Microsurgical Testicular Sperm Extraction Research Articles

The Role of Artificial Intelligence in Male Infertility: Evaluation and Treatment: A Narrative Review

Male infertility has affected an increasingly large population over the past few decades, affecting over 186 million people globally. The advent of assisted reproductive technologies (ARTs) and artificial intelligence (AI) has changed the landscape of diagnosis and treatment of male infertility. Through an extensive literature review encompassing the PubMed, Google Scholar, and Scopus databases, various AI techniques such as machine learning (ML), artificial neural networks (ANNs), deep learning (DL), and natural language processing (NLP) were examined in the context of evaluating seminal quality, predicting fertility potential, and improving semen analysis. Research indicates that AI models can accurately estimate the quality of semen, diagnose problems with sperm, and provide guidance on reproductive health decisions. In addition, developments in smartphone-based semen analyzers and computer-assisted semen analysis (CASA) are indicative of initiatives to improve the price, portability, and accuracy of results. Future directions point to possible uses for AI in ultrasonography assessment, microsurgical testicular sperm extraction (microTESE), and home-based semen analysis. Overall, AI holds significant promise in revolutionizing the diagnosis and treatment of male infertility, offering standardized, objective, and efficient approaches to addressing this global health challenge.

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.

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

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

Effectiveness of, and Satisfaction with, a Microsurgical Testicular Sperm Extraction Knowledge and Skills Masterclass for a World-Wide Audience.

This is the first study to assess the impact of an online microsurgical testicular sperm extraction (mTESE) masterclass. We: 1) describe the masterclass's scientific content; 2) appraise the participants' acquisition of knowledge; 3) gauge whether the extent of improvement of the participants' knowledge/skills was influenced by demographic/professional attributes; and 4) evaluate the participants' satisfaction. This masterclass comprised five didactic lectures followed by 4 case discussions. Online surveys assessed the above objectives using a baseline questionnaire including demographics and past mTESE experience/training, a 24-question pre- and post-quiz, and a satisfaction questionnaire. Participants were between 20-70 years old, with 80.37% males, mainly from Asia, Africa, and Europe, from clinical backgrounds (69.3%), and in public practice (64.4%). Half the sample reported no past mTESE training and very low skills, ≈60% wanted considerably more training, and 50% felt that good training was not readily available. Satisfaction was 98% to >99%. Pre- and post-quiz comparisons confirmed remarkable improvements in knowledge/skills, exhibiting five striking characteristics. Improvements were a) Broad i.e., across 19 of the 24 mTESE questions; b) Deep, of magnitude, as pre-/post-quiz scores improved from mean 13.71±4.13 to 17.06±4.73; c) Highly significant, consistently with p-values <0.001; d) Inclusive i.e., all participants enhanced their mTESE knowledge/skills regardless of demographic/professional attributes; and, e) Differential, e.g., non-clinical/clinical participants improved, but the former improved relatively significantly more, those with ≤5-year experience improved significantly more than those with >5-year, those in public practice significantly more than private practice participants, and those with lower self-rating in performing mTESE significantly more than those with higher self-rating. The masterclass was successful with very high satisfaction levels, and markedly improved mTESE knowledge/skills among the participants. Global Andrology Forum's model can be adopted by organizations with similar goals. Future research needs to evaluate such training to develop a practically non-existent evidence base.

A successful outcome in a case of nonobstructive azoospermia with repeat surgical sperm retrieval (SSR)-testicular sperm aspiration followed by microsurgical testicular sperm extraction

Azoospermia is a major cause of male infertility, either obstructive or nonobstructive azoospermia (NOA). However, such couples should be offered surgical sperm retrieval to enable them to become parents with their own gametes. Cases of NOA will have higher retrieval rate with microsurgical testicular sperm extraction (micro-TESE), even though, in some cases, it may be a repeat procedure. Presenting here a case of successful twin gestation after intracytoplasmic sperm injection with sperms retrieved successfully by micro-TESE after a previous failed frozen embryo transfer with a very poor retrieval by a testicular sperm aspiration in a case of NOA.

