Successful 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.

P-079 Transcriptomic Analysis of Seminal Plasma in NOA Men as a Predictor of Successful Testicular Sperm Extraction

Abstract Study question Could transcriptomic profiling of semen ejaculate be used to predict successful testicular sperm retrieval for men with idiopathic non-obstructive azoospermia (iNOA)? Summary answer Transcriptomic analysis of seminal plasma RNA in iNOA men revealed gene imbalances that consistently correlated with the success of retrieving spermatozoa via a testicular biopsy. What is known already Although microdissection testicular sperm extraction (m-TESE) in NOA men results in successful spermatozoa retrieval in about 60% of the cases, it is difficult to predict which cases will fail to recover sperm. While several algorithms have been proposed to make this prediction, such as age, serum FSH, inhibin B, and genetics, there is no one factor that can do so reliably. Even histopathology fails to be more accurate, and it is 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. Study design, size, duration Over a 3-year period, 23 men diagnosed with iNOA underwent repeated extensive semen analyses and were deemed azoospermic. These patients were categorized based on whether spermatozoa were subsequently retrieved (+Sperm) or not (-Sperm) at micro-TESE. Transcriptomic analysis was performed by RNAseq, and significant differentially expressed gene (DEG) profiles were assessed and compared between the two cohorts. DNAseq was then used to confirm our findings. Participants/materials, setting, methods RNA and DNA were isolated from seminal plasma using a commercially available spin column kit and sequenced by Illumina HiSeq 3000/4000 platform at 2x150bp. Transcriptomic profiling was carried out in comparison to a fertile donor control and among the two cohorts. An absolute log2fold change of > 1 and a P-value of < 0.0005 were considered statistically significant. Main results and the role of chance Transcriptomic analyses of ejaculates from 23 azoospermic men were assessed for a total of 21,855 genes against a fertile donor control. Subsequently, 11/23 (47.8%) men (39.0±12yrs) underwent successful testicular sperm retrievals. Their DEG profiles revealed 1,409 imbalanced genes. However, 13 were consistently imbalanced among them: 8 involved in spermatogenesis and 5 in sperm function. Alternatively, for the 12 men in the –Sperm cohort (34.3±5yrs), 1,265 imbalanced genes were identified with 12 common imbalanced genes associated with spermatogenesis (n = 5), sperm function (n = 3), sperm maturation (n = 1), and cell cycle regulation (n = 3). When comparing the DEG profiles between the + and –Sperm cohorts, 8 commonly shared imbalanced genes were identified. IGSF11-AS1, a gene expressed in the testis and implicated in spermatid development, was consistently underexpressed in all –Sperm men. TPTE2, a testis-specific gene regulating spermatogenesis, was overexpressed in 81.8% (9/11) of the individuals in the +Sperm cohort and conversely underexpressed in the -Sperm group. Most interestingly, NEU1, involved in acrosome development and fertilization, was consistently overexpressed in all individuals of the +Sperm group, yet clearly underexpressed in the entire –Sperm group. DNAseq showed that the NEU1 gene exhibited a synonymous mutation for the +Sperm group and a frameshift mutation in the –Sperm group. Limitations, reasons for caution Using noninvasive RNAseq and DNAseq on the seminal plasma has allowed us to identify DEGs that may be used to predict whether a patient with iNOA will have a successful or failed retrieval with micro-TESE. However, these results are preliminary and should be further validated in a larger study cohort. Wider implications of the findings Transcriptomics on the ejaculates of men with iNOA represents a noninvasive tool to detect the presence of residual spermatogenesis. Once confirmed, these findings may help guide patients in weighing their exposure to anesthesia and surgical risks. This would help to mitigate patient emotional and financial distress. Trial registration number N/A

P-034 Rate of testicular histology failure in predicting successful testicular sperm extraction in Non-Obstructive Azoospermia

