Successful Sperm Retrieval Research Articles

Microdissection testicular sperm extraction outcomes in azoospermic patients post-orchidopexy surgery: A systematic review and meta-analysis.

Cryptorchidism is a common cause of male infertility, often necessitating microdissection testicular sperm extraction (m-TESE) for sperm retrieval post-surgery. However, uncertainties persist regarding m-TESE outcomes and influencing factors following cryptorchidism surgery. A systematic review and meta-analysis were conducted to evaluate sperm retrieval rates (SRR) among patients undergoing m-TESE after cryptorchidism surgery. Factors including age at orchidopexy, age at m-TESE, type of cryptorchidism, serum hormone levels, testicular volume, and interval from surgery to m-TESE were analyzed for their impact on SRR.Nine studies encompassing 935 patients were included. The overall SRR was 57% (95% confidence interval [CI] 51% to 63%). Compared to patients with negative sperm retrieval (SR-), patients with positive sperm retrieval (SR+) underwent m-TESE at an older age (1.81 years; 95% CI 1.17 to 2.45) and orchidopexy at a younger age (-3.35 years; 95% CI -6.34 to -0.36). Different types of cryptorchidism (including high scrotal, inguinal canal, intra-abdominal) significantly influenced SRR (P<0.05). Serum testosterone, follicle-stimulating hormone, luteinizing hormone levels and testicular volume showed no significant correlation with SRR (P>0.05). Furthermore, SR- patients typically experienced shorter intervals from orchidopexy to m-TESE compared to SR+ patients (34.09 months; 95% CI 0.40 to 67.77). Earlier orchidopexy and much later m-TESE procedures, as well as undescended testis closer to the scrotum, increase the likelihood of successful sperm retrieval. Orchidopexy for cryptorchidism should be done as early as possible, whether it is performed before 18 months of age or detected at a much older age. In patients with undetected cryptorchidism and azoospermia after puberty, m-TESE should not be performed immediately after orchidopexy, the optimal interval from orchidopexy to m-TESE still requires further study.

A Nomogram Predicting Testicular Sperm Extraction Success in Men With Non-obstructive Azoospermia: A Multi-center Study

ObjectivesTo develop an efficient and easy-to-use nomogram which can predict testicular sperm extraction(TESE) success in men with non‐obstructive azoospermia(NOA) by using pre-operative parameters. Materials and MetodsData of 3093 men who underwent TESE for NOA were included in this study. Demographic data, testis volumes, presence of varicocele, length of infertility, history of previous surgeries, history of genitourinary infections, smoking status, chromosome abnormalities, presence of Y-chromosome microdeletion, family history of infertility, testis biopsy, surgical data, sperm retrieval rate, final pathology obtained at testicular sperm extraction, follicle stimulating hormone, luteinizing hormone, testosterone levels were recorded. The primary outcome was to develop an efficient nomogram which can predict the TESE success in men with NOA. The secondary outcomes were identifying the significant pre-operative parameters which are associated with success in TESE. ResultsSperm retrieval rate was 50.2%(1553/3093). Testis volume, history of varicocelectomy, chromosome abnormalities, presence of Y-chromosome microdeletion were shown to affect sperm retrieval rate significantly(p<0.05). Sperm retrieval success was higher in men with older age, higher testis volume(>10mL), lower follicle stimulating hormone level(≤ 12.92mIU/mL), lower luteinizing hormone level, and higher testosterone level(p<0.05). Only testis volume and patient’s age were associated with succesful sperm retrieval in multivariate logistic regression analysis. ConclusionIn men with NOA, high testis volume, old age, low follicle stimulating hormone level, low luteinizing hormone level, and high testosterone level are advantageous for successful sperm retrieval in TESE. Herein we present a nomogram which can predict the outcome of TESE in men with NOA with adequate success.

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

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

Human sperm RNA in male infertility.

