Summary Human embryonic stem cells (hESCs) hold great promise for cell therapy as a source of diverse differentiated cell types. One key bottleneck to realizing such potential is allogenic immune rejection of hESC-derived cells by recipients. Here, we optimized humanized mice (Hu-mice) reconstituted with a functional human immune system that mounts a vigorous rejection of hESCs and their derivatives. We established knock-in hESCs that constitutively express CTLA4-Ig and PD-L1 before and after differentiation, denoted CP hESCs. We then demonstrated that allogenic CP hESC-derived teratomas, fibroblasts, and cardiomyocytes are immune protected in Hu-mice, while cells derived from parental hESCs are effectively rejected. Expression of both CTLA4-Ig, which disrupts T-cell co-stimulatory pathways, and PD-L1, which activates T-cell inhibitory pathway, is required to confer immune protection as neither was sufficient on their own. These findings are instrumental for developing a strategy to protect hESC-derived cells from allogenic immune responses without requiring systemic immune suppression.

Increased female BMI negatively affected live births conceived via IVF. Regarding ICSI, no significant differences were found in the outcomes in terms of parental BMI. The singleton neonates' NBWs increased with parental BMI conceived via IVF/ICSI. However, parental BMI did not significantly affect the NBWs of twins conceived via IVF/ICSI.

We retrospectively analyzed clinical data from 45,912 in vitro fertilization/intracytoplasmic sperm injection cycles in our reproductive medical center. We compared the clinical outcomes of three different ovarian hyperstimulation protocols in poor ovarian responders (classified by the POSEIDON criteria) to determine the most effective protocol for each POSEIDON group. In POSEIDON groups 1 and 3, the early-follicular-phase longacting GnRH-agonist long (EFLL) protocol was associated with higher pregnancy rates per transfer and higher live birth rates than the mid-luteal-phase short-acting GnRH-agonist long (MLSL) and GnRH-antagonist protocols. We also examined the relationship between advanced age and reproductive outcomes, and observed a negative correlation between age and live birth rate for each protocol (EFLL:

In recent years, applications of stem cells have already involved in all domains of life science and biomedicine. People try to establish human embryonic stem cell lines (hESCs) in order to carry out hESC-related studies. In this study, we explored what embryos are conducive to the establishment of hESCs. The discarded embryos from in vitro fertilization-embryo transfer (IVF-ET) cycles were sequentially incubated into blastocysts, and then the inner cell mass (ICM) was isolated and incubated in the mixed feeder layer. The cell lines which underwent serial passage were identified. After a total of 1,725 discarded embryos from 754 patients were incubated, 448 blastocysts were formed with 123 high-quality blastocysts. The blastulation rate was significantly higher in the discarded embryos with non-pronucleus (0PN) or 1PN than in the discarded embryos with 2PN or ≥3PN. The blastulation rate of the D3 embryos with 7-9 blastomeres was higher. Among the originally incubated 389 ICMs, 22 hESCs with normal karyotype were established, and identified to be ESCs. Therefore, in establishing hESCs with discarded embryos, D(3) 0PN or 1PN embryos with 7-9 blastomeres should be first selected, because they can improve high-quality blastulation rate which can increase the efficiency of hESC establishment.

Background: Female overweight/obesity has been reported to be associated with compromised pregnancy outcomes in fresh embryo transfer cycles. It is unclear whether the cumulative live birth rate (CLBR) is adversely affected after all viable embryos are transferred from the first ovarian stimulation cycle. Objectives: To investigate whether the CLBR was compromised in obese women. Method: A total of 9,772 young women underwent their first IVF/ICSI cycles from January 2012 to October 2017. Pregnancy outcomes were compared according to female BMI. Results: Among 1,671 women with polycystic ovary syndrome (PCOS), those with a BMI ≥ 28 kg/m 2 had a lower cumulative clinical pregnancy rate (CCPR) and CLBR during the first complete ovarian stimulation cycle. Additionally, the pregnancy loss rate was increased in this group, although the difference was not significant. Among the 8,101 women without PCOS, the CCPR and CLBR of obese patients was also significantly decreased, and this group also showed increased pregnancy loss rates. Moreover, overweight women also had a decreased CLBR. Conclusions: Female obesity adversely affected the CLBR after utilizing the viable embryos from first oocytes retrieval.