Does the use of hernia mesh in surgical inguinal hernia repairs cause male infertility? A systematic review and descriptive analysis

In the Singh 2012 study (Level I_1b), there were a total of 117 patients with a mean age of 45.6 ± 16.2 years (range 17–79). In Group I, 32 patients underwent TEP and 28 underwent TAPP. Group II had 57 patients that underwent open mesh repair. The follow-up time was preoperatively and postoperatively set at 3 months. There was no significant difference between those two groups in testicular functions, preoperatively. There were statistically significant decreases in the testicular volume, preoperatively and postoperatively in the open group (P = 0.01), but there was no significant difference, preoperatively and postoperatively in the LAP group (P = 0.3). There was also statistical significance in the resistive index, preoperatively and postoperatively in the open group (P = 0.07) and the LAP group (P = 0.04). In the LAP group, there was no significant difference in FSH levels (P = 0.4) and testosterone (P = 0.3) between preoperatively and postoperatively; however the decrease was significant in LH levels (P = 0.01) after operation. In the open group, there was statistical significance in FSH (P = 0.01), LH (P = 0.001), and testosterone (P = 0.02) between preoperatively and postoperatively. This trial suggested that laparoscopic repair may be more suitable for preserving testicular functions [31]. In the Akbulut 2003 study (level I_1b); there were a total of 60 patients with the age of 50.5 ± 4.4 (range 24–71). The follow-up time was 3 months. 26 patients were randomized and divided into the TEP group (13 patients) and Lichtenstein hernia repair (LHR) group (13 patients). There were no significant differences between preoperative and postoperative in both groups in regards to LH (P > 0.05) and FSH levels (P > 0.05). However, the decrease was significantly different in the testicular volume and testosterone levels in the TEP group (P < 0.05) compared to the LHR group (P > 0.05). It was indicated that the procedures would not alter LH, FSH, or testosterone values, but TEP could lead to a reduction in testicular volume within the normal limits [46]. Schouten 2012 designed a protocol for cohort studies in order to evaluate fertility after endoscopic TEP hernia repair, but no data has been published [29]. In Stula 2014 (II_2b), there were a total of 543 patients with a mean age of 61 years (ranging 33–81). The follow-up time ranged from five to 6 months. There were 29 patients who underwent TAPP and 53 patients under open tension-free hernia repair. There was no significant difference between the two groups in baseline. The anti-sperm antibodies (ASA) value significantly increased in the open group after operation (P < 0.001), but there was no significant difference in the TAPP group (P = 0.133). There was significant change in the resistive index (P < 0.001) and capsular artery level (P = 0.02) of the resistive index (RI), in patients who underwent TAPP. End-diastolic velocity (EDV) showed significant differences on the testicular artery level (P = 0.032) in patients in the open group. This study showed that mesh hernia repairs, open or laparoscopically, caused only a transitory change in testicular blood flow, but there was no clinical significant difference [27]. In the Stula 2012 study (level II_2b), there were a total of 43 patients with 62 years (range 33-81 years). The follow-up time was 5 months. There were 15 who underwent the TAPP procedure and 28 in the open (open tension-free hernia repair). This trial indicated that inguinal hernia mesh repairs do not have a clinical significant influence on testicular flow and sperm autoimmunity [30].

In Bansal 2017 (level I_1b), the RCT was divided into the TAPP group with 80 patients and TEP group with 80 patients. The mean age was 40.5 ± 12.4 (rang 18–60). The follow-up time was 3 months and 6 months. There was no significant difference in testicular volume (P > 0.05), testicular resistivity index (P > 0.05), FSH (P > 0.05), testosterone level (P > 0.05), and LH (P > 0.05) between the two groups at the 3 month or 6 month follow-up [13].

In Peters’ 2010 study (level I_1b), there were a total of 59 patients with an age range of 20–50 years. The patients were randomized into three groups: heavyweight polypropylene (Marlex®) with 20 patients, lightweight mesh (VyproII®) with 20 patients, and lightweight mesh (TiMesh®) with 19 patients, and all of the patients underwent TEP. The follow-up was at 1 year. This study suggests that the use of lightweight meshes for male patients with TEP could influence sperm motility (P = 0.013) at the 1 year follow-up [35]. In Peeters’ 2014 study (level I_1b), he utilized the same patients as Peters’ 2010, but the follow-up time was increased to 3 years. There was decreased sperm motility after 1 year, but there was no significant difference among the three groups in semen volume (P > 0.05), concentration (P > 0.05), motility (P > 0.05), a-glucosidase (P > 0.05) and morphology (P > 0.05) after 3 years. In Langenbach’s 2006 study (evidence, level V), he mentioned a change in testicular volume, but there were no detailed data supporting the observation [28].

