in infertile couples , male factors account for almost half of the cases of infertility . these male factors can be ascribed to infection , immunological factors , anatomical malformations , or chemical insult . besides these factors a constitutional chromosomal abnormality can be found in about 15% of azoospermic men and in 6% of men with oligozoospermia [ 2 - 4 ] . in addition to determining the development of spermatogenesis , the human y chromosome has an important role . the prevalence of y chromosome microdeletions is approximately 7% , with a range of 1% to 35% ; the range depends on research methods and the selection of patients . microdeletion of the long arm of the y chromosome is frequently correlated with the failure of spermatogenesis . each region of the y chromosome microdeletion is known as an azoospermia factor ( azf ) , including factors a , b , and c. a schematic depiction of the location of the azf regions in the y chromosome is shown in fig . y chromosome microdeletion most frequently involves the azfc region ( 60% ) , less frequently the azfb region ( 16% ) , and only rarely the azfa interval ( 5% ) . larger y chromosome microdeletions involving two or three azf regions are diagnosed in 14% of cases . before the development of in vitro fertilization with intracytoplasmic sperm injection ( icsi ) and sperm retrieval techniques , such as multiple testicular sperm extraction ( tese ) , however , with the use of icsi and current sperm extraction technologies , recent studies have reported that successful pregnancies are possible [ 10 - 12 ] . in addition , recent studies have shown that spermatozoa can be retrieved from men with azfc region microdeletion , thus increasing the chances of conception [ 13 - 15 ] . in the present study , we evaluated the clinical characteristics , sperm retrieval rates , and birth rates of a relatively large number of infertile patients with y chromosome microdeletions of the azfb or azfc region . we also investigated the effects of each type of y chromosome microdeletion with respect to the chance of retrieving spermatozoa with tese and birth rates . the patients were selected from an institutional review board - approved database of cases from march 2004 to june 2011 . infertile patients with nonobstructive azoospermia ( noa ) or severe oligoasthenoteratozoospermia ( oats ) were enrolled this study . all of the men who presented themselves to our center for evaluation of male factor infertility underwent a thorough history and comprehensive physical evaluation . the initial laboratory evaluation included semen analysis and a hormonal profile ( follicle - stimulating hormone [ fsh ] , luteinizing hormone [ lh ] , testosterone , estradiol [ e2 ] , sex - hormone binding globulin [ shbg ] ) . on the basis of the results of the semen analysis and hormone profile , the patients were divided into two groups : patients with noa and patients with severe oats . additionally , we offered y chromosome microdeletion gene screening to all of the patients with noa and severe oats . the noa diagnosis was confirmed by multiple tese for diagnostic and therapeutic purposes . a retrospective chart review was then performed . , we divided the two groups according to y chromosome analysis into the y chromosome microdeletion group and the no microdeletion group . the " no microdeletion group " referred to patients with noa or oats who visited the hospital and received a chromosome microdeletion test and were confirmed to not have any abnormalities . a total of 110 men with y chromosome microdeletions were then divided into two subgroups . we then evaluated the clinical characteristics , sperm retrieval rates , and birth rates of patients with y chromosome microdeletion of azfb and/or azfc . y chromosome microdeletions were confirmed with multiplex polymerase chain reaction ( pcr ) . in the men who were found to have a failure of a sequence - tagged site ( sts ) on the y chromosome , single primer pairs were used to confirm the absence of each site in a pcr reaction on multiple occasions . if no sperm were identified within the pellet , multiple teses were performed . multiple tese procedures were performed with either multiple - site biopsies or with single , large incisions with multiple samplings . all biopsy sample collections included evaluation by inverted microscopy for the presence of viable spermatozoa . the procedures were performed in conjunction with the infertility centers that planned the in vitro fertilization cycles with icsi or sperm freezing . student 's t - test was used for continuous data to evaluate comparisons between the groups . the chi - squared test and the statistical analyses were performed by using the ibm spss ver . 