PGT-A preimplantation genetic testing for aneuploidies and embryo selection in routine ART cycles: Time to step back?

Embryo aneuploidies may be responsible for implantation failures, miscarriages and affects IVF outcomes. A variety of technologies have been implemented to individuate euploid embryos in IVF treatments, which is named preimplantation genetic testing for aneuploidies (PGT-A). According to this strategy, a better embryo selection should increase IVF results. In reality, several issues remain unaddressed including the sampling strategy, involving the test outcomes, and the frequent occurrence of embryo mosaicism, affecting the criteria for selection of supposed viable embryos and possibly posing an ethical dilemma. Safety issues are in place, including perinatal and postnatal consequences of embryo sampling and the epigenetic weaknesses from a prolonged in vitro culture, necessary for trophectoderm biopsy. On the other side, chromosome number mistakes are progressively recognized as physiologic events in the early pre-implantation embryo with many corrective mechanisms in place and their destiny in the post-implantation development is unclear. Accordingly, the increasing precision of the diagnostic tools should be used to investigate the effect of such interventions within rigorous research programs in the sake of improved clinical outcomes. Meantime the diagnosis of embryo aneuploidies in IVF cycles should be considered as a research tool and systematic implementation in clinical practice may appear unjustified.     

Evaluación del desarrollo psicomotor hasta los 3 años de edad de niños españoles concebidos por técnicas de reproducción asistida (FIV/ICSI): estudio prospectivo de cohorte controlado

IntroductionMore than five million children have been conceived by assisted reproductive techniques (ART) around the world. Most authors agree that there are no differences in psychomotor development in comparison to naturally conceived children. However, these results are still contradictory.ObjectiveTo determine whether children born from a cohort of ART-clinical gestations have a higher risk of suffering neurodevelopmental disorders in comparison to a control group. The potential associated ART-factors associated were also determined.Material and methodsThe study included the assessment of children up to 3 years old conceived by ART, and born from a cohort of women treated by the reproduction unit of a public hospital from May 2012 to May 2014. A simultaneous assessment was made of matched controls, by following the newborn naturally conceived after the ART-case, of the same group of maternal age, gestational age, and type of gestation.ResultsThere were 243 clinical gestations and 267 ART-newborns, of which 231 were assessed (87%). A simultaneous assessment was carried out in 208/230 controls (90%). There were no differences in neurodevelopmental disorders (global developmental delay, autism spectrum or language delay). Multivariate analysis of potential ART factors only showed an association between transfer of frozen embryos with language delay that has not been previously described.ConclusionsThere were no differences between groups after adjusting the results according to maternal age, multiple pregnancy, and other possible confounding factors, supporting that the role of these factors may be more relevant than the ART itself. The association between frozen embryo transfer and language delay has not been previously described. Thus, more studies are needed to confirm or refute this relationship.     

DHF-BAHPC molecule exerts ameliorative antioxidant status and reduced cadmium-induced toxicity in zebrafish (Danio rerio) embryos

In this study, we report the antioxidant and antitoxic potential of chemically synthesized 4-oxo-2-phenyl-4H-chromene-7,8-diyl bis((1-amino-2-hydroxypropyl)carbamate) (DHF-BAHPC) compound using in vitro and in vivo assays. The DHF-BAHPC was synthesized by linking 7,8-Dihydroxyflavone (DHF) with two molecules of Fmoc-threonine and characterized by Ultraviolet-visible spectroscopy (UV–vis), Fourier-transform infrared spectroscopy (FT-IR), ¹H NMR, ¹³C NMR and Mass spectrometry (MS). In vitro, antioxidant assay results revealed that DHF-BAHPC has a dose-dependent radical scavenging potential towards DPPH, ABTS, FRAP and H₂O₂ radicals with an IC₅₀ range of 15.45, 66.27, 25.71, 4.375 μg/mL, respectively. Furthermore DHF-BAHPC treatment significantly altered cadmium (Cd) intoxicated zebrafish embryos by rescuing the developmental changes associated with severe histological and reduced the level of defensive antioxidant activities (SOD, CAT, GPx and GST). The overall results of the present study represented that DHF-BAHPC may be used as a potential drug in redox-based therapeutics.     

Effect of transdermal estrogen dose regimen for endometrial preparation of frozen-thawed embryo transfer on reproductive and obstetric outcomes

PurposePrevious studies have reported different methods of estrogen administration during endometrial preparation for frozen‐thawed embryo transfer (FET). This study aimed to investigate a beneficial regimen of transdermal estrogen administration for FET.MethodsWe investigated the reproductive and obstetric outcomes of FET by comparing the increasing dose (ID) group that mimics changes in serum estradiol during the menstrual cycle and the constant dose (CD) group. Transdermal patches were used for estrogen administration in both groups. In our hospital, we targeted 315 cycles of the ID group in which FET was performed in 2017 and 324 cycles of the CD group in which FET was performed in 2018. In all cases, single embryo transfer was performed.ResultsAll were singleton pregnancies. There was no difference in clinical pregnancy rate (28.9% vs 28.2%, P =.837) and live birth rate (17.3% vs 21.4%, P =.201) between the ID and CD groups. Spontaneous abortion rate was significantly lower in the CD group than in the ID group (37.2% vs 23.0%, P =.041). There was no difference in obstetrical outcomes.ConclusionsIt was considered that the simple CD regimen may be more beneficial than the complicated ID regimen.     