Options after a failed microsurgical testicular sperm extraction

Options after a failed microsurgical testicular sperm extraction

Testicular Apoptosis and Proliferation in Relation to Body Mass Index and m-TESE Success in Nonobstructive Azoospermic Men

Male infertility occurs due to the disruption of the balance of proliferation and apoptosis in the testicular tissue. It is important to show the effect of increased body mass index, which is one of the factors that disrupts this balance of apoptosis and proliferation, not only at the blood hormone level but also at the tissue level. For this reason, the present study is aimed at demonstrating the relation between body mass index and cell turnover in the testis using immunohistochemical methods. In the present study, patients were grouped as normal, overweight and obese, and as m-TESE positive and negative. The sperm retrieval rate with microsurgical testicular sperm extraction (m-TESE) was 41.67%. Histological diagnosis of testicular tissues was made with hematoxylin and eosin and Masson’s trichrome staining. Apoptosis and proliferation in the testicular tissue were demonstrated by TUNEL and PCNA immunohistochemical methods, respectively. It was concluded that BMI had no significant effect on reproductive hormone profile (FSH, LH, and testosterone), m-TESE success, apoptosis, and proliferation in testicular tissue in nonobstructive azoospermic men. In addition TUNEL positivity and proliferative index was found to be significantly correlated with testicular histology and m-TESE outcome.

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

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

Testosterone to Luteinizing Hormone Ratio as a Potential Predictor of Sperm Retrieval in Non-Obstructive Azoospermia Patients.

This study assessed the outcomes of microsurgical testicular sperm extraction (mTESE) and potential preoperative predictors of sperm retrieval (SR) in patients with non-obstructive azoospermia (NOA). Clinical data of 111 NOA patients who underwent mTESE was reviewed retrospectively. Baseline patient characteristics, including age, body mass index (BMI), testicular volumes, and preoperative endocrine levels, such as testosterone (T), follicle-stimulating hormone (FSH), serum-luteinizing hormone (LH), prolactin, sex hormone-binding globulin (SHBG), FSH/LH ratio along with T/LH ratio, were analyzed. After categorizing the patients into two groups based on SR success or failure, logistic regression analysis was performed to identify the preoperative predictors of successful SR. Sixty-eight patients had successful SR (61.3%), whereas 43 patients (38.7%) showed negative results. Failed SR group had elevated serum FSH and LH levels, whereas successful SR patients had a significantly larger testicular volume (p<0.001). Moreover, the successful group had a higher T/LH ratio (p<0.001). Multivariate logistic analysis showed that the T/LH ratio, serum FSH levels, and bilateral testicular volumes were significantly associated with successful sperm extraction. In addition to traditional predictors, such as testicular volume and preoperative FSH levels, the T/LH ratio is a potential independent predictor of successful SR in infertile patients with NOA.

A dual-center study of predictive factors for sperm retrieval through microdissection testicular sperm extraction and intracytoplasmic sperm injection outcomes in men with non-mosaic Klinefelter syndrome.

This study evaluated the predictors of sperm retrieval (SR) in non-mosaic Klinefelter syndrome (KS) patients undergoing microsurgical testicular sperm extraction (mTESE). The cutoff values of the predictors of SR and overall pregnancy rates after intracytoplasmic sperm injection (ICSI) were analyzed for the positive SR (PSR) cases. The study was a dual-center retrospective study. Overall 118 patients with KS underwent mTESE between January 2011 and July 2021. Clinicopathological factors including comorbidities, endocrine profiles, and testicular volumes were analyzed. A total of 58 patients showed PSR (49.2%) and 60 patients (50.8%) had negative SR (NSR). The mean overall age of the patients was 32.5 years. The NSR patients had a significantly greater prevalence of obesity, diabetes mellitus, and cerebrovascular disease. The PSR group had a significantly higher left testis mean volume (p=0.039). The differences between the two study groups regarding follicular-stimulating hormone, luteinizing hormone, and testosterone variations at 1 and 3 months after mTESE were insignificant. Preoperative mean neutrophil-to-lymphocyte ratio was significantly greater in the NSR group (p=0.011), but the platelet-to-lymphocyte ratio showed no significant difference between the two study groups. A live child birth was achieved in 53.4% of the PSR patients. Multivariate logistic analysis showed that total testicular volume >3.93 mL, left testis volume >1.79 mL, and neutrophil-to-lymphocyte ratio ≤1.82 were significantly associated with PSR. mTESE-ICSI is a feasible method for KS patients to have a child, and total testicular volume, left testis volume, and neutrophil-to-lymphocyte ratio might be predictors of successful SR.

Clinical, cytogenomic, and molecular characterization of isodicentric Y-chromosome and prediction of testicular sperm retrieval outcomes in azoospermic and severe oligozoospermic infertile men.

