Underwent Microdissection Testicular Sperm Extraction Research Articles

O-258 Clinical factors associated with sperm retrieval success in hypogonadal nonobstructive azoospermic males undergoing microdissection testicular sperm extraction

Abstract Study question What factors are associated with sperm retrieval (SR) success through microdissection testicular sperm extraction (micro-TESE) in nonobstructive azoospermic (NOA) males with biochemical hypogonadism? Summary answer The SR success in hypogonadal NOA males is associated with FSH levels, pre-micro-TESE hormonal stimulation, presence of clinical varicocele, varicocelectomy history, and testicular histopathology results. What is known already Previous studies have investigated clinical predictors for SR success in NOA males, such as testicular volume, genetic status, and testicular histopathology, but these factors cannot be modified before SR. On the other hand, pre-SR hormonal stimulation and varicocele repair have shown potential for improving SR rates, although the evidence is inconclusive due to heterogeneity in patients and treatments. This lack of information makes it difficult for clinicians to determine whether medical or surgical interventions should be used before SR in NOA patients. Study design, size, duration This observational cohort study involved 616 hypogonadal NOA patients with primary spermatogenic failure who underwent micro-TESE at a University-affiliated center for male reproductive health between 2014 and 2021. Biochemical hypogonadism was defined as total testosterone (T) levels <350 ng/dL, measured from morning venous samples. All patients were naïve concerning previous SR attempts and were categorized into two groups based on whether they received pre-SR hormonal stimulation with recombinant gonadotropins (hCG alone or combined with FSH). Participants/materials, setting, methods Patients aged 23-55 underwent comprehensive clinical, laboratory, and histopathological evaluations for NOA. Multivariable logistic regression analysis explored the associations between patient variables and micro-TESE success. Adjusted risk ratio (aRR) assessed the relationship between SR success and relevant predictors. SR rates were compared between patients receiving hormonal stimulation and those who did not. Logistic regression analysis evaluated the effect of baseline FSH levels, stratified by normogonadotropic (<12 IU/L) and hypergonadotropic (≥12 IU/L) classes, on SR success. Main results and the role of chance The overall micro-TESE success rate was 56.6%. Independent predictors of SR success included baseline FSH levels (aRR 0.98, 95% CI 0.96-0.99, p = 0.04), pre-SR hormonal stimulation (aRR 1.52, 1.28-1.73, p = 0.0002), the presence of clinical varicocele (aRR 0.09, 0.01-0.66, p = 0.04), history of previous varicocelectomy (aRR 1.53, 1.14-1.84, p = 0.01), and testicular histopathology results (p < 0.05). Patients who received hormonal stimulation achieved higher SR success rates than untreated patients (62.5% [182/291] vs. 51.4% [167/325], p = 0.006; aRR 1.52, 95% CI 1.28-1.73). Among patients receiving hCG-based hormonal stimulation, pre-micro-TESE T levels and Delta T (absolute increase in T levels from baseline) were associated with SR success (p < 0.0001). A pre-micro-TESE T level of 418.5 ng/dL (AUC: 0.78) and a Delta T of 258 ng/dL (AUC: 0.76) distinguished treated patients with positive and negative SR outcomes. Subgroup analysis by baseline FSH levels showed that normogonadotropic individuals (aRR 1.41, 1.16-1.58, p = 0.002) benefited from hormonal stimulation, whereas hypergonadotropic subjects did not (aRR 1.20, 0.86-1.50, p = 0.23). The frequency of patients showing biochemical hypogonadism after hCG stimulation was reduced to 22.3% (65/291). The micro-TESE postoperative complication rate was 2.3% (14/616), while the frequency of patients exhibiting adverse effects presumably attributed to hormonal stimulation was 10.3% (30/291). Limitations, reasons for caution Limitations of the study include its observational nature and the absence of pregnancy data. The study focused on micro-TESE as the SR method and hormonal stimulation solely based on hCG (as monotherapy or associated with FSH), so results may differ with other treatments. Wider implications of the findings Our study underscores the complexity of counseling hypogonadal men with NOA, stressing the significance of assessing various factors. While our findings suggest potential benefits from pre-SR interventions, particularly hormonal stimulation and varicocele repair, none of the identified predictors can definitively determine the likelihood of successful SR. Trial registration number NCT05110391

Testicular ultrasonic microvascular density in assessing spermatogenesis and predicting successful sperm retrieval.

The relationship between microcirculatory disorders and testicular spermatogenesis is an area of ongoing interest among urologists. The objective of this prospective observational study was to investigate the correlation between testicular microcirculation and spermatogenesis, as well as the predictive value of ultrasonic microvascular density (UMVD) and ultrasonographic volume estimation (UVE) in successful sperm retrieval among men with non-obstructive azoospermia (NOA). Testicular UMVD derived from Angio PLUSTM Planwave Ultrasensitive Imaging (AP), UVE were obtained. Participants were divided into 4 groups (normozoospermia; asthenozoospermia, teratozoospermia, or asthenoteratozoospermia; oligozoospermia; NOA). The study included a total of 875 participants. No significant difference was found in UMVD-mean between different semen groups (P>0.05). A total of 108 participants with NOA underwent microdissection testicular sperm extraction (micro-TESE). Participants with successful sperm retrieval (40 cases) showed significant differences in testicular UMVD and UVE compared to those with negative retrieval (68 cases) (P<0.01). We generated receiver operating characteristic (ROC) curves for UMVD and testicular UVE to differentiate participants with successful sperm retrieval from those without. The area under the curve (AUC) was 0.760 [95% confidence interval (CI): 0.658-0.849, P<0.01] for UMVD and 0.716 (95% CI: 0.609-0.822, P<0.01) for testicular UVE, respectively. The optimal cutoff value was determined based on the maximum Youden index. When UMVD was set at 28.50/cm2, its sensitivity and specificity were calculated as 57.5% and 85.3%, respectively. For testicular UVE, a cutoff value of 8.94 mL resulted in a sensitivity of 60.0% and specificity of 82.4%. Combining UMVD with testicular UVE improved diagnostic performance (AUC: 0.856, 95% CI: 0.772-0.929, P<0.01) with a sensitivity of 79.4% and specificity of 77.5%. The present study demonstrates the utility of AP as a predictive tool for successful sperm retrieval prior to micro-TESE. Furthermore, the combination of testicular UMVD and UVE provides a highly valuable diagnostic approach for predicting micro-TESE success and can be routinely implemented before the procedure. A testicular UMVD exceeding 28.50/cm2 and a testicular UVE larger than 8.94 mL strongly indicate favorable outcomes in terms of sperm retrieval.

