlag 1993; Nieschlag 1995/1998). Blinding Blinding is virtually impossible in surgical trials unless sham surgery is performed. Blinding is not likely to make a difference to objective outcomes (pregnancy and live birth rate). All studies were rated at low risk of bias. In one study, blinding was done for outcome assessors (Al Said 2008). For further details on the risk of selection bias in those studies not integrated in meta‐analyses, see Figure 2, Figure 3, and Characteristics of included studies. Incomplete outcome data The number of dropouts after randomisation and the losses to follow‐up ranged from 1.3% to 54%. We assessed the following studies as at low risk of attrition bias. (Abdel‐Meguid 2011a; Breznik 1993; Dohle 2010; Ghanaie 2012; Ketabchi 2018a; Ketabchi 2018b; Krause 2002; Madgar 1995; Nieschlag 1995/1998; Pan 2013; Pocek 1999; Sun 2012; Yavetz 1992; Zheng 2012). Complete follow‐up was done in two studies (Gontero 2005; Sautter 2002). Thirty studies did not mention the number of dropouts after randomisation and the losses to follow‐up or reported unclear data (Al Kandari 2007; Al Said 2008; Barbalias 1998; Barry 2012; Bo 1996; Cayan 2000; Chen 1996; De Rose 2003; Fang 2013; Fayez 2010; Gao 2015; Gao 2017; Grasso 2000; Hargreave 1996; Meng 2017; Min 2011; Nieschlag 1993; Nilsson 1979; Niu 2017; Pu 2014; Punekar 1999; Qi 2009; Ren 2015; Song 2012; Su 2017; Telkar 2012; Unal 2001; Yang 2017; Yamamoto 1996; Zhang 2015a); we considered these studies to be at unclear risk of attrition bias. One study used a per‐protocol approach (Bryniarski 2016), and one study only included participants who had completed a minimum of 12 months of follow‐up (Chaudhary 2000); we considered these studies to be at unclear risk of attrition bias. For further details on the risk of selection bias in those studies not integrated in meta‐analyses, see Figure 2, Figure 3, and Characteristics of included studies. Selective reporting For infertility interventions, live birth and pregnancy rate are the most important outcomes, and no other outcomes were consistently reported. Varicocele recurrence and hydrocele formation were also often reported. When the protocol or a trial registration was available, we compared it with the publication and could not detect selective reporting (Bryniarski 2016; Ketabchi 2018a). One study did not account for incomplete data (Cayan 2000). In 45 studies, no protocol or trial registry entry was available, so selective reporting bias remains unclear. For further details on the risk of selection bias in those studies not integrated in meta‐analyses, see Figure 2, Figure 3, and Characteristics of included studies. Other potential sources of bias Nine studies (10 references) reported no baseline differences (Abdel‐Meguid 2011a; Al Kandari 2007; Al Said 2008; Dohle 2010; Krause 2002; Madgar 1995; Nieschlag 1993; Nieschlag 1995/1998); one study reported no difference in baseline age (Unal 2001); and 38 studies did not report if there were baseline differences (Barbalias 1998; Barry 2012; Breznik 1993; Bryniarski 2016; Cayan 2000; Chaudhary 2000; Chen 1996; Fang 2013; Fayez 2010; Gao 2015; Gao 2017; Ghanaie 2012; Gontero 2005; Grasso 2000; Hargreave 1996; Ketabchi 2018a; Ketabchi 2018b; Meng 2017; Min 2011; Nilsson 1979; Niu 2017; Pan 2013; Pocek 1999; Pu 2014; Punekar 1999; Qi 2009; Ren 2015; Sautter 2002; Song 2012; Su 2017; Sun 2012; Telkar 2012; Unal 2001; Yamamoto 1996; Yang 2017; Yavetz 1992; Zhang 2015a; Zheng 2012). We assessed these studies as at unclear risk of bias. The period of untreated follow‐up was three months in one study (Sautter 2002), three to 24 months in one study (Yang 2017), six months in four studies (Gao 2015; Gao 2017; Gontero 2005; Niu 2017), six to 18 months in one study (Ren 2015), 12 to 40 months in one study (Unal 2001), 12 months in 15 studies (16 references) (Abdel‐Meguid 2011a; Barbalias 1998; Bryniarski 2016; Fayez 2010; Ghanaie 2012; Grasso 2000; Ketabchi 2018a; Krause 2002; Madgar 1995; Nieschlag 1993; Nieschlag 1995/1998; Pan 2013; Pu 2014; Punekar 1999; Yamamoto 1996), six to 18 months in one study (Chen 1996), 18 months in two studies (Al Kandari 2007; Yavetz 1992), 12 to 28 months in one study (Al Said 2008), 24 months in two studies (Ketabchi 2018b; Qi 2009), and > 36 months in two studies (Breznik 1993; Nilsson 1979). The period of untreated follow‐up was not mentioned in 17 studies (Barry 2012; Breznik 1993; Cayan 2000; Chaudhary 2000; De Rose 2003; Dohle 2010; Fang 2013; Hargreave 1996; Meng 2017; Min 2011; Pocek 1999; Song 2012; Su 2017; Sun 2012; Telkar 2012; Zhang 2015a; Zheng 2012). Studies with an untreated follow‐up duration of over 12 months can report unjustifiably higher pregnancy rates, which is also a source of bias. Likewise, shorter follow‐up periods may not capture varicocele recurrences or adverse events that occur later on, which is another source of bias. For further details on the risk of selection bias in those studies not integrated in meta‐analyses, see Figure 2, Figure 3, and Characteristics of included studies. Effects of interventions See: Table 1; Table 2; Table 3; Table 4 1. Comparison: treatment versus non‐surgical, non‐radiological, delayed, or no treatment Primary outcomes 1.1. Live birth We are uncertain whether surgical or radiological treatment improves live birth rates compared to no treatment. One RCT compared surgical treatment with no treatment and demonstrated higher live birth rates in men who had treatment (Ghanaie 2012), whilst the other study compared surgical treatment with no treatment and showed similarly low live birth rates in both groups (Grasso 2000) (surgical treatment: 38%, no treatment: 6%; risk ratio (RR) 6.50, 95% confidence interval (CI) 2.40 to 17.63; 1 RCT, N = 136; surgical treatment: 3%, no treatment: 6%; RR 0.50, 95% CI 0.05 to 5.26; 1 RCT, N = 68; I2 = 74%, very low‐certainty evidence). When pooling these two studies, heterogeneity was very high (Tau2 = 2.44, I2 = 74%), and the confidence interval was very broad (RR 2.27, 95% CI 0.19 to 26.93), reducing the meaningfulness of the pooled effect estimate (Analysis 1.1, Figure 4). 1.2. Adverse events No studies reported on adverse events. Secondary outcomes 1.3. Pregnancy Treatment may improve pregnancy rates compared to delayed or no treatment (RR 1.55, 95% CI 1.06 to 2.26; 13 RCTs, N = 1193, I2 = 65%, low‐certainty evidence). This suggests that couples without treatment or delayed treatment have a 21% chance of pregnancy, whilst the pregnancy rate after surgical or radiological treatment is between 22% and 48% (Analysis 1.2, Figure 5) (Abdel‐Meguid 2011a; Bo 1996; Breznik 1993; Dohle 2010; Ghanaie 2012; Ketabchi 2018a; Ketabchi 2018b; Krause 2002; Madgar 1995; Nieschlag 1995/1998; Nilsson 1979; Unal 2001; Yamamoto 1996). Treatment may improve pregnancy rates compared to delayed or no treatment in men with abnormal semen analysis and a clinical varicocele (RR 1.94, 95% CI 1.23 to 3.05; 7 RCTs, N = 693, I2 = 61%, low‐certainty evidence). This suggests that couples without treatment or delayed treatment have a 21% chance of pregnancy, whilst the pregnancy rate after surgical or radiological treatment is between 26% and 64% (Abdel‐Meguid 2011a; Dohle 2010; Ketabchi 2018a; Ketabchi 2018b; Krause 2002; Madgar 1995; Nieschlag 1995/1998). Two studies were not integrated in the analysis as they reported conflicting data (De Rose 2003; Hargreave 1996). De Rose 2003 reported a pregnancy rate of 27.7% in the treatment group compared to 46% in the no treatment group. Hargreave 1996 reported a pregnancy rate of 31.3% in the treatment group compared to 14.4% in the no treatment group. In both studies, the percentages were conflicting, as they were not able to be calculated with the number of participants reported in each group. Given the percentages reported, there were likely dropouts in both studies; however, this was not reported. 1.4. Varicocele recurrence No studies reported on varicocele recurrence. 1.5. Quality of life No studies reported on quality of life. 2. Comparison: surgical versus radiological treatment Primary outcomes 2.1. Live birth We are uncertain about the effect of surgical versus radiological treatment on live birth (RR 1.49, 95% CI 0.66 to 3.37; 1 RCT, N = 155, very low‐certainty evidence) (Analysis 2.1) (Fayez 2010). 2.2. Adverse events We are uncertain about the effect of surgical versus radiological treatment on hydrocele formation (RR 4.24, 95% CI 0.53 to 33.76; 3 RCTs, N = 248, I2 = 60%, very low‐certainty evidence; pain (RR 11.00, 95% CI 0.64 to 190.26; 1 RCT, N = 58, very low‐certainty evidence); epididymitis (RR 3.00, 95% CI 0.33 to 27.18; 1 RCT, N = 58, very low‐certainty evidence); haematoma (RR 0.14, 95% CI 0.01 to 2.65; 1 RCT, N = 58, very low‐certainty evidence); and suture granuloma (RR 3.00, 95% CI 0.13 to 70.74; 1 RCT, N = 58, very low‐certainty evidence) (Analysis 2.2; Analysis 2.3; Analysis 2.4; Analysis 2.5; Analysis 2.6) (Fayez 2010; Nieschlag 1993; Sautter 2002). Secondary outcomes 2.3. Pregnancy We are uncertain about the effect of surgical versus radiological treatment on pregnancy rate (RR 1.13, 95% CI 0.75 to 1.70; 5 RCTs, N = 456, I2 = 19%, low‐certainty evidence). This suggests that if the pregnancy rate following radiological treatment is 19%, the pregnancy rate following surgical treatment would be between 14% and 32% (Analysis 2.7) (Chen 1996; Fayez 2010; Nieschlag 1993; Nieschlag 1995/1998; Yavetz 1992). 2.4. Varicocele recurrence We are uncertain about the effect of surgical versus radiological treatment on varicocele recurrence (RR 1.31, 95% CI 0.82 to 2.08; 3 RCTs, N = 380, I2 = 0%, low‐certainty evidence). This suggests that if the varicocele recurrence rate following radiological treatment is 14%, the varicocele recurrence rate following surgical treatment would be between 11% and 29% (Analysis 2.8) (Barbalias 1998; Fayez 2010; Yavetz 1992). 2.5. Quality of life No studies reported on quality of life. 3. Comparison: surgical treatment versus other surgical treatment Primary outcomes 3.1a Live birth No studies reported on live birth. 3.2a Adverse events We are uncertain of the effect of microscopic subinguinal surgical treatment compared to other surgical treatment on hydrocele formation (RR 0.23, 95% CI 0.05 to 1.14; 4 RCTs, N = 372, I2 = 15%, very low‐certainty evidence) (Analysis 3.2) (Pan 2013; Punekar 1999; Ren 2015; Song 2012). Two studies reported on hydrocele formation, but reported their results per number of varicoceles instead of per participant (Al Kandari 2007; Al Said 2008). Al Kandari 2007 reported zero men with hydrocele formation in the microscopic subinguinal surgical treatment group compared to 17 in the other surgical treatment group. The difference was statistically significant in favour of the microscopic subinguinal treatment group. Al Said 2008 reported zero men with hydrocele formation in the microscopic subinguinal surgical treatment group compared to 12 in the other surgical treatment group. The difference was statistically significant in favour of the microscopic subinguinal treatment group. We are uncertain of the effect of microscopic subinguinal surgical treatment compared to other surgical treatment on testicular atrophy rates (RR 0.18, 95% CI 0.02 to 1.89; 3 RCTs, N = 538, I2 = 38%, very low‐certainty of evidence); haematoma (RR 0.76, 95% CI 0.11 to 5.16; 2 RCTs, N = 418, I2 = 0%, very low‐certainty evidence); pain (RR 0.33, 95% CI 0.07 to 1.49; 1 RCT, N = 298, very low‐certainty evidence), wound infection (RR 1.66, 95% CI 0.24 to 11.62; 1 RCT, N = 298, very low‐certainty evidence); oedema (RR 0.20, 95% CI 0.02 to 1.67; 1 RCT, N = 140, very low‐certainty evidence); and abdominal distention (RR 0.20, 95% CI 0.02 to 1.72; 2 RCTs, N = 192, I2 = 3%, very low‐certainty evidence) (Analysis 3.3; Analysis 3.4; Analysis 3.5; Analysis 3.6; Analysis 3.7; Analysis 3.8) (Al Kandari 2007; Al Said 2008; Min 2011; Punekar 1999; Song 2012). Secondary outcomes 3.3a Pregnancy Microscopic subinguinal surgical treatment probably results in a slight improvement in pregnancy rates compared to other surgical treatments (RR 1.18, 95% CI 1.02 to 1.36; 12 RCTs, N = 1473, I2 = 0%, moderate‐certainty evidence). This suggests that couples with microscopic subinguinal surgical treatment have a 10% to 14% chance of pregnancy after treatment, whilst the pregnancy rate in couples after other surgical treatments is 10% (Analysis 3.1, Figure 6) (Al Kandari 2007; Al Said 2008; Bryniarski 2016; Fang 2013; Gao 2017; Min 2011; Pan 2013; Punekar 1999; Qi 2009; Ren 2015; Song 2012; Su 2017). 3.4a Varicocele recurrence Microscopic subinguinal surgical treatment probably reduces the risk of varicocele recurrence (RR 0.48, 95% CI 0.29 to 0.79; 14 RCTs, N = 1565, I2 = 0%, moderate‐certainty evidence). This suggests that 0.4% to 1.1% of men who undergo microscopic subinguinal surgical treatment experience recurrent varicocele, whilst 1.4% of men who undergo other surgical treatments do (Analysis 3.9, Figure 7) (Fang 2013; Gao 2015; Gontero 2005; Meng 2017; Min 2011; Pan 2013; Pu 2014; Punekar 1999; Ren 2015; Song 2012; Su 2017; Yang 2017; Zhang 2015a; Zheng 2012). Two studies reported on varicocele recurrence, but reported their results per number of varicoceles instead of per participant (Al Kandari 2007; Al Said 2008). Al Kandari 2007 reported one man with varicocele recurrence in the microscopic subinguinal surgical treatment group compared to nine in the other surgical treatment group. The difference was statistically significant in favour of the microscopic subinguinal surgical treatment group. Al Said 2008 reported four men with varicocele recurrence in the microscopic subinguinal surgical treatment group compared to 41 in the other surgical treatment group. The difference was statistically significant in favour of the microscopic subinguinal surgical treatment group. One study compared microscopic inguinal surgical treatment versus laparoscopic surgical treatment and was not included in the meta‐analysis, as microscopic inguinal surgical treatment is a different surgical treatment from microscopic subinguinal surgical treatment, and the latter is of higher clinical relevance deserving its own comparison (Niu 2017). The study reported one man with varicocele recurrence in the microscopic inguinal surgical treatment group compared to eight in the laparoscopic surgical treatment group. The difference was statistically significant in favour of the microscopic inguinal surgical treatment group. 3.5a Quality of life No studies reported on quality of life. Primary outcomes 3.1b Live birth No studies reported on live birth. 3.2b Adverse events We are uncertain of the effect of open inguinal surgical treatment compared to retroperitoneal surgical treatment on hydrocele formation (RR 1.03, 95% CI 0.31 to 3.47; 6 RCTs, N = 765, I2 = 61%, very low‐certainty evidence) (Analysis 4.2) (Barbalias 1998; Barry 2012; Cayan 2000; Chaudhary 2000; Pu 2014; Telkar 2012). Two studies reported on hydrocele formation, but reported their results per number of varicoceles instead of per participant (Al Kandari 2007; Al Said 2008). Al Kandari 2007 reported seven men with hydrocele formation in the open inguinal surgical treatment group compared to 10 in the retroperitoneal surgical treatment group. The difference was not statistically significant. Al Said 2008 reported four men with hydrocele formation in the open inguinal treatment group compared to eight in the retroperitoneal surgical treatment group. The difference was not statistically significant. We are uncertain of the effect of open inguinal surgical treatment compared to retroperitoneal surgical treatment on testicular atrophy (RR 0.33, 95% CI 0.01 to 7.87; 3 RCTs, N = 430, I2 = 0%, very low‐certainty evidence); haematoma (RR 3.75, 95% CI 0.62 to 22.71; 3 RCTs, N = 338, I2 = 0%, very low‐certainty evidence); pain (RR 0.86, 95% CI 0.29 to 2.56; 2 RCTs, N = 266, I2 = 0%, very low‐certainty evidence); wound infection rates (RR 2.96, 95% CI 0.79 to 11.07; 4 RCTs, N = 368, I2 = 0%, very low‐certainty evidence); oedema (RR 1.20, 95% CI 0.60 to 2.40; 2 RCTs, N = 175, I2 = 0%, very low‐certainty evidence); epididymitis (RR 0.61, 95% CI 0.11 to 3.52; 1 RCT, N = 115, very low‐certainty evidence); epididymo‐orchitis (RR 2.00, 95% CI 0.19 to 21.18; 1 RCT, N = 80, very low‐certainty evidence); pneumoscrotum (RR 0.33, 95% CI 0.01 to 7.95; 1 RCT, N = 80, very low‐certainty evidence); subcutaneous emphysema (RR 0.33, 95% CI 0.01 to 7.95; 1 RCT, N = 80, very low‐certainty evidence); inferior epigastric bleeding (RR 0.33, 95% CI 0.01 to 7.95; 1 RCT, N = 80, very low‐certainty evidence); persistence of dilated veins (RR 0.22, 95% CI 0.03 to 1.82; 1 RCT, N = 72, very low‐certainty evidence); and wound erythema (RR 5.00, 95% CI 0.26 to 96.13; 1 RCT, N = 30, very low‐certainty evidence) (Analysis 4.3; Analysis 4.4; Analysis 4.5; Analysis 4.6; Analysis 4.7; Analysis 4.8; Analysis 4.9; Analysis 4.10; Analysis 4.11; Analysis 4.12; Analysis 4.13; Analysis 4.14) (Al Said 2008; Barry 2012; Chaudhary 2000; Fang 2013; Su 2017; Telkar 2012). Secondary outcomes 3.3b Pregnancy We are uncertain of the effect of open inguinal surgical treatment compared to retroperitoneal surgical treatment on pregnancy rate (RR 1.02, 95% CI 0.82 to 1.27; 5 RCTs, N = 889, I2 = 0%, low‐certainty evidence). This suggests that if the pregnancy rate following retroperitoneal surgical treatment is 26%, the pregnancy rate following surgical treatment would be between 21% and 33% (Analysis 4.1) (Al Kandari 2007; Al Said 2008; Cayan 2000; Fang 2013; Su 2017). 3.4b Varicocele recurrence We are uncertain of the effect of open inguinal surgical treatment compared to retroperitoneal surgical treatment on varicocele recurrence rates (RR 1.03, 95% CI 0.43 to 2.46; 8 RCTs, N = 1063, I2 = 71%, very low‐certainty evidence). This suggests that if the rate of varicocele recurrence following retroperitoneal treatment is 11%, the rate following open inguinal surgical treatment would be between 5% and 27% (Analysis 4.15) (Barbalias 1998; Barry 2012; Cayan 2000; Chaudhary 2000; Fang 2013; Pu 2014; Su 2017; Sun 2012). Two studies reported on varicocele recurrence, but reported their results per number of varicoceles instead of per participant (Al Kandari 2007; Al Said 2008). Al Kandari 2007 reported seven men with varicocele recurrence in the open inguinal surgical treatment group compared to nine in the retroperitoneal surgical treatment group. The difference was not statistically significant. Al Said 2008 reported 16 men with varicocele recurrence in the open inguinal treatment group compared to 25 in the retroperitoneal surgical treatment group. The difference was not statistically significant. 3.5b Quality of life No studies reported on quality of life. 4. Comparison: radiological treatment versus other radiological treatment Primary outcomes 4.1 Live birth No studies reported on live birth. 4.2 Adverse events No studies reported on adverse events. Secondary outcomes 4.3 Pregnancy No studies reported on pregnancy rate. 4.4 Varicocele recurrence One study compared two types of radiological treatment (sclerotherapy versus embolisation) and reported 13% varicocele recurrence in both groups. Due to the broad confidence interval, no valid conclusion could be drawn (RR 1.00, 95% CI 0.16 to 6.20; 1 RCT, N = 30, very low‐certainty evidence) (Analysis 5.1) (Pocek 1999). 4.5 Quality of life No studies reported on quality of life.

