Chromosome analysis of epididymal and testicular sperm in azoospermic patients undergoing ICSI

BACKGROUND: Although ICSI provides a way of treating azoospermic men, concern has been raised about the potential risk for transmission of genetic abnormalities to the offspring. We quantified the incidence of chromosomal abnormalities in epididymal and testicular sperm retrieved from azoospermic patients undergoing ICSI. METHODS: Individual testicular sperm were collected from testicular biopsies with an ICSI pipette, and epididymal sperm were retrieved by microsurgical epididymal sperm aspiration. Samples were processed by fluorescent in-situ hybridization (FISH) for chromosomes 18, 21, X and Y and the results compared with those from normal ejaculated samples. RESULTS: The overall aneuploidy rate of 11.4% in men with non-obstructive azoospermia was significantly higher (P = 0.0001) than the 1.8% detected in epididymal sperm from men with obstructive azoospermia and also the 1.5% found in ejaculated sperm. No significant difference was found between the epididymal and ejaculated samples. When the chromosomal abnormalities were analysed, gonosomal disomy was the most recurrent abnormality in both obstructive and non-obstructive azoospermic patients, while autosomal disomy was the most frequent in ejaculated sperm. CONCLUSIONS: Sperm of non-obstructive azoospermic men had a higher incidence of chromosomal abnormalities, of which sex chromosome aneuploidy was the most predominant. Genetic counselling should be offered to all couples considering infertility treatment by ICSI with testicular sperm.     

Chromosome analysis of spermatozoa extracted from testes of men with non-obstructive azoospermia

Infertile men with azoospermia now have the possibility of fathering children by testicular sperm extraction combined with intracytoplasmic sperm injection. However, there are concerns about the risk of chromosomal abnormalities in their spermatozoa. We have studied aneuploidy frequencies for chromosomes 13, 21, X and Y by multicolour fluorescence in-situ hybridization (FISH) in testicular spermatozoa extracted from three men with non-obstructive azoospermia. The men were 34-37 years of age and had normal follicle-stimulating hormone (FSH) concentrations and normal 46,XY somatic karyotypes. A total of 3324 spermatozoa was analysed. The infertile patients had an elevated frequency of disomy for chromosomes 13, 21, XY disomy compared to controls but none of these reached statistical significance. Also there was no significant difference in the sex ratio or the frequency of diploidy in azoospermic patients compared to normal control donors. This first report on chromosomal aneuploidy in spermatozoa extracted from testes of patients with non-obstructive azoospermia suggests that some azoospermic men do not have a substantially increased risk of chromosomally abnormal spermatozoa.     

Incidence of sperm chromosomal abnormalities in a risk population: relationship with sperm quality and ICSI outcome

BACKGROUND: An increased incidence of chromosome abnormalities has been reported in sperm samples of many infertile men by fluorescence in-situ hybridization (FISH). METHODS: Sperm aneuploidy and diploidy rates for chromosomes 13, 18, 21, X and Y were evaluated in 63 patients with normal karyotypes using dual and triple-colour FISH techniques. Indications for sperm FISH analysis were: recurrent miscarriages of unknown aetiology (RM, n = 40), repeated implantation failure after intracytoplasmic sperm injection (ICSI) (IF, n = 19), previous Down's syndrome pregnancies (n = 3), and meiotic abnormalities (MA, n = 1). Nine healthy normozoospermic donors were also evaluated as a control group. RESULTS: A significant increase in the incidence of sex chromosome disomies was found in the RM, IF and MA groups. Oligoasthenoteratozoospermic patients (n = 21) showed significantly higher rates of diploidy and disomies for sex chromosomes and chromosomes 18 and 21 than normozoospermic patients (n = 14). Thirty-one patients with normal and seven with abnormal FISH results had undergone several ICSI treatments (108 and 23 cycles respectively). Couples with abnormal sperm FISH results showed decreased pregnancy and implantation rates and increased miscarriage rates. CONCLUSIONS: Patients with a clinical background of recurrent miscarriages of unknown aetiology or implantation failure after ICSI are at risk of showing sperm chromosomal abnormalities, the incidence of which is higher in oligoasthenoteratozoospermic patients.     

