E2 level > 2950 pg/ml on hCG trigger day is an independent predictor for birthweight loss of full-term singletons born after fresh embryo transfers in non-PCOS patients.

BACKGROUND: Previous studies have demonstrated that the supraphysiological E2 level is negatively correlated with birthweight. However, the cut-off value of E2 level that significantly affects birthweight is unknown, and there is no definite conclusion regarding this level. Our study aimed to explore the threshold of the effect of E2 levels on birthweight. DESIGN: A retrospective cohort study of 1846 samples was performed. All patients ≤42-years-old underwent autologous IVF cycles between August 1st, 2016 and April 30th, 2020. We categorized our data into four groups according to the E2 level: Group 1: ≤2000 pg/mL; Group 2: 2001-3000 pg/mL; Group 3: 3001-4000 pg/mL; and Group 4: > 4000 pg/mL. RESULTS: The results of the multivariate regression analyses showed that when the E2 level was 3001-4000 pg/mL (adjusted ß: - 89.64, 95% [CI]: - 180.29 to - 6.01; P = 0.0336) and greater than 4000 pg/mL (adjusted ß: - 138.10, 95% [CI]: - 272.87 to - 10.33; P = 0.0181), weight loss was significant. Furthermore, the odds of full-term SGA were 1.40 times higher with E2 levels of 3001-4000 pg/mL (adjusted OR: 1.40, 95% [CI]: 1.090 to 3.18; P = 0.0256) and 2.55 times higher with E2 > 4000 pg/mL (adjusted OR: 2.55, 95% [CI]: 1.84 to 3.86; P = 0.0063) compared to the reference group. It can also be seen from the adjusted curves and the threshold effects that when the E2 level > 2950 pg/mL and > 3121 pg/mL, the incidence of SGA increased and the birthweight decreased, respectively. CONCLUSIONS: Our data suggest that E2 levels > 2950 pg/mL is an independent predictor for greater odds of full-term SGA singletons born after fresh embryo transfer.

Comparison of embryo implantation potential between time-lapse incubators and standard incubators: a randomized controlled study.

RESEARCH QUESTION: What are the potential clinical benefits of embryo culture and assessment in a time-lapse incubator compared with a standard incubator using static assessment? DESIGN: This large multicentre, single-blinded, randomized controlled study included 1224 participants randomly assigned (1:1) to the time-lapse or standard incubator group. In all patients one or two embryos were transferred on day 3. The primary outcome was the implantation rate in the first embryo transfer cycle. Secondary outcomes included the cumulative implantation rate, live birth rate in the first embryo transfer cycle and cumulative live birth rate. RESULTS: Among 1224 participants recruited, 1182 underwent embryo transfer. The number of successfully implanted embryos in the first transfer cycle was significantly higher in the time-lapse incubator group (time-lapse group: 52.35%, standard incubator group: 47.11%, P = 0.014). The implantation rate in the first embryo transfer cycle was still significantly higher in the time-lapse group than the standard incubator group after adjusting for age, body mass index, medical centre and embryo status (relative risk 1.11, 95% confidence interval 1.02-1.20, P = 0.020). However, the cumulative implantation rate, live birth rate in the first embryo transfer cycle and cumulative live birth rate were not statistically different between the groups. CONCLUSIONS: The implantation rate in the first embryo transfer cycle was significantly improved in the time-lapse group, but the effect of the time-lapse system on the cumulative implantation rate or cumulative live birth rate was not significant. The embryo assessment method offered by time-lapse systems rather than an undisturbed environment may play an important role in improving the implantation rate in the first embryo transfer cycle. These results are only applicable to young patients.

The effect of ovarian stimulation on aneuploidy of early aborted tissues and preimplantation blastocysts: comparison of the GnRH agonist long protocol with the GnRH antagonist protocol.