Incidental seminoma in nonobstructive azoospermia: a case report

To report on the incidental finding of invasive seminoma in a patient with nonobstructive azoospermia during microdissection testicular sperm extraction. Case report. A single patient diagnosed with nonobstructive azoospermia underwent microdissection testicular sperm extraction, and an incidental finding of invasive seminoma was made upon histopathological analysis. An incidental discovery of invasive seminoma was observed in the sample pathology obtained during the microdissection testicular sperm extraction. Consequently, the patient underwent further diagnostic workup and a radical orchiectomy. Men with male factor infertility are at increased risk of testicular cancer. As such, it is imperative to incorporate a thorough physical examination and relevant imaging into their diagnostic process. Additionally, it is advisable to include histopathological analysis for all individuals undergoing microdissection testicular sperm extraction.

Age, Sperm Retrieval, and Testicular Histology in Klinefelter Syndrome.

We sought to examine sperm retrieval and testicular histology in males of different ages with Klinefelter syndrome. We identified all males with Klinefelter syndrome who underwent microdissection testicular sperm extraction at our institution from 1995 to 2020. Patients were divided into adolescent (<20 years) and adult (≥20 years) cohorts. Histology and sperm retrieval were compared using chi-square statistics. Multivariable logistic regression models were used to examine factors associated with successful sperm retrieval. We identified 217 males with Klinefelter syndrome, of whom 59 were adolescents and 158 were adults. Adults were stratified into 10-year groupings (20-29 years, n = 62; 30-39 years, n = 88; ≥40 years, n = 8). Approximately 17% of adolescents had testis histology containing germ cells compared with 15% of the 20 to 29-year cohort, 14% of the 30 to 39-year cohort, and 0% over 40 years. In comparison to adolescents (53%), the sperm retrieval rate was significantly higher in the 20 to 29-year cohort (71%, P = .04) and lower in the ≥40-year cohort (13%, P = .03). In multivariable analysis, the presence of hypospermatogenesis on testis biopsy (OR 5.8, P = .03) was associated with higher odds of successful sperm retrieval. Younger males more frequently had germ cell-containing testis histology, however this finding was not associated with a higher odds of sperm retrieval. Reproductive urologists should counsel azoospermic males with Klinefelter syndrome that sperm retrieval during adolescence for fertility preservation is not required and can be performed in young adulthood.

Testicular sperm aspiration has a poor effect in predicting micro-TESE outcomes in NOA patients with AZFc deletion

BackgroundTesticular sperm aspiration (TESA) is widely used in the diagnosis and management of nonobstructive azoospermia. However, its ability for predicting microdissection testicular sperm extraction in nonobstructive azoospermia (NOA) patients with AZFc deletion remains uncertain. To investigate whether TESA affected the sperm retrieval rate (SRR) in NOA patients with AZFc deletion, a retrospective analysis of the clinical data of NOA patients with AZFc deletion who underwent microdissection testicular sperm extraction (micro-TESE) was conducted. The effects of age, testicular volume, follicle-stimulating hormone (FSH) levels, luteinizing hormone (LH) levels, testosterone (T) levels and TESA on the SRR were analyzed in this group of patients.ResultsA total of 181 individuals had their sperm successfully collected and underwent micro-TESE, with an SRR of 67.4%. The patients were separated into two groups based on their micro-TESE results (sperm acquisition and nonsperm acquisition), with no significant variations in age, testicular volume, FSH levels, LH levels, or T levels between the two groups. There was no significant difference in the SRR between any of the groups into which patients were classified based on reproductive hormone reference value ranges. Binary logistic regression was used to explore the absence of significant effects of age, testicular volume, FSH levels, LH levels, and T levels on sperm acquisition in patients undergoing micro-TESE. In the preoperative testicular diagnostic biopsy group, the sperm acquisition and nonsperm acquisition groups had SRRs of 90.1% and 65.1%, respectively. More significantly, there was no significant difference in the SRR between the negative preoperative testicular diagnostic biopsy group and the nonpreoperative testicular diagnostic biopsy group (65.1 vs. 63.8%, p = 0.855).ConclusionThere is a high probability of successful sperm acquisition in the testis of men undergoing micro-TESE. In this group of patients, age, testicular volume, FSH levels, LH levels, and T levels may have little bearing on the micro-TESE outcome. In patients whose preoperative TESA revealed the absence of sperm, the probability of obtaining sperm by micro-TESE remained high (65.1%); negative TESA results appeared to not influence the SRR (63.8%) in patients undergoing micro-TESE.

