Association between early embryo morphokinetics plus cumulus cell gene expression and assisted reproduction outcomes in polycystic ovary syndrome women.

RESEARCH QUESTION: Can a combination of time-lapse morphokinetic parameters and cumulus cell gene expression in polycystic ovary syndrome (PCOS) women be used to predict assisted reproductive treatment outcome? DESIGN: A total of 547 embryos from 100 intracytoplasmic sperm injection (ICSI) cycles were evaluated. Fifty women with PCOS and 50 women who were categorized as tubal factor infertility were recruited. Time-lapse records were annotated for time to pronuclear fading (tPNf), time to 2 to 8 cells (t2-t8), reverse cleavage, direct cleavage and also for the presence of multinucleation. Expression levels of three genes involved in mitotic divisions, diaphanous-related formin 2 (DIAPH2), nibrin (NBN) and NIMA-related protein kinase (NEK4), were measured in 100 associated cumulus cell samples using quantitative real-time polymerase chain reaction. RESULTS: Expression of DIAPH2 and NBN was significantly higher in the embryos of PCOS patients that resulted in implantation, biochemical and clinical pregnancies as well as live birth compared with embryos that were negative for these outcomes (P <0.01). However, in the tubal factor group, NBN gene expression was significantly higher in embryos resulting in biochemical pregnancy, clinical pregnancy and live birth (P <0.01) only. Multivariate logistic regression analysis showed that tPNf together with DIAPH2 gene expression were independent prognostic factors of clinical pregnancy rate and live birth in both groups. CONCLUSIONS: Some time-lapse embryo parameters may be related to cumulus gene expression and clinical outcome. Furthermore, the expressions of cumulus cell genes involved in mitotic divisions are significantly associated with ICSI outcome using Day 3 embryo transfer.

Assessing ICSI outcome by combining non-invasive indicators: Early time-lapse morphokinetics and apoptosis in associated cumulus cells among women with the polycystic ovarian syndrome.

Cumulus cells features and embryo developmental events can be considered as noninvasive indicators for embryo selection and clinical outcomes. A combination of time-lapse morphokinetic parameters and cumulus cell apoptosis in women with polycystic ovarian syndrome (PCOS) was evaluated for predicting pregnancy outcome. We assessed a total of 547 embryos from 100 intracytoplasmic sperm injection (ICSI) cycles. Time-lapse records were interpreted in time to pronuclear fading (tPNf), time to 2 to 8 cells (t2-t8), direct cleavage, reverse cleavage, and also for the presence of multinucleation. Percentages of apoptosis were identified in 100 associated cumulus cell samples using the TDT-mediated dUTP-biotin nick end-labeling assay. The significant decrease of apoptotic cumulus cells was detected in patients with chemical and clinical pregnancies as well as live birth among patients PCOS and in the tubal infertility group (p > 0.05). Furthermore, significantly higher implantation rate and also significantly lower cases of early pregnancy loss were observed in the group of oocytes with less apoptotic cumulus cells. Multivariate logistic regression analysis showed that tPNf together with cumulus cell apoptosis were independent prognostic factors of chemical pregnancy, clinical pregnancy rate, and live birth. Time-lapse embryo parameters may not reflect the cumulus cell apoptosis rate. However, the rate of apoptotic cumulus cells is significantly associated with ICSI outcome using Day 3 embryo transfer.

Moderate Ischemic Mitral Regurgitation After Posterolateral Myocardial Infarction in Sheep Alters Left Ventricular Shear but Not Normal Strain in the Infarct and Infarct Borderzone.

BACKGROUND: Chronic ischemic mitral regurgitation (CIMR) is associated with poor outcome. Left ventricular (LV) strain after posterolateral myocardial infarction (MI) may drive LV remodeling. Although moderate CIMR has been previously shown to affect LV remodeling, the effect of CIMR on LV strain after posterolateral MI remains unknown. We tested the hypothesis that moderate CIMR alters LV strain after posterolateral MI. METHODS: Posterolateral MI was created in 10 sheep. Cardiac magnetic resonance imaging with tags was performed 2 weeks before and 2, 8, and 16 weeks after MI. The left and right ventricular volumes were measured, and regurgitant volume indexed to body surface area (regurgitant volume index) was calculated as the difference between left ventricle and right ventricle stroke volumes divided by body surface area. Three-dimensional strain was calculated. RESULTS: Circumferential strain (Ecc) and longitudinal strain (Ell) were reduced in the infarct proper, MI borderzone, and remote myocardium 16 weeks after MI. In addition, radial circumferential (Erc) and radial longitudinal (Erl) shear strains were reduced in remote myocardium but increased in the infarct and borderzone 16 weeks after MI. Of all strain components, however, only Erc was affected by regurgitant volume index (p = 0.0005). There was no statistically significant effect of regurgitant volume index on Ecc, Ell, Erl, or circumferential longitudinal shear strain (Ecl). CONCLUSIONS: Moderate CIMR alters radial circumferential shear strain after posterolateral MI in sheep. Further studies are needed to determine the effect of shear strain on myocyte hypertrophy and the effect of mitral repair on myocardial strain.

