Successful pregnancy and delivery following microdissection testicular sperm extraction and intracytoplasmic sperm injection for non-obstructive azoospermia after microsurgical varicocelectomy: A case report and review of the literature.

Although surgical varicocele treatment is generally considered to result in improved reproductive outcomes, we encountered a rare case of postoperative azoospermia in an infertile male patient who underwent microsurgical varicocelectomy for a palpable left-sided varicocele with concomitant cryptozoospermia. More than 1 year after varicocelectomy, the patient still had not recovered from azoospermia. Thereafter, he underwent microdissection testicular sperm extraction (micro-TESE), allowing him and his partner to obtain one good quality blastocyst via intracytoplasmic sperm injection following oocyte retrievals. Finally, the couple had a successful pregnancy following a frozen embryo transfer, and a live male infant was subsequently delivered to them at 39 weeks and 5 days. In cases of severe testicular dysfunction, varicocelectomy may worsen the postoperative semen parameters until azoospermia. Therefore, it is important to consider preoperative sperm cryopreservation and to explore the possibility of subsequent TESE.

Interpretable machine learning models for predicting clinical pregnancies associated with surgical sperm retrieval from testes of different etiologies: a retrospective study.

BACKGROUND: The relationship between surgical sperm retrieval of different etiologies and clinical pregnancy is unclear. We aimed to develop a robust and interpretable machine learning (ML) model for predicting clinical pregnancy using the SHapley Additive exPlanation (SHAP) association of surgical sperm retrieval from testes of different etiologies. METHODS: A total of 345 infertile couples who underwent intracytoplasmic sperm injection (ICSI) treatment with surgical sperm retrieval due to different etiologies from February 2020 to March 2023 at the reproductive center were retrospectively analyzed. The six machine learning (ML) models were used to predict the clinical pregnancy of ICSI. After evaluating the performance characteristics of the six ML models, the Extreme Gradient Boosting model (XGBoost) was selected as the best model, and SHAP was utilized to interpret the XGBoost model for predicting clinical pregnancies and to reveal the decision-making process of the model. RESULTS: Combining the area under the receiver operating characteristic curve (AUROC), accuracy, precision, recall, F1 score, brier score, and the area under the precision-recall (P-R) curve (AP), the XGBoost model has the best performance (AUROC: 0.858, 95% confidence interval (CI): 0.778-0.936, accuracy: 79.71%, brier score: 0.151). The global summary plot of SHAP values shows that the female age is the most important feature influencing the model output. The SHAP plot showed that younger age in females, bigger testicular volume (TV), non-tobacco use, higher anti-müllerian hormone (AMH), lower follicle-stimulating hormone (FSH) in females, lower FSH in males, the temporary ejaculatory disorders (TED) group, and not the non-obstructive azoospermia (NOA) group all resulted in an increased probability of clinical pregnancy. CONCLUSIONS: The XGBoost model predicts clinical pregnancies associated with testicular sperm retrieval of different etiologies with high accuracy, reliability, and robustness. It can provide clinical counseling decisions for patients with surgical sperm retrieval of various etiologies.

Reproductive characteristics and success rate of intracytoplasmic sperm microinjection in spinal cord injury infertile men: Retrospective cohort study.