Factors associated with undergoing microdissection testicular sperm extraction among men with non-obstructive azoospermia following evaluation by a reproductive urologist.

Microdissection testicular sperm extraction (mTESE) is the gold standard treatment for men with non-obstructive azoospermia (NOA). However, many men do not elect to pursue this surgical intervention. We aimed to identify factors associated with NOA patients undergoing mTESE after initial evaluation by a reproductive urologist (RU) through a retrospective cohort study. We retrospectively reviewed NOA patient who underwent evaluation by a RU between 2002-2018. Demographic and clinical data were collected. Our primary outcome was electing to undergo mTESE. 44.4% (75/169) of NOA men underwent mTESE. These patients earned significantly higher median neighborhood income ($133,000 vs. $97,000, P<0.001), spent fewer years trying to conceive before seeking care {1.3 [interquartile range (IQR): 1-3] vs. 2.3 (IQR: 1-5), P=0.012}, and were more likely to be married (79.7% vs. 53.9%, P=0.001). On univariate analysis, married men [odds ratio (OR) 3.37, 95% confidence interval (CI): 1.67-6.79, P=0.001] and men with higher neighborhood income (OR 1.14, 95% CI: 1.06-1.21, P<0.001) were more likely to undergo mTESE, while couples attempting to conceive for a longer period of time prior to initial evaluation were less likely to undergo mTESE (OR 0.79, 95% CI: 0.68-0.92, P=0.003). On multivariable regression analysis, marital status and years attempting to conceive remained significantly associated with NOA patients undergoing mTESE (OR 4.61, 95% CI: 1.16-18.25, P=0.03; OR 0.67, 95% CI: 0.52-0.88, P=0.003, respectively). Higher neighborhood income and marital status were positively associated with patients undergoing mTESE, while couples who attempted to conceive for a longer period of time before seeking infertility care were less likely to undergo mTESE.

Anti-Müllerian hormone predicts positive sperm retrieval in men with idiopathic non-obstructive azoospermia-findings from a multi-centric cross-sectional study.

Is it possible to identify a reliable marker of successful sperm retrieval (+SR) in men with idiopathic non-obstructive azoospermia (iNOA) undergoing microdissection testicular sperm extraction (mTESE)? A higher likelihood of +SR during mTESE is observed in men with iNOA and lower preoperative serum anti-Müllerian hormone (AMH) levels, with good predictive accuracy achieved using an AMH threshold of <4 ng/ml. AMH has been previously linked to +SR in men with iNOA undergoing mTESE prior to ART. A multi-centre cross-sectional study was carried out with a cohort of 117 men with iNOA undergoing mTESE at three tertiary-referral centres. Data from 117 consecutive white-European men with iNOA presenting for primary couple's infertility associated with a pure male factor at three centres were analysed. Descriptive statistics was applied to compare patients with negative (-SR) versus +SR at mTESE. Multivariate logistic regression models were fitted to predict +SR at mTESE, after adjusting for possible confounders. Diagnostic accuracy of the factors associated with +SR was assessed. Decision curve analyses were used to display the clinical benefit. Overall, 60 (51.3%) men had an -SR and 57 (48.7%) had a +SR at mTESE. Patients with +SR had lower levels of baseline AMH (P = 0.005) and higher levels of estradiol (E2) (P = 0.01). At multivariate logistic regression analysis, lower levels of AMH (odds ratio: 0.79; 95% CI: 0.64-0.93, P = 0.03) were associated with +SR at mTESE, after adjusting for possible confounders (e.g. age, mean testicular volume, FSH, and E2). A threshold of AMH <4 ng/ml achieved the highest accuracy for +SR at mTESE, with an AUC of 70.3% (95% CI: 59.8-80.7). Decision curve analysis displayed the net clinical benefit of using an AMH <4 ng/ml threshold. There is a need for external validation in even larger cohorts, across different centres and ethnicities. Systematic reviews and meta-analysis to provide high level of evidence are lacking in the context of AMH and SR rates in men with iNOA. Current findings suggest that slightly more than one in two men with iNOA had -SR at mTESE. Overall, men with iNOA with lower levels of AMH had a significantly higher percentage of successful SR at surgery. A threshold of <4 ng/ml for circulating AMH ensured satisfactory sensitivity, specificity, and positive predictive values in the context of +SR at mTESE. This work was supported by voluntary donations from the Urological Research Institute (URI). All authors declare no conflict of interest. N/A.

