Sperm Retrieval In Men Research Articles

Technologies to improve sperm retrieval in men undergoing micro-TESE for NOA.

Nonobstructive azoospermia (NOA) is considered the most challenging clinical scenario for infertile men and current treatments leave many men unsuccessful at being able to achieve a pregnancy with their partner using their own sperm. Microdissection testicular sperm extraction (micro-TESE) is the choice for men with NOA desiring to father children with their own gametes. Micro-TESE results in the highest numbers of sperm cells retrieved for use with in vitro fertilization/intracytoplasmic sperm injection. With suboptimal micro-TESE success rates of sperm retrieval and then pregnancy and live birth using the retrieved sperm with in vitro fertilization/intracytoplasmic sperm injection, advances to improve outcomes are necessary. This article comprehensively reviews the technologies investigated to date to improve the outcomes for men undergoing micro-TESE.

Clinical predictors of successful outcomes for couples with nonobstructive azoospermic male partners undergoing micro-TESE.

Nonobstructive azoospermia (NOA) is the most challenging and complex clinical scenario for infertile men. Besides circumstances such as hypogonadotropic hypogonadism, surgical sperm retrieval is typically necessary, and microdissection testicular sperm extraction (micro-TESE) is the procedure of choice for men with NOA desiring to father children with their own gametes. Micro-TESE results in the highest numbers of sperm cells retrieved for use with in vitro fertilization/intracytoplasmic sperm injection (ICSI) in comparison to all other techniques for surgical sperm retrieval in men with NOA. Several factors may affect sperm retrieval rate and ICSI outcomes, including the patient's age, testicular volume, histopathological and genetic profile, and serum hormone levels. This article aims to review the medical literature describing predictors of successful micro-TESE and the outcomes of ICSI in men with NOA.

O-260 Identifying seminiferous tubules for sperm retrieval during microdissection testicular sperm extraction (M-TESE) using deep learning

Abstract Study question Is it possible to utilize artificial intelligence (AI) in the selection of seminiferous tubules for sperm retrieval during microdissection testicular sperm extraction (M-TESE)? Summary answer AI algorithm was able to segment seminiferous tubules deemed to be good candidates for sperm retrieval with IoU of 0.746 and F1 score of 72.5%. What is known already M-TESE is an advanced surgical procedure reserved for sperm retrieval in men with non-obstructive azoospermia (NOA). Meta-analysis have shown M-TESE might be superior in relation to sperm retrieval rates and postsurgical complications when compared to conventional techniques. Limitations of the technique are the relatively long learning curve for the surgeons and the longer intraoperative time required to identify the tubules with active spermatogenesis. Convolutional neural networks (CNNs) have been shown to successfully identify areas of interest in medical images such as CT and MRI scans. The possibility of utilizing trained CNNs in M-TESE procedures has so far not been studied. Study design, size, duration This is a cross sectional study analyzing image data gathered during M-TESE procedures including the first five men enrolled in a prospective study designed specifically to test the utilization of AI in the treatment of NOA. All participants signed written informed consent. Images were collected intraoperatively with low and high resolution cameras according to predefined protocol. Participants/materials, setting, methods CNN model with down and upsampling architecture was trained using patch-based technique with corresponding labelled truth image pairs based on combination of semi-automated hue saturation value thresholding and manual segmentation of seminiferous tubules. Tubules were allocated into two different classes by the operating surgeon according to the visual perception of their morphology as type 1 (i.e. larger, opaque, good candidates for micro dissection) and type 2 (i.e. sclerotic or atrophic; unlikely to harbor active spermatogenesis). Main results and the role of chance CNN models were trained on 1809 patches with corresponding ground truth segmented images. Two algorithms were tested: the first was trained solely to detect and semantically distinguish type 1 seminiferous tubules. The second was trained to semantically segment the major anatomical structures: tunica albuginea, testicular parenchyma, blood vessels; lobules and the two types of seminiferous tubules describe above. Validation was performed on 988 image patches not previously shown to the algorithm. After grid search for optimal learning rate and augmentation the first algorithm was able to segment type 1 tubules with F1 score of 72.5% and Jaccard Index (IoU) of 0.746. Training took 856 minutes on 48 core high performance computer (HPC) equipped with single graphics processing unit (GPU). Same computational environment was used in the training of the second algorithm. This model was able to segment anatomical structures such as parenchyma (IoU=0.732) and testicular lobules (IoU=0.683) but performed sub optimally on the clinically relevant type 1 tubules (IoU=0.432). The first trained algorithm was able to segment a single high resolution surgical image in 3.4 seconds on an HPC. However, the same procedure took 5.5 minutes on standard desktop computer with 8 core Intel processor without GPU. Limitations, reasons for caution The number of patients is relatively small and therefore more training data would be needed to achieve robust performance. Training data were labelled by single surgeon limiting the generalizability and possibly biasing the selection process. The need of HPC environment for real time segmentation can limit the clinical use. Wider implications of the findings This pilot study shows the potential of AI to help in choosing suitable tubules for micro dissection, shortening the learning curve for young andrological surgeons. The access to cluster based computation is getting easier by the day and can soon allow instant intraoperative AI segmentation, thus shortening the surgical procedure. Trial registration number NA

