Pathogenic missense variation in PABPC1L/EPAB causes female infertility due to oocyte maturation arrest at the germinal vesicle stage.

Women undergoing controlled ovarian hyperstimulation prior to in vitro fertilization (IVF) are treated using various protocols to induce multiple follicular growths. Complete failure of all oocytes to mature during IVF cycles is rare; however, it is a known cause of primary female infertility. Recently, pathogenic variations in a few genes have been identified in women with oocyte maturation defects; however, the underlying genetic causes remain largely unknown.This study included a Turkish family comprising three sisters with recurring oocyte maturation arrest at the germinal vesicle stage after multiple ovarian stimulations. Exome sequencing revealed a homozygous missense variant (c.1037C>T, p.Ala346Val) in the EPAB gene (also known as PABPC1L) in all three affected sisters, which was either absent or heterozygous in the unaffected family members. Functional experiments confirming the pathogenicity of the variant were performed by transfecting HEK293T cells and demonstrated the instability and increased rate of proteolysis of the mutated PABPC1L/EPAB protein. The identified variant, located in the well-conserved fourth RNA recognition motif (RRM4), in silico 3D modelling suggested changes in the physical properties of the pathogenic variant of PABPC1L/EPAB. Our findings validate PABPC1L/EPAB as an essential genetic contributor to the oocyte maturation process in humans and have direct implications for the genetic counselling of patients and their family members.

Evaluation of Dual Trigger with Combination of Gonadotropin-Releasing Hormone Agonist and Human Chorionic Gonadotropin in Improving Oocyte-Follicle Ratio in Normo-Responder Patients.

OBJECTIVE: Our aim was to compare the efficacy of two triggering method one with dual triggering with gonadotropin-realising hormon (GnRH) agonist plus standard dosage human chorionic gonadotropin (hCG) and the other with hCG only for final oocyte maturation on oocyte/follicle ratio and pregnancy rates in normoresponders in GnRH antagonist cycles in invitro fertilization-intrastoplasmic sperm injection (IVF-ICSI). MATERIAL METHODS: In this retrospective study, all patients underwent GnRH antagonist protocol. When at least ≥3 follicles reached ≥17 mm diameter, 116 patients received dual trigger with GnRH agonist plus hCG (1mg Leuprolide acetate plus 10.000 IU uhCG) and 178 patients received uhCG (10.000 IU u hCG) for final oocyte maturation. All follicles ≥10 mm diameter were aspirated. Number of oocytes and metaphase II oocytes retrieved per aspirated follicles, implantation rate, and clinical pregnancy rate per cycle was recorded. RESULTS: There was no statistically significant difference in terms of metaphase II oocyte ratio per aspirated follicle, implantation rate and clinical pregnancy rate between the dual trigger group and hCG only group (45.7% vs. 51%; 35.4% vs.30.3% and 45%vs. 40% respectively). Oocyte/ follicle ratio was significantly higher in dual trigger group (68.2%vs 63.8% p=0,028). CONCLUSIONS: Dual triggering in normal responders with a GnRH-agonist and a standard dosage of hCG is superior to hCG only protocol in terms of oocyte/follicle ratio but does not improve metaphase II oocyte, implantation and clinical pregnancy rates in GnRH-antagonist cycles. Dual triggering method may be beneficial in patients with immature oocytes and emty follicle syndrome.

Aortic stiffness in patients with wilson's disease.

AIM: Wilson's disease (WD) presents with different phenotypes. Neurologic and liver involvement in WD are well documented. Few reports demonstrated cardiac and vascular involvement. Several studies showed an association between serum copper levels and atherosclerosis. Although WD is the prototype disease of copper metabolism, atherosclerosis has not been studied yet. The aim of this study is to assess aortic stiffness in WD. MATERIALS AND METHODS: Aortic pulse wave velocity (PWV), augmentation pressure (AP), augmentation index (AIx), central aortic systolic, diastolic, mean, and pulse pressures were measured using SphygmoCor (AtCor Medical) device in 32 patients with WD and 24 healthy controls. RESULTS: Patients with WD and healthy controls were similar in terms of age sex, body mass index (BMI), and liver and kiney functions. However, patients with WD were anemic and thrombocytopenic. Echocardiographic parameters including left ventricular, atrial dimensions, and systolic and diastolic functions were similar between two groups. Patients with WD and healthy controls were compared. Baseline characteristics including age, sex, and BMI did not differ between groups. Central aortic systolic, diastolic, mean, and pulse pressures were similar between the groups. AP, AIx, and PWV did not differ between groups as well. CONCLUSION: Aortic stiffness in WD was similar in healthy controls.

Serum endocan levels in patients with cardiac syndrome X.

BACKGROUND: Endocan is a recently introduced marker of endothelial dysfunction and is also associated with inflammation and atherosclerosis. To date, the relationship between cardiac syndrome X (CSX) and endocan has not been studied. The objective of this study was to compare the serum endocan levels of patients with CSX with those of control subjects. PATIENTS AND METHODS: In this study, 50 patients were included in the CSX group and 28 patients in the control group. Patients with pathological conditions that could potentially influence endothelial functions were excluded. Endocan serum concentrations were measured using an enzyme-linked immunosorbent assay. RESULTS: The mean endocan level of the CSX group was significantly higher than that of the control group (3051.3 ± 1900.5 ng/l vs. 2088.1 ± 522.2 ng/l; p = 0.002). There was no difference between the two groups in terms of age, gender, hypertension, diabetes mellitus, dyslipidemia, and smoking status. In receiver operating characteristic (ROC) curve analysis, endocan levels greater than 2072 ng/l had a 72% sensitivity and 54% specificity (p = 0.002) for accurately predicting a diagnosis of CSX. CONCLUSION: The results of this study suggest that patients with CSX have higher endocan levels. Therefore, endocan may be valuable in helping uncover the underlying pathogenesis of CSX.