BACKGROUND: Thanks to modern methods of assisted reproduction (ART), parenthood has become an attainable goal for couples in which the male partner has experienced spinal cord injury (SCI). OBJECTIVE: The aim of our study was to determine the success of the treatment of infertile patients with SCI with intracytoplasmic sperm injection (ICSI) of cryopreserved sperm obtained by the testicular sperm aspiration (TESA) procedure. METHODS: In this retrospective study 156 infertile couples were included, in which the male partner is primarily infertile due to azoospermia. Infertile couples were divided into two groups. The first group (n= 82) includes men with SCI, and the second (n= 74) men with obstructive azoospermia (OA) as the cause of infertility. All infertile men were examined and processed in the diagnostic procedure, and based on the urological findings, surgical extraction of sperm from the testicles was indicated. Exclusion criteria were the age of women over 40 and men over 45. RESULTS: We found that the quality of sperm was worse in the group with SCI, compared to the group with OA, but without statistical significance. Zenica and Johnsen score (p= 0.001; p= 0.000) showed worse semen characteristics in the group with SCI.     There were no significant differences in the average number of embryos (p= 0.698), pregnancy rates per cycle (p= 0.979) and pregnancy rates per embrio transfer (ET), clinical pregnancy rates per ET (p= 0.987) and delivery rates per ET (p= 0.804) in couples with SCI, compared to couples with OA. CONCLUSION: Based on the results of this research, the TESA and ICSI procedures can be recommended as a successful method in the treatment of male infertility caused by azoospermia due to SCI.

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: A cohort study. SETTING: University-affiliated male reproductive health center. PATIENT(S): A total of 616 consecutive patients with NOA and hypogonadism (total testosterone [T] levels <350 ng/dL) underwent micro-TESE between 2014 and 2021. All patients had no prior sperm retrieval (SR) history. INTERVENTION(S): Patients aged 23-55 years underwent comprehensive clinical, laboratory, and histopathological diagnostic evaluation for NOA and were further categorized into two cohorts on the basis of pre-SR hormonal stimulation. MAIN OUTCOME MEASURE(S): A 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 (aORs) and 95% confidence intervals (CIs) were computed to assess the relationship between SR success and relevant predictors. Sperm retrieval rates were compared between patients receiving or not hormonal stimulation, and logistic regression analysis evaluated the effect of baseline follicle-stimulating hormone levels (i.e., normogonadotropic vs. hypergonadotropic classes) on SR success. RESULT(S): The overall micro-TESE success rate was 56.6%. Baseline follicle-stimulating hormone levels (aOR, 0.97; 95% CI, 0.94-0.99), pre-SR hormonal stimulation (aOR, 2.54; 95% CI, 1.64-3.93), presence of clinical varicocele (aOR, 0.05; 95% CI, 0.01-0.51), history of previous varicocelectomy (aOR, 2.55; 95% CI, 1.26-5.16), and testicular histopathology were independent predictors of SR success. Among hormone-pretreated patients, pre-micro-TESE T levels and delta T (an absolute increase in T levels from baseline) were associated with SR success. A pre-micro-TESE T level of 418.5 ng/dL (area under the curve value: 0.78) and a delta T of 258 ng/dL (area under the value: 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(S): This study underscores the association between clinical factors and micro-TESE success in hypogonadal men with NOA. Although causality is not established, our findings suggest that these patients may benefit from pre-SR interventions, particularly hormonal stimulation and varicocele repair. CLINICAL TRIAL REGISTRATION NUMBER: NCT05110391.

Role of Follicle-stimulating Hormone, Inhibin B, and Anti-Müllerian Hormone in Predicting Sperm Retrieval from Men with Nonobstructive Azoospermia Undergoing Microdissection Testicular Sperm Extraction: A Systematic Review and Meta-analysis.

