Genetic Diagnosis in Infertile Men with Numerical and Constitutional Sperm Abnormalities C ¸ ig ˘dem C ¸ inar, 1 Cenk Yazıcı, 2 S ¸ ebnem Ergu ¨ nsu, 1 C ¸ ag ˘ rı Beyazyu ¨ rek, 3 Dilara Javadova, 1 Yaman Sag ˘ lam, 3 Tufan Tarcan, 2 and Ahmet Ilter Gu ¨ ney 1 Infertile men having numerical or structural sperm defects may carry several genetic abnormalities (karyotype abnormalities, Y chromosome microdeletions, cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations, androgen receptor gene mutations, and abnormalities seen in sperm cells) leading to this situation. First we aimed to investigate the relationship between the numerical and constitutional (morphological) sperm anomalies and the genetic disorders that can be seen in infertile males. Our other aim was to compare two different kinds of kits that we use for the detection of Y chromosome microdeletions. Sixty-three infertile males [44 non- obstructive azoospermic, 8 severe oligozoospermic, and 11 oligoasthenoteratozoospermic] were investigated in terms of somatic chromosomal constitutions and microdeletions of the Y chromosome. Sperm aneuploidy levels were analyzed by fluorescence in situ hybridization (FISH) in sperm cells obtained from the semen of six OAT patients. Microdeletion and sex chromosome aneuploidy (47,XXY) rates in somatic cells were found to be ap- proximately 3.2% and 4.7%, respectively. Sperm aneuploidy rates were determined as 9%, 22%, and 47% in three patients out of six. Two of these three patients also had high rates of head anomalies in semen samples. High correlation was found between sperm aneuploidy rates and sperm head anomalies. Since the introduction of the assisted reproductive techniques for the treatment of severe male infertility, genetic tests and genetic counseling became very important due to the transmission of genetic abnormalities to the next generation. Thus in a very near future, for a comprehensive male infertility panel, it will be essential to include additional genetic tests, such as CFTR gene mutations, sperm mitochondrial DNA mutations, and androgen receptor gene mutations, besides the conventional chromosomal analyses, Y chromosome microdeletion detection, and sperm-FISH analyses. Introduction I n almost 50% of infertile couples, who constitute 15% of the whole population, the problem is related to the male. Male reproduction problems are associated with many genetic disorders. In previous studies, it has been shown that there is a relationship between poor semen parameters and abnormal somatic karyotype like Klinefelter syndrome (47,XXY), Y chromosome microdeletions, and chromosomal abnormalities in spermatozoa. The genetic abnormalities constitute an essential part of the research related with infertility and assisted reproductive techniques (ARTs). In recent years, the problems encountered in reproduction are known to be linked not only to the somatic chromosomal abnormalities, but also to the cytogenetical ab- normalities found in reproductive cells of infertile men with normal somatic karyotype (Moore and Persaud, 1998). In many studies based on this subject, insufficient semen parameters (such as low sperm concentration, low motility, and abnormal morphology), Y chromosome microdeletions, and chromo- somal abnormalities in sperm (such as aneuploidies and trans- locations) were found to be in relationship with each other. Patients with nonobstructive azoospermia (NOA) or se- vere oligozoospermia may have microdeletions on the long arm of the Y chromosome (Yq11), especially in DAZ (deleted in azoospermia) region. These patients cannot produce sperm because of the absence of the genes that are important in spermatogenesis. Deletions in AZF (azoospermic factor) re- gion can cause severe spermatogenic defects ranging from NOA to oligospermia. Y deletions are reported in 10% of azoospermic and severe oligozoospermic men (Kremer et al., 1997; Loginova et al., 2003; Raicu et al., 2003). Most of the Y chromosome microdeletions are subdivided into three AZF regions: AZFa, AZFb, and AZFc. 1 Department of Medical Genetics, School of Medicine, Marmara University, Istanbul, Turkey. 2 Department of Urology, School of Medicine, Marmara University, Istanbul, Turkey. 3 Genetic Diagnosis Center, Memorial Hospital, Istanbul, Turkey. GENETIC TESTING Volume 12, Number 2, 2008 ª Mary Ann Liebert, Inc. Pp. 195–202 DOI: 10.1089=gte.2007.0056 195