Zsuzsanna Molnár

Correlation study between sperm concentration, hyaluronic acid-binding capacity and sperm aneuploidy in Hungarian patients.

Infertile men with low sperm concentration and/or less motile spermatozoa have an increased risk of producing aneuploid spermatozoa. Selecting spermatozoa by hyaluronic acid (HA) binding may reduce genetic risks such as chromosomal rearrangements and numerical aberrations. Fluorescence in-situ hybridization (FISH) has been used to evaluate the presence of aneuploidies. This study examined spermatozoa of 10 oligozoospermic, 9 asthenozoospermic, 9 oligoasthenozoospermic and 17 normozoospermic men by HA binding and FISH. Mean percentage of HA-bound spermatozoa in the normozoospermic group was 81%, which was significantly higher than in the oligozoospermic (P<0.001), asthenozoospermic (P<0.001) and oligoasthenozoospermic (P<0.001) groups. Disomy of sex chromosomes (P=0.014) and chromosome 17 (P=0.0019), diploidy (P=0.03) and estimated numerical chromosome aberrations (P=0.004) were significantly higher in the oligoasthenozoospermic group compared with the other groups. There were statistically significant relationships (P<0.001) between sperm concentration and HA binding (r=0.658), between sperm concentration and estimated numerical chromosome aberrations (r=-0.668) and between HA binding and estimated numerical chromosome aberrations (r=-0.682). HA binding and aneuploidy studies of spermatozoa in individual cases allow prediction of reproductive prognosis and provision of appropriate genetic counselling. Infertile men with normal karyotypes and low sperm concentrations and/or less motile spermatozoa have significantly increased risks of producing aneuploid (diminished mature) spermatozoa. Selecting spermatozoa by hyaluronic acid (HA) binding, based on a binding between sperm receptors for zona pellucida and HA, may reduce the potential genetic risks such as chromosomal rearrangements and numerical aberrations. In the present study we examined sperm samples of 45 men with different sperm parameters by HA-binding assay and fluorescence in-situ hybridization (FISH). Mean percentage of HA-bound spermatozoa in the normozoospermic group was significantly higher than the oligozoospermic, the asthenozoospermic and the oligoasthenozoospermic groups. Using FISH, disomy of sex chromosomes and chromosome 17, diploidy and estimated numerical chromosome aberration frequencies were significantly higher in the oligoasthenozoospermic group compared with the three other groups. A significant positive correlation was found between the sperm concentration and the HA-binding capacity, and significant negative correlations between the sperm concentration and the estimated numerical chromosomes aberrations as well as between the HA-binding ability and the estimated numerical chromosome aberrations were identified. We conclude that HA-binding assay and sperm aneuploidy study using FISH may help to predict the reproductive ability of selected infertile male patients and to provide appropriate genetic counselling.

Adolescent hodgkin lymphoma: Are treatment results more favorable with pediatric than with adult regimens?

Background The aim of our work was to compare the treatment modalities and the survival rates in adolescents (14 to 21 y) with Hodgkin lymphoma (HL) treated with adult (A) or with pediatric (P) regimens. Procedure From January 1990 to December 2004, 134 (A) and 111 (P) adolescents with HL were treated. Male:female ratio was 1:1.48 (A) and 1:1.36 (P), the mean-age 18.6 (A) and 15.8 years (P), respectively. Results The patients were treated either with doxorubicin, bleomycin, vinblastine and dacarbazine (A) or with OPPA/OEPA±COPP regimens (P). About 82% (A) and 89% (P) of the patients received radiotherapy. Relapse rates were 13% (A) and 14% (P). Fourteen patients died in group (A) and 9 in group (P). There were no significant differences in the overall survival and event-free survival rates at 5 and 10 years between the 2 patients groups. For children under age of 18 years old overall survival was 92.8±3% at 5 and 89.6±3% at 10 years in group (P) and 89.4±4% at 5 years and 83.1±6% at 10 years (P=0.2822) in group (A). For children under the age of 18 years event-free survival was 82.4±4% at 5 and 10 years in group (P) and 69.6±7% at 5 years and 59.1±8% at 10 years (P=0.0192) in group (A). Conclusion In case of the patients younger than 18 years, the survival rates are more favorable by using pediatric regimens, so these patients might have a benefit if they are treated in pediatric institutes.