Background and objective: No clear-cut markers for predicting positive sperm retrieval (+SR) at microdissection testicular sperm extraction (mTESE) have been identified thus far. Our aim was to conduct a systematic review and meta-analysis to evaluate the ability of follicle-stimulating hormone (FSH), inhibin B (InhB), and anti-Müllerian hormone (AMH) to predict +SR in men with nonobstructive azoospermia (NOA) undergoing mTESE. Methods: We performed a search in the PubMed, EMBASE, Web of Science, and Scopus databases according to the Preferred Reporting Items for Systematic Review and Meta-analysis statement. Thirty-four publications were selected for inclusion in the analysis. Key findings and limitations: Overall, the mean +SR rate was 45%. Pooled standardized mean difference (SMD) values revealed significant hormonal differences between the +SR and -SR groups, with lower FSH (SMD -0.30), higher InhB (SMD 0.54), and lower AMH (SMD -0.56) levels in the +SR group. Pooled odds ratios (Ors) revealed no significant prediction of +SR by either FSH (OR 1.03, 95% confidence interval [CI] 1.00-1.06) or InhB (OR 1.01, 95% CI 1.00-1.02), despite variations in baseline levels and study heterogeneity. Conversely, AMH had significant predictive value (OR 0.82, 95% CI 0.73-0.92), with lower baseline levels in the +SR group. InhB and FSH levels were higher in the +SR group, while InhB exhibited the opposite trend. Conclusions and clinical implications: Despite study heterogeneity, our meta-analysis findings support the ability of AMH to predict +SR for men with NOA undergoing mTESE. Patient summary: We conducted a review and analysis of results from previous studies. Our findings show that for men with an infertility condition called nonobstructive azoospermia, blood levels of anti-Müllerian hormone can predict successful extraction of sperm using a microsurgical technique. Levels of two other hormones did not predict successful sperm extraction.

Association between embryo morphokinetic development and intracytoplasmic sperm injection with epididymal sperm via time-lapse imaging.

The objective of this study was to investigate the impact of sperm source on embryo morphokinetics and the clinical outcomes of intracytoplasmic sperm injection (ICSI) cycles by considering the clustering of data (multiple embryos per patient that share a comparable developmental timing). This matched cohort study was performed at a private university-affiliated in vitro fertilization center. Women who underwent ICSI with epididymal sperm between January 2019 and December 2020 (the percutaneous epididymal sperm aspiration group, n = 32 cycles) were matched with women who underwent ICSI with ejaculated sperm because of idiopathic male factor infertility (the male factor infertility [MFI] group, n = 32 cycles) or female infertility (the control group, n = 32 cycles). Embryos were cultured in a time-lapse imaging incubator, and morphokinetic development was recorded and compared among the groups. Significantly slower divisions were observed in embryos derived from epididymal sperm than in those derived from the MFI and control groups. Embryos derived from epididymal sperm had a significantly lower KIDScore (3.1 ± 0.2) than did those derived from ejaculated spermatozoa from the MFI (5.4 ± 0.1) and control (5.6 ± 0.2, p < 0.001) groups. Epididymal sperm-derived embryos showed a significantly greater occurrence of multinucleation (23.2%) than did those derived from ejaculated sperm from the MFI and control groups (2.8% and 3.7%, p < 0.001, respectively). Epididymal sperm-derived embryos were significantly more likely to undergo direct or reverse cleavage (11.1%) than ejaculated sperm-derived embryos in the control group (4.3%, p = 0.001). In conclusion, delayed cell cleavage and increased incidences of blastomere multinucleation and abnormal cleavage patterns are observed when epididymal-derived sperm are used for ICSI.

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.

Intratesticular Testosterone and Its Precursors among Azoospermic Men: A Pilot Study.

