P–552 Delayed blastocyst development is associated with a higher risk of aneuploidy in patients of advanced maternal age

Study question Is delayed blastocyst development, assessed by the day of trophectoderm (TE) biopsy, associated with higher rates of aneuploidy? Summary answer Our findings show an association between delayed blastocyst development and poorer prognosis, in terms of euploidy rates, in patients of advanced maternal age. What is known already Extended culture of embryos past day 5 of development has become routine practice in all freeze-all cycles, including those applying preimplantation genetic testing for aneuploidies (PGT-A). As healthy live births have been obtained from day 6 and day 7 blastocysts, increasing the pool of embryos available for PGT-A is beneficial, particularly for patients of advanced maternal age who face higher cancellation rates. Nevertheless, the association between delayed blastocyst development and aneuploidy rates remains unclear. As current studies have reported opposing findings, detailed analysis of the chromosomal constitution of slowly developing embryos remains paramount. Study design, size, duration Retrospective, international, multicentre cohort study of 4211 patients undergoing preimplantation genetic testing for aneuploidy (PGT-A) from January 2016 to July 2020. We evaluated the chromosomal status of 14757 blastocysts tested using TE biopsy and next generation sequencing (NGS). Both autologous and donation cycles were included in the analysis. Cycles were excluded if they utilised preimplantation genetic testing for monogenic disorders (PGT-M) or preimplantation genetic testing for structural rearrangements (PGT-SR). Participants/materials, setting, methods We evaluated euploidy, aneuploidy and mosaicism rates reported in day 5 (n = 9560), day 6 (n = 4753) and day 7 (n = 262) blastocysts, stratified by SART-defined maternal age categories (<35, 35–37, 38–40, 41–42, >42). We further assessed the type and frequency of abnormalities reported in all blastocysts classified as clinically unsuitable, according to the day of biopsy. Finally, we examined the specific chromosomes affected in embryos diagnosed with a single uniform (n = 3882) or single mosaic (n = 518) abnormality. Main results and the role of chance The mean maternal age within our patient cohort was 39.9±3.7. Overall, slowly developing blastocysts were significantly more likely to be classified as clinically unsuitable (60.6%) compared to day 5 embryos (55.2%; p < 0.0001). This correlation was also observed when stratified by age, with the exception of the <35 age group (p = 0.25). Markedly, the risk of aneuploidy in slowly developing blastocysts became progressively higher with advancing maternal age (p < 0.0001). We did not observe any significant differences in the types of abnormalities diagnosed in slowly developing embryos compared to day 5 blastocysts. Nevertheless, abnormalities affecting all chromosomes were present at the blastocyst stage. Single trisomies and monosomies were the most frequent across all age groups, and were equally prevalent in day 5, 6 and 7 blastocysts. These most commonly affected chromosomes 16, 22, 21 and 15. We observed no significant differences in the incidence of segmental aneuploidies in relation to the day of biopsy, across all age groups. When considered separately, day 7 blastocysts presented with higher rates of structural aberrations, however low numbers limited statistical power. Finally, delayed blastocyst development was not associated with higher mosaicism rates (p = 0.79). Interestingly, single mosaic trisomies and monosomies were most frequently associated with chromosome 19. Limitations, reasons for caution Due to the retrospective nature of the study, full elucidation of all potential confounders may not be possible in all instances. The low number of day 7 blastocysts limited statistical power. As such, the results from day 6 and day 7 embryos were evaluated together. Wider implications of the findings: Our findings offer an important clinical resource for counselling patients of advanced maternal age. Maternal aging may be associated with a higher incidence of aneuploidy in slowly developing blastocysts. Nevertheless, extended culture increases the pool of biopsiable blastocysts, ultimately improving the chance of having a euploid embryo for transfer. Trial registration number NA

Oxytocin modulation of self-other distinction is replicable and influenced by oxytocin receptor (OXTR) genotype