Abstract Study question Does testicular histology predict successful or unsuccessful TEsticular Sperm Extraction (TESE) in Non-Obstructive Azoospermia (NOA) patients? Summary answer Testicular histology failed to predict successful TESE in 1 of 3 NOA patients. What is known already The management of patients with Non-Obstructive Azoospermia (NOA) involves TEsticular Sperm Extraction (TESE) combined with IntraCytoplasmic Sperm Injection (ICSI). Sperm retrieval is successful in up to 50% of men with NOA; however, there is no single clinical finding or investigation that can accurately predict a positive outcome. Previous studies have concluded that testicular histology is the best predictor of a successful or unsuccessful TESE. Study design, size, duration This is a retrospective study of 525 patients who underwent TESE between January 2018 and December 2020 in Humanitas Fertility Center. Participants/materials, setting, methods The cohort was dived in five groups: 287 NOA, 95 necrozoospermia, 18 anejaculation, 1 testicular trauma and 124 Obstructive Azoospermia (OA) patients. Main results and the role of chance Sperm was retrieved and cryopreserved in 218/287 patients with NOA (75,95%), 55/95 in necrozoospermia (57,89%), 18/18 anejaculation (100%), 1/1 testicular trauma (100%) and 120/124 in OA patients (96,77%). Interesting that, when we compare sperm recovery data through TESE with the histological assessment (HA) of corresponding testicular biopsy, we found discordance against HA. In particular we retrieved spermatozoa in 218 NOA patients but in 74 of them HA failed to detect them (33,94%). Moreover HA failed to detect spermatozoa in 8/55 (14,54%) in case of necrozoospermia, 1/18 (5,55%) in anejaculation and 10/120 (8,33%) in OA patients. Limitations, reasons for caution Testis's heterogeneity is a limitation of the study. Wider implications of the findings We found a discordance when HA is compared with sperm recovery data of corresponding testicular biopsy. This data suggest that in case of testicular diagnostics histology in 33,94% of NOA cases there is a wrong diagnosis and 1 of 3 patients it doesn’t retrieve and cryopreserve spermatozoa when it could. Trial registration number N A

Predictive factors of successful testicular sperm extraction for non-obstructive azoospermia with a history of bilateral cryptorchidism and normal testosterone.

This study aimed to assess the predictive factors of successful sperm retrieval in non-obstructive azoospermia with a history of bilateral cryptorchidism. This retrospective study included 103 patients with azoospermia who had micro-dissection testicular sperm extraction between January 2010 and January 2020. The median (range) age of the patients and their wives in the study group was 33 (21-44) and 24 (19-33)years, respectively. The patients with low testosterone level (<3ng/dl) were prescribed with human chorionic gonadotropin 5,000IU injection every 3days for 3months. Those with persistent low testosterone even after hormonal stimulation were excluded. Sperms were retrieved from 64 (62%) patients, whilst failed in 39 (38%) patients. On univariate analysis, the median testicular volume was significantly larger in the successful group versus the failed group (p<.001), serum FSH and serum LH were significantly lower in the successful group (p=.001), serum testosterone was significantly higher in the successful group compared to the failed group (p<.001) and the age of orchidopexy was lower in the successful group versus the failed group (p=.016). On multivariate analysis, the average testicular volume and the serum testosterone levels were independent factors for successful sperm retrieval.

TESTICULAR SPERM EXTRACTION (TESE) FOR INTRACYTOPLASMIC SPERM INJECTION (ICSI) IN SUB-SAHARAN AFRICA - A TWO - YEAR MULTI-CENTRE REVIEW IN GHANA

Several factors have been found to influence successful testicular sperm extraction treatment outcomes. This study evaluated treatment outcomes and assessed predictors of clinical pregnancy in obstructive azoospermia treated with testicular sperm extraction and intracytoplasmic sperm injection in Ghana.

P–038 Clinical outcomes of 77 testicular sperm extraction treatment cycles in non-mosaic Klinefelter syndrome patients

