Clinical outcomes of vitrified-warmed autologous oocyte cycles with 15-year follow-up at a single UK centre: consistent and predictable results.

RESEARCH QUESTION: What were the clinical outcomes from 332 autologous vitrified- warmed oocyte cycles derived from 3182 elective autologous oocyte freeze cycles carried out between 2008 and 2022 in a single-centre series? DESIGN: In this retrospective observational study, outcomes in 299 patients returning to use their frozen oocytes between 2015 and 2023 were analysed. RESULTS: A total of 3328 elective oocyte vitrification cycles were performed in 2280 patients. The return rate to use oocytes was 14% (299/2171). Mean ages were 37.6 years at storage and 40 at warming. Ninety-three clinical pregnancies and 77 healthy live births were recorded. The live birth rate (LBR) was 24% (39/163) per fresh transfer and 17% (39/227) per embryo transferred. Stratified by age at freezing, the LBR per embryo transferred was 26% (12/47) in participants under 35 years, 20% (24/118) in those 35-39 years and 5% (3/62) in those 40+ years. Frozen embryo transfers (FET) achieved a 30% (24/80) LBR per embryo transfer and a 27% (24/90) LBR per embryo transferred. PGT-A for embryo selection doubled the LBR compared with FET from an untested embryo after one attempt (40% versus 21%). In patients aged over 40 years, the cumulative LBR reached 42% per patient in euploid FET. CONCLUSION: The proportion of patients who returned to use their stored oocytes and the clinical outcomes were consistent with other recent reports and challenges the prevalent critical narrative regarding elective oocyte freezing for fertility preservation. The results are now comparable to routine IVF. Not everyone who returns to use their oocytes will conceive, but for those choosing to preserve their fertility, oocyte freezing can provide reproducible and reassuring results.

ASPP2 maintains the integrity of mechanically stressed pseudostratified epithelia during morphogenesis.

During development, pseudostratified epithelia undergo large scale morphogenetic events associated with increased mechanical stress. Using a variety of genetic and imaging approaches, we uncover that in the mouse E6.5 epiblast, where apical tension is highest, ASPP2 safeguards tissue integrity. It achieves this by preventing the most apical daughter cells from delaminating apically following division events. In this context, ASPP2 maintains the integrity and organisation of the filamentous actin cytoskeleton at apical junctions. ASPP2 is also essential during gastrulation in the primitive streak, in somites and in the head fold region, suggesting that it is required across a wide range of pseudostratified epithelia during morphogenetic events that are accompanied by intense tissue remodelling. Finally, our study also suggests that the interaction between ASPP2 and PP1 is essential to the tumour suppressor function of ASPP2, which may be particularly relevant in the context of tissues that are subject to increased mechanical stress.

Dietary restriction in ILSXISS mice is associated with widespread changes in splicing regulatory factor expression levels.

Dietary restriction (DR) represents one of the most reproducible interventions to extend lifespan and improve health outcomes in a wide range of species, but substantial variability in DR response has been observed, both between and within species. The mechanisms underlying this variation in effect are still not well characterised. Splicing regulatory factors have been implicated in the pathways linked with DR-induced longevity in C. elegans and are associated with lifespan itself in mice and humans. We used qRT-PCR to measure the expression levels of a panel of 16 age- and lifespan-associated splicing regulatory factors in brain, heart and kidney derived from three recombinant inbred strains of mice with variable lifespan responses to short-term (2 months) or long-term (10 months) 40% DR to determine their relationship to DR-induced longevity. We identified 3 patterns of association; i) splicing factors associated with DR alone, ii) splicing factors associated with strain alone or iii) splicing factors associated with both DR and strain. Tissue specific variation was noted in response to short-term or long-term DR, with the majority of effects noted in brain following long-term DR in the positive responder strain TejJ89. Association in heart and kidney were less evident, and occurred following short-term DR. Splicing factors associated with both DR and strain may be mechanistically involved in strain-specific differences in response to DR. We provide here evidence concordant with a role for some splicing factors in the lifespan modulatory effects of DR across different mouse strains and in different tissues.