Impact of short abstinence versus testicular sperm on sperm DNA fragmentation: a systematic review and meta-analysis.

PURPOSE: Optimal sperm DNA integrity is essential for fertilization and embryo health. Research indicates that testicular sperm (TS), obtained via TESA or TESE, typically show lower sperm DNA fragmentation (SDF) than ejaculated sperm after standard abstinence. Shortening abstinence to less than 2 days might reduce SDF, offering a less invasive and more cost-effective alternative to surgical sperm retrieval. Yet, no studies have directly compared the efficacy of shorter abstinence against TS extraction for lowering SDF. Our meta-analysis aims to address this gap by comparing SDF levels in TS to those in ejaculated sperm after a short abstinence period. METHODS: Meta-analysis of 16 randomized controlled and prospective observational studies included 4 on TS and 12 on short abstinence ejaculation. The meta-analysis followed MOOSE guidelines, scrutinizing databases including Cochrane Library, Web of Science, Embase, MEDLINE(R), and PUMBED up to November 16, 2023. The analysis was conducted using RevMan. The observational studies' methodological quality was assessed using the Newcastle-Ottawa Scale, and the overall evidence quality was evaluated following the GRADE criteria. To compare short ejaculation duration and TS (are not directly compared in the literature) for SDF levels, we analyzed relevant data from studies of each method. We adjusted the participant numbers in the TS group by 1/3 and included each TS study three times, to perform a comparison against the short duration studies which were in a ratio of 1:3. This approach maintained an unaltered cumulative subject count for the meta-analysis of TS studies. RESULTS: A total of 641 patients were included, comprising 120 and 521 patients with SDF measurements following TS and ejaculation after a short abstinence period, respectively. The studies had varied inclusion criteria, with not all patients having an initial elevated SDF. Some studies had incomplete details on age and other demographics. However, the mean ± SD age of 93 TS patients was 38.15 ± 5.48 years vs. 37.7 ± 6.0 years of 444 short abstinence patients, demonstrating no significant difference (P = 0.544). Short abstinence durations ranged from 1 to 48 h. Diverse DNA fragmentation tests were used: TUNEL assay in three testicular sperm studies, SCD assay in one, and in the short abstinence group, four used TUNEL and six used SCD assays, along with one each using SCSA and Halosperm. The mean ± SD SDF was lower in the TS group than in the short abstinence group (mean difference - 9.48, 95%CI - 12.45 to - 6.52, P < 0.001, I2 = 85%). Sensitivity analysis revealed that no single study significantly influenced the results. Employing the GRADE criteria, the initial assessment categorized the overall quality of evidence as low due to the observational nature of the acquired data. All studies were of medium to high quality. CONCLUSION: This study suggests testicular sperm may be better than ejaculated sperm for improving SDF in infertility cases. Direct comparisons are needed, before deeming short abstinence less effective. Future research should directly compare reproductive outcomes using both methods.

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.

Development of a deep-learning model for detecting positive tubules during sperm recovery for nonobstructive azoospermia.

To enhance surgical testicular sperm retrieval outcome for men with nonobstructive azoospermia, a deep-learning model was developed to identify positive seminiferous tubules by labeling 110 images with sperm-containing tubules sampled during microdissection testicular sperm extraction as training and validation data. After training, the model achieved an average precision of 0.60.

Association between anti-Müllerian hormone concentrations and sperm retrieval outcomes in patients with idiopathic nonobstructive azoospermia: a systematic review and meta-analysis.

ABSTRACT: Microdissection testicular sperm extraction (mTESE) is commonly performed to retrieve sperm in the testes for assisted reproductive techniques in patients with idiopathic nonobstructive azoospermia (iNOA). However, the success rate of sperm retrieval varies among individuals. We aim to investigate the association between clinical parameters and sperm retrieval outcomes in patients with iNOA. We searched PubMed, EMBASE, and Web of Science from database inception to August 2, 2023. The main measure was whether sperm retrieval was successful in patients with iNOA who underwent mTESE. Pooled estimates of the sperm retrieval rate and weighted mean differences were calculated using random-effects models. The overall sperm retrieval rate was 36.8% (95% confidence interval [CI]: 27.5%-46.0%, I2 = 95.0%) in nine studies comprising 1892 patients with iNOA. No significant differences were found in age, testicular volume, serum total testosterone concentrations, or inhibin B concentrations between positive and negative sperm retrieval outcomes. Lower anti-Müllerian hormone concentrations in patients with iNOA were associated with a positive outcome of mTESE (weighted mean differences: -2.70; 95% CI: -3.94--1.46, I2 = 79.0%). In conclusion, this study shows a significant relationship between anti-Müllerian hormone and sperm retrieval outcomes in patients with iNOA, while age, testicular volume, total testosterone, and inhibin B show no significant association. These findings have important implications for assessing the potential success of sperm retrieval and selecting appropriate treatment strategies in patients with iNOA.