Summary of main results We found that any treatment (surgical or radiological) may be more effective in increasing pregnancy rates than delayed or no treatment. Any treatment (surgical or radiological) was found to be more effective in increasing pregnancy rates in participants with abnormal semen parameters and clinical varicocele; however, we acknowledge that the findings of subgroups are merely observational. Our findings failed to offer valid evidence that any treatment (surgical or radiological) has a positive or negative effect on live birth. Evidence on varicocele recurrence, adverse events, or quality of life was lacking. When comparing surgical with radiological treatment, we could draw no valid conclusions that surgical treatment or radiological treatment was the superior method in improving the chance of live birth or pregnancy. The evidence on varicocele recurrence and adverse events (hydrocele formation, pain, epididymitis, haematoma, and suture granuloma) was also inconclusive. Evidence on quality of life was lacking for this comparison. When comparing surgical treatments with each other, microscopic subinguinal surgical treatment showed higher pregnancy rates and lower varicocele recurrence rates than other surgical treatments. However, given the inconclusive evidence, we are uncertain if the type of surgery affects live birth or adverse events. Evidence on quality of life was missing. Comparing open inguinal surgical treatment with retroperitoneal surgical treatment, we could draw no valid conclusions that one of these surgical approaches was the superior method in terms of live birth, pregnancy rates, varicocele recurrence rate, and adverse events. Evidence on quality of life was lacking for this comparison. The only study comparing radiological treatments reported solely on varicocele recurrence, and due to methodological limitations, we were unable to draw any firm conclusions about efficacy. Overall completeness and applicability of evidence Only three of the 48 included studies reported on the primary efficacy outcome of live birth. These studies compared any surgical or radiological treatment versus non‐surgical, non‐radiological, delayed, or no treatment, and surgical treatment versus radiological treatment. The evidence base for the most patient‐relevant outcome is thus very limited. More studies (33) reported on pregnancy, which is a relevant outcome but could be inflated by miscarriages or still birth, and is ultimately not as patient relevant as live birth. In addition, most studies lacked definitions of pregnancy, leaving it unclear whether pregnancy referred to clinical pregnancy (sonographically proven) or early stages of pregnancy (only confirmed by a positive pregnancy test). The scope was expanded for the 2021 review due to the clinical relevance of the 'treatment versus treatment' comparison. We found that microscopic subinguinal surgical treatment was superior to other surgical treatment in terms of pregnancy rate and varicocele recurrence. The certainty of evidence was moderate. The results for pregnancy rates, varicocele recurrence, and adverse events for other surgical comparisons were inconclusive due to very broad confidence intervals. One study that compared treatments directly reported on live birth. No study reported on quality of life. Although the majority of included studies focused solely on couples with male factor infertility, older studies did not always specify that women had no known fertility problems. This should be considered when interpreting the findings. Quality of the evidence The clinical and statistical heterogeneity of the studies and the small numbers of participants should be taken into account, and the overall certainty of the evidence was rated mostly as low or very low for all outcomes (see Table 1; Table 2; Table 3; Table 4). Reasons for downgrading the certainty of evidence were mainly imprecision (small studies, broad confidence intervals), as well as inconsistency (high I2 as indicator for heterogeneity) and high risk of bias. A funnel plot for the comparison 'treatment versus non‐surgical, non‐radiological, delayed, or no treatment' and the outcome of pregnancy rate was not suggestive of publication bias. In the other meta‐analyses, fewer than 10 studies were included, so we did not conduct funnel plots. Consequently, the risk of publication bias cannot be ruled out. Potential biases in the review process The decision to include studies which included normozoospermic men from infertile couples is disputable (Breznik 1993; Ghanaie 2012; Nilsson 1979; Unal 2001; Yamamoto 1996), but was based on the decision to broaden the scope of the review and represent a wide number of men for whom varicocelectomy is deemed appropriate. Given their allocation by randomisation, these men were evenly distributed between the experimental group and the controls. Also, the decision to include studies that accepted men with subclinical varicocele is disputable (Breznik 1993; Grasso 2000; Nilsson 1979; Unal 2001; Yamamoto 1996). The AUA/ASRM and EAU state that normospermia and subclinical varicocele are no indication for surgical treatment (Schlegel 2021; EAU 2018). A literature search regarding the relationship between grade of varicocele and the response to varicocelectomy showed different outcomes, ranging from no improvement of semen analysis after treatment of subclinical varicocele to significant improvement. However, live birth or pregnancy rate was not an outcome in these studies. For this reason we performed a subgroup analysis that excluded these studies (Breznik 1993; Grasso 2000; Nilsson 1979; Unal 2001; Yamamoto 1996). Future updates of this review might consider altering the protocol alongside the guidelines of the AUA and EAU, only including men with abnormal semen analysis and clinical varicocele, as this patient group is more relevant for clinical practice and more likely to show a positive benefit from treatment. Agreements and disagreements with other studies or reviews This review covers a long period of time. Particularly in the older studies, study methodology was far from perfect. Although the findings of our previous meta‐analyses are consistent with some non‐Cochrane Reviews (Baazeem 2011; Cocuzza 2008; French 2008; Marmar 2007), the current updated review suggests that there might be some value in varicocelectomy in selected men. A recent non‐Cochrane Review also found similar findings, exhibiting a significant difference in spontaneous pregnancy rates in men with clinical and subclinical varicocele and abnormal semen analysis (Kim 2013). However, this paper reported on the same papers included in the 2012 review (Kroese 2012). A recent non‐Cochrane Review comparing microscopic surgical treatment (subinguinal and inguinal) to laparoscopic treatment reported similar results, indicating that microscopic treatment results in lower recurrence rates and fewer adverse events (Wang 2020). One systematic review comparing treatment methods found no significant difference in spontaneous pregnancy rates, however found reduced rates of varicocele recurrence and hydrocele formation after microsurgical treatment compared to laparoscopic or open surgical treatment (Ding 2012). However, this review included data from two papers that reported their results for varicocele recurrence and adverse events per number of varicocele instead of per number of men, thus mixing the denominators. These papers were included in our review for the outcome pregnancy rate, which they reported per number of men, but data were not included for the other outcomes (Al Kandari 2007; Al Said 2008). Another systematic review comparing retroperitoneal treatment, microsurgical inguinal treatment, and microscopic subinguinal treatment found that microscopic inguinal surgical treatment resulted in statistically significantly higher spontaneous pregnancy rates when compared to high ligation and subinguinal treatment; however, the studies reporting this were not RCTs and were from the early 2000s (Schauer 2012). The comparison in our review focused on microscopic subinguinal surgical treatment, which is currently viewed as the gold standard. Schauer 2012 also reported higher spontaneous pregnancy rates in treatment groups compared to no treatment groups, which is in line with our results. However, these results are again subject to interpretation, given that this review contained studies that were not RCTs (Schauer 2012). Another systematic review comparing various treatments (laparoscopic treatment, retroperitoneal treatment, open inguinal and subinguinal treatments, microsurgical subinguinal and inguinal treatments, percutaneous venous embolisation, Tauber antegrade sclerotherapy, retrograde sclerotherapy, and no treatment) to one another found that inguinal microsurgical treatment, subinguinal microsurgical treatment, open inguinal treatment, and laparoscopic varicocelectomy led to statistically significantly higher pregnancy rates (Wang 2015). Subinguinal and inguinal microsurgical treatment also showed lower levels of varicocele recurrence. Furthermore, Tauber antegrade sclerotherapy and subinguinal microsurgical treatment led to a lower rate of hydrocele formation. However, this review contained studies that were not RCTs (Wang 2015). Authors' conclusions Implications for practice. Varicocele treatment, when compared to non‐surgical, non‐radiological, delayed, or no treatment, showed a beneficial effect on pregnancy rate amongst 1193 men with mixed semen analysis. Nine men would need to be treated for one to benefit. Microscopic subinguinal surgical treatment, when compared to other surgical treatment, showed a beneficial effect on pregnancy rate amongst 1473 men. Ten men would need to be treated for one to benefit. The same comparison showed a beneficial effect on varicocele recurrence rate amongst 1565 men. Fifteen men would need to be treated for one to benefit. The direct comparison of other treatment methods did not permit us to draw any valid conclusions about the superiority or inferiority of one intervention over another on pregnancy, varicocele recurrence, or adverse events. How any of these interventions impact quality of life is unclear, as this outcome was not measured in any study. Implications for research. The ideal trial design for the 'treatment versus non‐surgical, delayed, or no treatment' comparison would be to compare a group of men undergoing the treatment procedure with the other group obtaining a sham surgical procedure. Any other design is potentially biased by the placebo effect of having had the operation performed. However, such a trial design would be difficult to obtain ethical committee approval, as it would put the control group at risk of surgical and anaesthetic complications without any possibility of benefit (Hargreave 1997). As all studies included in the current review mostly considered invasive treatment, blinding of the investigator, participant, or assessor to the procedure performed was rarely performed. However, the outcome measures of this review, live birth and pregnancy rate, were unambiguous. As a result, apart from the placebo effect, no other negative factors of the lack of blinding were presumed to have affected the conclusions drawn. Although a trial is the most optimal design to assess the efficacy of the 'treatment versus treatment' comparison, potential bias cannot be ruled out, particularly as the the studies were not blinded. However, as blinding was difficult due to the nature of the invasive treatments performed and as lack of blinding was unlikely to influence the outcomes assessed, all studies were graded at a low risk of bias for blinding. Nevertheless, studies that could implement blinding and mitigate potential bias would be ideal. The studies included in the current review of varicocele treatment were heterogeneous. This indicates the need for a large, properly conducted randomised controlled trial of varicocele treatment in men with varicocele and sperm defects, from couples with otherwise unexplained subfertility. However, we realise that it will become increasingly difficult to conduct such a study, as the introduction of in vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI) in the fertility clinic will make many men reluctant to take the risk of being allocated to the no‐treatment arm of such a study, whilst a robust treatment of proven effectiveness is readily available in the form of IVF/ICSI. The issue will be further compounded by the fact that as many couples today tend to delay their first pregnancy, they are likely to feel pressed for time to conceive once they have decided in their mid‐ to late‐thirties to seek professional help for their fertility issues. Nevertheless, in countries or couples where IVF/ICSI is not a feasible option, varicocele treatment will continue to be performed and contribute to clinical knowledge and research. In the future, authors should strive to report adverse events alongside outcomes, as this was poorly done in the studies assessed and has large implications on the overall success and practicality of the treatment of varicoceles. What's new | Date | Event | Description | |---|---|---| | 22 August 2020 | New citation required and conclusions have changed | The scope of the review was expanded. In addition to the comparison 'treatment (surgery or radiological treatment) versus non‐surgical treatment, no, or delayed treatment', direct comparisons of different surgical treatments with each other, different radiological treatments with each other, and surgical treatments with radiological treatments were included in this review. This resulted in the inclusion of 38 new studies. A total of 48 studies are now included in the review. We deemed a random‐effects model to be more appropriate than a fixed‐effect model, and this was subsequently applied to all meta‐analyses. | | 22 August 2020 | New search has been performed | There is a new author team for this update. They have expanded the scope of the review and added 38 new studies: Al Kandari 2007; Al Said 2008; Barbalias 1998; Barry 2012; Bo 1996; Bryniarski 2016; Cayan 2000; Chaudhary 2000; Chen 1996; De Rose 2003; Fang 2013; Fayez 2010; Gao 2015; Gao 2017; Ghanaie 2012; Gontero 2005; Hargreave 1996; Ketabchi 2018a; Ketabchi 2018b; Meng 2017; Min 2011; Nieschlag 1993; Niu 2017; Pan 2013; Pocek 1999; Pu 2014; Punekar 1999; Qi 2009; Ren 2015; Sautter 2002; Song 2012; Su 2017; Sun 2012; Telkar 2012; Yang 2017; Yavetz 1992; Zhang 2015a; Zheng 2012. | History Protocol first published: Issue 2, 1995 Review first published: Issue 1, 2001 | Date | Event | Description | |---|---|---| | 2 February 2012 | New search has been performed | Anja Kroese and Natascha de Lange added to authoring team. | | 21 October 2008 | Amended | 'Risk of bias' figures added. | | 22 April 2008 | Amended | Converted to new review format | | 22 April 2008 | New citation required but conclusions have not changed | Jane Clarke added to authoring team. | | 15 January 2008 | New citation required and conclusions have changed | Substantive amendment | | 22 November 2007 | New search has been performed | Two new studies found and excluded. | | 25 October 2007 | New search has been performed | Search string revised and re‐run. | Notes In the 2004 update, three new randomised controlled trials (RCTs) were included in the review; one ongoing study was added; and further detail was added to the narrative sections of the review. In the 2008 update, two new RCTs were considered for inclusion that were excluded. In the 2009 update, no new RCTs were included. In the 2012 update, six new RCTs were included. In the 2020/2021 update, three new RCTs were included in the original comparison. The scope was expanded to compare treatment to treatment, and 37 additional studies in five new comparisons were included.

The authors of the 2021 update thank John Collins, Johannes LH Evers, Jane Clarke, Anja CJ Kroese, Natascha M de Lange, and Patrick Vandekerckhove for their contributions to previous versions of this review. The authors also thank Yuan Chi and Huisi Wang for searching the Chinese databases for studies of interest following reference list checking, and Milon Au Yeung for performing the translations of the Chinese papers. Appendices Appendix 1. Cochrane Gynaecology and Fertility Specialised Register search strategy Searched 4 April 2020 ProCite platform

CONTAINS "varicocoele" or "varicocele" or "male factor subfertility" or "male factor" or "male infertility" or "male subfertility" or "subfertility‐male" or "sperm" or Title CONTAINS "varicocoele" or "varicocele" or "male factor subfertility" or "male factor" or "male infertility" or "male subfertility" or "subfertility‐male" or "sperm" AND

CONTAINS "ligation" or "ligation of spermatic vein" or "Ligausre vessel sealing" or "artery ligation" or "vein ligation" or "veinembolization" or "surgery" or "Surgical" or "surgical ligation" or "*Surgical‐Procedures,‐Laparoscopic" or "varicocele‐embolization" or "varicocele ligation" or "varicocele‐outcome" or "varicocelectomy" or "varicocoelectomy" or "varicocolectomy" or "embolisation" or "embolization" or "varicocoele repair" or Title CONTAINS "ligation" or "ligation of spermatic vein" or "Ligausre vessel sealing" or "artery ligation" or "vein ligation" or "veinembolization" or "surgery" or "Surgical" or "surgical ligation" or "*Surgical‐Procedures,‐Laparoscopic" or "varicocele‐embolization" or "varicocele ligation" or "varicocele‐outcome" or "varicocelectomy" or "varicocoelectomy" or "varicocolectomy" or "embolisation" or "embolization" or "varicocoele repair" (173 records) Appendix 2. CENTRAL via the Cochrane Register of Studies Online (CRSO) search strategy Searched 4 April 2020 Web platform #1 MESH DESCRIPTOR Varicocele EXPLODE ALL TREES 145 #2 (Varicocele* or Varicocoele*):TI,AB,KY 384 #3 MESH DESCRIPTOR Infertility, Male EXPLODE ALL TREES 713 #4 ((male* or men) adj7 (infertil* or subfertil*)):TI,AB,KY 1202 #5 #1 OR #2 OR #3 OR #4 1821 #6 MESH DESCRIPTOR Urologic Surgical Procedures, Male EXPLODE ALL TREES 2479 #7 (Varicocelectom* or Varicocoelectom*):TI,AB,KY 220 #8 ((Varicocele* or Varicocoele*) adj5 (repair* or correct*)):TI,AB,KY 29 #9 MESH DESCRIPTOR Ligation EXPLODE ALL TREES 598 #10 MESH DESCRIPTOR Microsurgery EXPLODE ALL TREES 630 #11 (Ligation* or microsurg*):TI,AB,KY 3761 #12 emboli?ation*:TI,AB,KY 2140 #13 surg*:TI,AB,KY 226474 #14 (occlusion adj3 sperm*):TI,AB,KY 5 #15 (sperm* adj3 vein*):TI,AB,KY 72 #16 (vessel* adj3 seal*):TI,AB,KY 220 #17 MESH DESCRIPTOR Embolization, Therapeutic EXPLODE ALL TREES 744 #18 #6 OR #7 OR #8 OR #9 OR #10 OR #11 OR #12 OR #13 OR #14 OR #15 OR #16 OR #17 229980 #19 #5 AND #18 429 Appendix 3. MEDLINE search strategy Searched from 1946 to 4 April 2020 OVID Platform 1 exp VARICOCELE/ (4452) 2 (Varicocele* or Varicocoele*).tw. (5140) 3 exp Infertility, Male/ (27512) 4 ((male* or men) adj7 (infertil* or subfertil*)).tw. (18231) 5 or/1‐4 (37961) 6 Urologic Surgical Procedures, Male/ (3463) 7 (Varicocelectom* or Varicocoelectom*).tw. (1231) 8 ((Varicocele* or Varicocoele*) adj5 (repair* or correct*)).tw. (539) 9 ligation/ or microsurgery/ (49635) 10 (Ligation* or microsurg*).tw. (98059) 11 emboli?ation*.tw. (47220) 12 surg*.tw. (1876292) 13 (occlusion adj3 sperm*).tw. (45) 14 (sperm* adj3 vein*).tw. (1037) 15 (vessel* adj3 seal*).tw. (969) 16 exp Embolization, Therapeutic/ (41062) 17 or/6‐16 (2006509) 18 5 and 17 (5006) 19 randomized controlled trial.pt. (503142) 20 controlled clinical trial.pt. (93595) 21 randomized.ab. (474917) 22 randomised.ab. (94956) 23 placebo.tw. (212175) 24 clinical trials as topic.sh. (190619) 25 randomly.ab. (330376) 26 trial.ti. (215880) 27 (crossover or cross‐over or cross over).tw. (84031) 28 or/19‐27 (1344105) 29 exp animals/ not humans.sh. (4685426) 30 28 not 29 (1236971) 31 18 and 30 (336) Appendix 4. Embase search strategy Searched from 1980 to 4 April 2020 OVID Platform 1 exp varicocele/ (6877) 2 (Varicocele* or Varicocoele*).tw. (6524) 3 exp male infertility/ (39235) 4 ((male* or men) adj7 (infertil* or subfertil*)).tw. (24969) 5 or/1‐4 (51955) 6 male genital system surgery/ or exp varicocelectomy/ (4397) 7 (Varicocelectom* or Varicocoelectom*).tw. (1799) 8 ((Varicocele* or Varicocoele*) adj5 (repair* or correct*)).tw. (748) 9 exp ligation/ (55157) 10 microsurgery/ (28261) 11 (Ligation* or microsurg*).tw. (121707) 12 emboli?ation*.tw. (68451) 13 surg*.tw. (2429523) 14 (occlusion adj3 sperm*).tw. (46) 15 (sperm* adj3 vein*).tw. (1133) 16 (vessel* adj3 seal*).tw. (1533) 17 exp artificial embolization/ (47263) 18 or/6‐17 (2593371) 19 5 and 18 (8002) 20 Clinical Trial/ (960848) 21 Randomized Controlled Trial/ (592972) 22 exp randomization/ (86518) 23 Single Blind Procedure/ (38349) 24 Double Blind Procedure/ (167879) 25 Crossover Procedure/ (62505) 26 Placebo/ (334252) 27 Randomi?ed controlled trial$.tw. (224126) 28 Rct.tw. (36215) 29 random allocation.tw. (1989) 30 randomly.tw. (433209) 31 randomly allocated.tw. (34527) 32 allocated randomly.tw. (2515) 33 (allocated adj2 random).tw. (811) 34 Single blind$.tw. (24275) 35 Double blind$.tw. (200281) 36 ((treble or triple) adj blind$).tw. (1119) 37 placebo$.tw. (298981) 38 prospective study/ (588837) 39 or/20‐38 (2396688) 40 case study/ (67672) 41 case report.tw. (396046) 42 abstract report/ or letter/ (1087762) 43 or/40‐42 (1541211) 44 39 not 43 (2343128) 45 (exp animal/ or animal.hw. or nonhuman/) not (exp human/ or human cell/ or (human or humans).ti.) (5937985) 46 44 not 45 (2180425) 47 19 and 46 (1099) Appendix 5. PsycINFO search strategy Searched from 1806 to 4 April 2020 OVID Platform 1 Varicoc$.tw. (27) 2 (male adj1 infertil$).tw. (153) 3 (male adj1 subfertil$).tw. (6) 4 or/1‐3 (183) 5 exp Surgery/ (70376) 6 varicocelectom$.tw. (3) 7 ligation$.tw. (1646) 8 emboli?ation$.tw. (272) 9 surg$.tw. (48623) 10 or/5‐9 (101306) 11 4 and 10 (16) Appendix 6. CINAHL search strategy Searched from 