Incidental seminoma in nonobstructive azoospermia: a case report.

Objective: To report on the incidental finding of invasive seminoma in a patient with nonobstructive azoospermia during microdissection testicular sperm extraction. Design: Case report. Patients: A single patient diagnosed with nonobstructive azoospermia underwent microdissection testicular sperm extraction, and an incidental finding of invasive seminoma was made upon histopathological analysis. Results: 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. Conclusions: 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.

Clinical Factors Impacting Microdissection Testicular Sperm Extraction Success in Hypogonadal Men with Nonobstructive Azoospermia.

OBJECTIVE: To explore factors influencing microdissection testicular sperm extraction (micro-TESE) success in hypogonadal men with nonobstructive azoospermia (NOA). DESIGN: Cohort study. SETTING: University-affiliated male reproductive health center. SUBJECTS: 616 consecutive NOA patients with hypogonadism (total testosterone [T] levels <350 ng/dL) undergoing micro-TESE between 2014 and 2021. All patients had no prior sperm retrieval (SR) history. EXPOSURE: Patients aged 23-55 underwent comprehensive clinical, laboratory, and histopathological diagnostic evaluation for NOA and were further categorized into two cohorts based on pre-SR hormonal stimulation. MAIN OUTCOME MEASURES: Multivariable logistic regression analysis explored the associations between patient variables and micro-TESE success, defined as the presence of viable spermatozoa in extracted specimens. Adjusted odds ratios (aOR) and 95% confidence intervals (CI) were computed to assess the relationship between SR success and relevant predictors. SR rates were compared between patients receiving or not hormonal stimulation, and logistic regression analysis evaluated the effect of baseline FSH levels (i.e., normogonadotropic vs. hypergonadotropic classes) on SR success. RESULTS: The overall micro-TESE success rate was 56.6%. Baseline FSH levels (aOR 0.97, 95% CI 0.94-0.99, p=0.04), pre-SR hormonal stimulation (aOR 2.54, 1.64-3.93, p=0.0002), presence of clinical varicocele (aOR 0.05, 0.01-0.51, p=0.04), history of previous varicocelectomy (aOR 2.55, 1.26-5.16, p=0.01), and testicular histopathology (p<0.01) were independent predictors of SR success. Among hormone-pretreated patients, pre-micro-TESE T levels and Delta T (absolute increase in T levels from baseline) were associated with SR success (p<0.05). 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 patients with positive and negative SR outcomes. Subgroup analysis showed that pre-SR hormonal stimulation yielded a greater benefit for normogonadotropic patients than for those who were hypergonadotropic. CONCLUSION: This study underscores the association between clinical factors and micro-TESE success in hypogonadal men with NOA. While causality is not established, our findings suggest that these patients may benefit from pre-SR interventions, particularly hormonal stimulation and varicocele repair.

Feasibility of high-frequency ultrasound for seminiferous tubule assessment and correlation of B-mode imaging with pathological findings in the testis in azoospermia.

PURPOSE: To determine the feasibility of high-frequency ultrasound (HFUS) for assessing seminiferous tubules and to understand high-resolution B-mode images of the testes in cases of azoospermia. METHODS: We verified how the histopathological images of testicular biopsy specimens can be observed using HFUS images and measurement analysis of seminiferous tubules was performed to 28 testes of 14 cases with azoospermia who underwent preoperative ultrasound and microdissection testicular sperm extraction (micro-TESE). The population consisted of obstructive azoospermia (OA) and non-obstructive azoospermia (NOA), including Sertoli cell-only syndrome (SCOS), and the other pathologies. Statistical verification of differences in seminiferous tubule diameters among preoperative ultrasound examination, ultrasound examination of pathological specimens, and histopathological specimens. We also examined the imagingpathology correlation via a case series presentation, aiming to identify imaging markers of testicular pathology and determine the possibility of predicting each condition. RESULTS: A comparison between HFUS images and histopathology from the same biopsy specimens suggested that ultrasonography could be seen as stereoscopic images due to its significantly greater slice thickness. The diameters of tubules were generally larger in pathological tissues as compared to ultrasonographic findings in OA and SCOS, but not in the other conditions. Comparisons provided insights into the predictability of SCOS and revealed imaging findings such as gaps between tubules and decreased diameter reflective of testicular damage. CONCLUSION: Seminiferous tubules can be observed however the diameter of seminiferous tubules varies in imaging and histopathology depending on the pathology. Imaging findings that reflect testicular damage and the predictability of SCOS were revealed in this study, but further verification is required.

