Sperm Retrieval Rate Research Articles

Challenges in differential diagnosis between obstructive and non‐obstructive azoospermia

AbstractBackgroundSome cases of non‐obstructive azoospermia (NOA) are characterized by normal clinical parameters, including testicular volume and levels of reproductive hormones, mimicking obstructive azoospermia (OA).MethodsWe performed a retrospective review of a consecutive series of 1417 patients undergoing primary surgical sperm retrieval between 2014 and 2023. Follicle‐stimulating hormone (FSH) level below 7.6 IU/l and normal testicular size with a long axis measurement >4.6 cm were used as criteria to suspect OA.ResultsFour hundred and eighteen patients with normal testicular volume and FSH levels had an initial diagnosis of OA. Among them, 243 (58.1%) had histological signs of spermatogenic dysfunction, and 175 (41.9%) had true OA. One hundred eleven patients had long‐standing obstruction (median: 16.5 years) with a median Bergmann–Kliesch score (BKS) of 5 (interquartile range [IQR]: 4–6) and 100% sperm retrieval rate (SRR), though some required microdissection testicular sperm extraction (microTESE). Fifty‐eight patients with a history of epididymo‐orchitis had a median BKS of 4 (IQR: 2–6) and 100% SRR. Twenty patients with a history of unjustified medical treatment for male infertility had a median BKS of 3 (IQR: 1–4) and 80% SRR. Fifty‐four patients had uniform maturation arrest with a 5.5% SRR on microTESE.ConclusionMen with normal testicular volume and FSH level may have evidence of spermatogenic failure on pathology. Patients with complicated seminal tract obstruction commonly have hypospermatogenesis, but true NOA caused by uniform maturation arrest may also be observed. Patient counseling for suspected OA should not be overly optimistic, and couples should be warned about possibility of conversion to microTESE and risks of negative sperm retrieval.

A detection model of testis-derived circular RNAs in serum for predicting testicular sperm retrieval rate in non-obstructive azoospermia patients.

Microdissection testicular sperm extraction is an effective method to retrieve sperm from non-obstructive azoospermia patients. However, its successful rate is less than 50%. To identify the predictive value of circular RNAs in serum for sperm retrieval rate in non-obstructive azoospermia patients. 180 non-obstructive azoospermia patients were recruited in this study, including 84 individuals with successful sperm retrieval and 96 individuals with failed sperm retrieval. Our study contained two phases. First, 20 patients, selected from the 180 patients, were included in screening cohort. In this cohort, the top 20 circular RNAs from our previous testicular circRNA profiles were verified between successful and failed sperm retrieval groups using real-time polymerase chain reaction. Six circular RNAs with the most significantly different expressions were selected for further verification. Second, the 180 patients were included as discovery cohort to verify the six circular RNAs. Circular RNAs were extracted from serum in each participant. Logistic regression analysis was further performed to identify the predictive value and the area under the curve analysis was used to evaluate diagnostic efficiency, sensitivity, and specificity. Six circular RNAs including hsa_circ_0058058, hsa_circ_0008045, hsa_circ_0084789, hsa_circ_0000550, hsa_circ_0007422, and hsa_circ_0004099 showed aberrant expressions between the successful and failed sperm retrieval group. In addition, both single-circular RNA panels and multi-circular RNA panels were finally verified to be significant in predicting sperm retrieval rate. Notably, multi-circular RNAs panels demonstrated better predictive abilities compared with single-circRNA panels, and the combined panel of six-circular RNAs (risk score=1.094×hsa_circ_0058058+0.697×hsa_circ_0008045+0.718×hsa_circ_0084789-0.591×hsa_circ_0000550-0.435×hsa_circ_0007422-1.017×hsa_circ_0004099-1.561) exhibited the best predictive ability in the present study with an AUC of 0.977, a sensitivity of 91.7% and a specificity of 86.5%. A higher risk score indicated a higher risk of failure in sperm retrieval. Our study was the first to report that testis-derived circular RNAs in serum have the ability to predict sperm retrieval rate in non-obstructive azoospermia patients, whether it is a single-circular RNA or a combination of multi-circular RNAs.