PURPOSE: The study aimed to comprehensively analyze testosterone and precursor concentrations in the testicular interstitial fluid (TIF) of men with azoospermia, exploring their significance in the testicular microenvironment and their correlation with testicular sperm retrieval outcomes. MATERIALS AND METHODS: We analyzed 37 TIF samples, including 5 from men with obstructive azoospermia (OA) and 32 from men with non-obstructive azoospermia (NOA). Liquid chromatography with tandem mass spectrometry quantified testosterone and precursor levels. Comparative assessments of the outcomes of testicular sperm retrieval were performed between the OA and NOA groups as well as among men with NOA. RESULTS: Men with NOA who had not undergone hormone treatment exhibited significantly higher intratesticular concentrations of testosterone (median 1,528.1 vs. 207.5 ng/mL), androstenedione (median 10.6 vs. 1.9 ng/mL), and 17-OH progesterone (median 13.0 vs. 1.8 ng/mL) than men diagnosed with OA. Notably, in the subgroup of patients with NOA subjected to medical treatment, men with successful sperm retrieval had significantly reduced levels of androstenedione (median androstenedione 5.7 vs. 18.5 ng/mL, p=0.004). Upon a more detailed analysis of these men who underwent hormone manipulation treatment, the testosterone/androstenedione ratio (indicative of HSD17B3 enzyme activity) was markedly increased in men with successful sperm retrieval (median: 365.8 vs. 165.0, p=0.008) compared with individuals with NOA who had unsuccessful sperm recovery. Furthermore, within the subset of men with NOA who did not undergo medical treatment before microdissection testicular sperm extraction but achieved successful sperm retrieval, the ratio of 17-OH progesterone/progesterone (indicative of CYP17A1 activity) was substantially higher. CONCLUSIONS: The study suggests distinct testosterone biosynthesis pathways in men with compromised spermatogenesis and those with normal spermatogenesis. Among NOA men with successful retrieval after hormone optimization therapy, there was decreased androstenedione and increased HSD17B3 enzyme activity. These findings have diagnostic and therapeutic implications for the future.

Testicular sperm retrieval for intracytoplasmic sperm injection: when to consider it after unsuccessful intracytoplasmic sperm injection with ejaculated sperm?

BACKGROUND: The question of whether patients are more likely to succeed with testicular sperm intracytoplasmic sperm injection (T-ICSI) after unsuccessful ICSI with ejaculated sperm (Ej-ICSI) remains unknown. OBJECTIVE: The study aimed to identify potential predictors of successful T-ICSI in men with idiopathic infertility and oligozoospermia (sperm concentration < 15 × 106/mL, non-azoospermic) who had previously experienced unsuccessful Ej-ICSI. MATERIALS AND METHODS: In total, 154 couples with male partners who had oligozoospermic conditions after two unsuccessful cycles of Ej-ICSI switched to T-ICSI. Before initiating T-ICSI, the sperm DNA fragmentation index (DFI) was assessed in ejaculated specimens. Participants were divided into two groups: group A (live birth (+), n = 60) and group B (live birth (-), n = 94). RESULTS: Fertilization, clinical pregnancy, live births, and miscarriages had rates of 72.7%, 44.2%, 39%, and 5.2%, respectively. The total motile sperm (TMS) count in group A was significantly higher (3.8 ± 1.5 million) than in group B (3 ± 1.6 million; p = 0.002). DFI was significantly higher in group A (24.2 ± 12.3) than in group B (18.1 ± 11; p = 0.001). Hormone levels and oocyte counts showed no statistically significant differences between groups. Multivariate regression analysis revealed that TMS (odds ratio [OR]: 1.46; 95% CI, 1.14-1.87, p = 0.003) and DFI (OR: 1.04; 95% CI, 1.01-1.08, p = 0.009) were found to be significant predictors of live birth outcomes. At a cutoff point of 2.55 (area under the curve [AUC] = 0.65), the optimal sensitivity and specificity values for TMS were 78% and 48%, respectively. At a cutoff point of 25.8 (AUC = 0.65), DFI had a maximum sensitivity of 51.7% and a specificity of 78.7%. CONCLUSIONS: TMS and DFI were found to be significant predictors of live birth outcomes in couples with oligozoospermic male partners undergoing T-ICSI. These findings may help clinicians tailor treatment strategies for this specific patient population.

Global Practice Patterns and Variations in the Medical and Surgical Management of Non-Obstructive Azoospermia: Results of a World-Wide Survey, Guidelines and Expert Recommendations.