Sex chromosome abnormalities are associated with male infertility. The aim of this study was to characterize the clinical, cytogenetic, and molecular findings of 12 infertile men with isodicentric Y-chromosome [idic(Y)] abnormalities diagnosed over a period of 13years. Chromosomal analyses of peripheral blood samples were done using standard procedures. Fluorescence in situ hybridization (FISH) analysis was performed on metaphase spreads of the patients. Multiplex polymerase chain reaction (PCR) using several sequence-tagged site (STS) primer sets within the long arm of Y-chromosome was used to detect AZF deletions.The breakpoints and copy number variations (CNV) were identified by array comparative genomic hybridization analysis (aCGH) analysis.The short-stature homeobox (SHOX) gene deletions were verified using multiplex ligation-dependent probe amplification (MLPA) analysis. Twelve infertile men were diagnosed cytogenetically with idic(Y). The karyotypes of two of the patients were non-mosaic, and the remaining karyotypes showed various degrees of mosaicism. SHOX gene deletion was found in two of the four patients with short stature, and the remaining two patients had shown a 45,X dominant cell line (33.3%). The most common breakpoints for idic(Yq) and idic(Yp) were found to be in Yq11.222 and Yp11.32, respectively. Semen analysis of ten patients (83.3%) demonstrated azoospermia, and the remaining two patients (16.7%) showed severe oligoasthenoteratozoospermia (OAT). In total, 33% (4/12) of idic(Y) patients with or without microsurgical testicular sperm extraction (microTESE) had sperm retrieval. Twelve patients with idic(Y) and different breakpoints of Y-chromosome were characterized using multiple detection strategies. Sperm retrieval outcomes of patients either with idic(Yp) or idic(Yq) showed the possibility to find sperm by microTESE.

Robotic Surgery for Male Infertility and Chronic Scrotal Content Pain.

Robot-assisted microsurgery is a trending approach for the treatment of male infertility and chronic scrotal pain. The advantages seem to include increased optical magnification, improved surgical efficiency, absent tremor, and similar outcomes with standard methods. This chapter covers robotic microsurgical application and techniques for: robot-assisted vasectomy reversal with vasovasostomy and vasoepididymostomy, varicocelectomy, microsurgical testicular sperm extraction, and targeted denervation of the spermatic cord.

Are Clinical Outcomes of Microdissection Testicular Sperm Extraction in Non-Obstructive Azoospermic Men Affected by the Use of Fresh or Frozen Gametes?

Background: Non-obstructive azoospermia (NOA) is a severe form of male factor infertility, evident in approximately 5% of infertile couples seeking fertility treatment. The combination of microsurgical testicular sperm extraction (mTESE) and ICSI has become one of the treatment options, with sperm motility positively associated with outcome success rates. Few studies have investigated whether use of fresh or thawed gamete combinations affect clinical outcomes. Aim: To determine the clinical outcomes of ICSI cycles using mTESE recovered testicular sperm of NOA patients and whether these are affected by the use of fresh or thawed gametes. Method: A retrospective study of NOA patients who underwent mTESE between March 2017 and September 2020. Clinical outcomes investigated included successful surgical sperm retrieval (SSR), sperm motility, fertilisation, embryo utilisation and live-birth/ongoing pregnancy rates. Results: A total of 105 NOA patients underwent mTESE, with a 65.7% successful SSR. In total 58 patients contributed to 72 ICSI cycles, with a 37.5% 2PN fertilisation rate and 29.4% live-birth/ongoing pregnancy rate. Cycles using only motile sperm had a greater fertilisation rate than those using a motile/non-motile sperm combination (51.7% vs 31.1%, p[Formula: see text]0.05). Compared with fresh, thawed testicular spermatozoa didn’t affect clinical outcomes, including live-birth/ongoing pregnancy rates (Fresh 18.2%; Thawed 17.9%; Odds ratio (OR) 1.02 (0.34-2.86) p=0.98). In contrast, use of thawed oocytes decreased fertilisation rate [Fresh-oocytes: 45.0%; Vitrified-oocytes: 35.5%; OR 1.47(1.03-2.10), p=0.03] but had no differences for other clinical outcomes, including live-birth/ongoing pregnancy rate (p=0.74). Importantly, injection of exclusively non-motile-spermatozoa (n=26 cycles) resulted in a very low fertilisation rate (2.7%) and no live-birth/ongoing pregnancies were recorded. Conclusion: Microdissection TESE is an effective treatment for NOA patients, with no clear negative effects of using thawed spermatozoa, however, the use of vitrified oocytes requires further investigation. The use of non-motile spermatozoa in mTESE ICSI cycles is discouraged.