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

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. 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. 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. 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.

A Machine Learning Approach for the Prediction of Testicular Sperm Extraction in Nonobstructive Azoospermia: Algorithm Development and Validation Study.

Testicular sperm extraction (TESE) is an essential therapeutic tool for the management of male infertility. However, it is an invasive procedure with a success rate up to 50%. To date, no model based on clinical and laboratory parameters is sufficiently powerful to accurately predict the success of sperm retrieval in TESE. The aim of this study is to compare a wide range of predictive models under similar conditions for TESE outcomes in patients with nonobstructive azoospermia (NOA) to identify the correct mathematical approach to apply, most appropriate study size, and relevance of the input biomarkers. We analyzed 201 patients who underwent TESE at Tenon Hospital (Assistance Publique-Hôpitaux de Paris, Sorbonne University, Paris), distributed in a retrospective training cohort of 175 patients (January 2012 to April 2021) and a prospective testing cohort (May 2021 to December 2021) of 26 patients. Preoperative data (according to the French standard exploration of male infertility, 16 variables) including urogenital history, hormonal data, genetic data, and TESE outcomes (representing the target variable) were collected. A TESE was considered positive if we obtained sufficient spermatozoa for intracytoplasmic sperm injection. After preprocessing the raw data, 8 machine learning (ML) models were trained and optimized on the retrospective training cohort data set: The hyperparameter tuning was performed by random search. Finally, the prospective testing cohort data set was used for the model evaluation. The metrics used to evaluate and compare the models were the following: sensitivity, specificity, area under the receiver operating characteristic curve (AUC-ROC), and accuracy. The importance of each variable in the model was assessed using the permutation feature importance technique, and the optimal number of patients to include in the study was assessed using the learning curve. The ensemble models, based on decision trees, showed the best performance, especially the random forest model, which yielded the following results: AUC=0.90, sensitivity=100%, and specificity=69.2%. Furthermore, a study size of 120 patients seemed sufficient to properly exploit the preoperative data in the modeling process, since increasing the number of patients beyond 120 during model training did not bring any performance improvement. Furthermore, inhibin B and a history of varicoceles exhibited the highest predictive capacity. An ML algorithm based on an appropriate approach can predict successful sperm retrieval in men with NOA undergoing TESE, with promising performance. However, although this study is consistent with the first step of this process, a subsequent formal prospective multicentric validation study should be undertaken before any clinical applications. As future work, we consider the use of recent and clinically relevant data sets (including seminal plasma biomarkers, especially noncoding RNAs, as markers of residual spermatogenesis in NOA patients) to improve our results even more.

Anti-Müllerian hormone predicts positive sperm retrieval in men with idiopathic non-obstructive azoospermia-findings from a multi-centric cross-sectional study.

