Bloomsbury report on mouse embryo phenotyping: recommendations from the IMPC workshop on embryonic lethal screening.

Identifying genes that are important for embryo development is a crucial first step towards understanding their many functions in driving the ordered growth, differentiation and organogenesis of embryos. It can also shed light on the origins of developmental disease and congenital abnormalities. Current international efforts to examine gene function in the mouse provide a unique opportunity to pinpoint genes that are involved in embryogenesis, owing to the emergence of embryonic lethal knockout mutants. Through internationally coordinated efforts, the International Knockout Mouse Consortium (IKMC) has generated a public resource of mouse knockout strains and, in April 2012, the International Mouse Phenotyping Consortium (IMPC), supported by the EU InfraCoMP programme, convened a workshop to discuss developing a phenotyping pipeline for the investigation of embryonic lethal knockout lines. This workshop brought together over 100 scientists, from 13 countries, who are working in the academic and commercial research sectors, including experts and opinion leaders in the fields of embryology, animal imaging, data capture, quality control and annotation, high-throughput mouse production, phenotyping, and reporter gene analysis. This article summarises the outcome of the workshop, including (1) the vital scientific importance of phenotyping embryonic lethal mouse strains for basic and translational research; (2) a common framework to harmonise international efforts within this context; (3) the types of phenotyping that are likely to be most appropriate for systematic use, with a focus on 3D embryo imaging; (4) the importance of centralising data in a standardised form to facilitate data mining; and (5) the development of online tools to allow open access to and dissemination of the phenotyping data.

Cost-effectiveness of cytogenetic evaluation of products of conception in the patient with a second pregnancy loss.

OBJECTIVE: To compare the cost of two strategies for managing the patient with recurrent pregnancy loss (RPL). DESIGN: Cost analysis using a decision analytic model was used to compare obtaining an evidence-based workup (EBW) for RPL versus obtaining a karyotype of the products of conception (POC) and proceeding with an EBW only in the setting of euploid POC. SETTING: Outpatient care. PATIENT(S): A simulated cohort of patients experiencing a second pregnancy loss. INTERVENTION(S): Not applicable. MAIN OUTCOME MEASURE(S): Total cost of investigating the cause of RPL after a second pregnancy loss. RESULT(S): For all age categories, obtaining a karyotype of POC was less costly than an evidenced-based RPL evaluation. Monte Caro analysis demonstrated a net economic benefit for the karyotype strategy ($4,498 [±$792] vs. $5,022 [±$1,130]). CONCLUSION(S): Our model suggests an economic advantage for obtaining a karyotype of POC in women with second miscarriage.

Is chromosome testing of the second miscarriage cost saving? A decision analysis of selective versus universal recurrent pregnancy loss evaluation.

OBJECTIVE: To compare the cost of selective recurrent pregnancy loss (RPL) evaluation, which is defined as RPL evaluation if the second miscarriage is euploid, versus universal RPL evaluation, which is defined as RPL evaluation after the second miscarriage. Traditionally, an RPL evaluation is instituted after the third miscarriage. However, recent studies suggest evaluation after the second miscarriage, which dramatically increases health care costs. Alternatively, chromosome testing of the second miscarriage, to determine whether an RPL evaluation is required, has been proposed. DESIGN: Decision-analytic model. SETTING: Academic medical center. PATIENT(S): Couples experiencing a second miscarriage of less than 10 weeks size. INTERVENTION(S): Selective versus universal RPL evaluation after the second miscarriage. MAIN OUTCOME MEASURE(S): Estimated cost for selective versus universal RPL evaluation. RESULT(S): The estimated cost of selective RPL evaluation after the second miscarriage was $3,352, versus $4,507 for universal RPL evaluation, resulting in a cost savings of $1,155. With stratification by maternal age groups, selective RPL evaluation resulted in increased cost savings with advancing maternal age groups. CONCLUSION(S): Selective RPL evaluation, which is based upon chromosome testing of the second miscarriage, is a cost-saving strategy for couples with RPL when compared with universal RPL evaluation. With advancing maternal age groups, the cost savings increased.