Intranasal oxytocin (OXT) has been associated with effects on diverse social-emotional domains in humans, however progress in the field is currently hampered by poor replicability. Limited statistical power and individual differences in biological factors, such as oxytocin receptor (OXTR) genetics, may have contributed to these variable findings. To this end, we present a pharmaco-genetic study aiming at (1) replicating previous findings suggesting that intranasal oxytocin (24 IU) blurs self-other distinction in a large sample of n = 170 male subjects, (2) determining whether variations in common receptor polymorphisms (rs237887, rs2268491, rs2254298, rs53576, rs2268498) influence sensitivity to oxytocin’s behavioral effects. Employing a validated oxytocin-sensitive trait judgment paradigm, we confirmed that it blurred self-other distinction in terms of decision time and subsequent memory. However, oxytocin only influenced decision time in rs53576 G carriers, whereas effects on memory performance were most pronounced in rs2268498 TT homozygotes. In summary, the current study replicates our previous findings showing that oxytocin blurs self-other distinction and suggests that sensitivity to its effects in this domain are receptor genotype dependent.

Development of a Within-Subject, Repeated-Measures Ego-Depletion Paradigm

Ego depletion is under scrutiny for low replicability, possibly reflecting the limited statistical power available in between-subject designs. In response, we created a within-subject, repeated-measures ego-depletion paradigm that repeatedly alternated depletion and recovery manipulations. Each manipulation was followed by measuring subjective fatigue, mood, and self-control performance. Across 12 studies (N = 754), participants reliably reported having lower energy and mood after depleting manipulations compared to after recovery manipulations. Depletion manipulations did not consistently affect behavioral self-control, although the depletion effect was meta-analytically significant (d = .045). Furthermore, unintended fatigue and practice effects occurred over the course of the paradigm, systematically interfering with the intended depletion effects. We recommend that depletion research takes advantage of within-subject designs across multiple sessions to avoid spillover effects between measurements.

Development of a Within-Subject, Repeated-Measures Ego Depletion Paradigm: Inconsistent Results and Future Recommendations

The ego-depletion effect is currently under scrutiny for low replicability, possibly reflecting the limited statistical power available in between-subject designs. In response, we created a within-subject, repeated-measures ego-depletion paradigm that repeatedly alternated depletion and recovery manipulations. Each manipulation was followed by measuring subjective fatigue, mood, and self-control performance. Across twelve studies (N = 754), participants reliably reported having less energy and lower mood after depleting manipulations compared to after recovery manipulations. Depletion manipulations did not consistently affect behavioral self-control, although the small effect was meta-analytically significant (d = .045). Furthermore, unintended fatigue and practice effects occurred over the course of the paradigm, systematically interfering with the intended depletion effects. We recommend that depletion research take advantage of within-subject designs without using repeated-measures.

Is Paternal Smoking at Conception a Risk for ADHD? A Controlled Study in Youth With and Without ADHD

Objective: Based on emerging preclinical findings suggesting that paternal smoking at conception may be a risk for ADHD in the offspring, we investigated whether a similar effect can be observed in humans. Method: We analyzed data from an opportunistic dataset of girl probands with ( N = 140) and without ( N = 122) ADHD with available information on paternal smoking at conception. Data were analyzed using Pearson’s chi-square tests and multiple logistic regression. Results: ADHD probands had a significantly higher rate of paternal smoking at conception than controls (35% vs. 23%, χ2 = 3.82, p = .05) with a significant odds ratio of 1.5. However, the association lost significance after controlling for paternal ADHD, most likely due to limited statistical power. Conclusion: While preliminary, findings suggest that paternal smoking at conception may be a risk factor for ADHD in the offspring.

EDITORIAL: Systematic reviews and meta-analysis

Conclusions about medical interventions or the causes of disease are based upon reviews of the scientific literature. Single studies usually have limited statistical power or may be difficult to interpret or generalize and so the findings from a single study can rarely justify a change in clinical practice or in an aetiological theory. Even when planning larger studies or mega-trials (Yusuf et al. 1984), a thorough review of existing literature is needed and the results of the study need to be placed in that context, though single studies can exert an important and powerful influence.