The function and value of specific sperm RNAs in apparently idiopathic male infertility are currently poorly understood. Whether differences exist in the sperm RNA profile between patients with infertility and fertile men needs clarification. Similarly, the utility of sperm RNAs in predicting successful sperm retrieval and assisted reproductive technique (ART) outcome is unknown. Patients with infertility and fertile individuals seem to have differences in the expression of non-coding RNAs that regulate genes controlling spermatogenesis. Several RNAs seem to influence embryo quality and development. Also, RNA types seem to predict successful sperm retrieval in patients with azoospermia. These findings suggest that sperm RNAs could influence decision-making during the management of patients with infertility. This evidence might help to identify possible therapeutic approaches aimed at modulating the expression of dysregulated genes in patients with infertility. Performing prospective studies with large sample sizes is necessary to investigate cost-effective panels consisting of proven molecular targets to ensure that this evidence can be translated to clinical practice.

Evaluation of the Results of Intracytoplasmic Sperm Injection and Microdissection Testicular Sperm Extraction Treatments in Patients with Nonobstructive Azoospermia According to Etiological Factors: A Retrospective Analysis

Objective: This study aimed to retrospectively compare the results of microdissection testicular sperm extraction (microTESE) and Intracytoplasmic sperm injection (ICSI) treatments in nonobstructive azoospermia (NOA) patients with different aetiologies. Determinants (clinical characteristics) for microTESE outcomes were compared between patients with successful sperm retrieval (SSR) and sperm retrieval failure (SRF). Methods: A total of 510 NOA patients who underwent microTESE between January 2015 and January 2024 were included in this study. Patients were classified according to the cause of NOA and SSR, fertilisation rate, clinical pregnancy, and overall live birth rate were evaluated. Results: The SSR rate was 44.1% in the whole population. The idiopathic patient group had the lowest SSR rate (X2: 34.81; p&lt;0.01). There was no difference between the groups in terms of fertilisation rate, clinical pregnancy and overall live birth rate. There was a negative correlation between age and SSR rates in patients with idiopathic NOA (t:-0.27; p&lt;0.01). SSR rates were higher in patients with cryptorchidism (right: t:0.8; P:0.003; left: t:0.72; p:0.002) and mumps orchitis (right: t:0.76; P&lt;0.01; left: t:0.76; p=0.003). Conclusion: Etiology has a significant role in terms of SSR in patients with NOA. SSR was found to be significantly less in patients with idiopathic NOA compared to other causes. In addition, age and testicular volume were significant predictive factors for SSR in patients with idiopathic and acquired NOA.

Second chance in fertility: a comprehensive narrative review of redo micro-TESE outcomes after initial failure.

When microdissection testicular sperm extraction (micro-TESE) fails, a redo procedure may be the only option for patients who want a biological child. However, there are many gaps of knowledge surrounding the procedure, which need to be addressed to help clinicians and patients make informed decisions. This review explores redo micro-TESE in the context of nonobstructive azoospermia (NOA). Literature was searched using Google Scholar, Medline, and PubMed. Search terms were "NOA" AND "second microdissection testicular sperm extractions" AND "redo microdissection testicles sperm extraction" AND "repeat microdissection testicular sperm extractions" AND "failed microdissection testicular sperm extractions" AND "salvage microdissection testicular sperm extractions". Only original articles in English were included. A total of nine articles were included, consisting of four retrospective and five prospective studies. The time gap between the first and second micro-TESE varied from 6 months to 24 months. Most of the included studies reported successful surgical sperm retrieval (SSR) in the second micro-TESE in the range of 10%-21%, except in one study where it reached 42%. It has not been presented any definitive information about the use of hormonal treatment or the benefit of varicocelectomy prior to the second micro-TESE. Patients with hypospermatogenesis and Klinefelter syndrome (KS) had the highest chance of success in redo surgery. In conclusion, redo micro-TESE following a negative procedure can lead to sperm recovery in 10%-21%. Patients with hypospermatogenesis and KS have a higher chance of success. There is no enough evidence to conclude which is the best hormonal stimulation if any before a redo surgery.

