Successful in vitro fertilization in women with Fontan physiology

PurposePatients with single ventricle anatomy palliated with Fontan operation are at risk for thromboembolism, arrhythmia, and heart failure rendering pregnancy high risk or even contraindicated. Infertility and high rates of first trimester miscarriage are not uncommon. In vitro fertilization (IVF) with or without gestational surrogacy can be an option, but poses risks during ovarian stimulation, oocyte retrieval, and the post-procedural period. We present six cases of women with complex congenital heart disease status post Fontan operation who underwent successful IVF.MethodsCase series from a single-center tertiary care setting.ResultsIndications for referral were cardiac or fertility concerns for pregnancy of the congenital cardiologist. One woman had mild volume overload after oocyte retrieval requiring furosemide and one experienced post-operative colitis. There were no thrombotic complications.ConclusionsA multidisciplinary team-based approach can result in successful oocyte retrieval and IVF in women with complex congenital heart disease and Fontan physiology.     

Evaluation of the association between hereditary thrombophilias and recurrent pregnancy loss: a meta-analysis

BACKGROUND: Recurrent pregnancy loss (RPL) is a significant clinical problem. Recently, thrombophilias have been implicated as a possible cause. Factor V Leiden (FVL) and prothrombin gene (G20210A) mutations are the most common types of hereditary thrombophilias, but are usually undiagnosed because most carriers are asymptomatic. The relationship between FVL, G20210A, and RPL has been investigated with conflicting results. This study analyzed existing data to determine whether an association exists. METHODS: A systematic review of the literature was performed. Only case-control studies that defined RPL as 2 or more pregnancy losses in the first or second trimester and that confirmed mutations by DNA analysis were included. Sixteen studies were selected for the FVL meta-analysis and 7 for the G20210A analysis. Stratified and multivariate logistic regression analyses were performed with the use of aggregate data. Results were confirmed by means of fixed- and random-effects meta-analyses models. RESULTS: The combined odds ratios for the association between RPL and FVL and between RPL and G20210A were 2.0 (95% confidence interval, 1.5-2.7; P<.001) and 2.0 (95% confidence interval, 1.0-4.0; P =.03), respectively. Similar results were produced by the logistic regression and both fixed- and random-effects meta-analysis models. CONCLUSIONS: Carriers of FVL or prothrombin gene mutations have double the risk of experiencing 2 or more miscarriages compared with women without thrombophilias. Hereditary thrombophilias may be an unrecognized cause of RPL. We recommend testing for these mutations in women with RPL.     

Increase of intracellular Ca2+ and relocation of E-cadherin during experimental decompaction of mouse embryos

To determine the role of intracellular Ca²⁺ in compaction, the first morphogenetic event in embryogenesis, we analyzed preimplantation mouse embryos under several decompacting conditions, including depletion of extracellular Ca²⁺, blocking of Ca²⁺ channels, and inhibition of microfilaments, calmodulin, and intracellular Ca²⁺ release. Those treatments induced decompaction of mouse morulae and simultaneously induced changes in cytosolic free Ca²⁺ concentration and deregionalization of E-cadherin and fodrin. When morulae were allowed to recompact, the location of both proteins recovered. In contrast, actin did not change its cortical location with compaction nor with decompaction-recompaction. Calmodulin localized in areas opposite to cell–cell contacts in eight-cell stage embryos before and after compaction. Inhibition of calmodulin with trifluoperazine induced its delocalization while morulae decompacted. A nonspecific rise of intracellular free Ca²⁺ provoked by ionomycin did not affect the compacted shape. Moreover, the same decompacting treatments when applied to uncompacted embryos did not produce any change in intracellular Ca²⁺. Our results demonstrate that in preimplantation mouse embryos experimentally induced stage-specific changes of cell shape are accompanied by changes of intracellular free Ca²⁺ and redistribution of the cytoskeleton-related proteins E-cadherin, fodrin, and calmodulin. We conclude that intracellular Ca²⁺ specifically is involved in compaction and probably regulates the function and localization of cytoskeleton elements.     

Powerful anticonvulsant action of IL-1 receptor antagonist on intracerebral injection and astrocytic overexpression in mice

IL-1beta and its endogenous receptor antagonist (IL-1Ra) are rapidly induced by seizures in the rodent hippocampus. Exogenously applied IL-1beta prolongs seizures in an IL-1R type I-mediated manner. This effect depends on N-methyl-d-aspartate receptor activation. We report here that intrahippocampal application of recombinant IL-1Ra or its selective endogenous overexpression in astrocytes under the control of glial acidic fibrillary protein promoter potently inhibits motor and electroencephalographic seizures induced by bicuculline methiodide in mice. Accordingly, transgenic mice show a reduced seizure-related c-fos mRNA expression in various forebrain areas compared with their wild-type littermates. Recombinant IL-1Ra was ineffective in mice deficient in IL-1R type I, having per se a delayed onset to generalized convulsions. These results demonstrate that IL-1Ra mediates potent anticonvulsant effects acting on IL-1R type I and suggest that the balance between brain IL-1beta and IL-1Ra represents a crucial mechanism to control seizure generalization.     

Preserving female fertility following cancer treatment: Current options and future possibilities

Children and women of reproductive age are increasingly surviving cancer diagnoses, and therefore long‐term quality‐of‐life issues are of greater importance at the time of diagnosis. Cancer therapies including radiation and chemotherapy can be detrimental to fertility, and therefore many patients are motivated to preserve fertility prior to cancer treatment. The only highly successful method in preserving fertility to date is embryo cryopreservation, which may not be appropriate for some patients due to age, delay in treatment, cancer type and stage, as well as availability of an acceptable sperm donor. Alternative methods including oocyte cryopreservation and ovarian tissue banking may also preserve fertility while providing additional flexibility to patients. In vitro ovarian follicle maturation following tissue banking is one potential approach that would not require a delay in cancer therapy for ovarian stimulation, would not require an immediate sperm donor, and does not carry the risk of reintroducing malignant cells following tissue transplantation. In vitro follicle culture systems have resulted in successful live births in the mouse. However, many challenges must be addressed in translating the system to the human. This review summarizes current approaches to fertility preservation and discusses recent developments and future challenges in developing a human in vitro follicle culture system. Pediatr Blood Cancer 2009;53:289–295. © 2009 Wiley‐Liss, Inc.     

Efficacy of phytosterols and fish-oil supplemented high-oleic-sunflower oil rich diets in hypercholesterolemic growing rats

Phytosterols (P) and fish-oil (F) efficacy on high-oleic-sunflower oil (HOSO) diets were assessed in hypercholesterolemic growing rats. Controls (C) received a standard diet for 8 weeks; experimental rats were fed an atherogenic diet (AT) for 3 weeks, thereafter were divided into four groups fed for 5 weeks a monounsaturated fatty acid diet (MUFA) containing either: extra virgin olive oil (OO), HOSO or HOSO supplemented with P or F. The diets did not alter body weight or growth. HOSO-P and HOSO-F rats showed reduced total cholesterol (T-chol), non-high-density lipoprotein-cholesterol (non-HDL-chol) and triglycerides and increased HDL-chol levels, comparably to the OO rats. Total body fat (%) was similar among all rats; but HOSO-F showed the lowest intestinal, epididymal and perirenal fat. However, bone mineral content and density, and bone yield stress and modulus of elasticity were unchanged. Growing hypercholesterolemic rats fed HOSO with P or F improved serum lipids and fat distribution, but did not influence material bone quality.