PURPOSE: Non-obstructive azoospermia (NOA) is a common, but complex problem, with multiple therapeutic options and a lack of clear guidelines. Hence, there is considerable controversy and marked variation in the management of NOA. This survey evaluates contemporary global practices related to medical and surgical management for patients with NOA. MATERIALS AND METHODS: A 56-question online survey covering various aspects of the evaluation and management of NOA was sent to specialists around the globe. This paper analyzes the results of the second half of the survey dealing with the management of NOA. Results have been compared to current guidelines, and expert recommendations have been provided using a Delphi process. RESULTS: Participants from 49 countries submitted 336 valid responses. Hormonal therapy for 3 to 6 months was suggested before surgical sperm retrieval (SSR) by 29.6% and 23.6% of participants for normogonadotropic hypogonadism and hypergonadotropic hypogonadism respectively. The SSR rate was reported as 50.0% by 26.0% to 50.0% of participants. Interestingly, 46.0% reported successful SSR in <10% of men with Klinefelter syndrome and 41.3% routinely recommended preimplantation genetic testing. Varicocele repair prior to SSR is recommended by 57.7%. Half of the respondents (57.4%) reported using ultrasound to identify the most vascularized areas in the testis for SSR. One-third proceed directly to microdissection testicular sperm extraction (mTESE) in every case of NOA while others use a staged approach. After a failed conventional TESE, 23.8% wait for 3 months, while 33.1% wait for 6 months before proceeding to mTESE. The cut-off of follicle-stimulating hormone for positive SSR was reported to be 12-19 IU/mL by 22.5% of participants and 20-40 IU/mL by 27.8%, while 31.8% reported no upper limit. CONCLUSIONS: This is the largest survey to date on the real-world medical and surgical management of NOA by reproductive experts. It demonstrates a diverse practice pattern and highlights the need for evidence-based international consensus guidelines.

Understanding posthumous sperm retrieval during war through a terror management theory perspective.

Terror Management Theory (Tmt, solomon et al., 1991) claims that individuals use three anxiety buffer mechanisms to regulate their death awareness - cultural worldviews, self-esteem, and proximity seeking. In this article, we use these three TMT anxiety buffers to explain the phenomenon of posthumous sperm retrieval, requested by spouses or parents, usually of young soldiers who died during their military service. Whereas this phenomenon has been known for some time, it increased dramatically in the initial days following the massacre conducted by the Hamas terrorist organization in Israel on October 7, 2023. We claim that this was an immediate reaction to this terror event, which posed a direct, existential threat to those who were exposed to the massacre and the soldiers who defended the country, but also to the entire Israeli society, as well as for Jews around the globe. We use interpretive phenomenology to qualitatively examine the phenomenon of retrieving sperm from dead young men, analyzing the requests to retrieve sperm posthumously as a sign of the need to provide these young men with symbolic immortality, on both personal and national levels. We integrate this explanation with the military ethos and the tendency of Israeli society to endorse familyist and pronatalist values to expand our understanding of this contemporary phenomenon in Israel.

The relationship of testicular stiffness with Johnsen score and sperm retrieval outcome in men with non-obstructive azoospermia.

