Although the beneficial effects of varicocelectomy have been well studied in oligoasthenoteratozoospermia (OAT) men, the benefits of this surgical procedure are still limited and controversial in men of non-obstructive azoospermia [15, 16]. In 1952, the first study on the importance of varicocelectomy for treatment of NOA was performed by Tulloch [17]; after that, several studies investigated the effects of varicocelectomy on NOA patients [7, 9, 10, 11, 13, 14].
Testicular blood drains by pampiniform plexus, and when dilatation of these plexus vessels happens, varicocele occurs. The small valves normally prevent the reverse blood flow, but when there is compression of the veins or defects in these valves develops vessel dilatation occurs. Through several mechanisms, varicocele can cause generalized deterioration and progressive impairment of sperm production and result in abnormal semen quality, varying from oligospermia to complete azoospermia [2, 5]. The disease can change the concentration, motility, morphology and structure of sperm DNA [18, 19].
The complete absence of sperm in the ejaculate is defined as azoospermia. It is found in up to 15% of infertile men [18,19,20]. For the proper management of patients in azoospermia condition, it is important to differentiate between obstructive and non-obstructive pathology [18,19,20,21]. Testicular function can be demonstrated by FSH, LH, total testosterone and oestradiol levels, but measurement of fructose level in semen helps to rule out obstructive diagnosis [18,19,20,21,22].
On karyotype analysis, Y-chromosome microdeletions related to around 15% of patients with NOA, while Klinefelter syndrome is one of the most frequent genetic alterations in azoospermic men [18, 23, 24]. The Y-chromosome has three regions known as AZFa, AZFb and AZFc, and they incorporate the information for the production and maturation of sperm cells [24]. Evaluation of this is really essential for counselling because these patients can transmit genetic disorders to the offspring and they are not likely to benefit from varicocele surgery [19, 21, 22, 24].
Azoospermia is an extreme testicular dysfunction in varicocele men and is a significant barrier to unassisted pregnancy. In recent literature, there are several studies focussed on the association between varicocele and azoospermia. In this study, we also investigated the relationship between these two and evaluated the effects of microsurgical varicocelectomy on azoospermia men.
Varicocele repair by the affected spermatic veins occlusion can result in improvements in semen parameters, scrotal discomfort and spontaneous pregnancy rates [25]. Surgical repair can be performed by inguinal, retroperitoneal, subinguinal or laparoscopic approaches [26].
For men with NOA who desires pregnancy contribution by their own biological materials, treatment options include TESA (testicular sperm aspiration) or TESE with ICSI. Our study suggested that in men who have NOA with varicocele, the options of reproduction increases following varicocelectomy. In NOA men, the real advantage of this procedure is the possibility of producing motile sperms in the ejaculate. The use of motile sperm from fresh ejaculate is preferable to TESE in preparation for ICSI [27]. Compared with sperm retrieved by TESE, the fresh ejaculated sperms have superior ICSI success rates. Another advantage is to avoid the invasive and potentially damaging procedure of TESE [28].
In this study, we treated a total of 104 patients of NOA with clinical varicocele by microsurgical subinguinal approach. After varicocele repair in these 104 patients, we detected motile sperms in the ejaculate of 19 patients (18.26%) and spontaneous pregnancy occurred in 2/19 (10.5%) patients. However, assisted reproductive technique was required in the majority of couples to initiate pregnancy.
The results of our study and the previous studies of microsurgical varicocelectomy are compared. Matthews et al. [11] reported 54.5% (12 out of 22) patients had motile sperm in the ejaculate and 27.7% spontaneous pregnancy rate after subinguinal microsurgical varicocelectomy. The study by Schlegel et al. [7] shows that 22.5% (7 of 31) patients had motile sperm in the ejaculate and 3.2% spontaneous pregnancy rate after varicocelectomy. Several studies on NOA have shown improvement benefits in semen parameters of 20–50% cases and even in spontaneous pregnancy rate [9, 13, 29]. Kim et al. [30] on the other side reported that despite a mean follow-up of 24 months, spontaneous pregnancy was not seen even a single patient of complete azoospermia (0 of 28).
Another finding of our study was that, in men of NOA with varicocele, treatment response (presence of sperms in ejaculate after varicocelectomy) was better in patients with higher grade and bilateral varicocele. A study by Kadioglu et al. [9] also reported the similar finding.
Testicular histology is considered to be a significant predictive factor of outcome [9, 11, 30]. Patients with maturation arrest at the spermatocyte stage and germ cell aplasia had not shown improved semen quality; on the other side, azoospermic men with hypospermatogenesis or maturation arrest at the spermatid stage had shown improved semen quality post-operatively [5, 11, 14]. In this study, testicular biopsy of 19 patients who had achieved motile sperm post-varicocelectomy we found hypospermatogenesis in 14 patients. So, this result again supports that the most important histopathological predictor of post-operative sperm in the ejaculate was hypospermatogenesis.
It is important to note that among the 104 patients, only 2 patients (1.9%) with SCO pattern were positive for motile sperms in the post-surgery semen analyses which occurred at 6 and 8 months post-operatively. On further follow-up, these patients relapsed again into azoospermia. This finding suggests that varicocele repair may induce spermatogenesis temporarily which could not be sustained for a long time. So in this subgroup of patients, once the patient has sperms in the semen, semen cryopreservation should be considered. Testicular biopsy data of this study suggest that some level of sperm production is essential for a good result after varicocelectomy. Few sperm production region may present in patients of SCO [31].
Our data did not show any relation between presence of unilateral or bilateral testicular atrophy and final result. These findings are near to those reported in a previous study [11].
Previous studies reported post-varicocelectomy hydrocele incidence around 6–10% of patients [32, 33]. In our study, hydrocele formation occurred in 4.8% (5/104) patients. Improvement in semen quality and fertility were not significantly affected by post-operative hydrocele formation, this is similar to findings from previous studies [34].
The clinical advantage of varicocele surgery is that a considerable number of men with NOA have an option to provide sperms by ejaculation, without the need of invasive testicular sperm retrieval procedures.
Pregnancy can be achieved even with only a single sperm due to advancement in assisted reproductive technology (ART). Small improvements in spermatogenesis may exert a profound effect on couples’ reproductive options. Recent reports of TESE in men with NOA indicate that sperms are recovered from testicular tissue in 50–60% of such men [35, 36].
In this study, SRR by MDTESE was 34.11% (29/85) in NOA men with varicocelectomy compared to 24.03% (25/104) in NOA cases without varicocele. The study by Inci et al. [23] showed the SRR 53% and 30% in treated and untreated group, respectively. Therefore, Sperm retrieval rate may increase after varicocele surgery in NOA men with varicocele as compared to NOA men with no varicocele. Live birth rate/embryo was 31.03% (9/29) in NOA men with varicocele in comparison with 24% (6/25) in NOA without varicocele.
These results suggest that microsurgical varicocelectomy should be considered in all patients of NOA with clinical varicocele before proceeding directly to TESE.
The present study was nonrandomized, retrospective with small sample size which limits the generalization of these findings. To validate these results, further prospective studies with randomization and large sample sizes are required in future.