二补助育汤对胚胎着床障碍小鼠子宫血管生成相关因子表达的影响

目的：探讨二补助育汤对胚胎着床障碍模型小鼠子宫内膜形态及血管生成素-1（Ang-1）mRNA、血管内皮生长因子（VEGF）mRNA的表达和定位的影响。方法：24只ICR雌性小鼠随机分为空白组、模型组、戊酸雌二醇组、二补助育汤组，每组6只，用米非司酮建立胚胎着床障碍动物模型，各组给予相应药物灌胃，妊娠第5天处死小鼠后，检测各组妊娠率、平均着床位点数、子宫内膜Ang-1和VEGF mRNA表达量及其蛋白定位。结果：模型组小鼠平均胚胎着床位点数、Ang-1 mRNA、VEGF mRNA表达量明显低于空白组（均P<0.05）；与模型组比较，二补助育汤组平均胚胎着床位点数、Ang-1 mRNA、VEGF mRNA表达量显著提高（均P<0.05）。结论：二补助育汤可提高子宫内膜Ang-1和VEGF蛋白表达量，促进子宫内膜血管生成，从而提高子宫内膜容受性。     

序贯培养体系和单一培养体系对人卵母细胞受精和早期胚胎发育的影响

目的：比较在体外受精/卵胞质内单精子显微注射（IVF/ICSI）治疗周期中序贯培养体系和单一培养体系对人类早期胚胎发育的影响，为人类辅助生殖技术中胚胎培养体系的选择和评估提供参考。方法：选取155例行IVF/ICSI助孕的患者，将同一个患者的卵子分为2组，分别在Vitrolife的序贯培养体系G-IVF/G1/G2培养液（序贯培养组）和Irvine的单一培养体系CSCC培养液（单一培养组）中进行体外受精和胚胎培养，观察2组不同培养体系中胚胎受精和胚胎早期发育情况。结果：与单一培养组比较，序贯培养组受精率、双原核（2PN）受精率和多核受精率差异均无统计学意义（P>0.05）。在IVF患者中，序贯培养组和单一培养组的卵裂率、可用胚胎率、优质胚胎率和囊胚形成率比较差异均无统计学意义（P>0.05）；在ICSI患者中，序贯培养组和单一培养组的卵裂率、可用胚胎率和囊胚形成率比较差异均无统计学意义（P>0.05），但序贯培养组优质胚胎率明显高于单一培养组（P=0.015）。在IVF和ICSI患者中，单一培养组第3天胚胎致密化的比例均明显高于序贯培养组（P=0.001）。在序贯培养组中胚胎形态表面光滑均匀，单一培养组中胚胎表面较为粗糙且有颗粒状。结论：G-IVF/G1/G2序贯培养体系和CSCC单一培养体系对人卵母细胞受精和早期胚胎发育的影响无明显差异。     

Low serum progesterone the day prior to frozen embryo transfer of euploid embryos is associated with significant reduction in live birth rates

Abstract

A retrospective cohort study was performed to examine whether, in artificial endometrial preparation for frozen embryo transfer (FET) cycles, progesterone (P) levels the day prior to embryo transfer of euploid embryos have an impact on pregnancy outcomes. In a private university clinic, 244 FETs between January 2016 and June 2017 were analyzed. Endometrial preparation was achieved with estradiol valerate and vaginal micronized progesterone. Serum P and estradiol levels the day prior to embryo transfer were measured. A multivariable analysis to assess the relationship between serum P level and pregnancy outcomes was performed, adjusted for confounding variables. Mean P value was 11.3?±?5.1?ng/ml. Progesterone levels were split in quartiles: Q1: ≤ 8.06?ng/ml; Q2: 8.07–10.64?ng/ml; Q3: 10.65–13.13?ng/ml; Q4: > 13.13?ng/ml. Patients included in the lower P quartile had a significantly higher miscarriage rate and significantly lower live birth rate (LBR) compared to the higher ones. A low serum P level (≤ 10.64?ng/ml) one day before FET is associated with a lower pregnancy and LBR following FET of euploid embryos.     

Development of the amniote ventrolateral body wall

In vertebrates, the trunk consists of the musculoskeletal structures of the back and the ventrolateral body wall, which together enclose the internal organs of the circulatory, digestive, respiratory and urogenital systems. This review gives an overview on the development of the thoracic and abdominal wall during amniote embryogenesis. Specifically, I briefly summarize relevant historical concepts and the present knowledge on the early embryonic development of ribs, sternum, intercostal muscles and abdominal muscles with respect to anatomical bauplan, origin and specification of precursor cells, initial steps of pattern formation, and cellular and molecular regulation of morphogenesis.     

