A new title to an old song: some observations on the conduct of meta-analyses.

The purpose of this commentary is to draw attention to some unsatisfactory features in the way that meta-analyses are presented in assisted reproduction journals. These features will be illustrated with reference to recently published papers. An appeal will be made for a more fastidious and rigorous approach to this statistical technique that has become a ubiquitous part of the research effort in assisted reproduction treatment.

The correlation determinant in tests for synchronization in neuronal spike data.

We present a statistical approach to the identification of correlated activity in multineuron spike data, based on the value of the correlation determinant. This approach is not compromised by the lack of independence often encountered in this kind of data. We illustrate our method by applying it both to simulated data and to data recorded from neurons in a forebrain region (intermediate medial mesopallium, IMM) of the behaving domestic chick and simultaneously from the corresponding contralateral region. There is no direct anatomical connection between the two sites, and the validity of this technique is strongly supported by the observation that when the test indicates significantly correlated activity for neurons within either hemisphere, this correlation is greatly reduced, and ultimately obliterated, by serial incorporation of activity from neurons in the opposite hemisphere. Since the value of individual correlation coefficients allied to the Bonferroni correction is often used as a diagnostic tool, we also present comparisons of that approach with our correlation determinant approach.

Common genetic effects on variation in impulsivity and activity in mice.

Impulsivity is a complex psychological construct that impacts on behavioral predispositions in the normal range and has been shown to have a genetic element through the examination of hereditary patterns of abnormal conditions such as attention deficit/hyperactivity disorder and obsessive compulsive disorder. In this study, we took advantage of the isogenic nature of inbred strains of mice to determine the contribution of genes to impulsive behaviors by examining the performance of four separate mouse strains in a novel murine delayed-reinforcement paradigm, during which the animals had to choose between rewards that were relatively small but available immediately and larger but progressively delayed rewards. To control for maternal effects, all the mice were cross-fostered to a common strain immediately after birth. Under these conditions, we found significant differences between the strains on behaviors indexing impulsive choice and on independent measures of locomotor activity, which subsequent heritability analysis showed could be related, in part, to genetic effects. Moreover, the two aspects of behavior were found to co-vary, with the more active animals also displaying more impulsive behavior. This was not attributable to mundane confounds related to individual task requirements but instead indicated the existence of common genetic factors influencing variation in both impulsivity and locomotor activity. The data are discussed in terms of the coexistence of impulsivity and hyperactivity, interactions between environmental and genetic effects, and possible candidate genes.

An appeal for statistical rigour.

Following recent comments by Jean Cohen in this journal, this short note is yet another appeal for a higher standard of statistical analysis in Assisted Reproduction Research. In order to avoid the conflicts and contradictions highlighted by Jean Cohen, it is imperative that the highest standards of numerical evaluation are maintained. To this end, research workers are urged to recruit statisticians to assist in the analysis and interpretation of their results, and in the preparation of their manuscripts. Statistical science is held in rather low esteem in many quarters, a situation that is aggravated by the publicity attached to contradictory findings. A higher standard of statistical analysis is required to restore the subject's standing among research workers.

On a fallacious invocation of the Barker hypothesis of anomalies in newborn rats due to mothers' food restriction in preimplantation phases.

A statistical re-evaluation indicates serious flaws in the paper by Kwong et al., reporting that low birthweight and impaired development, and perhaps anomalous preimplantation embryo growth, were associated with food restriction during the preimplantation period. This paper has been used to confirm that early forms of protein deprivation in the preimplantation phase carry risks to IVF children. Errors in interpreting the nature of their study and a failure to apply the correct principles of statistical analysis in their hierarchical data structure have led to their flawed investigation. It is therefore proposed that such serious flaws cast doubt on their conclusions. The findings reported in this study should be withdrawn, and a rigorous statistical evaluation should be carried out to provide a proper assessment of the data.

Monozygotic twinning following assisted conception: an analysis of 81 consecutive cases.

BACKGROUND: This study attempts to identify risk factors for monozygotic (MZ) twinning following assisted conception. METHODS: Eighty-one MZ twinning pregnancies that occurred over a 7-year period in our IVF/embryo transfer programme were evaluated. These were compared with 4224 non-MZ pregnancies from the same period. RESULTS: The overall incidence of MZ twinning was 1.88% (81/4305) of all clinical pregnancies. A total of 63% (51/81) of the MZ pregnancies included one or more other implantations as well. MZ twinning was unrelated to maternal age, paternal age, gonadotrophin dosage, peak estradiol and progesterone levels, number of oocytes collected, and number of embryos replaced. Patients with MZ twinning had significantly more attempts at assisted reproduction than those with non-MZ multiple pregnancy. A logistic regression analysis suggested a role, albeit not emphatic, for the zona pellucida in MZ twinning. Twenty-four of the 65 MZ cases with known placentation were monoamniotic. This incidence far exceeds that seen following spontaneous conception (P < 0.0001). CONCLUSIONS: The risk of monoamniotic twinning is increased following IVF/embryo transfer. Zona pellucida disruption appears to increase the incidence of MZ twinning. However, the overall micromanipulation data together with the unexpected placentation data suggest that zona-mediated embryo splitting is not the only mechanism of twinning under artificial conditions.