Myofilament dysfunction contributes to impaired myocardial contraction in the infarct border zone.

After myocardial infarction, a poorly contracting nonischemic border zone forms adjacent to the infarct. The cause of border zone dysfunction is unclear. The goal of this study was to determine the myofilament mechanisms involved in postinfarction border zone dysfunction. Two weeks after anteroapical infarction of sheep hearts, we studied in vitro isometric and isotonic contractions of demembranated myocardium from the infarct border zone and a zone remote from the infarct. Maximal force development (Fmax) of the border zone myocardium was reduced by 31 ± 2% versus the remote zone myocardium (n = 6/group, P < 0.0001). Decreased border zone Fmax was not due to a reduced content of contractile material, as assessed histologically, and from myosin content. Furthermore, decreased border zone Fmax did not involve altered cross-bridge kinetics, as assessed by muscle shortening velocity and force development kinetics. Decreased border zone Fmax was associated with decreased cross-bridge formation, as assessed from muscle stiffness in the absence of ATP where cross-bridge formation should be maximized (rigor stiffness was reduced 34 ± 6%, n = 5, P = 0.011 vs. the remote zone). Furthermore, the border zone myocardium had significantly reduced phosphorylation of myosin essential light chain (ELC; 41 ± 10%, n = 4, P < 0.05). However, for animals treated with doxycycline, an inhibitor of matrix metalloproteinases, rigor stiffness and ELC phosphorylation were not reduced in the border zone myocardium, suggesting that doxycycline had a protective effect. In conclusion, myofilament dysfunction contributes to postinfarction border zone dysfunction, myofilament dysfunction involves impaired cross-bridge formation and decreased ELC phosphorylation, and matrix metalloproteinase inhibition may be beneficial for limiting postinfarct border zone dysfunction.

Left ventricular myocardial contractility is depressed in the borderzone after posterolateral myocardial infarction.

BACKGROUND: Contractility in the borderzone (BZ) after anteroapical myocardial infarction (MI) is depressed. We tested the hypothesis that BZ contractility is also decreased after posterolateral MI. METHODS: Five sheep underwent posterolateral MI. Magnetic resonance imaging (MRI) was performed 2 weeks before and 16 weeks after MI, and left ventricular (LV) volume and regional strain were measured. Finite element (FE) models were constructed, and the systolic material parameter, Tmax, was calculated in the BZ and remote myocardium by minimizing the difference between experimentally measured and calculated LV strain and volume. Sheep were sacrificed 17 weeks after MI, and myocardial muscle fibers were taken from the BZ and remote myocardium. Fibers were chemically demembranated, and isometric developed force, Fmax, was measured at supramaximal [Ca(2+)]. Routine light microscopy was also performed. RESULTS: There was no difference in Tmax in the remote myocardium before and 16 weeks after MI. However, there was a large decrease (63.3%, p = 0.005) in Tmax in the BZ when compared with the remote myocardium 16 weeks after MI. In addition, there was a significant reduction of BZ Fmax for all samples (18.9%, p = 0.0067). Myocyte cross-sectional area increased by 61% (p = 0.021) in the BZ, but there was no increase in fibrosis. CONCLUSIONS: Contractility in the BZ is significantly depressed relative to the remote myocardium after posterolateral MI. The reduction in contractility is due at least in part to a decrease in contractile protein function.

Staged repair of giant recurrent omphalocele and gastroschesis "camel-litter method"-a new technique.

The aim of this article is to present a new Technique of giant omphaloceles repair in neonatal period and also later in life in patients that the primary repair has been failed. From 1999 to 2006, seven consecutive children (male/female ratio 0.4) with giant omphalocele (n=6) and Gastroschesis (n=2) were underwent this new operation in our center. In this technique, there were two operations. The mean of hospital stay was 38 days (range, 23-42 days), and full enteral feeding was achieved on the 8 to 25 postoperative day (Mean, 14 day). The final closure, in all patients was achieved between the 14 to 32 days after the first operation (Mean, 21 day). Mechanical ventilation was necessary for the mean of 5 days (range, 2-8 days). All patients are alive and have no complication due to the operation (1 month-7 years). Giant omphalocele and Gastroschesis can be safely repaired. The placement of an intraperitoneal tissue expander and traction of abdominal muscles can create the needed space for closure in several weeks in patients with giant omphalocele/ Gastroschesis.

Moderate mitral regurgitation accelerates left ventricular remodeling after posterolateral myocardial infarction.