19.0 ( ibm co. , armonk , ny , usa ) . the patients were selected from an institutional review board - approved database of cases from march 2004 to june 2011 . infertile patients with nonobstructive azoospermia ( noa ) or severe oligoasthenoteratozoospermia ( oats ) were enrolled this study . all of the men who presented themselves to our center for evaluation of male factor infertility underwent a thorough history and comprehensive physical evaluation . the initial laboratory evaluation included semen analysis and a hormonal profile ( follicle - stimulating hormone [ fsh ] , luteinizing hormone [ lh ] , testosterone , estradiol [ e2 ] , sex - hormone binding globulin [ shbg ] ) . on the basis of the results of the semen analysis and hormone profile , the patients were divided into two groups : patients with noa and patients with severe oats . additionally , we offered y chromosome microdeletion gene screening to all of the patients with noa and severe oats . the noa diagnosis was confirmed by multiple tese for diagnostic and therapeutic purposes . a retrospective chart review was then performed . , we divided the two groups according to y chromosome analysis into the y chromosome microdeletion group and the no microdeletion group . the " no microdeletion group " referred to patients with noa or oats who visited the hospital and received a chromosome microdeletion test and were confirmed to not have any abnormalities . a total of 110 men with y chromosome microdeletions were then divided into two subgroups . we then evaluated the clinical characteristics , sperm retrieval rates , and birth rates of patients with y chromosome microdeletion of azfb and/or azfc . y chromosome microdeletions were confirmed with multiplex polymerase chain reaction ( pcr ) . in the men who were found to have a failure of a sequence - tagged site ( sts ) on the y chromosome , single primer pairs were used to confirm the absence of each site in a pcr reaction on multiple occasions . multiple tese procedures were performed with either multiple - site biopsies or with single , large incisions with multiple samplings . all biopsy sample collections included evaluation by inverted microscopy for the presence of viable spermatozoa . the procedures were performed in conjunction with the infertility centers that planned the in vitro fertilization cycles with icsi or sperm freezing . student 's t - test was used for continuous data to evaluate comparisons between the groups . the chi - squared test and the statistical analyses were performed by using the ibm spss ver . 19.0 ( ibm co. , armonk , ny , usa ) . of the 289 men with male factor infertility who underwent screening for y chromosome microdeletions at our center , y chromosome microdeletions were detected in 110 patients ( 38.0% ) . of these 110 patients , 83 were classified as having noa and 27 were classified as having severe oats . mean age , mean fsh , mean lh , mean testosterone , mean e2 , and mean shbg were not significantly different between the no microdeletion patients and the y chromosome microdeletion patients . with the exception of those subjects who refused the multiple tese procedure , 30 of the 83 noa patients with y chromosome microdeletions underwent multiple tese procedures . the other 53 did not undergo tese owing to a previously known diagnostic tese result from another institution , personal refusal , or loss to follow - up . of the 30 patients , 9 had azfb - c microdeletion and 21 had azfc microdeletion . multiple tese successfully retrieved sperm in 8 of 30 patients with y chromosome microdeletions ( 26.6% ) . multiple tese had similar success with y chromosome microdeletion patients and no microdeletion patients ( 8/30 [ 26.6% ] vs. 21/82 [ 25.6% ] , p=0.298 ) . a total of 23/138 patients ( 16.6% ) with no microdeletion achieved live birth , as did 20/82 patients ( 24.3% ) with y chromosome microdeletions . the difference in the birth rate between the no microdeletion group and the y chromosome microdeletion group was significant ( p=0.007 ) . however , because female infertility factors were not available in these data , this result seems questionable . the different clinical characteristics of the two groups are shown in table 2 . among the azfb - c microdeletion patients , 25 patients ( 86.2% ) had noa and 4 patients ( 13.8% ) had severe oats . of the severe oats patients with azfb - c microdeletion , the sperm count range was from motile 2 - 3 sperm / high power field [ hpf ] to 0.810/ml . patients with azfc microdeletion had a higher prevalence of severe oats ( noa , n=58 [ 71.6% ] vs. oats , n=23 [ 28.4% ] ) . in the severe oats patients with azfc microdeletion , the sperm count range was from motile 2 - 3 in contrast , multiple tese successfully retrieved sperm in 8 of 21 ( 38.0% ) noa patients with azfc microdeletions . multiple