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.

No abstract

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.

Measuring ovarian volume has been suggested as a possible screening test to assess a woman's ovarian reserve. For such a screening tool to be clinically useful, knowledge of its precision and reproducibility is essential. Recent advances in ultrasound scanning techniques allow the measurement of volumes in three dimensions rather than the traditional estimation from two dimensions. Transvaginal 2-dimensional (2D) and 3-dimensional (3D) ultrasound examinations were performed on 49 women attending a tertiary centre for investigation or treatment for subfertility between January and May 2006. Two observers calculated ovarian volume using both 2D (prolate ellipsoid formula) and 3D techniques [virtual organ computer-aided analysis (VOCAL)] with rotation steps of 30 degrees (3D-30). For the four comparisons (inter- and intra-observer; 2D and 3D-30) intraclass coefficients of 0.97 to 0.98, and standard errors ranging from 17% to 14% (for inter-observer 2D and intra-observer 3D, respectively) were obtained. The corresponding coefficients of repeatability ranged from 33% to 28%. These results suggest that measurement of transvaginal ovarian volumes using both 2D and 3D ultrasound is imprecise for individuals. The imprecision is greater for lower ovarian volumes, which may be important in clinical practice. The average of two or more measurements is likely to be more accurate than a single measurement.

Loss of donor anonymity reduced by half those willing to consider donation in all age groups. The future of this service depends on recruitment of donors willing to be identified. Consideration of older donors may be an option if adequate counselling occurs.