1961 to 4 April 2020 EBSCO Platform | # | Query | Results | | S31 | S18 AND S30 | 281 | | S30 | S19 OR S20 OR S21 OR S22 OR S23 OR S24 OR S25 OR S26 OR S27 OR S28 OR S29 | 1,590,647 | | S29 | TX allocat* random* | 13,134 | | S28 | (MH "Quantitative Studies") | 30,191 | | S27 | (MH "Placebos") | 13,639 | | S26 | TX placebo* | 70,802 | | S25 | TX random* allocat* | 13,134 | | S24 | (MH "Random Assignment") | 67,568 | | S23 | TX randomi* control* trial* | 219,192 | | S22 | TX ( (singl* n1 blind*) or (singl* n1 mask*) ) or TX ( (doubl* n1 blind*) or (doubl* n1 mask*) ) or TX ( (tripl* n1 blind*) or (tripl* n1 mask*) ) or TX ( (trebl* n1 blind*) or (trebl* n1 mask*) ) | 1,211,294 | | S21 | TX clinic* n1 trial* | 292,478 | | S20 | PT Clinical trial | 110,410 | | S19 | (MH "Clinical Trials+") | 316,937 | | S18 | S5 AND S17 | 1,410 | | S17 | S6 OR S7 OR S8 OR S9 OR S10 OR S11 OR S12 OR S13 OR S14 OR S15 OR S16 | 694,604 | | S16 | vessel* N3 seal* | 194 | | S15 | sperm* N3 vein* | 53 | | S14 | surg* | 679,435 | | S13 | emboli?ation* | 13,284 | | S12 | (MM "Embolization, Therapeutic+") | 7,096 | | S11 | Ligation* or microsurg* | 11,093 | | S10 | (MM "Microsurgery+") | 1,903 | | S9 | (MM "Ligation") | 356 | | S8 | (Varicocele* or Varicocoele*) N5 (repair* or correct*) | 68 | | S7 | Varicocelectom* or Varicocoelectom* | 207 | | S6 | (MM "Surgery, Urologic, Male+") | 6,564 | | S5 | S1 OR S2 OR S3 OR S4 | 9,960 | | S4 | (male* or men) N7 (infertil* or subfertil*) | 2,226 | | S3 | (MM "Infertility") | 8,655 | | S2 | Varicocele* or Varicocoele* | 672 | | S1 | (MM "Varicocele") | 365 | Appendix 7. Web of Knowledge search strategy Searched 4 April 2020 Web platform See Figure 43 for strategy Data and analyses Comparison 1. Varicocele treatment versus non‐surgical, non‐radiological, delayed, or no treatment. | Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size | |---|---|---|---|---| | 1.1 Live birth | 2 | 204 | Risk Ratio (M‐H, Random, 95% CI) | 2.27 [0.19, 26.93] | | 1.2 Pregnancy | 13 | 1193 | Risk Ratio (M‐H, Random, 95% CI) | 1.55 [1.06, 2.26] | | 1.2.1 Pregnancy in men with abnormal semen analysis and clinical varicocele | 7 | 693 | Risk Ratio (M‐H, Random, 95% CI) | 1.94 [1.23, 3.05] | | 1.2.2 Pregnancy in men with normal semen analysis and subclinical varicocele or where unspecified | 6 | 500 | Risk Ratio (M‐H, Random, 95% CI) | 1.09 [0.55, 2.18] | Comparison 2. Surgical treatment versus radiological treatment. | Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size | |---|---|---|---|---| | 2.1 Live birth | 1 | Risk Ratio (M‐H, Random, 95% CI) | Totals not selected | | | 2.2 Adverse event: hydrocele formation | 3 | 284 | Risk Ratio (M‐H, Random, 95% CI) | 4.24 [0.53, 33.76] | | 2.3 Adverse event: pain | 1 | Risk Ratio (M‐H, Random, 95% CI) | Totals not selected | | | 2.4 Adverse event: epididymitis | 1 | Risk Ratio (M‐H, Random, 95% CI) | Totals not selected | | | 2.5 Adverse event: haematoma | 1 | Risk Ratio (M‐H, Random, 95% CI) | Totals not selected | | | 2.6 Adverse event: suture granuloma | 1 | Risk Ratio (M‐H, Random, 95% CI) | Totals not selected | | | 2.7 Pregnancy | 5 | 456 | Risk Ratio (M‐H, Random, 95% CI) | 1.13 [0.75, 1.70] | | 2.8 Varicocele recurrence | 3 | 380 | Risk Ratio (M‐H, Random, 95% CI) | 1.31 [0.82, 2.08] | Comparison 3. Microscopic subinguinal surgical treatment versus other surgical treatment. | Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size | |---|---|---|---|---| | 3.1 Pregnancy | 12 | 1473 | Risk Ratio (M‐H, Random, 95% CI) | 1.18 [1.02, 1.36] | | 3.2 Adverse event: hydrocele formation | 4 | 372 | Risk Ratio (M‐H, Random, 95% CI) | 0.23 [0.05, 1.14] | | 3.3 Adverse event: testicular atrophy | 3 | 538 | Risk Ratio (M‐H, Random, 95% CI) | 0.18 [0.02, 1.89] | | 3.4 Adverse event: haematoma | 2 | 418 | Risk Ratio (M‐H, Random, 95% CI) | 0.76 [0.11, 5.16] | | 3.5 Adverse event: pain | 1 | Risk Ratio (M‐H, Random, 95% CI) | Totals not selected | | | 3.6 Adverse event: wound infection | 1 | Risk Ratio (M‐H, Random, 95% CI) | Totals not selected | | | 3.7 Adverse event: oedema | 1 | Risk Ratio (M‐H, Random, 95% CI) | Totals not selected | | | 3.8 Adverse event: abdominal distention | 2 | 192 | Risk Ratio (M‐H, Random, 95% CI) | 0.20 [0.02, 1.72] | | 3.9 Varicocele recurrence | 14 | 1565 | Risk Ratio (M‐H, Random, 95% CI) | 0.48 [0.29, 0.79] | Comparison 4. Open inguinal surgical treatment versus retroperitoneal surgical treatment. | Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size | |---|---|---|---|---| | 4.1 Pregnancy | 5 | 889 | Risk Ratio (M‐H, Random, 95% CI) | 1.02 [0.82, 1.27] | | 4.2 Adverse event: hydrocele formation | 6 | 765 | Risk Ratio (M‐H, Random, 95% CI) | 1.03 [0.31, 3.47] | | 4.3 Adverse event: testicular atrophy | 3 | 430 | Risk Ratio (M‐H, Random, 95% CI) | 0.33 [0.01, 7.87] | | 4.4 Adverse event: haematoma | 3 | 338 | Risk Ratio (M‐H, Random, 95% CI) | 3.75 [0.62, 22.71] | | 4.5 Adverse event: pain | 2 | 266 | Risk Ratio (M‐H, Random, 95% CI) | 0.86 [0.29, 2.56] | | 4.6 Adverse event: wound infection | 4 | 368 | Risk Ratio (M‐H, Random, 95% CI) | 2.96 [0.79, 11.07] | | 4.7 Adverse event: oedema | 2 | 175 | Risk Ratio (M‐H, Random, 95% CI) | 1.20 [0.60, 2.40] | | 4.8 Adverse event: epididymitis | 1 | Risk Ratio (M‐H, Random, 95% CI) | Totals not selected | | | 4.9 Adverse event: epididymo‐orchitis | 1 | Risk Ratio (M‐H, Random, 95% CI) | Totals not selected | | | 4.10 Adverse event: pneumoscrotum | 1 | Risk Ratio (M‐H, Random, 95% CI) | Totals not selected | | | 4.11 Adverse event: subcutaneous emphysema | 1 | Risk Ratio (M‐H, Random, 95% CI) | Totals not selected | | | 4.12 Adverse event: inferior epigastric bleeding | 1 | Risk Ratio (M‐H, Random, 95% CI) | Totals not selected | | | 4.13 Adverse event: persistence of dilated veins | 1 | Risk Ratio (M‐H, Random, 95% CI) | Totals not selected | | | 4.14 Adverse event: wound erythema | 1 | Risk Ratio (M‐H, Random, 95% CI) | Totals not selected | | | 4.15 Varicocele recurrence | 8 | 1063 | Risk Ratio (M‐H, Random, 95% CI) | 1.03 [0.43, 2.46] | Comparison 5. Radiological treatment (sclerotherapy) versus radiological treatment (embolisation). | Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size | |---|---|---|---|---| | 5.1 Varicocele recurrence | 1 | Risk Ratio (M‐H, Random, 95% CI) | Totals not selected | Characteristics of studies Characteristics of included studies [ordered by study ID] Abdel‐Meguid 2011a. | Study characteristics | || | Methods | Study design: Randomised controlled trial Study grouping: Parallel group | | | Participants | Inclusion criteria: Married, overall healthy men 20 to 39 years of age who had had infertility for > 1 year of unprotected intercourse, clinically palpable unilateral orbilateral varicoceles (grade I, II, or III), and impaired semen quality (at least 1 of the following semen characteristics: sperm concentration 20 million/mL, progressively motile sperm 50%, or morphologically normal sperm 30%) were considered eligible for the study. Exclusion criteria: Patients with unilateral or bilateral subclinical or recurrent varicoceles, normal semen parameters, azoospermia, an abnormal hormonal profile, additional causes of infertility, significant medical diseases, smoking, occupational heat exposure, female partner 35 years of age or older, associated female factor infertility, or unstable marriage. Patients who refused randomisation were excluded from study entry. Patients who explicitly elected or rejected surgery or initially elected to have an observation period before considering surgery afterwards were excluded as well to avoid undermining the randomisation process. Pretreatment: Additional Characteristics ‐ Intervention: Primary infertility: 40/73 participants (54.8%); secondary infertility: 33/73 participants (45.2%); varicocele unilateral left: 53/73 participants (72.6%); varicocele bilateral: 20/73 participants (27.4%); Grade 1: 38/93 participants (40.9%); Grade 2: 28/93 participants (30.1%); Grade 3: 27/93 participants (29%) Additional Characteristics ‐ Comparator: Primary infertility: 38/72 participants (52.8%); secondary infertility: 34/72 (47.2%); varicocele unilateral left: 53/72 participants (73.6%); varicocele bilateral: 19/72 participants (26.4%); Grade 1: 36/91 (39.6%); Grade 2: 30/91 (33%); Grade 3: 25/91 (27.5%) Age: Mean (SD) ‐ Intervention: Mean age of participants: 28.4 (5.7) years; mean age of participant's wife: 25.3 (4.1) years Age: Mean (SD) ‐ Comparator: Mean age of participants: 29.3 (5.7) years; mean age of participant's wife: 25.8 (4.3) years Number of Participants at Randomisation and Outcome ‐ Intervention: 75, 73 (2 participants excluded from analysis (lost to follow‐up ‐ travelled abroad)) Number of Participants at Randomisation and Outcome ‐ Comparator: 75, 72 (3 participants excluded from analysis (discontinued intervention ‐ withdrawal or requested surgery)) | | | Interventions | Intervention Characteristics Intervention Surgical Treatment: Subinguinal microsurgical varicocelectomy with arterial and lymphatic sparing Comparator No treatment | | | Outcomes | (Undefined) pregnancy rateOutcome type: Dichotomous | | | Identification | Sponsorship source: Not reported Country: Saudi Arabia Setting: Single centre Author name: Abdel‐Maguid Institution: Ghodran General Hospital, Kingdom of Saudi Arabia Email: [email protected] Address: Department of General Surgery, PO Box 14, Baljrashi 22888, Kingdom of Saudi Arabia | | | Notes | Authors were contacted for additional data but did not respond. | | | Risk of bias | || | Bias | Authors' judgement | Support for judgement | | Random sequence generation (selection bias) | Low risk | Quote: "A simple random allocation sequence was computer generated." | | Allocation concealment (selection bias) | Low risk | Quote: "...concealed by an independent research assistant. Randomisation–allocation concealment to both investigators and participants was ascertained by using sequentially numbered, opaque envelopes containing the assigned intervention. | | Blinding of participants and personnel (performance bias) All outcomes | Low risk | Quote: "...neither the participants nor the investigators were blinded to the intervention after allocation." Blinding unlikely to influence outcomes. | | Blinding of outcome assessment (detection bias) All outcomes | Low risk | Not reported. Blinding unlikely to influence outcomes. | | Incomplete outcome data (attrition bias) All outcomes | Low risk | Attrition and exclusions reported. 2 men lost to follow‐up, 5 excluded from analysis. | | Selective reporting (reporting bias) | Unclear risk | No protocol found. | | Other bias | Low risk | None | Al Kandari 2007. | Study characteristics | || | Methods | Study design: Randomised controlled trial Study grouping: Parallel group | | | Participants | Inclusion criteria: Patients with infertility, scrotal pain, and atrophy in adolescence and varicocele. All with clinically palpable varicoceles Exclusion criteria: Not reported Additional Characteristics ‐ Intervention: Unilateral: 28, bilateral: 12 Additional Characteristics ‐ Comparator: Unilateral: 30, bilateral: 10 Additional Characteristics ‐ 2nd Comparator: Unilateral: 35, bilateral: 5 Age: Mean (SD) intervention: 28.5 (7) Age: Mean (SD) comparator: 30 (8) Age: Mean (SD) 2nd comparator: 29 (9) Number of Participants at Randomisation and Outcome ‐ Intervention: 40, 40 (52 varicoceles) Number of Participants at Randomisation and Outcome ‐ Comparator: 40, 40 (50 varicoceles) Number of Participants at Randomisation and Outcome ‐ 2nd Comparator: 40, 40 (45 varicoceles) | | | Interventions | Intervention Characteristics Intervention Surgical Treatment: Open inguinal varicocelectomy Comparator Surgical Treatment: Laparoscopic varicocelectomy 2nd Comparator Surgical Treatment: Subinguinal microscopic varicocelectomy | | | Outcomes | Adverse events ‐ abdominal distentionOutcome type: Adverse event Adverse events ‐ haematoma Outcome type: Adverse event Adverse events ‐ hydrocele formation Outcome type: Adverse event Varicocele recurrence Outcome type: Adverse event (Undefined) pregnancy rate Outcome type: Dichotomous | | | Identification | Sponsorship source: Not reported Country: Egypt Setting: Single centre Author name: Al‐Kandari Institution: Department of Surgery, Kuwait University, Kuwait City, Kuwait Email: [email protected] Address: Not reported | | | Notes | Varicocele recurrence and hydrocele formation were reported per number of varicocele treated instead of per participant and were thus not included. Authors were contacted for additional data but did not respond. | | | Risk of bias | || | Bias | Authors' judgement | Support for judgement | | Random sequence generation (selection bias) | Unclear risk | Not reported | | Allocation concealment (selection bias) | Unclear risk | Not reported | | Blinding of participants and personnel (performance bias) All outcomes | Low risk | Not reported. Blinding unlikely to influence outcomes. | | Blinding of outcome assessment (detection bias) All outcomes | Low risk | Not reported. Blinding unlikely to influence outcomes. | | Incomplete outcome data (attrition bias) All outcomes | Unclear risk | Attrition and exclusions not reported. | | Selective reporting (reporting bias) | Unclear risk | No protocol found. | | Other bias | Low risk | None | Al Said 2008. | Study characteristics | || | Methods | Study design: Randomised controlled trial Study grouping: Parallel group | | | Participants | Inclusion criteria: Patients with clinically palpable varicoceles, all of whom complained of infertility Exclusion criteria: Patients operated on by different surgeons, those who underwent varicocelectomy for indications other than infertility, and those refusing to enter randomisation were excluded. Patients with subclinical varicocele, defined as scrotal venous reflux without any palpable distention of the pampiniform plexus, were also excluded from study. Additional Characteristics ‐ Intervention: Unilateral: 41, bilateral: 51 Additional Characteristics ‐ Comparator: Unilateral: 40, bilateral: 54 Additional Characteristics ‐ 2nd Comparator: Unilateral: 69, bilateral: 43 Age: Mean (SD) ‐ Intervention: 34 (7.8) Age: Mean (SD) ‐ Comparator: 33 (7.9) Age: Mean (SD) ‐ 2nd Comparator: 34 (6.6) Number of Participants at Randomisation and Outcome ‐ Intervention: 92, 92 (143 varicoceles) Number of Participants at Randomisation and Outcome ‐ Comparator: 94, 94 (148 varicoceles) Number of Participants at Randomisation and Outcome ‐ 2nd Comparator: 112, 112 (155 varicoceles) | | | Interventions | Intervention Characteristics Intervention Surgical Treatment: Open inguinal varicocelectomy Comparator Surgical Treatment: Laparoscopic varicocelectomy 2nd Comparator Surgical Treatment: Subinguinal microsurgical varicocelectomy | | | Outcomes | Adverse events ‐ wound infectionOutcome type: Adverse event Adverse events ‐ scrotal haematoma Outcome type: Adverse event Adverse events ‐ postoperative scrotal pain Outcome type: Adverse event Adverse events ‐ hydrocele formation Outcome type: Adverse event Varicocele recurrence Outcome type: Dichotomous Adverse events ‐ testicular atrophy Outcome type: Dichotomous (Undefined) pregnancy rate Outcome type: Dichotomous | | | Identification | Sponsorship source: Not reported Country: Quatar Setting: Single centre Author name: Al‐Said Institution: Urology Department, Urology and Nephrology Center, Mansoura, Egypt Email: [email protected] Address: Not reported | | | Notes | Varicocele recurrence and hydrocele formation were reported per number of varicocele treated instead of per participant and were thus not included. Authors were contacted for additional data but did not respond. | | | Risk of bias | || | Bias | Authors' judgement | Support for judgement | | Random sequence generation (selection bias) | Unclear risk | Not reported | | Allocation concealment (selection bias) | Unclear risk | Not reported | | Blinding of participants and personnel (performance bias) All outcomes | Low risk | Not reported. Blinding unlikely to influence outcomes. | | Blinding of outcome assessment (detection bias) All outcomes | Low risk | Quote: "The investigators who performed post‐operative followup, semen analyses, and sonography were blinded to the varicocelectomy technique." Blinding unlikely to influence outcomes. | | Incomplete outcome data (attrition bias) All outcomes | Unclear risk | Attrition not reported. Exclusions reported. | | Selective reporting (reporting bias) | Unclear risk | No protocol found. | | Other bias | Low risk | None | Barbalias 1998. | Study characteristics | || | Methods | Study design: Randomised controlled trial Study grouping: Parallel group | | | Participants | Baseline Characteristics Inclusion criteria: After gynaecological evaluation failed to show any pathology. Men with clinically diagnosed varicocele Exclusion criteria: Men with subclinical varicoceles Additional Characteristics ‐ Intervention: All patients had normal serum levels of testosterone, luteinising hormone, follicle stimulating hormone, prolactin, estradiol, and thyroid function. Additional Characteristics ‐ Comparator: All patients had normal serum levels of testosterone, luteinising hormone, follicle stimulating hormone, prolactin, estradiol, and thyroid function. Additional Characteristics ‐ 2nd Comparator: Not reported Additional Characteristics ‐ 3rd Comparator: Not reported Age: Mean (SD) ‐ Intervention: Not reported Age: Mean (SD) ‐ Comparator: Not reported Age: Mean (SD) ‐ 2nd Comparator: Not reported Age: Mean (SD) ‐ 3rd Comparator: Not reported Number of Participants at Randomisation and Outcome ‐ Intervention: 22, 22 Number of Participants at Randomisation and Outcome ‐ Comparator: 22, 22 Number of Participants at Randomisation and Outcome ‐ 2nd Comparator: 22, 22 Number of Participants at Randomisation and Outcome ‐ 3rd Comparator: 22, 22 | | | Interventions | Intervention Characteristics Intervention Surgical Treatment : Retroperitoneal Comparator Surgical Treatment: Inguinal 2nd Comparator Surgical Treatment: Subinguinal 3rd Comparator Radiological Treatment: Percutaneous venous embolisation | | | Outcomes | Varicocele recurrenceOutcome type: Dichotomous | | | Identification | Sponsorship source: Not reported Country: Greece Setting: Single centre Author name: Barbalias Institution: Department of Urology, University of Patras Email: Not reported Address: Patras, Greece | | | Notes | Correspondence email was not provided, so authors were not contacted for additional data. | | | Risk of bias | || | Bias | Authors' judgement | Support for judgement | | Random sequence generation (selection bias) | Low risk | Quote: "Patients were allocated into four groups in a randomised fashion by computer‐assigned numbers in a 1:1 ratio for each study group." | | Allocation concealment (selection bias) | Unclear risk | Not reported | | Blinding of participants and personnel (performance bias) All outcomes | Low risk | Not reported. Blinding unlikely to influence outcomes. | | Blinding of outcome assessment (detection bias) All outcomes | Low risk | Not reported. Blinding unlikely to influence outcomes. | | Incomplete outcome data (attrition bias) All outcomes | Unclear risk | Attrition and exclusions not reported. | | Selective reporting (reporting bias) | Unclear risk | No protocol found. | | Other bias | Low risk | None | Barry 2012. | Study characteristics | || | Methods | Study design: Randomised controlled trial Study grouping: Parallel group | | | Participants | Inclusion criteria: Patients with infertility, pain, and cosmetic issues due to a large varicocele Exclusion criteria: Abdominal ultrasonography to rule out a kidney tumour as the cause of the varicocele Additional Characteristics ‐ Intervention: Grade I: 25 (18.3%); Grade II: 27 (19.8%); Grade III: 17 (12.6%). 3 right side, 8 left side, 29 bilateral Additional Characteristics ‐ Comparator: Grade I: 23 (16.9%); Grade II: 24 (17.6%); Grade III: 20 (14.8%). 