Is it possible to identify a reliable marker of successful sperm retrieval (+SR) in men with idiopathic non-obstructive azoospermia (iNOA) undergoing microdissection testicular sperm extraction (mTESE)? A higher likelihood of +SR during mTESE is observed in men with iNOA and lower preoperative serum anti-Müllerian hormone (AMH) levels, with good predictive accuracy achieved using an AMH threshold of <4 ng/ml. AMH has been previously linked to +SR in men with iNOA undergoing mTESE prior to ART. A multi-centre cross-sectional study was carried out with a cohort of 117 men with iNOA undergoing mTESE at three tertiary-referral centres. Data from 117 consecutive white-European men with iNOA presenting for primary couple's infertility associated with a pure male factor at three centres were analysed. Descriptive statistics was applied to compare patients with negative (-SR) versus +SR at mTESE. Multivariate logistic regression models were fitted to predict +SR at mTESE, after adjusting for possible confounders. Diagnostic accuracy of the factors associated with +SR was assessed. Decision curve analyses were used to display the clinical benefit. Overall, 60 (51.3%) men had an -SR and 57 (48.7%) had a +SR at mTESE. Patients with +SR had lower levels of baseline AMH (P = 0.005) and higher levels of estradiol (E2) (P = 0.01). At multivariate logistic regression analysis, lower levels of AMH (odds ratio: 0.79; 95% CI: 0.64-0.93, P = 0.03) were associated with +SR at mTESE, after adjusting for possible confounders (e.g. age, mean testicular volume, FSH, and E2). A threshold of AMH <4 ng/ml achieved the highest accuracy for +SR at mTESE, with an AUC of 70.3% (95% CI: 59.8-80.7). Decision curve analysis displayed the net clinical benefit of using an AMH <4 ng/ml threshold. There is a need for external validation in even larger cohorts, across different centres and ethnicities. Systematic reviews and meta-analysis to provide high level of evidence are lacking in the context of AMH and SR rates in men with iNOA. Current findings suggest that slightly more than one in two men with iNOA had -SR at mTESE. Overall, men with iNOA with lower levels of AMH had a significantly higher percentage of successful SR at surgery. A threshold of <4 ng/ml for circulating AMH ensured satisfactory sensitivity, specificity, and positive predictive values in the context of +SR at mTESE. This work was supported by voluntary donations from the Urological Research Institute (URI). All authors declare no conflict of interest. N/A.

Follicle-stimulating hormone and Inhibin B as predictors of successful sperm retrieval in men undergoing testicular sperm extraction: A review of 44 cases and meta-analysis.

The aim of the study and meta-analysis was to evaluate the predictive value of follicle-stimulating hormone (FSH) and inhibin B in sperm retrieval in men with non-obstructive azoospermia NOA. A total of 44 patients with a mean age of 36.1 years (SD=+/- 6.17) was included. We had 19 patients with successful sperm retrieval and 25 with failure. All patients had a normal karyotype. There was no difference between groups regarding patients mean age, prolactin or FSH. Patients with successful sperm retrieval had a significantly higher inhibin B level (134.62(+/-64,35) vs. 72.36(+/-67.78), p=0.006) and, paradoxically a higher body weight (92.38(+/-11.38) vs. 83.76(+/-11.90), p=0.027). The forest plots showed that a higher FSH level was significantly correlated with a negative success rate. Ahigher Inhibin B level was associated with a higher successful sperm retrieval (p=0.00001 respectively, p=0.0002). Surgical sperm retrieval could be, in some cases, the only chance to have a biological offspring.

Evaluation of the Utility of Seminal Plasma Resistin and Leptin in Predicting Successful Surgical Sperm Retrieval in Men with Non-Obstructive Azoospermia.

The purpose of the current study was evaluation of the utility of seminal plasma (SP) resistin and leptin in predicting successful surgical sperm retrieval (SSR) in men with non-obstructive azoospermia (NOA). This prospective comparative study was conducted in the andrology clinic of a specialized fertility center. In total, 53 NOA men as candidates for either first time micro-testicular sperm extraction (micro-TESE) or repeat micro-TESE and 28 normozoospermic controls were included. ELISA was used for measurement of SP resistin and leptin levels in all participants. Significance level was defined as p<0.05. The current study demonstrated a significant positive correlation between estradiol (E2) level in serum and SP resistin (r=0.342, p=0.025). Also, there was a highly significant positive correlation between SP leptin and SP resistin (r=0.568, p= 0.001). Interestingly, SP leptin was the only variable that demonstrated a significant correlation with eventful micro-TESE outcome in men who underwent micro-TESE for the first time. Finally, ROC curve showed that SP leptin level of 4.05 ng/ml predicted successful SSR in men who underwent micro-TESE for the first time with a sensitivity of 73.3% and a specificity of 75% as 11 out of 27 (41%) cases showed eventful micro-TESE at or above this cut-off level [AUC of 0.747, 95% CI, lower bound of 0.555, and upper bound of 0.939, p=0.030]. SP leptin can be used as a non-invasive biomarker to predict successful SSR in NOA cases undergoing first time micro-TESE, while SP resistin failed to play the same role.