Abstract Study question What are the clinical results of patients with azoospermia and nonmosaic Klinefelter syndrome, using fresh and cryopreserved sperm? Summary answer The results showed a recovery rate of testicular sperm in the order of 40% and a life newborn rate of 52% when using fresh sperm What is known already In Klinefelter syndrome (KS), the rates of successful testicular sperm retrieval were shown to be similar either using conventional TESE or micro-TESE (Corona et al., 2017), which highlights that the variability observed between studies is due to differences in patient characteristics. There are a few works with a large number of KS patients elucidating the clinical outcomes using fresh and cryopreserved testicular sperm. However, these studies revealed contradictory outcomes, either revealing better (Greco et al., 2013; Vicdan et al., 2016) or worst (Madureira et al., 2014) results with cryopreserved testicular sperm, or finding no differences (Chen et al, 2019). Study design, size, duration This study includes all patients up to 2019 presenting azoospermia due to non-mosaic Klinefelter syndrome (n = 76) that went for infertility consultations in a private fertility clinic. Patients were evaluated by the same Urologist. The genetic analysis of the patients was performed at an academic institution. At examination patients did not refer other complaints besides infertility, and referred to have not received any hormone replacement therapy in the past. Participants/materials, setting, methods The 76 azoospermic patients with non-mosaic Klinefelter syndrome (KS) were treated by testicular sperm extraction (TESE) followed by intracytoplasmic sperm injection (ICSI), using fresh and cryopreserved testicular sperm. Most patients used fresh testicular sperm, where others preferred to postpone ICSI treatment cycles and used cryopreserved testicular sperm. Aneuploidy screening in children was performed by prenatal diagnosis and MLPA (Multiplex ligation-dependent probe amplification). Full embryological, clinical and newborn outcomes are provided. Main results and the role of chance Of the 76 patients with non-mosaic Klinefelter syndrome, one repeated the testicular sperm extraction (TESE) procedure. Testicular sperm were recovered in 31/77 (40.3%) of the cases. Comparisons between the 31 cases with successful sperm recover (group–1) and the 46 cases without a successful TESE (group–2) revealed no significant differences regarding age, time of infertility, testicular volume, serum levels of FSH, LH and testosterone, total number of testicular fragments analyzed, and time of search in samples. The mean male age was 34 years. In most of the cases, the testicular volume was reduced (96.1%), the levels of FSH (98.3%) and LH (94.1%) were increased, and the levels of testosterone were normal (77.6%). There were 25 intracytoplasmic sperm injection (ICSI) treatment cycles using fresh testicular sperm and 22 ICSI treatment cycles using frozen testicular sperm. The rates of fertilization (63.5% fresh sperm vs 41.6% frozen sperm), implantation (37% fresh sperm vs 13.2% frozen sperm), clinical pregnancy (60.9% fresh sperm vs 19% frozen sperm), live birth delivery (52.2% fresh sperm vs 19% frozen sperm) and newborn (65.2% fresh sperm vs 23.8% frozen sperm) were higher in the group using fresh testicular sperm. Chromosome analysis of the 21 newborn was normal. Limitations, reasons for caution Although presenting a high number of cases with azoospermic non-mosaic Klinefelter syndrome treated with testicular sperm extraction and intracytoplasmic sperm injection, future studies are needed with a higher number of cycles using frozen testicular sperm, in order to confirm or rebut that the freezing methodology affects negatively the clinical outcomes. Wider implications of the findings: Data adds further information regarding testicular sperm retrieval rates and use of fresh or frozen testicular sperm in Klinefelter syndrome (KS) patients. High newborn rates were obtained only with fresh testicular sperm. Results also reassure KS patients about the safety relative to any abnormal chromosomal transmission to the born children. Trial registration number Not applicable

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.

Prediction of sperm extraction in non-obstructive azoospermia patients: a machine-learning perspective.

Can a machine-learning-based model trained in clinical and biological variables support the prediction of the presence or absence of sperm in testicular biopsy in non-obstructive azoospermia (NOA) patients? Our machine-learning model was able to accurately predict (AUC of 0.8) the presence or absence of spermatozoa in patients with NOA. Patients with NOA can conceive with their own biological gametes using ICSI in combination with successful testicular sperm extraction (TESE). Testicular sperm retrieval is successful in up to 50% of men with NOA. However, to the best of our knowledge, there is no existing model that can accurately predict the success of sperm retrieval in TESE. Moreover, machine-learning has never been used for this purpose. A retrospective cohort study of 119 patients who underwent TESE in a single IVF unit between 1995 and 2017 was conducted. All patients with NOA who underwent TESE during their fertility treatments were included. The development of gradient-boosted trees (GBTs) aimed to predict the presence or absence of spermatozoa in patients with NOA. The accuracy of these GBTs was then compared to a similar multivariate logistic regression model (MvLRM). We employed univariate and multivariate binary logistic regression models to predict the probability of successful TESE using a dataset from a retrospective cohort. In addition, we examined various ensemble machine-learning models (GBT and random forest) and evaluated their predictive performance using the leave-one-out cross-validation procedure. A cutoff value for successful/unsuccessful TESE was calculated with receiver operating characteristic (ROC) curve analysis. ROC analysis resulted in an AUC of 0.807 ± 0.032 (95% CI 0.743-0.871) for the proposed GBTs and 0.75 ± 0.052 (95% CI 0.65-0.85) for the MvLRM for the prediction of presence or absence of spermatozoa in patients with NOA. The GBT approach and the MvLRM yielded a sensitivity of 91% vs. 97%, respectively, but the GBT approach has a specificity of 51% compared with 25% for the MvLRM. A total of 78 (65.3%) men with NOA experienced successful TESE. FSH, LH, testosterone, semen volume, age, BMI, ethnicity and testicular size on clinical evaluation were included in these models. This study is a retrospective cohort study, with all the associated inherent biases of such studies. This model was used only for TESE, since micro-TESE is not performed at our center. Machine-learning models may lay the foundation for a decision support system for clinicians together with their NOA patients concerning TESE. The findings of this study should be confirmed with further larger and prospective studies. The study was funded by the Division of Obstetrics and Gynecology, Soroka University Medical Center, there are no potential conflicts of interest for all authors.