In this group, there were two studies: Lal 2016 (level III_3b) and Skawran 2011 (level III_3b). In the Lal 2016 study, there were a total of 28 patients: 24 with unilateral hernia, 4 with bilateral hernia who underwent TEP. The mean age was 42.4 years (range 18–72). The resistive index was followed-up at 24 h, 1 week, and 3 months and compared preoperatively against postoperatively. There was no significant difference in resistive indexes of testicular, capsular, and intratesticular arteries during any time postoperatively [15]. In the Skawran 2011 study, there were a total of 59 patients with an age range of 18–60 years who underwent a bilateral TEP repairs. In the prospectively (light mesh) group, there were 21 patients, the preoperative values were compared with postoperative values, and the follow-up time was 3 months. It showed that there were no statistical differences between preoperative and postoperative in testicular volume, testicular perfusion, FSH, LH, testosterone, and testicular function (ejaculate volume) (P > 0.05). There were 38 patients in the retrospective (heavy mesh) group where the follow-up was determined at ≥3 months. Again, there was no significant difference between the prospective group and retrospective group in testicular volume, testicular perfusion, FSH, LH, and ejaculate volume (P > 0.05) [33].

Singh et al. reported that there were significant decreases in testosterone, LH, and FSH with less growth in testicular volume under the laparoscopic group; however there was no significant difference in testicular atrophy in either the open repair with polypropylene mesh (heavyweight) or the laparoscopic inguinal hernia repair with polypropylene mesh groups [31]. Akbulut et al. reported that there was no significant difference in the TEP group or the Lichtenstein group in FSH, LH, testosterone, and testicular volume, but TEP may have decreased testicular volume post-operation to the normal limits with type I-b, II-a [44]. The diverse results with Singh et al. may have been caused by the small sample size, type of hernia, or possibly human error. For example, some TAPP procedures might have been mistakenly placed in the laparoscopic group. Stula et al. reported that mesh hernia repairs under open tension-free hernia repair or TAPP were only changed in the resistive index, end diastolic velocity, and peak systolic velocity in the early postoperative period but returned to a normal value, which they believe has no clinical significance. However, they did not compare the heavyweight against the light heavyweight; instead they only mentioned that the heavyweight mesh was used in the open hernia repair group. The age range included was from 17 to 81 years old, so the normal fluctuations might be related with age [27]. This result was similar to an earlier study published by Stula et al., in 2012 [30]. Overall, inguinal hernia mesh repair under open tension-free hernia repair or TAPP did not have clinical significance on testicular flow and immunological response. Thus, these results from the studies indicate that polypropylene mesh LAP inguinal repair did not alter male infertility during either procedure.

Bansal et al. suggested that there was no change in testicular and sexual function after TAPP compared with TEP. According to the publication, changes in male infertility have no relation to the techniques used for TAPP or TEP; however they did not mention mesh in the procedures. Rather, the authors thought that handling the testicular vessels and cord structures during dissection may change the etiology of testicular dysfunction after open mesh repair [13].

Peeters et al. indicated that VyproII® or TiMesh® (lightweight mesh) decreased sperm motility when compared to Marlex® mesh (heavyweight) after a 1 year follow-up, but there was no significant difference after 3 years. In contrast, the lightweight mesh groups had a lower recurrence rate and no chronic pain, so lightweight mesh could be the superior choice [28, 35]. Junge et al. suggested that using modern low weight, large, porous, and elastic samples could have a benefit on the integrity of the vas deferens, when mesh is the required material to be used in younger patients undergoing open hernia repair [47].

Lal et al. indicated that laparoscopic TEP operations do not alter testicular flow dynamics at 24 h, 1 week, or 3 months postoperative [15]. Skawarn et al. suggested that there was no evidence of impaired fertility after TEP operation with light or heavy mesh [33]. There was no case report found regarding infertility caused by the LAP procedure. The reason behind this is that the LAP procedure allows for less damage and stress to the spermatic cord.

Gvenetadze et al. indicated that the Gvenetadze method was better than Lichtenstein’s in preventing male infertility when undergoing open surgery [16]. Kiladze et al. suggested that the Gvenetadze method prevented male infertility though spermatic cord isolation from mesh in bilateral hernia procedures compared to the Lichtenstein hernia repair [37]. Contrarily, Sucullu et al. and Aydede et al. indicated that whether the Lichtenstein, mesh plug method, posterior pre-peritoneal mesh repair, or anterior tension-free repair were used, none of the procedures caused infertility. Thus, it seems that numerous hernia repair methods which are performed routinely in the clinic do not lead to infertility [35, 42, 45].

