Anđelka Radojčić Badovinac

Chromosome studies in patients with defective reproductive success.

PROBLEM: The objective of this study was to evaluate the contribution of chromosomal anomalies to decreased fertility in humans.
 METHOD OF STUDY: In order to investigate the aetiology of infertility in our population and to assess the karyotype in a group of infertile couples and individuals with fertility problems, 782 persons (259 couples, 158 male and 106 female) with different clinical diagnoses of sterility and infertility were analysed cytogenetically.
 RESULTS: The overall frequency of major chromosomal aberration was 13.1% (103/783), which suggests that fertility or sterility problems in this population are due to chromosomal aberrations. Couples experiencing repeated spontaneous abortions, having malformed children or having sterility problems had chromosomal abnormalities in 18.0% (47/259 couples) of the population studied, and constituted chromosomal disorders occured in couples seeking IVF and ICSI with prevalence of 22.2% (8/38 couples), especially minor mosaicism of sex chromosomes in the female partners. The prevalence of chromosome abnormalities in infertile men was 17.7% (28/158), and in subfertile females, it was 26.4% (28/106).
 CONCLUSIONS: These results could indicate an increased tendency to miotic sex chromosome non‐disjuction in humans.

Angiotensin-Converting Enzyme Insertion/Deletion Gene Polymorphism in Lung Cancer Patients

Lung cancer is a complex disease, and many factors, including environmental and occupational exposure, cigarette smoking, and genetics, contribute to its progression. Angiotensin-converting enzyme (ACE) is an important regulator of blood pressure and cardiovascular homeostasis. Plasma levels of ACE depend on an insertion/deletion (I/D) polymorphism in its gene. Current correlation data between lung cancer and the ACE I/D polymorphism are contradictory or insufficient. We investigated whether the ACE I/D polymorphism is associated with a risk for lung cancer development in the Croatian population, representing the first report in a population of Slavic origin. A total of 308 lung cancer patients and 353 control subjects were genotyped for the ACE I/D polymorphism by polymerase chain reaction. The observed distribution of genotypes and alleles showed no significant difference between total patients and controls (p>0.050). However, in a subgroup of nonsmall cell lung cancer patients with squamous cell carcinoma, a significantly higher frequency of the DD genotype (37.7% vs. 27.8%, p=0.030, OR=1.57, 95% CI=1.05-2.36) and D allele was observed compared with the control group (61.3% vs. 52.8%, p=0.015, OR=1.41, 95% CI=1.07-1.87). The DD genotype of ACE may contribute to a higher risk of developing squamous cell carcinoma in the Croatian population.

The impact of hemochromatosis mutations and transferrin genotype on gonadotropin serum levels in infertile men

OBJECTIVE To address the possibility that HFE mutations and TF gene polymorphism cause dysfunction of spermatogenesis and/or the hypothalamic-pituitary-gonadal axis via contribution to long-term iron overload in the testes and brain. DESIGN Case-control and association study. SETTING Clinic of obstetrics and gynecology and university-based research laboratory. PATIENT(S) 127 infertile men (including 97 with idiopathic infertility) and 188 controls of proven fertility. INTERVENTION(S) Polymerase chain reaction/restriction fragment length polymorphism (PCR-RFLP). MAIN OUTCOME MEASURE(S) HFE mutations and transferrin allelic polymorphism, and testosterone, prolactin, and gonadotropin serum levels. RESULT(S) The frequencies of the analyzed alleles and genotypes showed no statistically significant difference between infertile men and controls. Sperm count and progressive sperm motility did not correlate with HFE or TF genotype, or their combination. After excluding patients with clinical hypogonadism or varicocele from further analysis, a statistically significant correlation between serum follicle-stimulating hormone and luteinizing hormone levels and the combined HFE H63D/TFC2 genotype was found in 97 men with idiopathic infertility. CONCLUSION(S) The combined HFE H63D/TF-C2 genotype contributed to 4.1% and 10.6% of follicle-stimulating hormone and luteinizing hormone variation, respectively, in infertile men, raising mean hormonal values above the normal physiologic range. Therefore, HFE and TF genes together may influence the hypothalamic-pituitary-gonadal axis, functioning at the pituitary or testes level.

Sperm Cell in ART

Infertility today represents a global problem. Male factor contributes in approximately 50% of infertile couples. In the last decade we are witnesses of the decreased quality of semen and the increased frequency of testicular cancer and cryptorchidism. Currently, the assessment of semen quality is based on the routine semen analysis including sperm count, morphology and motility. Although variation and combination among these three main factors articulate few diagnosis, nowadays developed assisted reproduction techniques (ART), especially intracytoplasmatic sperm injection (ICSI) may be used to treat most of the male infertility problems. In general we can say that traditional semen parameters provide a limited degree of diagnostic information, thus we are aware that these indexes of diagnosis should be revisited, which includes more specific test of sperm assessments, such as DNA tests and sperm proteome. Spermatogenesis is a process that includes physiological, morphological and biochemical changes. After a complex process from the round diploid spermatogonia to haploid spermatozoa, a mature sperm just has an ability to fertilize a mature oocyte. If any errors occur during spermatogenesis process, appropriate sperm will not be produced. Thus, in our ART practice, it is important to understand normal physiology of spermatogenesis and find the reason of abnormal situation.