Outcome Of Testicular Sperm Extraction Research Articles

Artificial intelligence: to a better predictive strategy for testicular sperm extraction outcome in azoospermia

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.

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.

P-536 Common variation in the PIN1 locus increases the genetic risk to suffer from Sertoli Cell Only syndrome

Abstract Study question Are the common genetic variants located in the PIN1 region associated with human male infertility due to severe spermatogenic failure (SPGF)? Summary answer PIN1 gene polymorphisms may play a relevant role in the development of Sertoli Cell Only syndrome (SCO), the most extreme form of SPGF. What is known already PIN1 is a relevant prolyl isomerase in humans, that catalyzes cis/trans isomerization of peptide bonds. It has a central role in cell cycle progression and cancer, and it has been linked to the immune system promoting inflammation and reactive-oxygen species. Pin1 gene is highly expressed in adult mice testes, particularly in spermatogonia and Sertoli cells, and it is required to control the proliferation of spermatogonial stem cells. Additionally, it controls the integrity of the blood-testis barrier, helping to maintain the immune privilege of the testis. Nevertheless, mutations in PIN1 have not yet been described in human male infertility cases. Study design, size, duration A genetic association study was performed including samples from 715 men diagnosed with SPGF and classified as suffering from non-obstructive azoospermia (NOA, n = 505) or severe oligospermia (SO, n = 210), and 1,058 matched unaffected male controls from the Iberian Peninsula (Spain and Portugal). Allelic association on SPGF susceptibility were evaluated by testing three PIN1 single nucleotide polymorphisms (SNPs; rs2287839, rs2233678, and rs62105751), which tagged most of the common genetic variation present in this locus. Participants/materials, setting, methods Participants signed an informed written consent approved by the ethical committees of each participating center. SO and NOA were clinically defined according to the guidelines of the World Health Organization. Genomic DNA from blood samples was genotyped using TaqMan assays and statistical analyses were carried out by the means of logistic regression models. An in silico functional prioritization of the associated variants and their linked polymorphisms was also performed. Main results and the role of chance A subtype-specific genetic association with the subset of NOA patients classified as suffering from SCO was identified for the three analyzed genetic variants under the additive model (rs2287839: P = 1.94E-02, rs2233678: P = 1.94E-02, rs62105751: P = 1.94E-02). The minor alleles showed strong risk effects for this subset (rs2287839: OR = 1.85 [1.17-2.93], rs2233678: OR = 1.62 [1.11-2.36], rs62105751: OR = 1.43 [1.06-1.93]). Dependence analysis showed that all associated variants tagged the same signal. The variants underlying the identified association signal were prioritized based on their functional impact on the PIN1 locus, being rs3810166 the most likely candidate for functionality. The minor allele of such variant (G) is in linkage disequilibrium with the observed rs2287839-G risk allele and it is predicted to affect both gene expression and isoform balance of PIN1. The rs3810166 SNP likely influences the binding affinity of both HDAC2 and NRSF transcription factors, which are involved in cell cycle progression and transcription, respectively. Moreover, the tagged variants rs28802413 and rs10425775 were also predicted to alter the binding of significant transcription factors of the spermatogenic process, such as SIN3A and NANOG. Limitations, reasons for caution Although the overall statistical power of the study cohort was appropriate to detect the expected effects, the sample sizes in the subtype analyses were considerably lower, which may influence the obtained results. Further analyses including a larger SCO cohort should be performed to confirm our findings. Wider implications of the findings The obtained results shed light into the genetic contribution of common variation to male infertility, which may contribute to design a future panel of genetic markers to predict the testicular sperm extraction outcome, avoiding surgical interventions in NOA cases in which the probability of spermatozoa finding is much reduced. Trial registration number Not applicable

P-057 Machine learning-based prediction of testicular sperm extraction: comparison of different preprocessing and models, required sample size and relevance of input biomarkers