Krnic et al. reported that 57 patients had non-complicated hernia procedures whereas 64 patients with incarcerated hernia. Bard Mesh was used in both groups. This study suggested that polypropylene mesh did not lead to any clinically significant problems on testicular flow in patients undergoing open hernia repair with either non-complicated or incarcerated hernia [14]. In the Ramadan et al. study, it showed that there was no significant change to testicular flow in the hernia side vs. non-hernia side; thus, different types of hernias may not impact infertility under the open hernia repair with mesh [38].

Hallen et al. performed an epidemiological survey in 2011, 232 in the bilateral mesh repair group and 112 in the non-mesh group were analyzed. There were no noteworthy effects in the testicular status of either group, according to the questionnaire. The authors believed that local legal circumstances and health care policies should be taken into consideration when doing sperm cryopreservation and the health care system should cover the cost of this fee if young men wish to have children later on in life [34]. The following year, Hallen et al. started a larger epidemiological survey where 0.9% (57/6281) of men were diagnosed with infertility after being operated on unilaterally without mesh compared to 0.59% (133/22420) of men with mesh. In the operated bilaterally, mesh on one side group, the infertility incidence was 0.87% (3/346). In operated bilaterally, mesh on both sides group, the incidence was 0.83% (19/2293) and in repeated repairs on any side, there was 0.77% (21/2701). The results showed that the incidence of infertility had no consequence in either the mesh groups with no-mesh groups, and mesh repair may continue to be used without major concern regarding the risk of male infertility [32].

In this group, these studies were retrospectives, case series, or case reports. Yan et al. and Brisinda et al. reported that there was no evidence that indicated that infertility was caused by the Lichtenstein or open tension-free hernia procedure [18, 40]. Khodari et al. mentioned that there were 69 azoospermia patients with a history of undergoing adult inguinal hernia repair surgery but did not describe the causes for the azoospermia [19]. Nagler et al. considered that a case with azoospermia was caused by mesh due to fibrosis of the vas deferens [43]. Yamaguchi et al. and Dohle et al. reported three cases with vas deferens obstruction after inguinal hernia repair with polypropylene mesh [39, 41]. Uzzo et al. reported in a 12 male beagle dog animal trial where half of the dogs were repaired using Marlex mesh and half had the classic Shouldice technique. There was a significant decrease in vasal luminal size with a marked soft tissue foreign body reaction identified in the Marlex mesh group [48].

Why could this change in procedure lead to infertility? There may be a relationship with mesh migration, surgeon skills, tightness of intraoperative suture or the surrounding tissue was not completely separated. The resulting postoperative bleeding, adhesions, and postoperative exercise frictions then trigger fibrosis which can lead to infertility. Chu et al. (level IV₄) reported two cases of testicular ischemia that were altered under inguinal hernia mesh repair, caused by the mesh loosening or removal [37]. Although there are fewer reports on vas deferens blockage, we still should focus on the standardization for operative procedures in order to lessen and ultimately, eliminate postoperative complications from the treatment. Another reason behind the cause of these medical concerns could be due to the level of the surgeon’s skill. For example, if the blood vessels were damaged during the intraoperative operation, it would lead to vas deferens ischemia, which could cause infertility. Some cases that are diagnosed as infertility may be associated instead with the inguinal hernia. Singh et al. indicated that long term inguinal hernia patients might suffer from impairment in testicular blood flow, which could also lead to infertility [31]. Additional factors that could impact infertility could include the patient’s age, work status, psychological factors, and the environment. Previously, our animal studies suggested that the distribution of inguinal hernia may be related to estrogen levels, and these estrogen levels may be associated with infertility. Aydede et al. suggested that mesh repair is still a safe surgery in patients with no children or those who are currently undergoing infertility treatment [45]; but in our opinion, if a young man desires to have children in the future and is apprehensive about potential issues to his fertility due to the surgical procedure, he should have his semen examined and stored preoperatively to avoid future problems and medical disputes.

The major limitations of our study were the following: 1) there was high clinical heterogeneity between the included RCTs, 2) there were small samples for these included studies, and 3) the period of treatment for each study and mesh were different. For some of these studies, there was insufficient data provided for meta-analysis, and the evidence was weak, so funnel plot and meta-analysis were not performed. That will lead to some publication bias and less strong evidence. Larger samples, rigorous design, multi-center RCTs performed using diverse populations, and different mesh/intervention groups would be necessary to enhance this evidence and support a stronger conclusion regarding infertility in these procedures.