Is sperm hyaluronic acid binding ability predictive for clinical success of intracytoplasmic sperm injection: PICSI vs. ICSI?

Abstract Although intracytoplasmic sperm injection (ICSI) is now a widely-used technique, it is still of interest to improve our knowledge as to which is the best spermatozoon to be selected for ICSI. Infertile men have increased risks of producing aneuploid spermatozoa. Using hyaluronic acid (HA)-binding sperm selection may reduce the genetic risks such as chromosomal aberrations of offspring. In the present study we examined the clinical success of ICSI with HA-selected sperm (‘physiologic’ ICSI, PICSI) compared to conventional ICSI, as well as the necessity to differentiate patients according to the initial HA-binding assay result (HBA score) and whether the sperm concentration or HBA score can provide additional information. We observed a significantly higher fertilization rate (FR) of the PICSI group with >60% HBA, implantation rate (IR) of the PICSI group with ≤60% HBA, and clinical pregnanacy rate (CPR) in every PICSI group compared to the ICSI groups (p < 0.01). We also observed a significantly higher life birth rate (LBR) in the PICSI group with ≤60% HBA compared to ICSI patients with ≤60% HBA (p < 0.001). The pregnancy loss rate (PLR) was significanly lower in PICSI patients compared to the ICSI group (p < 0.0001). The FR, IR, CPR, and LBR of the PICSI group with <50% HBA were significantly higher and the PLR was lower than in the ICSI group with <50% HBA (p < 0.01). A statistically significant correlation was found between the sperm concentration and the HA-binding capacity (r = 0.62, p < 0.001). We found a closer relationship between HBA score and FR (r = 0.53, NS) than between sperm concentration and FR (r = 0.14, NS). HBA could be considered for sperm selection prior to ICSI because of its success and apparant ability to reduce genetic complications. However, this must be extended to a larger study.

Follow-up of thrombin generation after prostate cancer surgery: global test for increased hypercoagulability.

Recent studies provided evidence that evaluation of thrombin generation identifies patients at thrombotic risk. Thrombin generation has a central role in hemorrhage control and vascular occlusion and its measurement provides new metrics of these processes providing sufficient evaluation of an individual’s hemostatic competence and response to anticoagulant therapy. The objective of the study is to assess a new measure of hypercoagulability that predisposes to venous thromboembolism in the postoperative period after radical prostatectomy. Pre- (day-1) and postoperative (hour 1, day 6, month 1 and 10) blood samples of 24 patients were tested for plasma thrombin generation (peak thrombin), routine hematology and hemostasis. Patients received low molecular weight heparin for thromboprophylaxis. Peak thrombin levels were higher in patients compared to controls at baseline (p<0.001), and elevated further in the early postoperative period (p<0.001). Longer general anesthesia and high body mass index were associated with increased thrombin generation after surgery (p = 0.024 and p = 0.040). D dimer and fibrinogen levels were higher after radical prostatectomy (p = 0.001 and p<0.001). Conventional clotting tests remained within the reference range. Our study contributed to the cognition of the hypercoagulable state in cancer patients undergoing pelvic surgery and revealed the course of thrombin generation after radical prostatectomy. Whilst it is unsurprising that thrombin generation increases after tissue trauma, further evaluation of this condition during the postoperative period would lead urologists to an international and well-supported consensus regarding thromboprophylaxis in order to provide better clinical outcome. Considering the routine evaluation of procoagulant activity and extending prophylactic anticoagulant therapy accordingly may potentially prevent late thrombotic events.

