The choice of embryo transfer catheter affects embryo implantation after IVF

OBJECTIVE: Comparison of two transfer catheters in an IVF program. DESIGN: Prospective, randomized clinical study. SETTING: A private tertiary care center for ART. PATIENT(S): 66 patients < 38 years of age undergoing IVF and/or ICSI. INTERVENTION(S): Patients were randomly assigned to undergo ET using the Tomcat catheter (n = 32) or the TDT catheter (n = 34). MAIN OUTCOME MEASURE(S): Primary outcome measures were implantation and pregnancy rates. Secondary outcome measures were contamination with blood and/or mucus on the tip of the catheter, cramping or patient discomfort, and time required to complete ET. RESULT(S): Use of the Tomcat catheter resulted in significantly higher implantation (25.2% vs. 8.4%) and clinical pregnancy rates (47% vs. 14.7%) compared with the TDT catheter. All secondary outcome measures were similar for both catheters. CONCLUSION(S): The choice of ET catheter may affect the success of IVF-ET cycles. Use of the Tomcat catheter compared with the TDT catheter seems to result in significantly better efficiency of the ET procedure and is more cost effective.     

Endometrial adenocarcinoma--presenting pathology is a poor guide to surgical management

We aimed to evaluate the correlation between the histological grade of endometrial cancer diagnosed on endometrial biopsy or curettage, with the definitive grade and stage of lesion as determined by surgery and histopathological examination and to make recommendations about the suitability of conservative surgery based on pre-operative determination of the grade of endometrial adenocarcinoma. A retrospective review of all patients with endometrial adenocarcinoma presenting to the Queensland Centre for Gynaecological Cancer from 1 January 1996 to 31 December 1998 was undertaken. Clinical and pathological data was abstracted from medical records and case notes of 460 patients. All histological specimens were prospectively reviewed by a panel consisting of gynaecologic pathologists, gynaecologic oncologists and other doctors involved in the treatment of patients with gynaecological malignancies. The percentage of patients whose management would have been optimised by full surgical staging at the time of initial surgery was calculated. Only 60%, 71%, and 84 % of the patients with a presenting diagnosis of grade 1, 2 and 3 endometrial adenocarcinomas respectively had this confirmed on final histopathology. Furthermore, using established criteria, 30%, 46% and 100% of patients presenting with grade 1, 2 and 3 endometrial adenocarcinoma required full surgical staging at the time of their primary surgery There is poor correlation between the pre-operative grade of endometrial cancer and the grade as determined on analysis of the resected uterus. The correlation is poorest with grade 1 endometrial adenocarcinoma, where strongest consideration is given to conservative surgery and the avoidance of subspecialty referral. There is a strong argument that all patients with a diagnosis of endometrial cancer made on endometrial biopsy or curettage, regardless of grade of malignancy, should be offered surgery where the option to perform concurrent comprehensive surgical staging is available.     

P53-status in primary ovarian carcinomas, ovarian metastases of neoplasms in other sites and benign ovarian tumors: predictive value in comparison to histopathological parameters

OBJECTIVE: The purpose of this study was to determine whether the tumor suppressor gene p53 can be used as a prognosis factor to assess individual patient risk in primary ovarian carcinoma. MATERIALS AND METHODS: The concentration of the mutated, as well as the wild type p53 was examined in 98 cases of ovarian carcinoma. Among 98 ovarian tumors examined, 77 were primary carcinomas, 14 tumors were metastasis of foreign tumors, and 7 were benign ovarian tumors. The pan-53 ELISA from Fa. Dianova was used to test for the p53 protein. RESULTS: The p53 protein concentration exhibited a wide range in the different tissue samples. Benign tumors contained significantly lower p53 concentrations than malignant tumors. After the data was analyzed using Kaplan-Meier, a p53 concentration of 507.1 pg/ml was established as cut-off point for assessing cancer prognosis as good or poor. Patients exhibiting p53 concentrations over 507.1 pg/ml had a median life expectancy of 20 months, and patients exhibiting lower tumor concentrations of p53 had a life expectancy of over 70 months. A significant relationship between patient life expectancy could also be shown for tumor stage and type, whereas not for tumor grading. CONCLUSIONS: Based on the results of this study, the routine measurement of p53 may allow for a better prognostic assessment of life expectancy of patients with primary ovarian carcinoma.     

