Abstract 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.

La infertilidad afecta a casi el 15% de las parejas que desean procrear, con una causa masculina en casi el 50% de los casos. Su tratamiento sólo puede concebirse dentro de un equipo multidisciplinario. Las causas secretoras o testiculares van en aumento, a veces asociadas a anomalías genéticas (síndrome de Klinefelter, anomalías del cromosoma Y en particular), locales (varicocele, orquitis) o iatrogénicas (quimioterapia y otros tratamientos tóxicos para la espermatogénesis) y representan más del 50% de los casos de infertilidad masculina. Ante la imposibilidad de encontrar espermatozoides aptos en el eyaculado, estas situaciones justifican, quizás después de una tentativa de mejora de la espermatogénesis, especialmente con la reparación de un varicocele, una exploración quirúrgica de búsqueda de espermatozoides, en ocasiones por microcirugía (TESE [extracción de espermatozoides testiculares] o micro-TESE) con cerca de un 40% de búsqueda positiva y con sólo un 10% de embarazos evolutivos. Se está evaluando el lugar de los tratamientos hormonales para estimular la espermatogénesis. Las causas excretoras u obstructivas son congénitas (ausencia de los conductos deferentes, anomalías de la encrucijada urogenital) o adquiridas (infecciones urogenitales, iatrogenia) y justifican la extracción quirúrgica de espermatozoides de la vía seminal (red testicular, epidídimo o conducto deferente) y/o testicular cuando la reparación quirúrgica no es posible (anastomosis epididimodeferencial, vasovasostomía, repermeabilización de los conductos eyaculadores). Por último, los trastornos de la eyaculación (diabetes, paraplejía, trastorno psicógeno, etc.) pueden causar infertilidad masculina y requerir la extracción quirúrgica de espermatozoides.

AIM: To assess the diagnostic performance of conventional ultrasound (US) and contrast-enhanced ultrasonography (CEUS) in the differential diagnosis of non-palpable intra-testicular tumours. MATERIALS AND METHODS: The local ethics review board approved the protocol, and all of the patients provided written informed consent. Between December 2011 and February 2014, men with non-palpable testicular tumours and normal tumour markers who were referred for surgery were included. The tumours were analysed by conventional US, including B-mode and colour Doppler US (CDUS) as well as by CEUS. Morphological aspects and qualitative and quantitative CEUS criteria, based on visual enhancement and time-intensity curves, were assessed for each lesion. RESULTS: Forty patients were ultimately included. Based on histopathological results, the tumours were classified into three groups: benign tumours (n=16), malignant tumours (n=15), and burned-out tumours (n=9). In B-mode, the morphological aspects were significantly different between benign and malignant tumours (p-values from 0.0002 to 0.008). Qualitative and quantitative analyses of the CEUS images revealed that burned-out tumours exhibited significantly less enhancement than malignant and benign tumours: in burned-out tumours, time-intensity curves were flat, whereas in both benign and malignant tumours the curves had a bell-shaped pattern. All intensity parameters were lower for burned-out tumours compared to benign and malignant tumours (p-value from 0.0001 to 0.026). Both benign and malignant tumours enhanced strongly, however, and no significant difference between the two was noted (p-value from 0.0721 to 0.0953). CONCLUSION: Unlike conventional US, which enable benign lesions to be differentiated from malignant or burned-out tumours, CEUS failed to enabled differentiation between benign lesions and malignant vascularised testicular tumours. CEUS appears to have the potential, however, to differentiate burned-out tumours from vascularised testicular tumours. (C) 2017 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Les tumeurs testiculaires découvertes lors d’un bilan d’infertilité sont souvent de faibles volumes. L’orchidectomie totale est le traitement de référence mais une chirurgie partielle peut s’envisager pour sauvegarder du parenchyme testiculaire et maintenir une fonction endocrine et exocrine. L’objectif de cette étude était d’étudier les particularités anatomopathologiques des tumeurs testiculaires chez les patients infertiles et d’étudier la faisabilité d’une orchidectomie partielle en première intention. Une étude rétrospective multicentrique a permis de rassembler les données issues de patients infertiles, chez qui a été mis en évidence une tumeur testiculaire au cours du bilan d’infertilité. Un total de 32 patients traités par orchidectomie partielle a été inclus. Les patients inclus étaient des hommes de tous âges qui consultaient pour une infertilité avec un spermogramme altéré et chez qui l’examen clinique et/ou une échographie confirmai(en)t le diagnostic de tumeur intratesticulaire. Les patients opérés d’une orchidectomie totale d’emblée ont été exclus. La moyenne d’âge était de 36 ans (IIQ 32–37). La moitié des patients étaient azoosperme (16/32), un quart oligosperme (8/32) et 28 % teratosperme (9/32). Le plus grand axe tumoral échographique était en moyenne de 8,7 mm (IIQ 5–10). Un total de 8/32 (25 %) des patients avaient une tumeur maligne (séminome 7/32, 22 % ; tératome 1/32, 3 %) et 24/32 (75 %) avaient une lésion bénigne (Leydigome 23/32, 72 % ; cicatrice fibreuse 1/32, 3 %). L’analyse extemporanée n’avait pas diagnostiqué le caractère malin dans 50 % (4/8), mais avait identifié 88 % (21/24) des tumeurs bénignes. Vingt-cinq pour cent des patients ont eu une orchidectomie totale complémentaire (8/32), dont 6/8 (75 %) parmi les patients atteint d’une tumeur maligne. Sur un suivi moyen de 26,1 mois (IIQ 8–31,3), un patient (3 %) a eu une récidive de type Leydigome homolatéral. Aucun patient n’avait de métastases. Un seul patient a donné paternité (3 %). Cette étude met en évidence, dans une population de patients infertiles, que des tumeurs de faibles volumes sont en majorité bénignes et de bon pronostic. L’analyse extemporanée restait aléatoire pour affirmer le diagnostic de malignité, mais présentait une bonne sensibilité pour identifier une tumeur bénigne. La sauvegarde de parenchyme testiculaire pourrait donc être envisagée en première intention chez des hommes infertiles avec une possibilité d’orchidectomie totale secondaire.