O-258 Clinical factors associated with sperm retrieval success in hypogonadal nonobstructive azoospermic males undergoing microdissection testicular sperm extraction

Abstract Study question What factors are associated with sperm retrieval (SR) success through microdissection testicular sperm extraction (micro-TESE) in nonobstructive azoospermic (NOA) males with biochemical hypogonadism? Summary answer The SR success in hypogonadal NOA males is associated with FSH levels, pre-micro-TESE hormonal stimulation, presence of clinical varicocele, varicocelectomy history, and testicular histopathology results. What is known already Previous studies have investigated clinical predictors for SR success in NOA males, such as testicular volume, genetic status, and testicular histopathology, but these factors cannot be modified before SR. On the other hand, pre-SR hormonal stimulation and varicocele repair have shown potential for improving SR rates, although the evidence is inconclusive due to heterogeneity in patients and treatments. This lack of information makes it difficult for clinicians to determine whether medical or surgical interventions should be used before SR in NOA patients. Study design, size, duration This observational cohort study involved 616 hypogonadal NOA patients with primary spermatogenic failure who underwent micro-TESE at a University-affiliated center for male reproductive health between 2014 and 2021. Biochemical hypogonadism was defined as total testosterone (T) levels &amp;lt;350 ng/dL, measured from morning venous samples. All patients were naïve concerning previous SR attempts and were categorized into two groups based on whether they received pre-SR hormonal stimulation with recombinant gonadotropins (hCG alone or combined with FSH). Participants/materials, setting, methods Patients aged 23-55 underwent comprehensive clinical, laboratory, and histopathological evaluations for NOA. Multivariable logistic regression analysis explored the associations between patient variables and micro-TESE success. Adjusted risk ratio (aRR) assessed the relationship between SR success and relevant predictors. SR rates were compared between patients receiving hormonal stimulation and those who did not. Logistic regression analysis evaluated the effect of baseline FSH levels, stratified by normogonadotropic (&amp;lt;12 IU/L) and hypergonadotropic (≥12 IU/L) classes, on SR success. Main results and the role of chance The overall micro-TESE success rate was 56.6%. Independent predictors of SR success included baseline FSH levels (aRR 0.98, 95% CI 0.96-0.99, p = 0.04), pre-SR hormonal stimulation (aRR 1.52, 1.28-1.73, p = 0.0002), the presence of clinical varicocele (aRR 0.09, 0.01-0.66, p = 0.04), history of previous varicocelectomy (aRR 1.53, 1.14-1.84, p = 0.01), and testicular histopathology results (p &amp;lt; 0.05). Patients who received hormonal stimulation achieved higher SR success rates than untreated patients (62.5% [182/291] vs. 51.4% [167/325], p = 0.006; aRR 1.52, 95% CI 1.28-1.73). Among patients receiving hCG-based hormonal stimulation, pre-micro-TESE T levels and Delta T (absolute increase in T levels from baseline) were associated with SR success (p &amp;lt; 0.0001). A pre-micro-TESE T level of 418.5 ng/dL (AUC: 0.78) and a Delta T of 258 ng/dL (AUC: 0.76) distinguished treated patients with positive and negative SR outcomes. Subgroup analysis by baseline FSH levels showed that normogonadotropic individuals (aRR 1.41, 1.16-1.58, p = 0.002) benefited from hormonal stimulation, whereas hypergonadotropic subjects did not (aRR 1.20, 0.86-1.50, p = 0.23). The frequency of patients showing biochemical hypogonadism after hCG stimulation was reduced to 22.3% (65/291). The micro-TESE postoperative complication rate was 2.3% (14/616), while the frequency of patients exhibiting adverse effects presumably attributed to hormonal stimulation was 10.3% (30/291). Limitations, reasons for caution Limitations of the study include its observational nature and the absence of pregnancy data. The study focused on micro-TESE as the SR method and hormonal stimulation solely based on hCG (as monotherapy or associated with FSH), so results may differ with other treatments. Wider implications of the findings Our study underscores the complexity of counseling hypogonadal men with NOA, stressing the significance of assessing various factors. While our findings suggest potential benefits from pre-SR interventions, particularly hormonal stimulation and varicocele repair, none of the identified predictors can definitively determine the likelihood of successful SR. Trial registration number NCT05110391

P-007 Surgical sperm retrieval rate in men with Klinefelter syndrome is associated with testicular volume - but not with body constitution or Sertoli cell markers