Background: The pathological Johnsen score (JS) is a quantitative histological scoring system used to assess spermatogenesis in men with nonobstructive azoospermia (NOA), while elastic modulus derived from shear wave elastography (SWE) is a diagnostic tool for evaluating spermatogenic dysfunction. In this prospective observational study, we aimed to investigate whether testicular stiffness measured by SWE could serve as a substitute for JS in predicting sperm retrieval outcomes in men with NOA. Methods: This prospective cohort study analyzed 140 testes from 115 consecutive outpatient participants with NOA who had sought treatment at the reproductive medical center of a tertiary care hospital between January 2018 and October 2021. Testicular volume, elastic modulus, JS, and sperm retrieval outcomes were calculated. Statistical differences in parameters between the positive and negative sperm retrieval groups were determined using the Mann-Whitney test. Spearman rank correlation analysis was performed to determine the correlations between JS and either testicular volumes or elastic modulus. Receiver operating characteristic (ROC) curves were drawn to evaluate the diagnostic performance of the testicular elastic modulus and testicular volume. Results: The JS correlated positively with testicular volume and negatively with the maximum elastic modulus (Emax) and mean elastic modulus (Emean), with correlation coefficients of 0.804, -0.686, and -0.456, respectively (P<0.01). There were significant differences in JS, testicular volume, and Emax between participants with positive and negative sperm retrieval of microdissection testicular sperm extraction (micro-TESE) (P<0.01). ROC curves were plotted for JS, testicular volume, and Emax to distinguish between participants with positive and negative sperm retrieval. The areas under the ROC curves (AUCs) were 0.783 [95% confidence interval (CI): 0.707-0.859; P<0.01], 0.737 (95% CI: 0.651-0.823; P<0.01), and 0.729 (95% CI: 0.643-0.814; P<0.01), respectively. When the cutoff value of JS was 4.5, its sensitivity and specificity were 60.3% and 89.6%, respectively. When the cutoff value of Emax was 3.75 kPa, its sensitivity and specificity were 79.1% and 64.4%, respectively. The sensitivity and specificity were 68.5% and 83.6%, respectively when the cutoff value of testicular volume was 8.17 mL. Emax combined with testicular volume improved this diagnostic value, with an AUC of 0.742 (95% CI: 0.657-0.828; P<0.01), and sensitivity and specificity were 83.6% and 68.5%, respectively. Conclusions: Our study suggests that the combination of testicular stiffness and volume measurements may serve as a viable alternative to pathological JS in predicting the likelihood of successful sperm retrieval prior to micro-TESE procedures.

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

Objective: 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. Design: A retrospective cohort study conducted between 2002 and 2017. Setting: An academic medical center. Patients: A total of 28 azoospermic postchemotherapy cancer survivors who underwent mTESE. Interventions: Chemotherapy exposure and mCED calculation. Main Outcome Measures: 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. Results: 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. Conclusion: 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.

Micromapping testicular sperm extraction: A new technique for microscopic testicular sperm extraction in nonobstructive azoospermia.

Purpose: In microscopic testicular sperm extraction (mTESE) for nonobstructive azoospermia (NOA), sperm can be recovered relatively easily in some cases, and mTESE may be retrospectively considered excessive. However, mTESE is routinely performed in the majority of NOA patients because of the difficulty in predicting tissue status. A minimally invasive and comprehensive sperm retrieval method that allows on-the-spot tissue assessment is needed. We have developed and evaluated a novel sperm retrieval technique for NOA called micromapping testicular sperm extraction (MMTSE). Methods: MMTSE involves dividing the testis into four sections and making multiple small needle holes in the tunica albuginea to extract seminiferous tubules and retrieve sperm. The sperm-positive group by MMTSE (Group I) underwent additional tissue collection (ATC) via a small incision, whereas the sperm-negative group by MMTSE (Group 0) underwent mTESE. Results: In total, 40 NOA participants underwent MMTSE. Group I included 15 patients and Group 0 included 25 patients. In Group 1, sperm were recovered from all patients by ATC. In Group 0, sperm were recovered in 4 of 25 cases using mTESE. Conclusions: MMTSE shows promise as a simple method that comprehensively searches testicular tissue and retrieves sperm using an appropriate method while minimizing patient burden.

Ethical Considerations in Post-Mortem Sperm Retrieval: A Comprehensive Review.

This comprehensive review delves into the moral and ethical dilemmas surrounding post-mortem sperm retrieval (PMSR) and its implications for creating new individuals. The paper examines the challenges posed by unusual requests for sperm retrieval from the deceased's widow and parents, as well as the broader socio-ethical considerations associated with PMSR. These requests have often been denied due to the absence of established laws and guidelines governing posthumous sperm retrieval and subsequent births, which were once deemed impossible. While some countries have implemented institutional policies to regulate its use to some extent, there remains a lack of standardized rules and procedures for the collection and retrieval of sperm after death. It is essential to introduce institutional guidelines to facilitate requests for assisted reproductive technology (ART) following successful sperm retrieval. Additionally, the development of PMSR legislation is necessary to ensure a proper balance between the moral rights and fundamental rights of the deceased, their family, and any current or future offspring, while providing adequate protection for all parties involved.