PURPOSE: To compare aneuploidy rates in early aborted tissues or blastocysts between in vitro fertilization (IVF) cycles after the gonadotropin-releasing hormone (GnRH) antagonist (GnRH-ant) protocol or the GnRH agonist (GnRH-a) long protocol. METHODS: This was a retrospective cohort study from a university-affiliated fertility center. In total, 550 early miscarriage patients who conceived through IVF/intracytoplasmic sperm injection (ICSI) after receiving the GnRH-ant or GnRH-a long protocol were analyzed to compare aneuploidy rates in early aborted tissues. To compare aneuploidy rates in blastocysts, 404 preimplantation genetic testing for aneuploidy (PGT-A) cycles with the GnRH-ant protocol or GnRH-a long protocol were also analyzed. RESULTS: For early miscarriage patients who conceived through IVF/ICSI, compared to the GnRH-a long protocol group, the GnRH-ant protocol group had a significantly higher rate of aneuploidy in early aborted tissues (48.51% vs. 64.19%). Regarding PGT-A cycles, the rate of blastocyst aneuploidy was significantly higher in the GnRH-ant protocol group than the GnRH-a long protocol group (39.69% vs. 52.27%). After stratification and multiple linear regression, the GnRH-ant regimen remained significantly associated with an increased risk of aneuploidy in early aborted tissues and blastocysts [OR (95% CI) 1.81 (1.21, 2.71), OR (95% CI) 1.65 (1.13, 2.42)]. Furthermore, the blastocyst aneuploidy rate in the GnRH-ant protocol group was significantly higher but only in young and normal ovarian responders [OR (95% CI) 5.07 (1.99, 12.92)]. CONCLUSION: Compared to the GnRH-a long protocol, the GnRH-ant protocol is associated with a higher aneuploidy rate in early aborted tissues and blastocysts. These results should be confirmed in a multicenter, randomized controlled trial.

[Influence of gender of reciprocal translocation carriers on the occurrence of embryonic chromosomal abnormalities].

OBJECTIVE: To explore the influence of gender of chromosomal translocation carriers on the occurrence of embryonic chromosomal aberrations. METHODS: A retrospective study was carried out. Data were collected from 235 couples carrying reciprocal translocations (1163 blastocysts) and 70 couples carrying Robertsonian translocations (351 blastocysts). The preimplantation genetic testing for structural rearrangement (PGT-SR) analysis of 1514 blastocysts were completed through next generation sequencing (NGS). RESULTS: After adjusting the confounding factors such as female age, AMH, ovarian stimulation regimen, and Gn dosage, the results showed that the risk for blastocyst chromosomal abnormalities was 0.41 [OR(95%CI), 1.41(1.06, 1.87), P < 0.05] times higher in female reciprocal translocation carriers and 1.02 [OR(95%CI), 2.02 (1.20, 3.40), P < 0.01] times higher in female Robertsonian translocation carriers compared with male carriers, respectively. Compared with male carriers, the risk of blastocyst chromosomal abnormalities was increased by 0.67 times [OR(95%CI), 1.67 (1.10, 2.56), P < 0.05] in female reciprocal translocation carriers over 30 years old and 1.06 times [OR(95%CI), 2.06 (1.02, 4.15), P = 0.0434, P < 0.05] in female Robertsonian translocation carriers between 25 and 30 years old. CONCLUSION: Compared with male carriers, female carriers of reciprocal or Robertsonian translocations have a higher risk for producing embryos with chromosomal abnormalities, and their age may also be a risk factor.

High-coverage targeted lipidomics revealed dramatic lipid compositional changes in asthenozoospermic spermatozoa and inverse correlation of ganglioside GM3 with sperm motility.