Frequency of hyper-, hypohaploidy and diploidy in ejaculate, epididymal and testicular germ cells of infertile patients

The hypothesis that sperm aneuploidy and diploidy increase as a function of spermatogenesis impairment was addressed. Ejaculated semen samples from a series of men (n = 22) with very low total normal motile count (1 x 10(6)) was analysed in terms of sperm aneuploidy and diploidy by in-situ hybridization and compared with controls (n = 10). Germ cell aneuploidy was also analysed in an additional series of infertile patients presenting unexplained infertility (n = 3), congenital absence of the vas deferens (CAVD) (n = 6) and non-obstructive azoospermia (n = 3) undergoing IVF, microsurgical epididymal sperm aspiration (MESA)/ICSI and testicular sperm extraction (TESE)/ICSI cycles respectively. In-situ hybridization for chromosomes 1, 17, X and Y was performed on ejaculate, epididymal and testicular spermatozoa. Significantly higher sperm aneuploidy and diploidy rates where found (for the four chromosomes analysed) in spermatozoa from oligoasthenoteratozoospermia (OAT) over controls (18 versus 2.28% and 2.8 versus 0.13% respectively; P < 0.001). Testicular germ cells had even higher rates of sperm aneuploidy and diploidy. However, in this group it was difficult to determine whether the cells analysed were dysmorphic spermatozoa or spermatids. The data warrant further investigation on the cytogenetic abnormalities found in most germ cells identified in testicular tissue biopsies of azoospermic patients.     

Analysis of chromosomal abnormalities in testicular and epididymal spermatozoa from azoospermic ICSI patients by fluorescence in-situ hybridization

BACKGROUND: An increased incidence of numerical chromosomal abnormalities has been reported in the ejaculated spermatozoa of infertile patients. However, there are few cytogenetic studies of testicular and epididymal spermatozoa, and their results are still controversial. METHODS: Fluorescence in-situ hybridization (FISH) analysis of chromosomes 13, 18, 21, X and Y was performed on seven testicular samples and two epididymal samples from patients with obstructive azoospermia (OA), and on 13 testicular samples from patients with non-obstructive azoospermia (NOA). Five ejaculated sperm samples from normozoospermic fertile donors were evaluated as a control group. RESULTS: Both epididymal sperm samples showed normal FISH results for the parameters analysed when compared with those of the control group. FISH results were abnormal in 29% (two of seven) of testicular samples from OA patients and in 54% (seven of 13) of those from NOA patients, although this difference was not statistically significant. Testicular samples from OA patients showed a significant increase of disomy for sex chromosomes (P<0.01), whereas NOA patients displayed significantly higher rates of diploidy (P<0.0001) and disomy for chromosomes 13 (P<0.0001), 21 (P<0.001) and sex chromosomes (P<0.0001) than the control group. CONCLUSIONS: Testicular spermatozoa from azoospermic patients present increased rates of chromosomal abnormalities, mainly of the sex chromosomes, which are particularly high in NOA patients.     

Increased aneuploidy in spermatozoa from testicular tumour patients after chemotherapy with cisplatin, etoposide and bleomycin

Testicular cancer is the most common neoplasia occurring in the young male population. The PEB (cisplatin, etoposide and bleomycin) adjuvant chemotherapy usually proposed after orchidectomy in non seminomatous tumours, and in metastatic seminomas, has improved the long-term survival of these patients. Following an azoospermic period, sperm cell recovery is generally observed after treatment delivery, but little is known about the genetic consequences on these new spermatozoa. To estimate the chromosomal consequences of this chemotherapy on sperm cells during the period of recovery of spermatogenesis, sperm cell aneuploidy was studied in testicular cancer patients, at 6-18 months after PEB adjuvant chemotherapy delivery, using fluorescence in-situ hybridization (FISH) of chromosomes 7, 16, 18, X and Y with specific DNA probes. A significant increase in the frequency of diploidy and disomy for chromosomes 16, 18 and XY was observed in treated patients compared with a healthy control group. Spermatozoa aneuploidy occurring during the spermatogenesis recovery period might be a possible side effect of the PEB regimen. Thus, practitioners should be advised to provide counselling about the need for an appropriate duration of contraception. Moreover, genetic counselling should be offered in cases of pregnancy occurring soon after the end of chemotherapy.     