MP01-09 GENE DOSAGE CHANGES IN CRYPTORCHID MEN WITH NONOBSTRUCTIVE AZOOSPERMIA

You have accessJournal of UrologyCME1 Apr 2023MP01-09 GENE DOSAGE CHANGES IN CRYPTORCHID MEN WITH NONOBSTRUCTIVE AZOOSPERMIA Aaron Brant, Caroline Kang, Anna Mielnik, Marisol O'Neill, Meade Haller, Peter Schlegel, and Dolores Lamb Aaron BrantAaron Brant More articles by this author , Caroline KangCaroline Kang More articles by this author , Anna MielnikAnna Mielnik More articles by this author , Marisol O'NeillMarisol O'Neill More articles by this author , Meade HallerMeade Haller More articles by this author , Peter SchlegelPeter Schlegel More articles by this author , and Dolores LambDolores Lamb More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003212.09AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Copy number variations (CNVs) are structural chromosomal defects causing microdeletions or microduplications. CNVs in the dosage-sensitive genes ADCY2, ADCY9, CRKL, KCTD13, RBFOX2, and ZEB2 occur more frequently in men with genitourinary anomalies such as cryptorchidism and hypospadias compared to the general male population. To evaluate the association of these CNVs with spermatogenic failure, the prevalence of CNVs in men with history of cryptorchidism who underwent microdissection testicular sperm extraction (mTESE) for non-obstructive azoospermia (NOA) was defined. METHODS: Whole blood DNA samples were collected from 101 men with cryptorchidism and NOA who presented for (mTESE) and two fertile control men. TaqMan quantitative polymerase chain reaction was used to assess copy numbers of ADCY2, ADCY9, CRKL, KCTD13, RBFOX2, and ZEB2 with each reaction performed in triplicate. Relative quantification values were obtained using CopyCaller Software. Fisher’s exact test was used to compare CNVs in cryptorchid men with NOA compared to CNV prevalence in the general male population from the Database of Genomic Variants. RESULTS: Of the 101 patients, 44 (44%) had bilateral cryptorchidism, 57 (56%) had unilateral cryptorchidism, and 51 (50%) had sperm retrieved with mTESE. Six patients (5.9%) had CNVs detected. Two men had microdeletions of CRKL, one had a microdeletion of ZEB2, and one had a microduplication of ADCY2. Two men with bilateral cryptorchidism had multiple CNVs detected: one had microdeletions of ADCY2, ADCY9, and RBFOX2, and one had microdeletions of ADCY9, CRKL, ZEB2 and a microduplication of KCTD13. Four of the six patients with detected CNVs (67%) had sperm retrieved on mTESE. Compared the general male population, men with cryptorchidism and NOA had higher prevalence of CNVs in ADCY2 (p=0.002), ADCY9 (p=0.004), CRKL (p<0.001), and ZEB2 (p<0.001). CONCLUSIONS: Approximately 6% of adult men with a history of cryptorchidism and NOA had gene dosage changes in ADCY2, ADCY9, CRKL, KCTD13, RBFOX2, or ZEB2, with two-thirds of these men having successful sperm retrieval on mTESE. As many of these CNVs are syndromic, genetic counseling may be warranted for men found to carry them. The functional consequences of these gene dosage changes on adult spermatogenesis remain to be fully elucidated. Source of Funding: n/a © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e5 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Aaron Brant More articles by this author Caroline Kang More articles by this author Anna Mielnik More articles by this author Marisol O'Neill More articles by this author Meade Haller More articles by this author Peter Schlegel More articles by this author Dolores Lamb More articles by this author Expand All Advertisement PDF downloadLoading ...

PD18-07 SERUM ANTI-MÜLLERIAN HORMONE IN RELATION TO SPERM RETRIEVAL RATE AND TESTICULAR HISTOPATHOLOGY IN NON-OBSTRUCTIVE AZOOSPERMIA

You have accessJournal of UrologyCME1 Apr 2023PD18-07 SERUM ANTI-MÜLLERIAN HORMONE IN RELATION TO SPERM RETRIEVAL RATE AND TESTICULAR HISTOPATHOLOGY IN NON-OBSTRUCTIVE AZOOSPERMIA Tomoki Takeda, Shoichiro Iwatsuki, Satoshi Nozaki, Hidenori Nishio, Hiroki Kubota, Yasue Kubota, Hiroyuki Kamiya, Hidetoshi Akita, Kentaro Mizuno, Yutaro Hayashi, Yukihiro Umemoto, and Takahiro Yasui Tomoki TakedaTomoki Takeda More articles by this author , Shoichiro IwatsukiShoichiro Iwatsuki More articles by this author , Satoshi NozakiSatoshi Nozaki More articles by this author , Hidenori NishioHidenori Nishio More articles by this author , Hiroki KubotaHiroki Kubota More articles by this author , Yasue KubotaYasue Kubota More articles by this author , Hiroyuki KamiyaHiroyuki Kamiya More articles by this author , Hidetoshi AkitaHidetoshi Akita More articles by this author , Kentaro MizunoKentaro Mizuno More articles by this author , Yutaro HayashiYutaro Hayashi More articles by this author , Yukihiro UmemotoYukihiro Umemoto More articles by this author , and Takahiro YasuiTakahiro Yasui More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003273.07AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Anti-Müllerian hormone (AMH) is secreted by Sertoli cells. Although AMH has been suggested as a marker of spermatogenesis, the relationship between serum AMH and spermatogenesis in non-obstructive azoospermia (NOA) is unclear. Therefore, we investigated the relationship between serum AMH and sperm retrieval rate (SRR), testicular histopathology in NOA. METHODS: The study population consisted of 237 patients with NOA who underwent microdissection testicular sperm extraction and had their serum AMH levels measured between January 2015 and December 2021. NOA patients were classified into serum AMH levels <0.1 (detection limit, n=27), 0.1-4 (n=76), 4-8 (n=58) and ≥8 ng/ml (n=76), and SRRs were compared. In addition, NOA patients were classified into TH (tubular hyalinization, n=15), SCO (Sertoli cell only syndrome, n=132), MA (maturation arrest, n=57) and HS (hypospermatogenesis, n=33) groups. The percentage of patients with serum AMH levels <0.1 ng/ml and serum AMH levels were compared. RESULTS: SRR were 3.7%, 40.8%, 36.2% and 23.7% for serum AMH levels <0.1, 0.1-4, 4-8 and ≥8 ng/ml, respectively (Figure 1A), with a significant difference between serum AMH levels <0.1 ng/ml and the other groups (p<0.01). The percentages of patients with serum AMH levels below 0.1 ng/ml were 86.7%, 10.6%, 0% and 0% in TH, SCO, MA and HS groups, respectively (Figure 1B), with a significant difference between TH and the other groups (p<0.01). Serum AMH levels were 0.11±0.04, 6.91±6.59, 7.75±7.09 and 5.77±3.58 ng/ml for the four groups, respectively (Figure 1C), with a significant difference between TH and the other groups (p<0.01). CONCLUSIONS: When the serum AMH value ≥0.1 ng/ml, the higher the serum AMH value, the lower the SRR. On the other hand, serum AMH levels <0.1 ng/ml may suggest hyalinization of seminiferous tubules, loss of Sertoli cells and low possibility of sperm retrieval. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e505 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Tomoki Takeda More articles by this author Shoichiro Iwatsuki More articles by this author Satoshi Nozaki More articles by this author Hidenori Nishio More articles by this author Hiroki Kubota More articles by this author Yasue Kubota More articles by this author Hiroyuki Kamiya More articles by this author Hidetoshi Akita More articles by this author Kentaro Mizuno More articles by this author Yutaro Hayashi More articles by this author Yukihiro Umemoto More articles by this author Takahiro Yasui More articles by this author Expand All Advertisement PDF downloadLoading ...

