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Study Question: Could whole-exome sequencing (WES) be useful in clinical practice for men with maturation arrest (MA) after a first testicular sperm extraction (TESE)?, Summary Answer: WES in combination with TESE yields substantial additional information and may potentially be added as a test to predict a negative outcome of a recurrent TESE in patients with MA., What Is Known Already: At present, the only definitive contraindications for TESE in men with non-obstructive azoospermia (NOA) are a 46,XX karyotype and microdeletions in the azoospermia factor a (AZFa) and/or AZFb regions. After a first negative TESE with MA, no test currently exists to predict a negative outcome of a recurrent TESE., Study Design, Size, Duration: In a cohort study, we retrospectively included 26 patients with idiopathic NOA caused by complete MA diagnosed after a first TESE., Participants/materials, Setting, Methods: Twenty-six men with MA at the spermatocyte stage in all seminiferous tubules, according to a histopathological analysis performed independently by two expert histologists, and a normal karyotype (i.e. no AZF gene microdeletions on the Y chromosome) were included. Single-nucleotide polymorphism comparative genomic hybridization array and WES were carried out. The results were validated with Sanger sequencing. For all the variants thought to influence spermatogenesis, we used immunohistochemical techniques to analyse the level of the altered protein., Main Results and the Role of Chance: Deleterious homozygous variants were identified in all seven consanguineous patients and in three of the 19 non-consanguineous patients. Compound heterozygous variants were identified in another 5 of the 19 non-consanguineous patients. No recurrent variants were identified. We found new variants in genes known to be involved in azoospermia or MA [including testis expressed 11 (TEX11), meiotic double-stranded break formation protein 1 (MEI1), proteasome 26s subunit, ATPase 3 interacting protein (PSMC3IP), synaptonemal complex central element protein 1 (SYCE1) and Fanconi anaemia complementation group M (FANCM) and variants in genes not previously linked to human MA (including CCCTC-binding factor like (CTCFL), Mov10 like RISC complex RNA helicase 1 (MOV10L1), chromosome 11 open reading frame 80 (C11ORF80) and exonuclease 1 (EXO1)]., Large Scale Data: Data available on request., Limitations, Reasons for Caution: More data are required before WES screening can be used to avoid recurrent TESE, although screening should be recommended for men with a consanguineous family background. WES is still a complex technology and can generate incidental findings., Wider Implications of the Findings: Our results confirmed the genetic aetiology of MA in most patients: the proportion of individuals with at least one pathologic variant was 50% in the overall study population and 100% in the consanguineous patients. With the exception of MEI1 (compound heterozygous variants of which were identified in two cases), each variant corresponded to a specific gene-confirming the high degree of genetic heterogeneity in men with MA. Our results suggest that WES screening could help to avoid recurrent, futile TESE in men with MA in general and in consanguineous individuals in particular, but these results need to be confirmed in future studies before clinical implementation., Study Funding/competing Interest(s): The study was funded by the Fondation Maladies Rares (Paris, France), Merck (Kenilworth, NJ, USA), IRSF (Montigny le Bretonneux, France) and Agence de la Biomédecine (Saint Denis, France). There are no competing interests., Trial Registration Number: N/A., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.)

The reported sperm retrieval rate (SRR) in patients with nonobstructive azoospermia (NOA) due to spermatogenic arrest (SA) is highly variable in the literature. This discrepancy could be explained by the heterogeneity of testicular tissues. Surprisingly, even though inhibin B levels reflect directly Sertoli cell function; no studies have evaluated this parameter in SA. We aimed to clarify the morphological and biological profile in 158 men with SA. From the total population, patients whose seminiferous tubules diameter was below 165 µm have higher SRR (46.9% vs. 27.4%, p < 0.05), lower inhibin levels and a higher frequency of nonuniform SA (71.9% vs. 38.7%, p < 0.001). On multivariate analysis, patients with late SA and a history of cryptorchidism were positively associated with successful sperm extraction. Patients with successful SRR and uniform SA exhibited inhibin levels twofold lower than those with failed TESE (45 pg/ml vs. 95 pg/ml, p < 0.05), whereas FSH levels were similar in the two groups. In this study, we showed for the first time that the mean diameter of the seminiferous tubules may be of value in the diagnosis of SA. Our results suggest that inhibin levels could be useful in the management of NOA with SA, along with FSH levels and testicular volume., (© 2018 Blackwell Verlag GmbH.)

