Contribution of genotypes in Prothrombin and Factor V Leiden to COVID-19 and disease severity in patients at high risk for hereditary thrombophilia.

Thrombotic and microangiopathic effects have been reported in COVID-19 patients. This study examined the contribution of the hereditary thrombophilia factors Prothrombin (FII) and Factor V Leiden (FVL) genotypes to the severity of COVID-19 disease and the development of thrombosis. This study investigated FII and FVL alleles in a cohort of 9508 patients (2606 male and 6902 female) with thrombophilia. It was observed that 930 of these patients had been infected by SARS-CoV-2 causing COVID-19. The demographic characteristics of the patients and their COVID-19 medical history were recorded. Detailed clinical manifestations were analyzed in a group of cases (n = 4092). This subgroup was age and gender-matched. FII and FVL frequency data of healthy populations without thrombophilia risk were obtained from Bursa Uludag University Medical Genetic Department's Exome Databank. The ratio of males (31.08%; 27.01%) and the mean age (36.85 ± 15.20; 33.89 ± 14.14) were higher among COVID-19 patients compared to non-COVID-19 patients. The prevalence of FVL and computerized tomography (CT) positivity in COVID-19 patients was statistically significant in the thrombotic subgroup (p < 0.05). FVL prevalence, CT positivity rate, history of thrombosis, and pulmonary thromboembolism complication were found to be higher in deceased COVID-19 patients (p < 0.05). Disease severity was mainly affected by FVL and not related to genotypes at the Prothrombin mutations. Overall, disease severity and development of thrombosis in COVID-19 are mainly affected by the variation within the FVL gene. Possible FVL mutation should be investigated in COVID-19 patients and appropriate treatment should be started earlier in FVL-positive patients.

Outcome of intracytoplasmic sperm injection using fresh and cryopreserved-thawed testicular spermatozoa in 83 azoospermic men with Klinefelter syndrome.

AIM: To report the outcome of intracytoplasmic sperm injection (ICSI) cycles using fresh or cryopreserved-thawed testicular spermatozoa of men with Klinefelter syndrome (KS). METHODS: Medical records of 83 azoospermic men with KS who underwent testicular sperm extraction (TESE) were reviewed. The clinical parameters for predicting sperm retrieval and fertilization, implantation, pregnancy and live birth rates of ICSI cycles in these patients were evaluated. RESULTS: A total of 88 TESE procedures were performed with sperm retrieval rates of 39.8% per cycle (35/88) and 42.1% per patient (35/83). None of the studied clinical parameters were found to be informative in predicting successful sperm recovery. A total of 41 embryo transfer cycles were carried out using fresh testicular spermatozoa in 30, cryopreserved-thawed spermatozoa in 10 and cryopreserved-thawed embryo replacement in one. The fertilization and clinical pregnancy rates were comparable at 52.7% and 51.6% with fresh and 48.3% and 60% with cryopreserved-thawed testicular spermatozoa groups, respectively. Twenty-two clinical pregnancies were obtained, including 14 singletons, five twins, two triplets and one quadruplet and ended with the delivery of 13 singletons and six twins. In total, out of 25 delivered fetuses, four died (3 female, 1 male) following delivery and 21 newborns (14 female, 7 male) were healthy with a female to male ratio of 2:1. Conclusions We concluded that no clinical or laboratory parameter predicts the presence of spermatozoa in patients with KS, except the TESE procedure itself. The use of fresh or cryopreserved-thawed spermatozoa on ICSI cycle outcomes are equally successful in patients with KS.

Prognostic impact of RUNX1 and ETV6 gene copy number on pediatric B-cell precursor acute lymphoblastic leukemia with or without hyperdiploidy.

