Compound heterozygous variants in CFTR with potentially reducing ATP-binding ability identified in Chinese infertile brothers with isolated congenital bilateral absence of vas deferens.

BACKGROUND: Isolated congenital bilateral absence of vas deferens (iCBAVD) in men results in obstructive azoospermia and is mainly caused by pathogenic variants in cystic fibrosis transmembrane conductance regulator (CFTR) or adhesion G protein-coupled receptor G2 (ADGRG2). METHODS: The next-generation sequencing (NGS) was used to screen the mutations in the proband, and Sanger sequencings were performed to validate the compound heterozygous variant of CFTR in his family members. Protein structure simulation was performed to discover the potential pathological mechanism. RESULTS: This study reported novel compound heterozygous CFTR mutations (NM:000492.4, Intron: 5T; c.3965_3969dupTTGGG: p.R1325Gfs*5) in two brothers with obstructive azoospermia. The compound heterozygous CFTR mutations were first screened out by NGS in an infertile male patient who exhibited iCBAVD from a nonconsanguineous Chinese family. Histological analysis of the testicular biopsy from this patient revealed normal spermatogenesis and mature spermatozoa were observed in the seminiferous tubules. Surprisingly, the same compound heterozygous CFTR mutations were also observed in his brothers who also exhibited iCBAVD, with their parents being a heterozygous carrier for the mutations, as verified by Sanger sequencing. Protein structure simulation revealed that these mutations potentially led to impaired ATP-binding ability of CFTR. CONCLUSION: We identified novel compound heterozygous CFTR mutations in two brothers and summarized the literature regarding CFTR mutation and male infertility. Our study may contribute to the genetic diagnosis of iCBAVD and future genetic counseling.

Evaluation for optimization effects of sperm floating plate / 临床检验杂志

Objective To compare the difference between sperm floating plate and density gradient centrifugation combined with swim-up in human sperm preparation.Methods The semen samples were obtained from 50 infertile men in the clinic of Reproductive Medi-cine of Northwest Women's and Children's Hospital excluding azoospermia,severe oligoasthenozoospermia and semen volume less than 2 mL.After semen liquefaction,the differences of sperm concentration,total progressively motile sperm count(TMSC),percentages of progressively motile sperm and normal morphology sperm,recovery rate and DNA fragmentation index(DFI)were measured by both the methods of sperm floating plate and density gradient centrifugation combined with swim-up,and the results were compared.Results Compared with the pre-sorting samples,sperm concentrations[(16.08±13.39)x 106/mL,(8.88±8.06)x 106/mL vs(60.05± 27.21)×106/mL],TMSC[(7.41±6.14)×106,(3.98±3.57)×106vs(22.24±13.74)×106]and DFI[(2.20±3.44)％,(5.20± 10.79)％vs(26.38±13.92)％]in the sorting groups by sperm floating plate and density gradient centrifugation combined with swim-up were decreased significantly,and the percentages of progressive motile sperm[(91.67±4.75)％,(87.86±7.90)％vs(40.21± 16.83)％]and normal morphology sperm[(9.58±5.08)％,(7.72±4.01)％vs(3.58±2.06)％]were increased significantly.Com-pared with the density gradient centrifugation combined with swim-up,the results of sperm floating plate were higher in sperm concen-tration,percentages of progressively motile sperm and normal morphology sperm,TMSC and sperm recovery rate[(30.74±13.70)％vs(17.09±9.20)％],but DFI was lower,time-consuming was shorter[(32.38±1.01)min vs(60.08±2.06)min],and the difference between the two groups was statistically significant(P＜0.05).Conclusion The sperm floating plate may have certain clinical applica-tion prospects in the future due to better parameters of sperm preparation than those of density gradient centrifugation combined with swim-up in simple operation and shorter time-consuming.

A case report of delayed recovery of obstructive azoospermia / 中华泌尿外科杂志

The causes of obstructive azoospermia are complex, mostly permanent, and it is very rare to return to normal without medication or surgery. This article analyzes the changes in the course of a patient with obstructive azoospermia without surgery and medication and the delayed return to normal sperm density. The reasons for its self-recovery: it might be related to asymptomatic epididymitis and ejaculatory duct cysts. The possibility of self-recovery in patients with obstructive azoospermia due to specific etiologies.