Assessing efficacy of day 3 embryo time-lapse algorithms retrospectively: impacts of dataset type and confounding factors

This study investigated the efficacy of four published day 3 embryo time-lapse algorithms based on different types of datasets (known implantation data [KID] and single embryo transfer [SET]), and the confounding effect of female age and conventional embryo morphology. Four algorithms were retrospectively applied to three types of datasets generated at Fertility North between February 2013 and December 2014: (a) KID dataset (n?=?270), (b) a subset of SET (n?=?144, end-point?=?implantation), and (c) SET (n?=?144, end-point?=?live birth), respectively. All four algorithms showed progressively reduced predictive power (expressed as area under the receiver operating characteristics curve and 95% confidence interval [CI]) after application to the three datasets (a–c): Liu (0.762 [0.701–0.824] vs. 0.724 [0.641–0.807] vs. 0.707 [0.620–0.793]), KIDScore (0.614 [0.539–0.688] vs. 0.548 [0.451–0.645] vs. 0.536 [0.434–0.637]), Meseguer (0.585 [0.508–0.663] vs. 0.56 [0.462–0.658] vs. 0.549 [0.445–0.652]), and Basile (0.582 [0.505–0.659] vs. 0.519 [0.421–0.618] vs. 0.509 [0.406–0.612]). Furthermore, using KID dataset, the association (expressed as odds ratio and 95% CI) between time-lapse algorithms and implantation outcomes lost statistical significance after adjusting for conventional embryo morphology and female age in 3 of the 4 algorithms (KIDScore 1.832 [1.118–3.004] vs. 1.063 [0.659–1.715], Meseguer 1.150 [1.021–1.295] vs. 1.122 [0.981–1.284] and Basile 1.122 [1.008–1.249] vs. 1.038 [0.919–1.172]). In conclusion, SET is a preferred dataset to KID when developing or validating time-lapse algorithms, and day 3 conventional embryo morphology and female age should be considered as confounding factors.     

Metabolomics: the perspective search of methods to overcome infertility

Abstract

Nowadays, the reproductive medicine has started to develop precipitously. Nevertheless, 60 to 80 millions of couples worldwide suffer from infertility. The etiology and pathogenesis of many diseases leading to infertility is still causing a lot of debates and needs to be researched further. In 25% of the cases, the cause of infertility may not be identified that forces couples to seek help in auxiliary reproductive technologies. However, even in this case the probability of a positive result makes up no more than 40%. In recent years, scientists' attention became increasingly driven to the so-called omics-disciplines, including metabolomics. Many researchers believe that metabolomics is that science which will give a possibility to improve the quality of diagnosis, will lead to a deeper understanding of the etiology and pathogenesis of diseases that lead to infertility and will improve the quality of the assessment of oocytes and embryos in IVF cycles.     

Melatonin‐related genes expressed in the mouse uterus during early gestation promote embryo implantation

Melatonin, a superior antioxidant, is an important molecule which regulates female reproduction due to its receptor‐mediated and receptor‐independent antioxidant actions. In this study, we investigated the effect of melatonin on early gestation in a mouse model. During early gestation, the expression of the melatonin's rate‐limiting enzyme, AANAT, gradually increased – in the uterus while the MT2 melatonin receptor was only expressed at day 2 of gestation and no MT1 was detected. Based on these findings, we conducted a melatonin injection experiment which demonstrated that 15 mg/kg melatonin significantly improved the number of implantation sites and the litter size. Also, the blastocyst and uterus were collected to identify the local action of melatonin. In the melatonin‐treated mice, the endometrium was thicker than in the control mice; melatonin also caused an increase in density of uterine glands, and the uterine gland index (UGI) was significantly elevated over that of the control. Serum steroid hormone measurements revealed that at day 6 of gestation (postimplantation), melatonin significantly downregulated the E₂ level, with no obvious effects on progesterone. Gene expression assay revealed that melatonin significantly upregulated expression of HB‐EGF, a crucial gene involved in implantation as well as its receptor ErbB1 in the blastocyst. In addition, PRA, an important gene which influences the decidual response and luminal cell differentiation, p53, which regulates uterine through leukaemia inhibitory factor (LIF), were both increased after melatonin treatment. These data suggest that melatonin and its MT2 receptor influence early gestation. Exogenous melatonin treatment can improve mouse embryo implantation and litter size, which may have important applications in human reproductive health and animal husbandry.     

Subharmonic,Non-linear Fundamental and Ultraharmonic Imaging of Microbubble Contrast at High Frequencies

There is increasing use of ultrasound contrast agent in high-frequency ultrasound imaging. However, conventional contrast detection methods perform poorly at high frequencies. We performed systematic in vitro comparisons of subharmonic, non-linear fundamental and ultraharmonic imaging for different depths and ultrasound contrast agent concentrations (Vevo 2100 system with MS250 probe and MicroMarker ultrasound contrast agent, VisualSonics, Toronto, ON, Canada). We investigated 4-, 6- and 10-cycle bursts at three power levels with the following pulse sequences: B-mode, amplitude modulation, pulse inversion and combined pulse inversion/amplitude modulation. The contrast-to-tissue (CTR) and contrast-to-artifact (CAR) ratios were calculated. At a depth of 8 mm, subharmonic pulse-inversion imaging performed the best (CTR = 26 dB, CAR = 18 dB) and at 16 mm, non-linear amplitude modulation imaging was the best contrast imaging method (CTR = 10 dB). Ultraharmonic imaging did not result in acceptable CTRs and CARs. The best candidates from the in vitro study were tested in vivo in chicken embryo and mouse models, and the results were in a good agreement with the in vitro findings.