SAT-043 Utility of Ultrasensitive Inhibin B Measurement for the Management of Men with Non-Obstructive Azoospermia

Inhibin B measurement by conventional assay(s) may be useful in the assessment of spermatogenesis in infertile male patients, especially in cases of azoospermia. Indeed, numerous previous studies have shown that Inhibin B could be helpful to predict a positive testicular sperm extraction (TESE). However, an undetectable Inhibin B concentration (<10pg/mL) does not predict a TESE failure in all cases. These findings explained that most medical centers have precluded the use of Inhibin B assay in the pre-operative hormonal assessment of azoospermic men. Recently, an ultrasensitive Inhibin B assay has been developed allowing the measurement of concentrations below 10pg/mL. The current study aims to assess the clinical relevance of this new assay in men with azoospermia with undetectable Inhibin B levels by conventional assay(s).Methods: This retrospective study included 71 non-obstructive azoospermic men who had undetectable Inhibin B levels (i.e. <10pg/mL by Gen II ELISA from Beckman Coulter, USA) and who underwent a TESE procedure between 2013 and 2019 in the Lille University Hospital. Serum LH, FSH and testosterone levels were systematically measured by routine immunoassays. Cryopreserved serum samples were used to perform ultrasensitive Inhibin B assay (Ultrasensitive Inhibin B, AL-195, Ansh Labs, USA). Additional hormonal assays including Inhibin A, Activin B and Activin A were performed on available subset of samples.Results: The TESE was successful, allowing sperm cryopreservation in 32.5 % (25/71) of the cases. No significant statistical difference was found in FSH, LH, or testosterone levels between patients with positive or negative TESE. By contrast, men with positive TESE had more than twice higher serum ultrasensitive Inhibin B levels (median 5.03pg/mL [1.93-8.5] vs. 2.19pg/mL [0.2-4.72], p=0.006). An ultrasensitive Inhibin B serum level >3.67 pg/mL (determined by ROC analysis) was associated with increased odds ratio (OR= 4.82; 95% CI: 1.647-12.93) for positive TESE. Inhibin A, Activin B and Activin A serum concentrations did not differ significantly between the two groups.Conclusion: FSH measurement which is routinely performed in men with azoospermia was not predictive of successful TESE whereas, Inhibin B was found to be a valuable marker in predicting TESE success in this population using ultrasensitive Inhibin B assay.

PD25-12 FERTILITY POTENTIAL OF MEN TREATED FOR UNCORRECTED BILATERAL CRYPTORCHIDISM AS ADULTS: A SYSTEMATIC LITERATURE REVIEW

