RESUMO
Thrombophilia and impaired placental vasculature are a major cause of adverse pregnancy outcome. In 2007, a new hereditary factor for obstetric complications and recurrent pregnancy loss (RPL) was identified as a sequence variation in the core promoter of the annexin A5 gene, ANXA5, called the M2 haplotype. M2 carriership has been demonstrated in couples with recurrent miscarriage and its origin is embryonic rather than specifically maternal, confirmed by subsequent papers. The M2 haplotype is the first report of a hereditary factor related to pregnancy pathology caused by embryonic-induced anticoagulation. It has been demonstrated that couples with RPL had equal and significantly increased M2 carriership and that maternal and paternal carriership confers equal risk. Given its importance for patients with RPL, and potentially implantation failure, this study assessed the incidence of carrier status for the M2 ANXA5 haplotype in both the male and female of couples attending five CARE IVF centres. In 314 patients (157 couples), 44% of couples (one or both partners), 24% of females, 26% of males and 37% of couples with unexplained infertility were M2 carriers. This high incidence has provoked further urgent studies on specific patient populations and on the value of post embryo-transfer therapy.
Assuntos
Aborto Habitual/genética , Anexina A5/genética , Heterozigoto , Aborto Habitual/epidemiologia , Adulto , Feminino , Fertilização in vitro , Triagem de Portadores Genéticos , Haplótipos , Humanos , Masculino , Pessoa de Meia-Idade , Regiões Promotoras Genéticas , Trombofilia/epidemiologia , Trombofilia/genéticaRESUMO
Insulin resistance is a recognized feature of PCOS (polycystic ovary syndrome). However, the molecular reason(s) underlying this reduced cellular insulin sensitivity is not clear. The present study compares the major insulin signalling pathways in skeletal muscle isolated from PCOS and controls. We measured whole-body insulin sensitivity and insulin signalling in skeletal muscle biopsies taken before and after acute exposure to hyperinsulinaemia in nine women diagnosed with PCOS and seven controls. We examined the expression, basal activity and response to in vivo insulin stimulation of three signalling molecules within these human muscle samples, namely IRS-1 (insulin receptor substrate-1), PKB (protein kinase B) and ERK (extracellular-signal-regulated kinase) 1/2. There was no significant difference in the expression, basal activity or activation of IRS-1 or PKB between PCOS and control subjects. However, there was a severe attenuation of insulin stimulation of the ERK pathway in muscle from all but two of the women with PCOS (the two most obese), and an accompanying trend towards higher basal phosphorylation of ERK1/2 in PCOS. These results are striking in that the metabolic actions of insulin are widely believed to require the IRS-1/PKB pathway rather than ERK, and the former has been reported as defective in some previous PCOS studies. Most importantly, the molecular defect identified was independent of adiposity. The altered response of ERK to insulin in PCOS was the most obvious signalling defect associated with insulin resistance in muscle from these patients.
Assuntos
Resistência à Insulina/fisiologia , Insulina/fisiologia , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Músculo Esquelético/enzimologia , Síndrome do Ovário Policístico/fisiopatologia , Adulto , Feminino , HumanosRESUMO
OBJECTIVE: To compare fixed daily doses of the recombinant FSH (rFSH) Gonal-F (150 IU vs. 225 IU) for ovarian stimulation in IVF-ET. DESIGN: Single-center prospective, randomized study. Assisted conception unit of a university hospital. One hundred twenty-four women aged 23-41 years participated in the study. Exclusion criteria were as follows: FSH of >10 IU/L, polycystic ovarian syndrome, one ovary or previous ovarian surgery, previous poor response to ovarian stimulation, or ovarian hyperstimulation syndrome (OHSS). INTERVENTION(S): Randomized to commence 150 IU or 225 IU of Gonal-F per day without dose alterations during treatment. MAIN OUTCOME MEASURE(S): Number of oocytes retrieved and total rFSH dose. RESULT(S): More oocytes were retrieved in women aged