Microsurgical Testicular Sperm Extraction: Predictive Factors and Outcomes for Men with Nonobstructive Azoospermia

Background. Nonobstructive azoospermia (NOA) is a frequent cause of male infertility, and microsurgical testicular sperm extraction (micro-TESE) is an effective technique for sperm retrieval in NOA cases. However, the predictive factors for successful sperm retrieval and the outcomes of micro-TESE in NOA patients are not fully understood. Methods. In this retrospective study, we evaluated the predictive value of preoperative data and outcomes of micro-TESE in 172 men with NOA who underwent the procedure between April 2012 and February 2021. Patients’ age, medical history, testicular size, hormonal profile, testicular histology, and sperm retrieval were recorded. Results. 172 cases of micro-TESE were performed (99 unilateral and 73 bilateral) and testicular sperm retrieval rate (SRR) was 72.7%. There was no statistical difference in age, testicular size, and hormonal profiles between positive SRR and negative SRR groups. Clinical varicocele and previous orchitis did not significantly affect the result of micro-TESE. Y chromosome microdeletions were detected in seven patients. On histological examination, hypospermatogenesis was found in 39% of patients who underwent testicular biopsy. SRR was higher in patients with hypospermatogenesis than in other groups. Conclusions. Testicular microdissection is an effective and safe procedure for nonobstructive azoospermia patients, regardless of the different etiologies and preoperative data. Age, testicular size, and hormonal levels did not predict the success of micro-TESE. The presence of hypospermatogenesis was associated with a higher SRR. Clinical varicocele and previous orchitis were not significantly associated with the outcome of micro-TESE.

Timing of Testicular Biopsy in Relation to Oocyte Retrieval and the Outcomes of Intracytoplasmic Sperm Injection.

We evaluate microscopic (micro) testicular sperm extraction (TESE) timing relative to oocyte retrieval on intracytoplasmic sperm injection outcome. Couples with nonobstructive azoospermia who underwent intracytoplasmic sperm injection with freshly retrieved spermatozoa were analyzed based on whether micro-TESE was performed at least 1 day prior to oocyte retrieval (TESE-day-before group) or on the day of oocyte retrieval (TESE-day-of group). Embryology and clinical outcomes were compared. The percentage of patients who underwent a successful testicular sperm retrieval was significantly lower in the TESE-day-before cohort (62%) than in the TESE-day-of cohort (69%; odds ratio [OR] 1.4, 95% CI [1.1, 1.7], P < .001). The fertilization rate was also found to be significantly lower in the TESE-day-before group (45%) than in the TESE-day-of group (53%; OR 1.4, 95% CI [1.2, 1.7], P = .01). Although the association between the cleavage rate and TESE timing was not statistically significant, the implantation rate was found to be significantly higher in the day-before cohort (28%) than in the day-of cohort (22%; OR 0.7, 95% CI [0.6, 0.9], P = .01). Nevertheless, it was found that the clinical pregnancy and delivery rates were not statistically significantly associated with the TESE timing. Although sperm retrieval and fertilization rates were lower in the TESE-day-before cohort, the 2 cohorts showed comparable embryologic and clinical outcomes. Micro-TESE can be performed before oocyte harvesting to provide physicians ample time to decide between cancelling oocyte retrieval or retrieving oocytes for cryopreservation.

A step closer to parenthood with non-obstructive azoospermia: Unveiling the impact of microdissection testicular sperm extraction in Australia's largest single-centre study.

