ICSI was first established in 1992 to treat couples with infertility due to low sperm quantity and quality who had undergone failed in-vitro fertilization or subzonal insemination7. Several sperm retrieval methods, including testicular sperm aspiration, cTESE and microTESE were designed to harvest sperm from the testes of men with azoospermia-related infertility3. In men with NOA, the successful retrieval rate was reported as 30–60% in a recent series5,8−10. The current study displayed no significant deviation from the typically reported sperm retrieval rate following the TESE procedure (66.1%).
A recent systematic review compared the outcomes of cTESE and microTESE and the overall sperm retrieval rate was significantly higher in the microTESE group (42.9–63% vs. 16.7–45%, p < 0.05). According to testicular histology, Sertoli cell-only and hypospermatogenesis showed more favorable results in the microTESE group (41% in microTESE vs. 6.3–29% in cTESE)11. Another study reported that microTESE was 1.5 times more superior for successful sperm retrieval than cTESE; however, no subgroup analyses were performed12. In the current study, there was no statistically significant difference in the sperm retrieval rate between the cTESE and microTESE groups (74.1% vs. 58.6, p = 0.22). Sub-analysis of the sperm retrieval rate according to testicular histopathology also revealed no statistically significant difference in the hypospermatogenesis, maturation arrest and Sertoli cell-only subgroups. Normal spermatogenesis could not be effectively analyzed because there were significant variations in patient characteristics (p < 0.05).
Some parameters have been previously reported to predict sperm retrieval. Higher testicular volume, lower levels of FSH and better histological features were investigated as sperm retrieval predictors by Doroteja et al. However, after multivariable analysis, better semen and histopathology remained the only predictive parameters5. A retrospective cohort analysis found that FSH level had a positive correlation between the success and failure groups in microTESE13. Yalcin Kizilkan et al. found that a previous successful testicular biopsy and higher testicular volume were predictive parameters for microTESE patients6. One study reported no predictors of successful outcomes, whereas tobacco usage was a predictor factor for patients with a negative TESE2. Another recent study concluded that there were no definite predictors for sperm retrieval, except for chromosome disease; however, Sertoli cell-only histopathology was associated with a reduced chance of harvesting spermatozoa14. Our univariate analysis revealed that lower levels of FSH, LH and prolactin, and higher testicular volume and better pathology were predictors of successful sperm retrieval. However, these parameters showed no statistically significant difference in the multivariate analysis except for the pathology result. Compared with normal spermatogenesis histopathology, Sertoli cell-only had lower sperm retrieval rates.
In addition, advanced paternal age is associated with male infertility caused by alternative reproductive hormone levels, sexual disorder or decreased sperm production15. Obesity can cause hormone alterations, increased systemic inflammation and increased testicular temperature, which can influence male fertility16. In the current study, in the group with normal spermatogenesis, those with a younger age showed higher rates of sperm retrieval (36.48 ± 5.14 vs. 45.00 ± 2.83, p = 0.03). In the Sertoli cell-only group, we found that those with a higher BMI had a higher rate of sperm retrieval (32.19 vs. 25.66 ± 2.46, p = 0.03). These findings could be due to the small number of patients included in the study which could have caused a sampling error.
Klinefelter syndrome, 47, XXY karyotype, is the most common genetic cause of male infertility and is found in 10% of azoospermia patients17. Until recently, it was considered to be a model of definite male infertility. A 54.5% − 72% sperm retrieval rate was reported in Klinefelter syndrome patients after microTESE18–20. However, Klinefelter patients with NOA still had a lower sperm retrieval rate than non-Klinefelter patients14. In the current study, spermatozoa were harvested from 0% of Klinefelter syndrome patients, which is not comparable with previous research; this is probably due to the low number of Klinefelter syndrome patients included. Y chromosome microdeletion was also a significant factor for NOA. The AZF located on the Y chromosome is the region for spermatogenesis and three overlapping regions named AZFa, AZFb and AZFc have been identified. AZFa or AZFb microdeletions are associated with maturation arrest or Sertoli cell-only syndrome21,22. Men with AZFa or AZFb microdeletions have minimal sperm retrieval success, whereas those with AZFc microdeletions have a reported success rate of approximately 50%23,24. The current study demonstrated that one patient with AZFa/AZFb microdeletions succeeded in recovering spermatozoa, whereas two other patients, one with a AZFa microdeletion and the other with AZFb/AZFc deletions failed to retrieve spermatozoa.
Complications such as hematoma, testicular fibrosis and testicular atrophy were less frequent in microTESE groups compared with cTESE groups11. The rates of hematoma and dehiscence were significantly different between the TESE-positive group and the TESE-negative group2. In the current study, the complication rate showed no significant difference between the cTESE and microTESE groups and there was also no significant difference in the subgroup histopathology analysis. A comparison of the positive and negative sperm retrieval groups also revealed no significant difference.
There were several limitations to the present study, including the fact that it was a single center study, its small cohort size and its retrospective nature. In addition, the current study only included Taiwanese patients and may not be comparable with Western populations or the entire NOA cohort. No standardized or long-term follow up was established. Finally, in future studies, predictor values of a successful pregnancy rate should also be analyzed rather than only those for sperm retrieval.
In conclusion, several parameters were found to predict the chance of successful spermatozoa retrieval in NOA patients in the univariate analysis, including lower levels of FSH, LH and prolactin, and a higher testicular volume and histopathology results. However, these parameters showed no statistically significant difference in the multivariate analysis except for histopathological features. The presence of Sertoli cell-only was a marker for a lower chance of sperm retrieval than normal spermatogenesis. A comparison of cTESE and microTESE revealed that there were no significant differences in the sperm retrieval rate for all patients, and the subgroups of hypospermatogenesis, maturation arrest and Sertoli cell-only.