Background: Inguinal hernia repair is one of the most performed surgeries in the world. It is recognized that any surgery of the pelvic floor may represent a risk factor of male infertility., Method: Retrospective study of patients with azoospermia and a history of adult inguinal hernia repair surgery and referred to our center between January 1990 and January 2011 for infertility., Results: Among 69 azoospermia patients with history of adult inguinal hernia repair surgery, 60 patients underwent surgical extraction of sperm that was successful in 75% (45/60). Positive extraction rate decreases in the subgroup of patients with risk factors for infertility (61.4%) as well as in the group with bilateral inguinal hernia (67.9%). There was no statistically significant difference in the positive rate of sperm retrieval according to surgical technique or according to the use of polypropylene mesh (P>0.05)., Conclusion: The obstruction of the vas deferens due to an inguinal hernia repair was a potential iatrogenic cause of male infertility that was rare and underestimated. The influence of using a polypropylene mesh was not clearly demonstrated. The management of these patients is based on prevention in order to identify patients with risk factors of infertility in order to propose a presurgery cryopreservation of sperm., Level of Evidence: 5., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

In azoospermic men with congenital bilateral absence of the vas deferens (CBAVD), it is not known whether the outcomes of intracytoplasmic sperm injection (ICSI) depend on the quality of testicular spermatogenesis (as determined histopathologically). We retrospectively studied the impact of spermatogenesis quality on ICSI outcomes in 108 azoospermic men with CBAVD consulting in a university hospital's department of andrology and reproductive biology. As part of an ICSI program, sperm samples were obtained from the epididymis [by microsurgical epididymal sperm aspiration (MESA); n = 47] or the testis [by testicular sperm extraction (TESE); n = 14] or both (MESA + TESE, n = 47). In the TESE group (i.e., TESE-only and MESA + TESE), spermatogenesis was normal in 21 of the 108 men (19.4%) and hypospermatogenesis occurred in 33 (30.5%). The fertilization rate was significantly lower in the hypospermatogenic group than in the normospermatogenesis group (65.6 and 72.9%, respectively; p = 0.02); this was also true for the embryo cleavage rate (88.6 and 92.1%, respectively; p = 0.007), and the proportion of embryos with fewer than 30% of enucleate fragments (79.5 and 86.9%, respectively; p = 0.02). Our study results showed that impaired spermatogenesis had a negative impact on certain early-stage biological outcomes of ICSI. In CBAVD, male factors are likely to exert a harmful effect on the early stages of embryo development., (© 2015 American Society of Andrology and European Academy of Andrology.)

Context: In the 1990's, congenital agenesis of the vas deferens was identified as a minor form of cystic fibrosis in relation to the frequency of mutations of the CFTR gene associated. It is responsible for masculine infertility by obstructive azoospermia; which is not accessible to a surgical treatment. However, surgical sperm retrieval and injection de spermatozoïde en intracytopasmique (ICSI) allow fatherhood for these patients., Patients and Methods: A retrospective analysis of 104 consecutive patients from 1996 to 2006. A comprehensive clinical, spermiologic, hormonal, imaging and genetic workup was carried on. The data from the surgical extractions and the attempts of ICSI were collected., Results: Seventy-five percent of the patients had a mutation of the CFTR gene; ultrasound imaging revealed a renal or a seminal vesicle abnormality in 20% and 84.5% of the patients, respectively. The association of a semen volume less than 2 mL with a pH less than 7.2, a fructose less than 2 and mean sudoral chlore greater than 60 mmol/L enabled an immediate identification of 30% of patients carrier of the mutation and without renal abnormality. The sperm extraction rate was 98%., Conclusion: A search for the CFTR gene mutations and an ultrasound imaging of the genito-urinary system are essential to the workup of these patients. The association of a semen volume less than 2 mL, a semen pH less than 7.2 and a fructose less than 2 must point towards a minor form of cystic fibrosis and prompt the workup of genetic abnormalities and sudoral chlore testing. The results of the sperm extraction combined to the technical advances of IVF/ICSI allow excellent pregnancy rates of 66% for the companions of these patients., (Copyright © 2013. Published by Elsevier Masson SAS.)

Background: In non-obstructive azoospermia (NOA), testicular sperm extraction (TESE) is successful in ≈ 50% of cases. A parameter for predicting TESE quality and pregnancy rates after ICSI of testicular spermatozoa is still lacking., Methods: We retrospectively evaluated the total testicular volume (TTV), hormone levels and TESE quality in 280 patients with NOA. After successful TESE, the characteristics of the ICSI cycles and the take-home baby rates were evaluated., Results: TESE was successful in 149 patients (53.2%). In a multivariate logistic regression analysis, only TTV, FSH and inhibin B were correlated with the TESE outcome. A score including these three parameters was the best predictor of successful TESE (positive likelihood ratio: +3.01). When the score was <18.5, TESE was successful in 77.4% of cases and 'sperm rich' (i.e. yielding >100 spermatozoa) in 91.1% of cases; 42.8% of couples took a baby home. The take-home baby rate did not depend on whether the score was <18.5 or between 18.5 and 3700. If the score was >3700, TESE was successful in 37.8% of cases and 'sperm rich' in 14.3% of cases; only one couple took a baby home (a rate of 7.7 versus 42.8% when the score was <18.5; P< 0.001). Owing to low sperm retrieval on the day of oocyte retrieval, fewer oocytes were injected when the score was >3700 than when <3700., Conclusions: Thanks to better knowledge of TESE quality, the present score could help to improve care and pre-ICSI counseling for patients with NOA.

