Defining Reference Ranges for Serum Anti-Müllerian Hormone on a Large Cohort of Normozoospermic Adult Men Highlights New Potential Physiological Functions of AMH on FSH Secretion and Sperm Motility.

BACKGROUND: Few studies to date have attempted to measure serum anti-Müllerian hormone (AMH) levels in adult men, and solid references ranges have not yet been defined in a large cohort. OBJECTIVE: In this study, we aimed, first, to establish the reference ranges for serum AMH and AMH-to-total testosterone ratio (AMH/tT) in adult males. Second, we investigated the relationship between serum AMH and both reproductive hormones and semen parameters. METHODS: This single-center retrospective study included 578 normozoospermic adult men. Serum AMH concentrations were determined with an automated sandwich chemiluminescent immunoassay. RESULTS: The median serum AMH was 43.5 pmol/L. The 2.5th and 97.5th percentile values for serum AMH and AMH/tT were 16.4 and 90.3 pmol/L and 0.45 and 3.43, respectively. AMH was positively correlated with inhibin B and sperm concentration and negatively correlated with age, follicle-stimulating hormone (FSH), and progressive sperm motility. Interestingly, using immunofluorescence, we documented for the first time that AMH type II receptor (AMH-R2) is expressed in ejaculated human spermatozoa and gonadotrophic cells in the postmortem pituitary gland. CONCLUSIONS: We establish a new age-specific reference range for serum AMH and AMH/tT. Moreover, AMH-R2 expression in human spermatozoa and gonadotrophic cells, together with the relationship between serum AMH levels and sperm motility or mean FSH levels, highlight new potential functions of AMH in regulating sperm motility or FSH secretion in adult men.

Non-obstructive idiopathic azoospermia vs azoospermia with antecedents of cryptorchidism: ways and probabilities of becoming parents.

BACKGROUND: Non-obstructive azoospermia (NOA) with history of cryptorchidism and idiopathic NOA are the most common forms of NOA without genetic aetiology. Of all patients with one of these two types of NOA, only a few will have a positive TEsticular Sperm Extraction (TESE). Of those with positive extraction followed by sperm freezing, not all will have a child after TESE-ICSI. What are the ways and probabilities of taking home a baby for patients with NOA and a history of cryptorchidism compared with patients with idiopathic NOA? RESULTS: Patients with idiopathic NOA or NOA and a history of cryptorchidism who underwent their first TESE were included. The patients were divided into two groups: Group 1 was composed of 125 patients with idiopathic NOA and Group 2 of 55 patients with NOA and a history of surgically treated cryptorchidism. Our results showed that more than half of the NOA patients succeeded in becoming parents. The main way to fulfil their plans for parenthood is to use sperm or embryo donation (72%) for men with idiopathic NOA, whereas the majority of men with NOA and a history of cryptorchidism had a child after TESE-ICSI (58.8%). CONCLUSIONS: In our centre, before considering TESE for a patient with NOA, we explain systematically TESE-ICSI alternatives (sperm donation, embryo donation or adoption). As a result, the couple can consider each solution to become parents.

RESUME: CONTEXTE: L'azoospermie non obstructive (ANO) avec un antécédent de cryptorchidie et l'ANO idiopathique sont les causes les plus fréquentes d'ANO sans étiologie génétique. Parmi les patients présentant un de ces 2 types d'ANO, seuls quelques-uns auront une extraction positive de spermatozoïdes testiculaires (TESE). Parmi les patients ayant une extraction positive suivie d'une congélation de spermatozoïdes, tous n'obtiendront pas de naissance après TESE-ICSI. Quels sont les moyens et les probabilités de « ramener un enfant à la maison ¼ pour les patients avec une ANO associée à un antécédent de cryptorchidie en comparaison à ceux présentant une ANO idiopathique ? RéSULTATS: De tels patients ont été inclus dans notre étude et divisés en deux groupes : Groupe 1 composé de 125 patients avec une ANO idiopathique et Groupe 2 de 55 patients avec une ANO associée à un antécédent de cryptorchidie traitée chirurgicalement. Nos résultats ont montré que plus de la moitié des patients atteints d'ANO ont réussi à devenir parents. Le principal moyen pour réaliser leur projet parental était le recours au don de sperme ou l'accueil d'embryons (72%) pour les hommes avec ANO idiopathique, alors que la majorité des hommes avec ANO et antécédent de cryptorchidie (58.8%) achevaient leur projet parental par TESE-ICSI. CONCLUSIONS: Dans notre centre, avant d'envisager une biopsie testiculaire chez un patient présentant une ANO, les alternatives (don de sperme, accueil d'embryon ou adoption) à la TESE-ICSI sont explicitées systématiquement. En conséquence, le couple peut envisager chaque solution pour devenir parent.