Needle biopsy vs. conventional surgical biopsy - biochemical analysis of various prognostic factors

OBJECTIVE: In which way is the biochemical analysis of fine needle biopsy comparable to the biochemical analysis of conventional surgical biopsy samples in the examination of prognosis factors in mammary carcinomas. MATERIAL AND METHODS: Conventional surgical biopsy and fine needle biopsy were performed on 63 mammary carcinomas. The results from the biochemical analysis of tissue samples, from each form of biopsy, with respect to estradiol and progesterone receptor, UPA and PAI-1, as well as Kathepsin D and the EGF receptor, were compared and statistically analyzed. RESULTS: When compared to conventional tissue biopsy samples, the sensitivity and specificity of the measured prognosis factors in fine needle biopsy tissue were variable for each parameter, but fell within the statistically safe margin of 86 to 100%. CONCLUSIONS: The biochemical analysis of the prognosis factors found in fine needle biopsy samples showed that fine needle biopsy is a viable alternative to intraoperative conventional surgical biopsy.     

Gestational carrier is an optimal method for pregnancy in patients with vaginal agenesis (Rokitansky syndrome)

OBJECTIVE: To evaluate the results of successful pregnancy for patients with Mayer-Rokitansky-Kuster-Hauser syndrome using a gestational carrier. METHODS: All gestational carrier patients who attended our infertility clinic between 1995 and 2002 were reviewed for this study. Of the patients, 6 women with MRKH syndrome had 12 ovarian stimulation cycles, which resulted in 12 fresh and 5 frozen embryo transfers into six gestational carriers. RESULTS: The mean number (+/-SD) of embryos obtained per cycle was 4.8 (+/-2.9). Either two (n = 15) or three (n = 2) embryos were transferred to the gestational carrier. Three pregnancies were achieved following fresh embryo transfer, which included one clinical pregnancy that ended in spontaneous abortion, a singleton, and a set of twins. The pregnancy rate for fresh embryo transfer was 25% per retrieval and 50% per patient. No pregnancy was achieved following frozen embryo transfer. CONCLUSION: Gestational carrier is shown to be an effective treatment for patients with Mayer-Rokitansky-Kuster-Hauser syndrome.     

Aromatase inhibition for ovarian stimulation: future avenues for infertility management

Ovarian stimulation is applied during infertility management either alone or in conjunction with intrauterine insemination and assisted reproductive technologies. At the present time, the two main medications used for ovarian stimulation include an oral antiestrogen, clomiphene citrate, and injectable gonadotropins. In spite of the high ovulation rate with the use of clomiphene citrate, the pregnancy rate is much lower. In clomiphene citrate failures, gonadotropin injections have generally been used as the next treatment option. Treatment with gonadotropins is difficult to control and characteristically associated with increased risk of severe ovarian hyperstimulation syndrome and high multiple pregnancies. Therefore, an effective oral treatment that could be used without risk of hyperstimulation and with minimal monitoring is the preferred therapy. We hypothesize that aromatase inhibitors can be administered early in the follicular phase to induce ovulation by releasing the hypothalamus or pituitary from estrogen negative feedback. Based on this hypothesis, we have reported the success of aromatase inhibitors in induction and augmentation of ovulation in addition to improving ovarian response to gonadotropin stimulation. Moreover, there are other potential applications for aromatase inhibitors in infertility management, including improving implantation in assisted reproduction and in-vitro maturation.     

Patient‐level Factors and the Quality of Care Delivered in Pediatric Emergency Departments

Objective

Quality of care delivered to adult patients in the emergency department (ED) is often associated with demographic and clinical factors such as a patient's race/ethnicity and insurance status. We sought to determine whether the quality of care delivered to children in the ED was associated with a variety of patient‐level factors.

Methods

This was a retrospective, observational cohort study. Pediatric patients (<18 years) who received care between January 2011 and December 2011 at one of 12 EDs participating in the Pediatric Emergency Care Applied Research Network (PECARN) were included. We analyzed demographic factors (including age, sex, and payment source) and clinical factors (including triage, chief complaint, and severity of illness). We measured quality of care using a previously validated implicit review instrument using chart review with a summary score that ranged from 5 to 35. We examined associations between demographic and clinical factors and quality of care using a hierarchical multivariable linear regression model with hospital site as a random effect.