Sperm chromosome studies in an infertile man with partial, complete asynapsis of meiotic bivalents

Meiotic and sperm chromosome studies were carried out in two semen samples from an infertile man with a 46,XY karyotype, oligoasthenoteratozoospermia and abundant exfoliation of spermatogenic cells. Meiotic preparations showed partial, complete asynapsis in a large proportion of metaphase I figures observed, and absence of metaphase II figures, while 24 of the 30 sperm chromosome karyotypes analysed were normal. The remaining sperm karyotypes were as follows: one with structural abnormalities, one with both structural abnormalities and hypohaploidy and four with hypohaploidy. The total frequency of chromosomal abnormalities (6.7%) is similar to that obtained by us in normal men (10.9%). The frequency of spermatozoa with structural abnormalities (6.7%) was not significantly different from that obtained by us in normal men (6.9%). These results suggest that, in some cases, asynaptic spermatogenic cells do not proceed further than metaphase I and only normal germ cells continue spermatogenesis.     

Chromosome analysis of epididymal and testicular spermatozoa in patients with azoospermia

Azoospermic patients can now father children once spermatozoa have been retrieved from the epididymis or the testis. However, there are concerns about the risk of chromosomal abnormalities since an increase in sperm aneuploidy rate has been reported in samples from patients with abnormal sperm parameters. The purpose of this study was therefore to evaluate the sperm aneuploidy and diploidy rates for chromosomes 8, 12, 18, X and Y in spermatozoa extracted from the epididymes (n=10) or the testes (n=6) of patients with azoospermia. Ejaculated spermatozoa of healthy men (n=14) served as control. Epididymal and testicular spermatozoa had an aneuploidy rate significantly higher than that found in ejaculated spermatozoa. The aneuploidy and diploidy rates of testicular spermatozoa were higher, but not significantly different, than those found in epididymal spermatozoa. This study has shown that azoospermic patients have an increased sperm aneuploidy rate. They should therefore be given appropriate genetic counselling before entering in-vitro fertilisation programs.     

Detection of calretinin expression in abnormal immature Sertoli cells in non-obstructive azoospermia

The current study identified for the first time calretinin expression in abnormal Sertoli cells of azoospermic men who underwent testicular biopsy for sperm recovery and application of the retrieved sperm by in vitro fertilization techniques. Testicular biopsies with various spermatogenic impairments were evaluated immunohistochemically for the expression of the calretinin calcium-binding protein and the marker for immaturity of Sertoli cells, cytokeratin-18 (CK-18). Distribution of the markers was assessed in testes demonstrating a histological phenotype of mixed atrophy, Sertoli cell-only, or normal spermatogenesis (obstructive-azoospermia) and in men carrying a deletion in the azoospermia factor region located on the Y chromosome. Calretinin-immunopositive immature Sertoli cells revealed by co-localization of both markers, calretinin and CK-18, were identified in the mixed atrophy group in seminiferous tubules demonstrating spermatogenic failure. Sertoli cells expressing both markers were rarely detected in all other groups. Leydig cells in all the assessed biopsies expressed calretinin and served as a built-in control for immunoreactivity. This pattern of calretinin-selective expression in immature Sertoli cells suggests a functional relationship between calretinin expression and the degree of Sertoli cell differentiation. Disorders of Sertoli cell differentiation as indicated by calretinin and/or CK-18 expression contribute to the multifactorial mechanisms underlying spermatogenic failure.     

Sperm aneuploidy and meiotic sex chromosome configurations in an infertile XYY male

BACKGROUND: There is little information regarding the behaviour of the extra Y chromosome during meiosis I in men with 47,XYY karyotypes and the segregation of the sex chromosomes in sperm. We applied immunofluorescent and FISH techniques to study the relationship between the sex chromosome configuration in meiotic germ cells and the segregation pattern in sperm, both isolated from semen samples of a 47,XYY infertile man. METHODS: The sex chromosome configuration of pachytene germ cells was determined by immunostaining pachytene nuclei for synaptonemal complex protein 3 (SCP3) and SCP1. FISH was subsequently performed to identify the sex chromosomes and chromosome 18 in pachytene cells. Dual- and triple-color FISH was performed on sperm to analyse aneuploidy for chromosomes 13, 18, 21, X, and Y. RESULTS: 46,XY/47,XYY mosaic pachytene cells were observed (22.2% vs. 77.8%, respectively). The XYY trivalent, and X+YY configurations were most common. While the majority of sperm were of normal chromosomal constitution, an increase in sex and autosome disomy was observed. CONCLUSIONS: The level of germ cell moscaicism and their meiotic sex chromosome configurations may determine sperm aneuploidy rate and fertility status in 47,XYY men. Our approach of immunostaining meiotic cells in the ejaculate is a novel method for investigating spermatogenesis in infertile men.     