4 right side, 9 left side, 27 bilateral Age: Mean (SD) ‐ Intervention: 24.9 (1.8) Age: Mean (SD) ‐ Comparator: 26.1 (0.9) Number of Participants at Randomisation and Outcome ‐ Intervention: 40, 40 Number of Participants at Randomisation and Outcome ‐ Comparator: 40, 40 | | | Interventions | Intervention Characteristics Intervention Surgical Treatment: 5‐millimetre laparoscopic varicocelectomy Comparator Surgical Treatment: Inguinal varicocele ligation | | | Outcomes | Varicocele recurrenceOutcome type: Dichotomous Adverse events ‐ hydrocele formation Outcome type: Dichotomous Adverse events ‐ wound infection Outcome type: Dichotomous Adverse events ‐ postoperative scrotal pain Outcome type: Dichotomous Pneumoscrotum Outcome type: Adverse event Subcutaneous emphysema Outcome type: Adverse event Haematoma Outcome type: Adverse event Epididymo‐orchitis Outcome type: Adverse event Inferior epigastric bleeding Outcome type: Adverse event | | | Identification | Sponsorship source: Not reported Country: Saudi Arabia Setting: Single centre Author name: Barry Institution: Department of Urology of Al‐Ansar Hospital, Madinah, Kingdom of Saudi Arabia Email: [email protected] Address: Not reported | | | Notes | Authors were contacted for additional data but did not respond. | | | Risk of bias | || | Bias | Authors' judgement | Support for judgement | | Random sequence generation (selection bias) | Low risk | Quote: "Patients were randomly assigned (using randomization software)" | | Allocation concealment (selection bias) | Unclear risk | Not reported | | Blinding of participants and personnel (performance bias) All outcomes | Low risk | Not reported. Blinding unlikely to influence outcomes. | | Blinding of outcome assessment (detection bias) All outcomes | Low risk | Not reported. Blinding unlikely to influence outcomes. | | Incomplete outcome data (attrition bias) All outcomes | Unclear risk | No attrition reported at follow‐up. Exclusions not reported. | | Selective reporting (reporting bias) | Unclear risk | Not protocol found. | | Other bias | Low risk | None | Bo 1996. | Study characteristics | || | Methods | Study design: Randomised controlled trial Study grouping: Parallel group | | | Participants | Inclusion criteria: Not reported Exclusion criteria: Not reported Additional Characteristics ‐ Intervention: Not reported Additional Characteristics ‐ Comparator: Not reported Age: Mean (SD) ‐ Intervention: Not reported Age: Mean (SD) ‐ Comparator: Not reported Number of Participants at Randomisation and Outcome ‐ Intervention: 31 (assumed from 62 total participants) Number of Participants at Randomisation and Outcome ‐ Comparator: 31 (assumed from 62 total participants) | | | Interventions | Intervention Characteristics Intervention Surgical Treatment: High ligation of the internal spermatic veins Comparator Observation | | | Outcomes | (Undefined) pregnancy rateOutcome type: Dichotomous | | | Identification | Sponsorship source: Not reported Country: China Setting: Single centre Author name: Bo Institution: Renji Hospital, Shanghai Second Medical University Email: Not reported Address: Not reported | | | Notes | Correspondence email was not provided, so authors were not contacted for additional data. | | | Risk of bias | || | Bias | Authors' judgement | Support for judgement | | Random sequence generation (selection bias) | Unclear risk | Not reported | | Allocation concealment (selection bias) | Unclear risk | Not reported | | Blinding of participants and personnel (performance bias) All outcomes | Low risk | Not reported. Blinding unlikely to influence outcomes. | | Blinding of outcome assessment (detection bias) All outcomes | Low risk | Not reported. Blinding unlikely to influence outcomes. | | Incomplete outcome data (attrition bias) All outcomes | Unclear risk | Attrition and exclusions not reported. | | Selective reporting (reporting bias) | Unclear risk | No protocol found. | | Other bias | Low risk | None | Breznik 1993. | Study characteristics | || | Methods | Study design: Randomised controlled trial Study grouping: Parallel group | | | Participants | Inclusion criteria: Men with subclinical (thermography, phlebography) and clinical varicoceles (WHO I‐III) Exclusion criteria: Female causes and previous treatment excluded. Men with azoospermia or an immunological cause for infertility were excluded. Pretreatment: There were no statistically significant differences between the 2 groups in terms of patient age, partner age, laterality, and grade of varicocele (P.05). Additional study characteristics (specifics on surgery, unilateral/bilateral) ‐ Intervention: Not reported Additional study characteristics (specifics on surgery, unilateral/bilateral) ‐ Comparator: 5 couples achieving pregnancy before surgery were transferred to the no treatment group. Age: Mean (SD) ‐ Intervention: Not reported Age: Mean (SD) ‐ Comparator: Not reported Number of Participants at Randomisation and Outcome ‐ Intervention: 47, 38 Number of Participants at Randomisation and Outcome ‐ Comparator: 49, 41 | | | Interventions | Intervention Characteristics Intervention Surgical Treatment: High ligation of spermatic vein and artery or embolisation (Gianturc's spiral) or sclerosation (of the internal spermatic vein) Comparator No treatment | | | Outcomes | (Undefined) pregnancy rateOutcome type: Dichotomous | | | Identification | Sponsorship source: Research Council of Slovenia Country: Slovenia Setting: Single centre Author name: Breznik Institution: University of Ljubljana Faculty of Medicine Email: Not reported Address: Gynecology Department, Unit for Human Reproduction and Endocrinology, Maribor Teaching Hospital, Ljubljanska 5, 62000 Maribor, Slovenia | | | Notes | Correspondence email was not provided, so authors were not contacted for additional data. | | | Risk of bias | || | Bias | Authors' judgement | Support for judgement | | Random sequence generation (selection bias) | Unclear risk | Not reported | | Allocation concealment (selection bias) | Unclear risk | Not reported | | Blinding of participants and personnel (performance bias) All outcomes | Low risk | Not reported. Blinding unlikely to influence outcomes. | | Blinding of outcome assessment (detection bias) All outcomes | Low risk | Not reported. Blinding unlikely to influence outcomes. | | Incomplete outcome data (attrition bias) All outcomes | Low risk | Attrition and exclusions reported. | | Selective reporting (reporting bias) | Unclear risk | No protocol found. | | Other bias | Low risk | None | Bryniarski 2016. | Study characteristics | || | Methods | Study design: Randomised controlled trial Study grouping: Parallel group | | | Participants | Inclusion criteria: Palpable left‐sided varicocoele, infertility (primary and secondary) over 12 months, oligozoospermia (15 million/mL), orasthenozoospermia (total motility 40% or progressive motility 32%), teratozoospermia (4%) or impaired vitality (58%) in semen analysis, male factor (no obvious female factor), no other suspected cause of infertility in men and normal TSH Exclusion criteria: Azoospermia, recurrent varicocoele, undescended testis, mumps, secondary hypogonadism, hyperprolactinaemia, testosterone/antioestrogen therapy, age over 40, history of testis cancer Additional Characteristics ‐ Intervention: Laparoscopic procedure is conducted by a surgeon trained in all laparoscopic procedures. Additional Characteristics ‐ Comparator: Microsurgical varicocelectomy is practised by an experienced urologist. Age: Mean (SD) ‐ Intervention: 31.6 (3.3) Age: Mean (SD) ‐ Comparator: 33.6 (2.7) Number of Participants at Randomisation and Outcome ‐ Intervention: 42, 37 Number of Participants at Randomisation and Outcome ‐ Comparator: 42, 37 | | | Interventions | Intervention Characteristics Intervention Surgical Treatment: Laparoscopic varicocelectomy Comparator Surgical Treatment: Microsurgical varicocelectomy | | | Outcomes | (Undefined) pregnancy rateOutcome type: Dichotomous | | | Identification | Sponsorship source: Not reported Country: Poland Setting: Single centre Author name: P Bryniarski Institution: Department of Urology, Medical University of Silesia in Katowice Email: [email protected] Address: University of Silesia, 3 Maja Street 13‐15, 41‐800 Zabrze, Poland | | | Notes | Authors were contacted for additional data but did not respond. | | | Risk of bias | || | Bias | Authors' judgement | Support for judgement | | Random sequence generation (selection bias) | Unclear risk | Not reported | | Allocation concealment (selection bias) | Unclear risk | Not reported | | Blinding of participants and personnel (performance bias) All outcomes | Low risk | Not reported. Blinding unlikely to influence outcomes. | | Blinding of outcome assessment (detection bias) All outcomes | Low risk | Not reported. Blinding unlikely to influence outcomes. | | Incomplete outcome data (attrition bias) All outcomes | Unclear risk | Attrition and exclusions not reported. This was a per‐protocol study (only participants with complete data were included in final analyses). | | Selective reporting (reporting bias) | Low risk | Protocol found and all outcomes reported. | | Other bias | Low risk | None | Cayan 2000. | Study characteristics | || | Methods | Study design: Randomised controlled trial Study grouping: Parallel group | | | Participants | Inclusion criteria:Documented left unilateral or bilateral varicocele on physical examination (Grade I, II, or III) and colour Doppler ultrasound (diameter of internal spermatic vein greater than 3 mm and/or venous reflux without Valsalva manoeuvre) Couples with primary infertility for more than 1 year Men between 20 and 35 years of age No history of past urologic surgery, infection, trauma, or congenital urogenital abnormality Negative screening sperm mixed agglutination reaction test for IgG and IgA Serum FSH level not more than 1.5 times normal (accepted normal FSH level 4 to 10 mIU/mL) 3 spermiograms with below‐normal counts (fewer than 20 million spermatozoa per millilitre) and/or a 1b motility (less than 50%) according to World Health Organization criteria 12 Normal gynaecologic assessment in the patient’s partner (no history of gynaecologic surgery or ovulatory abnormalities according to the gynaecologic evaluation) Exclusion criteria: Not reported Additional Characteristics ‐ Intervention: 124 unilateral, 90 bilateral Additional Characteristics ‐ Comparator: 128 unilateral, 108 bilateral Age: Mean (SD) ‐ Intervention: 28.896 (4.87), partner age: 23.78 (2.78) Age: Mean (SD) ‐ Comparator: 29.566 (3.31), partner age: 23.18 (2.34) Number of Participants at Randomisation and Outcome ‐ Intervention: 232 Number of Participants at Randomisation and Outcome ‐ Comparator: 236 | | | Interventions | Intervention Characteristics Intervention Surgical Treatment: High ligation surgery (retroperitoneal) Comparator Surgical Treatment: Microsurgical high inguinal varicocelectomy (open inguinal) | | | Outcomes | (Undefined) pregnancy rateOutcome type: Dichotomous | | | Identification | Sponsorship source: Not reported Country: Turkey Setting: Single centre Author name: Cayan Institution: Department of Urology, Mersin University Faculty of Medicine Email: Not reported Address: P.K. 202, Tarsus, 33400 Turkey | | | Notes | Varicocele recurrence rates were reported per number of varicocele, and so could not be included in meta‐analysis. Pregnancy rates were reported per participant, and were therefore included. Correspondence email was not provided, so authors were not contacted for additional data. | | | Risk of bias | || | Bias | Authors' judgement | Support for judgement | | Random sequence generation (selection bias) | Unclear risk | Not reported | | Allocation concealment (selection bias) | Unclear risk | Not reported | | Blinding of participants and personnel (performance bias) All outcomes | Low risk | Not reported. Blinding unlikely to influence outcomes. | | Blinding of outcome assessment (detection bias) All outcomes | Low risk | Not reported. Blinding unlikely to influence outcomes. | | Incomplete outcome data (attrition bias) All outcomes | Unclear risk | Attrition and exclusions not reported. | | Selective reporting (reporting bias) | High risk | No protocol found. Incomplete outcome data for pregnancy rate and hydrocele formation groups that were not accounted for in paper. | | Other bias | Low risk | None | Chaudhary 2000. | Study characteristics | || | Methods | Study design: Randomised controlled trial Study grouping: Parallel group | | | Participants | Inclusion criteria: History of infertility (undefined) and clinical or subclinical varicocele Exclusion criteria: Those participants who did not complete 12 months of follow‐up were excluded. Age: Mean (SD) ‐ Intervention: 26.8 years (average for all participants in study) Age: Mean (SD) ‐ Comparator: 26.8 years (average for all participants in study) Number of Participants at Randomisation and Outcome ‐ Intervention: 34 Number of Participants at Randomisation and Outcome ‐ Comparator: 38 | | | Interventions | Intervention Characteristics Intervention Surgical Treatment: Surgical low ligation, inguinal approach (lvanissevich and Gregorian techniques) Comparator Surgical Treatment: Surgical high ligation, retroperitoneal approach (Paloma technique) | | | Outcomes | Varicocele recurrenceOutcome type: Dichotomous Adverse events ‐ hydrocele formation Outcome type: Dichotomous Adverse events ‐ wound infection Outcome type: Dichotomous Adverse events ‐ testicular atrophy Outcome type: Dichotomous Adverse events ‐ scrotal haematoma Outcome type: Adverse event Persistence of dilated veins Outcome type: Adverse event | | | Identification | Sponsorship source: Not reported Country: Pakistan Setting: Single centre Author name: Chaudary Institution: Fauji Foundation Hospital, Rawalpindi, Pakistan and Armed Forces Institute of Urology, Rawalpindi, Pakistan Email: Not reported Address: Fauji Foundation Hospital, Rawalpindi, Pakistan | | | Notes | Correspondence email was not provided, so authors were not contacted for additional data. | | | Risk of bias | || | Bias | Authors' judgement | Support for judgement | | Random sequence generation (selection bias) | Unclear risk | Not reported | | Allocation concealment (selection bias) | Unclear risk | Not reported | | Blinding of participants and personnel (performance bias) All outcomes | Low risk | Not reported. Blinding unlikely to influence outcomes. | | Blinding of outcome assessment (detection bias) All outcomes | Low risk | Not reported. Blinding unlikely to influence outcomes. | | Incomplete outcome data (attrition bias) All outcomes | Unclear risk | Only participants who completed a minimum of 12 months of follow‐up were included in the analysis. | | Selective reporting (reporting bias) | Unclear risk | No protocol found. | | Other bias | Low risk | None | Chen 1996. | Study characteristics | || | Methods | Study design: Randomised controlled trial Study grouping: Parallel group | | | Participants | Inclusion criteria: Men with varicocele (grade not mentioned). Diagnosis and duration of infertility unclear. Exclusion criteria: Not reported Age: Mean (SD) ‐ Intervention: Not reported Age: Mean (SD) ‐ Comparator: Not reported Intervention type: Ligation (technique not specified) Comparator type: Embolisation (technique not specified) Number of Participants at Randomisation and Outcome ‐ Intervention: 25, 25 Number of Participants at Randomisation and Outcome ‐ Comparator: 21, 21 | | | Interventions | Intervention Characteristics Intervention Surgical Treatment: Ligation (technique not specified) Comparator Radiological Treatment: Embolisation (technique not specified) | | | Outcomes | (Undefined) pregnancy rateOutcome type: Dichotomous | | | Identification | Sponsorship source: Not reported Country: China Setting: Multicentre Author name: Chen Institution: Ninty‐Seventh Hospital of PLA Email: Not reported Address: Xuzhou 221004 | | | Notes | Correspondence email was not provided, so authors were not contacted for additional data. | | | Risk of bias | || | Bias | Authors' judgement | Support for judgement | | Random sequence generation (selection bias) | Unclear risk | Not reported | | Allocation concealment (selection bias) | Unclear risk | Not reported | | Blinding of participants and personnel (performance bias) All outcomes | Low risk | Not reported. Blinding unlikely to influence outcomes. | | Blinding of outcome assessment (detection bias) All outcomes | Low risk | Not reported. Blinding unlikely to influence outcomes. | | Incomplete outcome data (attrition bias) All outcomes | Unclear risk | No attrition reported at follow‐up. Exclusions not reported. | | Selective reporting (reporting bias) | Unclear risk | No protocol found. | | Other bias | Low risk | None | De Rose 2003. | Study characteristics | || | Methods | Study design: Randomised controlled trial Study grouping: Parallel group | | | Participants | Inclusion criteria: Not reported Exclusion criteria: Not reported Age: Mean (SD) ‐ Intervention: Not reported Age: Mean (SD) ‐ Comparator: Not reported Age: Mean (SD) ‐ 2nd Comparator: Not reported Number of Participants at Randomisation and Outcome ‐ Intervention: 20 Number of Participants at Randomisation and Outcome ‐ Comparator: 20 Number of Participants at Randomisation and Outcome ‐ 2nd Comparator: 20 | | | Interventions | Intervention Characteristics Intervention Non‐surgical Treatment: Menotropin Comparator Surgical Treatment: Menotropin plus surgery 2nd Comparator Surgical Treatment: Varicocelectomy | | | Outcomes | (Undefined) pregnancy rateOutcome type: Dichotomous | | | Identification | Sponsorship source: Not reported Country: Italy Setting: Single centre Author name: De Rose Institution: Clinica Urologia di Genova Luciano Giuliani Email: Not reported Address: Genova, Italy | | | Notes | Correspondence email was not provided, so authors were not contacted for additional data. | | | Risk of bias | || | Bias | Authors' judgement | Support for judgement | | Random sequence generation (selection bias) | Unclear risk | Not reported | | Allocation concealment (selection bias) | Unclear risk | Not reported | | Blinding of participants and personnel (performance bias) All outcomes | Low risk | Not reported. Blinding unlikely to influence outcomes. | | Blinding of outcome assessment (detection bias) All outcomes | Low risk | Not reported. Blinding unlikely to influence outcomes. | | Incomplete outcome data (attrition bias) All outcomes | Unclear risk | Attrition and exclusions not reported. | | Selective reporting (reporting bias) | Unclear risk | No protocol found. | | Other bias | Low risk | None | Dohle 2010. | Study characteristics | || | Methods | Study design: Randomised controlled trial Study grouping: Parallel group | | | Participants | Inclusion criteria: Men with no other abnormalities than clinical varicocele (confirmed by ultrasound) and subnormal semen analysis. Duration of (undefined) subfertility > 1 year. Age women < 36 years Exclusion criteria: Azoospermia, obvious female subfertility causes Age: Mean (SD) ‐ Intervention: Men 32.9 years, women 29.6 years Age: Mean (SD) ‐ Comparator: Men 32.7 years, women 29.3 years Number of Participants at Randomisation and Outcome ‐ Intervention: 65, 60 Number of Participants at Randomisation and Outcome ‐ Comparator: 63, 58 | | | Interventions | Intervention Characteristics Intervention Surgical Treatment: Surgical repair (technique not specified) Comparator Delayed treatment after 1 year (ART or varicocele repair) | | | Outcomes | (Undefined) pregnancy rateOutcome type: Dichotomous | | | Identification | Sponsorship source: Not reported Country: The Netherlands Setting: Single centre Author name: Dohle Institution: Andrology Unit of the Department of Urology, Erasmus MC Email: Not reported Address: Rotterdam, the Netherlands | | | Notes | Just a published abstract. Author confirmed there was no other paper published. Has not undergone peer review. | | | Risk of bias | || | Bias | Authors' judgement | Support for judgement | | Random sequence generation (selection bias) | Unclear risk | Not reported | | Allocation concealment (selection bias) | Unclear risk | Not reported | | Blinding of participants and personnel (performance bias) All outcomes | Low risk | Not reported. Blinding unlikely to influence outcomes. | | Blinding of outcome assessment (detection bias) All outcomes | Low risk | Not reported. Blinding unlikely to influence outcomes. | | Incomplete outcome data (attrition bias) All outcomes | Low risk | Attrition and exclusions reported. | | Selective reporting (reporting bias) | Unclear risk | No protocol found. | | Other bias | Low risk | None | Fang 2013. | Study characteristics | || | Methods | Study design: Randomised controlled trial Study grouping: Parallel group | | | Participants | Inclusion criteria: Infertile patients underwent physical examination and scrotum colour Doppler ultrasound to confirm varicocele (diameter greater than 0.3 cm) and see reflux. Exclusion criteria: Not reported Additional Characteristics ‐ Intervention: Unilateral: 26, bilateral: 4, Grade II: 10, Grade III: 20 Additional Characteristics ‐ Comparator: Unilateral: 24, bilateral: 6, Grade II: 9, Grade III: 21 Additional Characteristics ‐ 2nd Comparator: Unilateral: 28, bilateral: 2, Grade II: 14, Grade III: 16 Age: Mean (SD) ‐ Comparator: 27.2 (2.82) Age: Mean (SD) ‐ Intervention: 26.9 (2.95) Age: Mean (SD) ‐ 2nd Comparator: 27.4 (3.30) Number of Participants at Randomisation and Outcome ‐ Intervention: 30, 30 Number of Participants at Randomisation and Outcome ‐ Comparator: 30, 30 Number of Participants at Randomisation and Outcome ‐ 2nd Comparator: 30, 30 | | | Interventions | Intervention Characteristics Intervention Surgical Treatment: Open surgery Comparator Surgical Treatment: Microscopic surgery 2nd Comparator Surgical Treatment: Laparoscopic surgery | | | Outcomes | Pregnancy rateOutcome type: Dichotomous Varicocele recurrence Outcome type: Dichotomous Adverse events ‐ testicular atrophy Outcome type: Dichotomous Adverse events ‐ scrotal haematoma Outcome type: Dichotomous | | | Identification | Sponsorship source: Not reported Country: China Setting: Single centre Author name: Fang Institution: Medical University Zhujiang Hospital Email: Not reported Address: Guangzhou, China Author phone number: Not reported | | | Notes | || | Risk of bias | || | Bias | Authors' judgement | Support for judgement | | Random sequence generation (selection bias) | Unclear risk | Not reported | | Allocation concealment (selection bias) | Unclear risk | Not reported | | Blinding of participants and personnel (performance bias) All outcomes | Low risk | Not reported. Blinding unlikely to influence outcomes. | | Blinding of outcome assessment (detection bias) All outcomes | Low risk | Not reported. Blinding unlikely to influence outcomes. | | Incomplete outcome data (attrition bias) All outcomes | Unclear risk | Attrition and exclusions not reported. | | Selective reporting (reporting bias) | Unclear risk | No protocol found. | | Other bias | Low risk | None | Fayez 2010. | Study characteristics | || | Methods | Study design: Randomised controlled trial Study grouping: Parallel group | | | Participants | Inclusion criteria: Infertility for at least 1 year and subnormal semen. 