Results

In the multivariable model, among the 620 ED encounters reviewed, we did not find any association between patient age, sex, race/ethnicity, and payment source and the quality of care delivered. However, we did find that some chief complaint categories were significantly associated with lower than average quality of care, including fever (–0.65 points in quality, 95% confidence interval [CI] = –1.24 to –0.06) and upper respiratory symptoms (–0.68 points in quality, 95% CI = –1.30 to –0.07).

Conclusion

We found that quality of ED care delivered to children among a cohort of 12 EDs participating in the PECARN was high and did not differ by patient age, sex, race/ethnicity, and payment source, but did vary by the presenting chief complaint.

     

Prion protein amyloidosis with divergent phenotype associated with two novel nonsense mutations in PRNP

Stop codon mutations in the gene encoding the prion protein (PRNP) are very rare and have thus far only been described in two patients with prion protein cerebral amyloid angiopathy (PrP-CAA). In this report, we describe the clinical, histopathological and pathological prion protein (PrP^Sc) characteristics of two Dutch patients carrying novel adjacent stop codon mutations in the C-terminal part of PRNP, resulting in either case in hereditary prion protein amyloidoses, but with strikingly different clinicopathological phenotypes. The patient with the shortest disease duration (27 months) carried a Y226X mutation and showed PrP-CAA without any neurofibrillary lesions, whereas the patient with the longest disease duration (72 months) had a Q227X mutation and showed an unusual Gerstmann-Sträussler-Scheinker disease phenotype with numerous cerebral multicentric amyloid plaques and severe neurofibrillary lesions without PrP-CAA. Western blot analysis in the patient with the Q227X mutation demonstrated the presence of a 7 kDa unglycosylated PrP^Sc fragment truncated at both the N- and C-terminal ends. Our observations expand the spectrum of clinicopathological phenotypes associated with PRNP mutations and show that a single tyrosine residue difference in the PrP C-terminus may significantly affect the site of amyloid deposition and the overall phenotypic expression of the prion disease. Furthermore, it confirms that the absence of the glycosylphosphatidylinositol anchor in PrP predisposes to amyloid plaque formation.     

EGF enhances the survival of dopamine neurons in rat embryonic mesencephalon primary cell culture.

Epidermal growth factor (EGF) immunoreactive material has been demonstrated to be present in the basal ganglia. In this study, we investigated the effect of EGF on cells cultured from 16-day embryonic rat mesencephalon, which included dopamine neurons that project to the striatum in vivo. EGF receptors were detected in untreated cultures by [125I]-EGF binding. Treatment of the cultures with EGF resulted in up to 50-fold increases in neuronal high-affinity dopamine uptake. Scatchard analysis of uptake kinetics and counting of tyrosine hydroxylase-immunoreactive cells suggest that the effect of EGF on uptake is due to increased survival and maturation of dopaminergic neurons. By contrast, the high-affinity uptake for serotonin was increased only threefold over its controls. There was no significant effect on high-affinity gamma-aminobutyric acid (GABA) uptake. These results suggest that EGF is acting as a neurotrophic agent preferential for dopaminergic neurons in E16 mesencephalic cultures. Immunocytochemistry for glial fibrillary acidic protein demonstrated an increase in astroglia with EGF treatment. Fluorodeoxyuridine, an agent that is toxic to proliferating cells was able to eliminate the effect of EGF on dopamine uptake, suggesting that EGF may be increasing dopaminergic cell survival largely through a population of dividing cells.     

Clinical trial of iproplatin (cis-dichloro-trans-dihydroxy-bis-isopropylamine platinum IV,CHIP) in patients with advanced breast cancer

Summary Twenty-five women with advanced breast cancer were treated in a phase II trial of iproplatin 275 mg/m² administered intravenously every 4 weeks. All patients had measurable or evaluable indicator lesions, and had undergone treatment with no more than one previous chemotherapy regimen, including adjuvant chemotherapy. Two of the twenty-four evaluable patients (8%) experienced major therapeutic responses. One patient had a complete regression of pulmonary nodules lasting 18 + months; another had a partial regression of metastatic disease in the liver (4 months). The inevaluable patient was ineligible for the study because of previous radiation to the indicator lesions on her chest wall; nonetheless, she experienced a 10 month partial regression of those nodules. Myelosuppression was generally dose limiting; thrombocytopenia was more profound, but leukopenia was more prolonged. Nausea, vomiting, diarrhea, and general malaise were prominent toxicities, and led to discontinuation of therapy in 4 patients. Iproplatin has limited activity in previously treated women with advanced breast cancer.