Abstract Study question Do sperm retrieval and pregnancy rates in men with Klinefelter syndrome (KS) depend upon sperm retrieval method, age, testicular volume, body weight, and hormone concentrations? Summary answer Successful sperm retrieval was significantly associated with total testicular volume but not with sperm retrieval method, age, body weight, BMI, FSH, inhibin-B or AMH. What is known already Testicular sperm can be retrieved from approximately 40% of men with KS, resulting in an average pregnancy rate of 16%. The sperm retrieval rate seems to be unrelated to the age of the man and to preoperative FSH-levels. A decrease in testosterone concentration is usually observed 3 months after surgery. Possible negative effects of testosterone substitution therapy prior to surgery and the predictive value of body constitution, testicular volume and the Sertoli cell markers, AMH and inhibin-B, for sperm retrieval success in KS men are only partly known. Study design, size, duration A total of 14 KS patients underwent subcapsular orchiectomy and 34 KS patients underwent m-TESE at Centre of Andrology &amp; Fertility Clinic, Odense University Hospital. Pre-surgery examination included ultrasonography of the testicles, genetic analyses (standard chromosome analysis and screening for Y microdeletions and CFTR variants) and hormone analyses (including FSH, LH, testosterone, estradiol, prolactin, TSH, AMH, inhibin-B). Testosterone, LH, and FSH were also measured 3 months after surgery. Participants/materials, setting, methods Forty-three men had a 47,XXY karyotype, while 5 (2 from the subcapsular group and 3 from the m-TESE group) had a mosaic karyotype including 47,XXY. Subcapsular orchiectomy was performed unilaterally, while m-TESE was usually performed bilaterally. To avoid freezing the sperm retrieved, oocytes from the female partner was aspirated and vitrified after FSH-stimulation according to our usual IVF protocols. Oocytes were thawed on the day of sperm retrieval and embryos transferred in estrogen-progesterone stimulated cycles. Main results and the role of chance Sperm were obtained in 19 (40%) of the 48 men with KS. In 10 couples (21%) pregnancy was obtained and 7 women (15%) gave birth to at least one child resulting in ten children (6 girls and 4 boys), while one pregnancy is still ongoing. In the group who had a subcapsular orchiectomy, 5 (36%) had sperm retrieved, and pregnancy was obtained in 3 (20%) cases. Two gave birth to a child, while the third woman have had several abortions, most likely due to large fibromyomas of the uterus. In the m-TESE group 14 (41%) had sperm retrieved, and pregnancy was obtained in 7 (21%) cases. Five women (15%) gave birth to 8 children, while 1 pregnancy is still ongoing and the seventh experienced an early pregnancy loss. Furthermore, 3 couples have still not embryos transferred. Sperm were found in 3 men (60%) with mosaic karyotype. Sperm retrieval success was significantly associated with testicular volume (mean total testicular volumes of 3.4 mL vs. 2.3 mL; p &amp;lt; 0.01) but not with age, height, body weight, BMI or preoperative FSH, inhibin-B or AMH levels. Testosterone levels measured 3 months after the surgery, did not differ between men irrespective of surgical method. Limitations, reasons for caution The numbers of patients are limited and randomized studies with sufficient power are difficult to perform. AMH and inhibin-B, were only measured in the m-TESE group. Wider implications of the findings In KS patients, sperm retrieval and pregnancy rates were similar irrespective of the sperm retrieval method. Also serum testosterone 3 months postoperatively and cosmetic results experienced by patients were similar. Multicenter studies and larger studies are needed to provide more detailed information of the potential predictors for successful sperm retrieval. Trial registration number Not applicable

O-259 Seminal plasma cell-free RNA to predict testicular biopsy sperm retrieval outcome in azoospermic men