Evaluation of an artificial intelligence-facilitated sperm detection tool in azoospermic samples for use in ICSI.

RESEARCH QUESTION: Can artificial intelligence (AI) improve the efficiency and efficacy of sperm searches in azoospermic samples? DESIGN: This two-phase proof-of-concept study began with a training phase using eight azoospermic patients (>10,000 sperm images) to provide a variety of surgically collected samples for sperm morphology and debris variation to train a convolutional neural network to identify spermatozoa. Second, side-by-side testing was undertaken on two cohorts of non-obstructive azoospermia patient samples: an embryologist versus the AI identifying all the spermatozoa in the still images (cohort 1, n = 4), and a side-by-side test with a simulated clinical deployment of the AI model with an intracytoplasmic sperm injection microscope and the embryologist performing a search with and without the aid of the AI (cohort 2, n = 4). RESULTS: In cohort 1, the AI model showed an improvement in the time taken to identify all the spermatozoa per field of view (0.02 ± 0.30  ×  10-5s versus 36.10 ± 1.18s, P < 0.0001) and improved recall (91.95 ± 0.81% versus 86.52 ± 1.34%, P < 0.001) compared with an embryologist. From a total of 2660 spermatozoa to find in all the samples combined, 1937 were found by an embryologist and 1997 were found by the AI in less than 1000th of the time. In cohort 2, the AI-aided embryologist took significantly less time per droplet (98.90 ± 3.19 s versus 168.7 ± 7.84 s, P < 0.0001) and found 1396 spermatozoa, while 1274 were found without AI, although no significant difference was observed. CONCLUSIONS: AI-powered image analysis has the potential for seamless integration into laboratory workflows, to reduce the time to identify and isolate spermatozoa from surgical sperm samples from hours to minutes, thus increasing success rates from these treatments.

A 20-year overview of fertility preservation in boys: new insights gained through a comprehensive international survey.