You have accessJournal of UrologyInfertility: Epidemiology & Evaluation II (PD25)1 Apr 2020PD25-12 FERTILITY POTENTIAL OF MEN TREATED FOR UNCORRECTED BILATERAL CRYPTORCHIDISM AS ADULTS: A SYSTEMATIC LITERATURE REVIEW Wade Muncey*, Rahul Dutta, Ryan P. Terlecki, Lynn L. Woo, and Kyle Scarberry Wade Muncey*Wade Muncey* More articles by this author , Rahul DuttaRahul Dutta More articles by this author , Ryan P. TerleckiRyan P. Terlecki More articles by this author , Lynn L. WooLynn L. Woo More articles by this author , and Kyle ScarberryKyle Scarberry More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000882.012AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Bilateral undescended testicles (bUDT) is typically recognized early in life, but may go unaddressed into adulthood. Guidelines on post-pubertal management are lacking, and the hormonal and fertility benefits of adult orchidopexy (OP) are not well established. We aim to conduct a literature review to determine an evidence-based approach to management. METHODS: A systematic literature review, conforming to the PRISMA statement, was conducted using the PubMed/Medline databases through October 2019 using the search terms “adult cryptorchidism” and “adult orchidopexy.” Any report or series including an adult (age>17) with untreated, bilateral undescended testicles was included. RESULTS: 51 reports were identified with 209 adults with uncorrected bUDT included for analysis. Semen analysis (SA) identified azoospermia in 100% (139/139). Unilateral (23%) or bilateral (77%) OP was performed in 132 men. Intraabdominal testicles were identified in 40 patients (30%), one or both inguinal testicles in 38 (29%), or unspecified location in 54 (41%). SA after OP was reported in 43 men (age 18-38) in 14 series with 11 cases (25.6%) identifying return of sperm to ejaculate. Five reports described delayed testicular sperm extraction (TESE) in 18 men with persistent azoospermia at a median of 8 (6-168) months after OP with success in 8 (44%). Only 1 report exists of sperm obtained after OP for intraabdominal testicles. The remainder had OP for inguinal testicles (13) or unspecified location (5). Successful paternity was reported in six men: natural conception (2), intrauterine insemination (1), intracytoplasmic sperm injection (ICSI) with ejaculated sperm (1), and TESE + ICSI (2). TESE was performed in 12 men at time of OP with 0% sperm retrieval. One man had successful TESE 84 months after failed TESE during OP. Pathology of 55 UDTs in 40 men following pre-OP biopsy (64%) or contralateral orchiectomy (36%) revealed no cases (0%) of mature spermatozoa identification and complete lack of germ cells in 51%. Median testosterone in 67 men was 360 ng/dl (90-700), with hypogonadism identified in 9 (13%), but normal puberty reported in all. One report noted de novo hypogonadism post-OP. CONCLUSIONS: Azoospermia is the rule in adults with uncorrected bUDT, but testosterone is sufficient for pubertal development. Adult orchidopexy can restore spermatogenesis, with retrieval noted from ejaculate or TESE. TESE of the uncorrected UDT is of limited benefit and should be abandoned and reserved for after OP. Source of Funding: None © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e543-e543 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Wade Muncey* More articles by this author Rahul Dutta More articles by this author Ryan P. Terlecki More articles by this author Lynn L. Woo More articles by this author Kyle Scarberry More articles by this author Expand All Advertisement PDF downloadLoading ...

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.

Testicular sperm extraction and intracytoplasmic sperm injection outcome in cancer survivors with no available cryopreserved sperm.

To assess rates of successful testicular sperm retrieval and intracytoplasmic sperm injection (ICSI) outcome in cancer survivors affected by non-obstructive azoospermia (NOA) or retrograde ejaculation (RE)/failure of emission (FOE). A retrospective analysis of cancer survivors who did not cryopreserve sperm prior to treatment undergoing testicular sperm extraction (TESE). Non-cancer NOA patients and neurologic RE/FOE were the control group. A total of 97 cancer survivors were offered TESE and 88 (91%) accepted. Sperm was retrieved and cryopreserved in 34/67 patients with NOA (50.7%) and in 21/21 patients affected by RE/FOE (100%). Sperm retrieval rates were similar in the control group (44.9% in NOA and 100% in RE/FOE). The ICSI cumulative pregnancy rate (60%) and live birth rate (40%) per couple in 30 NOA men did not differ from controls (50.0 and 46.5%, respectively; p = 0.399/0.670). The cumulative pregnancy rate (66.7%) and live birth rate (55.6%) in 18 RE/FOE men did not differ from the control group (38.9 and 33.3%, respectively; p = 0.181/0.315). The cancer type and the resulting infertility disorder (NOA or RE/FOE) were not associated with ICSI outcomes. Female partner age was inversely related to the cumulative live birth rate, being fourfold lower (11.5%) in women ≥ 40years and 48.8% in younger women (p = 0.0037). The rate of successful TESE and the ICSI outcome in cancer survivors with NOA and RE/FOE is the same as non-cancer azoospermic patients. Female partner age (older than 40years) was associated with a significant reduction in live birth rates after TESE-ICSI procedures.