RADIOLOGIE ET IMAGERIE MEDICALE : Genito-urinaire - Gyneco-obstetricale - Mammaire - 34-450-A-15

Taking advantage of the high mass transfer in the bulk solution of fluidized-bed reactor (FBR), and the benefits of simultaneous particle separation and ozone catalysis on ceramic membranes, we proposed a hybrid fluidized-bed reactor (HFBR) based on arrayed ceramic membranes (ACMs) coupled with powdered activated carbon (PAC) for efficient catalytic ozonation. The optimum HFBR performance on a pilot scale was found at PAC addition of 3 g/L, ozone dosage of 25 mg/L, hydraulic retention time of 60 min and auxiliary aeration strength of 5 m3/h. During the 30-day treatment of coal-gasification secondary effluent (200 L/h), the HFBR system revealed not only a 117% increase in ozone utilization efficiency (ΔCOD/ΔO3) upon pure ozonation but also a highly purified effluent with better sterilization and low residual bromate (∼11 μg/L). Low-molecular-weight organic fragments and acids, as well as phthalate esters were identified as the main products in this process. By density functional theory (DFT) calculations, it was found the main functional groups (carbonyls, –C=O) on the PAC could be protected from direct ozonation in the presence of ozone-degradable organics (e.g. phenolic and aliphatic compounds) in the wastewater through an ozone-competing reaction, which prevented the rapid inactivation of the PAC in catalytic ozonation. A longer service life and cheaper materials for ceramic membranes would benefit low operation costs for the HFBR. Moreover, the addition of PAC could greatly reduce ozone demand by ∼60% in the HFBR, and therefore decrease energy consumption by ∼30%. Hence, the HFBR was proved to be a highly competitive technology for wide application in the near future.