STUDY QUESTION: Twenty years after the inception of the first fertility preservation programme for pre-pubertal boys, what are the current international practices with regard to cryopreservation of immature testicular tissue? SUMMARY ANSWER: Worldwide, testicular tissue has been cryopreserved from over 3000 boys under the age of 18 years for a variety of malignant and non-malignant indications; there is variability in practices related to eligibility, clinical assessment, storage, and funding. WHAT IS KNOWN ALREADY: For male patients receiving gonadotoxic treatment prior to puberty, testicular tissue cryopreservation may provide a method of fertility preservation. While this technique remains experimental, an increasing number of centres worldwide are cryopreserving immature testicular tissue and are approaching clinical application of methods to use this stored tissue to restore fertility. As such, standards for quality assurance and clinical care in preserving immature testicular tissue should be established. STUDY DESIGN SIZE DURATION: A detailed survey was sent to 17 centres within the recently established ORCHID-NET consortium, which offer testicular tissue cryopreservation to patients under the age of 18 years. The study encompassed 60 questions and remained open from 1 July to 1 November 2022. PARTICIPANTS/MATERIALS SETTING METHODS: Of the 17 invited centres, 16 completed the survey, with representation from Europe, Australia, and the USA. Collectively, these centres have cryopreserved testicular tissue from patients under the age of 18 years. Data are presented using descriptive analysis. MAIN RESULTS AND THE ROLE OF CHANCE: Since the establishment of the first formal fertility preservation programme for pre-pubertal males in 2002, these 16 centres have cryopreserved tissue from 3118 patients under the age of 18 years, with both malignant (60.4%) and non-malignant (39.6%) diagnoses. All centres perform unilateral biopsies, while 6/16 sometimes perform bilateral biopsies. When cryopreserving tissue, 9/16 centres preserve fragments sized ≤5 mm3 with the remainder preserving fragments sized 6-20 mm3. Dimethylsulphoxide is commonly used as a cryoprotectant, with medium supplements varying across centres. There are variations in funding source, storage duration, and follow-up practice. Research, with consent, is conducted on stored tissue in 13/16 centres. LIMITATIONS REASONS FOR CAUTION: While this is a multi-national study, it will not encompass every centre worldwide that is cryopreserving testicular tissue from males under 18 years of age. As such, it is likely that the actual number of patients is even higher than we report. Whilst the study is likely to reflect global practice overall, it will not provide a complete picture of practices in every centre. WIDER IMPLICATIONS OF THE FINDINGS: Given the research advances, it is reasonable to suggest that cryopreserved immature testicular tissue will in the future be used clinically to restore fertility. The growing number of patients undergoing this procedure necessitates collaboration between centres to better harmonize clinical and research protocols evaluating tissue function and clinical outcomes in these patients. STUDY FUNDING/COMPETING INTERESTS: K.D. is supported by a CRUK grant (C157/A25193). R.T.M. is supported by an UK Research and Innovation (UKRI) Future Leaders Fellowship (MR/S017151/1). The MRC Centre for Reproductive Health at the University of Edinburgh is supported by MRC (MR/N022556/1). C.L.M. is funded by Kika86 and ZonMW TAS 116003002. A.M.M.v.P. is supported by ZonMW TAS 116003002. E.G. was supported by the Research Program of the Research Foundation-Flanders (G.0109.18N), Kom op tegen Kanker, the Strategic Research Program (VUB_SRP89), and the Scientific Fund Willy Gepts. J.-B.S. is supported by the Swedish Childhood Cancer Foundation (TJ2020-0026). The work of NORDFERTIL is supported by the Swedish Childhood Cancer Foundation (PR2019-0123; PR2022-0115), the Swedish Research Council (2018-03094; 2021-02107), and the Birgitta and Carl-Axel Rydbeck's Research Grant for Paediatric Research (2020-00348; 2021-00073; 2022-00317; 2023-00353). C.E is supported by the Health Department of the Basque Government (Grants 2019111068 and 2022111067) and Inocente Inocente Foundation (FII22/001). M.P.R. is funded by a Medical Research Council Centre for Reproductive Health Grant No: MR/N022556/1. A.F. and N.R. received support from a French national research grant PHRC No. 2008/071/HP obtained by the French Institute of Cancer and the French Healthcare Organization. K.E.O. is funded by the University of Pittsburgh Medical Center and the US National Institutes of Health HD100197. V.B-L is supported by the French National Institute of Cancer (Grant Seq21-026). Y.J. is supported by the Royal Children's Hospital Foundation and a Medical Research Future Fund MRFAR000308. E.G., N.N., S.S., C.L.M., A.M.M.v.P., C.E., R.T.M., K.D., M.P.R. are members of COST Action CA20119 (ANDRONET) supported by COST (European Cooperation in Science and Technology). The Danish Child Cancer Foundation is also thanked for financial support (C.Y.A.). The authors declare no competing interests. TRIAL REGISTRATION NUMBER: N/A.

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

PURPOSE: We evaluate microscopic (micro) testicular sperm extraction (TESE) timing relative to oocyte retrieval on intracytoplasmic sperm injection outcome. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

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

Objective: 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). Patients and Methods: 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. Results: 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. Conclusion: 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.

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

BACKGROUND: Microdissection testicular sperm extraction is an effective method to retrieve sperm from non-obstructive azoospermia patients. However, its successful rate is less than 50%. OBJECTIVES: To identify the predictive value of circular RNAs in serum for sperm retrieval rate in non-obstructive azoospermia patients. MATERIALS AND METHODS: 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. RESULTS: 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. DISCUSSION AND CONCLUSION: 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.

Financial decision analysis based on "willingness to pay" for surgical sperm retrieval approaches among men with non-obstructive azoospermia in the United States.