MP43-01 DOES INTRA-OPERATIVE MICROSCOPIC SPERM EVALUATION IMPACT MTESE SPERM RETRIEVAL RATES FOR MEN WITH NOA?: A PROPORTIONAL META-ANALYSIS

You have accessJournal of UrologyCME1 Apr 2023MP43-01 DOES INTRA-OPERATIVE MICROSCOPIC SPERM EVALUATION IMPACT MTESE SPERM RETRIEVAL RATES FOR MEN WITH NOA?: A PROPORTIONAL META-ANALYSIS Brittany Berk, John Ernandez, Catherine Gu, Alexandra Berger, and Martin Kathrins Brittany BerkBrittany Berk More articles by this author , John ErnandezJohn Ernandez More articles by this author , Catherine GuCatherine Gu More articles by this author , Alexandra BergerAlexandra Berger More articles by this author , and Martin KathrinsMartin Kathrins More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003289.01AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Microsurgical testicular sperm extraction (mTESE) is the gold standard for surgical sperm retrieval in men with nonobstructive azoospermia (NOA). Intraoperative table-top microscopic specimen analysis can be utilized to identify viable sperm for in-vitro fertilization, and also provides information regarding the necessity of bilateral testicular exploration and helps determine the end of the surgery. In this study, we investigated the impact of intraoperative microscopic analysis on mTESE sperm retrieval rates (SRR). METHODS: A PubMed search was performed for studies on men with NOA undergoing mTESE with a primary outcome of SRR. Studies on obstructive azoospermia, Klinefelter’s syndrome cohorts, and review articles were excluded. Only the most recent publication from a given academic institution’s cohort was considered (Figure 1). Each study was categorized based on whether the manuscript described utilization of intraoperative microscopy to identify viable sperm. The number of patients who underwent mTESE, and the number of patients who had successful sperm retrieval, were recorded for each study and combined within groups. Differences in SRR between the groups was determined using Chi-square testing. RESULTS: 182 articles were identified in our initial search, of which 36 were included in the final analysis. 20 studies were categorized as “(+) Intraoperative Microscopic Guidance”, and 7 studies were “(-) Intraoperative Microscopic Guidance”. In the (+) group, a total of 3923 cases were included with a cumulative SRR of 51.0% (95% CI 49.4–52.5, and in the (-) group, a total of 877 cases were included with a cumulative SRR of 46.0% (95% CI 42.7–49.4). The estimated difference in SRR between the two groups was 4.94% [95% CI 1.28%-8.57%]. On chi-squared analysis, there was a statistically significant difference in SRR [X2=7.007; p = 0.0081]. CONCLUSIONS: In this proportional meta-analysis, we found a significantly higher SRR for men with NOA undergoing mTESE with intraoperative microscopic analysis. These findings support increased utilization of real time microscopic assessment of specimens to guide intraoperative decision-making and optimize outcomes while also possibly preventing unnecessary extensive exploration. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e601 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Brittany Berk More articles by this author John Ernandez More articles by this author Catherine Gu More articles by this author Alexandra Berger More articles by this author Martin Kathrins More articles by this author Expand All Advertisement PDF downloadLoading ...

Inhibin B-to-Anti-Mullerian Hormone Ratio as Noninvasive Predictors of Positive Sperm Retrieval in Idiopathic Non-Obstructive Azoospermia.

The lack of clinically useful biomarkers for predicting micro-TESE outcomes in males with idiopathic NOA. To find clinically reliable serum reproductive hormone markers to predict the outcome of sperm retrieval in men with idiopathic NOA undergoing micro-TESE. We analyzed the clinical data of 168 men with idiopathic NOA treated with micro-TESE. The clinical predictors of a successful sperm retrieval were put to the test using logistic regression analysis. The clinical net benefit was calculated using a decision-curve analysis, and the predictive power of each variable was assessed using the ROC-derived area under the curve. Between positive group and negative group for sperm retrieval, there was a statistically significant difference in INHB, AMH, and INHB/AMH. AMH, INHB, and INHB/AMH were each independent predictors of successful sperm retrieval, with INHB (OR1.02, p = 0.03), AMH (OR0.85, p = 0.01), INHB/AMH (OR1.08, p &lt; 0.01). The ROC curve determined the optimal cut-off values for serum INHB and INHB/AMH in positive sperm retrieval patients undergoing micro-TESE. 21.51 pg/mL was the cut-off value for INHB. The cut-off value for INHB/AMH was 3.19, which had a 86.3% sensitivity and a 53.8% specificity. Using INHB and INHB/AMH prior to micro-TESE sperm retrieval in idiopathic NOA patients improved the net benefit of positive sperm retrieval, and the net benefit score of INHB/AMH was better than that of INHB, according to decision analysis curves. Serum INHB have predictive value for sperm retrieval outcomes in idiopathic NOA patients undergoing micro-TESE. Combining INHB and AMH, INHB/AMH seems to be a better predictor.