Aneuploidy rate in spermatozoa of selected men with abnormal semen parameters

A large proportion of patients with oligoasthenoteratozoospermia (OAT) have an abnormal karyotype and hence they produce aneuploid gametes. However, a normal karyotype does not exclude the chance of having germ cell aneuploidy, since an altered intra-testicular environment not only damages spermatogenesis, but may also disrupt the mechanisms controlling chromosomal segregation during meiosis. Therefore, this study was undertaken to evaluate the rate of aneuploidy in the spermatozoa of selected patients with abnormal sperm parameters. For this purpose, sperm aneuploidy rate for chromosomes 8, 12, 18, X and Y was evaluated by multicolour fluorescence in-situ hybridization (FISH) in nine patients with teratozoospermia alone and 19 OAT patients of presumably testicular origin. Thirteen normozoospermic healthy men served as controls. Patients with teratozoospermia or OAT had significantly greater disomy and diploidy rates compared with controls, whereas the rate of nullisomy was similar. XY disomy was very low in all groups, suggesting that chromosomal non-disjunction occurs mainly during the second meiotic division. Autosome 12 disomy rate was low in both patients and controls. There was a marked variability of total sperm aneuploidy rate in both groups of patients. Sperm aneuploidy rate was negatively correlated with sperm concentration and particularly with the percentage of normal forms. In conclusion, patients with teratozoospermia or OAT have an increased rate of sperm aneuploidy. This increase is similar in both groups, suggesting that teratozoospermia may be the critical sperm parameter associated with aneuploidy.     

Morphology assessment and fluorescence in situ hybridization of the same spermatozoon using a computerized cell-scanning system

BACKGROUND: Poor sperm morphology is statistically associated with an increase in the incidence of chromosome abnormalities. Our aim was to examine the possible correlation between chromosomal aberrations and sperm morphology in the same cell. METHODS: 12349 spermatozoa from 7 teratozoospermic and one globozoospermic patients, and from 3 fertile donors were analyzed using a system which scans for cell morphology and chromosomal ploidy in the same cell using digital technology. RESULTS: Chromosomal aberrations were detected in 5.3% of teratozoospermic cases and in 6.7% in the globozoospermic patient compared with 1.6% in donors (P < 0.0001). Chromosomal aberrations were more common in abnormally formed sperm compared with normal spermatozoa: 4.5% vs 1.3% in the teratozoospermic group and 2.0% vs 0.3% in the control group (NS), especially frequent among sperm with two heads or two tails (52.1-77.2%) or extreme head deformations (10.6-11.1%) irrespective of grouping, and in mild amorphous heads in the globozoospermic patients (20.2%). The frequency of chromosomal aberrations in morphologically normal sperm was comparable whether derived from teratozoospermic or normospermic patients. CONCLUSIONS: The computerized cell-scanning system demonstrated the relationship between chromosomal aberrations and sperm morphology in the same spermatozoon. The incidence of chromosomal aberrations was positively linked to abnormal sperm morphology, the more severe the abnormality, the higher the incidence of aneuploidy.     

Partial deletions in the AZFc region of the Y chromosome occur in men with impaired as well as normal spermatogenesis

BACKGROUND: Partial deletions of the AZFc region of the Y chromosome were reported to be a significant risk factor for oligo-/azoospermia. In this study, we assessed the occurrence and frequency of partial AZFc microdeletions in patients with spermatogenic failure and in controls with normal spermatogenesis. METHODS: In a retrospective study design, gr/gr, b1/b3 and b2/b3 deletions were analysed by multiplex PCR in 170 men with normal spermatogenesis and 348 men with non-obstructive oligo-/azoospermia. RESULTS: gr/gr deletions were found in 14 men with oligozoospermia or azoospermia (4.0%) and in three normozoospermic men (1.8%) (NS). b1/b3 deletions were found both in controls (n=1) and in patients (n=1). b2/b3 deletions were significantly more frequent in the normozoospermic (five out of 170) than in the oligo-/azoospermic men (two out of 348). Three novel partial AZFc deletion patterns were found in four oligo-/azoospermic men. No correlation with semen or other clinical parameters was found. CONCLUSIONS: The frequency of gr/gr deletions is not significantly increased in men with oligo-/azoospermia, indicating that they are not sufficient per se to cause spermatogenetic impairment and infertility. b1/b3 and b2/b3 deletions are probably irrelevant for spermatogenesis. Novel deletion patterns found exclusively in infertile men suggest that other, still unexplored partial deletions might contribute to spermatogenic failure.     