Non-obstructive azoospermia (NOA) diagnosis poses challenges for couples seeking parenthood. Microdissection testicular sperm extraction (MD-TESE) excels in retrieving testicular sperm cells for NOA cases. However, limited live birth data in Australian NOA patients hinders accurate counselling. This study aimed to determine the likelihood of infertile couples with a male partner diagnosed with NOA conceiving biological children using MD-TESE / intracytoplasmic sperm injection (ICSI). A retrospective cohort study included 108 NOA men treated at a public fertility unit and a private fertility centre (May 2009-May 2022). live birth rate (LBR); secondary outcomes: sperm retrieval rate, pregnancy rate, and neonatal outcomes. Among 108 patients undergoing MD-TESE, the positive sperm retrieval rate (PSRR) was 64.8% (70/108). Histology best predicted sperm retrieval success, with hypo-spermatogenesis yielding a 94.1% PSRR. Age, testicular volume, and hormonal parameters had no significant impact. Mean male age: 35.4 years; mean partner age: 32.7 years. Fertilisation rate: 50.7%. LBR per initiated cycle: 58.7% (37/63); per embryo transfer: 63.8% (37/58); per initially diagnosed NOA man: 34.3% (37/108). Cumulative LBR: 74.1% (43/58); twin rate: 10.8% (4/37). No neonatal deaths or defects were observed among 47 live offspring. This study provides valuable data for counselling NOA couples on the probability of conceiving biological offspring. MD-TESE and ICSI yielded favourable PSRR (64.8%) and LBR (63.8%). However, couples should be aware that once NOA is confirmed, the chance of taking home a baby is 34%.

MicroRNAs in spermatogenesis dysfunction and male infertility: clinical phenotypes, mechanisms and potential diagnostic biomarkers.

Infertility affects approximately 10-15% of couples worldwide who are attempting to conceive, with male infertility accounting for 50% of infertility cases. Male infertility is related to various factors such as hormone imbalance, urogenital diseases, environmental factors, and genetic factors. Owing to its relationship with genetic factors, male infertility cannot be diagnosed through routine examination in most cases, and is clinically called 'idiopathic male infertility.' Recent studies have provided evidence that microRNAs (miRNAs) are expressed in a cell-or stage-specific manner during spermatogenesis. This review focuses on the role of miRNAs in male infertility and spermatogenesis. Data were collected from published studies that investigated the effects of miRNAs on spermatogenesis, sperm quality and quantity, fertilization, embryo development, and assisted reproductive technology (ART) outcomes. Based on the findings of these studies, we summarize the targets of miRNAs and the resulting functional effects that occur due to changes in miRNA expression at various stages of spermatogenesis, including undifferentiated and differentiating spermatogonia, spermatocytes, spermatids, and Sertoli cells (SCs). In addition, we discuss potential markers for diagnosing male infertility and predicting the varicocele grade, surgical outcomes, ART outcomes, and sperm retrieval rates in patients with non-obstructive azoospermia (NOA).

Testicular volume is a noninvasive predictor of sperm retrieval failure in idiopathic nonobstructive azoospermia.

We investigated the prognostic importance of noninvasive factors in predicting sperm retrieval failure in idiopathic nonobstructive azoospermia (iNOA). We studied 193 patients with nonobstructive azoospermia who underwent microsurgical testicular sperm extraction. The Chi-square test and Mann-Whitney U tests for clinical parameters and seminiferous tubule distribution were used for between-group comparisons. A logistic regression analysis was conducted to identify predictors of retrieval failure. Area under the receiver operating characteristic curve for each variable was evaluated, and the net clinical benefit was calculated using a clinical decision curve. Patients with iNOA had a lower sperm retrieval rate than those with known causes. Moreover, testicular volume was an independent factor affecting sperm extraction outcomes (odds ratio = 0.79, P < 0.05). The testicular volume cut-off value was 6.5 ml (area under the curve: 0.694). The patients with iNOA were categorized into two groups on the basis of the distribution of seminiferous tubules observed. The sperm retrieval rate and testicular volume were significantly different between the groups with a uniform or heterogeneous tubule distribution. There was also a significant association between a uniform tubule distribution and testicular volume. In conclusion, a testicular volume of more than 6.5 ml effectively predicts microsurgical testicular sperm extraction failure due to a uniform tubule distribution in patients with iNOA.

Microdissection testicular sperm extraction in non-obstructive azoospermic patients with solitary testis: a retrospective case-control study.