Feasibility of repeat microdissection testicular sperm extraction within 6 months for nonobstructive azoospermia.

Microdissection testicular sperm extraction (mTESE) is the mainstay of sperm retrieval in men with nonobstructive azoospermia (NOA). Some experts believe that a resting period of ≥6 months is required between procedures to ensure better sperm retrieval rates and fewer complications. However, no scientific studies have investigated how long patients should wait before arranging a second mTESE procedure. This retrospective study aimed to evaluate whether good success rates are still achieved when a repeat mTESE procedure is performed within 6 months. Total 146 patients with NOA who underwent mTESE twice from the same testis between May 2012 and September 2019 were retrospectively collected. These patients were categorized into three groups according to the time interval between the two mTESE surgeries, with 44, 60, and 42 patients undergoing a repeat mTESE after <3 months (group I), between 3 and 6 months (group II), and >6 months (group III) after the first procedure, respectively. No significant differences were observed between groups in terms of patient characteristics and preoperative hormone profiles. Overall sperm retrieval rates did not differ among the three groups (93.2%, 90.0%, and 88.1% in groups I, II, and III, respectively [ p = 0.719]), nor did fertility outcomes, including rates of fertilization, biochemical pregnancy, clinical pregnancy, and cumulative live births. Sperm retrieval rates for repeat mTESE procedures were consistently high, even when the second procedure was performed within 6 months of the first. Repeat mTESE within 6 months is not a limitation for patients with NOA, if required clinically.

The predictive factors of successful sperm retrieval for men with Y chromosome AZFc microdeletion.

To identify key predictors for successful sperm retrieval in men with AZFc microdeletion. Totally, 71 infertile men with confirmed AZFc microdeletion were studied. For each patient, the endocrine profile including serum follicle stimulating hormone (FSH), luteinizing hormone, total testosterone, prolactin, and estradiol was recorded, along with intratesticular testosterone levels (ITT), age, and testicular size. The factors were further analyzed to determine the key predictors for successful sperm retrieval. Of the 71 men with AZFc microdeletion, 52 (73.2%) were classified as having non-obstructive azoospermia (NOA), 7 (9.9%) as having cryptozoospermia, and 12 (15.8%) as having severe oligoasthenoteratozoospermia. Of the 52 men with azoospermia, 47 received microdissection testicular sperm retrieval, and sperm retrieval was successful in 35 of those cases (74.5%). A significantly lower serum FSH (p = 0.03) was found in those patients from whom sperm could be successfully retrieved. The area under the receiving operating characteristic curve for FSH was determined to be 0.721. Using an FSH cutoff point of 12.95 mIU/mL, the model for predicting successful sperm retrieval was found to have 51.4% sensitivity, 83.3% specificity, 90.0% positive predictive value, and 37.0% negative predictive value. ITT levels were obtained from 7 NOA patients, the mean ITT and the mean ITT/serum testosterone ratio was 1932.8ng/ml and 567.2 in 6 men with successful sperm retrieval, whereas, in a patient with fail sperm retrieval, the levels were 2370ng/ml and 393.0. Men exhibiting AZFc microdeletion with discernible spermatogenesis from whom sperm was successfully retrieved by mTESE generally presented with relatively lower FSH levels.

Factors predicting successful sperm retrieval in men with nonobstructive Azoospermia: A single center perspective.

Predicting successful sperm retrieval is essential in counseling infertile men with Azoospermia.ObjectivesTo assess the predictors of successful sperm extraction in men with nonobstructive Azoospermia.Patients and MethodsA retrospective study included all patients with nonobstructive Azoospermia from January 2018 to May 2019. Subdivided into two groups, group I (negative sperm retrieval) and group II (positive sperm retrieval).ResultsA total of 108 patients with a mean age of 36.8 ± 10 years were included. The rate of successful sperm retrieval was 47.2%. Group I included 57 patients (52.8%) with a mean age of 33.98 ± 6.18, and group II included 51 patients (47.2%) with a mean age of 40.04 ± 12.22 (p = 0.008). Follicular stimulating hormone (FSH) levels were significantly higher in group I (18.55 ± 13 vs. 7.97 ± 7.11; p < 0.004). Similarly, in group I, luteinizing hormone was significantly higher (11.4 ± 7.45 vs. 5.9 ± 4.4; p < 0.001). Age and FSH were the independent predictors of successful micro‐TESE. Additionally, successful pregnancies were 13.7% of patients, 28.6% of which gave rise to living birth.ConclusionPatients' age and serum FSH are independent predictors of successful sperm retrieval for infertile men with nonobstructive Azoospermia; young patients with high FSH levels could have little chance of sperm retrieval.