Mosaic status in lymphocytes of infertile men with or without Klinefelter syndrome

BACKGROUND: Gonosomal aneuploidies such as Klinefelter syndrome (47,XXY) are the most frequent chromosomal aberration in infertile men. Normally the chromosomal status of patients is detected by karyotyping of up to 20 metaphase spreads of lymphocyte nuclei, whereby low grade mosaicism may be overlooked. To test whether Klinefelter patients with 47,XXY karyotype or infertile men with 46,XY karyotype represent gonosomal mosaicisms, we performed meta- and interphase fluorescence in situ hybridization (FISH) on 45 men. METHODS AND RESULTS: A total of 400 interphase and 40 metaphase lymphocyte nuclei per patient were scored after hybridization with DNA probes specific for chromosomes X and Y, and chromosome 9 as a control. On the basis of conventional karyotype, hormone levels and clinical appearance, patients were subdivided into 18 Klinefelter syndrome patients with 47,XXY (group I), 11 Klinefelter syndrome-like patients with normal karyotype, 46,XY (group II) and six non-Klinefelter-like infertile patients with normal 46,XY karyotype (group III). Ten normal men (group IV) served as controls. Testicular volume in the Klinefelter group I was smaller compared with group II (P = 0.016), group III (P < 0.001) and group IV (P < 0.001). In addition, testicular volumes in group II were lower compared with group III and group IV (P < 0.004). No significant differences between the aneuploidy rate analysed by FISH in interphase nuclei and metaphases were found in either single patients or groups. Patients with Klinefelter syndrome, 47,XXY (group I) or with symptoms similar to those in Klinefelter patients 46,XY (group II) showed a similar aneuploidy rate (group I 7.1 +/- 4.0% and group II 4.6 +/- 3.4%) and two 47,XXY patients with a high prevalence for normal 46,XY lymphocytes had sperm in their ejaculate. However, in general, no correlations between FISH mosaic status and serum hormone parameters, nor with ejaculate parameters were found. CONCLUSIONS: The results suggest that 47,XXY patients with an increased incidence of XY cells (average of 4.2 +/- 2.3) may have a higher probability of germ cells as we found sperm only in the ejaculate of Klinefelter syndrome patients with mosaic 46,XY cells (6.0 and 7.0%). On the other hand, 46,XY patients with mosaic sex chromosome aneuploidies detected by FISH analysis more often show symptoms of hypogonadism phenotypically resembling Klinefelter syndrome.     

Do morphological anomalies reflect chromosomal aneuploidies?: case report

In cases of severe teratozoospermia, the current morphological criteria used to assess chromosomal status is insufficient for the selection of spermatozoa for intracytoplasmic sperm injection (ICSI). Case histories are reported of four patients presenting 100% teratozoospermia, and the integrity of their individual chromosomal statuses is determined using a three-colour fluorescence in-situ hybridization (FISH) technique. Patient 1 presented shortened flagella syndrome, patient 2 globozoospermia, patient 3 spermatozoa with irregular acrosomes, and patient 4 macrocephalic spermatozoa with associated multiple flagella. Three-colour FISH analysis using chromosome X, Y and 1-specific probes showed that approximately 95% of the spermatozoa analysed from patients 1, 2 and 3 presented X,1 and Y,1 signals, X,Y ratios and aneuploidy/diploidy rates comparable with those observed in normal controls. In contrast, patient 4 showed a highly elevated Y to X sex ratio and a highly elevated aneuploidy/diploidy rate. Three-colour FISH analysis thus demonstrates an increased incidence of chromosomal abnormalities in association with macrocephalic spermatozoa. Moreover, the analysis shows that in patients affected with either globozoospermia, shortened flagella syndrome or a condition of abnormal acrosomal spermatozoa, no association exists between chromosomal status and phenotype. Since these patients display normal haploid, sex chromosome and aneuploidy status, ICSI can be conceivably offered as a treatment for their infertility.     