Abstract Study question Is there a way to assess seminal plasma of NOA men to predict a successful sperm retrieval at testicular biopsy? Summary answer Multi-omics approach in seminal plasma of NOA men provides reliable prediction on the spermatogenic activity within the seminiferous tubule. What is known already Microdissection testicular sperm extraction (m-TESE) in NOA men successfully retrieved spermatozoa in about 60% of the cases. While several algorithms have been investigated aiming at estimating spermatogenic progress such as age, serum FSH, inhibin B, and genetics, there is no specific assay that can do so reliably. Even histopathology is often inconclusive while equally invasive. Recently, epigenetic analysis on testicular biopsy specimens has shown a differential gene expression in relation to the origin of azoospermia and spermatogenic function (Cheung, et al, 2024, in press). Study design, size, duration Over a 4-year period, twenty-eight men were deemed azoospermic following several failed extensive semen analyses. Transcriptomic analysis was performed by RNAseq on seminal fluid and the specific gene expression were evaluated and compared. In addition, DNAseq and proteomics were carried out to confirm our findings. These patients then underwent micro-TESE by a single surgeon and were divided into two cohorts based on whether spermatozoa was successfully retrieved or not. Participants/materials, setting, methods RNA and DNA were isolated from seminal plasma using a commercial kit and sequenced by Illumina HiSeq3000/4000 platform. Differentially expressed genes (DEGs) were assessed and compared to a fertile donor control using DESeq2 and Gene Ontology analysis. An absolute log2fold change of &amp;gt; 1 and a P-value of &amp;lt; 0.0005 were considered statistically significant. Gene mutations were detected by CLC Genomic Server 9.0. Main results and the role of chance Transcriptomic in 28 ejaculates from iNOA men browsed 21,855 genes against a fertile donor. Of 3,505 imbalanced genes, 12 were consistently imbalanced in 12 men, while 19 genes were imbalanced in remaining 16. Among the 2 cohorts, 8 common imbalanced genes were found. Particularly TPTE2, a testis-specific gene that regulates spermatogenesis, was overexpressed in 10/12 men (OE-12-cohort), while underexpressed in the remainder 16 (UE-16-cohort). DNAseq showed that TPTE2 was conserved in the OE-12-cohort, while exhibiting a frameshift mutation in the UE-16-cohort. Most interestingly, NEU1, a gene involved in acrosome development and fertilization, was found to be consistently and concurrently overexpressed in the OE-12-cohort, while being convserly underexpressed in all the men in the UE-16 cohort. DNAseq confirmed the NEU1 gene exhibited a synonymous mutation in the OE-12 and a frameshift mutation in the UE-16-cohort. About 1-2 months after the DEG analysis was completed, all of the patients underwent m-TESE. The 12 men from the OE-12-cohort all had successful retrieval of spermatozoa at m-TESE, conversely the 16 men from the UE-16-cohort all consistently failed to yield spermatozoa at testicular surgery in spite of extensive search for several hours and by multiple embryologists. Moreover, histopathology confirmed spermatogenic status in both OE-12&amp;UE-16-cohorts. Limitations, reasons for caution Using non-invasive RNAseq and DNAseq on the seminal plasma has allowed us to identify DEGs that may be used to predict whether a patient with iNOA would have a successful or failed sperm retrieval with micro-TESE. However, these results are preliminary and should be further validated in larger study cohort. Wider implications of the findings Transcriptomics on the ejaculates of men with iNOA represents a noninvasive tool to detect presence of residual spermatogenesis. If confirmed by further studies, this precision medicine method may be utilized in order to properly counsel patients regarding their future prognosis. Trial registration number Not applicable

P-075 A new clinically relevant classification of seminiferous tubules in Klinefelter Syndrome patients based on the karyotype of the Sertoli cells

