Embryo Transfer Strategies for Women with Recurrent Implantation Failure During the Frozen-thawed Embryo Transfer Cycles:Sequential Embryo Transfer or Double-blastocyst Transfer?

Objective Both sequential embryo transfer(SeET)and double-blastocyst transfer(DBT)can serve as embryo transfer strategies for women with recurrent implantation failure(RIF).This study aims to compare the effects of SeET and DBT on pregnancy outcomes.Methods Totally,261 frozen-thawed embryo transfer cycles of 243 RIF women were included in this multicenter retrospective analysis.According to different embryo quality and transfer strategies,they were divided into four groups:group A,good-quality SeET(GQ-SeET,n=38 cycles);group B,poor-quality or mixed-quality SeET(PQ/MQ-SeET,n=31 cycles);group C,good-quality DBT(GQ-DBT,n=121 cycles);and group D,poor-quality or mixed-quality DBT(PQ/MQ-DBT,n=71 cycles).The main outcome,clinical pregnancy rate,was compared,and the generalized estimating equation(GEE)model was used to correct potential confounders that might impact pregnancy outcomes.Results GQ-DBT achieved a significantly higher clinical pregnancy rate(aOR 2.588,95%CI 1.267–5.284,P=0.009)and live birth rate(aOR 3.082,95%CI 1.482–6.412,P=0.003)than PQ/MQ-DBT.Similarly,the clinical pregnancy rate was significantly higher in GQ-SeET than in PQ/MQ-SeET(aOR 4.047,95%CI 1.218–13.450,P=0.023).The pregnancy outcomes of GQ-SeET were not significantly different from those of GQ-DBT,and the same results were found between PQ/MQ-SeET and PQ/MQ-DBT.Conclusion SeET relative to DBT did not seem to improve pregnancy outcomes for RIF patients if the embryo quality was comparable between the two groups.Better clinical pregnancy outcomes could be obtained by transferring good-quality embryos,no matter whether in SeET or DBT.Embryo quality plays a more important role in pregnancy outcomes for RIF patients.

Live births from in vitro fertilization-embryo transfer following the administration of gonadotropin-releasing hormone agonist without gonadotropins:Two case reports

BACKGROUND The prevalence of female infertility between the ages of 25 and 44 is 3.5%to 16.7%in developed countries and 6.9%to 9.3%in developing countries.This means that infertility affects one in six couples and is recognized by the World Health Organization as the fifth most serious global disability.The International Committee for Monitoring Assisted Reproductive Technology reported that the global total of babies born as a result of assisted reproductive technology procedures and other advanced fertility treatments is more than 8 million.Advancements in controlled ovarian hyperstimulation procedures led to crucial accomplishments in human fertility treatments.The European Society for Human Reproduction and Embryology guideline on ovarian stimulation gave us valuable evidence-based recommendations to optimize ovarian stimulation in assisted reproductive technology.Conventional ovarian stimulation protocols for in vitro fertilization(IVF)–embryo transfer are based upon the administration of gonadotropins combined with gonadotropin-releasing hormone(GnRH)analogues,either GnRH agonists(GnRHa)or antagonists.The development of ovarian cysts requires the combination of GnRHa and gonadotropins for controlled ovarian hyperstimulation.However,in rare cases patients may develop an ovarian hyper response after administration of GnRHa alone.CASE SUMMARY Here,two case studies were conducted.In the first case,a 33-year-old female diagnosed with polycystic ovary syndrome presented for her first IVF cycle at our reproductive center.Fourteen days after triptorelin acetate was administrated(day 18 of her menstrual cycle),bilateral ovaries presented polycystic manifestations.The patient was given 5000 IU of human chorionic gonadotropin.Twenty-two oocytes were obtained,and eight embryos formed.Two blastospheres were transferred in the frozen-thawed embryo transfer cycle,and the patient was impregnated.In the second case,a 37-year-old woman presented to the reproductive center for her first donor IVF cycle.Fourteen days after GnRHa administration,the transvaginal ultrasound revealed six follicles measuring 17-26 mm in the bilateral ovaries.The patient was given 10000 IU of human chorionic gonadotropin.Three oocytes were obtained,and three embryos formed.Two high-grade embryos were transferred in the frozen-thawed embryo transfer cycle,and the patient was impregnated.CONCLUSION These two special cases provide valuable knowledge through our experience.We hypothesize that oocyte retrieval can be an alternative to cycle cancellation in these conditions.Considering the high progesterone level in most cases of this situation,we advocate freezing embryos after oocyte retrieval rather than fresh embryo transfer.