BACKGROUND: It has been previously demonstrated that cholesterol content and cholesterol/phospholipid ratio were significantly higher in asthenozoospermia and oligoasthenoteratozoospermia. The majority of published studies have investigated the fatty acid composition of phospholipids rather than lipids themselves. This study evaluated the lipid composition of asthenozoospermic and normozoospermic spermatozoa, and identified the exact lipid species that correlated with sperm motility. METHODS: A total of 12 infertile asthenozoospermia patients and 12 normozoospermia subjects with normal sperm motility values were tested for semen volume, sperm concentration, count, motility, vitality and morphology. High-coverage targeted lipidomics with 25 individual lipid classes was performed to analyze the sperm lipid components and establish the exact lipid species that correlated with sperm motility. RESULTS: A total of 25 individual lipid classes and 479 lipid molecular species were identified and quantified. Asthenozoospermic spermatozoa showed an increase in the level of four lipid classes, including Cho, PE, LPI and GM3. A total of 48 lipid molecular species were significantly altered between normozoospermic and asthenozoospermic spermatozoa. Furthermore, the levels of total GM3 and six GM3 molecular species, which were altered in normozoospermic spermatozoa versus asthenozoospermic spermatozoa, were inversely correlated with sperm progressive and total motility. CONCLUSIONS: Several unique lipid classes and lipid molecular species were significantly altered between asthenozoospermic and normozoospermic spermatozoa, revealing new possibilities for further mechanistic pursuits and highlighting the development needs of culture medium formulations to improve sperm motility.

Improving the clinical outcomes by extended culture of day 3 embryos with low blastomere number to blastocyst stage following frozen-thawed embryo transfer.

PURPOSE: This study aimed to investigate whether the extended culture of day 3 (D3) embryos with low blastomere number to blastocyst following frozen-thawed embryo transfer improved the clinical outcomes. METHODS: This was a retrospective study of clinical data of women undergoing in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles in the Tangdu Hospital. The patients were divided into groups with 4-5, 6, 7-9 and > 9 cells based on the blastomere number of D3 embryos. The clinical outcomes were compared. RESULTS: In fresh transfer cycles, the implantation and clinical pregnancy rates significantly decreased, while the abortion rate significantly increased in the groups with 4-5 and 6 cells compared with those with 7-9 and > 9 cells. In frozen-thawed transfer cycles, the clinical pregnancy and implantation rates for a single blastocyst transfer cycle showed no significant differences in the groups with 4-5 and 6 cells compared with those with 7-9 and > 9 cells. However, the abortion rate was significantly higher in the group with 4-5 cells than in that with 7-9 and > 9 cells. In the double blastocyst transfer cycle, the clinical pregnancy rate showed no significant differences among the groups with 4-5, 6, and 7-9 cells. CONCLUSION: The implantation and clinical pregnancy rates of D3 embryos with 6 cells significantly decreased; these embryos were not considered as high-quality embryos. Extended culture of D3 embryos with ≤ 6 blastomeres to blastocysts, particularly 6-cell embryos, resulted in a similar clinical pregnancy rate as that of blastocysts derived from D3 embryos with ≥ 7 blastomeres.

Alpha-lipoic acid improves the maturation and the developmental potential of goat oocytes in vitro.

Oxidative stress inevitably occurs during oocyte maturation in vitro. α-lipoic acid (α-LA) has a strong antioxidant capacity, but the effect of α-LA on parthenogenetic activation of oocytes was rarely reported. This study aims to investigate the effect of supplementing α-LA to in vitro maturation medium on the subsequent developmental ability of goat parthenogenetic embryos during oocytes maturation. In the study, the goat cumulus-oocyte complex was divided into the experimental (with 25 µmol/L α-LA) and the control (without α-LA) groups. Oxidase expression was measured using RT-qPCR. After 18-22 hr of maturation, the oocytes were then parthenogenetic activated. The total antioxidant capacity of embryos was measured after 0, 24, 48, 72 and 96 hr of culture. Rates of oocyte maturation and the rates of development for parthenogenetic embryos in the α-LA group were significantly improved by 7.88% (p < .05) and 5.41% (p < .05) compared with those in the control group, respectively. After 24 hr, the difference in total antioxidant capacity was extremely significant in both groups. An evident decrease in the control group and a minor decrease in the α-LA group were observed (p < .01). The ratio of inner cell mass cells to the total cell number of blastocysts in the α-LA group increased compared with that in the control group (p < .05) on day 8. α-LA significantly promoted the expression of SOD and GPX4 of parthenogenetic blastocysts and maturated oocytes. α-LA (25 µmol/L) improved the maturation rate and the developmental competence of the parthenogenetic activation of oocytes, which might be mediated by maintaining the total antioxidant ability of oocytes during the culture period.

