Changes in Testosterone Levels Following Surgical Sperm Retrieval in Men with Non-Obstructive Azoospermia: Systematic Review and Meta-Analysis.

PURPOSE: Surgical sperm retrieval (SSR) is used to extract spermatozoa for use with intracytoplasmic sperm injection in men with obstructive and non-obstructive azoospermia (NOA). The procedure may lead to segmental devascularization, postoperative fibrosis, and atrophy with a subsequent decrease in testosterone. The aim of the study is to investigate the impact of SSR on serum levels of total testosterone (TT), follicle-stimulating hormone (FSH), luteinizing hormone (LH) testicular volume, and sexual function in infertile azoospermic men. MATERIALS AND METHODS: In this systematic review and meta-analysis (SRMA), we searched articles in "PubMed" and "Scopus" exploring the impact of SSR on TT, FSH, LH, and testicular volume. The full-text articles were screened to assess eligibility before data extraction, quality assessment, and meta-analysis. RESULTS: Seventeen studies meeting the inclusion criteria were finally analyzed and included 1,685 infertile, azoospermic men. Patients underwent SSR and were followed in the postoperative period (one week to 32 months). The analysis showed a significant reduction in TT (mean difference [MD] 3.81 nmol/L, 95% confidence interval [CI] 0.55:7.06; p=0.02) compared to pre-SSR values. We also observed insignificant differences in serum FSH (MD 5.08 IU/L, 95% CI -5.6:15.8; p=0.35), LH (MD -2.96 IU/L, 95% CI -6.31:0.39; p=0.08), and no change in testicular volume (MD 0.07 mL, 95% CI -1.92:2.07; p=0.94) after SSR. Sexual dysfunction was associated with hypogonadism, depression, and anxiety, especially in men with unsuccessful SSR and Klinefelter syndrome. CONCLUSIONS: The results of this SRMA indicate a significant reduction in TT after SSR. Sexual dysfunction after testicular sperm extraction and the potential negative impact of future SSR repeat should be considered during preoperative counseling.

Sperm extraction in nonmosaic Klinefelter syndrome patients: A case series and literature review of sperm extraction in Klinefelter syndrome patients.

Objectives: Klinefelter syndrome (KF) is a group of chromosomal disorders with at least one extra X chromosome in male individuals that leads to infertility and diminished hair growth in affected males. In this study, we present a case series of 16 nonmosaic KF and an extensive literature review. Patients and Methods: This is a retrospective study including 16 nonmosaic Klinefelter Syndrome patients that underwent micro-testicular sperm extraction (m-TESE) at our center between January 2016 and December 2022. Frequencies and percentages were used to present categorical variables, whereas continuous variables were presented as the median and interquartile range (IQR). The sperm retrieval rate (SRR) was assessed using a one-sample proportions test with continuity correction. Fisher's exact test was to assess the differences between patients with negative and positive retrieval in terms of the categorical variables. A Wilcoxon rank-sum test was applied to explore the between-group differences in the numerical variables. A literature search was performed for additional publications of discussing m-TESE among KF patients. Results: The median (IQR) age of patients was 40.0 years (34.5-47.0). All of the patients had nonobstructive azoospermia, and the majority of them (93.8%) had primary infertility. The most common histopathological findings were atrophic tubules (57.1%), followed by Sertoli cell-only (28.6%). Sperm retrieval was positive for two patients with a rate of 12.5% (95% confidence interval 2.2 to 39.6). Patients with positive sperm retrieval were significantly younger than their peers with negative retrieval (median = 28.0, IQR = 27.5 to 28.5 vs. median = 41.5, IQR = 35.8 to 47.0, P = 0.031). The successful conception rate was 100% (n = 2) using intracytoplasmic sperm injection with a birth rate of 100% (n = 2). Conclusion: Our observed SRR among nonmosaic KF patients was marginally lower than the reported literature. Younger-age patients were significantly more likely to benefit from the procedure.

Israeli men's attitudes toward posthumous reproduction and prior consent amid ongoing armed conflict.