Outcomes of Microdissection Testicular Sperm Extraction/Intracytoplasmic Sperm Injection in Cases of Nonobstructive Azoospermia: A Retrospective Study

The outcomes and safety of intracytoplasmic sperm injection (ICSI) using testicular sperm have been controversial. We evaluated ICSI results, pregnancy outcomes, and neonatal health conditions using testicular sperm from patients with obstructive (OA) or nonobstructive (NOA) azoospermia. We further compared the ICSI outcomes after use of fresh versus cryopreserved testicular sperm from men with NOA. We included 314 men with NOA who underwent microdissection testicular sperm extraction (mTESE) and 303 with OA who underwent testicular sperm aspiration; both groups underwent ICSI. Therefore, 101 and 329 ICSI cycles were performed for mTESE and aspirated sperms, respectively. Furthermore, fresh and thawed embryos from both groups were transplanted to evaluate fertilization and pregnancy rates (NOA, 15 fresh and 123 thawed; OA, 59 fresh and 393 thawed). Finally, of the 101 ICSI cycles performed for NOA patients, 56 fresh-sperm cycles and 45 thawed-sperm cycles were performed to evaluate ICSI outcomes. Fertilization rates and two-pronuclear (2PN) fertilization rates were significantly lower in the NOA group than in the OA group. However, the 2PN cleavage rate, the high-quality embryo rate, the blastocyst formation rate, and the available blastocyst rate showed no significant intergroup differences. In addition, the pregnancy outcomes and neonatal health conditions were statistically similar. Finally, compared with thawed sperm, the fresh-sperm group had a higher 2PN fertilization rate and a higher high-quality embryo rate. However, blastocyst formation and available blastocyst rates were similar between the two groups. Patients with NOA achieved the same favorable results in embryo development, clinical pregnancy, and live birth capability as did OA patients. Neonatal conditions were not affected by type of azoospermia (NOA versus OA). For patients with NOA, fresh testicular sperm is superior to frozen-thawed testicular sperm in embryo development as evaluated at the cleavage stage, but we find no superiority evaluating at the stage of blastocyst formation.

P-011 Deep testicular tissue dissection is most often required to retrieve testicular sperm in patients with non-obstructive azoospermia undergoing microdissection testicular sperm extraction

Abstract Study question How successful is sperm retrieval from the testicular surface of patients with non-obstructive azoospermia (NOA) undergoing microdissection testicular sperm extraction (mTESE)? Summary answer Enough good quality sperm for ICSI could be retrieved from the testicular surface in only 33 out of 224 patients (14.7%) What is known already Due to the anatomic singularity of NOA, characterized by the heterogeneous distribution of histologically and functionally distinct seminiferous tubules, retrieving enough good quality sperm for ICSI may require a complete testicular dissection. While conventional TESE (cTESE) may reach only the seminiferous tubules located in the testis surface, mTESE allows the nearly complete exploration of the whole testicular parenchyma. This is the reason why mTESE provides better sperm retrieval rates compared to cTESE, according to two systematic reviews and one meta-analysis: the superiority of mTESE compared to cTESE, however, has been challenged by a recent meta-analysis. Study design, size, duration Retrospective cohort study on 224 patients, aged 37 (20-54) years, who underwent unilateral (71, 31.7%) or bilateral (153, 68.3%) mTESE from January 2018 through May 2021. 175 patients were naïve for mTESE, while 49 underwent a salvage mTESE following one or more previously failed conventional TESE. Participants/materials, setting, methods The testis was opened like a book following a transversal incision of the testis covering two-thirds to three-quarters of its circumference: the entire surface of the testicular parenchyma was explored first in search for dilated seminiferous tubules. If no/ not enough sperm were retrieved, the testis was opened till to be fully bivalve, and the deeper portion of the testicular parenchyma was explored both into hilum direction and orthogonally to the para-equatorial section plan. Main results and the role of chance Sperm was retrieved in 114 patients (50.8%), 67 (94.3%) undergoing unilateral and 47 (30.7%) undergoing bilateral mTESE: only 15/153 (9.8%) had their testicular sperm retrieved in the second testis following the unsuccessful sperm retrieval in the first testis, while in the remaining cases sperm had to be retrieved from both testes to obtain enough good quality sperm for ICSI. Histopathology demonstrated Sertoli-cell only syndrome in 65.6% of operated testes, while maturation arrest was found in 19.8%, hypospermatogenesis in 12.6% and hyalinosis in 1.5%. Sperm were obtained from the testis surface in 33 out of 114 patients (28.9%); in the remaining patients a deeper dissection was needed. No difference was seen among patients with sperm found in the surface or requiring deeper dissection in terms of age, testis volume, serum testosterone level, and histopathological subcategories; although serum FSH and LH level were significantly lower in patients with sperm retrieved from the testicular surface, on multivariate logistic regression they were not found to predict the chance of retrieving sperm from the surface (OR 0.96, 95% CI 0.92-1.007, p = 0.104 and OR 0.95, 95% CI 0.85-1.06, p = 0.405, respectively). Limitations, reasons for caution the amount of testicular tissue dissected was strictly dependent upon the chance of finding enough sperm for ICSI in the specimens handled by the biologist in the operating room: we cannot exclude that in some patients enough sperm could be obtained from the testis surface following further extensive search Wider implications of the findings mTESE is to be preferred to cTESE, since in most patients with NOA seminiferous tubules containing sperm may be found in the deeper portion of the testicular parenchyma. This may be particularly true for patients with unfavorable histopathological patterns, such as Sertoli cell only syndrome or maturation arrest. Trial registration number Not applicable

