The study investigated the predictive value of ultrasound parameters and hormone level for successful SR in azoospermia. The results have shown that higher testicular volume is a good predictor for successful SR. The SR rate in this study was 24.2% (with NOA patients). SR rates ranged from 16.7 – 48.8% in the conventional TESE [11, 22]. Ramasamy et al reported SR rate was 32% with conventional TESE and 57% with Micro-TESE, Ishikawa T et al shown that SR rate was 42% as they performed Micro-TESE for NOA patients [23, 24]. The different results between these studies could be partially explained by the different characteristics of the patients (OA, NOA) and sperm recovery methods (TESA, PESA, TESE or Micro-TESE).
FSH is a glycoprotein that stimulates Sertoli function and some studies considered that it concerned to androgen production, which are necessary for fertility. Azoospermia has been a consistent finding in men with loss of function mutations in FSHβ [25]. Serum FSH could predict the existence of sperm which was retrieved by conventional TESE [24]. Elevated plasma levels of FSH above 19.4 mIU/mL can suggest no spermatogenesis and hence unsuccessful SR [16]. Although FSH is useful marker for evaluation of the presence of sperm in NOA patients, it is dependent to the pathologic etiology of azoospermia and may not always be a good predictive factor [19, 20]. The different demographic characteristics in each study may explain these differences in the results. Li et al. considered FSH to only reflect the global spermatogenesis function but stated that FSH cannot determine the function of an isolated area in a testis. Micro-TESE is able to retrieve sperm even if the spermatogenesis function of the testis was very low, which could be the reason why FSH could not precisely predict the SR rate of micro-TESE [20]. In our study, we found that the FSH levels did indeed differ greatly in patients with whom sperm was retrieved successfully vs patients where sperm was not retrieved (see table 2).
LH was not commonly investigated as a predictor of SR outcome. In contrast to FSH, LH appears to have little role in spermatogenesis outside of inducing gonadal testosterone production. Cissen et al. found that LH was predictive for successful SR [7]. Enatsu et al. demonstrated older age and non‐idiopathic etiology were significantly associated with the probability of successful SR; however, they found no significant effects of testicular volume, FSH, LH, or testosterone on SR [17]. We found that LH seemed to be higher in unsuccessful patient than successful patients, with 13.42 mIU/ml and 5.86 mIU/ml, respectively (p = 0.0001).
In our study, varicocele was found in 13 cases (11.2%). Varicoceles were present in 26% of Chinese infertility patients [26]. The diagnosis of varicocele by spectral Doppler analysis has a sensitivity of approximately 97% and a specificity of 94% [27]. Although the relation between varicocele and male infertility has been demonstrated in many studies, the exact mechanism of the effect of varicocele on spermatogenesis is still unknown [26]. In our study, there was no significant difference between varicoceles and SR outcome. Scrotal ultrasound has a role in the diagnosis of the etiologies of male infertility. Abdulwahed et al. divided 268 infertile males into OA versus NOA based on histopathology, they found that decreased testicular volume and varicoceles (intra- and extra-testicular) were the most common abnormalities of NOA patients using ultrasonography. In contrast, epididymitis, spermatocele and duct ectasia were the most common in OA patients with a sensitivity 87% but only 30% specificity. Therefore scrotal ultrasound is used to exclude these diagnoses [14].
In this study, the mean total testicular volume of NOA was 13.67±12.1ml (Right testis 6.77 ±5.8ml, left testis 6.9±6.66ml). Sharath et al. (2013) found, mean testicular volume is 15ml (right testis 7.62±4.056ml, left testis 6.99±3.60ml) in male with abnormal semen analysis [10]. There is a distinction in selection of sperm recovery methods in OA patients (TESA, Percutaneous Biopsy, PESA, MESA) vs NOA patients (TESE, micro TESE). Testicular volume was found to be statistically significant between OA and NOA (mean testicular volume of OA and NOA patients are 11.6ml and 8.3ml, respectively, p<0.05) [28]. Huang et al. showed that a combination of FSH >9.2mIU/ml and right testis size <15ml might be used to distinguish NOA from OA, the positive predictive value for NOA was 99.2% and 81.8% for OA [18]. There was a significant difference in testicular volume between successful and unsuccessful SR group (22.84ml versus 9.0ml, P<0.001), higher testicular volume increased the chance of a successful SR. With a total volume lower than 7.8ml there is a 96.47% of having absence of sperm, and with a total volume higher than 28ml there is of 88.89% chance of sperm present in the sample. Tang WH et al. and Enatsu N et al. found that testicular volume of successful SR was higher than that of unsuccessful SR but there was no statistical significance between the two groups [17, 29]. Salehi et al (2017) performed TESE and micro-TESE in 170 NOA patients and found that testicular volume was related to surgical SR results (OR,10.5, p<0.01) [11]. The result was similar to Boitrelle’s study [15]. In OA sperm production was totally normal so SR rate by TESA or PESE was very high. Levine et al. assessed the effect of PESA and TESA in NOA and OA and found that SRR in NOA was 47% and OA this rate amounted to 100% [12].
In fact, it is difficult to predict the outcome of surgical SR with only testicular volume or any hormone values as well because many factors can affect process of spermatogenesis so a combination of these values might prove to be more reliable. After multivariate logistic regression analysis, the proportion of sperm improved with increasing of total testicular volume particular in NOA patients. It was found that, for every unit increase in total volume, the chance of successful SR rises by approximately 11%. Boitrelle et al. found that there was no significant difference between two groups (sperm present and no sperm) with age, testosterone, LH but they found that a combination of FSH concentration, inhibin B, and total testicular volume was the best predictor of TESE outcome (AUC=0.663) [15]. Li H et al. analyzed five studies with a total of 1764 cases involving testicular volume and found AUC=0.6389, indicating a low predictive [20]. Some studies showed that testicular volume did not affect the SR rate for micro-TESE. They suggested that testicular volume was an influential factor on successful SR, as it is correlated with spermatogenesis, but topographical variations in testicular pathology can occur, so testicular volume may not be a good predictive factor for successful SR for ICSI [19].
From our research, preoperative variables, namely FSH and testicular volume may predict success of SR in men with non-obstructive azoospermia and the combination of the variables may be even more predictive. Boitrelle et al developed a formula to predict TESE outcome, including three parameters: total testicular volume, FSH and inhibin B, shown to be the best predictor of successful TESE (positive likelihood ratio:+3.01) [15]. Histopathological examination has been the most reliable predictive factor of SRR to date. However, it is not recommended to perform the testicular biopsy just to predict the SRR of microdissection TESE [20]. We believe that the trial for SR should not be denied to any azoospermic men based solely on the values of the preoperative variables. The patient should be informed, prior to the operation that finding mature cells may not be guaranteed (even in cases with normal FSH and testicular volume) and allowed to make an informed decision on whether to proceed.