BACKGROUND: From October 7, 2023, until August 28, 2024, 187 posthumous sperm retrieval (PSR) procedures have been conducted on deceased men, 171 of whom are soldiers. PSR was predominantly initiated by parents to cope with their profound loss. However, the attitudes of Israeli men toward this procedure are unknown. OBJECTIVE: This study aims to investigate the attitudes of Israeli men toward prior consent to PSR and posthumous-assisted reproduction (PAR) initiated by partner or parents. METHODS: A cross-sectional study of 600 Israeli men aged 18-49 years who were questioned in February-April 2024 amid the ongoing armed conflict. The questionnaire included demographic details, role in the conflict, and attitudes toward PSR/PAR. Multivariable logistic regression analysis was used to assess agreement for PSR/PAR after adjustment for possible confounders. RESULTS: The average age of participants was 32 years, with 52% married or in a committed relationship and 6.5% self-identified as having same-sex relationships. The majority were secular (63%), 21% were traditional (21%), and 16% were religious. In terms of involvement in the ongoing conflict, 35% served in combat, 21% in non-combat roles, and 44% did not participate. Most men (71%) prefer pre-documenting their PSR preferences, with 70% advocating for consent during recruitment for regular military service and 78% before reserve service. Regarding PAR, 37% opposed it at their partner's request, while 47% opposed it at their parents' request. In a multivariable model, the odds of approval of PAR following parental request were four- and three-fold higher among traditional and secular versus religious men (odds ratio, OR = 4.1, 95% CI: 2.0-8.1 and OR = 3.3, 95% CI: 1.8-6.2, respectively) and following the request of a partner, twice higher among traditional and secular versus religious (OR = 2.0, 95% CI: 1.1-4.2 and OR = 2.0, 95% CI: 1.1-3.6, respectively). CONCLUSION: While it is understandable that grieving parents seek solace through PSR, consent should be obtained from the men themselves, as a considerable proportion do not support the process as it is currently performed.

The experience of transfeminine adolescents and their parents regarding fertility preservation via testicular sperm extraction (TESE): a qualitative study.

STUDY QUESTION: How do transfeminine adolescents and their parents experience fertility preservation via testicular sperm extraction (TESE)? SUMMARY ANSWER: Participants experienced the TESE process positively when provided with appropriate guidance to navigate the decisional dilemma between preserving future biological parenthood and the pressure to start puberty suppression early. WHAT IS KNOWN ALREADY: Sperm banking through ejaculation is not feasible for all transfeminine adolescents due to genital dysphoria and early puberty; for this group, TESE is the only alternative. However, during early puberty, they must postpone or pause puberty suppression until spermatogenesis is fully developed. STUDY DESIGN, SIZE, DURATION: All consecutive TESE patients in our centre and their parents were invited to participate. Between December 2022 and May 2023, we included 6 adolescents and 10 parents. We used a qualitative approach based on semi-structured interviews to study the experience of the transfeminine adolescents and their parents. PARTICIPANTS/MATERIALS, SETTING, METHODS: Transfeminine adolescents diagnosed with gender dysphoria in early puberty (Tanner stage ≥2) who underwent TESE before the start of puberty suppression or gender-affirming hormones participated in this study. The interviews were recorded, manually transcribed and analysed using reflective thematic analysis focusing on understanding the participants' experiences of puberty and fertility preservation and the various factors and social processes influencing their decision to undergo TESE. MAIN RESULTS AND THE ROLE OF CHANCE: Transfeminine adolescents decide to undergo invasive fertility preservation because of a possible, future desire for parenthood. Parents stressed the importance of preventing future decisional regret. They both saw masturbation to obtain a semen sample as unreachable. Even though TESE is a surgical procedure with possible complications and pain afterwards, this alternative seemed less dysphoric to them.Adolescents had to postpone the start of puberty suppression, waiting for spermatogenesis to complete. Given the unpredictable development of puberty, they felt a lot of stress and anxiety during this period and were primarily concerned about the lowering of their voice. Because of this puberty-related stress, they were constantly balancing their motivations for fertility preservation against the early start of puberty suppression to prevent unwanted irreversible pubertal body changes. To support this decisional dilemma, adolescents and their parents need adequate communication with each other and their healthcare providers to reflect on their stress for pubertal change. Furthermore, close, continuous surveillance of their current mental state by their parents, together with their psychologist and pubertal development by their physicians, is needed. Despite the challenging decision and postponement of puberty suppression, they retrospectively experienced it positively without any regret. LIMITATIONS, REASONS FOR CAUTION: All adolescents successfully underwent TESE, with viable spermatozoa obtained and without complications. This may result in a more positive reflective experience regarding fertility preservation. Furthermore, the perspectives of adolescents with the intention of TESE but who already started with puberty suppression before the preservation were not included. WIDER IMPLICATIONS OF THE FINDINGS: This study helps healthcare providers improve their counselling and guidance of transfeminine adolescents who consider postponing puberty suppression for fertility preservation via TESE. The adolescents and their parents know more clearly what to expect during fertility preservation. Specific peer-support programs may facilitate the decision process for upcoming adolescents. STUDY FUNDING/COMPETING INTEREST(S): No external funding was used for this study. None of the authors have any conflicts of interest. TRIAL REGISTRATION NUMBER: Not applicable.