Estimation of B-inhibin and anti mullerian hormone in functional azoospermia and their correlations with surgical sperm retrieval: A prospective case-control study.

OBJECTIVES: The current study estimated the levels of anti mullerian hormone (AMH) and inhibin-B and reproductive hormones in non obstructive azoospermic (NOA) cases and obstructive azoospermic (OA) cases as well as comparing between them as regards the sensitivity and specificity in determining the sperm retrieval hope in the NOA cases. Finally, we analyzed any potential correlation between all the hormones measured in the current study. METHODS: The current case control study was conducted at the andrology outpatient clinic from June (2021) to March (2022). The study recruited 135 participants divided equally into three groups NOA cases, OA cases and controls, respectively. RESULTS: The mean inhibin-B was significantly lower in the NOA cases compared to the OA cases and the controls. There was a positive moderate correlation between AMH and Inhibin-B. Also, there was a positive moderate correlation between inhibin-B and free testosterone (FT) and positive weak correlation between beta Inhibin and leutinizing hormone (LH). CONCLUSIONS: The current study asserts the observation that inhibin-B is also expressed by Leydig cells as it has demonstrated positive correlations with FT and LH.

Genetic profiling of azoospermic men to identify the etiology and predict reproductive potential.

PURPOSE: To identify germline mutations related to azoospermia etiology and reproductive potential of surgically retrieved spermatozoa, and to investigate the feasibility of predicting seminiferous tubule function of nonobstructive azoospermic men by transcriptomic profiling of ejaculates. MATERIALS AND METHODS: Sperm specimens were obtained from 30 men (38.4 ± 6 years) undergoing epididymal sperm aspiration for obstructive azoospermia (OA, n = 19) acquired by vasectomy, or testicular biopsy for nonobstructive azoospermia (NOA, n = 11). To evaluate for a correlation with azoospermia etiology, DNAseq was performed on surgically retrieved spermatozoa, and cell-free RNAseq on seminal fluid (n = 23) was performed to predict spermatogenesis in the seminiferous tubule. RESULTS: Overall, surgically retrieved sperm aneuploidy rates were 1.7% and 1.8% among OA and NOA cohorts, respectively. OA men carried housekeeping-related gene mutations, while NOA men displayed mutations on genes involved in crucial spermiogenic functions (AP1S2, AP1G2, APOE). We categorized couples within each cohort according to ICSI clinical outcomes to investigate genetic causes that may affect reproductive potential. All OA-fertile men (n = 9) carried mutations in ZNF749 (sperm production), whereas OA-infertile men (n = 10) harbored mutations in PRB1, which is essential for DNA replication. NOA-fertile men (n = 8) carried mutations in MPIG6B (stem cell lineage differentiation), whereas NOA-infertile individuals (n = 3) harbored mutations in genes involved in spermato/spermio-genesis (ADAM29, SPATA31E1, MAK, POLG, IFT43, ATG9B) and early embryonic development (MBD5, CCAR1, PMEPA1, POLK, REC8, REPIN1, MAPRE3, ARL4C). Transcriptomic assessment of cell-free RNAs in seminal fluid from NOA men allowed the prediction of residual spermatogenic foci. CONCLUSIONS: Sperm genome profiling provides invaluable information on azoospermia etiology and identifies gene-related mechanistic links to reproductive performance. Moreover, RNAseq assessment of seminal fluid from NOA men can help predict sperm retrieval during testicular biopsies.

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.

Ex-vivo microscopic oncotesticular sperm extraction: step-by-step surgical technique at time of radical orchiectomy.