Multi-stage screening cell-free seminal mRNAs to diagnose completion of meiosis and predict testicular sperm retrieval in men with non-obstructive azoospermia.

Differential diagnosis of men with subtypes of non-obstructive azoospermia (NOA) is important for their treatment. Many genes are transcripted during meiosis. We hypothesized that some of these genes can be detected in cell-free seminal message RNA (mRNAs) (cfs-mRNA) and be developed as non-invasive biomarkers for diagnosing NOA subtypes. To screen cfs-mRNA to diagnose the completion of meiosis and predict successful sperm retrieval (SR) in men with NOA. NOA patients who visited our institutes from September 2018 to December 2020 for testicular histopathological diagnosis (n = 109) or testicular SR (n = 92) were screened for participation in the study. Microarray and real-time quantitative polymerase chain reaction were used in five stages to obtain candidate cfs-mRNAs for comparisons between patients with early maturation arrest (eMA, meiosis not completed) and late MA or hypospermatogenesis (meiosis completed) and between NOA patients with successful SR and SR failure. Twelve cfs-mRNAs were selected based on this comparison between men with eMA and hypospermatogenesis and their gene expression and function information. Of these, AKAP1, BOLL, TCP11 and SETX predominantly derived from testes and germ cells were proposed as candidate cfs-mRNAs. Further quantification in men with NOA demonstrated significantly higher levels of BOLL cfs-mRNA (p < 0.0001) in men with late MA or hypospermatogenesis (n = 23), compared with men with eMA (n = 51); and significantly higher levels (p < 0.0001) in patients with successful SR (n = 44) when compared with patients with SR failure (n = 37). Interestingly, with a similar cutoff value, BOLL cfs-mRNA showed high sensitivity and specificity in diagnosing late MA and hypospermatogenesis (>404 copies/ml) and predicting successful SR (>415 copies/ml). Correlation of BOLL mRNA levels was observed in paired semen and testicular tissues. We propose that BOLL cfs-mRNA is a promising non-invasive marker for diagnosing the completion of meiosis and predicting successful testicular SR in men with NOA.

MP31-08 EXOGENOUS TESTOSTERONE THERAPY IN MEN WITH KLINEFELTER SYNDROME NEGATIVELY IMPACTS SPERM RETRIEVAL

You have accessJournal of UrologyInfertility: Therapy (MP31)1 Sep 2021MP31-08 EXOGENOUS TESTOSTERONE THERAPY IN MEN WITH KLINEFELTER SYNDROME NEGATIVELY IMPACTS SPERM RETRIEVAL Caroline Kang, Nahid Punjani, and Peter N. Schlegel Caroline KangCaroline Kang More articles by this author , Nahid PunjaniNahid Punjani More articles by this author , and Peter N. SchlegelPeter N. Schlegel More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002035.08AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Men with Klinefelter syndrome (KS) classically have testicular failure and are at risk for both testosterone (T) deficiency and infertility. T replacement therapy (TRT) often is initiated in adolescence for its potential neurodevelopmental benefits. Unfortunately, exogenous T has a defined adverse effect on spermatogenesis. We sought to examine the effect of exogenous T on sperm retrieval in men with KS. METHODS: All men with KS undergoing sperm retrieval by microdissection testicular sperm extraction (mTESE) performed by a single surgeon between 1995-2020 were reviewed. Demographic data and hormone-modifying agents, such as human chorionic gonadotropin (hCG) and aromatase inhibitors (AI), administered prior to mTESE were obtained. History or current use of exogenous T was recorded and categorized based on formulation into either short- (gel or foam) or long-acting (pellets or injection) groups. Descriptive statistics and SRR are reported. Patients with incomplete data on hormone therapy as well as repeat procedures on the same patient were excluded. RESULTS: A total of 290 sperm retrievals were performed on KS men during the study period. Fourteen men had a history of exogenous TRT or were currently using T at time of mTESE (Table 1). Median age was 34 years (interquartile range (IQR) 31–36), and median testis size was 1.3 mL (IQR 1.0–1.5). Five men had a remote history of TRT up to 2 years prior to mTESE, and received hCG and AI hormone therapy prior to retrieval. Of these, all five (100%) had successful sperm retrieval. In five men receiving topical testosterone and concurrent AI and/or hCG at time of mTESE, only two (40%) had successful sperm retrieval. No men receiving continuous delivery of exogenous testosterone (e.g., injectable or pellet) with concurrent hCG had sperm identified during mTESE. CONCLUSIONS: Exogenous TRT is common in KS patients. Long-acting (e.g. injectable or implantable T) therapy suppresses gonadotropin production and sperm production, predisposing men to failed sperm retrieval. However, T monotherapy with short-acting (e.g. topical) formulations together with AIs can maintain endogenous gonadotropin production and spermatogenesis; such therapy is consistent with sperm retrieval in KS men. Additional prospective trials are needed to elucidate the effects of T on sperm retrieval in KS patients. Source of Funding: CK and NP are supported in part by the Frederick J. and Theresa Dow Wallace Fund of the New York Community Trust © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e557-e558 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Caroline Kang More articles by this author Nahid Punjani More articles by this author Peter N. Schlegel More articles by this author Expand All Advertisement Loading ...