Combined Trifocal and Microsurgical Testicular Sperm Extraction Enhances Sperm Retrieval Rate in Low-Chance Retrieval Non-Obstructive Azoospermia.

Background: Low-chance retrieval non-obstructive azoospermic (NOA) patients are a subpopulation of NOA patients. The objective of this study is to compare the surgical outcome of microsurgical-assisted testicular sperm extraction (M-TeSE) and combined trifocal/M-TeSE in low-chance retrieval NOA patients. Material and Methods: A single-center retrospective analysis of NOA patients who underwent testicular sperm extraction was performed. Low-chance retrieval NOA (testicular volume < 10 cc and FSH > 12.4 UI/L) was set as the inclusion criteria. Re-do TeSE procedures were excluded from the current analysis. Data were extrapolated from clinical records and operative notes. We compared data from patients who underwent classic M-TeSE (group A) with that from patients submitted to combined trifocal/M-TeSE (group B). Sperm retrieval rate (SRr) was the primary outcome of the study. Surgical outcomes and postoperative complications were evaluated. A multivariate analysis was conducted to investigate predictive factors for positive SR. Results: Overall, 80 patients (60 patients in Group A and 20 patients in Group B) fulfilled the inclusion criteria. The average (SD) age was 35 (8.2) years. The average preoperative FSH was 27.5 (13) UI/L. The average testicular volume was 6.3 (3) cc on the left side and 6.8 (2.5) cc on the right. Groups were similar in terms of preoperative parameters. The overall SRr was 28%. Patients in group B had higher SRr than those in group A (29.4% vs. 26.9%, p < 0.03). We identified a significant association between testicular histopathology and positive SR (hypospermatogenesis 100%, spermatogenic arrest 32%, and Sertoli cell-only syndrome 22%). The histopathology report was the only significant predicting factor for SR in the multivariate analysis. Conclusion: The combined trifocal and M-TeSE approach is safe and may represent a valuable approach to enhance the SRr in low-chance retrieval NOA. The histopathology report is confirmed to be the only valuable predicting factor for a positive SR.

Are Clinical Outcomes of Micro-TESE in Non-obstructive Azoospermic Men Affected by the Use of Fresh or Frozen Gametes?

Background: The combination of microsurgical testicular sperm extraction (mTESE) and intracytoplasmic sperm injection (ICSI) has become a common management option, with sperm motility being positively associated with successful outcomes. However, few studies have investigated whether the use of fresh or thawed gamete combinations affect clinical outcomes. Objectives: To determine whether the clinical outcomes of ICSI cycles using mTESE recovered testicular sperm of non-obstructive azoospermia (NOA) patients are affected by using fresh or thawed gametes. Material and Methods: A retrospective study was conducted of NOA patients who underwent mTESE between 2017 and 2020 at Monash IVF assisted reproductive clinics in Melbourne, Australia. The impact of gamete fresh/frozen status and sperm motility was investigated on clinical outcomes such as fertilization, blastocyst formation, clinical pregnancy, and live birth rates (LBRs). Results:A total of 103 NOA patients underwent mTESE, with a 65.1% successful surgical-sperm-retrieval. In total 56 patients contributed to 68 ICSI cycles, with a 35.1% fertilization rate and 25% LBR per embryo transfer. Compared with fresh testicular sperm, thawed testicular sperm did not affect clinical outcomes, including LBRs [16.7% vs 12.0%; odds ratio (OR) 0.68 (0.18–2.70)]. However, the use of thawed oocytes had a negative effect on fertilization rates [fresh-oocytes, 37.8%; vitrified-oocytes, 34.5%; OR 0.86 (0.02–0.48)]. Cycles using only motile sperm had a greater fertilization rate than those using a combination of motile and non-motile sperm (49.6% vs 37.2%, p ¡ 0.05). Importantly, when exclusively non-motile sperm were available (n = 26 cycles) their injection resulted in a very low fertilization rate (2.7%) and no live births were recorded. Conclusion: Micro-TESE is an effective treatment for NOA patients, with no clear advantage of using fresh over thawed sperm, however, the use of vitrified compared with fresh oocytes requires further investigation. Importantly, patients should be informed of the poor outcomes with the use of non-motile sperm in mTESE ICSI cycles.