Abstract Study question Can a new seminiferous tubule classification be made that indicates the chance of sperm retrieval by TESE in Klinefelter Syndrome (KS) patients? Summary answer Spermatogonia are only present in tubules with euploid Sertoli cells. Classification of tubules based on Sertoli cell ploidy may predict sperm retrieval success with TESE. What is known already KS patients can have children thanks to focal spermatogenesis. However, this can only happen if sperm is produced. Histological classification of seminiferous tubules in these patients has been made based on the maturity of the Sertoli cells (type A and type B seminiferous tubules). However, so far there is no classification predicting the presence of germ cells. In case two X chromosomes are present, one is inactivated. The histone-3-lysine-27-tri-methylation (H3K27me3) protein is involved in X chromosome inactivation and its immunohistochemical staining may be used for a new seminiferous tubule classification based on the karyotype of Sertoli cells. Study design, size, duration Inactive X (Xi) chromosomes were immunohistochemically stained with H3K27me3 and seminiferous tubules were classified as Xi+ tubules (presence of inactive X in Sertoli cells) or Xi- tubules (absence of inactive X in Sertoli cells). Testicular biopsies were used from 17 non-mosaic KS adult patients. Participants/materials, setting, methods After tissue fixation, processing, and paraffin embedding, sections were cut at 5 µm. Immunohistochemical staining was applied with antibodies H3K27me3 (for inactive X chromosome), MAGE-A4 (for spermatogonia), and SOX9 (for Sertoli cells). Seminiferous tubules in testicular sections were classified as Xi+ or Xi- tubules and analyzed for the presence of spermatogonia or focal spermatogenesis. X chromosome number in spermatogonia and Sertoli cells was confirmed by the FISH method using chromosome 18, Y, and X probes. Main results and the role of chance A total of 311 (18±16) seminiferous tubule sections were analyzed in testicular tissue of 17 KS men. Of the 311 tubules analyzed, 253 (14±16) of the tubules were Xi- tubules and 58 (3±4) were Xi+ tubules. Spermatogonia were present in 41 of the Xi- tubules. As an exception, only one patient had spermatogonia in two Xi+ tubules, but these tubules were immature and spermatogenesis was not observed. Ongoing spermatogenesis was observed in two of Xi- tubules in one of the patients. Sixteen of the patients had both Xi- tubules and Xi+ tubules in their testicular sections. In 13 of these 16 patients with Xi- tubules, sperm was either obtained as a result of TESE or spermatogonia were observed in the Xi- tubules. Limitations, reasons for caution In Klinefelter patients, there are few seminiferous tubules due to widespread testicular fibrosis and degeneration of seminiferous tubules. Studies including more patient samples are needed for more definitive and comprehensive conclusions. Wider implications of the findings Spermatogonia are only present in tubules with euploid Sertoli cells. Therefore, we hypothesize that focal spermatogenesis only can occur in tubules with euploid Sertoli cells. Xi+ and Xi- seminiferous tubule classification based on H3K27me3 staining may thus be used to predict sperm production in KS patients. Trial registration number Not applicable

Testicular ultrasonic microvascular density in assessing spermatogenesis and predicting successful sperm retrieval.

The relationship between microcirculatory disorders and testicular spermatogenesis is an area of ongoing interest among urologists. The objective of this prospective observational study was to investigate the correlation between testicular microcirculation and spermatogenesis, as well as the predictive value of ultrasonic microvascular density (UMVD) and ultrasonographic volume estimation (UVE) in successful sperm retrieval among men with non-obstructive azoospermia (NOA). Testicular UMVD derived from Angio PLUSTM Planwave Ultrasensitive Imaging (AP), UVE were obtained. Participants were divided into 4 groups (normozoospermia; asthenozoospermia, teratozoospermia, or asthenoteratozoospermia; oligozoospermia; NOA). The study included a total of 875 participants. No significant difference was found in UMVD-mean between different semen groups (P>0.05). A total of 108 participants with NOA underwent microdissection testicular sperm extraction (micro-TESE). Participants with successful sperm retrieval (40 cases) showed significant differences in testicular UMVD and UVE compared to those with negative retrieval (68 cases) (P<0.01). We generated receiver operating characteristic (ROC) curves for UMVD and testicular UVE to differentiate participants with successful sperm retrieval from those without. The area under the curve (AUC) was 0.760 [95% confidence interval (CI): 0.658-0.849, P<0.01] for UMVD and 0.716 (95% CI: 0.609-0.822, P<0.01) for testicular UVE, respectively. The optimal cutoff value was determined based on the maximum Youden index. When UMVD was set at 28.50/cm2, its sensitivity and specificity were calculated as 57.5% and 85.3%, respectively. For testicular UVE, a cutoff value of 8.94 mL resulted in a sensitivity of 60.0% and specificity of 82.4%. Combining UMVD with testicular UVE improved diagnostic performance (AUC: 0.856, 95% CI: 0.772-0.929, P<0.01) with a sensitivity of 79.4% and specificity of 77.5%. The present study demonstrates the utility of AP as a predictive tool for successful sperm retrieval prior to micro-TESE. Furthermore, the combination of testicular UMVD and UVE provides a highly valuable diagnostic approach for predicting micro-TESE success and can be routinely implemented before the procedure. A testicular UMVD exceeding 28.50/cm2 and a testicular UVE larger than 8.94 mL strongly indicate favorable outcomes in terms of sperm retrieval.