tese was more likely to succeed in azfc microdeletion patients than in azfb - c microdeletion patients ( p=0.041 ) . the sperm retrieval rates of each group are also shown in table 2 . among the azfc microdeletion patients ( n=18 , 29.0% ) , the resulting birth rate was higher than that of the azfb - c microdeletion patients ( n=2 , 9.5% ) . because no sperm was retrieved with multiple tese in noa patients with azfb - c microdeletion , the birth rate in these patients was zero . in contrast , 2 out of 3 ( 75% ) severe oats patients with azfb - c microdeletion were able to conceive . in the noa patients with azfc microdeletion , 8 patients had a chance to conceive through icsi . moreover , in severe oats patients with azfc microdeletion , 9 patients gave birth through icsi and one patient gave birth through natural conception . however , the birth rate did not differ significantly between the azfb - c microdeletion patients and the azfc microdeletion patients ( p=0.085 ) . in this study , we observed that the incidence of y chromosome microdeletions was relatively high compared with previous studies . we also observed an association between y chromosome microdeletions and birth rates with multiple tese . more spermatozoa were retrieved in patients with azfc microdeletion with multiple tese than in patients with azfb - c microdeletion ( 8/21 [ 38.0% ] vs. 0/9 [ 0% ] , p=0.041 ) . we also observed that severe oats patients with larger y chromosome microdeletions such as azfb - c could conceive with icsi . y chromosome microdeletions have been frequently identified in infertile men with azoospermia or very low sperm concentrations in the ejaculate . our study showed a rate of y chromosome microdeletions of 110/289 ( 38.0% ) among the patients with noa and severe oats . this was a much higher rate than the reported prevalences of y chromosomal microdeletions of 9.6% to 19.4% at other asian centers . in other studies , it was argued that these large variations could be due to the selection of patient groups , to ethnic differences , to genetic background , or to the sts marker sets used . additionally , in our study , another factor increasing the incidence of y chromosomal microdeletion was selection bias , such as the referral pattern . our institution specializes in assisted reproductive technique , and our screened population might have been more phenotypically severe than men treated at other institutions . according to tsujimura et al . , among 60 patients with noa , the spermatozoa retrieval rate for patients with y chromosome microdeletion was similar to that of patients without y chromosome microdeletion ( 33.3% vs. 37.0% ) . in our study , the sperm retrieval rate was similar between no microdeletion patients and y chromosome microdeletion patients ( 21/82 [ 25.6% ] vs. 8/30 [ 26.6% ] , p=0.298 ) . the birth rates of patients with y chromosome microdeletions were significantly different from those in patients with no microdeletion ( p=0.007 ) ; however , when viewed objectively , this conclusion seems somewhat questionable because data regarding female infertility factors were not available . the type of y chromosome microdeletion ( azfa , b , c ) has been proposed as a potential prognostic factor for sperm retrieval in men undergoing multiple tese . deletions including and extending beyond the azfc region ( i.e. , azfb - c , azfa - b - c ) have been correlated with the complete absence of testicular spermatozoa , and the presence of an azfb microdeletion is a significantly adverse prognostic finding for multiple tese . although the type of y chromosome microdeletion is a prognostic factor , large series of patients with microdeletions involving the azfb region have not been fully characterized in the published literature . we characterized 110 men with azfb and/or azfc microdeletions to evaluate prognostic values for sperm retrieval in these patients on the basis of the specific region of the microdeletion . the association between azfc microdeletions and spermatogenesis has been demonstrated previously [ 12,14,19 - 21 ] . clearly , patients with azfc microdeletions have variable capacities to produce sperm , with some producing no spermatozoa within the seminiferous tubules and others producing a quantity of sperm sufficient to survive epididymal transit and appear in the ejaculate . according to van golde et al . , out of 300 oats patients , 8 had azfc microdeletion ( 2.7% ) , whereas no azfa or azfb deletions were found . in our study , 4 of the oats patients ( 5.2% ) had azfb - c microdeletion and 23 ( 30.2% ) had azfc microdeletion . this study enrolled only patients with severe oats , which resulted in a higher prevalence of the microdeletion , but an inverse relation between microdeletion length and sperm productivity can