Cytogenetic investigations were performed in 781 couples prior to intracytoplasmic sperm injection (ICSI) because of severe male infertility or fertilization failures in previous in-vitro fertilization attempts. Out of these 1562 patients, 1012 had a normal karyotype without any aberrations (64.8%), 204 patients had an abnormal karyotypes (13.1%). These chromosome aberrations included constitutional aberrations (4.4%), fragile sites of autosomes (3.0%), low level mosaicism of sex chromosomes (4.0%) and secondary structural chromosome aberrations (4.2%). Combinations of different types of abnormalities were stated. Another 346 patients (22.1%) showed single cell aberrations; the significance of these is unclear at the moment. Constitutional chromosome aberrations were detected in 69 patients. The following chromosome aberrations were observed: 35 sex chromosomal aberrations (comprising hyperploidies of X or Y chromosomes, mosaicisms and derivative X and Y chromosomes), 34 autosomal aberrations including 14 reciprocal translocations, five Robertsonian translocations, six inversions, one marker chromosome, one trisomy 18 mosaicism and seven other structural aberrations. Three autosomal regions showed fragile sites: 6q13 in 2.9% of the patients, 17p12 and 10q24 in 0.05% each. In conclusion, our data show that a high number of infertile couples in an ICSI programme are affected by chromosome aberrations which occur in both sexes. It is suggested that a chromosomal analysis should be performed on both partners before ICSI treatment is initiated.

We evaluated the frequency of chromosomal aberrations and microdeletions of the Y chromosome in a sample of 204 patients included in an intracytoplasmic sperm injection (ICSI) programme. The prevalence of Y chromosome deletions in males with severely or only moderately reduced sparm counts is mainly unknown, so that patients were chosen with sperm counts ranging from mild oligozoospermia to azoospermia. While six out of 158 (3.8%) patients showed constitutional chromosomal aberrations, only two out of 204 (0.98%) patients were diagnosed with a microdeletion of Yq11. One had a terminal deletion in subinterval 6 of Yq11.23 which included the DAZ gene and a corresponding sperm count < 0.1 x 10(6) spermatozoa/ml. The second patient had an isolated deletion of marker Y6PH54c, a more proximal site in subinterval 5 on Yq11.23, but repeatedly showed sperm counts of 3-8 x 10(8) spermatozoa/ml. Thus, of the 158 patients who underwent a combined cytogenetic and Y-microdeletion screening, eight patients (5.1%) showed chromosomal abnormalities, either at the cytogenatic (n = 6) or the molecular level (n = 2). In conclusion, although rare in number, microdeletions of the Y chromosome can also be observed in patients with moderately reduced sperm counts. A more proximal site of the deletion breakpoint does not necessarily imply a more severe impairment of spermatogenesis than a distal deletion site. In our sample, the overall frequency of constitutional chromosomal aberrations exceeded the incidence of microdeletions of the Y chromosome even in patients with idiopathic azoo- or severe oligozoospermia.

Small supernumerary marker chromosomes (SMC) are a heterogeneous group of chromosomes with an estimated frequency of approximately 0.14-0.72 per 1000 newborns and higher frequencies in particular populations such as the mentally retarded or infertile males. With a frequency of about 50%, derivatives of chromosome 15 represent the most common SMC. Here we present the results of a detailed analysis of 32 SMC(15) carriers who were ascertained in pre- or post-natal routine cytogenetic diagnostics. SMC(15) with euchromatic content led to mental and psychomotor retardation. In contrast, SMC(15) without euchromatin were found to have no influence on the carrier's phenotype but were detected with a high incidence among infertile males. The majority of SMC(15) are pseudodicentric homologous rearrangements. Based on our investigations a further characterization of der(15) was possible.

Here we describe a group of 14 patients carrying different X-autosome translocations and exhibiting phenotypes that demonstrate the range of alterations induced by such aberrations. All male carriers of an X-autosome translocation in our investigation group were infertile, whereas fertility in the female carriers was dependent on the position of the break-point in the X chromosome. Fertile women with translocation break-points outside of the critical region (Xq13-q26) in some cases passed on the translocation to their offspring. In balanced female carriers in our group, the normal X chromosome was usually inactivated, allowing full expression of genes on the translocated segments. In one case, disruption of the dystrophine gene in Xp21 led to the manifestation of Duchenne muscular dystrophy in a female carrier. Inactivation of the derivative X (Xt) in a balanced female carrier led to a partial monosomy of the autosome/disomy of the X chromosome and resulted in an aberrant phenotype. In unbalanced carriers, Xt is generally late-replicating/inactive, although failed spreading of inactivation to the autosomal segment often results in a partial trisomy, as evidenced by the case of an unbalanced translocation carrier in our group.

Robertsonian translocations 13/14 are the most common chromosome rearrangements in humans. However, most studies aimed at determining risk figures are more than 20 years old. Their results are often contradictory regarding important topics in genetic counseling such as infertility and unfavorable pregnancy outcomes. Here, we present a study on a sample of 101 previously unreported pedigrees of der(13;14)(q10;q10). In order to minimize problems of partial ascertainment, we included families with a wide range of reasons of ascertainment such as birth of a child with congenital anomalies, prenatal diagnosis due to maternal age, fertility problems and recurrent pregnancy loss. No evidence of increased infertility rates of female and male carriers was found. The detected miscarriage frequency of female carriers was higher than previously reported (27.6 +/- 4.0% of all spontaneous pregnancies). This may be explained by an over-correction of earlier studies, which excluded all unkaryotyped miscarriages. In three out of 42 amniocenteses, translocation trisomies 13 were diagnosed (7.1 +/- 4.0% of all amniocenteses). The frequency of stillbirths was 3.3 +/- 1.6% for female carriers and 1.4 +/- 1.4% for male carriers. A low risk for the live birth of translocation trisomy 13 children was confirmed since no live born children with trisomy 13 or Pätau syndrome were detected in the ascertainment-corrected sample.