Construction of m6A-Related Gene Prediction Model and Subtype Analysis in Non-Obstructive Azoospermia Based on Bioinformatics.

Non-obstructive azoospermia (NOA) is a severe and common cause of male infertility. Currently, the most reliable predictor of sperm retrieval success in NOA is histopathology, but preoperative testicular biopsy often increases the difficulty of sperm retrieval surgery. This study aims to explore the characteristics of N6-methyladenosine (m6A) modification in NOA patients and investigate the potential biomarkers and molecular mechanisms for pathological diagnosis and treatment of NOA using m6A-related genes. NOA-related datasets were downloaded from the GEO database. Based on the results of LASSO regression analysis, a prediction model was established from differentially expressed m6A-related genes, and the predictive performance of the model was evaluated using ROC curves. Cluster analysis was performed based on differentially expressed m6A-related genes to evaluate the differences in different m6A modification patterns in terms of differentially expressed genes (DEGs), biological features, and immune features. There were significant differences in eight m6A-related genes between NOA samples and healthy controls. The ROC curves showed excellent predictive performance for the diagnostic models constructed with ALKBH5 and FTO. DEGs of two m6A modification subtypes indicated the influence of m6A-related genes in the biological processes of mitosis and meiosis in NOA patients, and there were significant immune differences between the two subtypes. The NOA pathological diagnostic models constructed with FTO and ALKBH5 have good predictive ability. We have identified two different m6A modification subtypes, which may help predict sperm retrieval success rate and treatment selection in NOA patients.

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

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.

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

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. 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. 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. 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.

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

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

A detection model of testis-derived circular RNAs in serum for predicting testicular sperm retrieval rate in non-obstructive azoospermia patients.

Microdissection testicular sperm extraction is an effective method to retrieve sperm from non-obstructive azoospermia patients. However, its successful rate is less than 50%. To identify the predictive value of circular RNAs in serum for sperm retrieval rate in non-obstructive azoospermia patients. 180 non-obstructive azoospermia patients were recruited in this study, including 84 individuals with successful sperm retrieval and 96 individuals with failed sperm retrieval. Our study contained two phases. First, 20 patients, selected from the 180 patients, were included in screening cohort. In this cohort, the top 20 circular RNAs from our previous testicular circRNA profiles were verified between successful and failed sperm retrieval groups using real-time polymerase chain reaction. Six circular RNAs with the most significantly different expressions were selected for further verification. Second, the 180 patients were included as discovery cohort to verify the six circular RNAs. Circular RNAs were extracted from serum in each participant. Logistic regression analysis was further performed to identify the predictive value and the area under the curve analysis was used to evaluate diagnostic efficiency, sensitivity, and specificity. Six circular RNAs including hsa_circ_0058058, hsa_circ_0008045, hsa_circ_0084789, hsa_circ_0000550, hsa_circ_0007422, and hsa_circ_0004099 showed aberrant expressions between the successful and failed sperm retrieval group. In addition, both single-circular RNA panels and multi-circular RNA panels were finally verified to be significant in predicting sperm retrieval rate. Notably, multi-circular RNAs panels demonstrated better predictive abilities compared with single-circRNA panels, and the combined panel of six-circular RNAs (risk score=1.094×hsa_circ_0058058+0.697×hsa_circ_0008045+0.718×hsa_circ_0084789-0.591×hsa_circ_0000550-0.435×hsa_circ_0007422-1.017×hsa_circ_0004099-1.561) exhibited the best predictive ability in the present study with an AUC of 0.977, a sensitivity of 91.7% and a specificity of 86.5%. A higher risk score indicated a higher risk of failure in sperm retrieval. Our study was the first to report that testis-derived circular RNAs in serum have the ability to predict sperm retrieval rate in non-obstructive azoospermia patients, whether it is a single-circular RNA or a combination of multi-circular RNAs.