Prediction Models for Successful Sperm Retrieval in Patients with Non-Obstructive Azoospermia Undergoing Microdissection Testicular Sperm Extraction: Is There Any Room for Further Studies?

Several prediction models for successful sperm retrieval (SSR) in patients with azoospermia due to spermatogenic dysfunction (also termed non-obstructive azoospermia—NOA) have been developed and published in the past years, however their resulting prediction accuracy has never been strong enough to translate their results in the clinical practice. This notwithstanding, the number of prediction models being proposed in this field is growing. We have reviewed the available evidence and found that, although patients with complete AZFc deletion or a history of cryptorchidism may have better probability of SSR compared to those with idiopathic NOA, no clinical or laboratory marker is able to determine whether a patient with NOA should or should not undergo microdissection testicular sperm extraction (mTESE) to have his testicular sperm retrieved. Further research is warranted to confirm the utility of evaluating the expression of noncoding RNAs in the seminal plasma, to individuate patients with NOA with higher probability of SSR.

FSH levels and testicular volumes are associated with the severity of testicular histopathology in men with non-obstructive azoospermia

PurposeThe purpose of this study is to assess a potential association between FSH levels and testicular volumes with the severity of testicular histopathology on testicular biopsy in men with non-obstructive azoospermia (NOA) undergoing microdissection testicular sperm extraction (microTESE).MethodsA retrospective chart review was performed from the electronic health records of men who underwent microTESE with NOA.ResultsEighty-six men with NOA underwent microTESE with concomitant testicular biopsy for permanent section to assess the testicular cellular architecture. The histopathological patterns were categorized by severity indicating the odds of sperm retrieval into 2 categories. The unfavorable category included Sertoli cell only pattern and early maturation arrest (n = 50) and the favorable category included late maturation arrest and hypospermatogenesis patterns (n = 36). In the men with unfavorable histopathologic patterns, the mean FSH level was 22.9 ± 16.6 IU/L, and the mean testicular volume was 10.4 ± 6.0 cc. This was in comparison to men with favorable histopathologic patterns revealing a mean FSH level of FSH 13.3 ± 12.0 with a mean testicular volume of 13.3 ± 5.9 cc. There was a statistically significant higher FSH level in men with unfavorable histopathology than favorable (p = 0.004) as well as a significant smaller mean testicular volume in men with unfavorable histopathology (p = 0.029).ConclusionsHigher serum FSH levels and smaller testicular volumes are associated with more severe testicular histopathological patterns in men with NOA.

Fertility outcomes and predictors for successful sperm retrieval and pregnancy in 327 azoospermic men with a history of cryptorchidism who underwent microdissection testicular sperm extraction.

Although few studies have reported fertility outcomes, no study has reported risk factors that might predict sperm retrieval and pregnancy in azoospermic men with a history of cryptorchidism in a large series. To investigate fertility outcomes and predictors for successful sperm retrieval and pregnancy in azoospermic men with a history of cryptorchidism who underwent microdissection testicular sperm extraction (mTESE). This retrospective observational study included 327 azoospermic men with a history of cryptorchidism who underwent mTESE. Fertility outcomes including sperm retrieval, fertilization rate, number of transferred embryos, pregnancy, miscarriage, and live birth rates were recorded. Sperm retrieval was observed in 172 (52.6%) of the patients. The mean fertilization, pregnancy, and live birth rates were 55.2%±20.5, 53.5%, and 44.8%, respectively. The sperm retrieval rate was significantly higher at the orchidopexy age of≤9.5years (70.8%) than the orchidopexy age of>9.5years (42.1%) (P=.000). Patients with total testicular volume of≥13.75mL had significantly higher sperm retrieval rate (65.2%) than the patients with total testicular volume of<13.75mL (45.5%) (P=.001). Patients with total testosterone level of≥300.5ng/dL had significantly higher sperm retrieval rate (65.6%) than the patients with total testosterone level of<300.5ng/dL (40.3%) (P=.000). Patients with follicle-stimulating hormone (FSH) level of≤17.25 mIU/ml had significantly higher sperm retrieval rate (72.3%) than the patients with FSH level of>17.25 mIU/mL (44.4%) (P=.000). Younger male and female ages, and higher fertilization rates were the parameters that might predict pregnancy. Infertile azoospermic men with a history of cryptorchidism have high sperm retrieval rate with mTESE. Patients who had orchidopexy at the age of≤9.5years, and having total testicular volumes of≥13.75mL with total testosterone level of>300.5ng/dL and FSH level of≤17.25 mIU/mL have higher success rate for sperm retrieval.