Obtaining sperm from the testis surgically and using these sperm with the intracytoplasmic sperm injection technique, has opened the way for the possibility of biological fathering in men with non-obstructive azoospermia (NOA). We aimed to evaluate our sperm retrieval rate (SRR) by microdissection testicular sperm extraction (micro-TESE) in NOA patients with solitary testis. In this retrospective case-control study, fortyfive patients with NOA who had a congenital or acquired solitary testis were included, between September 2003 and January 2022. These patients were randomly matched with patients with NOA who had bilateral testes, using a 1:3 matching ratio. We found that SRR by micro-TESE in patients with solitary testis was similar to NOA patients with bilateral testis (51.1% vs. 50.4%). Age, infertility period, ejaculate volume, serum levels of follicle stimulating hormone (FSH), luteinizing hormone (LH) and testosterone, history of varicocelectomy, history of orchiopexy, testicular stimulation therapy before micro-TESE, testicular volume, genetic status, TESE side, micro-TESE success, complications and histopathological evaluation results of both groups were evaluated, there was a statistically significant difference in only serum FSH and LH levels. There was no difference between the groups in terms of complications and hormonal effects in the early postoperative period. Micro-TESE in NOA patients with solitary testis has similar sperm retrieval and complication rates as NOA patients with bilateral testis.

Investigating discordance between embryologists and histopathologists: analysis of multiple factors in mTESE sperm retrieval outcomes.

The objective of the study is to primarily highlight the consistency between the embryologist and the histopathologist in microdissection testicular sperm extraction and to explore the factors affecting sperm retrieval. The research included 91 patients, aged 20 to 47, who visited our Reproductive Technology center from July 2020 to June 2023. Patient data were collected retrospectively, including demographics, physical exams, lab tests, radiological assessments, genetic analyses, medical histories and histopathological results. Using the Johnsen scoring system for evaluation, the histopathologist identified mature spermatozoa in the specimen in some patients (Johnsen score 8-10); however, the embryologist only declared successful sperm retrieval in 66.6% of them. Overall sperm retrieval rates were lower than expected at 40%. Significant factors influencing sperm retrieval rates included Follicle Stimulating Hormone (p = 0.001), Luteinizing Hormone (p = 0.007), testicular volume (p < 0.001), histopathology (p < 0.001), and alcohol consumption (p = 0.007). A logistic regression model was used to identify the independent predictors of successful sperm retrieval. FSH (p = 0.038), testicular volume (p < 0.001), histopathology (p < 0.001), and alcohol consumption (p = 0.013) emerged as significant predictive factors for the outcome of sperm retrieval. As a result, in addition to patient-related factors, the consistency between the pathologist and embryologist also affects sperm retrieval rates.

Comparison of sperm retrieval rate between superficial and deep dissection during microscopic testicular sperm extraction.

The purpose of the study was to compare the outcome of microscopic testicular sperm extraction (micro-TESE) between superficial and deep dissection on the same testicle in terms of sperm retrieval rate (SRR). In a retrospective study from June 2019 to October 2021, 44 patients with nonobstructive azoospermia who underwent micro-TESE with positive results (mature sperm identified) were included. Eight patients were excluded from the study due to deficient documentation on superficial and deep dissection. A total of 36 patients were included; 60 testicles were examined for superficial and deep biopsies. Testicular histopathology was performed in all patients, and a hormonal evaluation was obtained before the micro-TESE attempt. Thirty-six patients and 60 testicles were included in the study. Of them, 47 (78.3%) testicles had positive results. Superficial TESE was positive in 38 (63.3%) testicles, and deep TESE was successful in 45 (75.0%) testicles. An improvement of 13.9% in the SRR was observed, following deep dissection. However, there was no statistically significant difference (P = 0.166). Rates of positive sperm retrieval (from any side) did not differ significantly based on patients' age, microdissection testicular sperm extraction sides, and hormonal concentrations; these differences were not apparent after superficial or deep TESE. The presented findings suggest that although successful SRRs of deep TESE were higher than that of its superficial counterpart, there was no significant statistical difference. A larger body of evidence is needed to provide a higher grade of recommendation.