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

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

In cases with raised sperm DNA fragmentation, can sperm selection by magnetic-activated cell sorting or testicular sperm aspiration help improve reproductive outcomes?

PURPOSE: To evaluate the efficacy of magnetic-activated cell sorting (MACS) or testicular sperm aspiration (TESA) to improve reproductive outcomes in cases with elevated sperm DNA fragmentation undergoing assisted reproduction. METHODS: This randomized controlled trial included couples with failed IVF cycles and sperm DNA fragmentation > 30%. Sperm DNA fragmentation was assessed using the sperm chromatin structure assay (SCSA) method. Participants were randomly assigned to either the MACS or TESA group. Testicular sperm retrieval was performed for the TESA group, while MACS involved sperm selection using magnetic beads. Extended blastocyst culture, freeze all policy of blastocysts by vitrification, and frozen embryo transfer were undertaken as per clinic's standard operating protocols. Blastocyst formation rate, implantation rate, miscarriage rate, multiple pregnancy rate, and live birth rate were analyzed and compared between MACS and TESA groups. RESULTS: There were no significant differences in female age, male age, or sperm DNA fragmentation index (DFI) between the MACS and TESA groups. The blastocyst conversion rate was slightly higher in the TESA group (39%) compared to the MACS group (32%). However, the MACS group had a higher implantation rate (50%) than the TESA group (35%). Miscarriage rates, multiple pregnancy rates, and live birth rates did not show statistically significant differences between the groups. A chi-squared test was conducted to compare categorical variables, and t-tests were done to compare continuous variables. CONCLUSION: In cases with raised sperm DNA fragmentation, sperm selection by MACS or TESA seems to offer comparable reproductive outcomes. There seems no superiority of one intervention over the other in cases with raised sperm DNA fragmentation undergoing assisted reproduction. Both interventions seem to be beneficial for couples seeking assisted reproduction with raised sperm DNA fragmentation.

Pregnancy and neonatal outcomes of ICSI using pentoxifylline to identify viable spermatozoa in patients with frozen-thawed testicular spermatozoa.

Introduction: Although the effectiveness of pentoxifylline (PF) as a selective inhibitor of phosphodiesterase to enhance sperm motility through increasing cyclic nucleotide in cases of absolute asthenozoospermia has been demonstrated for ICSI, data related to babies born from the PF-ICSI are still severely lacking. Concerns have been raised regarding the potential embryotoxicity of PF due to the controversial results obtained from the analysis of this compound on animal embryo development. This study aimed to determine whether the application of PF to trigger frozen-thawed TESA (testicular sperm aspiration) spermatozoa increases the risk of adverse obstetric and neonatal outcomes compared with non-PF frozen-thawed TESA ICSI and conventional ICSI using fresh ejaculation. Materials and methods: A total of 5438 patients were analyzed in this study, including 240 patients underwent PF-TESA ICSI (ICSI using PF triggered frozen-thawed testicular spermatozoa), 101 patients underwent non-PF TESA ICSI (ICSI using frozen-thawed testicular spermatozoa) and 5097 patients underwent conventional ICSI using fresh ejaculation. Propensity score matching was executed to control the various characteristics of patients. Results: No significant differences in pregnancy outcomes were observed among the three groups (PF-TESA ICSI, non-PF TESA ICSI and conventional ICSI), including biochemical pregnancy, clinical pregnancy, implantation, miscarriage, ectopic pregnancy, multiple pregnancy, and live birth, following propensity score matching. Additionally, neonatal outcomes were found to be similar among the three groups, with no statistical differences observed in the birth defect, birth weight, gestational age, preterm birth, and early-neonatal death. Discussion and conclusion: PF-ICSI may be an alternative treatment in patients using frozen-thawed testicular spermatozoa, resulting in comparable pregnancy and neonatal outcomes.