A comprehensive assessment of predictors of fertility outcomes in men with non-obstructive azoospermia undergoing microdissection testicular sperm extraction

BackgroundMicrodissection testicular sperm extraction (microTESE) in men with non-obstructive azoospermia (NOA) is the procedure that results in the highest number of sperm cells retrieved for in vitro fertilization (IVF). This study presents a novel assessment of predictors of sperm retrieval as well as downstream embryology and pregnancy outcomes in cases of men with NOA undergoing microTESE.MethodsA retrospective chart review of 72 men who underwent microTESE for predictors of fertility outcomes including sperm retrieved at microTESE, embryology progression to embryo transfer (ET), clinical pregnancy, live birth, and surplus sperm retrieved for additional IVF/intracytoplasmic injection cycles beyond one initial cycle. Statistical models for each of these outcomes were fitted, with a p-value of < 0.05 considered significant for the parameters estimated in each model.ResultsSeventy-two men underwent microTESE, and 51/72 (70.8%) had sperm retrieved. Of those, 29/43 (67.4%) reached ET. Of the couples who underwent ET, 21/29 (72.4%) achieved pregnancy and 18/29 (62.1%) resulted in live birth. Of the men with sperm retrieved, 38/51 (74.5%) had surplus sperm cryopreserved beyond the initial IVF cycle.Age, testicular volume, FSH, and testicular histopathology were assessed as predictors for sperm retrieved at microTESE, progression to ET, pregnancy, live birth, and surplus sperm. There were no preoperative predictors of sperm retrieval, clinical pregnancy, or live birth. Age predicted reaching ET, with older men having increased odds. FSH level had a negative relationship with surplus sperm retrieved. Men with hypospermatogenesis histology had higher rates of sperm retrieval, clinical pregnancy, live birth, and having surplus sperm.ConclusionsMen who underwent microTESE with a hypospermatogenesis histopathology had better outcomes, including higher rates of sperm retrieval, clinical pregnancy, live birth, and having surplus sperm retrieved. Increasing male partner age increased the odds of reaching ET. No other clinical factors were predictive for the outcomes considered.

420 - Fertility outcomes and predictors for successful sperm retrieval and pregnancy in 327 azoospermic men with a history of cryptorchidism who underwent microdissection testicular sperm extraction

Background Although few studies have reported fertility outcomes, no study has reported risk factors that might predict sperm retrieval and pregnancy in azoospermic men with a history of cryptorchidism in a large series. Objectives To investigate fertility outcomes and predictors for successful sperm retrieval and pregnancy in azoospermic men with a history of cryptorchidism who underwent microdissection testicular sperm extraction (mTESE). Materials and methods This retrospective observational study included 327 azoospermic men with a history of cryptorchidism who underwent mTESE. Fertility outcomes including sperm retrieval, fertilization rate, number of transferred embryos, pregnancy, miscarriage, and live birth rates were recorded. Results Sperm retrieval was observed in 172 (52.6%) of the patients. The mean fertilization, pregnancy, and live birth rates were 55.2%±20.5, 53.5%, and 44.8%, respectively. The sperm retrieval rate was significantly higher at the orchidopexy age of ≤ 9.5 years (70.8%) than the orchidopexy age of > 9.5 years (42.1%) (P = .000). Patients with total testicular volume of ≥ 13.75 mL had significantly higher sperm retrieval rate (65.2%) than the patients with total testicular volume of 17.25 mIU/mL (44.4%) (P = .000). Younger male and female ages, and higher fertilization rates were the parameters that might predict pregnancy. Conclusions Infertile azoospermic men with a history of cryptorchidism have high sperm retrieval rate with mTESE. Patients who had orchidopexy at the age of ≤ 9.5 years, and having total testicular volumes of ≥ 13.75 mL with total testosterone level of > 300.5 ng/dL and FSH level of ≤ 17.25 mIU/mL have higher success rate for sperm retrieval.

Prediction of microdissection testicular sperm extraction outcome in men with idiopathic nonobstruction azoospermia

The aim of the present study is to assess whether the preoperative clinical indicators have an impact on sperm retrieval rate (SRR) in men with idiopathic nonobstructive azoospermia (NOA).We retrospectively studied 241 consecutive men with NOA who underwent microdissection testicular sperm extraction from 2016 to 2019 in the Reproductive Medicine Center, including 154 patients diagnosed with idiopathic NOA. They were grouped according to preoperative indicators, including average testicular volume, follicle-stimulating hormone (FSH), luteinizing hormone, Testosterone (T), and pathology, respectively.The overall SRR was 20.0% (31/155). Men with testicular volume of ≤5 mL had significant higher SRR than men with testes 5 to 10 and ≥10 mL (35.6% vs 12.3%, P = .002; 35.6% vs 16.2, P = .049, respectively). The SRR in men with FSH ≥ 24.8 mIU/mL was significant higher, compared with FSH level of 12.4 to 24.8 mIU/mL (32.6% vs 15.8%, P = .033). Men with Sertoli cell-only had significantly lower SRR than other pathological type (8.1%). Men with an FSH ≥ 24.8 mIU/mL in testicular volume ≤5 mL group had a significantly higher SRR than FSH level of 12.4 to 24.8 mIU/mL in testicular volume of ≤5 to 10 mL group (44.0% vs 11.4%, P = .002). Men with a luteinizing hormone level of 8.6 to 17.2 mIU/mL in testicular volume of 5 to 10 mL group had a poor prognosis, with an SRR of only 6.5%.Severely reduced testicular volume (≤5 mL) and severely increased FSH level (≥24.8 mIU/mL) had the better sperm retrieval outcome, which can be used as independent predictors in men with idiopathic NOA. And a combination of testicular volume and the hormone seemed to be useful in further increase predictive value.