OBJECTIVE: To determine the most financially optimal surgical approach for testicular sperm retrieval for men with non-obstructive azoospermia. DESIGN: A decision tree was created examining five potential surgical approaches for men with non-obstructive azoospermia pursuing one cycle of intracytoplasmic sperm injection. An expected financial net loss was determined for each surgical option based on couples' willingness to pay for one cycle of intracytoplasmic sperm injection resulting in pregnancy. The branch with the lowest expected net loss was defined as the most optimal financial decision (minimizing loss to a couple). Fresh testicular sperm extraction implied testicular sperm extraction was performed in conjunction with programmed ovulation induction. Frozen testicular sperm extraction implied testicular sperm extraction was performed initially, and ovulation induction/intracytoplasmic sperm injection was canceled if sperm retrieval failed.  The surgical options included fresh conventional testicular sperm extraction, with and without "back-up" sperm cryopreservation, fresh microsurgical testicular sperm extraction, with and without "back-up" sperm cryopreservation, and frozen microsurgical testicular sperm extraction. Success was defined as pregnancy after one intracytoplasmic sperm injection cycle. MATERIALS AND METHODS: Probabilities of successful sperm retrieval with conventional testicular sperm extraction/microsurgical testicular sperm extraction, post-thaw sperm cellular loss following frozen microsurgical testicular sperm extraction, ovulation induction/intracytoplasmic sperm injection cycle out-of-pocket costs, intracytoplasmic sperm injection pregnancy rates for men with non-obstructive azoospermia, standard conventional testicular sperm extraction cost and average willingness to pay for intracytoplasmic sperm injection cycle were gathered from the systematic literature review. Costs were in USD and adjusted to inflation (as of April 2020). Two-way sensitivity analysis was performed on varying couples' willingness to pay for one cycle of intracytoplasmic sperm injection and varying microsurgical testicular sperm extraction out-of-pocket costs. RESULTS: According to our decision tree analysis (assuming minimum microsurgical testicular sperm extraction cost of $1,000 and willingness to pay of $8,000), the expected net loss for each branch was as follows: -$17,545 for fresh conventional testicular sperm extraction, -$17,523 for fresh microsurgical testicular sperm extraction, -$9,624 for frozen microsurgical testicular sperm extraction, -$17,991 for fresh conventional testicular sperm extraction with "backup", and -$18,210 for fresh microsurgical testicular sperm extraction with "backup". Two-way sensitivity analysis with a variable willingness to pay values and microsurgical testicular sperm extraction and in-vitro fertilization costs confirmed that frozen microsurgical testicular sperm extraction consistently presented the lowest net loss compared to other options. Interestingly, when directly comparing fresh microsurgical testicular sperm extraction and conventional testicular sperm extraction with "back-up", scenarios with decreasing willingness to pay and lower microsurgical testicular sperm extraction costs demonstrated fresh conventional testicular sperm extraction with "back-up" as more optimal than fresh microsurgical testicular sperm extraction with "back-up". CONCLUSIONS: For those couples who must pay out of pocket, our study suggests that frozen microsurgical testicular sperm extraction is the most financially optimal decision for the surgical management of non-obstructive azoospermia, regardless of microsurgical testicular sperm extraction cost and the couple's willingness to pay.

Predictors of successful salvage microdissection testicular sperm extraction (mTESE) after failed initial TESE in patients with non-obstructive azoospermia: A systematic review and meta-analysis.

BACKGROUND: There has been no systematic review and meta-analysis to analyze and summarize the predictive factors of successful sperm extraction in salvage microdissection testicular sperm extraction. OBJECTIVES: We aimed to investigate the factors predicting the result of salvage microdissection testicular sperm extraction in patients with non-obstructive azoospermia who failed the initial microdissection testicular sperm extraction or conventional testicular sperm extraction. MATERIALS AND METHODS: We conducted a systematic literature search in PubMed, Web of Science, EMBASE, and the Cochrane Library for literature that described the characteristics of patients with non-obstructive azoospermia who underwent salvage microdissection testicular sperm extraction after failing the initial microdissection testicular sperm extraction or conventional testicular sperm extraction published prior to June 2022. RESULTS: This meta-analysis included four retrospective studies with 332 patients with non-obstructive azoospermia who underwent a failed initial microdissection testicular sperm extraction and three retrospective studies with 177 non-obstructive azoospermia patients who underwent a failed conventional testicular sperm extraction. The results were as follows: among non-obstructive azoospermia patients whose first surgery was microdissection testicular sperm extraction, younger patients (standard mean difference: -0.28, 95% confidence interval [CI]: -0.55 to -0.01) and those with smaller bilateral testicular volume (standard mean difference: -0.55, 95% CI: -0.95 to -0.15), lower levels of follicle-stimulating hormone (standard mean difference: -0.86, 95% CI: -1.18 to -0.54) and luteinizing hormone (standard mean difference: -0.68, 95% CI: -1.16 to -0.19), and whose testicular histological type was hypospermatogenesis (odds ratio: 3.52, 95% CI: 1.30-9.53) were more likely to retrieve spermatozoa successfully, while patients with Sertoli-cell-only syndrome (odds ratio: 0.41, 95% CI: 0.24-0.73) were more likely to fail again in salvage microdissection testicular sperm extraction. Additionally, in patients who underwent salvage microdissection testicular sperm extraction after a failed initial conventional testicular sperm extraction, those with testicular histological type of hypospermatogenesis (odds ratio: 30.35, 95% CI: 8.27-111.34) were more likely to be successful, while those with maturation arrest (odds ratio: 0.39, 95% CI: 0.18-0.83) rarely benefited. CONCLUSION: We found that age, testicular volume, follicle-stimulating hormone, luteinizing hormone, hypospermatogenesis, Sertoli-cell-only syndrome, and maturation arrest were valuable predictors of salvage microdissection testicular sperm extraction, which will assist andrologists in clinical decision-making and minimize unnecessary injury to patients.