Contribution of serum anti-Müllerian hormone in the management of azoospermia and the prediction of testicular sperm retrieval outcomes: a study of 155 adult men.

BACKGROUND: Testicular sperm extraction (TESE) is the method of choice for recovering spermatozoa in patients with azoospermia. However, the lack of reliable biomarkers makes it impossible to predict sperm retrieval outcomes at TESE. To date, little attention has been given to anti-Müllerian hormone (AMH) serum levels in adult men with altered spermatogenesis. In this study we aimed to investigate whether serum concentrations of AMH and the AMH to total testosterone ratio (AMH/T) might be predictive factors for sperm retrieval outcomes during TESE in a cohort of 155 adult Caucasian men with azoospermia. RESULTS: AMH serum levels were significantly lower in nonobstructive azoospermia (NOA) that was unexplained, cryptorchidism-related, cytotoxic and genetic (medians [pmol/l] = 30.1; 21.8; 26.7; 7.3; and p = 0.02; 0.001; 0.04; <0.0001, respectively]) compared with obstructive azoospermia (OA) (median = 44.8 pmol/l). Lowest values were observed in cases of genetic NOA (p < 0.0001, compared with unexplained NOA) and especially in individuals with non-mosaic Klinefelter syndrome (median = 2.3 pmol/l, p <0.0001). Medians of AMH/T values were significantly lower in genetic NOA compared to unexplained, cryptorchidism-related NOA as well as OA. Only serum concentrations of AMH differed significantly between positive and negative groups in men with non-mosaic Klinefelter syndrome. The optimal cut-off of serum AMH was set at 2.5 pmol/l. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of this cut-off to predict negative outcomes of SR were 100 %, 76.9 %, 66.6 %, 100 and 84.2 %, respectively. CONCLUSIONS: Serum AMH levels, but not AMH/T values, are a good marker for Sertoli and germ cell population dysfunction in adult Caucasian men with non-mosaic Klinefelter syndrome and could help us to predict negative outcomes of SR at TESE with 100 % sensitivity when serum levels of AMH are below 2.5 pmol/l.

RéSUMé: INTRODUCTION: L'extraction chirurgicale de spermatozoïdes testiculaires (ECST) est la méthode qui permet d'offrir aux hommes ayant une azoospermie des chances de paternité via l'assistance médicale à la procréation. Cependant, le manque de biomarqueurs fiables rend impossible de prédire les résultats de l'ECST. À ce jour, peu d'attention a été accordée aux valeurs sériques d'hormone anti-müllérienne (AMH) chez les hommes adultes ayant une spermatogenèse altérée. Dans cette étude, nous avons cherché à déterminer si les concentrations sériques d'AMH et le rapport AMH sur testostérone totale (AMH/T) pouvaient être des facteurs prédictifs des résultats de l'ECST dans une cohorte de 155 hommes adultes caucasiens ayant une azoospermie. RéSULTATS: Les concentrations sériques d'AMH étaient significativement plus faibles dans l'azoospermie non-obstructive (ANO) non inexpliquée, ANO associée à un antécédent de cryptorchidie, ANO d'origine cytotoxique et génétique (médianes [pmol/l] = 30,1; 21,8; 26,7; 7,3; et p = 0,02; 0,001; 0,04; <0,0001, respectivement) comparativement au groupe contrôle d'azoospermie obstructive (AO) (médiane = 44,8 pmol/l). Les plus faibles valeurs ont été observées dans le groupe d'ANO d'origine génétique (p = 0,0001, par rapport à l'ANO non inexpliquée) et particulièrement chez les individus avec un syndrome de Klinefelter (médiane = 2,3 pmol/l, p <0,0001). Seules les concentrations sériques d'AMH différaient significativement entre les individus avec résultats positifs et négatifs d'extraction de spermatozoïdes chez les hommes atteints d'un syndrome de Klinefelter non mosaïque. Un seuil optimal du taux sérique d'AMH a été fixé à 2,5 pmol/l. La sensibilité, la spécificité, la valeur prédictive positive, la valeur prédictive négative et l'exactitude de ce seuil pour prédire un résultat négatif étaient de 100 %, 76,9 %, 66,6 %, 100 % et 84,2 %, respectivement. CONCLUSIONS: Seules les concentrations sérique d'AMH, et non pas le rapport AMH/T, sont un bon marqueur du dysfonctionnement des cellules de Sertoli ainsi que des cellules germinales chez les hommes adultes caucasiens atteints du syndrome de Klinefelter non mosaïque. Elles peuvent prédire un résultat négatif du prélèvement de spermatozoïdes lors de l'ECST avec une sensibilité de 100 % lorsque les niveaux sériques sont inférieurs à 2,5 pmol/l.