Efficacy of recombinant Marek’s disease virus vectored vaccines with computationally optimized broadly reactive antigen (COBRA) hemagglutinin insert against genetically diverse H5 high pathogenicity avian influenza viruses

The genetic and antigenic drift associated with the high pathogenicity avian influenza (HPAI) viruses of Goose/Guangdong (Gs/GD) lineage and the emergence of vaccine-resistant field viruses underscores the need for a broadly protective H5 influenza A vaccine. Here, we tested experimental vector herpesvirus of turkey (vHVT)-H5 vaccines containing either wild-type clade 2.3.4.4A-derived H5 inserts or computationally optimized broadly reactive antigen (COBRA) inserts with challenge by homologous and genetically divergent H5 HPAI Gs/GD lineage viruses in chickens. Direct assessment of protection was confirmed for all the tested constructs, which provided clinical protection against the homologous and heterologous H5 HPAI Gs/GD challenge viruses and significantly decreased oropharyngeal shedding titers compared to the sham vaccine. The cross reactivity was assessed by hemagglutinin inhibition (HI) and focus reduction assay against a panel of phylogenetically and antigenically diverse H5 strains. The COBRA-derived H5 inserts elicited antibody responses against antigenically diverse strains, while the wild-type-derived H5 vaccines elicited protection mostly against close antigenically related clades 2.3.4.4A and 2.3.4.4D viruses. In conclusion, the HVT vector, a widely used replicating vaccine platform in poultry, with H5 insert provides clinical protection and significant reduction of viral shedding against homologous and heterologous challenge. In addition, the COBRA-derived inserts have the potential to be used against antigenically distinct co-circulating viruses and future drift variants.     

Impact of the one-carbon metabolism on oocyte maturation,fertilization, embryo quality,and subsequent pregnancy

PurposeTo investigate impact of the one‐carbon metabolism (OCM) on oocyte maturity and embryo development.MethodsThis prospective study analyzed 18 women who agreed to participate. We measured the OCM biomarkers’ concentrations including Vitamin B12 (VB12), folic acid (FA), and homocysteine (Hcy) in serum and follicular fluid (FF), and assessed their correlation. We also evaluated the influence of such OCM biomarker concentrations in mono‐FF on oocyte maturation, fertilization, embryo quality, and consequent pregnancy after embryo transfers.ResultsAll biomarkers showed a high concentration variability in different follicles of each woman, but their mean levels correlated with the serum levels. Among the 106 collected oocytes, 92 were mature, 59 were fertilized, and 16 yielded good‐quality embryos. We performed 26 single embryo transfers, and 7 patients achieved clinical pregnancies. VB12 concentration (FF) was significantly lower in fertilized than unfertilized oocytes by univariate analysis. In multivariate logistic analysis, a significant correlation was found between FA concentration (FF) <14.25 ng/mL and good‐quality embryos and between Hcy concentration (FF) <4.9 nmol/mL and clinical pregnancy.ConclusionOCM in FF may affect fertilization, embryo quality, and clinical pregnancy.     

冻融胚胎移植周期的黄体支持方案

恰当的黄体支持方案有利于子宫内容受性的建立和胚胎早期发育，是决定冻融胚胎移植（FET）妊娠成功的关键因素。FET常用的内膜准备方案包括自然周期、激素替代周期及卵巢温和刺激周期。激素替代周期常规进行黄体支持目前已无异议，但自然周期及温和刺激周期是否需要进行黄体支持尚存争议。对于黄体支持的药物选择、开始及持续时间目前仍缺乏统一标准。文章将围绕近年来FET不同内膜准备方案的黄体支持进行综述，希望可以为临床FET时黄体支持方案的制定和选择提供参考。     

获卵数低多囊卵巢综合征患者再次促排卵的妊娠结局及影响因素分析#br#

Objective?To investigate the impact of different ovulation induction protocols on the clinical outcomes and analyze related factors when polycystic ovarian syndrome(PCOS) patients whose number of eggs obtained last time equal to or less than five received the ovarian hyperstimulation treatment again. Methods?The retrospective analysis was made on the clinical data of 242 PCOS patients whose number of eggs obtained last time was equal to or less than five in in vitro fertilization and embryo transfer(IVF/ICSI) in the Reproductive Center of Peking University Third Hospital from January 2011 to December 2018 who received the ovulation induction treatment again. The amount of Gn used, the number of eggs obtained, and the pregnancy outcome of different ovulation induction protocols was compared. At the same time, the multi-factor linear regression analysis model was used to analyze the related factors affecting the accumulative live birth rate. Results?242 patients used the ultra-long protocol, long protocol, short protocol, and antagonist protocol for ovarian hyperstimulation. The number of eggs obtained was 12.46±2.66, 12.28±86, 10.64±1.77, 13.25±0.97, respectively. There was no statistical difference among different groups (P=0.780). The amount of Gn used and the number of days of use in the antagonist protocol group was significantly smaller than those of the ultra-long protocol and long protocol groups (P＜0.05). The amount of Gn used in the ultra-long protocol group was significantly bigger than that of the long protocol, short protocol, and antagonist protocol groups (P＜0.05). In 115 transplant cycles, the rate of embryo implantation, clinical pregnancy rate, and accumulative live birth rate of different ovulation induction protocols had no statistical difference (P＞0.05). The multi-factor regression analysis showed that the treatment method was the important affecting factor of the accumulative live birth rate (P＜0.05) and the number of eggs obtained was a mediating variable. Conclusion?For PCOS patients whose number of eggs obtained last time was not big, after another time of ovulation induction, the average number of eggs obtained maybe bigger than ten and an ideal reproduction assistance outcome could be achieved.