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.

Thanks to better knowledge of TESE quality, the present score could help to improve care and pre-ICSI counseling for patients with NOA.

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), PZ0.0026). The combination of a FSH O7.8 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.

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We retrospectively evaluated the clinical and hormonal profiles, sperm extraction outcomes and testicular histology parameters in 120 azoospermic men with normal serum follicle-stimulating hormone (FSH) level. Microsurgical epididymal sperm aspiration (MESA) and testicular sperm extraction (TESE) were performed in 33 and 87 cases, respectively. Sperm were successfully retrieved in all the MESA procedures and in 65 of the TESE procedures. The mean serum FSH and inhibin B levels and the testicular volume differed significantly according to whether or not sperm were retrieved. The threshold serum inhibin B value for predicting successful TESE was 123.5pg/mL (sensitivity: 69.7%; specificity: 66.7%). The 13 patients with Sertoli cell only syndrome (SCOS) had a higher mean serum FSH level and a lower mean serum inhibin B level than the other phenotypes. TESE was negative for 11 of the 13 SCOS men. The mean±SD inhibin B level was significantly lower in patients with 5-10IU/L of FSH than those with 2-5IU/L of FSH (108.30±53.86 vs. 175.23±70.17pg/mL, respectively). The sperm retrieval rates were 71.42% for the group with 5-10IU/L of FSH and 87.32% for the group with 2-5IU/L of FSH. Ten of the 13 SCOS men had a FSH level between 5 and 10IU/L. The clinical pregnancy rate was significantly lower (p=0.04) in the group with 5-10IU/L (50%) of FSH than in the group with 2-5IU/L (77.5%) of FSH. In conclusion, there is no FSH value below which spermatogenesis is always found. Inhibin B assays and clinical assessments are thus of particular value in men with normal serum FSH levels.

BackgroundThe value of varicocele repair and the latter's impact on semen parameters are still subject to debate.MethodsWe 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.ResultsAt M0, the median sperm concentration was 5.78 [0.84-37.70] × 106/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] × 106/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.ConclusionsEmbolization 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.

Banking of ejaculated sperm is helpful for cryptozoospermic patients.