Objective. - Analyzing the results and validating the procedure of testicular sperm extraction (TESE) performed on the day of oocyte retrieval in non obstructive azoospermia (NOA) patients.Patients and methods. - Sixty TESE were performed on the day of oocyte retrieval (dOR), in 52 NOA men. Patients were sorted into three groups according to the results of the surgical procedure: 1: sperm recovery with possible sperm freezing (n = 20); 2: sperm recovery without freezing (n = 27); 3: "negative" biopsy (n = 13). ICSI outcomes in the two groups with sperm recovery were compared to those of ICSI performed with frozen-thawed sperm obtained from TESE performed (n = 13).Results. - The rate of positive sperm retrieval was 78%. While the overall clinical pregnancy rate was 50%, no difference in the fertilization, implantation and clinical pregnancy rates was found in the two groups with positive sperm retrieval as compared to frozen-thawed sperm group. Twelve pregnancies were obtained in patients without further sperm cryopreservation.Conclusion. - After TESE in NOA men, cryopreserved sperm produced comparable results with freshly obtained sperm. However, TESE performed on dOR can offer the opportunity, in patients with rare sperm that might not survive freeze-thaw, to have a possible fresh embryo transfer. Couples should be counselled regarding the possibility of oocyte retrieval without sperm for ICSI. (C) 2010 Elsevier Masson SAS. All rights reserved.

Evaluer l’IRM pelvienne pour l’analyse morphologique des voies génitales profondes chez l’homme infertile suspect de malformation ou d’occlusion génitale. Depuis 3 ans sur 3000 patients adressés pour exploration échographique d’une hypofertilité, 35 patients ont bénéficié d’une IRM pelvienne pour suspicion de malformation des voies génitales ou obstacle sur les voies séminales. Protocole d’examen : antenne de surface (phase-array cardiaque), T2 dans les 3 plans, T1 axial. On retrouve des agénésies ou atrésies déférentielles ou vésiculaires chez 8 patients, une dilatation des confluents vésiculo-déférentiels ou des vésicules séminales chez 14 patients, des abouchements ectopiques urétéraux chez 3 patients, des urétérocèles chez 2 patients, des kystes compressifs chez 4 patients, un adénocarcinome de l’utricule chez 1 patient. Une stagnation spermatique au sein des voies génitales apparaît hypersignal T1 est retrouvée chez 6 patients. Certaines de ces malformations entrent dans le cadre de pathologies connues : syndrome de Noonan, syndrome de Kalman de Morsier, syndrome de Prune Belly, imperforation anale. Les anomalies de signal de la zone périphérique prostatique, à type de plages en hypo-signal T2 ou d’hyposignal diffus concernent 33 patients sur 35, dont la moitié ne montrait pas d’anomalie échographique, et l’autre moitié présentait des plages hyperéchogènes. L’IRM permet une meilleure analyse objective des voies génitales profondes et complète l’échographie transrectale. Les anomalies de signal prostatique dans ces pathologies sont peu décrites et étant donné leur fréquence dans cette série, elles pourraient faire l’objet d’une étude prospective plus large : les remaniements infectieux ou inflammatoires ou l’environnement biochimique de la prostate peuvent-ils être à l’origine d’hypofertilité masculine ?

An infertility evaluation should be performed if a couple has not achieved conception after one year of unprotected intercourse. An evaluation should be performed earlier if male or female infertility risk factors exist and if the couple questions its fertility potential. The initial screening of the male should include a reproductive history and a physical examination performed by a urologist or a specialist in male fertility and two semen analyses. Additional procedures and testing may be used to elucidate problems discovered during the full evaluation. The minimal initial endocrine evaluation should include serum total testosterone and serum follicle-stimulating hormone levels. An endocrine evaluation should be performed if sperm concentration is abnormally low, sexual function is impaired, and when other clinical findings suggest a specific endocrinopathy. A postejaculatory urinalysis should be performed if ejaculate volume is less than 1 mL, except in patients with bilateral vasal agenesis or possible hypogonadism. With a diagnosis of retrograde ejaculation, specific management should be considered before advising assisted reproductive technology. Scrotal ultrasonography is indicated when physical examination of the scrotum is difficult or inadequate, or when a testicular mass is suspected. Transrectal ultrasonography (TRUS) is indicated in patients who are azoospermic or have a low ejaculate volume. Specialized testing of semen is not required for routine diagnosis of male infertility. However, some tests may be useful for a few patients to identify a male factor contributing to unexplained infertility, or to select therapy (e.g., assisted reproductive technology). Before performing intracytoplasmic sperm injection, karyotyping and Y-chromosome analysis should be offered to men who have nonobstructive azoospermia and severe oligospermia. Genetic testing for gene mutations of the ABCC7 (ex-CFTR) gene should be offered to male and female partners before proceeding with treatments that use the sperm of men with congenital bilateral absence of the vasa deferentia or congenital unilateral abnormality of the seminal tract. Genetic counseling may be offered when a genetic abnormality is suspected in the male or female partner, and it should be provided when a genetic abnormality is detected. Genetic testing in the female partner, when non symptomatic, should only be advised by a physician from a multidisciplinary team registered by the ministry of health. Evaluation by testis biopsy and deferentography should be performed by a urologist or an andrologist registered for sperm retrieval.

