Offspring physiology following the use of IVM, IVF and ICSI: a systematic review and meta-analysis of animal studies

OnlinePublBackground: Since the birth of the first baby using IVF technology in 1978, over 10 million children have been conceived via ART. Although most aspects of ARTs were developed in animal models, the introduction of these technologies into clinical practice was performed without comprehensive assessment of their long-term safety. The monitoring of these technologies over time has revealed differences in the physiology of babies produced using ARTs, yet due to the pathology of those presenting for treatment, it is challenging to separate the cause of infertility from the effect of treatments offered. The use of systematic review and meta-analysis to investigate the impacts of the predominant ART interventions used clinically in human populations on animals produced in healthy fertile populations offers an alternative approach to understanding the long-term safety of reproductive technologies. Objective and Rationale: This systematic review and meta-analysis aimed to examine the evidence available from animal studies on physiological outcomes in the offspring conceived after IVF, IVM or ICSI, compared to in vivo fertilization, and to provide an overview on the landscape of research in this area. Search Methods: PubMed, Embase and Commonwealth Agricultural Bureaux (CAB) Abstracts were searched for relevant studies published until 27 August 2021. Search terms relating to assisted reproductive technology, postnatal outcomes and mammalian animal models were used. Studies that compared postnatal outcomes between in vitro-conceived (IVF, ICSI or IVM) and in vivo-conceived mammalian animal models were included. In vivo conception included mating, artificial insemination, or either of these followed by embryo transfer to a recipient animal with or without in vitro culture. Outcomes included birth weight, gestation length, cardiovascular, metabolic and behavioural characteristics and lifespan. Outcomes: A total of 61 studies in five different species (bovine, equine, murine, ovine and non-human primate) met the inclusion criteria. The bovine model was the most frequently used in IVM studies (32/40), while the murine model was mostly used in IVF (17/20) and ICSI (6/8) investigations. Despite considerable heterogeneity, these studies suggest that the use of IVF or maturation results in offspring with higher birthweights and a longer length of gestation, with most of this evidence coming from studies in cattle. These techniques may also impair glucose and lipid metabolism in male mice. The findings on cardiovascular outcomes and behaviour outcomes were inconsistent across studies. Wider Implications: Conception via in vitro or in vivo means appears to have an influence on measurable outcomes of offspring physiology, manifesting differently across the species studied. Importantly, it can be noted that these measurable differences are noticeable in healthy, fertile animal populations. Thus, common ART interventions may have long-term consequences for those conceived through these techniques, regardless of the pathology underpinning diagnosed infertility. However, due to heterogeneous methods, results and measured outcomes, highlighted in this review, it is difficult to draw firm conclusions. Optimizing animal and human studies that investigate the safety of new reproductive technologies will provide insight into safeguarding the introduction of novel interventions into the clinical setting. Cautiously prescribing the use of ARTs clinically may also be considered to reduce the chance of promoting adverse outcomes in children conceived before long-term safety is confidently documented.Kiri H. Beilby, Ezra Kneebone, Tessa J. Roseboom, Indah M. van Marrewijk, Jeremy G. Thompson, Robert J. Norman, Rebecca L. Robker, Ben Willem J. Mol, and Rui Wan

The effect of stress and coping on surgical performance during simulations

Objective: This study investigates the effects of surgeons' stress levels and coping strategies on surgical performance during simulated operations. Methods: Thirty surgeons carried out each a non-crisis and a crisis scenario of a simulated operation. Surgeons' stress levels were assessed by several measures: self-assessments and observer ratings of stress, heart rate, heart rate variability, and salivary cortisol. Coping strategies were explored qualitatively and quantified to a coping score. Experience in surgery was included as an additional predictor. Outcome measures consisted of technical surgical skills using Objective Structured Assessment of Technical Skill (OSATS), nontechnical surgical skills using Observational Teamwork Assessment for Surgery (OTAS), and the quality of the operative end product using End Product Assessment (EPA). Uni- and multivariate linear regression were used to assess the independent effects of predictor variables on each performance measure. Results: During the non-crisis simulation, a high coping score and experience significantly enhanced EPA (β1, 0.279; 0.009–0.460; P= 0.04; β2, 0.571; 4.328–12.669, P< 0.001; respectively). During the crisis simulation, a significant beneficial effect of the interaction of high experience and low stress on all performance measures was found (EPA: β, 0.537; 2.079–8.543; OSATS: β, 0.707; 8.708–17.860; OTAS: β, 0.654; 13.090–30.483; P< 0.01). Coping significantly enhanced nontechnical skills (β, 0.302; 0.117–1.624, P= 0.03). Conclusions: Clinicians' stress and coping influenced surgical performance during simulated operations. Hence, these are critical factors for the quality of health care

Stress Management Training for Surgeons - a randomised controlled intervention study

Background: Stress and coping influence performance. In this study, we evaluate a novel stress management intervention for surgeons. Methods: A randomized control group design was used. Sixteen surgeons were allocated to either the intervention or control group. The intervention group received training on coping strategies, mental rehearsal, and relaxation. Performance measures were obtained during simulated operations and included objective-structured assessment of technical skill, observational teamwork assessment for surgery, and end product assessment rated by experts. Stress was assessed using the state-trait-anxiety-inventory, observer rating, coefficient of heart rate variability (C_HRV), and salivary cortisol. The number of applied surgical coping strategies (number of coping strategies [NC]) was assessed using a questionnaire. A t test for paired samples investigated any within-subject changes, and multiple linear regression analysis explored between-subject effects. Interviews explored surgeons' perceptions of the intervention. Results: The intervention group showed enhanced observational teamwork assessment for surgery performance (t = –2.767, P < 0.05), and increased coping skills (t = –4.690, P < 0.01), and reduced stress reflected inheart rate variability (t = –4.008, P < 0.01). No significant changes were identified in the control group. Linear regression analysis confirmed a significant effect on NC (β = –0.739, P < 0.01). Qualitative data analysis revealed improved technical skills, decision making, and confidence. Conclusions: The intervention had beneficial effects on coping, stress, and nontechnical skills during simulated surgery