Abstract Study question Can advanced machine learning applied to the preoperative assessment predict the testicular sperm extraction outcome in azoospermic context and how many patients are required? Summary answer Despite encouraging results (AUC = 92.0%, sensitivity = 83.9% and specificity = 84.2%), integrating new biomarkers would probably be more relevant than enrolling additional patients. What is known already Testicular sperm extraction (TESE) is an essential therapeutic tool for the male infertility management and is often the “last hope” before gamete donation for these patients. However, it is an invasive procedure and is successful in up to 50%. Until now, no model is sufficiently powerful to accurately predict the success of sperm retrieval in TESE. Among the few models already developed, the findings are highly disparate despite having common input data (preoperative assessment). Moreover, only few types of machine learning models and procedures have been investigated. Performances were mostly capped despite the inclusion sometimes of more than 1000 patients. Study design, size, duration Data of 175 patients who underwent TESE between 2012 and 2021 were retrospectively analyzed. The performances of a wide range of preprocessing methods and machine learning models (state-of-the-art methods in machine learning) we explored, evaluated, and compared. The objective was to predict the presence or absence of spermatozoa, using 17 parameters (clinical, hormonal, genetic, history) from the preoperative assessment. The study protocol was approved by a local ethics committee (IRB CER-2021-041). Participants/materials, setting, methods After data preprocessing (standardization…), Machine Learning models (Bayesian Naive Classification, logistic regression, k-nearest neighbor classifier, support vector machine, random forests, GradientBoosting and XGBoost) and Deep Learning models were tested. The validation procedure consisted of splitting the dataset into a training set and test set. Beyond the standard metrics (sensitivity, specificity, AUC-ROC), the identification of the most relevant variables and the learning curve to determine the optimal patient number to be included were performed. Main results and the role of chance At least one live spermatozoon was found in the testicular tissue of 104 (59.4%) patients (positive TESE) out of 175. The best performing model (Random Forest with appropriate preprocessing) obtained the following results on the test set: AUC = 92.0%, sensitivity = 83.9% and specificity = 84.2%, leading to an efficient tool, which gives additional and more relevant information than the different variables taken separately. Inhibin B, FSH and history of cryptorchidism were the variables with the most discriminating power. However, a plateau in the model performance was observed (beyond 110 patients), whatever the approach or the preprocessing used. A trend curve shows that beyond 110 patients, no improvement can be observed and cast doubt about the power of the traditional preoperative parameters assessed before TESE. The classic preoperative assessment can probably not fully predict the TESE outcomes. Further work is needed to be enhance with new hypothesis and the use of new biomarkers to be integrated into the models. Limitations, reasons for caution The main limitation was the monocentric design and the use of retrospective data. Wider implications of the findings Machine learning models can provide the basis for an enhanced decision support system tool in the context of azoospermia. Indefinitely increasing the number of participants is not likely to be the solution: further hypotheses and biomarkers integration into the models will probably be necessary to improve performance. Trial registration number not applicable

Fertility in men with Klinefelter's syndrome

Patients with a Klinefelter syndrome (KS), defined by a 47 XXY karyotype, were long considered infertile. Testicular sperm extraction (TESE) now allows them to access fatherhood. We will present the data of studies since first experiment of TESE. Several factors influencing TESE outcome were proposed in these different studies. Among them, clinical and hormonal parameters have reported by few studies, age has been one of the most discussed prognostic factor of positive sperm retrieval rate. Data seems to show that TESE carried out before an age greater than 30 has a poorer prognosis for positive sperm retrieval. In few studies performed in younger patient, before 20 years, SRR was closed to result for 20 to 30 year old patients. Offering a TESE before 16 years old does not improve positive sperm extraction rate. In fact, the few studies carried out before the age of 16 were of poorer prognosis, most often linked to insufficient maturation of the residual gametes. In addition, androgen therapy, frequently prescribed in case of Klinefelter syndrome, did not seem to show any effect on sperm retrieval but only few studies were interested in the possible impact of this treatment. In conclusion, further studies are necessary to determine the interest of new markers to predict the chance of sperm retrieval, taking into account age, hormonal therapy.

Whole-exome sequencing in patients with maturation arrest: a potential additional diagnostic tool for prevention of recurrent negative testicular sperm extraction outcomes.