BACKGROUND: Chronic ischemic mitral regurgitation (MR) is associated with poor outcome. However, the effect of chronic ischemic MR on left ventricular (LV) remodeling after posterolateral myocardial infarction (MI) remains controversial. We tested the hypothesis that moderate MR accelerates LV remodeling after posterolateral MI. METHODS: Posterolateral MI was created in 10 sheep. Cardiac magnetic resonance imaging was performed 2 weeks before and 2, 8, and 16 weeks after MI. Left ventricular and right ventricular volumes were measured, and regurgitant volume was calculated as the difference between LV and right ventricle stroke volumes. RESULTS: Multivariate mixed effects regression showed that LV volumes at end diastole and end systole and LV sphericity were strongly correlated with both regurgitant volume (p < 0.0001, p = 0.0086, and p = 0.0007, respectively) and percent infarct area (p = 0.0156, p = 0.0307, and p < 0.0001, respectively). Conversely, whereas LV hypertrophy (LV wall volume) increased from 2 weeks to 16 weeks after MI, there was no effect of either regurgitant volume or percent infarct. CONCLUSIONS: Moderate MR accelerates LV remodeling after posterolateral MI. Further studies are needed to determine whether mitral valve repair is able to slow or reverse MI remodeling after posterolateral MI.

Twin fetus in fetu with immature teratoma: a case report and review of the literature.

Fetus in fetu is an extremely rare condition in which a fetus or fetus-like structure with a vertebral axis is seen in the body of its twin. This paper presents a case of fetus in fetu in a two- day-old female newborn who was referred for an abdominal mass, biliary vomiting, and feeding intolerance. After plain abdominal X-ray and ultrasonography, the patient underwent abdominal surgery with the primary diagnosis of teratoma or fetus in fetu. We found a retroperitoneal mass that consisted of double fetus in fetu and a separate undetermined mass. The pathologic examination confirmed double fetus in fetu and revealed a separate immature teratoma. She was discharged from the hospital after seven days in a healthy and normal condition. The level of serum alpha-fetoprotein was normal after three months of follow-up.

Partial cholecystectomy as a safe and viable option in the emergency treatment of complex acute cholecystitis: a case series and review of the literature.

Partial cholecystectomy (PC) is an alternative choice to standard cholecystectomy in situations with increased risk of Calot's components injury. We reported our experience with the patients treated with PC and reviewed the literature. Fifty-four patients with complex acute cholecystitis underwent PC, including conventional partial cholecystectomy (CPC; n = 48) and laparoscopic partial cholecystectomy (LPC; n = 6). The clinical diagnosis was verified by ultrasonography. In addition, we reviewed 1190 published cases (1972-2005) who underwent a "nonconventional" surgery for severe cholecystitis, including cholecystostomy, CPC, or LPC. Review of the literature, including our cases, showed a male:female ratio of 1.3:1. The major operative indication was severe acute cholecystitis. Procedures included cholecystostomy (65.8%) and PC (34.2%). In the follow-up (n = 1190), biliary leak (4.8%), retained stones (4.6%), recurrent symptoms (2.3%), wound infections (1.9%), persistent biliary fistula (0.9%), and prolonged biliary drainage (0.2%) were found, with an overall mortality rate of 9.4 per cent. In 133 patients, because of postoperative complications (e.g., recurrent symptoms, remaining common bile duct stones, or persistence of bile fistula), reoperation was necessary, including 121 cases (90.1%) of cholecystectomy, whereas the other 11 patients underwent other procedures such as common bile duct exploration or closure of the fistula. The surgical trend for complex acute cholecystitis treatment has been changed from only cholecystostomy to a spectrum of cholecystostomy, CPC, and LPC with the progressive increase of PC. The proportion of the LPC compared with CPC has also increased during recent years. It seems that PC is a safe procedure for treating complicated acute cholecystitis. Whether the indication and need for alternative techniques to standard cholecystectomy is changing should be evaluated in future studies.

Surgical treatment of patients with wandering spleen: report of six cases with a review of the literature.

Wandering spleen, which is defined as a spleen without peritoneal attachments, is a rare disease and a delay in the clinical and/or radiological diagnosis may lead to splenic torsion, infarction, and necrosis. Owing to the physiologic importance of the spleen, especially in children, and the risk of postsplenectomy sepsis, early diagnosis and splenopexy are recommended. In the present article, we describe the results of our management of this rare problem on six patients, and we review all available literature from 1895 to 2005. Briefly, our technique includes flap creation from parietal peritoneum and settlement of spleen in the fossa splenica. Free edges of this flap are stitched to the stomach and the left end of transverse colon and the beginning of the descending colon. The body of the stomach was stitched to the abdominal wall to prevent gastric volvulus, while the fundus region was fixed to the diaphragm to support the spleen. Finally, an omental patch was stitched to the intact abdominal wall above the flap. In conclusion, the procedure of splenopexy without using mesh is considered to be a safe and curative modality for wandering spleen without imposing any undue risk of infection or foreign material reaction.