F. Marcelli

Seminal plasma levels of anti-Müllerian hormone and inhibin B are not predictive of testicular sperm retrieval in nonobstructive azoospermia: a study of 139 men

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.

The serum inhibin B concentration and reference ranges in normozoospermia

OBJECTIVE Although an inhibin B assay may be useful in the assessment of testicular function in a number of genital conditions, reliable reference ranges are still lacking. The present study sought to establish the reference range for serum inhibin B by applying the updated Gen II assay. DESIGN This prospective study included 818 men referred for semen analysis: 377 were normozoospermic (reference group) and 441 presented at least one abnormal semen parameter (case group). METHODS Semen parameters were interpreted according to the 2010 World Health Organization manual and Davids modified classification for normal morphology. The inhibin B concentration was determined with the current ELISA. RESULTS In the reference group, the 2.5th percentile for inhibin B was 92 pg/ml and the 97.5th percentile for FSH was 7.8 IU/l. In the overall population, an inhibin B level <92 pg/ml was associated with increased odds ratio (OR; 95% CI) for oligozoospermia (16.93 (9.82-29.18), P<0.0001), asthenozoospermia (4.87 (2.88-8.10), P<0.0001), and teratozoospermia (2.20 (1.31-3.68), P=0.0026). The combination of a FSH >7.8 IU/l and an inhibin B <92 pg/ml was associated with greater OR for oligozoospermia (98.74 (23.99-406.35), P<0.0001) than for each hormone considered separately. CONCLUSIONS A new reference range for serum inhibin B was established by the use of updated immunoassay. The correlations between hormone levels and semen parameters highlighted the importance of establishing these values with respect to the spermogram. When combined with FSH assay, the inhibin B range may be of value in the evaluation of spermatogenesis in a number of male genital conditions.

Management of testicular lesions in a population of infertile patients

INTRODUCTION Testicular parenchyma abnormalities and testis cancers are more frequent in infertile men, hence the guidelines recommending a systematic scrotal ultrasound. METHODS A retrospective review of all patients treated with total or partial orchidectomy, from January, 2000 to July, 2010, for a testicular lesion discovered during an infertility evaluation work-up. Physical, examination data, type of surgery and pathological results were reported. RESULTS Forty-five patients were treated. The majority of tumors (80%) were non palpable, and incidentally discovered with scrotal ultrasonography. Eight cases were partial orchidectomies, and 37 cases were radical orchidectomies. A frozen section examination was performed in 13 cases, and led to two radical orchidectomies. Standard histological examination revealed 33 (73.3%) benign lesions (11 Leydig cell hyperplasias, 17 Leydig cell tumors, five Sertoli cell tumors) and 10 (22.2%) malignant lesions (nine seminomas and one teratoma). Ten patients had a Klinefelter syndrome, for whom all the lesions were benign. CONCLUSION The majority of non-palpable testicular lesions, discovered by ultrasonography in a population of infertile men were benign tumors. Conservative management in this context appears to be an option, to preserve the endocrine function and the fertility of these patients, while being ontologically safe.

Truncating Mutations in the Adhesion G Protein-Coupled Receptor G2 Gene ADGRG2 Cause an X-Linked Congenital Bilateral Absence of Vas Deferens

In 80% of infertile men with obstructive azoospermia caused by a congenital bilateral absence of the vas deferens (CBAVD), mutations are identified in the cystic fibrosis transmembrane conductance regulator gene (CFTR). For the remaining 20%, the origin of the CBAVD is unknown. A large cohort of azoospermic men with CBAVD was retrospectively reassessed with more stringent selection criteria based on consistent clinical data, complete description of semen and reproductive excurrent ducts, extensive CFTR testing, and kidney ultrasound examination. To maximize the phenotypic prioritization, men with CBAVD and with unilateral renal agenesis were considered ineligible for the present study. We performed whole-exome sequencing on 12 CFTR-negative men with CBAVD and targeted sequencing on 14 additional individuals. We identified three protein-truncating hemizygous mutations, c.1545dupT (p.Glu516Ter), c.2845delT (p.Cys949AlafsTer81), and c.2002_2006delinsAGA (p.Leu668ArgfsTer21), in ADGRG2, encoding the epididymal- and efferent-ducts-specific adhesion G protein-coupled receptor G2, in four subjects, including two related individuals with X-linked transmission of their infertility. Previous studies have demonstrated that Adgrg2-knockout male mice develop obstructive infertility. Our study confirms the crucial role of ADGRG2 in human male fertility and brings new insight into congenital obstructive azoospermia pathogenesis. In men with CBAVD who are CFTR-negative, ADGRG2 testing could allow for appropriate genetic counseling with regard to the X-linked transmission of the molecular defect.

Cryptorchidie : de la physiopathologie à l’infertilité

Cryptorchidism is a defect of testicular descent. Hormonal, genetic and environmental factors might also contribute to the aetiology of cryptorchidism and its increased incidence in recent years in industrialised countries. Cryptorchidism itself might be considered a complex disease. This testicular pathology represents the best-characterized risk factor for reduced fertility and testicular cancer. The purpose of this review is to better understand physiopathology and mechanisms of infertility in men with history of cryptorchidism.