STUDY QUESTIONCould whole-exome sequencing (WES) be useful in clinical practice for men with maturation arrest (MA) after a first testicular sperm extraction (TESE)?SUMMARY ANSWERWES in combination with TESE yields substantial additional information and may potentially be added as a test to predict a negative outcome of a recurrent TESE in patients with MA.WHAT IS KNOWN ALREADYAt present, the only definitive contraindications for TESE in men with non-obstructive azoospermia (NOA) are a 46,XX karyotype and microdeletions in the azoospermia factor a (AZFa) and/or AZFb regions. After a first negative TESE with MA, no test currently exists to predict a negative outcome of a recurrent TESE.STUDY DESIGN, SIZE, DURATIONIn a cohort study, we retrospectively included 26 patients with idiopathic NOA caused by complete MA diagnosed after a first TESE.PARTICIPANTS/MATERIALS, SETTING, METHODSTwenty-six men with MA at the spermatocyte stage in all seminiferous tubules, according to a histopathological analysis performed independently by two expert histologists, and a normal karyotype (i.e. no AZF gene microdeletions on the Y chromosome) were included. Single-nucleotide polymorphism comparative genomic hybridization array and WES were carried out. The results were validated with Sanger sequencing. For all the variants thought to influence spermatogenesis, we used immunohistochemical techniques to analyse the level of the altered protein.MAIN RESULTS AND THE ROLE OF CHANCEDeleterious homozygous variants were identified in all seven consanguineous patients and in three of the 19 non-consanguineous patients. Compound heterozygous variants were identified in another 5 of the 19 non-consanguineous patients. No recurrent variants were identified. We found new variants in genes known to be involved in azoospermia or MA [including testis expressed 11 (TEX11), meiotic double-stranded break formation protein 1 (MEI1), proteasome 26s subunit, ATPase 3 interacting protein (PSMC3IP), synaptonemal complex central element protein 1 (SYCE1) and Fanconi anaemia complementation group M (FANCM) and variants in genes not previously linked to human MA (including CCCTC-binding factor like (CTCFL), Mov10 like RISC complex RNA helicase 1 (MOV10L1), chromosome 11 open reading frame 80 (C11ORF80) and exonuclease 1 (EXO1)].LARGE SCALE DATAData available on requestLIMITATIONS, REASONS FOR CAUTIONMore data are required before WES screening can be used to avoid recurrent TESE, although screening should be recommended for men with a consanguineous family background. WES is still a complex technology and can generate incidental findings.WIDER IMPLICATIONS OF THE FINDINGSOur results confirmed the genetic aetiology of MA in most patients: the proportion of individuals with at least one pathologic variant was 50% in the overall study population and 100% in the consanguineous patients. With the exception of MEI1 (compound heterozygous variants of which were identified in two cases), each variant corresponded to a specific gene—confirming the high degree of genetic heterogeneity in men with MA. Our results suggest that WES screening could help to avoid recurrent, futile TESE in men with MA in general and in consanguineous individuals in particular, but these results need to be confirmed in future studies before clinical implementation.STUDY FUNDING/COMPETING INTEREST(S)The study was funded by the Fondation Maladies Rares (Paris, France), Merck (Kenilworth, NJ, USA), IRSF (Montigny le Bretonneux, France) and Agence de la Biomédecine (Saint Denis, France). There are no competing interests.TRIAL REGISTRATION NUMBERN/A.

For patients with non-obstructive azoospermia, the outcome of testicular sperm extraction correlates with self-esteem, sexual health and the quality of the couple\u2019s relationship

BackgroundA very small number of studies have indicated that azoospermia or negative testicular sperm extraction (TESE) outcomes are linked to depression or erectile dysfunction. However, the data are often weak, conflicting and gathered with non-validated questionnaires. Hence, we performed a cross-sectional study of 44 men with non-obstructive azoospermia. Levels of self-esteem and the quality of the couple’s sex life and overall relationship were assessed with validated questionnaires before and after the TESE procedure as a function of the TESE outcome.ResultsA positive TESE outcome (n = 24) was associated with a statistically significant increase in self-esteem (particularly with regard to family aspects), sexual health and couples’ adjustment quality. In contrast, a negative TESE outcome (n = 20) was associated with statistically significant decreases in self-esteem, erectile function, intercourse satisfaction, orgasmic function, couples’ adjustment quality and all aspects of the couple’s relationship (consensus, cohesion, satisfaction and affection).ConclusionFor men with non-obstructive azoospermia (NOA), negative TESE outcomes may have a negative impact on self-esteem and the quality of the couple’s sex life and overall relationship. This should be borne in mind when counselling men with NOA and their partners to (ideally) help them to cope with and decrease the harmful impacts of azoospermia and negative TESE.