Sperm retrieval outcomes of contralateral testis in men with nonobstructive azoospermia and unsuccessful unilateral microdissection testicular sperm extraction.

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A Prior History of Cryptozoospermia Is Associated with a Significantly Higher Chance of a Successful Microdissection Testicular Sperm Extraction Compared to Non-Obstructive Azoospermia.

BACKGROUND: Our study sought to evaluate the rates of successful sperm retrieval following microdissection testicular sperm extraction (mTESE) in patients with a prior history of cryptozoospermia, compared to patients with non-obstructive azoospermia (NOA). METHODS: A retrospective chart analysis evaluating all mTESE procedures was performed from January 2004 to August 2018. Inclusion criteria involved all males >18 years of age with a diagnosis of cryptozoospermia and/or NOA that underwent a mTESE. The patient's genetic profile, hormonal profile, semen analysis, testicular volumes, pathology and comorbidities were analyzed. RESULTS: We identified 40 patients with cryptozoospermia and 221 patients with NOA. Successful mTESE occurred in 34/40 (85%) cryptozoospermic males compared to 104/221 (48%) NOA males (p < 0.001). In univariate and multivariate analyses, patients with cryptozoospermia were more likely to undergo a successful mTESE than patients with NOA (OR 5.56 [1.79-17.29], p = 0.003; OR 5.41 [1.94-15.08], p = 0.0013), respectively. Factors that were associated with a statistically significant lower chance of successful mTESE included Sertoli-cell only pathology, pre-operative testosterone < 300 ng/dL and FSH > 7.6 mIU/mL. CONCLUSION: Despite patients with a history of cryptozoospermia having a significantly higher chance of a successful sperm retrieval than patients with NOA, couples should be counselled on the possibility of an unsuccessful sperm extraction, in order to optimize the pre-operative IVF planning and to manage operative expectations.

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

OBJECTIVE: 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. PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Novel predictors for livebirth delivery rate in patients with idiopathic non-obstructive azoospermia based on the clinical prediction model.

Objective: To build a prediction model for live birth delivery per intracytoplasmic sperm injection (ICSI) in iNOA patients by obtaining sperm by microdissection testicular sperm extraction (mTESE). Methods: A retrospective cohort study of 377 couples with iNOA male partners treated with 519 mTESE-ICSI cycles was conducted from September 2013 to July 2021 at the Reproductive Medical Centre of Peking University Third Hospital. Following exclusions, 377 couples with iNOA male partners treated with 482 mTESE-ICSIs were included. A prediction model for live birth delivery per ICSI cycle was built by multivariable logistic regression and selected by 10-fold cross-validation. Discrimination was evaluated by c-statistics and calibration was evaluated by the calibration slope. Results: The live birth delivery rate per mTESE-ICSI cycle was 39.21% (189/482) in these couples. The model identified that the presence of motile sperm during mTESE, bigger testes, higher endometrial thickness on the day of human chorionic gonadotrophin (hCG) administration (ET-hCG), and higher quality embryos are associated with higher live birth delivery success rates. The results of the model were exported based on 10-fold cross-validation. In addition, the area under the mean ROC curve was 0.71 ± 0.05 after 10-fold cross-validation, indicating that the prediction model had certain prediction precision. A calibration plot with an estimated intercept of -1.653 (95% CI: -13.403 to 10.096) and a slope of 1.043 (95% CI: 0.777 to 1.308) indicated that the model was well-calibrated. Conclusion: Our prediction model will provide valuable information about the chances of live birth delivery in couples with iNOA male partners who have a plan for mTESE-ICSI treatment. Therefore, it can improve and personalize counseling for the medical treatment of these patients.