An integrative prediction model of successful sperm retrieval for men with non-obstructive azoospermia.

Microdissection testicular sperm extraction (micro-TESE) is an efficient method for obtaining spermatozoa from patients with non-obstructive azoospermia, but the overall success rate of this surgery is only approximately one-third. This study aimed to construct an integrative prediction model for andrologists to assess the preoperative success retrieval rate. A total of 217 patients diagnosed with non-obstructive azoospermia at the First Affiliated Hospital of Nanjing Medical University were included, in whom sperm was successfully retrieved in 71 patients. We retrospectively analyzed their clinical characteristics and pathological features. Single factor analysis and logistic regression analysis were utilized to validate the predictive performance, and the area under the curve (AUC) analysis was conducted to further assess the clinical diagnostic value of the model. The results showed that a history of Klinefelter syndrome or cryptorchidism, FSH (Follicle Stimulating Hormone) levels, and testicular pathology contributed differently to the nomogram prediction model. Relatively normal FSH levels, a history of Klinefelter syndrome or cryptorchidism, and favorable testicular pathological types were assigned higher scores, with higher scores often accompanying a preferable success rate of sperm retrieval. The integrated model showed good prediction performance, with an AUC (Area Under the Curve) of 0.781 (95% CI (confidence interval) 0.713-0.849). Overall, our integrative model demonstrates excellent prediction performance and may assist andrologists in balancing the benefits of surgery preoperatively.

Differences in clinical outcomes between men with mosaic Klinefelter syndrome and those with non-mosaic Klinefelter syndrome.

This study compared the clinical outcomes of men with Klinfelter syndrome based on karyotype. The authors analyzed the outcomes of microdissection testicular sperm extraction (micro-TESE) performed on 57 patients with Klinfelter syndrome (KS) at our clinic. The average ages of the non-mosaic and mosaic KS groups were 32.2 ± 4.8 and 45.9 ± 13.1 years, respectively. The sperm retrieval rates of the non-mosaic and mosaic KS groups were 46.5% (20/43) and 50.0% (7/14), respectively. The fertilization rates after intracytoplasmic sperm injection did not significantly differ between the non-mosaic and mosaic KS groups. The mosaic KS group had higher cleavage and blastocyst development rates than the non-mosaic KS group (72.2% vs. 96.2% and 30.5% vs. 44.7%, respectively). The group using motile sperm had better outcomes than the group using immotile sperm. The embryo transfer outcomes of the non-mosaic and mosaic KS groups did not significantly differ (clinical pregnancy rate: 28.0% vs. 20.7%, miscarriage rate: 14.3% vs. 33.3%, production rate per transfer: 22.0% vs. 13.8%, and production rate per case: 58.8% vs. 57.1%). Compared with the non-mosaic KS group, the mosaic KS group had significantly better intracytoplasmic sperm injection outcomes because of the higher utilization rate of motile sperm.

Sperm retrieval rate and patient factors in azoospermia factor c microdeletion azoospermia: a systematic review.

To reveal the overall sperm retrieval rate (SRR) and range in patients with azoospermia factor c (AZFc) microdeletion azoospermia by microdissection testicular sperm extraction (mTESE) and discuss the differences of preoperative patient factors among studies with various SRRs. We searched PubMed, Web of Science and Embase until February 2023. All studies reporting SRRs by mTESE and required parameters of patients with AZFc microdeletions were included. The primary outcome was the SRR and, if available, the pregnancy rate (PR) and live-birth rate (LBR) after intracytoplasmic sperm injection were also investigated as secondary outcomes. Eventually 11 cohort studies were included in this review. A total number of 441 patients underwent mTESE and in 275 of them sperm was obtained, reaching an overall SRR of 62.4%. The SRRs among studies had a wide range from 25.0% to 85.7%. The studies reporting higher SRRs generally had older mean ages, and higher follicle-stimulating hormone and testosterone levels. Only four studies provided practical data on pregnancies and live-born children of patients with AZFc microdeletions, so the overall PR and LBR were unavailable. The overall SRR of patients with AZFc microdeletion azoospermia was 62.4%. The effect of patient factors in SR needs further evidence in future work.

