The relationship between common mutations in CFTR, AR genes, Y chromosome microdeletions and karyotyping abnormalities with very severe oligozoospermia in Iranian men.

BACKGROUND: Male infertility due to very severe oligozoospermia has been associated with some genetic risk factors. OBJECTIVE: To investigate the distribution of the mutations in the CFTR gene, the CAG-repeat expansion of the AR gene, also Y chromosome microdeletions and karyotyping abnormalities in very severe oligozoospermia patients. METHODS: In the present case-control study, 200 patients and 200 fertile males were enrolled. All patients and control group were karyotyped. Microdeletions were evaluated using multiplex PCR. Five common CFTR mutations were genotyped using the ARMS-PCR technique. The CAG-repeat expansion in the AR gene was evaluated for each individual using sequencing. RESULTS: Overall 4% of cases shows a numerical and structural abnormality. 7.5% of patients had a deletion in one of the AZF regions on Yq, and 3.5% had a deletion in two regions. F508del was the most common (4.5%) CFTR gene mutation; G542X, and W1282X were detected with 1.5% and 1% respectively. One patient was found to have AZFa microdeletion and F508del in heterozygote form; one patient had AZFb microdeletion with F508del. F508del was seen as compound heterozygous with G542X in one patient and with W1282X in the other patient. The difference in the mean of the CAG-repeats in the AR gene in patients and control groups was statistically significant (P = 0.04). CONCLUSION: Our study shows the genetic mutations in men with severe oligozoospermia and given the possibility of transmission of these disorders to the next generation by fertilization, counseling and genetic testing are suggested for these couples before considering ICSI.

The prevalence of common CFTR gene mutations and polymorphisms in infertile Iranian men with very severe oligozoospermia.

Due to progress in infertility etiology, several genetic bases of infertility are revealed today. This study aimed to investigate the distribution of mutations in the CFTR gene, M470V polymorphism, and IVS8 poly T. Furthermore, we aimed to examine the hotspot exons (4, 7, 9, 10, 11, 20, and 21 exons) to find a new mutation in cystic fibrosis transmembrane conductance regulator (CFTR) gene among infertile Iranian men very severe oligozoospermia (<1 million sperm/mL ejaculate fluid). In the present case-control study, 200 very severe oligozoospermia (20-60s) and 200 fertile men (18-65s) were registered. Five common CFTR mutations were genotyped using the ARMS-PCR technique. The M470V polymorphism was checked out by real-time PCR, and poly T and exons were sequenced. The F508del was the most common (4.5%) CFTR gene mutation; G542X and W1282X were detected with 1.5% and 1%, respectively. N1303K and R117H were detected in 0.5% of cases. F508del was seen as a heterozygous compound with G542X in one patient and with W1282X in the other patient. Also, in the case of M470V polymorphism, there are differences between the case and control groups (p=0.013). Poly T assay showed statistical differences in some genotypes. The study showed no new mutation in the exons mentioned above. Our results shed light on the genetic basis of men with very severe oligozoospermia in the Iranian population, which will support therapy decisions among infertile men.

Endorectal ultrasonography performance in staging rectal cancer before and after neoadjuvant chemoradiotherapy.

AIM: To evaluate accuracy of endorectal ultrasonography (ERUS) both in staging and restaging rectal cancer after neoadjuvant chemoradiotherapy treatment. METHODS: In a group of 80 patients with rectal cancer, we retrospectively selected 67 patients and divided in two groups: 41 patients affected by a stage I were investigated with a single preoperative endorectal sonography; 26 patients with locally advanced rectal cancer (stage II or more) were restaged after neoadjuvant treatment, which consisted of 5,040 cGy in 28 daily fractions associated with continuous infusion of 5-Fluorouracil. All patients underwent surgery and ERUS findings were subsequently compared with histological findings. RESULTS: Diagnostic accuracy of ERUS in the first group of patients was high: in fact T-staging was accurate in 85% of cases. Results in the second group were significantly less accurate, with a correct T-staging just for 47% of cases. Nodes involvement was correctly evaluated in 86% of cases for the first group and in 63% of cases for the second one. CONCLUSIONS: Endorectal sonography is a valid staging modality for early rectal malignancy. Advanced cancer is treated with neoadjuvant preoperative chemoradiotherapy which is associated with better outcome than postoperative treatment. We found endorectal sonography, based on the layer model of rectal wall, often fails restaging and we think we have to develop new criteria for a correct preoperative assessment after neoadjuvant chemoradiation. KEY WORDS: Endorectal ultrasonography, Neoadjuvant chemoradiotherapy, Rectal cancer, Staging.