be inferred . in noa patients , we report that 81 men with azfc microdeletions had a sperm retrieval rate of 38.0% . this result is lower than the data from a large cohort of men with azfc microdeletion studied by oates et al . , who showed that men with azfc microdeletions had a 67% sperm retrieval rate . the reason for the lower retrieval rate may be that the selection of patients differed from other institutions or the multiple tese technique differed from other institutions . many studies have reported that mature spermatozoa are obtained in approximately 50% of patients with azfc microdeletions , despite reduced fertilization rates and worse embryo scores after icsi . we reported that 18/62 men ( 29.0% ) with azfc microdeletions conceived children : one patient through natural conception and 17 patients through icsi procedures . microdeletions of the azfb region occur more commonly in conjunction with deletions of the azfc region . moreover , with large deletions , including those in the azfa - b - c and azfb - c regions , birth rates have not been widely reported . kamp et al .   reported that sperm retrieval was unsuccessful in all cases of azfb microdeletion . also described seven azoospermic patients with microdeletions , including microdeletions of the entire azfb region ; all of their subjects failed to retrieve spermatozoa or sperm in multiple tese . .   reported on the impact of azfb microdeletions in infertile men , and their findings have been widely discussed . in essence , their findings indicate that in cases of microdeletions that remove the entire azfb region , the probability of obtaining testicular spermatozoa for successive icsi is virtually zero . in our data , we also found that we were unable to retrieve sperm from azoospermic patients with azfb - c microdeletions . however , two patients with severe oats with azfb - c microdeletions had a successful chance of pregnancy through icsi . it seems that noa men with deletions of the azfb - c region have almost no possibility of sperm retrieval with tese . however , if a patient has oats with azfb - c microdeletion , icsi is a possible treatment option . although larger y chromosome microdeletion such as azfb - c microdeletion has a poor prognosis , it is possible that sperm can be retrieved by multiple tese . in many centers , y chromosome microdeletion analysis is still not performed as a routine measure , and as a result , the findings are used for genetic counseling but are not considered to have prognostic value . however , we emphasize that evaluations of y chromosome microdeletions in infertile men with noa and severe oats should be performed before undertaking assisted reproductive techniques , such as multiple tese and icsi . in this study , we showed that a reasonable percentage of couples with y chromosome microdeletions have a chance to conceive . in noa and oats patients , a test for y chromosome microdeletion not only provides essential information for genetic counseling , but also helps the patients and their physicians make more informed decisions about sperm retrieval . nonetheless , our findings might have a limited scope . the high incidence of y chromosome microdeletions that we observed might reflect selection bias due to referral patterns . furthermore , we had trouble collecting precise information about past pregnancies or birth history on the basis of recorded information and phone calls , and as a result , some patient information was missing . we also had a limitation in our ability to predict the ultimate sperm production capabilities of the male offspring of men with azf microdeletion . because genetic testing data from the male offspring in our study were not available , we could not address the inheritance of the y chromosome microdeletions . in noa and oats patients , no significant difference in the sperm retrieval rate was shown between the y chromosome microdeletion group and the no microdeletion group . even though the group with no y chromosome microdeletion showed a better birth rate than did the y chromosome microdeletion group , the difference was not clinically significant . noa patients with azfc microdeletion reached successful conception with tese , whereas the azfb - c microdeletion patients did not . patients with short microdeletions in the y chromosome such as azfc microdeletion have better prognoses for sperm retrieval and an increased chance of conception compared with patients with larger microdeletions such as azfb - c microdeletion . however , this does not mean that azfb - c microdeletion patients are completely infertile . two patients in the azfb - c microdeletion group with oats were able to conceive with icsi . the sperm - producing ability is not completely abolished in the azfb - c microdeletion group .