MP21-04 SUCCESSFUL SPERM RETRIEVAL FOR MEN WITH Y CHROMOSOME AZFC MICRODELETION

You have accessJournal of UrologyInfertility: Epidemiology & Evaluation I (MP21)1 Sep 2021MP21-04 SUCCESSFUL SPERM RETRIEVAL FOR MEN WITH Y CHROMOSOME AZFC MICRODELETION I-Shen Huang, Wei-Jen Chen, and William J Huang I-Shen HuangI-Shen Huang More articles by this author , Wei-Jen ChenWei-Jen Chen More articles by this author , and William J HuangWilliam J Huang More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002006.04AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Among the genetic aberrations contributing to male infertility, the deletion of the AZFc region of the Y chromosome is a common cause of spermatogenetic failure and the chances for successful surgical sperm extraction from azoospermic men with AZFc region microdeletion are relatively good. Nevertheless, it is still a challenge to procure sperm from a sizeable proportion of individuals with AZFc microdeletion, even when meticulous surgical measures are employed. The objective of this study is to identify predictive factors for successful sperm retrieval in men with AZFc microdeletion. METHODS: 76 infertile men were studied, each having Y chromosome AZFc microdeletion at some time during a 10-year period, as confirmed by multiplex polymerase chain reaction (PCR) amplification of STS (sequence tagged site). For each patient, the endocrine profile including serum follicle stimulating hormone (FSH), luteinizing hormone (LH), total testosterone (TT), prolactin (PRL) and estradiol (E2) was recorded, along with intratesticular testosterone level (ITT), age and testicular size. The factors were further analyzed to determine the key predictors for successful sperm retrieval. RESULTS: Of the 76 men with AZFc microdeletion, 56 were classified as having non-obstructive azoospermia (NOA), 8 as having cryptozoospermia, and 12 as having severe oligoasthenoteratozoospermia (OAT). Of the 56 men with azoospermia, 50 received microdissection TESE (mTESE), and sperm retrieval was successful in 37 of those cases (74 %). A significantly lower serum FSH (P = 0.02) was found in those patients from whom sperm could be successfully retrieved. On the other hand, parameters such as levels of LH, TT, PRL, E2, testicular volume and age were not found to be correlated with successful sperm recovery. The area under the receiving operating characteristic (ROC) curve (AUC) for FSH was determined to be 0.721. Using an FSH cut-off point of 12.95 mIU/mL according to Youden’s index, the model for predicting successful sperm retrieval was found to have 51.4% sensitivity, 84.6% specificity, 90.5% positive predictive value (PPV) and 37.9% negative predictive value (NPV). CONCLUSIONS: Men exhibiting AZFc microdeletion with discernible spermatogenesis from whom sperm was successfully retrieved by mTESE generally presented with relatively lower FSH levels. Source of Funding: nil © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e347-e347 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information I-Shen Huang More articles by this author Wei-Jen Chen More articles by this author William J Huang More articles by this author Expand All Advertisement Loading ...

Hormonal markers as noninvasive predictors of sperm retrieval in non-obstructive azoospermia.