Do partial AZFc deletions affect the sperm retrieval rate in non-mosaic Klinefelter patients undergoing microdissection testicular sperm extraction?

BackgroundThe purpose of this study is to evaluate the prognostic factors for sperm retrieval and determine if Y chromosome deletion is associated with deleterious effects on spermatogenesis in non-mosaic Klinefelter patients. Whether Y chromosome deletion determines the sperm retrieval rate in non-mosaic Klinefelter patients has not yet been addressed.MethodsWe retrospectively collected medical records of azoospermic patients from Sep 2009 to Dec 2018, and enrolled 66 non-mosaic 47, XXY patients who were receiving mTESE. The predictive values of patients age, serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone, prolactin, estradiol and Y chromosome deletion were assessed for successful sperm recovery.ResultsTesticular sperm recovery was successful in 24 (36.4%) of 66 men. The mean age (36.0 vs. 36.6 years), and levels of FSH (30.0 vs 36.9 IU/L), LH (17.7 vs 21.9 IU/L), testosterone (2.4 vs. 2.1 ng/ml), prolactin (9.1 vs. 8.8 ng/ml), and estradiol (19.4 vs. 22.3 pg/ml) did not show any significant difference when comparing patients with and without successful sperm retrieval. Partial deletion of azoospermic factor c (AZFc) was noted in 5 (20.8%) of 24 patients with successful sperm retrieval, including three b2/b3 and two gr/gr deletion cases, whereas 4 (9.5%) of 42 patients with unsuccessful sperm retrieval were noted to have AZFc partial deletion (one b2/b3, one sY1206 and two gr/gr deletion), though the difference was not statistically significant (p = 0.27).ConclusionAccording to present results, age and AZFc partial deletion status should not be a deterrent for azoospermic males with non-mosaic Klinefelter syndrome to undergo mTESE.

Sperm retrieval success and testicular histopathology in idiopathic nonobstructive azoospermia.

Prior studies have investigated sperm retrieval rates in men with nonobstructive azoospermia (NOA) secondary to specific etiologies, yet most cases of NOA are idiopathic. We compared sperm retrieval rates and testicular histopathology in idiopathic NOA (iNOA) and nonidiopathic NOA (niNOA). We performed a retrospective review of men with NOA who underwent microdissection testicular sperm extraction (microTESE) between 2000 and 2016. Men with no history of malignancy or cryptorchidism and negative genetic evaluation were considered idiopathic. Multivariable regression determined the association between idiopathic etiology and primary outcomes of sperm retrieval and active spermatogenesis on histopathology. Among 224 men, 86 (38.4%) were idiopathic, 75 (33.5%) were nonidiopathic, and 63 (28.1%) did not undergo genetic testing. Median age and serum testosterone were higher among iNOA or no testing versus niNOA. Median follicle-stimulating hormone (FSH) was lower among iNOA or no testing versus niNOA. A higher proportion of iNOA or no testing versus niNOA had a clinical varicocele. Sperm retrieval rates were similar between iNOA, niNOA, and no testing (41.8% vs 48.0% vs 55.6%, respectively; P = 0.255). Active spermatogenesis was seen in a higher proportion of iNOA or no testing versus niNOA (31.4% and 27.0% vs 16.0%, P = 0.073). On multivariable analysis, iNOA was not associated with sperm retrieval or spermatogenesis (P = 0.430 and P = 0.078, respectively). Rates of sperm retrieval and spermatogenesis on testis pathology were similar in men with iNOA and niNOA. These data will be useful to clinicians in preoperative counseling for men with NOA and negative genetic evaluation.

Pregnancy and Neonatal Outcomes in Azoospermic Men After Intracytoplasmic Sperm Injection Using Testicular Sperm and Donor Sperm.

BackgroundThe safety of intracytoplasmic sperm injection (ICSI) with testicular sperm in azoospermic men has been a concern. We evaluated ICSI outcomes, including neonatal outcomes, in children born using testicular sperm or donor sperm.Material/MethodsNinety-nine males with nonobstructive azoospermia (NOA) who underwent microdissection testicular sperm extraction (micro-TESE) and 126 males with obstructive azoospermia (OA) were included in this study. Sixty-one patients with NOA used donor sperm for ICSI on the day of oocyte retrieval when no spermatozoa were identified by micro-TESE on the day before oocyte retrieval. ICSI outcomes were compared among OA, donor, and NOA groups.ResultsThere was no statistical difference in terms of female partner characteristics among OA, donor, and NOA groups. The normal fertilization rate (P=0.005), high quality embryo rate (P=0.014), implantation rate (P<0.001), clinical pregnancy rate (P=0.015), live birth rate (P=0.043) were significant lower in the NOA group, compared with the donor sperm group. The normal fertilization rate was significant lower in the NOA group than the OA group (P<0.001), but the live birth rate was not significantly lower (P=0.058). The high-quality embryo rate (P=0.014) and implantation rate (P=0.009) were lower in the OA group than the donor group. No differences between groups were observed in our study regarding neonatal parameters of the infants born.ConclusionsThe fertilization and pregnancy outcomes were negatively affected by using testicular sperm from males with NOA. Once a live birth was achieved, there was no difference in neonatal outcomes.