Analysis of 29 Targeted Genes for Non-Obstructive Azoospermia: The Relationship between Genetic Testing and Testicular Histology.

To analyze the presence of potentially pathogenic variants of 29 candidate genes known to cause spermatogenic failure (SPGF) in patients with non-obstructive azoospermia (NOA) who underwent testicular histology. Forty-eight patients with unexplained NOA referred to the Department of Transfusion Medicine and Transplantation Biology, University Hospital Center Zagreb, Zagreb, Croatia for testicular biopsy. They were divided into three groups: those who had cryptorchidism (n=9), those with varicocele (n=14), and those with idiopathic NOA (n=25). All included patients underwent blood withdrawal for next-generation sequencing (NGS) analysis and gene sequencing. We found a possible genetic cause in 4 patients with idiopathic NOA (16%) and in 2 with cryptorchidism (22%). No pathogenic or possibly pathogenic mutations were identified in patients with varicocele. Variants of undetermined significance (VUS) were found in 11 patients with idiopathic NOA (44%), 3 with cryptorchidism (33%), and 8 patients with varicocele (57%). VUSs of the USP9Y gene were the most frequently as they were found in 14 out of 48 patients (29%). In particular, the VUS USP9Y c.7434+14del was found in 11 patients. They showed varied histological pictures, including Sertoli cell-only syndrome, mixed atrophy, and hypospermatogenesis, regardless of cryptorchidism or varicocele. No direct correlation was found between the gene mutation/variant and the testicular histological picture. Different mutations of the same gene cause various testicular histological pictures. These results suggest that it is not the gene itself but the type of mutation/variation that determines the testicular histology picture. Based on the data presented above, it remains challenging to design a genetic panel with prognostic value for the outcome of testicular sperm extraction in patients with NOA.

MP31-05 PREDICTION OF MICRODISSECTION TESTICULAR SPERM EXTRACTION OUTCOME IN POST-CHEMOTHERAPY AZOOSPERMIC MEN USING CYCLOPHOSPHAMIDE EQUIVALENT DOSE

You have accessJournal of UrologyInfertility: Therapy (MP31)1 Sep 2021MP31-05 PREDICTION OF MICRODISSECTION TESTICULAR SPERM EXTRACTION OUTCOME IN POST-CHEMOTHERAPY AZOOSPERMIC MEN USING CYCLOPHOSPHAMIDE EQUIVALENT DOSE Shi-Jie Tsai, I-shen Huang, and William J. Huang Shi-Jie Tsai Shi-Jie Tsai More articles by this author , I-shen HuangI-shen Huang 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.0000000000002035.05AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Cancer per se or therapies, particularly treatment involved with chemotherapy, appears to potentiate gonadal toxicity. For men with persistent postchemotherapy azoospermia, fatherhood can be possibly achieved via microdissection testicular sperm extraction (mTESE) combine with intracytoplasmic sperm injection (ICSI). Yet, the recovery of viable testicular sperm with mTESE is unpredictable in this population. Using cyclophosphamide equivalent dose (CED) as a means of quantifying exposure to alkylating agent, a cytotoxic agent that has been demonstrated to disrupt spermatogenesis, we sought to discover the sperm retrieval rate in men with persistent azoospermia postchemotherapy in relation to CED. METHODS: We retrospectively reviewed records of 910 patients with the diagnosis of non-obstructive azoospermia who had undergone mTESE between 2010 to 2018 in our institution and enrolled 14 patients with a prior history of chemotherapy. The oncological data and chemotherapy regimen of each individual were reviewed. For each patient’s regimen received, a CED was calculated using the equation proposed by Daniel Green et al. in 2014. The pretreatment hormone profile, CED, and outcomes of mTESE were analyzed. RESULTS: Testicular spermatozoa were successfully retrieved in 6 (43%) of the patients. The mean patient age was 36 years (range, 27-42 years) and the mean time interval from chemotherapy to mTESE was 10.4 years (range, 1-26 years). Although CED and alkylating agent exposure were not predictive factors for successful sperm retrieval (p=0.14), however, no men with CED >4000 mg/m2 (n=4) had viable sperm detected in testis during mTESE. As for the other 10 patients without alkylating agent exposure (i.e. CED=0 mg/m2), sperm can be recovered in 6 (60%) of them. Regarding cancer subtypes, patients diagnosed with testicular non-seminomatous germ cell tumor had favorable sperm retrieval rate (3/5, 60%), compared to patients with non-Hodgkin’s lymphoma (0/3, 0%) or leukemia (1/2, 50%), respectively. CONCLUSIONS: The chance of successful sperm retrieval using mTESE for men with persistent postchemotherapy azoospermia and a calculated CED >4000 mg/m2 is zero. These patients should be properly counseled with the CED model before pursuing surgical sperm retrieval . Source of Funding: None © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e556-e557 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Shi-Jie Tsai More articles by this author I-shen Huang More articles by this author William J. Huang More articles by this author Expand All Advertisement Loading ...