Objective: To evaluate the seminal levels of the Sertoli anti-Müllerian hormone (AMH) and inhibin B in the testicular sperm extraction (TESE) in nonobstructive azoospermia., Design: Prospective study., Setting: Reproductive biology division in a university hospital., Patient(s): One hundred thirty-nine men., Intervention(s): Men were classified on the basis of positive and negative TESE., Main Outcome Measure(s): Seminal levels of AMH and inhibin B, serum levels of FSH and inhibin B, testicular volume, sperm retrieval, and spermatogenesis., Result(s): The mean serum FSH and inhibin B concentrations were 21.4 IU/L and 54.68 pg/mL. Spermatozoa were retrieved in 43.17% of the men. Mean seminal AMH and inhibin B concentrations were 12.06±37.30 pmol/L and 142.72±950.91 pmol/L, respectively. Seminal AMH and inhibin B levels were simultaneously undetectable in 35.97% of subjects. Seminal plasma levels of AMH and inhibin B were positively correlated, as were seminal and serum inhibin B concentrations. The successful and failed TESE groups did not differ significantly in terms of either AMH or inhibin B seminal plasma concentrations. Combining the latter parameters with the serum FSH level did not improve the predictive value for successful TESE. The presence or absence of germ cells did not have a statistically significant relationship with seminal plasma AMH and inhibin B concentrations., Conclusion(s): There is no value in seminal plasma levels of AMH and inhibin B as criteria for sperm extraction in men with nonobstructive azoospermia., (Copyright © 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Azoospermia may be obstructive (blockage of the genital ducts) or non-obstructive (a lack of testicular production). The distinction is based on an ensemble of clinical, spermiological, hormonal, ultrasound, genetic and histological data. Azoospermia is the main indication for testicular biopsy for therapeutic and diagnostic purposes. Testicular spermatozoids are processed in the reproductive biology laboratory (simultaneously with oocyte retrieval or not) for in vitro fertilization with intra-cytoplasmic sperm injection. The histological study of spermatogenesis is usually performed on a testicular biopsy sample taken at the same time and provides additional diagnostic information on infertility. Histological alterations in the testicular tissues are frequently observed in azoospermic men. In non-obstructive azoospermia, three histological situations prevail: hypospermatogenesis, Sertoli-cell-only syndrome and germ cell arrest. One can distinguish between pure forms (in which all the seminiferous tubules have the same appearance) and mixed forms (in which the tubules' aspects are heterogeneous). Hypospermatogenesis is highly prevalent in azoospermia and is characterized by a low, basal level of spermatozoid production. The prevalence of Sertoli-cell-only syndrome varies from 27 to 68% and the mean spermatozoid recovery rate is between 16 and 33%. Germ cell arrests are rare phenotypes and have a poor prognosis for spermatozoid recovery. Overall, histological examination (still the only way to fully describe spermatogenesis) must be qualitative and quantitative, with the adoption of a standardized, universally understood terminology. It is essential to compare the histological data with (i) recovery of testicular spermatozoids, (ii) clinical, ultrasound, hormonal and genetic data and (iii) the outcome of IVF/ICSI procedures., (2010 Elsevier Masson SAS. All rights reserved.)

Introduction: Cryptorchidism is a common and possible etiology of male infertility., Objectives: This is a retrospective study of 142 azoospermic men with history of cryptorchidism. A testicular sperm extraction (TESE) was performed for each of them, between 1995 and 2005, to realize in vitro fecundation with intracytoplasmic sperm injection (ICSI)., Material and Methods: We studied the clinical pattern (age at the treatment, unilateral or bilateral cryptorchidism), hormonal levels (total testosterone and FSH) and ultrasound examinations in this population. Then, we studied the rates of successful TESE according to these various characteristics., Results: The main origin of azoospermia is non obstructive (secretory). A great majority of the patients (71.8%) has benefited of an orchidopexy before the age of 10 years which does not seem to represent a factor of better forecast of surgical extraction of sperm cells. In the subgroup of the bilateral cryptorchidy, the rate of extraction was 63% (55/87). In the subgroup of the one-sided cryptorchidy, it was 61.9% (36/42)., Conclusion: For us, history of cryptorchidism is an etiology of good prognosis for azoospermia, since the rate of TESE with positive sperm retrieval is 65%. In our population, the subgroups of patients whose FSH is normal and/or whose testicular volume is higher than 10 cm3 are those whose forecast is still better, because the rate of TESE with positive sperm retrieval is 75%.

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