Predictive factors for sperm retrieval from males with azoospermia who are eligible for testicular sperm extraction (TESE)

ABSTRACTThe aim of this study was to evaluate the predictive value of factors in infertile male patients to retrieve sperm from their testicles before they undergo testicular sperm extraction (TESE). In total, 64 males were enrolled in this study. Infertility was identified as obstructive azoospermia (OA); non-obstructive azoospermia (NOA); Klinefelter syndrome (KS); and cryptozoospermia (Crypt). Age, body mass index and concomitant conditions were noted. Testicular volumes, serum levels of Follicle-Stimulating Hormone (FSH), Luteinizing Hormone (LH), testosterone (T) and prolactin were investigated. Sperm retrieval after TESE was noted as positive or negative. Average age of the cases was 36.8 years. TESE success rate of testicular sperm retrieval rate was 50.0%. Majority of men (83.9%) had a 46, XY karyotype, minority had genetic anomalies, and 5 of were diagnosed with KS – all were TESE-negative. There was no statistical difference in age, testicular volume, presence of varicocele and microcalcifications or hormonal levels in the TESE-positive and negative groups. Smoking as an independent variable was the only risk factor statistically showing (OR = 0.269; p = 0.045) prediction of negative sperm retrieval after the TESE procedure. None of the parameters investigated herein predicted successful TESE outcomes. However, in cases with negative TESE only smoking was identified as a predictive factor for negative sperm retrieval and was established as a risk factor.Abbreviations: AZF: azoospermia factor; BMI: body mass index; Crypt: cryptozoospermia; FSH: Follicle-Stimulating Hormone; ICSI: intracytoplasmic sperm injection; IU: international unit; KS: Klinefelter syndrome; LH: Luteinizing Hormone; mL: milliliter; NOA: non-obstructive azoospermia; OA: obstructive azoospermia; T: testosterone; TESA: testicular sperm aspiration; TESE: testicular sperm extraction

Relationship between testicular histopathology and the success of testicular sperm extraction in patients with non-mosaic Klinefelter syndrome

ObjectiveTo investigate the effect of testicular histopathology on the success of microscopic testicular sperm extraction (mTESE) and the factors that could predict the success of mTESE in patients with non-mosaic Klinefelter syndrome (KS). Material and methodsForty-one KS patients diagnosed with non-obstructive azoospermia (NOA) who had undergone mTESE at our clinic were included in the study. The patients were divided into 5 groups according to the histopathology results: hyalinisation of tubules (HT), sertoli cell only (SCO), early maturation arrest (EMA), late maturation arrest (LMA), and hypospermatogenesis (HS). The groups were compared with regard to age, duration of infertility, hormone profile, testicular volume, and sperm retriveal rate. The clinical features of the patients with mTESE from whom sperm could or could not be obtained were also compared with the aim of investigating the predictive value of testicular histopathology and the other variables for prediction of the success of mTESE. ResultsSperm could be obtained through mTESE in 13 out of 41 patients (31.7%). A statistically significant difference was determined between the groups with regard to the rate of sperm collection. No significant difference was determined between the histopathology groups with regard to the other variables. A statistically significant difference was determined between the groups from whic sperm could be collected or not with regard to age, Johnsen criteria, SCO, EMA and LMA variables. Multi-variate analysis revealed that age and Johnsen score were the independent variables predictive for success of mTESE. ConclusionThe present study has revealed that impairment in testicular histopathology negatively affects the success of mTESE and that it is a predictive factor for the success of mTESE in patients with KS. Increased patient age was also determined to negatively affect the success of mTESE and the operation was demonstrated to be more successful before 34 years of age.

