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Background: Non-elective freeze-all policy has been increasingly utilized in assisted reproductive treatment, but the optimal timing of frozen-thawed embryo transfer (FET) after controlled ovarian stimulation (COS) remains to be investigated.Methods: This retrospective cohort study included 2,998 patients who underwent their first FETs after the first COS cycles using the non-elective freeze-all strategy from Jan 2013 to Dec 2016 at a tertiary-care academic medical center. Patients were divided into the "immediate" group in which FET took place within the first menstrual cycle after oocyte retrieval, and the "delayed" group where FET started after one or more menstrual cycles following COS. Results:The mean interval between oocyte retrieval and FET was 33.3±5.8 days in the immediate group (n=280; 9.3%) and 91.3±19.4 days in the delayed group (n=2,718; 90.7%). Cycles with delayed FET had a significantly lower live birth rate than those with immediate FET before [1,246/2,718 (45.8%) vs. 156/280 (55.7%); P=0.002] and after propensity score matching (PSM) [123/280 (43.9%) vs. 156/280 (55.7%); P=0.005]. When controlling for a number of confounding factors by multivariable logistic regression analysis, the risk remained significant with the adjusted odds ratio (aOR) [95% confidence interval (CI)] of 0.69 (0.53-0.90) and 0.60 (0.42-0.85) before and after matching, respectively.Conclusions: Performing FET immediately within the first menstrual cycle following COS was associated with a higher chance to achieve live birth compared with delaying FET to subsequent cycles in a non-elective freeze-all policy. However, further randomized controlled trials are still needed to confirm this conclusion.

Adipose-derived stem cell (ADSC) is an alternative and less invasive source of mesenchymal stem cells which can be used to develop biological treatment strategies for tissue regeneration, and their therapeutic applications hinge on an understanding of their physiological characteristics. N6-Methyladenosine (m6A) is the most common chemical modification of mRNAs and has recently been revealed to play important roles in cell lineage differentiation and development. However, the role of m6A modification in the vascular smooth muscle cell (VSMC) differentiation of ADSCs remains unclear. Herein, we investigated the expression of N6-adenosine methyltransferases (Mettl3) and demethylases (Fto and Alkbh5) and found that Mettl3 was upregulated in ADSCs undergoing vascular smooth muscle differentiation induction. Moreover, silence of Mettle3 reduced the expression level of VSMC-specific markers, including α-SMA, SM22α, calponin, and SM-MHC. Meanwhile, Mettl3 knockdown also decreased the expression of paracrine factors, including VEGF, HGF, TGF-β, GM-CSF, bFGF, and SDF-1. In addition, our results suggested that hypoxia stress promotes the ADSC differentiate into VMSCs and regulates the secretion of VEGF, HGF, TGF-β, GM-CSF, bFGF, and SDF-1 by mediating Mettl3 gene expression. These observations might contribute to novel progress in understanding the role of epitranscriptomic regulation in the VSMC differentiation of ADSCs and provide a promising perspective for new therapeutic strategies for tissue regeneration.