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Pre-eclampsia (PE) complicates 2%–8% of all pregnancies and is an important cause of perinatal morbidity and mortality worldwide. In order to reduce these complications and to develop possible treatment modalities, it is important to identify women at risk of developing PE. The use of biomarkers in early pregnancy would allow appropriate stratification into high and low risk pregnancies for the purpose of defining surveillance in pregnancy and to administer interventions. We used formal methods for a systematic review and meta-analyses to assess the accuracy of all biomarkers that have been evaluated so far during the first and early second trimester of pregnancy to predict PE. We found low predictive values using individual biomarkers which included a disintegrin and metalloprotease 12 (ADAM-12), inhibin-A, pregnancy associated plasma protein A (PAPP-A), placental growth factor (PlGF) and placental protein 13 (PP-13). The pooled sensitivity of all single biomarkers was 0.40 (95% CI 0.39–0.41) at a false positive rate of 10%. The area under the Summary of Receiver Operating Characteristics Curve (SROC) was 0.786 (SE 0.02). When a combination model was used, the predictive value improved to an area under the SROC of 0.893 (SE 0.03). In conclusion, although there are multiple potential biomarkers for PE their efficacy has been inconsistent and comparisons are difficult because of heterogeneity between different studies. Therefore, there is an urgent need for high quality, large-scale multicentre research in biomarkers for PE so that the best predictive marker(s) can be identified in order to improve the management of women destined to develop PE.

Assisted reproduction and preimplantation genetic diagnosis (PGD) involve various complicated techniques, each of them with its own problems. However, the greatest problem with PGD for chromosome abnormalities is not of a technical nature but is a biological phenomenon: chromosomal mosaicism in the cleavage stage embryo. Here, we present a hypothetical, quantitative model for the development of chromosomally normal, abnormal and mosaic embryos. The arising of mosaicism in 2-8-cell embryos was described by a binomial probability model on the occurrence of mitotic events inducing chromosomal changes in the blastomeres. This model converted the 'mean' rate of mosaicism found in cross-sectional studies (60%) into an equal rate of mosaic embryos at arrival at the 8-cell stage (59.8%). The disappearance of > 90% of the mosaic embryos or the mosaicism itself from surviving embryos during the morula stage was explained by mitotic arrest of most of the mitotically changed cells under increasing cell cycle control. In our model, 25.9 and 14.3% of the embryos at the 8-cell stage are normal and abnormal respectively. The remaining 59.8% of the embryo shows mosaicism: 34.6% of abnormal/normal cells and 25.2% of abnormal/abnormal cells. The high proportion of abnormal and mosaic embryos together explains the high rate of abnormal laboratory findings in PGD for chromosomal abnormalities and aneuploidy screening. The poor representation of a 1- or 2-cell biopsy for the 7- or 6-cell post-biopsy embryo in the case of mosaicism explains the high rate of false-negative and false-positive results.

The introduction of prenatal screening requires rapid high-throughput diagnosis of common aneuploidies. Multiplex ligation-dependent probe amplification (MLPA) allows for quick, easily automated multiplex testing of these aneuploidies in one polymerase chain reaction. We performed a large prospective study using MLPA on 4000 amniotic fluid (AF) samples including all indications and compared its value to karyotyping and fluorescence in situ hybridization (FISH). MLPA can reliably determine common aneuploidies with 100% sensitivity and 100% specificity. Moreover, some mosaic cases and structural chromosome aberrations were detected as well. In cases of a male fetus, triploidies can be detected by an aberrant pattern of probe signals, which mimics maternal cell contamination (MCC). Macroscopic blood contamination was encountered in 3.2% of the AF samples. In 20% of these samples, an MLPA pattern was found consistent with MCC, although there were no false negatives of the most common aneuploidies. As the vast majority of inconclusive results (1.7%) is due to potential MCC, we designed a protocol in which we determine whether MLPA can be performed on blood-contaminated AF samples by testing if blood is of fetal origin. Then, the number of inconclusive results could be theoretically reduced to 0.05%. We propose an alternative interpretation of relative probe signals for rapid aneuploidy diagnosis (RAD). We discuss the value of MLPA for the detection of (submicroscopic) structural chromosome anomalies. MLPA is a reliable method that can replace FISH and could be used as a stand-alone test for RAD instead of karyotyping.

Objective To obtain face and construct validity for a new training course to be used in any type of box/video trainer and to give a comprehensive overview of validated exercises for box/video training.Design Cross-sectional study.Setting University Medical Centre.Population Students, residents and consultants.Methods Participants (n = 42) were divided into three groups according to their laparoscopic experience: 'Novices' (n = 18), 'Intermediates' (n = 14) and 'Experts' (n = 10). A laparoscopic training course consisting of six exercises was constructed. To emphasise precision, a penalty score was added. Every participant performed two repetitions of the exercises; total score per exercise was calculated. To determine face validity, participants filled in a questionnaire after completion of the exercises. An evidence-based literature search for validated box/video trainer exercises was performed.Main outcome measures Face and construct validity.Results The mean score of the 'experts' was set as the training target. Total scores appeared to be positively correlated with individual's laparoscopic experience. The overall score and the score for each exercise were significantly higher in the intermediate and expert groups when compared with the novice group (P £ 0.001). All participants completed the questionnaire. The overall assessment of the exercises was considered to be good. The course was found to be most appropriate for training residents year 1-3.Conclusion Face and construct validity for an inexpensive course for box/video training was established. A comprehensive and practical overview of all validated and published exercises for box/ video trainers is provided to facilitate an inexpensive, but optimal and tailored selection for training purposes.Keywords Box training, education, laparoscopy, simulation, validated exercises, video training.Please cite this paper as: Schreuder H, van den Berg C, Hazebroek E, Verheijen R, Schijven M. Laparoscopic skills training using inexpensive box trainers: which exercises to choose when constructing a validated training course. BJOG 2011;118:1576-1584. IntroductionTo perform laparoscopic surgery safely, several unique psychomotor skills are required from the surgeon. These include adaptation to the conversion from three-dimensional to two-dimensional vision, bi-manual dexterity, handling long instruments with an amplified tremor, dealing with the fulcrum effect and reduced tactile feedback. Simulation can be used to master these skills. Training on simulation models leads to a faster pace of the learning curve of the individual surgeon in a safe environment, thereby decreasing the burden on operating time and costs and increasing patient safety.1,2 Different simulation models and scenarios have been introduced and incorporated into various laparoscopic training curricula. 3 In general, these models can be categorised as in vivo anaesthetised or ex vivo animal trainers, high-fidelity and low-fidelity virtual reality simulators and inanimate box or video trainers.