Etudier les données de l’échographie scrotale chez une série de patients porteurs de l’aneuploïdie gonosomique XXY (syndrome de Klinefelter). Deux mille patients ont bénéficié d’une échographie scrotale pour infertilité. Trente d’entre eux se sont avérés être porteurs d’une aneuploïdie gonosomique XXY homogène (Syndrome de Klinefelter). Les mosaïques ont été exclues. Nous rapportons les données de leur échographie testiculaire ainsi que leur suivi. Tous les patients présentaient une hypotrophie testiculaire importante, en moyenne 1,9 cm3 par testicule. Vingt quatre patients avaient des anomalies de l’échostructure : très grossière (12 patients), multimicro ou macronodulaire (14 patients). Des microlithiases de grade 1 ont été retrouvées chez 10 patients. Une exploration pour nodule hypoéchogène vascularisé dominant, avec chirurgie d’exérèse partielle a été réalisée chez 4 patients. Il s’agissait d’hyperplasie leydigienne ou de petite tumeur bénigne à cellule de Leydig. La constatation d’une hypotrophie testiculaire sévère (It ; 3 cm3), bilatérale et associée à des nodules et quelques microlithiases doit faire évoquer une aneuploïdie gonosomique type Klinefelter. Ces patients ayant une production limite ou insuffisante de testostérone, l’orchidectomie abusive doit être évitée : les nodules hypoéchogènes plus volumineux seront surveillés ou devront bénéficier d’une chirurgie partielle, car il s’agit le plus souvent de tumeur ou d’hyperplasie bénigne à cellule de Leydig.

Micro-Raman scattering experiments have been performed on the ternary solid solution in the Zn4Sb3-Cd4Sb3 system. Ten samples were studied; their compositions go from Zn4Sb3 to Zn3.1Cd0.9Sb3. The homogeneity of these samples was checked by X-ray diffraction and electron microprobe analysis. The corresponding lattice parameters were calculated and their concentration dependence exhibits a small negative deviation from Vegard's law between end members of the Zn4Sb3-Cd4Sb3 system.Three peaks and one shoulder are easily observable in the Raman spectrum of P-Zn4Sb3. These peaks are still present when the zinc atoms are substituted by cadmium ones. As the intensities of the Raman lines were observed to be very sensitive to the direction of the microcrystallites, only the change of the position could be discussed. From these experiments, we can suggest that the peak at about 155 cm(-1) should imply essentially Sb-Sb bondings while the peaks at about 172 cm(-1) and 320 cm(-1) must also imply Cd-Sb and Zn-Sb bondings. (c) 2006 Elsevier B.V. All rights reserved.

(Y;autosome) translocations have been reported in association with male infertility. Different mechanisms have been suggested to explain the male infertility, such as deletion of the azoospermic factor (AZF) on the long arm of the Y chromosome, or meiosis impairment. We describe a new case with a de novo unbalanced translocation t(Y;22) and discuss the genotype-phenotype correlation. A 36 year old male with azoospermia was found to have a mosaic 45,X/46,X, + mar karyotype. Fluorescence in situ hybridization (FISH) showed the presence of a derivative Y chromosome containing the short arm, the centromere and a small proximal part of the long-arm euchromatin of the Y chromosome and the long arm of chromosome 22. The unstable small marker chromosome included the short arm and the centromere of chromosome 22. This unbalanced translocation t(Y;22)(q11.2;q11.1) generated the loss of the long arm of the Y chromosome involving a large part of AZFb, AZFc and Yq heterochromatin regions. Testicular tissue analyses showed sperm in the wet preparation. Our case shows the importance of documenting (Y;autosome) translocations with molecular and testicular tissue analyses.