2 sonographic criteria for varicocele assessment were used for inclusion and follow‐up comparison: diameter of the largest veins > 3 mm and time of regurge > 2 s during straining. Exclusion criteria: Not reported Additional Characteristics ‐ Intervention: The groups were comparable regarding mean ages of the participants, duration of infertility, and wife age. Unilateral: 22, bilateral: 33 Additional Characteristics ‐ Comparator: The groups were comparable regarding mean ages of the participants, duration of infertility, and wife age. Unilateral: 27, bilateral: 24 Additional Characteristics ‐ 2nd Comparator: The groups were comparable regarding mean ages of the participants, duration of infertility, and wife age. Unilateral: 23, bilateral: 26 Age: Mean (SD) ‐ Intervention: No specific age mentioned, but reportedly comparable to other groups. Age: Mean (SD) ‐ Comparator: No specific age mentioned, but reportedly comparable to other groups. Age: Mean (SD) ‐ 2nd Comparator: No specific age mentioned, but reportedly comparable to other groups. Number of Participants at Randomisation and Outcome ‐ Intervention: 55, 55 Number of Participants at Randomisation and Outcome ‐ Comparator: 51, 51 Number of Participants at Randomisation and Outcome ‐ 2nd Comparator: 49, 49 | | | Interventions | Intervention Characteristics Intervention Surgical Treatment: Open surgical inguinal ligation of spermatic veins (Ivanissevich technique) Comparator Radiological Treatment: Scrotal antegrade sclerotherapy (Tauber’s technique) 2nd Comparator Radiological Treatment: Subinguinal antegrade sclerotherapy | | | Outcomes | Live birthOutcome type: Dichotomous (Undefined) pregnancy rate Outcome type: Dichotomous Varicocele recurrence Outcome type: Dichotomous Adverse events ‐ hydrocele formation Outcome type: Dichotomous Adverse events ‐ wound infection Outcome type: Dichotomous Fever Outcome type: Adverse event Haematoma Outcome type: Adverse event Orchialgia Outcome type: Adverse event | | | Identification | Sponsorship source: Not reported Country: Egypt Setting: Single centre Author name: Fayez, for correspondence: Fathy (see below) Institution: Department of Andrology, Sexology and Sexually Transmitted Diseases, Cairo University Hospital Email: [email protected] Address: Ahmed Fathy Shaheen, 3 Street 105, Maadi 11431 Helwan, Egypt | | | Notes | Authors were contacted for additional data but did not respond. | | | Risk of bias | || | Bias | Authors' judgement | Support for judgement | | Random sequence generation (selection bias) | Unclear risk | Not reported | | Allocation concealment (selection bias) | Low risk | Quote: "Patients were then randomly assigned to the three treatment methods by the ‘closed envelopes’ method." | | Blinding of participants and personnel (performance bias) All outcomes | Low risk | Not reported. Blinding unlikely to influence outcomes. | | Blinding of outcome assessment (detection bias) All outcomes | Low risk | Not reported. Blinding unlikely to influence outcomes. | | Incomplete outcome data (attrition bias) All outcomes | Unclear risk | No attrition reported at follow‐up. Exclusions not reported. | | Selective reporting (reporting bias) | Unclear risk | No protocol found. | | Other bias | Low risk | None | Gao 2015. | Study characteristics | || | Methods | Study design: Randomised controlled trial Study grouping: Parallel group | | | Participants | Inclusion criteria: Patients with varicocele infertility and distension who were treated in the hospital from January 2012 to December 2013 Exclusion criteria: Not reported Age: Mean (SD) ‐ Comparator: Not reported Age: Mean (SD) ‐ Intervention: Not reported Number of Participants at Randomisation and Outcome ‐ Intervention: 45, 45 Number of Participants at Randomisation and Outcome ‐ Comparator: 43, 43 | | | Interventions | Intervention Characteristics Intervention Surgical Treatment: Microscopic surgery Comparator Surgical Treatment: Laparoscopic surgery | | | Outcomes | Varicocele recurrenceOutcome type: Dichotomous Adverse events ‐ hydrocele formation Outcome type: Dichotomous | | | Identification | Sponsorship source: Not reported Country: China Setting: Single centre Author name: Gao Institution: First People's Hospital of Zhengzhou Email: Not reported Address: Zhengzhou, China Author phone number: Not reported | | | Notes | || | Risk of bias | || | Bias | Authors' judgement | Support for judgement | | Random sequence generation (selection bias) | Unclear risk | Not reported | | Allocation concealment (selection bias) | Unclear risk | Not reported | | Blinding of participants and personnel (performance bias) All outcomes | Low risk | Not reported. Blinding unlikely to influence outcomes. | | Blinding of outcome assessment (detection bias) All outcomes | Low risk | Not reported. Blinding unlikely to influence outcomes. | | Incomplete outcome data (attrition bias) All outcomes | Unclear risk | Attrition and exclusions not reported. | | Selective reporting (reporting bias) | Unclear risk | No protocol found. | | Other bias | Low risk | None | Gao 2017. | Study characteristics | || | Methods | Study design: Randomised controlled trial Study grouping: Parallel group | | | Participants | Inclusion criteria: Doppler ultrasound‐diagnosed veins, married with normal sex life and > 1 year infertility, consent given Exclusion criteria: Severe heart, liver, kidney, and other basic diseases, obstructive azoospermia, spouse infertility, epididymitis and orchitis, on medication to improve sperm quality 3 months before enrolment Age: Mean (SD) ‐ Comparator: 29.83 (4.57) Age: Mean (SD) ‐ Intervention: 30.18 (4.61) Additional Characteristics ‐ Intervention: Unilateral: 28, bilateral: 19, Grade 1: 13, Grade II: 21, Grade III: 13 Additional Characteristics ‐ Comparator: Unilateral: 29, bilateral: 18, Grade 1: 15, Grade II: 20, Grade III: 12 Number of Participants at Randomisation and Outcome ‐ Intervention: 47, 47 Number of Participants at Randomisation and Outcome ‐ Comparator: 47, 47 | | | Interventions | Intervention Characteristics Intervention Surgical Treatment: Microscopic surgery Comparator Surgical Treatment: Laparoscopic surgery | | | Outcomes | (Undefined) pregnancy rateOutcome type: Dichotomous Adverse events ‐ hydrocele formation Outcome type: Dichotomous Adverse events ‐ testicular atrophy Outcome type: Dichotomous Adverse events ‐ scrotal oedema Outcome type: Dichotomous Adverse events ‐ epididymitis Outcome type: Dichotomous | | | Identification | Sponsorship source: Not reported Country: China Setting: Single centre Author name: Gao Institution: Traditional Chinese Medicine Hospital of Yuxi City Email: Not reported Address: Yunnan, China Author phone number: Not reported | | | Notes | || | Risk of bias | || | Bias | Authors' judgement | Support for judgement | | Random sequence generation (selection bias) | Unclear risk | Not reported | | Allocation concealment (selection bias) | Unclear risk | Not reported | | Blinding of participants and personnel (performance bias) All outcomes | Low risk | Not reported. Blinding unlikely to influence outcomes. | | Blinding of outcome assessment (detection bias) All outcomes | Low risk | Not reported. Blinding unlikely to influence outcomes. | | Incomplete outcome data (attrition bias) All outcomes | Unclear risk | Attrition and exclusions not reported. | | Selective reporting (reporting bias) | Unclear risk | No protocol found. | | Other bias | Low risk | None | Ghanaie 2012. | Study characteristics | || | Methods | Study design: Randomised controlled trial Study grouping: Parallel group | | | Participants | Inclusion criteria: Women recruited due to recurrent pregnancy loss (2 or more first trimester miscarriages and presence of a clinical varicocele) Exclusion criteria: Female partners > 40, female factor infertility, abnormal testes on physical examination, total testicular volume of 12 mL on ultrasonography, alcohol or substance abuse, severe general diseases and endocrinopathies, abnormal semen analysis (according to WHO), positive antisperm antibody assay Additional Characteristics ‐ Intervention: Grade 1: 17, Grade II: 41, Grade III: 10 Additional Characteristics ‐ Comparator: Grade 1: 15, Grade II: 42, Grade III: 11 Age: Mean (SD) ‐ Intervention: 36.1 (4.2), partner age: 29.1 (3.7) Age: Mean (SD) ‐ Comparator: 36.8 (4.6), partner age: 28.8 (3.4) Number of Participants at Randomisation and Outcome ‐ Intervention: 68, 68 Number of Participants at Randomisation and Outcome ‐ Comparator: 68, 68 | | | Interventions | Intervention Characteristics Intervention Surgical Treatment: Varicocelectomy Comparator Observation (delayed therapy) | | | Outcomes | Live birthOutcome type: Dichotomous Pregnancy Outcome type: Dichotomous Miscarriage Outcome type: Adverse event | | | Identification | Sponsorship source: Not reported Country: Iran Setting: Single centre Author name: Ghanie Institution: Urology Research Center, Guilan University of Medical Sciences, Rasht, Iran Email: [email protected] Address: Mohammad Reza Safarinejad, MD, PO Box 19395‐1849, Tehran, Iran | | | Notes | Authors were contacted for additional data but did not respond. | | | Risk of bias | || | Bias | Authors' judgement | Support for judgement | | Random sequence generation (selection bias) | Unclear risk | Not reported. Women who were unable to conceive were selected first, and then their husbands were recruited. Women were given consecutive study numbers and then allocated via them. | | Allocation concealment (selection bias) | Unclear risk | Not reported | | Blinding of participants and personnel (performance bias) All outcomes | Low risk | Not reported. Blinding unlikely to influence outcomes. | | Blinding of outcome assessment (detection bias) All outcomes | Low risk | Not reported. Blinding unlikely to influence outcomes. | | Incomplete outcome data (attrition bias) All outcomes | Low risk | Attrition and exclusions reported. | | Selective reporting (reporting bias) | Unclear risk | Protocol reported but not retrievable. | | Other bias | Low risk | None | Gontero 2005. | Study characteristics | || | Methods | Study design: Randomised controlled trial Study grouping: Parallel group | | | Participants | Inclusion criteria: Patients with male factor infertility, pain, semen abnormality, and/or testicular hypotrophia with primary varicocele Exclusion criteria: Previous inguinal hernia repair, patients requesting general anaesthesia Age: Mean (SD) ‐ Intervention: 25.13 (6.58) Age: Mean (SD) ‐ Comparator: 24.68 (6.00) Number of Participants at Randomisation and Outcome ‐ Intervention: 47, 47 Number of Participants at Randomisation and Outcome ‐ Comparator: 50, 50 | | | Interventions | Intervention Characteristics Intervention Surgical Treatment: Microscopic subinguinal varicocelectomy Comparator Surgical Treatment: Microscopic inguinal varicocelectomy | | | Outcomes | Varicocele recurrenceOutcome type: Dichotomous | | | Identification | Sponsorship source: None Country: Italy Setting: Single centre Author name: Gontero Institution: Clinica Urologica, Università del Piemonte Orientale Email: [email protected] Address: Clinica Urologica, Università del Piemonte Orientale, Novara, Italy | | | Notes | Authors were contacted for additional data but did not respond. | | | Risk of bias | || | Bias | Authors' judgement | Support for judgement | | Random sequence generation (selection bias) | Unclear risk | Not reported | | Allocation concealment (selection bias) | Unclear risk | Not reported | | Blinding of participants and personnel (performance bias) All outcomes | Low risk | Not reported. Blinding unlikely to influence outcomes. | | Blinding of outcome assessment (detection bias) All outcomes | Low risk | Not reported. Blinding unlikely to influence outcomes. | | Incomplete outcome data (attrition bias) All outcomes | Low risk | No attrition reported at follow‐up. Exclusions reported. | | Selective reporting (reporting bias) | Unclear risk | No protocol found. | | Other bias | Low risk | None | Grasso 2000. | Study characteristics | || | Methods | Study design: Randomised controlled trial Study grouping: Parallel group | | | Participants | Inclusion criteria: Men over 30 years old with a 1‐year history of infertility, ultrasound‐confirmed Hirsch grade I left varicocele and seminal analysis showing oligo‐, astheno‐, or teratozoospermia (according to WHO criteria) Exclusion criteria: Patients who wished to pursue assisted reproduction techniques during the study time frame. Female causes of infertility not mentioned. Age: Mean (SD) ‐ Intervention: Range 30 to 38 years Age: Mean (SD) ‐ Comparator: Range 30 to 38 years Number of Participants at Randomisation and Outcome ‐ Intervention: 34, 34 Number of Participants at Randomisation and Outcome ‐ Comparator: 34, 34 | | | Interventions | Intervention Characteristics Intervention Surgical Treatment: Left spermatic vein ligation (Palomo technique) Comparator Observation | | | Outcomes | Live birth (paternity)Outcome type: Dichotomous | | | Identification | Sponsorship source: None declared. Country: Italy Setting: Single centre Author name: Grasso Institution: Scientific Institute H. San Raffaele Email: Not reported Address: Department of Urology, Ospedale di Desio, Via Mazzini, 1, Milan, Italy | | | Notes | Correspondence email was not provided, so authors were not contacted for additional data. | | | Risk of bias | || | Bias | Authors' judgement | Support for judgement | | Random sequence generation (selection bias) | Unclear risk | Not reported | | Allocation concealment (selection bias) | Unclear risk | Not reported | | Blinding of participants and personnel (performance bias) All outcomes | Low risk | Not reported. Blinding unlikely to influence outcomes. | | Blinding of outcome assessment (detection bias) All outcomes | Low risk | Not reported. Blinding unlikely to influence outcomes. | | Incomplete outcome data (attrition bias) All outcomes | Unclear risk | Attrition and exclusions not reported. | | Selective reporting (reporting bias) | Unclear risk | No protocol found. | | Other bias | Low risk | None | Hargreave 1996. | Study characteristics | || | Methods | Study design: Randomised controlled trial Study grouping: Parallel group | | | Participants | Inclusion criteria: Men with varicocele and poor semen quality whose female partner had normal tubal patency and ovulation Exclusion criteria: Female factor infertility Age: Mean (SD) ‐ Intervention: Not reported Age: Mean (SD) ‐ Comparator: Not reported Intervention type: Operation (not specified) Comparator type: Observation (delayed operation by 1 year) Number of Participants at Randomisation and Outcome ‐ Intervention: 248 men randomised, no follow‐up figures mentioned. Number of Participants at Randomisation and Outcome ‐ Comparator: 248 men randomised, no follow‐up figures mentioned. | | | Interventions | Intervention Characteristics Intervention Surgical Treatment: Operation (not specified) Comparator Observation (delayed operation by 1 year) | | | Outcomes | (Undefined) pregnancy rateOutcome type: Dichotomous | | | Identification | Sponsorship source: None declared. Country: Scotland Setting: Single centre Author name: Hargreave Institution: Western General Hospitals NHS Trust Email: Not reported Address: Department of Urology, Western General Hospitals NHS Trust, Edinburgh, EH4TXU | | | Notes | Correspondence email was not provided, so authors were not contacted for additional data. | | | Risk of bias | || | Bias | Authors' judgement | Support for judgement | | Random sequence generation (selection bias) | Unclear risk | Not reported | | Allocation concealment (selection bias) | Unclear risk | Not reported | | Blinding of participants and personnel (performance bias) All outcomes | Low risk | Not reported. Blinding unlikely to influence outcomes. | | Blinding of outcome assessment (detection bias) All outcomes | Low risk | Not reported. Blinding unlikely to influence outcomes. | | Incomplete outcome data (attrition bias) All outcomes | Unclear risk | Attrition and exclusions not reported. | | Selective reporting (reporting bias) | Unclear risk | No protocol found. | | Other bias | Low risk | None | Ketabchi 2018a. | Study characteristics | || | Methods | Study design: Randomised controlled trial Study grouping: Parallel group | | | Participants | Inclusion criteria: Clinical varicocele, at least 1 abnormal semen parameter, female partner 35 years old Exclusion criteria: Teratozoospermia, bilateral varicoceles, recurrent varicoceles, operation complication (large hydroceles, testis atrophy, or those with a history of exposure to risk factors (addiction, cytotoxic agents, hormonal medicine, and hyperthermal job environments)) Age: Mean (SD) ‐ Intervention: 25.0 (2.7) Age: Mean (SD) ‐ Comparator: 25.0 (2.7) Number of Participants at Randomisation and Outcome ‐ Intervention: 98, 67 Number of Participants at Randomisation and Outcome ‐ Comparator: 98, 71 | | | Interventions | Intervention Characteristics Intervention Surgical Treatment: Subinguinal microscopical varicocelectomy Comparator Observation | | | Outcomes | (Undefined) pregnancy rateOutcome type: Dichotomous | | | Identification | Sponsorship source: Kerman Medical Sciences University Country: Iran Setting: Single centre Author name: Ketabchi Institution: Kerman Medical Sciences University Email: [email protected] Address: Urology Department, Bahonar Hospital, Kerman, Iran (code: 7613747181) | | | Notes | || | Risk of bias | || | Bias | Authors' judgement | Support for judgement | | Random sequence generation (selection bias) | Low risk | Randomised by block sequence (information from author correspondence) | | Allocation concealment (selection bias) | Unclear risk | Not reported | | Blinding of participants and personnel (performance bias) All outcomes | Low risk | Not reported. Blinding unlikely to influence outcomes. | | Blinding of outcome assessment (detection bias) All outcomes | Low risk | Not reported. Blinding unlikely to influence outcomes. | | Incomplete outcome data (attrition bias) All outcomes | Low risk | Attrition and exclusions reported. | | Selective reporting (reporting bias) | Low risk | Protocol found, and all outcomes reported. | | Other bias | Low risk | None | Ketabchi 2018b. | Study characteristics | || | Methods | Study design: Randomised controlled trial Study grouping: Parallel group | | | Participants | Inclusion criteria: Patients with left side clinical varicocele (Grade 1 to 3) with sperm abnormalities in count, shape, and/or progressive motility detected in 2 semen analyses samples Exclusion criteria: Patients with bilateral varicoceles, subclinical varicoceles, azoospermia, leukocytospermia, previous reproductive organ surgery, secondary infertility, with higher‐age wives (> 35 years), acupuncture experience, or history of using drugs that affect the genitourinary system during the last year Age: Mean (SD) ‐ Intervention: 33.4 Age: Mean (SD) ‐ Comparator: 32.0 Number of Participants at Randomisation and Outcome ‐ Intervention: 24, 24 Number of Participants at Randomisation and Outcome ‐ Comparator: 28, 28 | | | Interventions | Intervention Characteristics Intervention Surgical Treatment: Subinguinal microscopical varicocelectomy Comparator Sham procedure | | | Outcomes | Pregnancy rateOutcome type: Dichotomous | | | Identification | Sponsorship source: Physiology Research Center of Kerman Medical Sciences University Country: Iran Setting: Single centre Author name: Ketabchi Institution: Kerman Medical Sciences University Email: [email protected] Address: Urology Department, Bahonar Hospital, Kerman, Iran (code: 7613747181) | | | Notes | This study had additional subgroups that received acupuncture, but they were not included in the analysis to align the study population with that of the rest of the studies. | | | Risk of bias | || | Bias | Authors' judgement | Support for judgement | | Random sequence generation (selection bias) | Low risk | Randomised by block sequence (information from author correspondence) | | Allocation concealment (selection bias) | Unclear risk | Not reported | | Blinding of participants and personnel (performance bias) All outcomes | Low risk | Not reported. Blinding unlikely to influence outcomes. | | Blinding of outcome assessment (detection bias) All outcomes | Low risk | Not reported. Blinding unlikely to influence outcomes. | | Incomplete outcome data (attrition bias) All outcomes | Low risk | Attrition and exclusions reported. | | Selective reporting (reporting bias) | Unclear risk | No protocol found. | | Other bias | Low risk | None | Krause 2002. | Study characteristics | || | Methods | Study design: Randomised controlled trial Study grouping: Parallel group | | | Participants | Inclusion criteria: Men from couples with > 1 year subfertility, with clinical varicoceles only. At least 1 of the following seminal findings: sperm count < 20 million/mL; < 50% progressive motile spermatozoa; or /= 12 mL Exclusion criteria: Subclinical varicoceles; symptomatic varicoceles; genital disease (e.g. cryptorchidism); severe general disease or endocrinopathy; use of drugs with effects on sperm; sperm count < 2 million/mL; progressive motility 1 million/mL leukocytes; testicular volume < 1 mL; untreated or untreatable female subfertility Age: Mean (SD) ‐ Intervention: 31.2 (5.6); partner age: 29.6 (3.9) Age: Mean (SD) ‐ Comparator: 33.5 (5.3); partner age: 30.1 (3.5) Age: Mean (SD) ‐ 2nd Comparator: 30.9; partner age: 28.45 Number of Participants at Randomisation and Outcome ‐ Intervention: 11, 6 (5 lost to follow‐up) Number of Participants at Randomisation and Outcome ‐ Comparator: 21, 10 (11 lost to follow‐up) Number of Participants at Randomisation and Outcome ‐ 2nd Comparator: 33, 14 (19 lost to follow‐up) | | | Interventions | Intervention Characteristics Intervention Radiological Treatment: Antegrade sclerotherapy Comparator Radiological Treatment: Retrograde sclerotherapy 2nd Comparator Treatment: No treatment | | | Outcomes | (Undefined) pregnancy rateOutcome type: Dichotomous | | | Identification | Sponsorship source: German Research Council. Kr 935/4‐1 Country: Germany Setting: Multicentre Author name: Krause Institution: Philips University Marburg Email: [email protected]‐marburg.de Address: Department of Andrology, University Hospital, Philipps University, Marburg, Deutschhausstr. 