FSHB −211 G&gt;T Polymorphism as Predictor for TESE Success in Patients With Unexplained Azoospermia

Testicular sperm extraction (TESE) followed by assisted reproductive techniques often remains the only therapeutic option for men with azoospermia due to spermatogenic failure. Reproductive parameters, such as gonadotropin levels and testicular volume or histopathology, contribute to the prediction of sperm retrieval rate (SRR) in TESE. However, there is an eminent lack of noninvasive predictive factors for TESE outcome. To clarify the impact of three common genetic variants affecting FSH and its cognate receptor on testicular histopathology patterns and SRR in TESE. We evaluated the association of the single-nucleotide polymorphisms (SNP) FSHB -211G>T (rs10835638), FSHR -29G>A (rs1394205), and FSHR c.2039A>G (rs6166) with testicular histopathology and SRR in patients with azoospermia. Tertiary referral center for andrology. Men (n = 1075) with azoospermia who underwent TESE (grouped by clinical pathologies). All participants underwent TESE. Testicular histopathology, SRR, and reproductive hormone levels. FSHB -211G>T was significantly associated with reduced chances of sperm retrieval in patients with unexplained azoospermia. Indicating an additional mechanism, the association of the SNP with SSR could not be solely attributed to decreased FSH levels. A common genetic factor was significantly associated with SRR in TESE. In perspective, a calculator or score including the noninvasive parameters FSH level, testicular volume, and FSHB haplotype should be considered to estimate the chances for sperm retrieval in men with azoospermia.

Evaluating the Outcome of Conventional Tese from Clinical Presentation in Patients with Non-Obstructive Azoospermia

Context: Several etiologies have been identified and some clinical factors might predict the probability of finding sperm in nonobstructive azoospermia (NOA). Aims: Find and correlate the clinical findings to the success of testicular sperm extraction (TESE). Settings and Design: Retrospective review of patients with NOA undergoing TESE in our department between 2012 and 2015. Methods and Material: We analyzed the sperm retrieval rate (SRR) based on testicular size, Follicle-Stimulating Hormone (FSH), Luteinizing Hormone (LH), total testosterone and prolactin levels as well as on the karyotype findings. We also report the results of ICSI based on clinical features. Statistical analysis used: Mann-Whitney U test; chi-square test; receiving operating characteristic and area under the curve; binary logistic regression. Results: 54 patients, mean age of 34, 57 years. The overall SRR was 51, 9%. Difference between negative and positive SRR regarding mean FSH (p=0,002) and mean LH (p=0,007) was found. No difference in SRR based on karyotype findings (p=0.127) or testicular size (p=0,336) was identified. A multivariate binary regression concluded that only FSH could be used as a predictor for TESE+. A FSH value 11,0UI/L the probability of TESE+ will be 24%. 28 patients proceeded to ICSI with clinical pregnancy and live birth rates of 20,7% and 17,2%. Conclusions: NOA patients should be fully assessed and informed about the probability of TESE+; FSH levels alone might be useful to do that. Furthermore those with normal FSH and normal testicular size can expect higher rates of sperm retrieval and live birth after ICSI.

Effects of clinical, laboratuary and pathological features on successful sperm retrieval in non-obstructive azoospermia

The study aims to evaluate the correlation of testicular sperm extraction (TESE) and histopathology with various features of non-obstructive azoospermia (NOA) cases who consulted to our university-based infertility clinic, and the probability of prompting couples about TESE success and to investigate the cost reduction chance through cost-beneficial aspects. One hundred and twenty-five patients were enrolled in this study. Age, unprotected intercourse period, age of puberty, and concomittant diseases were noted. Testicular volumes were measured. The correlations between genetic test results and serum levels of Follicle-Stimulating Hormone (FSH), Luteinizing Hormone (LH), free testosterone, prolactine were investigated. The incidence of NOA among infertile men was found to be 15.1%. Median age of the cases was 33.1 years. Decrease in TESE success rate was seen in the group aged >30, and those who practiced unprotected intercourse for more than 10 years. TESE success rate was 40 percent. The required negative correlation between FSH levels, and testicular volume was not observed when the patient had additional diseases and/or genitourinary surgery. FSH and LH levels were significantly different between TESE- positive and negative groups (p=0.006, and p=0.001 respectively). Success rate in bilateral TESE group was 14.2%, and 96% of TESE- negative patients had bilateral TESE. Fifteen of 118 patients had Y chromosome microdeletions. These results were similar in both TESE- positive and negative group. None of the parameters investigated herein predicted succesful TESE outcomes. However, in cases with increased FSH and AZFa/AZFb deletion before application of bilateral TESE, in cases of increased FSH and AZFa/AZFb deletion, detailed information should be given to these patients about low success rates and risk of disease inheritance which may reduce procedural costs. Knowing groups with poor prognosis, may help rearrangement of the appropriation of infertility in health policies.

