Clinical use of monopronucleated zygotes following blastocyst culture and preimplantation genetic screening, including verification of biparental chromosome inheritance.

In assisted reproduction, embryos derived from monopronucleated (1PN) zygotes are considered abnormal and unsuitable for clinical use. Outcomes of 1PN-derived embryos designated for preimplantation genetic screening (PGS) were analysed. These embryos, especially from intracytoplasmic sperm injection (ICSI), were found to have a low developmental potential; 1PN and 2PN day 5 blastocyst development for IVF was 14.8% versus 36.4% (P < 0.0001), and for ICSI, 6.6% versus 34.0% (P < 0.0001), respectively. With the use of comparative genomic hybridization or next-generation sequencing, PGS was successfully carried out for 74 IVF and 32 ICSI 1PN-derived blastocysts, revealing adjusted abnormality rates of 39.7% and 40.6%, respectively. Additionally, 24 female 1PN-derived blastocysts underwent testing for biparental inheritance, with one ICSI-derived embryo demonstrating paternal only contribution, thus presenting a risk for complete hydatidiform molar pregnancy. Single embryo transfer of 20 IVF and six ICSI 1PN-derived blastocysts with no detectable abnormalities resulted in nine clinical pregnancies. Six have been delivered and three are ongoing, with no anomalies reported to date. The limitation of this study is that pronuclear status was determined through one static observation. The results suggest that 1PN-derived embryos, in which euploidy and biparental inheritance have been established, can provide a source of clinically useful embryos.

Barriers to genuine consumer and carer participation from the perspectives of Australian systemic mental health advocates.

BACKGROUND: Consumer and carer participation in mental health service development and evaluation has widespread nominal support. However, genuine and consistent participation remains elusive due to systemic barriers. AIMS: This paper explores barriers to reform for mental health services from the perspectives of consumers and carers actively engaged in advocating for improvements in the mental health system. METHOD: Qualitative research with two mental health systemic advocacy organisations analysed 17 strategic communication documents and nine interviews to examine barriers to reform and participation identified by consumer and carer advocates and staff. RESULTS: A number of individual-level barriers were described, however advocates gave more focus to systemic barriers, for which five themes emerged. These reflected lack of awareness, limited participation opportunities, slow progress for change, policy issues and mental health culture including stigma. CONCLUSIONS: Findings highlight systemic barriers to participation for consumer and carer advocates as a whole and the influence of these barriers on the individual experiences of those engaged in advocacy and representation work. Participants also emphasised the need for leadership to overcome some of these obstacles and move towards genuine consumer and carer participation and reform. Findings are discussed in the context of power within mental health systems.

Recruiting general practitioners for surveys: reflections on the difficulties and some lessons learned.

Surveys of GPs are essential to facilitate future planning and delivery of health services. However, recruitment of GPs into research has been disappointing with response rates declining over recent years. This study identified factors that facilitated or hampered GP recruitment in a recent survey of Australian GPs where a range of strategies were used to improve recruitment following poor initial responses. GP response rates for different stages of the survey were examined and compared with reasons GPs and leaders of university research networks cited for non-participation. Poor initial response rates were improved by including a questionnaire in the mail-out, changing the mail-out source from an unknown research team to locally known network leaders, approaching a group of GPs known to have research and training interests, and offering financial compensation. Response rates increased from below 1% for the first wave to 14.5% in the final wave. Using a known and trusted network of professionals to endorse the survey combined with an explicit compensation payment significantly enhanced GP response rates. To obtain response rates for surveys of GPs that are high enough to sustain external validity requires an approach that persuades GPs and their gatekeepers that it is worth their time to participate.

Clinical case presentation: life threatening Group A sepsis secondary to HyCoSy.

Hysterosalpingo contrast sonography (HyCoSy) is a commonly performed procedure in the investigation of infertility. Infection is an uncommon complication of this procedure. Should it occur, it is generally mild and amenable to outpatient treatment with oral antibiotics. We present a case of an immunosuppressed woman who underwent HyCoSy for investigation of secondary infertility and developed life-threatening sepsis with Group A streptococcus.

Asynchronous glands in the endometrium of women with recurrent reproductive failure.

