Chromosomal abnormalities in 1354 Japanese patients with azoospermia due to spermatogenic dysfunction
Venue: International journal of urology official journal of the Japanese Urological Association

Azoospermia is typically classified into OA and ASD, formerly known as NOA. OA is characterized by normal spermatogenesis, but impaired sperm transport from the testes to the urethra, whereas ASD involves intratesticular defects in sperm production. ASD or NOA is diagnosed in approximately 60% of azoospermic men with testicles of small volume and elevated levels of FSH. The introduction of the ICSI technique has facilitated the management of ASD patients by allowing for in vitro fertilization using sperm retrieved from their own testes by TESE. However, ASD is associated with an increased risk of chromosomal abnormalities. ICSI in such cases can increase the chances of bypassing the transmission of chromosomal abnormalities to the offspring. Therefore, cytogenetic analysis of patients with ASD is mandatory before undertaking measures for assisted reproduction, including ICSI. Several studies have been carried out worldwide regarding chromosomal abnormalities in infertile men, and the reported frequencies of chromosomal abnormalities vary widely because of the differences in the definitions of NOA adopted in the studies. In the present study, we used the term ASD, rather than NOA, to define azoospermia due to the absence or deficiency of seminiferous tubules that contain mature spermatozoa, as confirmed by micro TESE. The purpose of the present study was to evaluate the types and frequencies of chromosomal abnormalities in more than 1300 Japanese patients with ASD. This study was designed as a retrospective investigation of the medical records of 1354 patients diagnosed with ASD by micro TESE at Dokkyo Medical University Koshigaya Hospital, Koshigaya, Saitama, Japan, between 2002 and 2014. The study protocol was approved by the institutional review board at Dokkyo Medical University Koshigaya Hospital. The mean age of the patients was 35.5 6.0 years. All patients were first evaluated by trained andrologists, followed by the conventional diagnostic work up, including history taking, genital examination, ultrasonographic examination, at least two separate semen analyses and hormonal analyses. Cytogenetic studies were carried out as part of the routine evaluation of male patients with suspected ASD. The patients were provided genetic counseling by clinical geneticists, and informed about the risk of transmitting chromosomal abnormalities to the offspring. Karyotype analysis was then carried out on peripheral blood lymphocytes by using the GTG banding technique at SRL (Tokyo, Japan) Chromosomal abnormalities were classified according to the recommendations of the International System for Chromosome Nomenclature (ISCN 2009) Polymorphic variants were classified as normal, whereas structural and numerical rearrangements were considered abnormal. In addition to classifying the chromosomal abnormalities, we determined the frequencies of each type of abnormality and examined its variations in our study population. Chromosomal abnormalities were identified in 327 (24.1% of the 1354 patients. Table 1 shows the major types of chromosomal abnormalities detected and their frequencies in our study population. Anomalies of sex chromosomes (22.5% were more frequent than those of autosomal chromosomes (1.6% among our ASD patients. Furthermore, Klinefelter syndrome was the most common sex chromosome anomaly detected, at a frequency of 18.8% (nonmosaic 17.1% mosaic 1.7% Table S1) Other gonosomal numerical aberrations detected were karyotypes 46,XX (0.6% 47,XYY (0.4% 47,X,i(Xq),Y (0.1% and 45,X/46,XY (0.6% Gonosomal structural aberrations were identified in 28 patients (2.0% and structural aberrations of the Y chromosome (1.8% were more frequent than those of the X chromosome (0.2% Table S2 lists the testicular histopathological findings obtained in cases of gonosomal structural aberrations. Among the autosomal chromosome anomalies, imbalance aberrations were identified in just two patients (0.1% Both these patients had Robertosonian translocation, and testicular biopsy showed that they had the Sertoli cell only syndrome. Our present study included only patients with ASD, as confirmed by micro TESE. This is the first and the largest survey of chromosomal abnormalities among Japanese ASD patients. Considering that approximately one in four patients in this large scale study had some chromosomal abnormality, we strongly emphasize that chromosomal analysis be carried out for