P–116 A 9-year monocentric retrospective analysis of glutaraldehyde-fixed and semithin section of testicular biopsies and TESE in azoospermic patients

Abstract Study question What is the outcome of testicular sperm extraction (TESE) after microinjection of frozen–thawed sperm and the correlation with histological analysis in azoospermic patients? Summary answer In our cohort of 240 azoospermic patients, sperm could be retrieved in 167 patients (69.6%). What is known already Testicular biopsy is a crucial assessment in reproductive practice with diagnostic and prognostic importance for ICSI. Divers histological procedures are used throughout the centres. There is increasing need to accurately analyse histological biopsies in order to characterise different type of spermatogenic failure and allows data storage of value in clinical practice and research. Compared with Bouin’s and formalin, glutaraldehyde fixed and semithin section of testicular biopsies have the advantage of yielding not only good cellular morphology but also it allows the possibility of performing electron microscopy. Study design, size, duration This is a monocentric retrospective study of TESE practice in azoospermic patients in Strasbourg University Hospital from February 2011 to December 2019. Participants/materials, setting, methods A total of 240 azoospermic patients underwent TESE followed by sperm cryopreservation when sperm were present and data of histological analysis and clinical outcome of ICSI were analysed. The analysis include initial hormonal status, type of azoospermia, body max index, classification of histological findings, freezing rate and outcome of ICSI-IVF procedure. Main results and the role of chance The mean age of 240 patients was 34.5 years. Out of all patients, 42% were diagnosed with obstructive azoospermia (OA) and 58% patients with non-obstructive azoospermia (NOA). There was no correlation of sperm retrieval with the body mass index. Overall, sperm could be retrieved in 69.6% patients. Spermatozoa were always successfully recovered in patients with normal testicular histological findings, 41.7% patients (n 100). Histological analysis revealed a Sertoli cell-only (SCO) syndrome in 27.5% cases (n 66), hypospermatogenesis in 14.2% (n 34), germ cell arrest in 7.9 (n 19) and mixed pattern in 8.3% (n 20). In patients with serum FSH concentrations >12 IU/l, 46% of patients (n 42) sperm were present at TESE. In patients with no sperm retrieval, 31.5% had normal FSH levels. Out of all men with elevated FSH, 63% had SCO pattern, 4% germ cell arrest, 21% hypospermatogenesis and 12% mixt patterns. In the group of patients with no sperm retrieved at TESE, histological analysis showed SCO in 69.9% cases, germ cell arrest in 15% and hypospermatogenesis in 9.6% of cases. Out of 167 patients with TESE and sperm cryopreservation, 126 patients undergone ICSI-IVF procedure and 80 babies were born. Limitations, reasons for caution This study is a retrospective analysis in a single centre. The cohort was not compared with groups of patients with different histological and fixation techniques. Wider implications of the findings: Accurate histological diagnosis is a prerequisite for research and clinical data collection and open the possibilities to include patients with NOA in subsequent detailed genetic screen. Trial registration number NA

Intrasurgical parameters associated with successful sperm retrieval in patients with non‐obstructive azoospermia undergoing salvage microdissection testicular sperm extraction