#337 : Six Characters of Seminiferous Tubules Appearances During Micro-Tese Related with Different Sperm Retrieval Rate

Background and Aims: For non-obstructive azoospermia (NOA) patients, micro-TESE is considered to have higher sperm retrieval rate (SRR) than traditional surgery. However, various clinical parameters are not reliable predictors for the presence of focal spermatogenesis and SRR. This study summarized the characters of seminiferous tubules appearances and investigated their relationship with SRR. Method: This was a retrospective study. From September 2014 to April 2023, 638 NOA patients treated with micro-TESE were divided into six groups according to the seminiferous tubules appearances (Group-A: homogeneously thick, Group-B: homogeneously thin, Group-C: seminiferous tubules were severe thin and loss the tubal appearance, Group-D: the testicles were filled with hyperplastic Leydig cells, seminiferous tubules were severe thin and rare, Group-E, thick tubules mixed with thin tubules, Group-F, extensive testicular microlithiasis). Age, testicular volume, serum FSH, testosterone level, SRR and the heterogeneous seminiferous tubules presenting rate (HSTPR) were compared. Results: Sperms were successfully retrieved in 333 cases (SRR=52.2%). There were no statistical differences in age, testicular volume, FSH and testosterone level between the patients who succeeded and failed to obtain sperm (Table 1, all [Formula: see text]&gt;0.05). The constituent ratio of etiology was different in the six groups (Table 2, [Formula: see text]&lt;0.05). Between the six groups, testicular volume, FSH, testosterone, SRR and HSTPR were statistically different (Table 3, all [Formula: see text]&lt;0.05). Conclusion: Age, testicular volume, FSH and testosterone were insufficient to predict the SRR of NOA patients. Micro-TESE is commended to terminated when sperm are retrieved in case that the seminiferous tubules are rare or too thin to present tubal appearance, thick tubules mix with thin tubules or extensive testicular microlithiasis present (Group C-F). If the tubules appear homogeneously thick or thin, micro-TESE would has less advantage comparing with conventional multiple TESE because of the difficulty to identify the differences between the tubules even if the sperm is finally retrieved (Group A-B).

#85 : Microdissection Testicular Sperm Extraction (Micro-Tese) in Men Non-Obstructive Azoospermia with Very Small Testicular Volume: A Case Series Report

Background and Aims: Testicular atrophy is a common clinical manifestation of NOA, with a rate of 79.1%. The results of sperm retrieval using the mTESE method in a special NOA for testicular atrophy with volume [Formula: see text]5ml are currently inconsistent. As a result, we present the results of sperm retrieval using the mTESE method to patient NOA, who has a bilateral testicular volume [Formula: see text]5ml. Methods: A case series report of NOA with bilateral testicular volume [Formula: see text]5ml that indicated mTESE surgery to collect sperm at the assisted reproductive technology center of Tam Anh Ha Noi General Hospital between January 2022 and December 2022. Results: Four of seven NOA patients (57.1%) had successful sperm retrieval using the mTESE method, with bilateral testicular volume [Formula: see text]5 ml and a mean FSH level of 40,5 ± 21,9 (24,1-87,6) mIU/mL. In which case, 3/4 of patients simply require surgery on the monolateral testicular is sufficient sperm. Conclusions: Testicular atrophy does not appear to impair sperm retrieval results by the mTESE method, even the sperm retrieval rate tends to be higher in NOA patients with bilateral testicular volume [Formula: see text] 5ml.

Varicocelectomy outcomes among patients with azoospermia and severe oligasthenoteratozoospermia.

