This study investigated the predictive value of ultrasound parameters and hormone levels for successful sperm retrieval in azoospermia. The sperm retrieval rate in this study was 49.3% which was similar to the results of Salehi et al. [16]. Ramasamy et al. reported sperm retrieval rates of 32% with conventional TESE and 57% with microsurgical testicular sperm extraction (Micro-TESE). [26] Similarly, Ishikawa T et al. showed that the sperm retrieval rate was 42% when they performed micro-TESE for NOA patients. [27] The various results between these studies could be partially explained by the various characteristics of the patients (OA, NOA) and the sperm recovery methods (TESA, PESA, TESE or Micro-TESE).
FSH is a glycoprotein that stimulates Sertoli function and some studies considered that it is associated with androgen production, which is necessary for fertility. Azoospermia has been a consistent finding in men with loss of function mutations in FSHβ. [28, 29] Serum FSH could predict the existence of sperm which could be retrieved by conventional TESE. [27] Elevated plasma levels of FSH above 19.4 mIU/mL can suggest no spermatogenesis and hence an unsuccessful sperm retrieval. [19] However, the predictive value of FSH remains contentious, with certain studies showing that FSH has a low predictive value for sperm retrieval. Although serum FSH is useful marker for the evaluation of the presence of sperm in NOA patients, it is dependent on the pathologic etiology of azoospermia and may not always be a reliable predictive factor. [22, 23] The various demographic characteristics in each study may explain the differences in these 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 global spermatogenesis function of the testis is very low. This could be the reason why FSH could not precisely predict the sperm retrieval rate of micro-TESE. [23] 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. However, the difference was not significant (see Table 3). In the NOA group, the median FSH level at which sperm was retrieved was found to be 23.17 IU/L versus 32.78 IU/L in men where sperm was not retrieved (P=0.062). Besides, 5.82 and 5.93 were the values of FSH in successful and unsuccessful semen retrieval in the OA patients, respectively.
LH is not commonly used as a predictor of sperm retrieval outcome. In males, LH stimulates Leydig cells to make and release testosterone into the testes and the blood. 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 also predictive for successful sperm retrieval. [9] Enatsu et al. demonstrated that older age and non‐idiopathic etiology were significantly associated with the probability of successful sperm retrieval. However, they found no significant effects on testicular volume, FSH, LH, or testosterone on sperm retrieval. [20] Our data also found no significance difference of LH value between the two groups in OA and NOA patients (P>0.05)
In our study, varicocele was found in 16 cases (11.8%). Varicoceles were present in 26% of Chinese male patients with infertility. [30] The diagnosis of varicocele by physical examination has a specificity of approximately 70%. In contrast, spectral Doppler analysis has a sensitivity of approximately 97% and a specificity of 94%. [31] Levinger U et al. found that the prevalence of varicocele increases with age. The prevalence of a varicocele increases 10% for each decade of life with the prevalence reaching 75% in the eight decade. [32] Although the relationship between varicocele and male infertility has been demonstrated in many studies, the exact mechanism of the effect of a varicocele on spermatogenesis remains unknown. [30] In our study, there was no significant difference between varicoceles and sperm retrieval outcomes. Scrotal ultrasound has a role in the diagnosis of the etiologies of male infertility. Abdulwahed et al. divided 268 infertile males into an OA versus NOA groups based on histopathology. The authors found, using ultrasonography, that decreased testicular volume and varicoceles (intra- and extra-testicular) were the most common abnormalities in NOA patients. 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. [17]