Bilateral versus unilateral cryptorchidism in nonobstructive azoospermia: Testicular sperm extraction outcomes.

Cryptorchidism is one of the most frequent causes of nonobstructive azoospermia (NOA) in adulthood. Although it is well known that spermatogenesis is more impaired in bilateral than in unilateral cryptorchidism, previous studies have only described small cohorts or inhomogeneous population. Consequently, we analyzed a cohort of 225 men with only a history of cryptorchidism as sole etiopathogenetic factor for NOA, and compared testicular sperm extraction (TESE) outcomes between men with bilateral versus unilateral cryptorchidism. Our results show no difference in follicle-stimulating hormone (FSH) levels and testicular volumes between men with a history of bilateral cryptorchidism compared to unilateral cryptorchidism (median: 21.3 IU l-1 vs 19.3 IU l-1, P = 0.306; and 7.2 ml vs 7.9 ml, P = 0.543, respectively). In addition, sperm retrieval rates were similar (66.2% vs 60.0%, P = 0.353). Using multivariate analysis, we have found that only a low inhibin B level (above the assay's detection limit) was positively associated with successful sperm retrieval (P < 0.05). Regarding intracytoplasmic sperm injection outcomes, we found that cumulative pregnancy rate and live birth rate per cycle were not statistically different between the two groups (17.4% vs 27.8%, P = 0.070; and 16.1% vs 26.4%, P = 0.067, respectively). Unexpectedly, there was no significant difference in hormonal profiles (FSH, luteinizing hormone [LH], testosterone, and inhibin B levels) and TESE outcomes between unilateral versus bilateral cryptorchidism. This suggests that a history of unilateral cryptorchidism could reflect a bilateral testicular impairment. Interestingly, inhibin B level might be a predictor of successful TESE.

New insights into the morphological and hormonal characteristics of spermatogenic arrest.

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.

Defining the human sperm microtubulome: an integrated genomics approach.

Sperm motility notably depends on the structural integrity of the flagellum and the regulation of microtubule dynamics. Although researchers have started to use "omics" techniques to characterize the human sperm's molecular landscape, the constituents responsible for the assembly, organization, and dynamics of the flagellum microtubule have yet to be fully defined. In this study, we defined a core set of 116 gene products associated with the human sperm microtubulome (including products potentially involved in abnormal ciliary phenotypes and male infertility disorders). To this end, we designed and applied an integrated genomics workflow and combined relevant proteomics, transcriptomics, and interactomics datasets to reconstruct a dynamic interactome map. By further integrating phenotypic information, we defined a disease-interaction network; this enabled us to highlight a number of novel factors potentially associated with altered sperm motility and male fertility. Lastly, we experimentally validated the expression pattern of two candidate genes (CUL3 and DCDC2C) that had never previously been associated with male germline differentiation. Our analysis suggested that CUL3 and DCDC2C's products have important roles in the sperm flagellum. Taken as a whole, our results demonstrate that an integrated genomics strategy can highlight relevant molecular factors in specific sperm components. This approach could be easily extended by including other "omics" data (from asthenozoospermic men, for example) and identifying other critical proteins from the human sperm microtubulome.

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.

Immunosuppressive drugs and fertility.

Immunosuppressive drugs are used in the treatment of inflammatory and autoimmune diseases, as well as in transplantation. Frequently prescribed in young people, these treatments may have deleterious effects on fertility, pregnancy outcomes and the unborn child. This review aims to summarize the main gonadal side effects of immunosuppressants, to detail the effects on fertility and pregnancy of each class of drug, and to provide recommendations on the management of patients who are seen prior to starting or who are already receiving immunosuppressive treatment, allowing them in due course to bear children. The recommendations for use are established with a rather low level of proof, which needs to be taken into account in the patient management. Methotrexate, mycophenolate, and le- and teri-flunomide, cyclophosphamide, mitoxanthrone are contraindicated if pregnancy is desired due to their teratogenic effects, as well as gonadotoxic effects in the case of cyclophosphamide. Anti-TNF-alpha and mTOR-inhibitors are to be used cautiously if pregnancy is desired, since experience using these drugs is still relatively scarce. Azathioprine, glucocorticoids, mesalazine, anticalcineurins such as cyclosporine and tacrolimus, ß-interferon, glatiramer-acetate and chloroquine can be used during pregnancy, bearing in mind however that side effects may still occur. Experience is limited concerning natalizumab, fingolimod, dimethyl-fumarate and induction treatments. Conclusion: At the time of prescription, patients must be informed of the possible consequences of immunosuppressants on fertility and of the need for contraception. Pregnancy must be planned and the treatment modified if necessary in a pre-conception time period adapted to the half-life of the drug, imperatively in relation with the prescriber of the immunosuppressive drugs.