[Artificial intelligence: to a better predictive strategy for testicular sperm extraction outcome in azoospermia]. / Intelligence artificielle : vers une meilleure stratégie de prédiction du résultat de la biopsie testiculaire dans un contexte d'azoospermie.

Azoospermia, defined as the absence of sperm in the semen, is found in 10-15 % of infertile patients. Two-thirds of these cases are caused by impaired spermatogenesis, known as non-obstructive azoospermia (NOA). In this context, surgical sperm extraction using testicular sperm extraction (TESE) is the best option and can be offered to patients as part of fertility preservation, or to benefit from in vitro fertilization. The aim of the preoperative assessment is to identify the cause of NOA and evaluate the status of spermatogenesis. Its capacity to predict TESE success remains limited. As a result, no objective and reliable criteria are currently available to guide professionals on the chances of success and enable them to correctly assess the benefit-risk balance of this procedure. Artificial intelligence (AI), a field of research that has been rapidly expanding in recent years, has the potential to revolutionize medicine by making it more predictive and personalized. The aim of this review is to introduce AI and its key concepts, and then to examine the current state of research into predicting the success of TESE.

Non-invasive biomarkers for sperm retrieval in non-obstructive patients: a comprehensive review.

Recent advancements in reproductive medicine have guided novel strategies for addressing male infertility, particularly in cases of non-obstructive azoospermia (NOA). Two prominent invasive interventions, namely testicular sperm extraction (TESE) and microdissection TESE (micro-TESE), have emerged as key techniques to retrieve gametes for assisted reproduction technologies (ART). Both heterogeneity and complexity of NOA pose a multifaceted challenge to clinicians, as the invasiveness of these procedures and their unpredictable success underscore the need for more precise guidance. Seminal plasma can be aptly regarded as a liquid biopsy of the male reproductive tract, encompassing secretions from the testes, epididymides, seminal vesicles, bulbourethral glands, and prostate. This fluid harbors a variety of cell-free nucleic acids, microvesicles, proteins, and metabolites intricately linked to gonadal activity. However, despite numerous investigations exploring potential biomarkers from seminal fluid, their widespread inclusion into the clinical practice remains limited. This could be partially due to the complex interplay of diverse clinical and genetic factors inherent to NOA that likely contributes to the absence of definitive biomarkers for residual spermatogenesis. It is conceivable that the integration of clinical data with biomarkers could increase the potential in predicting surgical procedure outcomes and their choice in NOA cases. This comprehensive review addresses the challenge of sperm retrieval in NOA through non-invasive biomarkers. Moreover, we delve into promising perspectives, elucidating innovative approaches grounded in multi-omics methodologies, including genomics, transcriptomics and proteomics. These cutting-edge techniques, combined with the clinical and genetics features of patients, could improve the use of biomarkers in personalized medical approaches, patient counseling, and the decision-making continuum. Finally, Artificial intelligence (AI) holds significant potential in the realm of combining biomarkers and clinical data, also in the context of identifying non-invasive biomarkers for sperm retrieval.

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.

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.

Proteomic biomarkers in seminal plasma as predictors of reproductive potential in azoospermic men.

Introduction: Azoospermia, characterized by an absence of sperm in the ejaculate, represents the most severe form of male infertility. While surgical sperm retrieval in obstructive azoospermia (OA) is successful in the majority of cases, patients with non-obstructive azoospermia (NOA) show retrieval rates of only about 50% and thus frequently have unnecessary surgery. Surgical intervention could be avoided if patients without preserved spermatogenesis are identified preoperatively. This prospective study aimed to discover biomarkers in seminal plasma that could be employed for a non-invasive differential diagnosis of OA/NOA in order to rationalize surgery recommendations and improve success rates. Methods: All patients signed written informed consent, underwent comprehensive andrological evaluation, received human genetics to exclude relevant pathologies, and patients with azoospermia underwent surgical sperm retrieval. Using label-free LC-MS/MS, we compared the proteomes of seminal plasma samples from fertile men (healthy controls (HC), n=8) and infertile men diagnosed with 1) OA (n=7), 2) NOA with successful sperm retrieval (mixed testicular atrophy (MTA), n=8), and 3) NOA without sperm retrieval (Sertoli cell-only phenotype (SCO), n=7). Relative abundance changes of two candidate markers of sperm retrieval, HSPA2 and LDHC, were confirmed by Western Blot. Results: We found the protein expression levels of 42 proteins to be significantly down-regulated (p ≤ 0.05) in seminal plasma from SCO NOA patients relative to HC whereas only one protein was down-regulated in seminal plasma from MTA patients. Analysis of tissue and cell expression suggested that the testis-specific proteins LDHC, PGK2, DPEP3, and germ-cell enriched heat-shock proteins HSPA2 and HSPA4L are promising biomarkers of spermatogenic function. Western blotting revealed a significantly lower abundance of LDHC and HSPA2 in the seminal plasma of men with NOA (SCO and MTA) compared to controls. Discussion: The results indicate that certain testis-specific proteins when measured in seminal plasma, could serve as indicators of the presence of sperm in the testis and predict the success of sperm retrieval. Used in conjunction with conventional clinical assessments, these proteomic biomarkers may assist in the non-invasive diagnosis of idiopathic male infertility.