Incidence of aneuploid spermatozoa from subfertile men: selected with motility versus hemizona-bound

Spermatozoa-zona pellucida binding selects for human spermatozoa with progressive motility, normal morphology and functional competency. We postulated that this gamete interaction would also act to select against spermatozoa with chromosomal numerical aberrations. Spermatozoa from 41 men participating in the intracytoplasmic sperm injection (ICSI) programme were evaluated for the incidence of aneuploidy of chromosomes 18, X and Y. The hemizona assay was utilized to determine whether zona-bound spermatozoa from these patients have a reduced incidence of aneuploidy compared with those selected by motility only in a standard swim-up procedure. Using multicolour fluorescence in-situ hybridization (FISH) with DNA probes specific for chromosomes 18, X and Y, the disomy rates for chromosomes 18, X, Y and XY were found to be 0.31, 0.27, 0.29 and 0. 14% respectively in the swim-up motile fraction, and 0.31, 0.33, 0. 32 and 0.19% respectively in the pellet fraction. Analysing the zona-bound spermatozoa, the disomy rates for chromosome 18, X, Y and XY were found to be 0.02, 0.15, 0.12 and 0.07% respectively. The zona-bound spermatozoa had a significantly lower frequency of aneuploidy than the swim-up motile fraction or the pellet fraction (P < 0.0001). The incidence of chromosome 18 aneuploidy, including both chromosome 18 disomy and nullisomy, in the swim-up motile fractions was significantly increased in patients with an abnormal or borderline hemizona index compared with those with a normal hemizona index (P < 0.05). We also found that a high incidence of sperm aneuploidy was associated to a certain extent with low fertilization rate, and with failure to achieve pregnancy through ICSI. This study suggests that the human zona pellucida has the capacity to select against aneuploid spermatozoa by an as yet undetermined mechanism.     

Maturation phenotype of Sertoli cells in testicular biopsies of azoospermic men

The involvement of Sertoli cells in different spermatogenic impairments has been studied by an immunohistomorphometric technique using cytokeratin-18 (CK-18) as a marker for immature Sertoli cells. CK-18 is known to be expressed in Sertoli cells during prenatal and prepubertal differentiation and is normally lost at puberty. Forty-nine azoospermic men were included in the current study. Quantitative measurements on testicular biopsies revealed the highest CK-18 expression in the mixed atrophy biopsies (22 men), a lower expression in the Sertoli cell-only (SCO) biopsies (12 men), and minimal residual staining in the group considered as representing normal spermatogenesis (six obstructive azoospermia patients). The cytokeratin immunopositive-stained tubules were associated either with arrest in spermatogenesis or with SCO. Examination of sections from nine men with microdeletions in the AZF region of the Y chromosome revealed that these men were either negative for CK-18 expression or showed only weak residual staining. This may suggest that the spermatogenic defect in the AZF-deleted men originates in the germ cell and has no impact on Sertoli cell maturation. The cause that determined the spermatogenic defect in the other cases of male infertility with high CK-18 expression may have damaged both the Sertoli and the germ cells.     

Detection of structural and numerical chromosomal abnormalities by ACM-FISH analysis in sperm of oligozoospermic infertility patients

BACKGROUND: Modern reproductive technologies are enabling the treatment of infertile men with severe disturbances of spermatogenesis. The possibility of elevated frequencies of genetically and chromosomally defective sperm has become an issue of concern with the increased usage of ICSI, which can enable men with severely impaired sperm production to father children. Several papers have been published reporting aneuploidy in oligozoospermic patients, but relatively little is known about chromosome structural aberrations in the sperm of these patients. METHODS: We examined sperm from infertile, oligozoospermic individuals for structural and numerical chromosomal abnormalities using a multicolour ACM fluorescence in situ hybridization (FISH) assay that utilizes DNA probes specific for three regions of chromosome 1 to detect human sperm that carry numerical chromosomal abnormalities plus two categories of structural aberrations: duplications and deletions of 1pter and 1cen, and chromosomal breaks within the 1cen-1q12 region. RESULTS: There was a significant increase in the average frequencies of sperm with duplications and deletions in the infertility patients compared with the healthy concurrent controls. There was also a significantly elevated level of breaks within the 1cen-1q12 region. There was no evidence for an increase in chromosome 1 disomy, or in diploidy. CONCLUSIONS: Our data reveal that oligozoospermia is associated with chromosomal structural abnormalities, suggesting that oligozoospermic men carry a higher burden of transmissible, chromosome damage. The findings raise the possibility of elevated levels of transmissible chromosomal defects following ICSI treatment.