Leydig cell metabolic disorder act as a new mechanism affecting for focal spermatogenesis in Klinefelter syndrome patients: a real world cross-sectional study base on the age.

Background: Klinefelter's syndrome (KS) was once considered infertile due to congenital chromosomal abnormalities, but the presence of focal spermatozoa changed this. The key to predict and promote spermatogenesis is to find targets that regulate focal spermatogenesis. Objective: To explore the trend of fertility changes in KS patients at different ages and identify potential therapeutic targets. Methods: Bibliometric analysis was used to collect clinical research data on KS from the Web of Science Core Collection (WoSCC) from 1992 to 2022. A cross-sectional study was conducted on 75 KS patients who underwent microscopic testicular sperm extraction (mTESE) from 2017 to 2022 in the real world. The reproductive hormones, testicular histopathology, androgen receptors, insulin-like factor 3 (INSL3) receptors and sperm recovery rate (SRR) were analyzed. Results: Male infertility, dysplasia, Sertoli cells, Leydig cells, testosterone and spermatogenesis were the research focuses related to KS. Luteinizing hormone (LH), testosterone, and INSL3 were evaluation indicators of Leydig cell function that fluctuate with age. Testosterone and LH peaked at ages 13-19 and 30-45, while INSL3 only peaked at ages 13-19. 27 patients (27/75) recovered sperm through mTESE and experienced SRR peaks at the ages of 20, 28, 34, and 37. The SRR of fibrosis patients was 46.15%, fatty degeneration was 7.14%, and melanosis was 40.00%. The INSL3 and androgen receptors were highly expressed and roughly balanced in focal spermatogenesis. Conclusion: Abnormal metabolism of Leydig cells led to imbalanced expression of INSL3 and androgen receptors, which might be a potential target for spermatogenesis in KS.

Evaluating the Predictive Value of Diagnostic Testicular Biopsy for Sperm Retrieval Outcomes in Men with Non-Obstructive Azoospermia.

BACKGROUND: Non-obstructive azoospermia (NOA) presents a challenge in male infertility management. This study aimed to assess the efficacy of diagnostic testicular biopsy (DTB) in predicting sperm retrieval success via therapeutic testicular biopsy (TTB) and to understand the role of systemic inflammation in microdissection testicular sperm extraction (mTESE) outcomes. METHODS: A retrospective analysis was conducted on 50 NOA males who underwent mTESE at the University of Ioannina's Department of Urology from January 2017 to December 2019. All participants underwent thorough medical evaluations, including semen analyses and endocrinological assessments. RESULTS: DTB did not detect spermatozoa in half of the patients who later showed positive sperm findings in TTB. Preoperative variables, such as age, plasma levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), total testosterone (TT), prolactin (PRL), estradiol (E2), and inflammation biomarkers (neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), monocyte-eosinophil ratio (MER)), were not consistently predictive of sperm retrieval success. Notably, TTB-negative patients had elevated NLR and PLR values, suggesting a possible link between systemic inflammation and reduced sperm retrieval during mTESE. CONCLUSIONS: The findings question the necessity of an initial DTB, which might provide misleading results. A negative DTB should not deter further TTB or intracytoplasmic sperm injection (ICSI) attempts. The study emphasizes the need for further research to refine diagnostic approaches and deepen the understanding of factors influencing sperm retrieval in NOA patients, ultimately enhancing their prospects of biological parenthood.

Noninvasive Prediction of Sperm Retrieval Using Diffusion Tensor Imaging in Patients with Nonobstructive Azoospermia.