Simultaneous expression analysis of deleted in azoospermia-family genes and CDC25A: their potential as a predictor for successful testicular sperm extraction

Fil: Gonzalez, Candela Rocio. Universidad Maimonides; Argentina. Consejo Nacional de Investigaciones Cientificas y Tecnicas; Argentina

Prediction model for live birth in ICSI using testicular extracted sperm.

Which parameters have a predictive value for live birth in couples undergoing ICSI after successful testicular sperm extraction (TESE-ICSI)? Female age, a first or subsequent started TESE-ICSI cycle, male LH, male testosterone, motility of the spermatozoa during the ICSI procedure and the initial male diagnosis before performing TESE were identified as relevant and independent parameters for live birth after TESE-ICSI. In reproductive medicine prediction models are used frequently to predict treatment success, but no prediction model currently exists for live birth after TESE-ICSI. A retrospective cohort study between 2007 and 2015 in two academic hospitals including 1559 TESE-ICSI cycles. The prediction model was developed using data from one centre and validation was performed with data from the second centre. We included couples undergoing ICSI treatment with surgically retrieved sperm from the testis for the first time. In the development set we included 526 couples undergoing 1006 TESE-ICSI cycles. In the validation set we included 289 couples undergoing 553 TESE-ICSI cycles. Multivariable logistic regression models were constructed in a stepwise fashion (P < 0.2 for entry). The external validation was based on discrimination and calibration. We included 224 couples (22.3%) with a live birth in the development set. The occurrence of a live birth was associated with lower female age, first TESE-ICSI cycle, lower male LH, higher male testosterone, the use of motile spermatozoa for ICSI and having obstructive azoospermia as an initial suspected diagnosis. The area under the receiver operating characteristic (ROC) curve was 0.62. From validation data, the model had moderate discriminative capacity (c-statistic 0.67, 95% confidence interval: 0.62-0.72) but calibrated well, with a range from 0.06 to 0.56 in calculated probabilities. We had a lack of data about the motility of spermatozoa during TESE, therefore, we used motility of the spermatozoa used for ICSI after freeze-thawing, information which is only available during treatment. We had to exclude data on paternal BMI in the model because too many missing values in the validation data hindered testing. We did not include a histologic diagnosis, which would have made our data set less heterogeneous and, finally, our model may not be applicable in centres which have a different policy for the indication for performing sperm extraction. The prognostic value of the model is limited because of a low 'area under the curve'. This model enables the differentiation between couples with a low or high chance to reach a live birth using TESE-ICSI. As such it can aid in the counselling of patients and in clinical decision-making. This study was partly supported by an unconditional grant from Merck Serono (to D.D.M.B. and K.F.) and by the Department of Obstetrics and Gynaecology of Radboud University Medical Center, Nijmegen, The Netherlands, the Department of Obstetrics and Gynaecology, Jeroen Bosch Hospital, Den Bosch, The Netherlands, and the Department of Obstetrics and Gynaecology, Academic Medical Center, Amsterdam, The Netherlands. Merck Serono had no influence in concept, design, nor elaboration of this study. Not applicable.

Expression ratio of histone demethylase KDM3A to protamine-1 mRNA is predictive of successful testicular sperm extraction in men with obstructive and non-obstructive azoospermia.

To evaluate the predictive value of histone demethylase KDM3A to protamine 1 (PRM1) mRNA expression ratio as a reliable marker of sperm retrieval in men with obstructive and non-obstructive azoospermia (NOA). Fifty eight azoospermic men, including 44 with NOA and 14 with obstructive azoospermia (OA). Testis tissue samples were collected from azoospermic men who have been referred for testicular sperm extraction (TESE) and micro-TESE. Relative expression ratio of KDM3A to PRM1 was analyzed after selection of approved reference genes. Histological classification of testis biopsies was performed. Sperm retrieval following TESE and micro-TESE was evaluated. A sperm retrieval prediction sensitivity of 95% was established when the Cq of PRM1 became smaller than the Cq of both KDM3A and GAPDH genes. However, azoospermic men with down-regulated KDM3A and decreased expression of PRM1 mRNA showed very low success for sperm retrieval (<25%), even after micro-TESE surgery. The KDM3A to PRM1 mRNA expression ratio can be used as a reliable marker of successful testicular sperm extraction in men with obstructive and non-obstructive azoospermia with 95% sensitivity.