Automated rare sperm identification from low-magnification microscopy images of dissociated microsurgical testicular sperm extraction samples using deep learning

To develop a machine learning algorithm to detect rare human sperm in semen and microsurgical testicular sperm extraction (microTESE) samples using bright-field (BF) microscopy for nonobstructive azoospermia patients. Spermatozoa were collected from fertile men. Testis biopsies were collected from microTESE samples determined to be clinically negative for sperm. A convolutional neural network based on the U-Net architecture was trained using 35,761 BF image patches with fluorescent ground truth image pairs to segment sperm. The algorithm was validated using 7,663 image patches. The algorithm was tested using 7,663 image patches containing abundant sperm, as well as 7,985 image patches containing rare sperm. Invitro fertilization center and university laboratories. Normospermic and nonobstructive azoospermia patients. None. Precision (positive predictive value [PPV]), recall (sensitivity), and F1-score of detected sperm locations. For sperm-only samples, our algorithm achieved 91% PPV, 95.8% sensitivity, and 93.3% F1-score at ×10 magnification. For dissociated microTESE samples doped with an abundant quantity of sperm, our algorithm achieved 84.0% PPV, 72.7% sensitivity, and 77.9% F1-score. For dissociated microTESE samples doped with rare sperm, our algorithm achieved 84.4% PPV, 86.1% sensitivity, and 85.2% F1-score. Rare sperm can be detected in patients' testis biopsy samples for potential subsequent use in invitro fertilization-intracytoplasmic sperm injection. A machine learning algorithm can use BF images at ×10 magnification to accurately detect sperm locations using automated imaging.

Effects of Chemo- and Radiation Therapy on Microsurgical Testicular Sperm Extraction for Men with Nonobstructive Azoospermia.

Men who survive cancer as children or young adults may have severe spermatogenic impairment with azoospermia requiring surgical sperm retrieval and assisted reproductive technologies. We assessed treatment outcomes from a large series of cancer patients with prior radiation and/or chemotherapy. Men with nonobstructive azoospermia who underwent initial microsurgical testicular sperm extraction from 1995-2020 from a high-volume surgeon at a single institution were identified. Those with a history of malignancy treated by radiation therapy and/or chemotherapy were included. The primary outcome was successful sperm retrieval. A total of 106 men were evaluated, of whom 57 received chemotherapy and radiation, 44 received only chemotherapy and 5 received only radiation. Sperm retrieval was successful in 39 of 106 (37%) men, with higher likelihood of retrieval in men who received only chemotherapy compared to men who received chemotherapy and radiation (61% vs 18%, p <0.001). None of the 18 patients who received chemotherapy with radiation to the pelvis had successful sperm retrieval, compared to 26% of patients who received chemotherapy with extra-pelvic radiation (p=0.02). Chemotherapy and radiation for cancer may result in nonobstructive azoospermia that can be treated to allow fertility. However, pelvic radiation therapy is associated with the worst prognosis for successful treatment with microsurgical sperm retrieval and in vitro fertilization; we observed no cases of successful retrieval in men who received pelvic radiation therapy. These data are useful for pretreatment counseling, suggesting that men with prior radiation therapy may not be candidates for surgical sperm retrieval.

Identification of deleterious variants in patients with male infertility due to idiopathic non-obstructive azoospermia

BackgroundNon-obstructive azoospermia (NOA) is the most severe type of male infertility, affecting 1% of men worldwide. Most of its etiologies remain idiopathic. Although genetic studies have identified dozens of NOA genes, monogenic mutations can also account for a small proportion of idiopathic NOA cases. Hence, this genetic study was conducted to explore the causes of monogenic variants of NOA in a cohort of Chinese patients.MethodsFollowing the screening using chromosomal karyotyping, Y chromosome microdeletion analyses, and sex hormone assessments, subsequent whole-exome sequencing analysis was performed in 55 unrelated idiopathic NOA patients with male infertility to explore potential deleterious variants associated with spermatogenesis. We also performed Sanger sequencing to demonstrate the variants. Testicular biopsy or microsurgical testicular sperm extraction was also performed to confirm the diagnosis of NOA and identify spermatozoa. Hematoxylin and eosin staining was performed to assess the histopathology of spermatogenesis.ResultsAbnormal testicular pathological phenotypes included Sertoli cell-only syndrome, maturation arrest, and hypospermatogenesis. Using bioinformatics analysis, we detected novel variants in two recessive genes, FANCA (NM_000135, c.3263C > T, c.1729C > G) and SYCE1 (NM_001143763, c.689_690del); one X-linked gene, TEX11 (NM_031276, c.466A > G, c.559_560del); and two dominant genes, DMRT1 (NM_021951, c.425C > T, c.340G > A) and PLK4 (NM_001190799, c.2785A > G), in eight patients, which corresponded to 14.55% (8/55) of the patients.ConclusionThis study presented some novel variants of known pathogenic genes for NOA. Further, it expanded the variant spectrum of NOA patients, which might advance clinical genetic counseling in the future.