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.

Achieving an optimal pregnancy outcome through the combined utilization of micro-TESE and ICSI in cryptorchidism associated with a non-canonical splicing variant in RXFP2.

PURPOSE: To identify the genetic cause of a cryptorchidism patient carrying a non-canonical splicing variant highlighted by SPCards platform in RXFP2 and to provide a comprehensive overview of RXFP2 variants with cryptorchidism correlation. METHODS: We identified a homozygous non-canonical splicing variant by whole-exome sequencing and Sanger sequencing in a case with cryptorchidism and non-obstructive azoospermia (NOA). As the pathogenicity of this non-canonical splicing variant remained unclear, we initially utilized the SPCards platform to predict its pathogenicity. Subsequently, we employed a minigene splicing assay to further evaluate the influence of the identified splicing variant. Microdissection testicular sperm extraction (micro-TESE) combined with intracytoplasmic sperm injection (ICSI) was performed. PubMed and Human Genome Variant Database (HGMD) were queried to search for RXFP2 variants. RESULTS: We identified a homozygous non-canonical splicing variant (NM_130806: c.1376-12A > G) in RXFP2, and confirmed this variant caused aberrant splicing of exons 15 and 16 of the RXFP2 gene: 11 bases were added in front of exon 16, leading to an abnormal transcript initiation and a frameshift. Fortunately, the patient successfully obtained his biological offspring through micro-TESE combined with ICSI. Four cryptorchidism-associated variants in RXFP2 from 90 patients with cryptorchidism were identified through a literature search in PubMed and HGMD, with different inheritance patterns. CONCLUSION: This is the first cryptorchidism case carrying a novel causative non-canonical splicing RXFP2 variant. The combined approach of micro-TESE and ICSI contributed to an optimal pregnancy outcome. Our literature review demonstrated that RXFP2 variants caused cryptorchidism in a recessive inheritance pattern, rather than a dominant pattern.

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.

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

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

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

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

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.

Case report: remedial microdissection testicular sperm extraction after onco-microdissection testicular sperm extraction failure.

BACKGROUND: Testicular cancer (TC) mostly occurs in men aged 14 to 44. Studies have shown that TC seriously damages male fertility, and 6% to 24% of patients with TC were even found to suffer from azoospermia when they are diagnosed. At present, some studies have pointed out that onco-microdissection testicular sperm extraction (mTESE) can extract sperm from tumor testicles. However, there are almost no reports on remedial measures after onco-mTESE failure. Given the valuable opportunity for fertility preservation in patients with TC and azoospermia, it is necessary to provide effective remedial methods for patients with failed onco-mTESE. METHODS: Two young men, who were diagnosed with TC and also found to have azoospermia, tried onco-mTESE while undergoing radical orchiectomy for fertility preservation. However, sperm extraction failed in both patients. Subsequently, the isolated testicular tissue of the patient in case 1 suffered from TC again, and the patient in case 2 was scheduled to receive multiple cycles of gonadotoxic chemotherapy. Because both had a plan to have a birth in the future, we performed remedial mTESE. RESULTS: Sperm was successfully extracted from both patients. The patient recovered well, without complications. The patient couple in case 1 underwent 1 intracytoplasmic sperm injection (ICSI) cycle but did not achieve clinical pregnancy. CONCLUSIONS: There is still an opportunity to extract sperm successfully using onco-mTESE, despite the difficulty of fertility preservation in TC patients with azoospermia. If sperm extraction from the tumor testis fails, implementing remedial mTESE as early as possible would likely preserve the last chance of fertility for these patients.