OBJECTIVE: To demonstrate the intraoperative surgical techniques required for simultaneous radical orchiectomy and microscopic oncotesticular sperm extraction (m-OncoTESE) in a step-by-step fashion. DESIGN: Video presentation. SETTING: University Hospital (University of Chicago). PATIENTS: A 37-year-old man (status after right orchiectomy at another institution for stage II-C testicular seminoma with positive preoperative tumor markers) was referred for contralateral orchiectomy of multifocal left testis mass and fertility preservation. Semen analysis before, microscopic testicular sperm extraction during, and semen or testicular specimen analysis after the first orchiectomy were unable to identify any sperm. A postoperative analysis of the m-OncoTESE performed on the left testis resulted in the cryopreservation of 200,000 motile sperm for future assisted reproductive technology (i.e., in vitro fertilization or in vitro fertilization-intracytoplasmic sperm injection). INTERVENTIONS: Left radical orchiectomy and left m-OncoTESE. MAIN OUTCOME MEASURES: A comprehensive visual documentation of m-OncoTESE surgical techniques with concurrent commentary detailing the reasons behind each surgical step. A brief discussion on the background of m-OncoTESE and alternative fertility preservation methods accompanies the procedure. RESULTS: This video provides a step-by-step guide to performing an m-OncoTESE (proceeding a radical orchiectomy in a patient with testicular cancer) as a means of fertility preservation in an azoospermic patient. Successful extraction and cryopreservation of testicular spermatozoa were achieved after targeted ex-vivo testicular microdissection. CONCLUSIONS: Sperm extraction via m-OncoTESE is a viable option for azoospermic patients with testicular cancer undergoing radical orchiectomies. The use of preoperative imaging and microsurgical techniques facilitates and optimizes surgical dissection and sperm recovery.

Effectiveness of, and Satisfaction with, a Microsurgical Testicular Sperm Extraction Knowledge and Skills Masterclass for a World-Wide Audience.

PURPOSE: This is the first study to assess the impact of an online microsurgical testicular sperm extraction (mTESE) masterclass. We: 1) describe the masterclass's scientific content; 2) appraise the participants' acquisition of knowledge; 3) gauge whether the extent of improvement of the participants' knowledge/skills was influenced by demographic/professional attributes; and 4) evaluate the participants' satisfaction. MATERIALS AND METHODS: This masterclass comprised five didactic lectures followed by 4 case discussions. Online surveys assessed the above objectives using a baseline questionnaire including demographics and past mTESE experience/training, a 24-question pre- and post-quiz, and a satisfaction questionnaire. RESULTS: Participants were between 20-70 years old, with 80.37% males, mainly from Asia, Africa, and Europe, from clinical backgrounds (69.3%), and in public practice (64.4%). Half the sample reported no past mTESE training and very low skills, ≈60% wanted considerably more training, and 50% felt that good training was not readily available. Satisfaction was 98% to >99%. Pre- and post-quiz comparisons confirmed remarkable improvements in knowledge/skills, exhibiting five striking characteristics. Improvements were a) Broad i.e., across 19 of the 24 mTESE questions; b) Deep, of magnitude, as pre-/post-quiz scores improved from mean 13.71±4.13 to 17.06±4.73; c) Highly significant, consistently with p-values <0.001; d) Inclusive i.e., all participants enhanced their mTESE knowledge/skills regardless of demographic/professional attributes; and, e) Differential, e.g., non-clinical/clinical participants improved, but the former improved relatively significantly more, those with ≤5-year experience improved significantly more than those with >5-year, those in public practice significantly more than private practice participants, and those with lower self-rating in performing mTESE significantly more than those with higher self-rating. CONCLUSIONS: The masterclass was successful with very high satisfaction levels, and markedly improved mTESE knowledge/skills among the participants. Global Andrology Forum's model can be adopted by organizations with similar goals. Future research needs to evaluate such training to develop a practically non-existent evidence base.