9, D‐35033 Marburg, Germany | | | Notes | Authors were contacted for additional data but did not respond. | | | Risk of bias | || | Bias | Authors' judgement | Support for judgement | | Random sequence generation (selection bias) | Low risk | Quote: "The allocation was strictly randomised and used two computer generated lists." | | Allocation concealment (selection bias) | Low risk | Quote: "The treatment allocation was centrally provided after registration by a telephone call." | | Blinding of participants and personnel (performance bias) All outcomes | Low risk | Not reported. Blinding unlikely to influence outcomes. | | Blinding of outcome assessment (detection bias) All outcomes | Low risk | Not reported. Blinding unlikely to influence outcomes. | | Incomplete outcome data (attrition bias) All outcomes | Low risk | Attrition and exclusions reported. | | Selective reporting (reporting bias) | Unclear risk | No protocol found. | | Other bias | Low risk | None | Madgar 1995. | Study characteristics | || | Methods | Study design: Randomised controlled trial Study grouping: Parallel group | | | Participants | Inclusion criteria: Patients with infertility for at least 12 months, between 21 and 45 years of age, with a visible or palpable left varicocele only, with no history of severe renal, liver, or any other physical illness or long‐term medication affecting male fertility were selected for the study. Participants had to exhibit abnormal semen analysis (on 2 different occasions) according to WHO criteria, with the restriction of sperm count 5 X 106/mL to 20 X 106/mL. Exclusion criteria: Signs of accessory gland infection, as inferred from the following criteria: (1) history with no urogenital infection; (2) no abnormal rectal palpation; (3) < 1 X 106 leukocytes per millilitre ejaculate; and (4) no disturbance in secretory function of accessory glands. Female factor infertility Age: Mean (SD) ‐ Intervention: 28.7 (3.8) Age: Mean (SD) ‐ Comparator: 28.7 (4.5) Number of Participants at Randomisation and Outcome ‐ Intervention: 25, 25 Number of Participants at Randomisation and Outcome ‐ Comparator: 20, 20 | | | Interventions | Intervention Characteristics Intervention Surgical Treatment: Immediate varicocelectomy (high ligation) Comparator Delayed varicocelectomy (high ligation) | | | Outcomes | (Undefined) pregnancy rateOutcome type: Dichotomous | | | Identification | Sponsorship source: Not reported Country: Israel Setting: Single centre Author name: Madgar Institution: Sheba Medical Center Email: Not reported Address: Tel Hashomer, Israel | | | Notes | Correspondence email was not provided, so authors were not contacted for additional data. | | | Risk of bias | || | Bias | Authors' judgement | Support for judgement | | Random sequence generation (selection bias) | Unclear risk | Not reported | | Allocation concealment (selection bias) | Unclear risk | Not reported | | Blinding of participants and personnel (performance bias) All outcomes | Low risk | Not reported. Blinding unlikely to influence outcomes. | | Blinding of outcome assessment (detection bias) All outcomes | Low risk | Not reported. Blinding unlikely to influence outcomes. | | Incomplete outcome data (attrition bias) All outcomes | Low risk | Attrition and exclusions reported. | | Selective reporting (reporting bias) | Unclear risk | Protocol registry number reported but not retrievable. | | Other bias | Low risk | None | Meng 2017. | Study characteristics | || | Methods | Study design: Randomised controlled trial Study grouping: Parallel group | | | Participants | Inclusion criteria: Not reported Exclusion criteria: Not reported Age: Mean (SD) ‐ Comparator: 30.25 (4.45) Age: Mean (SD) ‐ Intervention: 28.64 (3.83) Additional Characteristics ‐ Intervention: Unilateral: 33, bilateral: 7, Grade II: 28, Grade III: 12 Additional Characteristics ‐ Comparator: Unilateral: 35, bilateral: 5, Grade II: 23, Grade III: 17 Number of Participants at Randomisation and Outcome ‐ Intervention: 40, 40 Number of Participants at Randomisation and Outcome ‐ Comparator: 40, 40 | | | Interventions | Intervention Characteristics Intervention Surgical Treatment: Microscopic surgery Comparator Surgical Treatment: Laparoscopic surgery | | | Outcomes | Varicocele recurrenceOutcome type: Dichotomous Adverse events ‐ scrotal oedema Outcome type: Dichotomous Adverse events ‐ scrotal pain Outcome type: Dichotomous Adverse events ‐ hydrocele formation Outcome type: Dichotomous Adverse events ‐ epididymitis Outcome type: Dichotomous Adverse events ‐ testicular atrophy Outcome type: Dichotomous | | | Identification | Sponsorship source: Not reported Country: China Setting: Single centre Author name: Meng Institution: 105th Hospital of PLA Email: Not reported Address: Hefei, China Author phone number: Not reported | | | Notes | || | Risk of bias | || | Bias | Authors' judgement | Support for judgement | | Random sequence generation (selection bias) | Unclear risk | Not reported | | Allocation concealment (selection bias) | Unclear risk | Not reported | | Blinding of participants and personnel (performance bias) All outcomes | Low risk | Not reported. Blinding unlikely to influence outcomes. | | Blinding of outcome assessment (detection bias) All outcomes | Low risk | Not reported. Blinding unlikely to influence outcomes. | | Incomplete outcome data (attrition bias) All outcomes | Unclear risk | Attrition and exclusions not reported. | | Selective reporting (reporting bias) | Unclear risk | No protocol found. | | Other bias | Low risk | None | Min 2011. | Study characteristics | || | Methods | Study design: Randomised controlled trial Study grouping: Parallel group | | | Participants | Inclusion criteria: Infertile men with varicocele Exclusion criteria: Not reported Pretreatment: No statistical differences between 2 groups in age, marriage, and lesion before operation. Additional Characteristics ‐ Intervention: Unilateral: 58, bilateral: 12, Grade II: 39, Grade III: 31 Additional Characteristics ‐ Comparator: Unilateral: 515, bilateral: 19, Grade II: 41, Grade III: 29 Age: Mean (SD) ‐ Intervention: 25.5 Age: Mean (SD) ‐ Comparator: 24.2 Number of Participants at Randomisation and Outcome ‐ Intervention: 70, 70 Number of Participants at Randomisation and Outcome ‐ Comparator: 70, 70 | | | Interventions | Intervention Characteristics Intervention Surgical Treatment: Microscopic spermatic vein low ligation Comparator Surgical Treatment: Laparoscopic spermatic vein high ligation | | | Outcomes | Adverse events ‐ bilateral scrotal oedemaOutcome type: Dichotomous | | | Identification | Sponsorship source: Not reported Country: China Setting: Single centre Author name: Xie Min Institution: Branch of First People's Hospital of Shanghai Jiaorong University Email: Not reported Address: Department of Urology, Branch of First People's Hospital of Shanghai Jiaorong University, Shanghai 200081, China | | | Notes | Correspondence email was not provided, so authors were not contacted for additional data. | | | Risk of bias | || | Bias | Authors' judgement | Support for judgement | | Random sequence generation (selection bias) | Unclear risk | Not reported | | Allocation concealment (selection bias) | Unclear risk | Not reported | | Blinding of participants and personnel (performance bias) All outcomes | Low risk | Not reported. Blinding unlikely to influence outcomes. | | Blinding of outcome assessment (detection bias) All outcomes | Low risk | Not reported. Blinding unlikely to influence outcomes. | | Incomplete outcome data (attrition bias) All outcomes | Unclear risk | Attrition and exclusions not reported. | | Selective reporting (reporting bias) | Unclear risk | No protocol found. | | Other bias | Low risk | None | Nieschlag 1993. | Study characteristics | || | Methods | Study design: Randomised controlled trial Study grouping: Parallel group | | | Participants | Inclusion criteria: Patients with varicocele on the left side were recruited from the infertility clinic of the Institute of Reproductive Medicine. Participants included in the study were required to meet the following criteria: (1) infertility for longer than 1 year, (2) varicocele Grade I to III on the left side, confirmed by palpation, ultrasonography, and Doppler sonography under Valsalva manoeuvre, (3) testicular volume on the left side smaller than on the right side, (4) subnormal semen parameters as assessed by WHO guidelines (1987) on 2 occasions about 3 months apart, (5) no other infertility‐related disease such as history of maldescended testes, infections or sperm antibodies or any general disease or chronic medication, (6) FSH not greater than 7 IU, the upper normal limit for fertile men established in our laboratory, and (7) fully investigated female partner including assessment of tubal patency, and without untreatable cause of infertility. Exclusion criteria: Not reported Pretreatment: There were no significant differences between the 2 groups before and after treatment in terms of semen and hormonal parameters except for progressive sperm motility. Age: Mean (SD) ‐ Intervention: 33.7 (5.2) Age: Mean (SD) ‐ Comparator: 34.1 (5.8) Number of Participants at Randomisation and Outcome ‐ Intervention: 38, 38 Number of Participants at Randomisation and Outcome ‐ Comparator: 33, 33 | | | Interventions | Intervention Characteristics Intervention Surgical Treatment: High retroperitoneal ligation according to Bernardi (1942) Comparator Radiological Treatment: Angiographic embolisation | | | Outcomes | Adverse events ‐ hydrocele formationOutcome type: Dichotomous (Undefined) pregnancy rate Outcome type: Dichotomous | | | Identification | Sponsorship source: Not reported Country: Germany Setting: Single centre Author name: Nieschlag Institution: Clemens‐Hospital Email: Not reported Address: Institute of Reproductive Medicine of the University, Steinfurter Strasse 107, D‐48149 Munster, Germany | | | Notes | Dr Nieschlag provided additional information on randomisation and allocation concealment: an independent statistician drafted a random list with the sequence of allocations to the groups. This list was kept locked in the secretariat, and each time a patient fulfilled the inclusion criteria, the secretary was asked which group the couple should be allocated to. | | | Risk of bias | || | Bias | Authors' judgement | Support for judgement | | Random sequence generation (selection bias) | Low risk | Quote: "Previously set randomisation list" established by random numbers (author correspondence). | | Allocation concealment (selection bias) | Low risk | List was kept locked in the secretariat. Each time a couple fulfilled the inclusion criteria, the secretary was asked to which group the couple should be allocated (information through author correspondence). | | Blinding of participants and personnel (performance bias) All outcomes | Low risk | Not reported. Blinding unlikely to influence outcomes. | | Blinding of outcome assessment (detection bias) All outcomes | Low risk | Not reported. Blinding unlikely to influence outcomes. | | Incomplete outcome data (attrition bias) All outcomes | Unclear risk | Attrition and exclusions reported, but the number of participants analysed in the results matches the number that completed the interventions; unclear how lost participants were adjusted for. | | Selective reporting (reporting bias) | Unclear risk | No protocol found. | | Other bias | Low risk | None | Nieschlag 1995/1998. | Study characteristics | || | Methods | Study design: Randomised controlled trial Study grouping: Parallel group | | | Participants | Inclusion criteria: Left‐sided clinical varicocele (Grade I to III); infertility persisting longer than 1 year despite regular unprotected intercourse; subnormal semen parameters as assessed by WHO guidelines Exclusion criteria: No other infertility‐related disease such as history of maldescended testes, infections, sperm antibodies (as detected by mixed agglutination reaction test), or any general disease or chronic medication; no obvious causes of infertility, such as anovulation, endometriosis, or tubal blockage, in the participant’s partner. Age: Mean (SD) ‐ Intervention: 33.1 (0.4), partner's age: 30.5 (0.5) Age: Mean (SD) ‐ Comparator: 32.8 (0.5), partner's age: 30.4 (0.4) Intervention type: Surgical ligation or angiographic embolisation of the spermatic vein Comparator type: Counselling Number of Participants at Randomisation and Outcome ‐ Intervention: 62 (30 ligation and 32 embolisation), 62 Number of Participants at Randomisation and Outcome ‐ Comparator: 63. 63 | | | Interventions | Intervention Characteristics Intervention Surgical Treatment: Surgical ligation or angiographic embolisation of the spermatic vein Comparator Counselling | | | Outcomes | (Undefined) pregnancy rateOutcome type: Dichotomous | | | Identification | Sponsorship source: None declared. Country: Germany Setting: Single centre Author name: Nieschlag Institution: Clemens‐Hospital Email: Not reported Address: Institute of Reproductive Medicine of the University, Domagkstr. 11, D‐48129 Munster, Germany | | | Notes | During study period, the WHO definition of normal morphology cut‐off changed from 50% to 30%. As participant assignment was random, all study groups were affected equally (mean date of entry into study not different). The only significant difference for achieving pregnancy was the female age at admittance to the study regardless of treatment modality: 28.8 years (pregnant) versus 31.1 years (not pregnant) (P < 0.05). Dr Nieschlag provided additional information on randomisation and allocation concealment: an independent statistician drafted a random list with the sequence of allocations to the groups. This list was kept locked in the secretariat, and each time a patient fulfilled the inclusion criteria, the secretary was asked which group the couple should be allocated to. | | | Risk of bias | || | Bias | Authors' judgement | Support for judgement | | Random sequence generation (selection bias) | Low risk | Quote: "The randomization scheme was established by random numbers before the first patient entered the study." | | Allocation concealment (selection bias) | Low risk | List was kept locked in the secretariat. Each time a couple fulfilled the inclusion criteria, the secretary was asked to which group the couple should be allocated (information through author correspondence). | | Blinding of participants and personnel (performance bias) All outcomes | Low risk | Not reported. Blinding unlikely to influence outcomes. | | Blinding of outcome assessment (detection bias) All outcomes | Low risk | Not reported. Blinding unlikely to influence outcomes. | | Incomplete outcome data (attrition bias) All outcomes | Low risk | Attrition and exclusions reported. | | Selective reporting (reporting bias) | Unclear risk | No protocol found. | | Other bias | Low risk | None | Nilsson 1979. | Study characteristics | || | Methods | Study design: Randomised controlled trial Study grouping: Parallel group | | | Participants | Inclusion criteria: Left clinical varicocele Exclusion criteria: Previous operation for hydrocele of the testis or inguinal hernia during childhood, mumps orchitis contracted during or after puberty, unilateral or bilateral testicular retention corrected or not corrected by operation. Azoospermic men as well as patients autoimmunised to spermatozoa and those with raised FSH were excluded. Female factor infertility Age: Mean (SD) ‐ Intervention: Not reported Age: Mean (SD) ‐ Comparator: Not reported Number of Participants at Randomisation and Outcome ‐ Intervention: 51, 51 Number of Participants at Randomisation and Outcome ‐ Comparator: 45, 45 | | | Interventions | Intervention Characteristics Intervention Surgical Treatment: Surgical ligation (Palomo technique) Comparator Observation | | | Outcomes | (Undefined) pregnancy rateOutcome type: Dichotomous | | | Identification | Sponsorship source: Not reported Country: Sweden Setting: Single centre Author name: Nilsson Institution: University of Gothenburg Email: Not reported Address: Department of Urology, Sahlgrenska sjukhuset and Department of Obstetrics and Gynaecology, Östra sjukhuset, Göteborg, Sweden | | | Notes | Correspondence email was not provided, so authors were not contacted for additional data. | | | Risk of bias | || | Bias | Authors' judgement | Support for judgement | | Random sequence generation (selection bias) | Unclear risk | Not reported | | Allocation concealment (selection bias) | Unclear risk | Not reported | | Blinding of participants and personnel (performance bias) All outcomes | Low risk | Not reported. Blinding unlikely to influence outcomes. | | Blinding of outcome assessment (detection bias) All outcomes | Low risk | Not reported. Blinding unlikely to influence outcomes. | | Incomplete outcome data (attrition bias) All outcomes | Unclear risk | Attrition and exclusions not reported. | | Selective reporting (reporting bias) | Unclear risk | No protocol found. | | Other bias | Low risk | None | Niu 2017. | Study characteristics | || | Methods | Study design: Randomised controlled trial Study grouping: Parallel group | | | Participants | Inclusion criteria: Patients with varicocele infertility and distension who were treated in the hospital from December 2015 to December 2016 Exclusion criteria: Not reported Age: Mean (SD) ‐ Comparator: 31.1 (3.4) Age: Mean (SD) ‐ Intervention: 31.7 (4.2) Additional Characteristics ‐ Intervention: Unilateral: 19, bilateral: 19, Grade II: 21, Grade III: 17 Additional Characteristics ‐ Comparator: Unilateral: 20, bilateral: 18, Grade II: 23, Grade III: 17 Number of Participants at Randomisation and Outcome ‐ Intervention: 38, 38 Number of Participants at Randomisation and Outcome ‐ Comparator: 38, 38 | | | Interventions | Intervention Characteristics Intervention Surgical Treatment: Microscopic surgery Comparator Surgical Treatment: Laparoscopic surgery | | | Outcomes | Varicocele recurrenceOutcome type: Dichotomous Adverse events ‐ hydrocele formation Outcome type: Dichotomous | | | Identification | Sponsorship source: Not reported Country: China Setting: Single centre Author name: Niu Institution: The Second People’s Hospital of Tianshui Email: Not reported Address: Tianshui, China Author phone number: Not reported | | | Notes | || | Risk of bias | || | Bias | Authors' judgement | Support for judgement | | Random sequence generation (selection bias) | Unclear risk | Not reported | | Allocation concealment (selection bias) | Unclear risk | Not reported | | Blinding of participants and personnel (performance bias) All outcomes | Low risk | Not reported. Blinding unlikely to influence outcomes. | | Blinding of outcome assessment (detection bias) All outcomes | Low risk | Not reported. Blinding unlikely to influence outcomes. | | Incomplete outcome data (attrition bias) All outcomes | Unclear risk | Attrition and exclusions not reported. | | Selective reporting (reporting bias) | Unclear risk | No protocol found. | | Other bias | Low risk | None | Pan 2013. | Study characteristics | || | Methods | Study design: Randomised controlled trial Study grouping: Parallel group | | | Participants | Inclusion criteria: Primary infertility (more than 1 year). Clinical varicocele confirmed by colour Doppler ultrasound. Semen analysis abnormal (oligozoospermia and/or asthenozoospermia and/or teratozoospermia) on at least 3 occasions and at least 1 month apart (all within 6 months before surgery – according to the WHO criteria). Serum hormone normal (FSH, LH, T, and PRL). Exclusion criteria: Secondary infertility. Men with subclinical varicocele, normal semen analyses, or aspermia. Surgical diseases (e.g. deformity, obstruction), congenital diseases (e.g. Klinefelter, Y chromosome deficiency), or endocrine diseases (e.g. Kallmann syndrome, hypercorticoidism). Female factor infertility Age: Mean (SD) ‐ Intervention: 29.5 (4.6) Age: Mean (SD) ‐ Comparator: 29.1 (4.1) Number of Participants at Randomisation and Outcome ‐ Intervention: 60, 59 Number of Participants at Randomisation and Outcome ‐ Comparator: 60, 56 | | | Interventions | Intervention Characteristics Intervention Surgical Treatment: Microsurgical varicocelectomy inguinal approach Comparator Surgical Treatment: Microsurgical varicocelectomy subinguinal approach | | | Outcomes | (Undefined) pregnancy rateOutcome type: Dichotomous Varicocele recurrence Outcome type: Dichotomous Adverse events ‐ hydrocele formation Outcome type: Dichotomous | | | Identification | Sponsorship source: Not reported Country: China Setting: Single centre Author name: Pan Institution: Nanjing University Email: [email protected] Address: Correspondence: Dr Yutian Dai, Department of Urology, Affiliated Drum Tower Hospital Nanjing University, School of Medicine, 321 Zhongshan Road, Nanjing 210008 China | | | Notes | Authors were contacted for additional data but did not respond. | | | Risk of bias | || | Bias | Authors' judgement | Support for judgement | | Random sequence generation (selection bias) | Unclear risk | Not reported | | Allocation concealment (selection bias) | Unclear risk | Not reported | | Blinding of participants and personnel (performance bias) All outcomes | Low risk | Not reported. Blinding unlikely to influence outcomes. | | Blinding of outcome assessment (detection bias) All outcomes | Low risk | Not reported. Blinding unlikely to influence outcomes. | | Incomplete outcome data (attrition bias) All outcomes | Low risk | Attrition and exclusions reported. | | Selective reporting (reporting bias) | Unclear risk | No protocol found. | | Other bias | Low risk | None | Pocek 1999. | Study characteristics | || | Methods | Study design: Randomised controlled trial Study grouping: Parallel group | | | Participants | Inclusion criteria: Patients suffering from symptomatic varicocele of the third to fourth degree according to Sarteschi ultrasonographic classification Exclusion criteria: Not reported Age: Mean (SD) ‐ Intervention: Not reported Age: Mean (SD) ‐ Comparator: Not reported Age: Mean (SD) ‐ 2nd Comparator: Not reported Number of Participants at Randomisation and Outcome ‐ Intervention: 15 Number of Participants at Randomisation and Outcome ‐ Comparator: 15 Number of Participants at Randomisation and Outcome ‐ 2nd Comparator: 15 | | | Interventions | Intervention Characteristics Intervention Radiological Treatment: Sclerotherapy (Aethoxysklerol) Comparator Radiological Treatment: Embolisation (Gianturco coils) 2nd Comparator Radiological Treatment: Sclero‐embolisation therapy (Aethoxysklerol and Gianturco coils) | | | Outcomes | Varicocele recurrenceOutcome type: Dichotomous | | | Identification | Sponsorship source: Not reported Country: Italy Setting: Single centre Author name: Pocek Institution: University of Rome Email: Not reported Address: Department of Radiology, 'Tor Vergata' University of Rome, S. Eugenio Hospital. P, Ie Umanesimo 10.00144 Rome, Italy | | | Notes | Correspondence email was not provided, so authors were not contacted for additional data. | | | Risk of bias | || | Bias | Authors' judgement | Support for judgement | | Random sequence generation (selection bias) | Unclear risk | Not reported | | Allocation concealment (selection bias) | Unclear risk | Not reported | | Blinding of participants and personnel (performance bias) All outcomes | Low risk | Not reported. Blinding unlikely to influence outcomes. | | Blinding of outcome assessment (detection bias) All outcomes | Low risk | Not reported. Blinding unlikely to influence outcomes. | | Incomplete outcome data (attrition bias) All outcomes | Low risk | No attrition or exclusions reported at follow‐up. | | Selective reporting (reporting bias) | Unclear risk | No protocol found. | | Other bias | Low risk | None | Pu 2014. | Study characteristics | || | Methods | Study design: Randomised controlled trial Study grouping: Parallel group | | | Participants | Inclusion criteria: Patients with infertility and discomfort underwent medical history, physical examination, and scrotal colour Doppler ultrasound examination (the diameter of the spermatic vein greater than or equal to 25 mm and visible venous reflux sign). Exclusion criteria: Secondary varicocele and subclinical varicocele were excluded. Additional Characteristics ‐ Intervention: Unilateral: 38, Grade l: 14, Grade II: 17, Grade III: 7 Additional Characteristics ‐ Comparator: Unilateral: 26, Grade l: 9, Grade II: 12, Grade III: 5 Additional Characteristics ‐ 2nd Comparator: Unilateral: 33, Grade l: 13, Grade II: 14, Grade III: 6 Age: Mean (SD) ‐ Comparator: 26.68 (3.69) Age: Mean (SD) ‐ Intervention: 25.23 (1.84) Age: Mean (SD) ‐ 2nd Comparator: 26.03 (2.08) Number of Participants at Randomisation and Outcome ‐ Intervention: 38, 38 Number of Participants at Randomisation and Outcome ‐ Comparator: 26, 26 Number of Participants at Randomisation and Outcome ‐ 2nd Comparator: 33, 33 | | | Interventions | Intervention Characteristics Intervention Surgical Treatment: Open surgery Comparator Surgical Treatment: Microscopic surgery 2nd Comparator Surgical Treatment: Laparoscopic surgery | | | Outcomes | Varicocele recurrenceOutcome type: Dichotomous Adverse events ‐ hydrocele formation Outcome type: Dichotomous | | | Identification | Sponsorship source: Not reported Country: China Setting: Single centre Author name: Pu Institution: The First Affiliated Hospital of Chongqing Medical University Email: [email protected] Address: Chongqing, China Author phone number: Not reported | | | Notes | || | Risk of bias | || | Bias | Authors' judgement | Support for judgement | | Random sequence generation (selection bias) | Unclear risk | Not reported | | Allocation concealment (selection bias) | Unclear risk | Not reported | | Blinding of participants and personnel (performance bias) All outcomes | Low risk | Not reported. Blinding unlikely to influence outcomes. | | Blinding of outcome assessment (detection bias) All outcomes | Low risk | Not reported. Blinding unlikely to influence outcomes. | | Incomplete outcome data (attrition bias) All outcomes | Unclear risk | Attrition and exclusions not reported. | | Selective reporting (reporting bias) | Unclear risk | No protocol found. | | Other bias | Low risk | None | Punekar 1999. | Study characteristics | || | Methods | Study design: Randomised controlled trial Study grouping: Parallel group | | | Participants | Inclusion criteria: Clinical left varicocele, primary infertility Exclusion criteria: Bilateral varicocele, severe hypergonadotrophic hypogonadism Age: Mean (SD) ‐ Intervention: Incomplete study data Age: Mean (SD) ‐ Comparator: Incomplete study data Number of Participants at Randomisation and Outcome ‐ Intervention: 50, 50 Number of Participants at Randomisation and Outcome ‐ Comparator: 50, 50 | | | Interventions | Intervention Characteristics Intervention Surgical Treatment: Subinguinal microsurgical varicocelectomy Comparator Surgical Treatment: Inguinal varicocelectomy | | | Outcomes | (Undefined) pregnancy rateOutcome type: Dichotomous Varicocele recurrence Outcome type: Dichotomous Adverse events ‐ hydrocele formation Outcome type: Dichotomous Testicular atrophy Outcome type: Adverse event | | | Identification | Sponsorship source: None declared. Country: India Setting: Single centre Author name: Punekar Institution: Seth G.S. Medical College and Kind Edward VII Memorial Hospital Email: Not reported Address: Department of Urology, KEM Hospital, Parel, Mumbai, 400 012, India | | | Notes | Correspondence email was not provided, so authors were not contacted for additional data. | | | Risk of bias | || | Bias | Authors' judgement | Support for judgement | | Random sequence generation (selection bias) | Unclear risk | Not reported | | Allocation concealment (selection bias) | Unclear risk | Not reported | | Blinding of participants and personnel (performance bias) All outcomes | Low risk | Not reported. Blinding unlikely to influence outcomes. | | Blinding of outcome assessment (detection bias) All outcomes | Low risk | Not reported. Blinding unlikely to influence outcomes. | | Incomplete outcome data (attrition bias) All outcomes | Unclear risk | Attrition and exclusions not reported. | | Selective reporting (reporting bias) | Unclear risk | No protocol found. | | Other bias | Low risk | None | Qi 2009. | Study characteristics | || | Methods | Study design: Randomised controlled trial Study grouping: Parallel group | | | Participants | Inclusion criteria: Infertile patients with varicocele who were treated in the hospital from September 2004 to December 2006 Exclusion criteria: Not reported Additional Characteristics ‐ Intervention: Not reported Additional Characteristics ‐ Comparator: Not reported Age: Mean (SD) ‐ Comparator: Not reported Age: Mean (SD) ‐ Intervention: Not reported Number of Participants at Randomisation and Outcome ‐ Intervention: 20, 20 Number of Participants at Randomisation and Outcome ‐ Comparator: 20, 20 | | | Interventions | Intervention Characteristics Intervention Surgical Treatment: Microscopic surgery Comparator Surgical Treatment: Laparoscopic surgery | | | Outcomes | (Undefined) pregnancy rateOutcome type: Dichotomous | | | Identification | Sponsorship source: Not reported Country: China Setting: Single centre Author name: Qi Institution: The Third Affiliated Hospital of Sun Yat‐sen University Email: [email protected] Address: Guangzhou, China Author phone number: Not reported | | | Notes | || | Risk of bias | || | Bias | Authors' judgement | Support for judgement | | Random sequence generation (selection bias) | Unclear risk | Not reported | | Allocation concealment (selection bias) | Unclear risk | Not reported | | Blinding of participants and personnel (performance bias) All outcomes | Low risk | Not reported. Blinding unlikely to influence outcomes. | | Blinding of outcome assessment (detection bias) All outcomes | Low risk | Not reported. Blinding unlikely to influence outcomes. | | Incomplete outcome data (attrition bias) All outcomes | Unclear risk | Attrition and exclusions not reported. | | Selective reporting (reporting bias) | Unclear risk | No protocol found. | | Other bias | Low risk | None | Ren 2015. | Study characteristics | || | Methods | Study design: Randomised controlled trial Study grouping: Parallel group | | | Participants | Inclusion criteria: Infertile patients not responding to conservative treatment with drugs, varicose pulse accompanied by scrotum swelling, pain, and discomfort, affecting the normal quality of life. Health check found abnormal semen quality and second‐degree diagnosis of scrotum ultrasound. Exclusion criteria: Subclinical varicocele (i.e. ultrasound diagnosis of scrotal venous return without any obvious dilation of the cranial venous plexus), varicocele due to urinary tract infection, other infection, epididymitis, tuberculosis, and other secondary causes Additional Characteristics ‐ Intervention: Unilateral: 23, bilateral: 17, Grade II: 30, Grade III: 10 Additional Characteristics ‐ Comparator: Unilateral: 25, bilateral: 15, Grade II: 28, Grade III: 12 Age: Mean (SD) ‐ Comparator: 26.75 (4.97) Age: Mean (SD) ‐ Intervention: 27.32 (4.96) Number of Participants at Randomisation and Outcome ‐ Intervention: 40, 40 Number of Participants at Randomisation and Outcome ‐ Comparator: 40, 40 | | | Interventions | Intervention Characteristics Intervention Surgical Treatment: Microscopic surgery Comparator Surgical Treatment: Laparoscopic surgery | | | Outcomes | (Undefined) pregnancy rateOutcome type: Dichotomous Varicocele recurrence Outcome type: Dichotomous Adverse events ‐ hydrocele formation Outcome type: Dichotomous | | | Identification | Sponsorship source: Not reported Country: China Setting: Single centre Author name: Ren Institution: The Affiliated Hospital of Qingdao University Email: [email protected] Address: Qingdao, China Author phone number: Not reported | | | Notes | || | Risk of bias | || | Bias | Authors' judgement | Support for judgement | | Random sequence generation (selection bias) | Unclear risk | Not reported | | Allocation concealment (selection bias) | Unclear risk | Not reported | | Blinding of participants and personnel (performance bias) All outcomes | Low risk | Not reported. Blinding unlikely to influence outcomes. | | Blinding of outcome assessment (detection bias) All outcomes | Low risk | Not reported. Blinding unlikely to influence outcomes. | | Incomplete outcome data (attrition bias) All outcomes | Unclear risk | Attrition and exclusions not reported. | | Selective reporting (reporting bias) | Unclear risk | No protocol found. | | Other bias | Low risk | None | Sautter 2002. | Study characteristics | || | Methods | Study design: Randomised controlled trial Study grouping: Parallel group | | | Participants | Inclusion criteria: Patients with infertility and pain with clinical and subclinical varicocele (all grades) Exclusion criteria: Not reported Age: Mean (SD) ‐ Intervention: 31 (range 16 to 45) Age: Mean (SD) ‐ Comparator: 31 (range 16 to 45) Number of Participants at Randomisation and Outcome ‐ Intervention: 29, 29 Number of Participants at Randomisation and Outcome ‐ Comparator: 29, 29 | | | Interventions | Intervention Characteristics Intervention Surgical Treatment: Laparoscopic varicocelectomy Comparator Radiological Treatment: Antegrade sclerotherapy | | | Outcomes | Adverse events ‐ hydrocele formationOutcome type: Dichotomous Adverse events ‐ postoperative scrotal pain Outcome type: Dichotomous Epididymitis Outcome type: Adverse event Adverse events ‐ haematoma Outcome type: Adverse event Suture granuloma Outcome type: Adverse event | | | Identification | Sponsorship source: Not reported Country: Switzerland Setting: Single centre Author name: Sautter Institution: University Hospital Zurich Email: [email protected] Address: Department of Urology, University Hospital, Zurich, Switzerland | | | Notes | Authors were contacted for additional data but did not respond. | | | Risk of bias | || | Bias | Authors' judgement | Support for judgement | | Random sequence generation (selection bias) | Unclear risk | Not reported | | Allocation concealment (selection bias) | Unclear risk | Not reported | | Blinding of participants and personnel (performance bias) All outcomes | Low risk | Not reported. Blinding unlikely to influence outcomes. | | Blinding of outcome assessment (detection bias) All outcomes | Low risk | Not reported. Blinding unlikely to influence outcomes. | | Incomplete outcome data (attrition bias) All outcomes | Low risk | No attrition or exclusions reported at follow‐up. | | Selective reporting (reporting bias) | Unclear risk | Not reported | | Other bias | Low risk | None | Song 2012. | Study characteristics | || | Methods | Study design: Randomised controlled trial Study grouping: Parallel group | | | Participants | Inclusion criteria: Infertile patients with varicocele Exclusion criteria: Not reported Age: Mean (SD) ‐ Intervention: 30.00 (5.29) Age: Mean (SD) ‐ Comparator: 30.56 (5.76) Additional Characteristics ‐ Intervention: Unilateral: 33, bilateral: 3 Additional Characteristics ‐ Comparator: Unilateral: 32, bilateral: 4 Number of Participants at Randomisation and Outcome ‐ Intervention: 36, 30 (adverse events), 21 (pregnancy) Number of Participants at Randomisation and Outcome ‐ Comparator: 36, 30 (adverse events), 23 (pregnancy) | | | Interventions | Intervention Characteristics Intervention Surgical Treatment: Microscopic varicocelectomy Comparator Surgical Treatment: Laparoscopic varicocelectomy | | | Outcomes | (Undefined) pregnancy rateOutcome type: Dichotomous Varicocele recurrence Outcome type: Dichotomous Adverse events ‐ hydrocele formation Outcome type: Dichotomous Adverse events ‐ abdominal distention Outcome type: Dichotomous | | | Identification | Sponsorship source: Not reported Country: China Setting: Single centre Author name: Song Institution: General Hospital of Chinese PLA Email: [email protected] Address: Department of Urology, General Hospital of Chinese PLA, Beijing 100853, China | | | Notes | Authors were contacted for additional data but did not respond. | | | Risk of bias | || | Bias | Authors' judgement | Support for judgement | | Random sequence generation (selection bias) | Unclear risk | Not reported | | Allocation concealment (selection bias) | Unclear risk | Not reported | | Blinding of participants and personnel (performance bias) All outcomes | Low risk | Not reported. Blinding unlikely to influence outcomes. | | Blinding of outcome assessment (detection bias) All outcomes | Low risk | Not reported. Blinding unlikely to influence outcomes. | | Incomplete outcome data (attrition bias) All outcomes | Unclear risk | Attrition and exclusions not reported. | | Selective reporting (reporting bias) | Unclear risk | No protocol found. | | Other bias | Low risk | None | Su 2017. | Study characteristics | || | Methods | Study design: Randomised controlled trial Study grouping: Parallel group | | | Participants | Inclusion criteria: Patients with infertility, distention, and pain with varicocele who were treated in the hospital from January 2012 to January 2016 Exclusion criteria: Not reported Age: Mean (SD) ‐ Intervention: 26.35 (3.32) Age: Mean (SD) ‐ Comparator: 26.28 (3.18) Age: Mean (SD) ‐ 2nd Comparator: 25.55 (2.98) Age: Mean (SD) ‐ 3rd Comparator: 25.65 (2.77) Additional Characteristics ‐ Intervention: Unilateral: 60 Additional Characteristics ‐ Comparator: Unilateral: 58 Additional Characteristics ‐ 2nd Comparator: Unilateral: 62 Additional Characteristics ‐ 3rd Comparator: Unilateral: 55 Number of Participants at Randomisation and Outcome ‐ Intervention: 60, 60 Number of Participants at Randomisation and Outcome ‐ Comparator: 58, 58 Number of Participants at Randomisation and Outcome ‐ 2nd Comparator: 62, 62 Number of Participants at Randomisation and Outcome ‐ 3rd Comparator: 55, 55 | | | Interventions | Intervention Characteristics Intervention Surgical Treatment: High spermatic vein ligation surgery Comparator Surgical Treatment: Subinguinal microscopic surgery 2nd Comparator Surgical Treatment: Inguinal microscopic surgery 3rd Comparator Surgical Treatment: Laparoscopic surgery | | | Outcomes | (Undefined) pregnancy rateOutcome type: Dichotomous Varicocele recurrence Outcome type: Dichotomous Adverse events ‐ scrotal oedema Outcome type: Dichotomous Adverse events ‐ epididymitis Outcome type: Dichotomous | | | Identification | Sponsorship source: Not reported Country: China Setting: Single centre Author name: Su Institution: The First Affiliated Hospital of Hebei North University Email: Not reported Address: Hebei Zhangjiakou, China Author phone number: Not reported | | | Notes | || | Risk of bias | || | Bias | Authors' judgement | Support for judgement | | Random sequence generation (selection bias) | Unclear risk | Not reported | | Allocation concealment (selection bias) | Unclear risk | Not reported | | Blinding of participants and personnel (performance bias) All outcomes | Low risk | Not reported. Blinding unlikely to influence outcomes. | | Blinding of outcome assessment (detection bias) All outcomes | Low risk | Not reported. Blinding unlikely to influence outcomes. | | Incomplete outcome data (attrition bias) All outcomes | Unclear risk | Attrition and exclusions not reported. | | Selective reporting (reporting bias) | Unclear risk | No protocol found. | | Other bias | Low risk | None | Sun 2012. | Study characteristics | || | Methods | Study design: Randomised controlled trial Study grouping: Parallel group | | | Participants | Inclusion criteria: Patients with infertility, pain, and abnormal semen parameters with bilateral varicocele Exclusion criteria: Patients with right‐sided or left‐sided varicocele were excluded. Age: Mean (SD) ‐ Intervention: 24.98 (3.02) Age: Mean (SD) ‐ Comparator: 25.08 (3.03) Age: Mean (SD) ‐ 2nd Comparator: 24.24 (4.63) Number of Participants at Randomisation and Outcome ‐ Intervention: 51, 51 Number of Participants at Randomisation and Outcome ‐ Comparator: 51, 51 Number of Participants at Randomisation and Outcome ‐ 2nd Comparator: 51, 51 | | | Interventions | Intervention Characteristics Intervention Surgical Treatment: Open inguinal varicocelectomy Comparator Surgical Treatment: Retroperitoneal varicocelectomy 2nd Comparator Surgical Treatment: Laparoscopic varicocelectomy | | | Outcomes | Varicocele recurrenceOutcome type: Dichotomous | | | Identification | Sponsorship source: Not reported Country: China Setting: Single centre Author name: Sun Institution: Fifth Affiliated Hospital of Sun Yat‐Sen University Email: [email protected] Address: Correspondence: Min‐bo Yan, Department of Urology, The Fifth Affiliated Hospital of Sun Yat‐sen University, Zhuhai 519000, China | | | Notes | Authors were contacted for additional data but did not respond. | | | Risk of bias | || | Bias | Authors' judgement | Support for judgement | | Random sequence generation (selection bias) | Unclear risk | Not reported | | Allocation concealment (selection bias) | Unclear risk | Not reported | | Blinding of participants and personnel (performance bias) All outcomes | Low risk | Not reported. Blinding unlikely to influence outcomes. | | Blinding of outcome assessment (detection bias) All outcomes | Low risk | Not reported. Blinding unlikely to influence outcomes. | | Incomplete outcome data (attrition bias) All outcomes | Low risk | No attrition or exclusions reported at follow‐up. | | Selective reporting (reporting bias) | Unclear risk | No protocol found. | | Other bias | Low risk | None | Telkar 2012. | Study characteristics | || | Methods | Study design: Randomised controlled trial Study grouping: Parallel group | | | Participants | Inclusion criteria: Patients with infertility, pain, and swelling with Grade II disease and above Exclusion criteria: Not reported Age: Mean (SD) ‐ Intervention: Not reported Age: Mean (SD) ‐ Comparator: Not reported Number of Participants at Randomisation and Outcome ‐ Intervention: 15, 15 Number of Participants at Randomisation and Outcome ‐ Comparator: 15, 15 | | | Interventions | Intervention Characteristics Intervention Surgical Treatment: Laparoscopic varicocelectomy Comparator Surgical Treatment: Open inguinal varicocelectomy | | | Outcomes | Adverse events ‐ wound infectionOutcome type: Dichotomous Adverse events ‐ hydrocele Outcome type: Dichotomous Adverse events ‐ wound erythema Outcome type: Dichotomous | | | Identification | Sponsorship source: None Country: India Setting: Single centre Author name: Telkar Institution: SN Medical College and HSK Hospital Email: [email protected] Address: SN Medical College and HSK Hospital, Bagalkot, Karnataka, India | | | Notes | Authors were contacted for additional data but did not respond. | | | Risk of bias | || | Bias | Authors' judgement | Support for judgement | | Random sequence generation (selection bias) | Unclear risk | Not reported | | Allocation concealment (selection bias) | Unclear risk | Not reported | | Blinding of participants and personnel (performance bias) All outcomes | Low risk | Not reported. Blinding unlikely to influence outcomes. | | Blinding of outcome assessment (detection bias) All outcomes | Low risk | Not reported. Blinding unlikely to influence outcomes. | | Incomplete outcome data (attrition bias) All outcomes | Unclear risk | Attrition and exclusions not reported. | | Selective reporting (reporting bias) | Unclear risk | No protocol found. | | Other bias | Low risk | None | Unal 2001. | Study characteristics | || | Methods | Study design: Randomised controlled trial Study grouping: Parallel group | | | Participants | Inclusion criteria: Left subclinical varicocele with seminal values varying from oligoasthenospermia to normospermia Exclusion criteria: Not reported Age: Mean (SD) ‐ Intervention: 32.2 (5.5) Age: Mean (SD) ‐ Comparator: 33.1 (6.7) Number of Participants at Randomisation and Outcome ‐ Intervention: 21, 21 Number of Participants at Randomisation and Outcome ‐ Comparator: 21, 21 | | | Interventions | Intervention Characteristics Intervention