Sharath et al. (2013) found that a mean testicular volume is 15 ml (right testis 7.62±4.056 ml, left testis 6.99±3.60 ml) in males with an abnormal semen analysis. [14] There is a distinction between the selection of sperm recovery methods in OA patients (TESA, Percutaneous Biopsy, PESA, MESA) vs NOA patients (TESE, micro TESE). In particular, we found that the median testicular volume was 14.46 ml (right testicular volume 14.32 ml and left testicular volume 14.60 ml) in OA patients compared to 4.68 ml (Right testis 4.67 and left testis 4.69 ml) in NOA patients. According to Moon et al. testicular volume was found to be statistically significant between the OA and NOA patients (mean testicular volume of OA and NOA patients was 11.6 ml and 8.3 ml, respectively, P<0.05). [33] Huang et al. showed that a combination of FSH >9.2 mIU/ml and right testis size <15 ml may be used to distinguish NOA patients from OA patients. The positive predictive value for NOA patients was 99.2% and for OA patients was 81.8%. [21] In fact, many studies showed that testicular volume was not reduced in OA patients. Despite the difference in testicular volume between these studies, the majority of studies showed that the mean total testicular volume in infertile males was lower than normal. There was an insignificant difference in total testicular volume between the successful and unsuccessful sperm retrieval groups (5.68 ml versus 4.46 ml in NOA group, P=0.138; 14.90 ml versus 11.14 ml in OA group, P=0.208). Tang WH et al. and Enatsu N et al. found that the testicular volume of the successful sperm retrieval group was higher than that of the unsuccessful sperm retrieval group, however there was no statistical significance between the two groups. [20, 34] Salehi et al. (2017) performed TESE and micro-TESE in 170 NOA patients and found that the sperm recovery rate was 48.8% and that testicular volume was related to the surgical sperm retrieval results (OR,10.5, P<0.01). [16] The result was similar to Boitrelle’s study. [18]
In our study, successful sperm retrieval in the OA and NOA groups was 88.3% and 18.4%, respectively (P<0.001). In the OA group, sperm production was totally normal, so the sperm retrieval rates via TESA or PESA was very high. Levine et al. assessed the effect of PESA and TESA in the NOA and the OA groups and found that SRR in the NOA group was 47% and OA this rate amounted to 100%. [35]
In fact, it is difficult to predict the outcome of surgical sperm retrieval with only testicular volume or any hormone value as many factors can affect the process of spermatogenesis. Therefore, a combination of these values may prove to be more reliable. However, after multivariate logistic regression analysis, we found no significance difference between the two groups according to the results of semen retrieval. Boitrelle et al. found that there was no significant difference between the two groups (sperm present and no sperm) with age, testosterone, or LH. However, they found that a combination of FSH concentration, inhibin B, and total testicular volume were the best predictors of TESE outcomes (AUC=0.663). [18] Li H et al. analyzed five studies with a total of 1764 patients involving testicular volume and found AUC=0.6389, indicating a low predictive value. [23] Boitrelle et al. developed a formula to predict TESE outcome that included three parameters: total testicular volume, FSH and inhibin B. This formula was shown to be the best predictor of successful TESE (positive likelihood ratio:+3.01). [18] Otherwise, certain studies showed that testicular volume did not affect the sperm retrieval rate for micro-TESE. These studies suggested that testicular volume was an influential factor in successful sperm retrieval, as it is correlated with spermatogenesis, however topographical variations in testicular pathology can occur. Consequently testicular volume may not be a good predictive factor for successful sperm retrieval for ICSI. [22, 36]
Ramasamy et al. found that BMI and age had no predictive value for sperm retrieval rates [37, 38] which was similar to the findings in our study. From our research, preoperative variables, namely FSH and testicular volume could not be used as a predictive factor for the success of sperm retrieval in men with non-obstructive azoospermia. Histopathological examination has been the most reliable predictive factor of SRR to date. However, it is contraindicated to perform a testicular biopsy just to predict the SRR of microdissection TESE. [23] We believe that a trial for sperm retrieval should not be denied to any man with azoospermia 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.
In conclusion, in a variety of optimal cut-off values for testis volume and endocrine profiles for men with azoospermia have been reported with controversial results. This study demonstrated that testicular volume and endocrine tests should not be used as predictive factors for sperm retrieval outcomes in infertile males with azoospermia, both in the OA and NOA groups.