Testicular Microlithiasis Defines a Subgroup of Azoospermic Men with Low Rates of Sperm Retrieval

ABSTRACT Introduction Testicular microlithiasis is prevalent in sub-fertile men but data regarding its association with sperm retrieval rates in azoospermic men are lacking. Objective To investigate the prevalence of testicular microlithiasis and its relationship with sperm retrieval rates and histopathology in azoospermic men. Methods Eighty-six consecutive men underwent scrotal ultrasonography prior to microsurgical testicular sperm extraction (microTESE). Sperm retrieval rate, testicular histopathology, testicular size, reproductive hormone estimation, karyotyping, Y chromosome microdeletion analyses and the presence of varicocele and hydrocele were compared between men with and without testicular microlithiasis. Results In total, sperm retrieval rate was 40%. Testicular microlithiasis was detected in 12 men (14%). In this subgroup, sperm retrieval rate was only 8% (1/12) as opposed to 45% (33/74) in azoospermic men with no evidence of microlithiasis (p=0.02). Mean right and left testicular diameters were significantly lower in the microlithiasis group compared to men without microlithiasis (2.4 cm vs. 3.2 cm and 2.4 cm vs. 3.3 cm, respectively, p=0.04). There was no significant difference in any other parameter between the groups (age, FSH levels, prevalence of XXY karyotype, Y chromosome microdeletions, sonographic varicoceles or hydroceles). All eleven patients with microlithiasis and no spermatozoa found were diagnosed with Sertoli cells only on histopathology. The patient with testicular microlithiasis and successful sperm extraction was diagnosed with mixed atrophy. Conclusions Among our cohort of azoospermic men who underwent scrotal ultrasound prior to microTESE, the presence of testicular microlithiasis was associated with very low sperm retrieval rates. Larger, prospective studies should be conducted to strengthen our results. Disclosure No

Predicting the testicular function in non-obstructive azoospermia via targeted gene panel

BackgroundMen with non-obstructive azoospermia constitute a challenging subgroup of male infertility patients in whom a genetic cause of defective spermatogenesis may be a contributing factor. The aim of this prospective observational cohort study was to determine whether assessment of meiotic nuclear division 1 (MND1) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) gene expression (MND1/GAPDH) in testicular tissue could be a prognostic indicator for sperm retrieval and ICSI outcome in patients with non-obstructive azoospermia. The study participants underwent clinical evaluation, conventional semen analysis, serum follicular stimulating hormone (FSH), testosterone assay, scrotal ultrasound examination, microsurgical testicular sperm extraction (mTESE), and assessment of MND1/GAPDH gene expression levels in testicular tissue via quantitative polymerase chain reaction (qPCR) techniques.ResultsThe MND1/GAPDH level was associated with the likelihood of identifying sperm in testicular biopsies (odds ratio (OR) 1.25, 95% confidence intervals (CI) 1.14 to 1.34, p < 0.0001), which was confirmed by the pairwise comparison of high vs. low levels of MND1/GAPDH (OR 5.34, 95% CI 1.97 to 13.16, p = 0.0006). The level of FSH was inversely associated with a lower chance of finding sperm (OR 0.37, 95% CI 0.20 to 0.65, p = 0.001). Compared with small testicular volume, normal volume was inversely associated with the chance of sperm presence (OR 0.16, 95% CI 0.06 to 0.47, p = 0.0002). However, there was no correlation between MND1/GAPDH levels and ICSI outcome.ConclusionGene expression analysis to predict the likelihood of sperm retrieval following mTESE in patients with non-obstructive azoospermia provides a new avenue for future research, diagnosis and treatment of male factor infertility. Before its wider clinical application, however, this proof-of-concept should be tested in a large multinational, multicenter observational study.