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The high demand of human placenta-derived mesenchymal stem cells (hPDMSCs) for therapeutic applications requires reproducible production of large numbers of well-characterized cells under well-controlled conditions. However, no method for fast hPDMSCs proliferation has yet been reported. In the present study, the feasibility of using a stirred bioreactor system to expand hPDMSCs was examined. hPDMSCs were cultured either in stirred bioreactors or in tissue culture flasks (T-flasks) for 5 days. Total cell density and several parameters of physical microenvironments were monitored in the two culture systems every 24 h. The maintenance of the antigenic phenotype of hPDMSCs before and after culturing in the stirred bioreactor system was cytometrically assessed. Data suggested that the physical microenvironment in the stirred bioreactors was much more favorable than that of the T-flasks. At the end of 144 h culturing, the total cell number was increased 1.73 times from the T-flasks to the stirred bioreactors. In addition, hPDMSCs could maintain their antigenic phenotype when cultured in stirred bioreactors. These results provide the initial assessment for large-scale hPDMSCs production using suspension culture bioreactors.

(Abstracted from N Engl J Med 2018;378:126–136) A previous randomized controlled trial involving women with polycystic ovary syndrome (PCOS) compared fresh-embryo transfer with elective freezing of all embryos followed by frozen-embryo transfer. The data showed that frozen-embryo transfer had a higher live-birth rate in these women compared with fresh-embryo transfer. Whether frozen-embryo transfer also increases live-birth rates among ovulatory women with infertility without PCOS is uncertain.

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BackgroundWith the development of embryo freezing and warming technology, frozen-thawed embryo transfer (FET) has been widely utilized. However, studies investigating the association between cryopreservation duration and FET outcomes are limited and controversial, and previous studies did not conduct stratification analyses based on demographic or clinical characteristics.MethodsThis multicenter retrospective study included 17,826 women who underwent their first FET following the freeze-all strategy during the period from January 2014 to December 2018. Duration of cryopreservation was categorized into five groups: 3–8 weeks, 8–12 weeks, 12–26 weeks, 26–52 weeks, and >52 weeks. Modified Poisson regression and multivariate logistic regression were used to assess the association between cryostorage time of vitrified embryos and transfer outcomes. Moreover, further stratification analyses were performed according to variables with p <0.05 in multivariate models.ResultsIn this large multicenter study, we observed that storage duration was inversely associated with the possibility of pregnancy and live birth (p <0.001), but not with the risk of ectopic pregnancy and miscarriage. Stratification analyses based on maternal age, the number of oocytes retrieved, and condition of embryo transferred indicated that the inverse correlation was significant in the subpopulation with characteristics: (1) less than 40 years old, (2) more than 3 oocytes retrieved, and (3) only high-quality blastocysts transferred.ConclusionThe results of this large, multicenter, retrospective study suggested that prolonged cryopreservation was inversely associated with the probability of pregnancy and live birth. Therefore, for patients who adopt a freeze-all strategy, early FET might achieve a better outcome.