Inhibitory effect of acetylshikonin on human gastric carcinoma cell line SGC-7901 in vitro and in vivo

AIM:To investigate the inhibitory effect of acetylshikonin on human gastric carcinoma cell line SGC-7901 and its mechanism. METHODS:MTT assay was used to assess the inhibitory effect of acetylshikonin on proliferation of SGC-7901 cells.Apopt osis-inducing effect was determined by flow cytometry and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling with Hoechst staining.Expression of mRNA and protein in Bcl-2 and Bax was analyzed by reverse transcription-polymerase chain reaction and Western blot.Antitumor effect of acetylshikonin on a mouse SGC-7901 model was also determined. RESULTS:Forty-eight hours after treatment with acetylshikonin,MTT assay showed that acetylshikonin inhibited the proliferation of SGC-7901 cells in a dose-dependent manner.The half maximal inhibitory concentration of acetylshikonin to SGC-7901 cells was 0.428±0.07 mg/L.Cell shrinkage,nuclear pyknosis and chromatin condensation,which are the characteristics of cell apoptosis,were observed in treated SGC-7901 cells and the percentage of apoptosis increased in a dose-dependent manner.Acetylshikonin downregulated the expression of Bcl-2 and up-regulated the expression of Bax in the treated SGC-7901 cells compared with the controls.The experiment in vivo showed that 0.5,1,and 2 mg/kg of acetylshikonin significantly inhibited the growth of tumor in the mouse SGC-7901 model,with an inhibitory rate of 25.00%-55.76%. CONCLUSION:Acetylshikonin inhibits the growth of SGC-7901 cells in vitro and in vivo by inducing cell apoptosis.

Use of cationic microbubbles targeted to P-selectin to improve ultrasound-mediated gene transfection of hVEGF_(165) to the ischemic myocardium

Gene therapies have been applied to the treatment of cardiovascular disease, but their use is limited by the need to deliver them to the right target. We have employed targeted contrast ultrasound-mediated gene transfection （TCUMGT） via ultrasound-targeted microbubble destruction （UTMD） to transfer therapeutic genes to specific anatomic and pathological targets. Phospholipid microbubbles （MBs） with pcDNA3.l-human vascular endothelial growth factor 165 （pcDNA3.I-hVEGFls5） plasmids targeted to P-selectin （MB＋P＋VEGFp） were created by conjugating monoclonal antibodies against P-selectin to the lipid shell. These microbubbles were divided into four groups： microbubble only （MB）, microbubble＋P-selectin （MB＋P）, microbubble＋pcDNA3.l-hVEGF185 plasmid （MB＋VEGFp）, and microbubbie＋ P-selectin＋pcDNA3.1-hVEGF185 piasmid （MB＋P＋VEGFp）. The reverse transcription polymerase chain reaction （RT-PCR） and enzyme-linked immunosorbent assay （ELISA） results showed that the VEGF gene was successfully transfected by TCUMGT and the efficiency is increased with P-selectin targeting moiety. UTMD-mediated delivery of VEGF increased myocardial vascular density and improved cardiac function, and MB＋P＋VEGFp delivery showed greater improvement than MB＋VEGFp. This study drew support from TCUGMT technology and took advantage of targeted ultrasound contrast agent to identify ischemic myocardium, release pcDNA3.1-hVEGF165 recombinant plasmid, and improve the myocardial microenvironment, so promoting the restoration of myocardial function.

Novel Crystallization Behaviors of Zr-Based Metallic Glass Under Thermo-Mechanical Coupled Fatigue Loading Condition

Novel crystallization behaviors of Zr55Cu30Al10Ni5 bulk metallic glass are investigated. On the one hand, mixed oxides, including CuO, CuAlO2, CuA12O4 and ZrO2, show sequential oxidation process determined by coupling effects of specific cyclic load and temperature. On the other hand, at a temperature (100℃) by far lower than Tg of 412 ℃, under cyclic loading condition, non-oxidized binary alloy CuZr2 is precipitated;the thermo-mechanical coupled effects of temperature below Tg, and fatigue accumulation on the non-oxidized crystallization behaviors are revealed. Meanwhile, at a constant temperature of 400 ℃, by comparing among the XRD patterns, respectively, obtained from tensile, creep and fatigue fractures, the dominating effect of cyclic load on the generation of non-oxidized CuZr2 is verified. Furthermore, the crystallization behavior of amorphous phases under cyclic loading condition is observed through TEM micrograph and diffraction pattern at 100℃.