Patients with non-obstructive azoospermia with a previously failed conventional testicular sperm extraction may undergo a salvage microdissection testicular sperm extraction with the probability of successful sperm retrieval being almost dependent upon the number of previous surgical attempts and to different histopathologic categories. To determine whether the seminiferous tubules pattern and the histological categories could affect the sperm retrieval rate in patients with non-obstructive azoospermia undergoing salvage microdissection testicular sperm extraction after failed conventional testicular sperm extraction. Seventy-nine patients undergoing unilateral or bilateral salvage microdissection testicular sperm extraction were evaluated. During microdissection testicular sperm extraction, if present, dilated tubules were retrieved, otherwise, tubules with slightly larger caliber than that of the surroundings were removed. When no dilated tubule or tubule with slightly larger caliber was found, not dilated tubules were excised. A prediction model was built with seminiferous tubules pattern and testis histology as covariates. Sperm retrieval was successful in 30 out of 79 patients. The prediction model correctly classified 88.3% of cases, explained the 29.7% variability of the outcome, and significantly predicted the microdissection testicular sperm extraction outcome with a sensitivity of 67.7% and a specificity of 90.2%, Both tubules with slightly larger caliber and not dilated tubules were negatively associated with the chance of retrieving spermatozoa. Among the histological categories, only early maturation arrest was significant to the model (log(SSR)=0.57 - 1.9SDT - 3.3NDT - 1.76EMA) (where SSR is sperm retrieval rate, SDT is tubule with slightly larger caliber, NDT is not dilated tubule, and EMA is early maturation arrest). The model had a clearly useful discrimination (area under the curve = 0.814), the estimated performance was 0.8105, and internal calibration was acceptable (p>0.05). Seminiferous tubules pattern and testis histology may reliably explain the salvage microdissection testicular sperm extraction outcome in all patients with non-obstructive azoospermia apart from those with early maturation arrest, where the homogeneous apparent seminiferous tubules pattern may be misleading. The outcome of salvage microdissection testicular sperm extraction can be predicted by the same intrasurgical parameters that have been demonstrated to predict the outcome of microdissection testicular sperm extraction in naïve patients with non-obstructive azoospermia.

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.

Ethnic Origin as a Parameter in the Prediction of Successful Testicular Sperm Extraction in Patients with Non-Obstructive Azoospermia

Background: The need for a reliable prediction model of testicular sperm extraction outcomes in non-obstructive azoospermia patients is inarguably of paramount importance. The aim of the present study was to determine whether a combination of available parameters would improve the prediction of successful sperm retrieval. Methods: A retrospective cohort study with a population of 119 patients who underwent Testicular Sperm Extraction - was conducted. We used univariate and multivariate binary logistic regression to identify the most reliable factors associated with the success of the surgical procedure. Results: Age and ethnicity were the only parameters that differed significantly between the patients who experienced successful testicular sperm extraction and those who did not. A comparison between patients of Jewish and Bedouin origin demonstrated that despite the fact that the Jewish population was significantly older, the sperm retrieval rate was much higher than it was in the Bedouin population-77.19% versus 54.88%. Conclusion: To the best of our knowledge, this is the first study to emphasize ethnic origin as an important parameter in the prediction of successful sperm retrieval in non-obstructive azoospermia patients.

Seminal Plasma Transcriptome and Proteome: Towards a Molecular Approach in the Diagnosis of Idiopathic Male Infertility.

As the “-omic” technology has largely developed, its application in the field of medical science seems a highly promising tool to clarify the etiology, at least in part, of the so-called idiopathic male infertility. The seminal plasma (SP) is made-up of secretions coming from the male accessory glands, namely epididymis, seminal vesicles, and prostate. It is not only a medium for sperm transport since it is able to modulate the female reproductive environment and immunity, to allow the acquisition of sperm competence, to influence the sperm RNA content, and even embryo development. The aim of this systematic review was to provide an updated and comprehensive description of the main transcripts and proteins reported by transcriptome and proteome studies performed in the human SP of patients with idiopathic infertility, in the attempt of identifying possible candidate molecular targets. We recurrently found that micro RNA (miR)-34, miR-122, and miR-509 are down-regulated in patients with non-obstructive azoospermia (NOA) and oligozoospermia compared with fertile controls. These molecules may represent interesting targets whose predictive role in testicular sperm extraction (TESE) or assisted reproductive techniques (ART) outcome deserves further investigation. Furthermore, according to the available proteomic studies, ECM1, TEX101, lectingalactoside-binding andsoluble 3 binding protein (LGALS3BP) have been reported as accurate predictors of TESE outcome. Interestingly, ECM1 is differently expressed in patients with different ART outcomes. Further prospective, ample-sized studies are needed to validate these molecular targets that will help in the counseling of patients with NOA or undergoing ART.