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 David's 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.

Sperm cryopreservation in adolescents and young adults with cancer: results of the French national sperm banking network (CECOS).

OBJECTIVE: To determine the feasibility of fertility preservation in adolescent males with cancer. DESIGN: Large multicenter retrospective study of male patients ≤20 years from 23 centers of a national network of sperm banks over a 34-year period. SETTING: Sperm banks. PATIENT(S): A total of 4,345 boys and young men aged 11 to 20 years. INTERVENTION(S): Age, cancer diagnosis, feasibility of sperm banking, and sperm parameters. MAIN OUTCOME MEASURE(S): Description of patients, and success of their fertility preservation. RESULT(S): We observed a mean yearly increase in referred patients of 9.5% (95% confidence interval, 9.1%-9.8%) between 1973 and 2007. Over the study period, the percentage of younger cancer patients who banked their sperm increased, especially in the 11-14 year age group, rising from 1% in 1986 to 9% in 2006. We found that 4,314 patients attempted to produce a semen sample, 4,004 succeeded, and sperm was banked for 3,616. The mean total sperm count was 61.75 × 10(6) for the 11-14 year age group, and 138.81 × 10(6) for the 18-20 year age group. It was noteworthy that intercenter variations in practices involving young patients seeking to preserve their fertility before cancer therapy were observed within this national network. CONCLUSION(S): Our results emphasize the need for decisive changes in public health policy to facilitate the access to reproductive health-care for young cancer patients.

[Male contraception]. / Contraception masculine.

Contraception allows within a heterosexual couple to have a more fulfilling as possible sexuality while protecting against the occurrence of unintended pregnancy. In a majority of couples, contraception is assumed by women. Currently, male contraceptive methods most commonly used are the male condom and vasectomy. Many other strategies, including hormonal contraceptive regimens, have been proposed and evaluated. The purpose of this review is to present an overview of the various current and future male contraceptive methods.

Testicular-sparing surgery for bilateral or monorchide testicular tumours: a multicenter study of long-term oncological and functional results.

OBJECTIVE: To review long-term oncological and functional outcomes of testicular-sparing surgery (TSS) in men presenting with bilateral or monorchide testicular tumours at one of five reference centres for testicular neoplasm and infertility. PATIENTS AND METHODS: We review 25 cases of bilateral synchrone and metachrone testicular tumours treated in five academic centres between 1984 and 2013. Clinical, biological, ultrasonography and pathological tumour findings, overall survival (OS) times, local or metastatic recurrence, pre- and postoperative hormonal profile, paternity and the need for androgen substitution were assessed. RESULTS: Eleven patients with a bilateral synchrone tumour and 14 patients with a testicular tumour on a solitary testicle underwent a tumorectomy. The mean (sem) patient age was 31.9 (1.04) years, total testosterone level was 4.5 (0.57) ng.mL and tumour size was 11.66 (1.49) mm. Tumour types were as follows: 11 seminoma, nine non-seminomatous or mixed germ cell tumours, four Leydig tumours, and one hamartoma. Frozen-section examination was performed in 14 patients, and matched the final pathological analysis in 11 patients. There was an OS rate of 100% and three patients (12%) presented with a local recurrence after a mean follow-up of 42.7 months. Radical orchiectomy was performed for six patients. No patient with a preserved testicle required androgen therapy; the mean postoperative total testosterone level was 4.0 ng/mL. No patient remained fertile after radiation therapy. CONCLUSIONS: TSS for bilateral testicular tumour is safe and effective in selected patients, and should be considered to avoid definitive androgen therapy. Adjuvant radiotherapy remains poorly described in the literature, leading to adjuvant treatment heterogeneity for testicular tumours.

Beneficial effects of varicocele embolization on semen parameters.