Varicocele is a reversible cause of male infertility. However, there are conflicting data available concerning the benefit of varicocele repair for patients with nonobstructive azoospermia (NOA) and severe oligoasthenoteratozoospermia (OAT). To address the benefit of varicocelectomy in patients with severe OAT and NOA with regard to their semen parameters and surgical sperm retrieval rate in those who underwent testicular sperm extraction (TESE) or testicular sperm aspiration (TESA). This retrospective cohort study was conducted on a sample of 13 patients diagnosed with NOA and severe OAT who underwent varicocelectomy for infertility treatment with no prespecified exclusion criteria. Thirteen patients were enrolled. Five patients were diagnosed with NOA; eight were diagnosed with severe OAT. For improvements in the semen parameters postoperatively, the semen concentration of all patients was significantly increased compared to the preoperative concentration (3.59 ± 10.0.8 vs. 0.25 ± 0.31, P = 0.02) and the remaining parameters were unchanged. Regarding sperm retrieval, three patients underwent TESE and two patients underwent TESA, in which all had positive results. Varicocele repair was found to improve the semen parameters in patients with NOA and severe OAT and produced a successful surgical sperm retrieval rate in all patients who underwent TESA or TESE.

Association of the minimal cyclophosphamide equivalent dose and outcome of microdissection testicular sperm extraction in patients with persistent azoospermia after chemotherapy

To investigate whether the minimal cyclophosphamide equivalent dose (mCED), a novel approach for estimating alkylating agent exposure, is associated with the sperm retrieval rates by microdissection testicular sperm extraction (mTESE) in azoospermic postchemotherapy cancer survivors. A retrospective cohort study conducted between 2002 and2017. An academic medical center. A total of 28 azoospermic postchemotherapy cancer survivors who underwent mTESE. Chemotherapy exposure and mCED calculation. The primary outcome was the association between the mCED and sperm retrieval rate using mTESE. The mCED value for each patient's regimen received was estimated using the lowest recommended dosing regimen from the range of recommended doses at the time of administration. Spermatozoa were successfully retrieved in 11 (39.3%) of the patients. Age at the time of receiving chemotherapy and mCED were significant factors associated with sperm retrieval. An mCED of <4,000 mg/m2 had a higher sperm retrieval rate (10/14, 71.4%) than an mCED of >4,000 mg/m2 (0/8, 0). The hormone levels were not significantly different when comparing patients with and without successful sperm retrieval. Seminoma, nonseminomatous germ cell tumor, and acute lymphoblastic leukemia had favorable sperm retrieval rates-100% (2/2), 66.7% (2/3), and 66.7% (2/3), respectively-although the numbers of patients in each group were small. Among this cohort of patients with cancer who required chemotherapy regimens, successful sperm retrieval by mTESE was only noted among cancer survivors receiving an mCED of <4,000 mg/m2.

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.

Clinical management of nonobstructive azoospermia: An update.

Approximately 1% of the general male population has azoospermia, and nonobstructive azoospermia accounts for the majority of cases. The causes vary widely, including chromosomal and genetic abnormalities, varicocele, drug-induced causes, and gonadotropin deficiency; however, the cause is often unknown. In azoospermia caused by hypogonadotropic hypogonadism, gonadotropin replacement therapy can be expected to produce sperm in the ejaculate. In some cases, upfront varicocelectomy for nonobstructive azoospermia with varicocele may result in the appearance of ejaculated spermatozoa; however, the appropriate indication should be selected. Each guideline recommends microdissection testicular sperm extraction for nonobstructive azoospermia in terms of successful sperm retrieval and avoidance of complications. Sperm retrieval rates generally ranged from 20% to 70% but vary depending on the causative disease. Various attempts have been made to predict sperm retrieval and improve sperm retrieval rates; however, the evidence is insufficient. Further evidence accumulation is needed for salvage treatment in cases of failed sperm retrieval. In Japan, there is inadequate provision on the right to know the origin of children born from artificial insemination of donated sperm and the rights of sperm donors, as well as information on unrelated family members, and the development of these systems is challenging. In the future, it is hoped that the pathogenesis of nonobstructive azoospermia with an unknown cause will be elucidated and that technology for omics technologies, human spermatogenesis using pluripotent cells, and organ culture methods will be developed.