Surgical Treatment: High ligation of internal spermatic vein Comparator Treatment: Clomiphene citrate 50 mg/day orally for 6 months | | | Outcomes | (Undefined) pregnancy rateOutcome type: Dichotomous | | | Identification | Sponsorship source: Not reported Country: Turkey Setting: Single centre Author name: Unal Institution: Department of Urology, School of Medicine, Harran University, Sanliurfa, Turkey Email: [email protected] Address: Dogan Unal MD, Harran Üniversitesi, TipFakultesi Hastanesi, Uroloji Anabilim Dali, TR‐63100, Sanliurfa, Turkey | | | Notes | Authors were contacted for additional data but did not respond. | | | Risk of bias | || | Bias | Authors' judgement | Support for judgement | | Random sequence generation (selection bias) | Unclear risk | Not reported | | Allocation concealment (selection bias) | Unclear risk | Not reported | | Blinding of participants and personnel (performance bias) All outcomes | Low risk | Not reported. Blinding unlikely to influence outcomes. | | Blinding of outcome assessment (detection bias) All outcomes | Low risk | Not reported. Blinding unlikely to influence outcomes. | | Incomplete outcome data (attrition bias) All outcomes | Unclear risk | Attrition and exclusions not reported. | | Selective reporting (reporting bias) | Unclear risk | No protocol found. | | Other bias | Low risk | None | Yamamoto 1996. | Study characteristics | || | Methods | Study design: Randomised controlled trial Study grouping: Parallel group | | | Participants | Inclusion criteria: Subclinical varicocele presenting with infertility Exclusion criteria: No subclinical varicocele Age: Mean (SD) ‐ Intervention: Not reported Age: Mean (SD) ‐ Comparator: Not reported Number of Participants at Randomisation and Outcome ‐ Intervention: 45, 45 Number of Participants at Randomisation and Outcome ‐ Comparator: 47, 40 | | | Interventions | Intervention Characteristics Intervention Surgical Treatment: Varicocelectomy: high ligation of the internal spermatic vein Comparator No treatment | | | Outcomes | (Undefined) pregnancy rateOutcome type: Dichotomous | | | Identification | Sponsorship source: Supported by Grant‐in‐Aid 07671716 for Scientific Research from the Ministry of Education, Science and Culture of Japan, Tokyo, Japan Country: Japan Setting: Single centre Author name: Yamamoto Institution: Departments of Urology and Radiology, Nagoya University School of Medicine Email: Not reported Address: Nagoya, Japan | | | Notes | Correspondence email was not provided, so authors were not contacted for additional data. | | | Risk of bias | || | Bias | Authors' judgement | Support for judgement | | Random sequence generation (selection bias) | Unclear risk | Not reported | | Allocation concealment (selection bias) | Unclear risk | Not reported | | Blinding of participants and personnel (performance bias) All outcomes | Low risk | Not reported. Blinding unlikely to influence outcomes. | | Blinding of outcome assessment (detection bias) All outcomes | Low risk | Not reported. Blinding unlikely to influence outcomes. | | Incomplete outcome data (attrition bias) All outcomes | Unclear risk | Attrition reported. Exclusions not reported. | | Selective reporting (reporting bias) | Unclear risk | No protocol found. | | Other bias | Low risk | None | Yang 2017. | Study characteristics | || | Methods | Study design: Randomised controlled trial Study grouping: Parallel group | | | Participants | Inclusion criteria: Patients who were married and had a normal sexual life for more than 1 year without childbearing, physical examination with palpable varicose veins, and/or spermatic ultrasound with a vein diameter ≥ 2 mm, and reflux in Valsal's test, abnormal semen quality (WHO Fourth Edition Semen Quality Reference Standard) Exclusion criteria: Unmarried patients, combined female infertility factors, surgery due to scrotum pain, and other diseases that cause abnormal semen quality Age: Mean (SD) ‐ Comparator: 25.8 Age: Mean (SD) ‐ Intervention: 26.6 Additional Characteristics ‐ Intervention: Unilateral: 90, bilateral: 58, Grade l: 12, Grade II: 98, Grade III: 38 Additional Characteristics ‐ Comparator: Unilateral: 49, bilateral: 21, Grade l: 6, Grade II: 51, Grade III: 3 Number of Participants at Randomisation and Outcome ‐ Intervention: 148, 148 Number of Participants at Randomisation and Outcome ‐ Comparator: 70, 70 | | | Interventions | Intervention Characteristics Intervention Surgical Treatment: Microscopic surgery Comparator Surgical Treatment: Laparoscopic surgery | | | Outcomes | Varicocele recurrenceOutcome type: Dichotomous Adverse events ‐ hydrocele formation Outcome type: Dichotomous | | | Identification | Sponsorship source: Not reported Country: China Setting: Single centre Author name: Yang Institution: The Central Hospital of Shan County Address: Shandong, China Author phone number: Not reported | | | Notes | || | Risk of bias | || | Bias | Authors' judgement | Support for judgement | | Random sequence generation (selection bias) | Low risk | Quote: "According to the digital table, they were randomly divided." | | Allocation concealment (selection bias) | Unclear risk | Not reported | | Blinding of participants and personnel (performance bias) All outcomes | Low risk | Not reported. Blinding unlikely to influence outcomes. | | Blinding of outcome assessment (detection bias) All outcomes | Low risk | Not reported. Blinding unlikely to influence outcomes. | | Incomplete outcome data (attrition bias) All outcomes | Unclear risk | Attrition and exclusions not reported. | | Selective reporting (reporting bias) | Unclear risk | No protocol found. | | Other bias | Low risk | None | Yavetz 1992. | Study characteristics | || | Methods | Study design: Randomised controlled trial Study grouping: Parallel group | | | Participants | Inclusion criteria: Clinical varicocele and infertility Exclusion criteria: Men who had additional pathologies which might interfere with fertility, and men whose partners were found to have any reproductive pathology were excluded. Age: Mean (SD) ‐ Intervention: Not reported Age: Mean (SD) ‐ Comparator: Not reported Age: Mean (SD) ‐ 2nd Comparator: Not reported Number of Participants at Randomisation and Outcome ‐ Intervention: 43, 43 Number of Participants at Randomisation and Outcome ‐ Comparator: 51, 51 Number of Participants at Randomisation and Outcome ‐ 2nd Comparator: 43, 43 | | | Interventions | Intervention Characteristics Intervention Radiological Treatment: Embolisation of the internal spermatic vein Comparator Surgical Treatment: Ivanissevich technique of high ligation of the spermatic veins Comparator Surgical Treatment: Bernardi technique of high ligation | | | Outcomes | Varicocele recurrenceOutcome type: Dichotomous (Undefined) pregnancy rate Outcome type: Dichotomous | | | Identification | Sponsorship source: Not reported Country: Israel Setting: Single centre Author name: Yavetz Institution: Sackler Faculty of Medicine, Tel Aviv University Email: Not reported Address: Institute for the Study of Fertility, Serlin Maternity Hospital, Tel Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel Aviv University, POB 7079, Tel Aviv 61 070, Israel | | | Notes | Correspondence email was not provided, so authors were not contacted for additional data. | | | Risk of bias | || | Bias | Authors' judgement | Support for judgement | | Random sequence generation (selection bias) | Unclear risk | Not reported | | Allocation concealment (selection bias) | Unclear risk | Not reported | | Blinding of participants and personnel (performance bias) All outcomes | Low risk | Not reported. Blinding unlikely to influence outcomes. | | Blinding of outcome assessment (detection bias) All outcomes | Low risk | Not reported. Blinding unlikely to influence outcomes. | | Incomplete outcome data (attrition bias) All outcomes | Low risk | No attrition or exclusions reported at follow‐up. | | Selective reporting (reporting bias) | Unclear risk | No protocol found. | | Other bias | Low risk | None | Zhang 2015a. | Study characteristics | || | Methods | Study design: Randomised controlled trial Study grouping: Parallel group | | | Participants | Inclusion criteria: Patients with infertility, distention, and discomfort with varicocele confirmed by physical examination, Valsalva test, and colour Doppler ultrasound to confirm varicocele (diameters greater than 2 mm) Exclusion criteria: Not reported Age: Mean (SD) ‐ Comparator: Not reported Age: Mean (SD) ‐ Intervention: Not reported Number of Participants at Randomisation and Outcome ‐ Intervention: 45, 45 Number of Participants at Randomisation and Outcome ‐ Comparator: 43, 43 | | | Interventions | Intervention Characteristics Intervention Surgical Treatment: Microscopic surgery Comparator Surgical Treatment: Laparoscopic surgery | | | Outcomes | Varicocele recurrenceOutcome type: Dichotomous Adverse events ‐ hydrocele formation Outcome type: Dichotomous | | | Identification | Sponsorship source: Not reported Country: China Setting: Single centre Author name: Zhang Institution: Shangcai County People's Hospital Address: Henan, China Author phone number: Not reported | | | Notes | || | Risk of bias | || | Bias | Authors' judgement | Support for judgement | | Random sequence generation (selection bias) | Unclear risk | Not reported | | Allocation concealment (selection bias) | Unclear risk | Not reported | | Blinding of participants and personnel (performance bias) All outcomes | Low risk | Not reported. Blinding unlikely to influence outcomes. | | Blinding of outcome assessment (detection bias) All outcomes | Low risk | Not reported. Blinding unlikely to influence outcomes. | | Incomplete outcome data (attrition bias) All outcomes | Unclear risk | Attrition and exclusions not reported. | | Selective reporting (reporting bias) | Unclear risk | No protocol found. | | Other bias | Low risk | None | Zheng 2012. | Study characteristics | || | Methods | Study design: Randomised controlled trial Study grouping: Parallel group | | | Participants | Inclusion criteria: Men with infertility, swelling, and abnormal semen parameters Exclusion criteria: Not reported Age: Mean (SD) ‐ Intervention: 22.0 Age: Mean (SD) ‐ Comparator: 24.0 Additional Characteristics ‐ Intervention: Unilateral: 21, bilateral: 6, Grade l: 20, Grade II: 10 Additional Characteristics ‐ Comparator: Unilateral: 22, bilateral: 8, Grade l: 22, Grade II: 8 Number of Participants at Randomisation and Outcome ‐ Intervention: 30, 30 Number of Participants at Randomisation and Outcome ‐ Comparator: 30, 30 | | | Interventions | Intervention Characteristics Intervention Surgical Treatment: Microsurgical subinguinal varicocelectomy Comparator Surgical Treatment: Laparoscopic high ligation of the inner spermatic veins | | | Outcomes | Varicocele recurrenceOutcome type: Dichotomous Adverse events ‐ hydrocele formation Outcome type: Dichotomous Adverse events ‐ scrotal oedema Outcome type: Dichotomous | | | Identification | Sponsorship source: Not reported Country: China Setting: Single centre Author name: Cai Zheng Institution: Suzhou Municipal Hospital Email: Not reported Address: Department of Urology, The Headquarters of Suzhou Municipal Hospital, Suzhou 215002, China | | | Notes | Correspondence email was not provided, so authors were not contacted for additional data. | | | Risk of bias | || | Bias | Authors' judgement | Support for judgement | | Random sequence generation (selection bias) | Unclear risk | Not reported | | Allocation concealment (selection bias) | Unclear risk | Not reported | | Blinding of participants and personnel (performance bias) All outcomes | Low risk | Not reported. Blinding unlikely to influence outcomes. | | Blinding of outcome assessment (detection bias) All outcomes | Low risk | Not reported. Blinding unlikely to influence outcomes. | | Incomplete outcome data (attrition bias) All outcomes | Low risk | No attrition or exclusions reported at follow‐up. | | Selective reporting (reporting bias) | Unclear risk | No protocol found. | | Other bias | Low risk | None | Abbreviations: ART: assisted reproductive technology; FSH: follicle stimulating hormone; IgA: immunoglobulin A; IgG: immunoglobulin G; IU: international units; LH: luteinising hormone; mIU: milli‐international units; PRL: prolactin; SA: semen analysis; SD: standard deviation; T: testosterone; TSH: thyroid stimulating hormone; WHO: World Health Organization Characteristics of excluded studies [ordered by study ID] | Study | Reason for exclusion | |---|---| | Abdel Maguid 2010 | Wrong study design | | Abdel Meguid 2011b | Wrong study design | | Abdelsalam 2017 | Wrong intervention | | Abrol 2014 | Wrong study design | | ACTRN12612001169831 | Wrong study design | | Adams 1983 | Wrong study design | | Akin 2014 | Wrong intervention. Comparing same intervention with different materials used for ligation | | Allameh 2018a | Wrong intervention. Comparing same intervention with variation in the treatment of accompanying vessels | | Allameh 2018b | Wrong intervention | | Arafa 2017 | Wrong study design | | Atmaja 2016 | Wrong study design | | Aziz 2018 | Wrong study design | | Baazeem 2011 | Wrong study design | | Badur 2015 | Wrong study design | | Bebars 2000 | Wrong study design | | Boxin 2012 | Wrong outcomes | | Broe 2016 | Wrong study design | | Cadeddu 2012 | Is an editorial comment | | Cantoro 2015 | Wrong study design | | Cayan 2017 | Wrong study design | | Chen 2010 | Wrong intervention. Comparing same intervention with variation in the treatment of accompanying vessels | | Chiba 2016 | Wrong study design | | Eisenberg 2011 | Wrong study design | | Fandella 1991 | Wrong outcomes | | Feneley 1997 | Wrong study design | | Gargouri 2015 | Wrong study design | | Ghanem 2004 | Wrong study design | | Grasso 1995 | Wrong intervention. Bilateral spermatic vein ligation not relevant, as varicocelectomy on the right side is mostly due to retroperitoneal tumour. | | Ha 2011 | Wrong intervention. Comparing same intervention with variation in either 1 or 2 surgical entry sites | | Hinev 2009 | Wrong patient population | | Iqbal 2004 | Wrong study design | | IRCT201409299014N43 | Wrong outcomes | | IRCT2016092524166N2 | Wrong study design | | Johnson 2017 | Wrong study design | | JPRN C000000377 | Trial terminated. | | Kalkan 2011 | Wrong study design | | Kang 2013 | Wrong intervention. Comparing same intervention with variation in the treatment of accompanying vessels | | Khan 2003 | Wrong study design | | Khan 2016 | Wrong study design | | Laven 1992 | Wrong patient population | | Matsuda 1993 | Wrong intervention | | Moursy 2014 | Wrong patient population | | NCT00767338 | Wrong intervention | | NCT03281915 | Wrong study design | | NCT03341897 | Wrong outcomes | | Paduch 1997 | Wrong patient population | | Park 2011 | Wrong study design | | Podkamenev 2002 | Wrong patient population | | Sayfan 1992 | Wrong study design | | Shamsa 2009 | Wrong study design | | Shioshvili 2003 | Wrong study design | | Siu 2016 | Wrong study design | | Sun 2018 | Wrong intervention | | Takeuchi 2014 | Wrong study design | | Tamhankar 2017 | Wrong study design | | Vanlangenhove 2012 | Wrong study design | | Vyas 2017 | Wrong intervention. Comparing same intervention with and without use of magnification | | Wang 2015 | Wrong study design | | Wang 2016 | Wrong study design | | Yamamoto 1995a | Wrong patient population | | Yamamoto 1995b | Wrong intervention | | Yamamoto 1995c | Wrong intervention | | Youssef 2015 | Wrong intervention. Comparing same intervention with variation in either 1 or 2 surgical entry sites | | Zhang 2015b | Wrong study design | | Zheng 2009 | Wrong intervention. Bilateral spermatic vein ligation not relevant, as varicocelectomy on the right side is mostly due to retroperitoneal tumour. | Characteristics of studies awaiting classification [ordered by study ID] Cavallini 2003. | Methods | Study design: Randomised controlled trial Study grouping: Parallel group | | Participants | Inclusion criteria: Not reported Exclusion criteria: Not reported Age: Mean (SD) ‐ Intervention: Not reported Age: Mean (SD) ‐ Comparator: Not reported Age: Mean (SD) ‐ 2nd Comparator: Not reported Number of Participants at Randomisation and Outcome ‐ Intervention: 41 Number of Participants at Randomisation and Outcome ‐ Comparator: 61 Number of Participants at Randomisation and Outcome ‐ 2nd Comparator: 54 | | Interventions | Intervention Characteristics Intervention Surgical Treatment: Surgery Comparator Non‐surgical Treatment: Cinnoxicam 2nd Comparator No Treatment: Placebo (glycerine suppository) | | Outcomes | No relevant outcomes reported. | | Notes | Authors were contacted for additional data but did not respond. | Feng 2017. | Methods | Study design: Randomised controlled trial Study grouping: Parallel group | | Participants | Inclusion criteria: Men with varicocele Exclusion criteria: Not reported Age: Mean (SD) ‐ Intervention: Not reported Age: Mean (SD) ‐ Comparator: Not reported Number of Participants at Randomisation and Outcome ‐ Intervention: 60 Number of Participants at Randomisation and Outcome ‐ Comparator: 60 | | Interventions | Intervention Characteristics Intervention Treatment: Open high ligation Comparator Treatment: Microscopic spermatic vein ligation | | Outcomes | No relevant outcome reported. | | Notes | Authors were contacted for additional data but did not respond. | Abbreviations: SD: standard deviation Characteristics of ongoing studies [ordered by study ID] NCT02695199. | Study name | Study design: Randomised controlled trial Study grouping: Parallel group | | Methods | Inclusion criteria: 20 to 39 years old who had infertility for more than 1 year and had clinical palpable varicoceles, impaired semen quality including sperm concentration < 15 million/mL or total motility < 40% or progressively motile < 32% (a + b), the 5th edited World Health Organization criteria was referred, with normal level of serum hormones including follicle stimulating hormone, luteinising hormone, thyroid hormones and prolactin, patient's spouse was healthy in reproduction Exclusion criteria: Subclinical varicocele, recurrent varicoceles, normal semen analyses, reasons for infertility other than varicoceles, refusing to enter randomisation, female partner older than 35 years, abnormal level of serum hormones, female factor infertility, significant surgical, congenital, or endocrine diseases | | Participants | Age: Mean (SD) ‐ Intervention: Not reported Age: Mean (SD) ‐ Comparator: Not reported Number of Participants ‐ Intervention: Not reported Number of Participants ‐ Comparator: Not reported | | Interventions | Intervention Characteristics Intervention Surgical Treatment: Laparoscopic varicocelectomy Comparator Surgical Treatment: Microsurgical subinguinal varicocelectomy | | Outcomes | Pregnancy rate, postoperative complications | | Starting date | 1 March 2016 | | Contact information | Sponsorship source: Not reported Country: China Setting: Single centre Author name: Mingzhen Yuan Institution: Second Hospital of Shandong University Email: [email protected] Address: Second Hospital of Shandong University | | Notes | Recruitment status unknown, completion date set for December 2017. | NCT02722187. | Study name | Study design: Randomised controlled trial Study grouping: Parallel group | | Methods | Inclusion criteria: Clinical varicocele, infertility duration of minimum 1 year, poor semen quality, otherwise unexplained infertility in the couple Exclusion criteria: Female infertility | | Participants | Age: Mean (SD) ‐ Intervention: Not reported Age: Mean (SD) ‐ Comparator: Not reported Number of Participants ‐ Intervention: 40 Number of Participants ‐ Comparator: 20 | | Interventions | Intervention Characteristics Intervention Surgical Treatment: Microsurgical subinguinal varicocelectomy Comparator Surgical Treatment: Laparoscopic varicocelectomy | | Outcomes | Pregnancy rate | | Starting date | 29 March 2016 | | Contact information | Sponsorship source: Not reported Country: Poland Setting: Single centre Author name: Dobroński P Institution: Medical University of Warsaw Email: [email protected] Address: Department of Urology Warsaw Medical University, Warsaw, Poland, 02‐005 | | Notes | Actively recruiting, completion date set for July 2019 | Abbreviations: SD: standard deviation Differences between protocol and review The outcome live birth is now a primary rather than a secondary outcome. We added 'treatment versus treatment' comparisons to the original 'treatment versus non‐surgical, delayed, or no treatment' comparison. A random‐effects model is now used, because no fixed‐effect can be assumed in these comparisons. The results are presented as risk ratios. Contributions of authors Emma Persad participated in the screening of the literature, data abstraction and data management, the analysis and interpretation of the data, and the preparation of the manuscript. Clare O'Loughlin participated in the screening of the literature and data abstraction. Simi Kaur participated in the screening of the literature and data abstraction. Nina Matyas participated in the screening of the literature and data abstraction. Gernot Wagner participated in the screening of the literature. Melanie Hassler‐Di Fratta gave clinical input and participated in the structuring of the review and the preparation of the manuscript. Barbara Nussbaumer‐Streit participated in the screening of the literature, the analysis and interpretation of the data, and the preparation of the manuscript. All authors provided feedback and agreed to the final version of this manuscript. Sources of support Internal sources - Internal support, Other MDSG editorial base External sources New Source of support, Other Declarations of interest EP, COL, SK, NM, GW, MH, and BNS have no conflicts of interest to declare. New search for studies and content updated (conclusions changed)

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