Live birth rates and perinatal outcomes when all embryos are frozen compared with conventional fresh and frozen embryo transfer: a cohort study of 337,148 in vitro fertilisation cycles

BACKGROUND: It is not known whether segmentation of an in vitro fertilisation (IVF) cycle, with freezing of all embryos prior to transfer, increases the chance of a live birth after all embryos are transferred. METHODS: In a prospective study of UK Human Fertilisation and Embryology Authority data, we investigated the impact of segmentation, compared with initial fresh embryo followed by frozen embryo transfers, on live birth rate and perinatal outcomes. We used generalised linear models to assess the effect of segmentation in the whole cohort, with additional analyses within women who had experienced both segmentation and non-segmentation. We compared rates of live birth, low birthweight (LB

Approaches to improve the diagnosis and management of infertility

Recent advances in our understanding of the causes of infertility and of assisted reproductive technology (ART) have led to the development of complex diagnostic tools, prognostic models and treatment options. The Third Evian Annual Reproduction (EVAR) Workshop Meeting was held on 26-27 April 2008 to evaluate evidence supporting current approaches to the diagnosis and management of infertility and to identify areas for future research efforts. Specialist reproductive medicine clinicians and scientists delivered presentations based on published literature and ongoing research on patient work-up, ovarian stimulation and embryo quality assessment during ART. This report is based on the expert presentations and subsequent group discussions and was supplemented with publications from literature searches and the authors' knowledge. It was agreed that single embryo transfer (SET) should be used with increasing frequency in cycles of ART. Continued improvements in cryopreservation techniques, which improve pregnancy rates using supernumerary frozen embryos, are expected to augment the global uptake of SET. Adaptation and personalization of fertility therapy may help to optimize efficacy and safety outcomes for individual patients. Prognostic modelling and personalized management strategies based on individual patient characteristics may prove to represent real progress towards improved treatment. However, at present, there is limited good-quality evidence to support the use of these individualized approaches. Greater quality control and standardization of clinical and laboratory evaluations are required to optimize ART practices and improve individual patient outcomes. Well-designed, good-quality studies are required to drive improvements to the diagnosis and management of ART processes

Ultrastructural characterization of the erythroid cells in a novel case of congenital anemia

Congenital dyserythropoietic anemia type I (CDA-I) is a rare genetic disease that affects erythropoiesis. On the other hand, hemoglobin H (HbH) disease is a severe form of alpha-thalassemia. We herein present ultrastructural and immunocytochemical data concerning the first reported case of congenital anemia with clinical and molecular diagnosis of HbH disease complicated by CDA-I-specific dysplasies of the erythroid cells. Fine structure and transmission electron microscope immumolabeling analysis of the bone marrow and peripheral blood samples were consistent with a potential co-existence of the two defects in the same patient, producing a novel and diagnostically important dyserythropoictic profile. In the patient under investigation both nuclear and plasma membrane of the erythroid cells are almost equally defective. The unknown defect causes the concomitant precipitation of beta- and alpha-globin chains (or hemoglobin), along with an unidentified protein(s). The unusual inclusions gain access to the euchromatin area and exhibit higher affinity for the plasma membrane than the classic inclusions of precipitated alpha- or beta-globin chains seen in thalassemia. The affected erythroid precursors are presented with severe nuclear distortions, endonuclear globin loads, morphological evidence of apoptosis and increased erythrophagocytosis. Plasma membrane distortions and the rate of protein precipitation were aggravated with differentiation. Our findings provide additional evidence for a specific activation of a beta-thalassemic-like mechanism in CDA-I, containing not only the hemoglobin biosynthesis as previously suggested, and interpret the prototypal hematological portrait, which is an HbH disease, modified and partially counterbalanced by the effect of CDA-I or an unidentified CDA-I-like disease. The reported data describe the complexity of the interactions between the CDA-I and the HbH disease, revealing essential pathogenic events of the novel anemia and, indirectly, of the CDA-I. (C) 2003 Elsevier Science (USA). All rights reserved

RETICULOCYTE COUNTING IN THALASSEMIC AND OTHER CONDITIONS WITH THE R-1000 SYSMEX ANALYZER

Precise reticulocyte counts are difficult to obtain by the manual method when their percentage in the blood is low or normal. In these instances, rapid reticulocyte counting by flow cytometry appears to offer more accuracy and precision. The purpose of this study was to establish reticulocyte counts in heterozygous beta-thalassemia for reference purposes and to evaluate the performance of the recently introduced apparatus R-1000 (Sysmex) in the very heterogeneous thalassemic and sickle-cell syndromes. We studied a total of 364 samples; 102 heterozygous beta-thalassemia carriers, 180 normal matched controls, 36 patients with thalassemia major or intermedia, and 46 patients with various sickle-cell syndromes. Reticulocyte counts (both as percentage and as total number) were higher in heterozygous beta-thalassemia than in normal controls (p < 0.001) and showed an inverse correlation with the respective hemoglobin values (p < 0.001). These results confirm the proposed slightly increased erythropoietic activity in heterozygous beta-thalassemia carriers. A drawback of the technique is that the reticulocyte-platelet discrimination error is signaled frequently in all conditions displaying a marked red cell heterogeneity, especially when these are associated with high reticulocyte numbers. This calls probably for readjustment of the corresponding algorithm. In addition, all these conditions show a significantly increased auramine-O mature red-cell nonspecific fluorescence

Physiologically important secondary modifications of red cell membrane in hereditary spherocytosis-evidence for in vivo oxidation and lipid rafts protein variations

Hereditary spherocytosis (HS) is a heterogeneous group of disorders. The abnormal red cell morphology (resulting in shortened cell survival) is due to a primary deficiency in spectrin, ankyrin-1, band 3 or protein 4.2. Secondary protein deficiencies are often observed and may be involved in the outcome of the disease. In the present study, we searched for secondary erythrocyte membrane protein alterations in HS, including the lipid raft associated proteins and the oxidative index. For this purpose, 12 patients with clinical and laboratory diagnosis of mild to typical HS were examined. Erythrocyte membrane ghosts and skeletons were subjected to SDS-PAGE and immunoblotting analysis using antibodies against red cell membrane proteins and DNP moiety, after 2,4-dinitrophenylhydrazine derivatization. Protein deficiencies, degradation, aggregation and enhanced binding of cytoplasmic components, band 8, hemoglobin and immunoglobulins G to the membrane as well as increased oxidative index, were found in the majority of the HS patients. Proportion of the membrane- and skeleton-bound globin was oxidized/denatured Hb or hemichromes and crosslinkings. Some HS membranes are deficient in lipid rafts proteins and contain sorcin. A context of these distortions is more pronounced in typical HS cases compared to the mild ones. Similar defects in thalassemia and senescent RBCs are dictated by increased oxidative stress and are positively correlated with perturbations in membrane properties. These data add some new insight in the field of HS pathophysiology and clinical variability. © 2006 Elsevier Inc. All rights reserved