Successful Sperm Retrieval and Clinical Pregnancies Following Micro-TESE and ICSI Treatments in Patients with Nonobstructive Azoospermia Due to Various Etiologies.

(1) Background: Nonobstructive azoospermia (NOA) etiologies affect the sperm retrieval rate (SRR) by microdissection testicular sperm extraction (micro-TESE) and the clinical outcomes following intracytoplasmic sperm injection (ICSI); (2) Methods: We investigated seven NOA etiologies. The SRR and clinical outcomes of 627 patients were analyzed between November 2017 and July 2022 in the Reproductive and Genetic Hospital of China International Trust and Investment Corporation-Xiangya (CITIC-Xiangya); (3) Results: The overall SRR was 39.4% (247/627). The SRR according to NOA etiologies were: Y chromosome azoospermia factor c microdeletions (26/46, 56.5%), Klinefelter syndrome (KS), 36/85, 42.4%), idiopathic (110/398, 27.6%), cryptorchidism (20/29, 69.0%), chromosome anomalies (7/13, 53.9%), orchitis (45/50, 90.0%), and cancer (3/6, 50.0%). The SRR were different for spermatogonia arrest (26/96, 27.1%), maturation arrest (76/177, 42.9%), and SCOS (30/80, 37.5%) according to histological examinations. The clinical pregnancy rate was similar among the NOA etiologies. The high-quality embryo rate differed between successful (54.7%) and unsuccessful (40.9%) pregnancies. Moreover, the successfully pregnant women (28.99 years) were younger than the unsuccessfully pregnant ones (30.92 years); (4) Conclusions: The SRR from patients with NOA was associated with the etiology and histological categories, while the clinical outcome was associated with the high-quality embryo rate and the female partner's age.

Non-Obstructive Azoospermia and Intracytoplasmic Sperm Injection: Unveiling the Chances of Success and Possible Consequences for Offspring.

Non-obstructive azoospermia (NOA) is found in up to 15% of infertile men. While several causes for NOA have been identified, the exact etiology remains unknown in many patients. Advances in assisted reproductive technology, including intracytoplasmic sperm injection (ICSI) and testicular sperm retrieval, have provided hope for these patients. This review summarizes the chances of success with ICSI for NOA patients and examines preoperative factors and laboratory techniques associated with positive outcomes. Furthermore, we reviewed possible consequences for offspring by the use of ICSI with testicular sperm retrieved from NOA patients and the interventions that could potentially mitigate risks. Testicular sperm retrieved from NOA patients may exhibit increased chromosomal abnormalities, and although lower fertilization and pregnancy rates are reported in NOA patients compared to other forms of infertility, the available evidence does not suggest a significant increase in miscarriage rate, congenital malformation, or developmental delay in their offspring compared to the offspring of patients with less severe forms of infertility or the offspring of fertile men. However, due to limited data, NOA patients should receive specialized reproductive care and personalized management. Counseling of NOA patients is essential before initiating any fertility enhancement treatment not only to mitigate health risks associated with NOA but also to enhance the chances of successful outcomes and minimize possible risks to the offspring.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.