BACKGROUND: The value of varicocele repair and the latter's impact on semen parameters are still subject to debate. METHODS: We analyse changes over time in initially abnormal sperm parameters and serum concentrations of testosterone, FSH and inhibin B after embolization treatment of males with high-grade varicocele. From 2007 to 2012, we recruited 47 male infertile patients with clinically visible left varicocele in the resting patient and at least one abnormal semen parameter. Sperm parameters and serum levels of total testosterone, FSH and inhibin B were measured prior to retrograde embolization (M0) and then 3 (M3) and 6 (M6) months afterwards. RESULTS: At M0, the median sperm concentration was 5.78 [0.84-37.70] × 10(6)/ejaculate. The mean ± SD sperm progressive motility, vitality and percentage of normal sperm were respectively, 21.83 ± 16.48%, 61.88 ± 15.98% and 12.88 ± 7.15%. The corresponding values at M3 were significantly higher (38.75 [3.96-95] × 10(6)/ejaculate, 29.32 ± 14.21%, 69.14 ± 14.86% and 19.03 ± 11.02%, respectively). The mean percentage of spermatozoa with a thin head was significantly lower at M6 (6.35 ± 5.29%) than at M0 (14.03 ± 13.09%). The mean serum testosterone, FSH and inhibin B levels did not change significantly over time. CONCLUSIONS: Embolization treatment in men with clinically visible left varicocele, abnormal sperm parameters and documented infertility is associated with a significant improvement in semen parameters including sperm head morphology.

INTRODUCTION: L'intérêt du traitement de la varicocèle clinique et son impact sur les paramètres spermatiques sont de nos jours toujours débattus. MÉTHODES: Nous avons analysé l'évolution dans le temps des paramètres spermatiques et les concentrations sériques de testostérone, FSH et inhibine B d'hommes infertiles ayant une varicocèle de haut grade traitée par embolisation rétrograde. De 2007 à 2012, 47 patients ayant une varicocèle clinique de grade 3 et au moins un paramètre de sperme anormal ont été recrutés. Les paramètres spermatiques et les taux de testostérone totale, de FSH et d'inhibine B sérique ont été mesurés avant embolisation (M0) et 3 (M3) et 6 (M6) mois après embolisation. RÉSULTATS: La numération spermatique médiane initiale de la population était de 5,78 [0,84-37,70] × 106 /éjaculat. Les moyennes ± déviation standard de la mobilité progressive, la vitalité et le pourcentage de spermatozoïdes normaux étaient respectivement de 21,83 ± 16,48%, 61,88 ± 15,98% et 12,88 ± 7,15%. A M3, les valeurs étaient significativement plus élevées (38,75 [3,96-95] × 106/éjaculat, 29,32 ± 14,21%, 69,14 ± 14,86% et 19,03 ± 11,02% respectivement). Le pourcentage moyen de spermatozoïdes à tête amincie était significativement plus faible à M6 (6,35 ± 5,29%) qu'à M0 (14,03 ± 13,09%). Les taux sériques moyens de la testostérone, FSH et inhibine B étaient comparables tout au long de la prise en charge des patients. CONCLUSION: L'embolisation de la varicocèle de haut grade chez les hommes ayant au moins un paramètre spermatique anormal est associée à une amélioration significative des paramètres spermatiques et notamment des spermatozoïdes à tête amincie.

Varicocele repair: does it still have a role in infertility treatment?

PURPOSE OF REVIEW: To review the role of varicocele repair in the treatment of male infertility. RECENT FINDINGS: Since the advent of technologies bypassing boundaries of natural selection, this question may seem outdated. Over the past 20 years, fertility has decreased, and testicular damage (cryptorchidism, tumors) has increased. Thus the exploration of the infertile male is still unavoidable. However, what should be done and assigned to the discovery of a varicocele?The issue raised is whether varicocele found during the review of the infertile couple should be treated or 'ignored'.This study will update significant findings with regards to the pathophysiology of varicocele-induced infertility, such as oxidative stress and role of varicocele in bilaterality of testicular damage. Benefits of varicocele repair in semen analysis and simplifications of assisted reproductive techniques are reported. But reviews of randomized clinical trials have raised doubts about the benefit of varicocele treatment in infertile men. SUMMARY: We conclude that varicocele repair may be effective in men with subnormal semen analysis, a clinical varicocele and otherwise unexplained infertility. Deleterious cofactors, like obesity or smoking, could also be reduced for the benefit of general health and fertility.

[Assessment of azoospermia and histological evaluation of spermatogenesis]. / Bilan d'une azoospermie et évaluation histologique de la spermatogenèse.

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.

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.