Objective To compare inter-observer agreement for clinical decision-making with cardiotocography (CTG) and combined CTG with ST-segment analysis (STAN).Design Experimental study.Setting Three hospital obstetrics departments in France.Population Thirty randomly selected nonreassuring CTG recordings during labour of women with singleton term pregnancies in cephalic position.Methods Seven obstetricians independently assessed the tracings, displayed in a random order on their computers, on two separate sessions, the first without and the second with STAN information. The observers received clinical information about the labour as the tracings continued and were asked whether they would intervene. For analysis, we considered that intervention was justified for the neonates with pH < 7.05 and that nonintervention was justified for those with a pH > 7.10 after spontaneous delivery. Main outcome measures Kappa values and rates of inter-observer agreement for intervention and for nonintervention.Results Kappa for inter-observer agreement was 0.50 (0.29-0.69) with CTG, and 0.67 (0.48-0.81) with CTG + STAN. The rate of inter-observer agreement for the decision to intervene was 73% (68-77%) with CTG and 70% (66-75%) with CTG + STAN (P = 0.4), and for the nonintervention decision it was 48% (42-54%) and 69% (64-74%), respectively (P < 0.0001). The rate of agreement for justified intervention was 94% (91-97%) with CTG and 85% (80-90%) with CTG + STAN (P < 0.001) and for justified nonintervention, 56% (48-63%) with CTG and 84% (79-89%) with CTG + STAN (P < 0.0001).Conclusions In cases with abnormal CTG, ST analysis may improve consistency in clinical decision-making and decrease unnecessary interventions, but may also lead on rare occasions to unjustified decisions not to intervene.

No mutation was identified among these six patients. Further work is needed, with a larger patient data set, to identify putative genes involved in this form of male infertility.

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Fragile X syndrome (FraX) is caused by the expansion of an unstable CGG repeat located in the Fragile X mental retardation 1 gene (FMR1) gene. Preimplantation genetic diagnosis (PGD) can be proposed to couples at risk of transmitting the disease, that is, when the female carries a premutation or a full mutation. We describe two new single-cell, single-round multiplex PCR for indirect and direct diagnosis of FraX on biopsied embryos. These tests include five unpublished, highly heterozygous simple sequence repeats, and the co-amplification of non-expanded CGG repeats for the direct test. Heterozygosity of the new markers ranged from 69 to 81%. The mean rate of non-informative marker included in the tests was low (26% and 23% for the new indirect and direct tests, respectively). This strategy allows offering a PGD for FraX to 96% of couples requesting it in our centre. A conclusive genotype was obtained in all cells with a rate of cells presenting an allele dropout ranging from 17% for the indirect test to 26% for the direct test. The new indirect test was applied for eight PGD cycles: 32 embryos were analysed, 9 were transferred and 3 healthy babies were born. By multiplexing these highly informative markers, robustness of the diagnosis is improved and the loss of potentially healthy embryos (because they are non-diagnosed or misdiagnosed) is limited. This may increase the chances of success of couples requesting a PGD for FraX, in particular, when premature ovarian insufficiency in premutated women leads to a reduced number of embryos available for analysis.

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There appears to be a small difference in CRL development between spontaneous pregnancies and pregnancies conceived by assisted reproductive technology (ART). Specific ultrasonographic curves for pregnancies conceived by ART would be more relevant and precise. The underlying pathophysiological mechanisms are not very clear and offer possibilities for future research.

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