Microsurgical Testicular Sperm Extraction: Predictive Factors and Outcomes for Men with Nonobstructive Azoospermia

Background. Nonobstructive azoospermia (NOA) is a frequent cause of male infertility, and microsurgical testicular sperm extraction (micro-TESE) is an effective technique for sperm retrieval in NOA cases. However, the predictive factors for successful sperm retrieval and the outcomes of micro-TESE in NOA patients are not fully understood. Methods. In this retrospective study, we evaluated the predictive value of preoperative data and outcomes of micro-TESE in 172 men with NOA who underwent the procedure between April 2012 and February 2021. Patients’ age, medical history, testicular size, hormonal profile, testicular histology, and sperm retrieval were recorded. Results. 172 cases of micro-TESE were performed (99 unilateral and 73 bilateral) and testicular sperm retrieval rate (SRR) was 72.7%. There was no statistical difference in age, testicular size, and hormonal profiles between positive SRR and negative SRR groups. Clinical varicocele and previous orchitis did not significantly affect the result of micro-TESE. Y chromosome microdeletions were detected in seven patients. On histological examination, hypospermatogenesis was found in 39% of patients who underwent testicular biopsy. SRR was higher in patients with hypospermatogenesis than in other groups. Conclusions. Testicular microdissection is an effective and safe procedure for nonobstructive azoospermia patients, regardless of the different etiologies and preoperative data. Age, testicular size, and hormonal levels did not predict the success of micro-TESE. The presence of hypospermatogenesis was associated with a higher SRR. Clinical varicocele and previous orchitis were not significantly associated with the outcome of micro-TESE.

Timing of Testicular Biopsy in Relation to Oocyte Retrieval and the Outcomes of Intracytoplasmic Sperm Injection.

We evaluate microscopic (micro) testicular sperm extraction (TESE) timing relative to oocyte retrieval on intracytoplasmic sperm injection outcome. Couples with nonobstructive azoospermia who underwent intracytoplasmic sperm injection with freshly retrieved spermatozoa were analyzed based on whether micro-TESE was performed at least 1 day prior to oocyte retrieval (TESE-day-before group) or on the day of oocyte retrieval (TESE-day-of group). Embryology and clinical outcomes were compared. The percentage of patients who underwent a successful testicular sperm retrieval was significantly lower in the TESE-day-before cohort (62%) than in the TESE-day-of cohort (69%; odds ratio [OR] 1.4, 95% CI [1.1, 1.7], P < .001). The fertilization rate was also found to be significantly lower in the TESE-day-before group (45%) than in the TESE-day-of group (53%; OR 1.4, 95% CI [1.2, 1.7], P = .01). Although the association between the cleavage rate and TESE timing was not statistically significant, the implantation rate was found to be significantly higher in the day-before cohort (28%) than in the day-of cohort (22%; OR 0.7, 95% CI [0.6, 0.9], P = .01). Nevertheless, it was found that the clinical pregnancy and delivery rates were not statistically significantly associated with the TESE timing. Although sperm retrieval and fertilization rates were lower in the TESE-day-before cohort, the 2 cohorts showed comparable embryologic and clinical outcomes. Micro-TESE can be performed before oocyte harvesting to provide physicians ample time to decide between cancelling oocyte retrieval or retrieving oocytes for cryopreservation.

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

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. 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). A retrospective cohort study included 108 NOA men treated at a public fertility unit and a private fertility centre (May 2009-May 2022). live birth rate (LBR); secondary outcomes: sperm retrieval rate, pregnancy rate, and neonatal outcomes. 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. 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%.

(336) Sperm Retrieval Success During Tese: Prognostic Factors in Non-obstructive Azoospermia Patients

(336) Sperm Retrieval Success During Tese: Prognostic Factors in Non-obstructive Azoospermia Patients