422 - The outcome of testicular sperm extraction in patients with non-obstructive azoospermia with a history of undescended testis

422 - The outcome of testicular sperm extraction in patients with non-obstructive azoospermia with a history of undescended testis

Prediction of microdissection testicular sperm extraction outcome in men with idiopathic nonobstruction azoospermia

The aim of the present study is to assess whether the preoperative clinical indicators have an impact on sperm retrieval rate (SRR) in men with idiopathic nonobstructive azoospermia (NOA).We retrospectively studied 241 consecutive men with NOA who underwent microdissection testicular sperm extraction from 2016 to 2019 in the Reproductive Medicine Center, including 154 patients diagnosed with idiopathic NOA. They were grouped according to preoperative indicators, including average testicular volume, follicle-stimulating hormone (FSH), luteinizing hormone, Testosterone (T), and pathology, respectively.The overall SRR was 20.0% (31/155). Men with testicular volume of ≤5 mL had significant higher SRR than men with testes 5 to 10 and ≥10 mL (35.6% vs 12.3%, P = .002; 35.6% vs 16.2, P = .049, respectively). The SRR in men with FSH ≥ 24.8 mIU/mL was significant higher, compared with FSH level of 12.4 to 24.8 mIU/mL (32.6% vs 15.8%, P = .033). Men with Sertoli cell-only had significantly lower SRR than other pathological type (8.1%). Men with an FSH ≥ 24.8 mIU/mL in testicular volume ≤5 mL group had a significantly higher SRR than FSH level of 12.4 to 24.8 mIU/mL in testicular volume of ≤5 to 10 mL group (44.0% vs 11.4%, P = .002). Men with a luteinizing hormone level of 8.6 to 17.2 mIU/mL in testicular volume of 5 to 10 mL group had a poor prognosis, with an SRR of only 6.5%.Severely reduced testicular volume (≤5 mL) and severely increased FSH level (≥24.8 mIU/mL) had the better sperm retrieval outcome, which can be used as independent predictors in men with idiopathic NOA. And a combination of testicular volume and the hormone seemed to be useful in further increase predictive value.

Obesity with High Body Mass Index Does Not Influence Sperm Retrieval in Males with Azoospermia.

BackgroundThe aim of this study was to evaluate the influence of male body mass index (BMI) on the retrieval of sperm from azoospermic patients who were undergoing testicular sperm extraction (TESE).Material/MethodsThe study included retrospective data of male patients suffering from non-obstructive azoospermia (NOA). Age, BMI, testicular volumes, the serum concentration of the follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone, and prolactin were investigated and collected.ResultsA total of 75 azoospermic males were evaluated between 2014 and 2019, including 35 patients (46.7%) with positive sperm retrieval. The majority of patients (57.3%) had normal BMI (between 20 kg/m2 and 25 kg/m2) or first degree obesity (from 25 kg/m2 to 30 kg/m2). No statistically significant correlation between BMI and positive sperm retrieval or hormone levels (LH, FSH, SHBG, prolactin) were found. However, lower serum testosterone levels were observed in patients with higher BMI (P=0.035). Receiver operating characteristic curve analysis showed that none of the hormones could potentially predict the positive outcome of TESE.ConclusionsThe hormonal levels or patient’s BMI could not predict positive sperm retrieval outcome, however a negative correlation between serum testosterone and BMI levels was calculated implicating influence on fertility.

Determining an optimal cut-off value for follicle-stimulating hormone to predict microsurgical testicular sperm extraction outcome in patients with non-obstructive azoospermia.