Enzymatic tissue processing after testicular biopsy in non-obstructive azoospermia enhances sperm retrieval.

What is the added value of enzymatic processing of testicular biopsies on testicular sperm retrieval (SR) rates for patients with non-obstructive azoospermia (NOA)? In addition to mechanical mincing, enzymatic digestion increased SR rates in testicular biopsies of NOA patients. Many studies focus on the surgical approach to optimize recovery of testicular sperm in NOA, and in spite of that, controversy still exists about whether the type of surgery makes any difference as long as multiple biopsies are taken. Few studies, however, focus on the role of the IVF laboratory and the benefit of additional lab procedures, e.g. enzymatic digestion, in order to optimize SR rates. This retrospective single-center cohort study included all patients who underwent their first testicular sperm extraction (TESE) by open multiple-biopsy method between January 2004 and July 2022. Only patients with a normal karyotype, absence of Y-q deletions and a diagnosis of NOA based on histology were included. The primary outcome was SR rate after mincing and/or enzymes. The secondary outcome was cumulative live birth (CLB) after ICSI with fresh TESE and subsequent ICSI cycles with frozen TESE. Multiple biopsies were obtained from the testis, unilaterally or bilaterally, on the day of oocyte retrieval. Upon mechanical mincing, biopsies were investigated for 30 min; when no or insufficient numbers of spermatozoa were observed, enzymatic treatment was performed using Collagenase type IV. Multivariable regression analysis was performed to predict CLB per TESE by adjusting for the following confounding factors: male FSH level, female age, and requirement of enzymatic digestion to find sperm. We included 118 patients, of whom 72 (61.0%) had successful SR eventually. Spermatozoa were retrieved after mechanical mincing for 28 patients (23.7%; 28/118) or after additional enzymatic digestion for another 44 patients (37.2%; 44/118). Thus, of the 90 patients requiring enzymatic digestion, sperm were retrieved for 44 (48.9%). Male characteristics were not different between patients with SR after mincing or enzymatic digestion, in regard to mean age (34.5 vs 34.5 years), testis volume (10.2 vs 10.6 ml), FSH (17.8 vs 16.9 IU/l), cryptorchidism (21.4 vs 34.1%), varicocele (3.6 vs 4.6%), or histological diagnosis (Sertoli-cell only 53.6 vs 47.7%, maturation arrest 21.4 vs 38.6%, sclerosis/atrophy 25.0 vs 13.6%).Of the 72 patients with sperm available for ICSI, 23/72 (31.9%) achieved a live birth (LB) after the injection with fresh testicular sperm (and fresh or frozen embryo transfers). Of the remaining 49 patients without LB, 34 (69.4%) had supernumerary testicular sperm frozen. Of these 34 patients, 19 (55.9%) continued ICSI with frozen testicular sperm, and 9/19 (47.4%) had achieved an LB after ICSI with frozen testicular sperm. Thus, the total CLB was 32/118 (27.1%) per TESE or 32/72 (44.4%) per TESE with sperm retrieved.Of the female characteristics (couples with sperm available), only female age (30.3 vs 32.7 years; P = 0.042) was significantly lower in the group with a LB, compared to those without.The CLB with testicular sperm obtained after enzymatic digestion was 31.8% (14/44), while the CLB with sperm obtained after mincing alone was 64.3% (18/28). Multivariable logistic regression analysis showed that when enzymatic digestion was required, it was associated with a significant decrease in CLB per TESE (OR: 0.23 (0.08-0.7); P = 0.01). Limitations of the study are related to the retrospective design. However, the selection of only patients with NOA, and specific characteristics (normal karyotype and absence Y-q deletion) and having their first TESE, strengthens our findings. Enzymatic processing increases the SR rate from testicular biopsies of NOA patients compared to mechanical mincing only, demonstrating the importance of an appropriate laboratory protocol. However, NOA patients should be counseled that when sperm have been found after enzymatic digestion, their chances to father a genetically own child may be lower compared to those not requiring enzymatic digestion. None reported. N/A.