Non-obstructive azoospermia (NOA) is one of the leading causes of male factor infertility, which results from impaired spermatogenesis. Currently, the sole feasible therapeutic option for men with NOA to father their biologic children is sperm retrieval by testicular sperm extraction (TESE) approaches followed by an intracytoplasmic sperm injection program. Nevertheless, the rate of sperm retrieval from NOA men following TESE has remained as low as 50%, leading to a significant number of unsuccessful TESE operations. Given that TESE is associated with multiple side effects, the prediction of TESE outcome preoperatively can abolish unnecessary operations and thereby prevent NOA patients from sustaining adverse side effects. As the process of spermatogenesis is under the regulation of hormones, the hormonal profile of serum and/or seminal plasma may contain useful information about spermatogenesis status and can potentially predict the chance of sperm retrieval from NOA patients. A large body of literature is available on the predictive capability of different serum and seminal plasma hormones such as FSH, LH, testosterone, inhibin B, AMH, estradiol, prolactin, and leptin in a stand-alone basis or combinational fashion with respect to the TESE outcome. The present review aimed to evaluate the potential of these hormonal markers as noninvasive predictors of sperm retrieval in men with NOA.

Two Decades from the Introduction of Microdissection Testicular Sperm Extraction: How This Surgical Technique Has Improved the Management of NOA.

The treatment of men with non-obstructive azoospermia (NOA) has improved greatly over the past two decades. This is in part due to the discovery of in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI), but also significantly due to improvements in surgical sperm retrieval methods, namely the development of microdissection testicular sperm extraction (mTESE). This procedure has revolutionized the field by allowing for identification of favorable seminiferous tubules while simultaneously limiting the amount of testicular tissue removed. Improving sperm retrieval rates is imperative in this cohort of infertile men as there are a limited number of factors that are predictive of successful sperm retrieval. Currently, sperm retrieval in NOA men remains dependent on surgeon experience, preoperative patient optimization and teamwork with laboratory personnel. In this review, we discuss the evolution of surgical sperm retrieval methods, review predictors of sperm retrieval success, compare and contrast the data of conventional versus mTESE, share tips for optimizing sperm retrieval outcomes, and discuss the future of sperm retrieval in men with NOA.

Nfertilite Tedavisinde TESE Başarısını Etkileyen Faktörler: Tek Merkez Deneyimi Ön Sonuçları

Objective: Today, infertility is a health problem with increasing treatment seeking. Testicular sperm extraction (TESE) is the only possible procedure to offer genetic parenting to men with nonobstructive azoospermia (NOA). Our aim in this study is to present our clinical experiences that affect the success of sperm retrieval in men with NOA in the light of the literature. Materials and Methods: In our study, patients who underwent TESE with a diagnosis of NOA between 2017-2020 were retrospectively analyzed. According to the TESE procedure; the patients were divided into two groups as conventional TESE and TESE performed under microscopic magnification (micro-TESE). Medical histories, hormone values, and physical examination findings of all patients were recorded. Results: Our micro-TESE success rate was found to be 100%. A positive correlation (rho 0.714, p = 0.009) was found between the factors affecting sperm retrieval , and the application of micro-TESE, and a negative correlation was detected with FSH levels (rho -0.759, p = 0.004). Conclusion: The success of sperm retrieval increases with the micro-TESE procedure. As FSH levels increase, sperm retrieval success rates decrease.

Evaluation of Microdissection Testicular Sperm Extraction (mTESE), Outcomes and Predictive Factors in Ireland: The Gold Standard for Men with Non-Obstructive Azoospermia.

Background:Microdissection testicular sperm extraction (mTESE) is the gold standard approach in sperm retrieval in men with non-obstructive azoospermia (NOA). The purpose of the study was to assess the outcomes for Irish men who have undergone mTESE with a single surgeon.Methods:This is a retrospective, single cohort study. Thirty-four patients underwent mTESE between September 2015 and June 2019. A p<0.05 was considered statistically significant.Results:In this study, sperm retrieval rate (SRR) was 47.06%. (16/34). The mean age in those who had retrieved sperm at mTESE was 37.9±2.6 years. Johnson Score (JS) and FSH were statistically different between successful and unsuccessful mTESE groups (p=0.017*10−5 and p=0.004, respectively). Optimal cutoff values for FSH, T and JS were 15 IU/L, 13 nmol/L and 5, respectively. The pregnancy rate was 63.64% (7/11) among men who went on to use mTESE sperm in an ICSI cycle.Conclusion:The combination of mTESE/Intracytoplasmic sperm injection (ICSI) is the best option available for men with NOA who prefer to achieve paternity using their own DNA. Given the overall SRRs in mTESE, it is imperative to continue research for a predictive model to better counsel azoospermic men regarding the use of mTESE. For this purpose, large, multicenter, randomized controlled trials are needed.