The ETV6/RUNX1 fusion gene is a valuable prognostic marker that is frequently observed in B-cell precursor acute lymphoblastic leukemia (B-cell ALL). However, the clinical significance of copy number aberrations in these genes remains unclear. In this study, the effects of various aberrations inETV6 and RUNX1 gene copy number on disease prognosis were evaluated in 21 pediatric patients diagnosed with B-cell ALL with/without t(12;21). The prognostic significance of changes in gene copy number of ETV6 or RUNX1 in the presence or absence of hyperdiploidy, trisomy 21, and t(12;21) translocation were also evaluated. RUNX1 gene copy number amplifications were detected in 83 % of the patients who lacked t(12;21) and in all of the patients with hyperdiploidy. Trisomy 21 was detected in 78 % of the patients with hyperdiploidy. Changes in ETV6 gene copy number were detected in patients who lacked both the t(12;21) translocation and RUNX1 gene copy number amplifications. However, RUNX1 gene copy number amplification and ETV6 deletion were observed in all of the patients with t(12;21). RUNX1 gene copy number amplification was associated with hyperdiploidy, but not with t(12;21). Thus, the evaluation of distinct FISH and cytogenetic patterns in patients with B-cell ALL may strengthen the prognostic significance of changes in gene copy number.

Genetic aspects of human male infertility: the frequency of chromosomal abnormalities and Y chromosome microdeletions in severe male factor infertility.

OBJECTIVE: The main purpose of this study is to detect the frequency and type of both chromosomal abnormalities and Y chromosome microdeletions in patients with severe male factor infertility and fertile control subjects. The association between the genetic abnormality and clinical parameters was also evaluated. METHODS: This study was carried out in 208 infertile and 20 fertile men. Results of 208 patients, 119 had non-obstructive azoospermia and 89 had severe oligoasthenoteratozoospermia (OAT). Seventeen out of 119 (14.3%) azoospermic patients and two out of 89 (2.2%) patients with OAT had Y chromosome microdeletions. In total, 19 cases with deletions were detected in 208 infertile men, with a frequency of 9.1%. The AZFc locus, mainly DAZ gene cluster was the most frequently deleted region. Five other cases with azoospermia (4.2%) and two cases with OAT (2.2%) had a chromosomal abnormality, with a total number of seven (3.4%). Including Y chromosome deletions and structural chromosome abnormalities, the rate of genetic abnormalities was 12.5% (26/208) in our patients. On the other hand, 20 men with proven fertility and fathers of five cases with microdeletions were genetically normal. Y chromosome deletions and chromosomal abnormalities were associated with various histological alterations in testis. Sertoli cell-only (SCO) syndrome and maturation arrest predominated in these cases, whereas hypospermatogenesis occurred more frequently in genetically normal patients. CONCLUSION: Various chromosomal abnormalities and deletions of Y chromosome can cause spermatogenic breakdown resulting in chromosomally derived infertility. All these findings strongly support the recommendation of genetic screening of infertile patients.

Birth of a healthy boy using fresh testicular sperm in a patient with Klinefelter syndrome combined with Kartagener syndrome.

OBJECTIVE: To report a case of Klinefelter syndrome combined with Kartagener syndrome. DESIGN: Case report. SETTING: Private IVF center. PATIENT(S): A 35-year-old man with Klinefelter syndrome combined with Kartagener syndrome causing primary infertility. INTERVENTION(S): Testicular sperm extraction (TESE) and intracytoplasmic sperm injection (ICSI). MAIN OUTCOME MEASURE(S): Sperm recovery, fertilization, and live birth. RESULT(S): Ovulation induction of the female partner, recovery of spermatozoa by TESE from the male partner and ICSI of 9 metaphase II oocytes resulted in two fertilized oocytes. The delivery of a healthy boy with normal anatomy and 46,XY karyotype was achieved after the transfer of only one 4-cell grade 1 embryo. CONCLUSION(S): To our knowledge, this case with nonmosaic Klinefelter syndrome combined with Kartagener's syndrome is unique and demonstrates the revolutionary aspects of assisted reproductive technologies (ART) concerning male factor infertility.