Immunodetection of Tau microtubule-associated protein in human sperm and testis

primary antibody was omitted. The slides were observed, and images were acquired with a confocal LSM710 microscope and an Axioplan microscope (both from Zeiss, Göttingen, Germany). Tau immunostaining was detected in all smeared spermatozoa (Figure 1a). The Tau protein was located in the sperm midpiece. In testicular tissue, Tau immunoreactivity was observed in both spermatocytes and spermatids (Figure 1b). In spermatocytes, cytoplasmic f luorescent dots were located all around the nucleus (Figure 1c). In elongated spermatids, the immunolabeled zone was situated behind the nucleus (Figure 1d). No staining was observed in spermatozoa or in tissue sections of control samples lacking primary antibody (Figure 1e and 1f). Over the last decades, few researchers have studied the presence of Tau protein in the reproductive tract. Two eminent, early studies reported the presence of Tau protein in the rodent and bovine testis.4,5 In human germ cells and spermatozoa, Tau may be involved in the regulation of microtubule proteins. The spermatozoon’s main microtubule-organizing centre is the centrosome complex. It has a role in sperm and zygote aster formation, and the development of the bipolar mitotic apparatus.7 Dysfunction of the centrosome complex will result in developmental abnormalities after fertilization. The epithelium of seminiferous tubules has a vast network of microtubules (particularly within the manchette, the axoneme, and the mitotic and meiotic spindles of germ cells).8 The presence of Tau in human testicular tissue suggests that this protein has a role in meiotic division in male germ cells and during their extension to spermatozoa. As has been suggested in the context of tauopathies,9 the aggregation, hyperphosphorylation and/or ubiquination of Tau might impair sperm microtubule function and transport. In summary, this study reports the immunoexpression of Tau microtubule-associated protein in human sperm and testis. We hypothesize that Tau is involved in the development of sperm in a man and thus may represent an additional parameter for sperm function in male fertility.

Prise en charge de l’infertilité masculine

Actuellement, en France, plus d’un couple sur dix va être amené à consulter un médecin pour infertilité. L’infertilité du couple se définit par l’absence de grossesse après un an de rapports sexuels réguliers sans contraception. Dans certaines conditions particulières (troubles du cycle chez la femme, antécédents médicochirurgicaux particuliers d’un ou des deux partenaires. . .), le bilan d’infertilité peut être réalisé plus rapidement avec une certaine légitimité. Ce bilan est indispensable dans la démarche étiologique et thérapeutique (cause curable ou orientation vers les techniques d’assistance médicale à la procréation). Une étiologie masculine est retrouvé dans près de 40 % des cas. Elle est soit isolée, soit associée également à un facteur féminin d’infertilité. C’est pourquoi, les bilans cliniques et spermiologiques de l’homme sont incontournables et doivent être réalisés systématiquement. Les dernières avancées en matière d’aide médicale à la procréation (AMP) avec la technique de fécondation in vitro avec micro-injection intracytoplasmique (FIV-ICSI) ont révolutionné les thérapeutiques proposées aux hommes infertiles par azoospermie ou oligozoospermie sévère et avec des anomalies spermatiques sévères (asthénozoospermie et/ou tératozoospermie majeures).

Description andrologique d’une population azoosperme avec une agénésie des canaux déférents consultant pour infertilité ☆

CONTEXT In the 1990s, 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.

Recueil chirurgical de spermatozoïdes dans un groupe de 50 patients avec un antécédent de cryptorchidie bilatérale: facteurs pronostics d’extraction

ResumeLa cryptorchidie dans sa forme bilatérale est un facteur sévère d’infertilité masculine. Nous avons colligé 50 hommes ayant comme antécédent une cryptorchidie bilatérale associée à une azoospermie sur une période de 1995 à 2001. Un bilan hormonal avec un dosage de la FSH et de la testostérone et une échographie de l’appareil uro-génital ont été réalisés chez tous les patients. La FSH était élevée dans 67% des cas et le volume testiculaire abaissé dans 70%, témoignant d’une origine sécrétoire à l’azoospermie. Une tentative de recueil chirurgical de spermatozoïdes par biopsies testiculaires bilatérales était entreprise en vue de la réalisation d’une ICSI. Le taux de recueil positif s’élève à 68%. En associant les différents facteurs pré-chirurgicaux (FSH, volume testiculaire), nous avons essayé de mettre en évidence un facteur prédictif de la présence de spermatozoïdes. La FSH, ainsi que le volume testiculaire, dans cette population, ne permettent pas de prédire de la présence de spermatozoïdes. La cryptorchidie bilatérale représente un antécédent de moins mauvais pronostic dans le groupe des azoospermies sécrétoires.AbstractBilateral cryptorchidism is a severe factor of male infertility. We evaluated the results of testicular sperm extraction in 50 men with nonobstructive azoospermia associated with cryptorchidism between 1995 to 2001. We evaluated clinical parameters predictive of successful sperm extraction.Serum follicle stimulating hormone (FSH) was elevated in 67% of cases and testicular volume was decreased in 70% of cases, confirming the secretory origin of the azoospermia. Serum follicle stimulating hormone (FSH), testicular volume and histological parameters were examined as predictive factors for sperm recovery. The positive sperm recovery rate was 68%.As in the population of men with nonobstructive azoospermia, the sperm recovery rate for patients with a history of orchidopexy is approximately 68% and there are currently no clinical parameters predicting successful sperm retrieval in this subpopulation of patients.