Meiotic segregation study of a novel t(3;6)(q21;q23) in an infertile man using fluorescence in situ hybridization (FISH)

Male carriers with balanced reciprocal translocations can produce a variable proportion of unbalanced gametes resulting in reproductive failures. The presence of a structural rearrangement may induce an interchromosomal effect. This is characterized by abnormal bivalents not involved in the reorganization thereby yielding non-disjunction, which would present as aneuploid spermatozoa for these chromosomes. In the present case report segregation analysis of the sperm and investigation of interchromosomal effect were carried out using cytogenetic and fluorescence in situ hybridization (FISH) analysis on blood lymphocytes. The karyotype of the patient was 46,XY,t(3;6)(q21;q23). During sperm segregation analysis a total of 2,002 sperms were evaluated, of which 46.8% showed normal/balanced (alternate segregation mode) and 53.2% of sperm showed an abnormal signal pattern. A significant difference in the frequency of the estimated number of chromosome anomalies was observed in the translocation carrier when compared to the normozoospermic group (P < 0.0001) and the oligozoospermic group (P < 0.0001). Meiotic segregation analysis of sperm together with aneuploidy assessment for X, Y, and 17 chromosomes using FISH allows for the determination of a reproductive prognosis in male balanced translocation carriers and can be used for appropriate genetic counseling.

[Influence of malignant tumors occurring in the reproductive age on spermiogenesis: studies on patients with testicular tumor and lymphoma].

INTRODUCTION The application of chemo- and radiotherapy results in good survival prognosis for young men with malignant tumors, but long-term gonadoxic effect has to be considered. In addition, malignant disease itself has a negative impact on spermiogenesis. AIM The aim of the authors was to examine the spermiogenetic effect of the most common tumors occurring in the reproductive age in men: testicular cancer, Hodgkin disease and non-Hodgkin disease. METHOD Spermiogram of men with testicular cancer (N = 68), Hodgkin disease (N = 37) and non-Hodgkin disease (N = 14) who were referred for sperm cryopreservation were analysed in the Reproductive Andrology Laboratory of the authors. RESULTS Azoospermia was found in 11.8% of all patients (N = 119), while 58.8% of the patients had oligozoospermia even before the treatment. Sperm concentration of men with testicular cancer was significantly lower than those with lymphomas (32.8 M/mL vs. 24.9 M/mL, p = 0.03). There was no difference in sperm concentration between the Hodgkin and non-Hodgkin lymphoma groups. CONCLUSIONS Spermiogenetic defect is more pronounced in men with testicular cancer than those with lymphomas. Cryopreservation before treatment for fertility preservation should be offered for all reproductive aged men with malignant disease, especially for those with testicular cancer.

Thyroglobulin level at week 16 of pregnancy is superior to urinary iodine concentration in revealing preconceptual and first trimester iodine supply

Abstract Pregnant women are prone to iodine deficiency due to the increased need for iodine during gestation. Progress has recently occurred in establishing serum thyroglobulin (Tg) as an iodine status biomarker, but there is no accepted reference range for iodine sufficiency during pregnancy. An observational study was conducted in 164 pregnant women. At week 16 of gestation urinary iodine concentration (UIC), serum Tg, and thyroid functions were measured, and information on the type of iodine supplementation and smoking were recorded. The parameters of those who started iodine supplementation (≥150 μg/day) at least 4 weeks before pregnancy (n = 27), who started at the detection of pregnancy (n = 51), and who had no iodine supplementation (n = 74) were compared. Sufficient iodine supply was found in the studied population based on median UIC (162 μg/L). Iodine supplementation ≥150 μg/day resulted in higher median UIC regardless of its duration (nonusers: 130 μg/L vs. prepregnancy iodine starters: 240 μg/L, and pregnancy iodine starters: 205 μg/L, p < .001, and p = .023, respectively). Median Tg value of pregnancy starters was identical to that of nonusers (14.5 vs. 14.6 μg/L), whereas prepregnancy starters had lower median Tg (9.1 μg/L, p = .018). Serum Tg concentration at week 16 of pregnancy showed negative relationship (p = .010) with duration of iodine supplementation and positive relationship (p = .008) with smoking, a known interfering factor of iodine metabolism, by multiple regression analysis. Serum Tg at week 16 of pregnancy may be a promising biomarker of preconceptual and first trimester maternal iodine status, the critical early phase of foetal brain development.