Objective To determine the optimal cut-off value for follicle stimulating hormone (FSH) to predict the outcome of microsurgical testicular sperm extraction (micro-TESE) in patients with nonobstructive azoospermia (NOA). Subjects and methods We included a total number of 180 patients with NOA. The serum level of FSH was determined and all the subjects underwent micro-TESE. We determined the optimal cut-off value for FSH and assessed whether the test could be effectively used as a successful predictor of sperm retrieval by calculating the Receiver Operating Characteristic (ROC) area under the curve. Results Overall we included a total number of 171 patients with mean age of 34.3 ± 8.6 years. The micro-TESE was considered to be successful in 79 (43.8%) while it failed in 92 (56.2%) patients. We found that the mean level of serum FSH was significantly higher in group those with failed micro-TEST compared to successful group (p < 0.001). The cut-off value for FSH was calculated to be 14.6 mIU/mL to predictive the outcome of micro-TESE with a sensitivity of 83.5% [73.5%-90.9%] and a specificity of 80.3% [69.5%-88.5%]. At this value, the other parameters were calculated to be PPV, 81.5%; NPV, 82.4; LR+, 4.23; and LR-, 0.21. Conclusions The results of the current study indicate that FSH plasma levels above 14.6 mIU/mL can be considered to be the failure predictor of the micro-TESE in NOA patients.

Sperm retrieval rates in non-mosaic Klinefelter patients undergoing testicular sperm extraction: What expectations do we have in the real-life setting?

A recent meta-analysis (Human Reproduction Update 23, 2017 and 265) reported positive sperm retrieval rates (SRR) in 50% of patients with Klinefelter syndrome (KS) undergoing testicular sperm extraction (TESE). However, these results do not reflect the rates of SR that we observe in clinical practice. We assessed the rate and potential predictors of SR in Klinefelter patients in the real-life setting. We reviewed clinical data of 103 KS men who underwent TESE between 08/2008 and 03/2019 at five tertiary referral Andrology centers. Patients underwent testis ultrasound, hormonal evaluation, and genetic testing. All patients were azoospermic based on the 2010 WHO reference criteria. Conventional TESE (cTESE) or microsurgical TESE (mTESE) was performed based on the surgeon's preference. We used descriptive statistics and logistic regression models to describe the whole cohort. Median (IQR) patient's age was 32 (24-37) years. Baseline serum FSH and total testosterone levels were 29.5 (19.9-40.9) mUI/mL and 3.8 (2.5-11.0) ng/mL, respectively. Conventional TESE and mTESE were performed in 38 (36.5%) and 65 (63.5%) men, respectively. The sperm retrieval rate was 21.4% (22/103 men). Fifteen patients used spermatozoa for ICSI and five ended in live birth children. Patients with positive SR were similar to those with a negative TESE in terms of clinical, hormonal, and procedural parameters (all P>.05). Logistic regression analyses confirmed the lack of association between clinical, hormonal, and procedural parameters with SR outcome. Given the conflicting results in the literature regarding SRR in KS, patients should be carefully counseled regarding TESE outcomes based on data from published literature and local results. In the real-life setting, we observed a lower SRR (21.4%) than that reported in meta-analyses in our cohort of KS patients. No associations between clinical, hormonal, and procedural variables with TESE success were found.

Letrozole before TESE in Non-Obstructive Azoospermia, Does It Affect Sperm Retrieval Rate, A Retrospective Study

Objective: This study was designed to evaluate the effect of letrozole 2.5 mg, an aromatase inhibitor, on the sperm retrieval rate (SRR) by the testicular sperm extraction (TESE) procedures that was done for the treatment of males with non-obstructive azoospermia (NOA).Materials and methods: Data was collected retrospectively from males diagnosed with non-obstructive azoospermia who underwent TESE procedure in the duration between May 2010 until June, 2018. The collected data includes the age of the patient, body mass index (BMI), testicular volume, hormonal profile (FSH LH, prolactin, testosterone), and the use of letrozole preoperatively. Logistic regression was done to address the association of these parameters to the sperm’s retrieval rate.Results: The study screaned 145 patients. Eighty patients fit the inclusion criteria and thus they were statistically analyzed. The use of letrozole was associated with negative TESE outcome (p=0.006), odd (0.154) CI 0.04-0.579. The other factors had no significant correlation to the TESE results.Conclusion: The evidence in this study showed an adverse effect of letrozole use on TESE results of those with high FSH.