Microdissection testicular sperm extraction (mTESE) is the first-line treatment plan for nonobstructive azoospermia (NOA). However, studies reported that the overall sperm retrieval rate (SRR) was 43% to 63% among men with NOA, implying that nearly half of the patients fail sperm retrieval. This study aimed to evaluate the diagnostic performance of parameters derived from diffusion tensor imaging (DTI) in predicting SRR in patients with NOA. Seventy patients diagnosed with NOA were enrolled and classified into two groups based on the outcome of sperm retrieval during mTESE: success (29 patients) and failure (41 patients). Scrotal magnetic resonance imaging was performed, and the DTI parameters, including mean diffusivity and fractional anisotropy, were analyzed between groups. The results showed that there was a significant difference in mean diffusivity values between the two groups, and the area under the curve for mean diffusivity was calculated as 0.865, with a sensitivity of 72.2% and a specificity of 97.5%. No statistically significant difference was observed in fractional anisotropy values and sex hormone levels between the two groups. This study demonstrated that the mean diffusivity value might serve as a useful noninvasive imaging marker for predicting the SRR of NOA patients undergoing mTESE.

Fertility preservation in transfeminine adolescents using TESE at the time of Histrelin Acetate subcutaneous implant placement: A Case Series.

BACKGROUND: Fertility preservation (FP) is an important aspect of the care of transgender patients in whom Gender Affirming Medical Treatment (GAT) may begin before puberty is completed. While there are overall few studies that can be used to guide conversations about long-term effects of GAT, there are concerns that GAT could negatively impact fertility. Prior studies have shown low utilization of FP in this population, with avoidance of delay in starting GAT cited as one of the most common reasons for foregoing FP. It is possible that strategies to mitigate delay in commencement of GAT can facilitate higher FP utilization, maintaining options for future family building. OBJECTIVE: To describe our institution's experience with Testicular Sperm Extraction (TESE) for FP and Histrelin Acetate (Supprelin) Subcutaneous Implantation for GAT commencement. STUDY DESIGN: A retrospective review of transfeminine adolescents at our institution from 2010 to 2022 who underwent TESE for FP at the time of Supprelin placement for GAT (FP/SP). Outcomes of interest included successful sperm retrieval, age at first visit to our institution's Transgender Multispecialty Service Health clinic (GeMS), age at time of FP/SP, testicular volume, and Tanner stage at time of FP/SP, and age when GnRH agonist (GnRHa) therapy was prescribed. Testosterone, LH, FSH, and Inhibin B values prior to combination FP/SP were also obtained. RESULTS: Ten patients from 2017 to 2022 underwent FP/SP after prescription of GnRHa based on Endocrine Society Guidelines. Successful sperm retrieval and storage was achieved in all patients. Median age at FP/SP was fourteen years 5.5 months (range 12y5m-16y8m). Median time from GnRHa prescription to FP/SP was two months (range 2-5 m). Mean testicular volume at time of FP/SP was 13.2 cc (SD 3.38 cc, range 8-17 cc), and median Tanner Stage was IV (range III-V). Average testosterone level was 301.60 (SD 173.04), LH 3.00 (SD 1.25), FSH 3.33 (SD 1.71), Inhibin B 208.50 (SD 87.44). CONCLUSIONS: Performing TESE for FP is feasible for transgender youth undergoing Histrelin implant placement, leading to short delays in starting GAT. Testicular volume and endocrine markers can provide preoperative insight into likelihood of successful sperm retrieval during TESE, are needed to identify which patients will have successful sperm retrieval to ensure optimal counseling and informed decision making for providers, patients and families.

Stepwise mini-incision microdissection testicular sperm extraction in NOA patients with a history of cryptorchidism: a case-control study.