Present Practice of Thrombosis Prophylaxis of Radical Prostatectomy in a European Country: A Hungarian Multicenter Study

Venous thromboembolism is a possible fatal complication after pelvic surgery. There is a lack of trials assessing the effect of prophylactic measures in urology. The aim of the study was to evaluate the practice of thrombosis prophylaxis in a Central European country. A questionnaire of performed radical prostatectomies, way of thrombosis prophylaxis and number of experienced thrombotic events was posted to all departments of urology in Hungary. With a response rate of 59%, 506 radical prostatectomies were reported. Low molecular weight heparin was administered by 100% of the departments. Graduated support stockings were applied by 37% of the patients. Early mobilization was the most common form of mechanic prophylaxis (57%). Thrombotic events were experienced in 1.4%, 0.2% were fatal. The thrombosis prophylaxis of patients undergoing radical prostatectomy is not unified. Due to the potential mortality of thrombotic complications it should be evaluated and prophylaxis should be recommended in urological guidelines.

Citogenetic and molecular genetic studies in infertility in East Hungary

INTRODUCTION In developed countries 10-15% of the couples are affected by infertility. In half of them genetic factors can be identified. AIMS We studied genetic alterations in infertility in Hungarian patients. METHODS Cyogenetic analyses were performed in 195 females and 305 males. In 17 females FMR1 mutations, in 150 males Y microdeletions, and aneuploidy were studied in the sperm of 28 males. In a carrier male sperm meiotic segregation was studied. RESULTS The most common aberrations in females were X chromosome aneuploidia and inversion (3.6%), while the same in males Klinefelter-syndrome (3.3%) and autosomal translocations (2%). In two females FMR1 premutation was found. While Y microdeletions were identified only in azoospermic and severe oligozoospermic men, partial microdeletions could also be detected in normozoospermic males. A higher aberration rate was found in cases with abnormality in both the number and motility of sperm. In a male patient with 46,XY,t(3;6)(q21;q23) karyotype, 53.2% of spem carried unbalanced chromosome assortment. CONCLUSIONS Knowledge of abnormalities may help in genetic counseling and choosing the most effective reproduction technique.

Hodgkin’s lymphoma in adolescents

UNLABELLED Adolescent patients with Hodgkins lymphoma (HL) are treated either in pediatric, or in adult oncological wards. AIM The aim of our work was to compare the treatment modalities and the survival rates in adolescents with HL treated in adult (A) or pediatric (P) institutes. METHODS From January 1990 to December 2004, 138 patients (14-21 years) with HL were treated in two adult institutes (A) and 107 in the 10 centres of the Hungarian Pediatric Oncology Network (P). RESULTS Male:female ratio was 1:1.15 (A) and 1:1.38 (P). The mean age was 18.6 (A) and 15.7 (P) years. There was no difference between the distribution of the stages in the two patient groups. The distribution of histological subtypes (A and P): nodular sclerosing 47% and 59%, mixed cellularity 45% and 25%, lymphocyte rich 1.5% and 10%, lymphocyte depleted 4% and 1%, nodular lymphocyte predominant 1.5% and 3% and unknown 1% and 2%. The majority of the patients were treated with ABVD (A) and OPPA/OEPA +/- COPP (P). One hundred and fifteen (A) and 97 (P) adolescents received irradiation therapy. 80% (A) and 91% (A) of the patients got radiotherapy. In group A 14%, in group P 13% of the patients had relapse. In group A 16 patients died and in group P 7. There was no significant difference in the overall survival (OS) rates at 5 and 10 years in the two patient groups. The event-free survival (EFS) was 76.5 +/- 4% and 72.5 +/- 4% at 5 and 10 years in group A, and 85.3 +/- 4% at both times in group P ( p = 0.0452). CONCLUSION Survival rates in HL are quite high, 80-90% of the patients can be cured. Event-free survival was higher in pediatric than in adult institutes. In case of patients younger than 18 years, the survival rates were much better in pediatric institutes, so these patients should be treated in pediatric institutes or with protocols used by the pediatricians.