Of 969 non-consecutive endometrial biopsies performed for investigation of recurrent reproductive failure, 20 cases (2.1%) showed the striking presence of retarded or asynchronous endometrial glands in otherwise unremarkable mid or late secretory endometrium. These glands were characterised by tall columnar cells with crowded nuclei showing increased reactivity for the proliferative marker MIB-1, occasional mitoses, greatly reduced or absent secretion, and persistent expression of oestrogen receptors and usually progesterone receptors and their isoforms typical of late proliferative phase endometrium. The nearby endometrial stromal cells exhibited no discernibly reduced reactivity for calretinin. These changes were seen in single glands (even portions of glands), or clusters of glands, adjacent to normal late secretory type endometrial glands and set in pseudodecidualised stroma characteristic of late luteal phase. Some examples also displayed adjacent glands with intermediate features and it is speculated that firstly, this is a relatively common phenomenon in women with recurrent miscarriage or implantation failure and with an unknown potential to affect implantation. Secondly, it is an intrinsic defect of the endometrium and can occur in sequential endometrial biopsies in the same patient. Thirdly, it differs from previously described patterns of so-called luteal phase defect or deficient secretory phase in that it occurs in the demonstrated presence of adequate progesterone effect on the endometrium and is associated with persistence rather than exaggerated down-regulation of receptors. Nevertheless, supplementary progesterone therapy (vaginal pessaries) for the first trimester appeared to have a beneficial therapeutic effect on reproductive outcome in these patients.

The distribution of immune cells and macrophages in the endometrium of women with recurrent reproductive failure. III: Further observations and reference ranges.

AIM: Abnormally functioning immunocompetent cells in the endometrium are thought to be responsible for at least some cases of recurrent reproductive failure [recurrent miscarriage or recurrent in vitro fertilisation (IVF) failure], but their detailed investigation has been hampered by a lack of a standardised protocol of counting such cells in study or control patients. The purpose of this study is to use a standardised protocol for the assessment of immune cells in the endometrial biopsies of a large cohort of women with recurrent reproductive failure and establish relevant reference ranges. METHOD: In a recent study, we reported the presence and distribution of selected immune cells and macrophages in the endometria from 222 women who had a routine endometrial biopsy for investigation of recurrent miscarriage or IVF failure. Since the completion of that study, a further 1767 cases have been examined, using the same assessment parameters of the earlier study. RESULTS: This updated analysis of 1989 endometrial biopsies provides reference ranges for CD8+, CD163+, CD56+ and CD57+ cells for individual 'days' of a normalised menstrual cycle. CD8+ T-cells displayed a modest (50%) increase in numbers in the luteal phase and periglandular aggregation was a useful indicator of a subtle focal endometritis, possibly of infective origin, and generally not identified in H&E sections. A rapid accumulation of CD163+ macrophages occurs in the superficial stroma after day 22 of the cycle, while a significant number of cases displayed single or clustered macrophages within glandular lumens of the superficial endometrium in luteal phase, especially after day 20 of the cycle. The significance of this change is unclear but may relate to a macrophage response to abnormal glandular secretion or to bleeding occurring at the time of ovulation. CD56+ uterine natural killer (uNK) cells show such a dramatic rise in both absolute numbers and percentage of stromal cells from day 22 of the standardised 28 day cycle that this needs to be taken into account in all clinical studies or individual assessments of endometrial biopsies. CD57+ NK cells are seen in small numbers in most cases and cell counts of greater than 10 per mm2 are regarded as abnormal. CONCLUSIONS: This large database provides a daily range which is the most accurate survey yet of uNK cell numbers. Co-location of CD8+ T-cells and CD56+ uNK cells in perviascular aggregates has been demonstrated.

Avoiding the use of agency staff in the operating department.

In January 2006 the BBC reported NHS trust debts of 1.07 billion pounds sterling in England (BBC 2006a). In April 2006 it reported that 7,000 job losses had already been confirmed (BBC 2006b)--although this figure could rise to as many as 13,000. Clarke (2006) identifies that many hospitals are now reducing their use of agency staff as one method of controlling unfunded expenditure. This makes economic sense: Clarke (2004) reported that the 2003-4 spend on agency staff for the whole of the UK was 1.64 billion pounds strling.