BACKGROUND: Although the orchiopexy is recommended for cryptorchidism to preserve male fertility, non-obstructive azoospermia (NOA) may occur in adulthood. Fortunately, a great many of azoospermic men may obtain sperm by microdissection testicular sperm extraction (mTESE). Due to the potential injuries caused by testicular diagnostic biopsy and vascular damage at the time of orchidopexy, minimal invasiveness is particularly important during mTESE, aims to reduce the surgical damage and avoids secondary testicular failure. This comparative study aims to investigate the efficacy of stepwise mini-incision mTESE technique by comparison with standard mTESE in the treatment of NOA patients with a history of cryptorchidism. RESULTS: A total of 73 mTESE procedures were divided into two groups: Group 1 included 37 cases performed by stepwise mini-incision mTESE, while Group 2 included 36 cases with standard mTESE. The overall sperm retrieval rate (SRR) in the two groups was 68.5% (50/73), with no significant difference in SRR between Group 1 (78.4%, 29/37) and Group 2 (58.3%, 21/36) (P = 0.1). In addition, 46.0% of the patients (17/37) obtained sperm in the first mini-incision step in Group 1, which was also equal to an overall SRR in Group 2 (58.3%, 21/36) (P = 0.3). The operation time in Group 1 (72.6 ± 33.9 min) was significantly shorter than that in Group 2 (90.4 ± 36.4 min) (P = 0.04). Patients with an orchidopexy age no more than 10 years old had a higher SRR (79.5%, 31/39) than others (55.9%, 19/34) (P = 0.03). There were no postoperative complications including wound infection, scrotal hematoma, persistent pain, and testicular atrophy during a follow-up period of at least 6 months. CONCLUSIONS: In conclusion, our study suggests that the stepwise mini-incision mTESE could be a promising approach for sperm retrieval in NOA men with a history of cryptorchidism. While the technique may potentially reduce operation time and surgical invasiveness, further research is needed to validate these findings on a larger scale. The results also suggest that age at orchidopexy may affect SRR and have important implications for the management of cryptorchidism.

RéSUMé: CONTEXTE: Bien que l'orchidopexie soit recommandée en cas de cryptorchidie afin de préserver la fertilité masculine, une azoospermie non obstructive (NOA) peut survenir à l'âge adulte. Heureusement, un grand nombre d'hommes azoospermiques peuvent obtenir des spermatozoïdes lors d'une extraction de spermatozoïdes testiculaire par microdissection (mTESE). En raison des potentielles lésions causées par la biopsie diagnostique testiculaire et des lésions vasculaires survenant au moment de l'orchidopexie, une approche minimalement  invasive est particulièrement importante pendant la mTESE;  elle vise à réduire les dommages chirurgicaux et à éviter une insuffisance testiculaire secondaire. La présente étude comparative a pour but d' étudier l'efficacité de la mTESE par mini-incision par étapes en comparaison avec la mTESE standard dans le traitement des patients NOA qui ont des antécédents de cryptorchidie. RéSULTATS: Au total, 73 procédures de mTESE ont été divisées en deux groupes: le Groupe 1 comprenait 37 cas effectués avec la mTESE par mini-incision par étapes, tandis que le Groupe 2 comprenait 36 cas réalisés par la mTESE standard. Le taux global de récupération de spermatozoïdes (SRR) dans les deux groupes était de 68, 5% (50/73), sans différence significative de SRR entre le Groupe 1 (78, 4%, 29/37) et le Groupe 2 (58, 3%, 21/36) (P = 0,1). De plus, 46% des patients (17/37) ont obtenu des spermatozoïdes lors de la première étape de mini-incision dans le Groupe 1, ce qui était identique au SRR global dans le Groupe 2 (58%, 21/36) (P = 0,3). Le temps opératoire du Groupe 1 (72, 6 ± 34 min) était significativement plus court que celui du Groupe 2 (90, 4 ± 36 min) (P = 0,04). Les patients dont l'orchidopexie avait été réalisée au plus tard à l'âge de 10 ans avaient un SRR plus élevé (79, 5%, 31/39) que les autres (55, 9%, 19/34) (P = 0,03). Il n'y a pas eu de complications postopératoires, que ce soit infection de la plaie, hématome scrotal, douleur persistante, ou atrophie testiculaire pendant une période de suivi d'au moins 6 mois. CONCLUSIONS: Notre étude suggère que la mTESE par mini-incision par étapes pourrait être une approche prometteuse pour la récupération de spermatozoïdes chez les hommes NOA ayant des antécédents de cryptorchidie. Bien que la technique puisse potentiellement réduire le temps d'opération et le caractère invasif du geste chirurgical, des recherches supplémentaires sont nécessaires pour valider ces résultats à plus grande échelle. Les résultats suggèrent également que l'âge à l'orchidopexie peut affecter le SRR et avoir des implications importantes pour la prise en charge de la cryptorchidie.

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

Background: 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. Methods: 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. Results: 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). Conclusions: 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.