Loss of methylation of H19-imprinted gene derived from assisted reproductive technologies can be mitigated by cleavage-stage embryo transfer in mice.

PURPOSE: Studies on rodents have shown that assisted reproductive technologies (ARTs) are associated with perturbation of genomic imprinting in blastocyst-stage embryos. However, the vulnerable developmental window for ART influence on the genomic imprinting of embryos is still undetermined. The purpose of this study was to establish the specific embryonic development stage at which the loss of methylation of H19 imprinting control regions (ICRs) was caused by ART occurrence. Additionally, we explored protocols to safeguard against possible negative impacts of ART on embryo H19 imprinting. METHODS: Mouse embryos were generated under four different experimental conditions, divided into four groups: control, in vitro culture (IVC), in vitro fertilization (IVF), and intracytoplasmic sperm injection (ICSI). The methylation levels of H19 ICR of the grouped or individual embryos were analyzed by bisulfite-sequencing PCR. RESULTS: Our data showed that the loss of methylation of H19 ICR in mouse blastocysts was inflicted to a similar extent by IVC, IVF, and ICSI. Specifically, we observed a significant loss of methylation of H19 ICR between the mouse 8-cell and morula stages. In addition, we revealed that the transfer of mouse embryos generated by ARTs in the uterus at the 8-cell stage induced the occurrence of methylation patterns in the blastocysts closer to the in vivo ones. CONCLUSIONS: Our findings indicate that the loss of methylation of H19 ICR caused by ARTs occurs between the 8-cell and the morula stages, and the transfer of cleavage embryos to the uterus mitigates the loss methylation of H19 derived by mice ARTs.

Climatology and changes in hourly precipitation extremes over China during 1970-2018.

Sub-daily precipitation extremes could intensify with temperature at a higher rate than the scaling for daily precipitation extremes, posing increasing risks to natural ecosystem and human society in the era of global warming. A systematic investigation of the climatology and spatiotemporal changes in sub-daily precipitation extremes is of paramount importance to inform future precipitation projection as well as to guide climate adaptation. Here, leveraging a newly proposed set of sub-daily extreme precipitation indices, we examine the climatology and changes in hourly precipitation extremes in mainland China across the major river basins during the warm period of 1970-2018. Our results show that the southern and eastern parts of China tend to experience more frequent hourly precipitation extremes with larger intensity, and the Pearl river basin has the most frequent and intense extreme precipitation at hourly timescale. The Southeast and Yangtze river basins and the mainland China as a whole have field significantly increasing trends in average and extreme precipitation intensities as well as in extreme precipitation frequencies. The intensification signals in hourly precipitation extremes of mainland China seem to emerge from internal climate variability around 2010, whereas average precipitation intensity since 1970 could become field significant earlier than 1999. Besides, we note a marked shift in the probability distributions of the extreme indices, with a wetting tendency toward more frequent and more intense precipitation extremes from the 1970-1999 period to the recent two decades in the 21st century. Our findings provide an alternative line of evidence for changes in precipitation extremes at hourly timescale over China and could contribute to societal decision-making for climate adaptation.

[Analysis of the Continuous Heavy Pollution Process in the Winter of 2016 in Beijing, Tianjin, and Hebei].

From December 16 to 21, 2016, continuous heavy haze occurred in the Beijing-Tianjin-Hebei region of China. To further understand the development mechanism of haze and improve the forecasting of haze events, a variety of data, background circulation, and the meteorological elements of this severe haze process were comprehensively analyzed. The results show that the process lasted for a long time, pollution intensity was high, influence area was wide, visibility was low, and external transport was the main cause. Aerosols were mainly distributed at a height of 600 m, and there was a certain extreme anomaly. The static weather index and air quality index showed a strong correlation. The air in the Beijing-Tianjin-Hebei region is controlled by zonal circulation in front of a high-pressure ridge, which maintains the westerly airflow. Cold-air activity is weak, and downflow is dominant. The water vapor content is low, the cloud cover is limited at high altitudes, and a warm ridge extends northwards at low altitudes. Limited static wind on the ground, high relative humidity, and low mixing-layer height are not conducive to the horizontal and vertical diffusion of pollutants.