Study on the optimal time limit of frozen embryo transfer and the effect of a long-term frozen embryo on pregnancy outcome.

In this retrospective study conducted at Sichuan Jinxin Xinan Women and Children's Hospital spanning January 2015 to December 2021, our objective was to investigate the impact of embryo cryopreservation duration on outcomes in frozen embryo transfer. Participants, totaling 47,006 cycles, were classified into 3 groups based on cryopreservation duration: ≤1 year (Group 1), 1 to 6 years (Group 2), and ≥6 years (Group 3). Employing various statistical analyses, including 1-way ANOVA, Kruskal-Wallis test, chi-square test, and a generalized estimating equation model, we rigorously adjusted for confounding factors. Primary outcomes encompassed clinical pregnancy rate and Live Birth Rate (LBR), while secondary outcomes included biochemical pregnancy rate, multiple pregnancy rate, ectopic pregnancy rate, early and late miscarriage rates, preterm birth rate, neonatal birth weight, weeks at birth, and newborn sex. Patient distribution across cryopreservation duration groups was as follows: Group 1 (40,461 cycles), Group 2 (6337 cycles), and Group 3 (208 cycles). Postcontrolling for confounding factors, Group 1 exhibited a decreased likelihood of achieving biochemical pregnancy rate, clinical pregnancy rate, and LBR (OR < 1, aOR < 1, P < .05). Furthermore, an elevated incidence of ectopic pregnancy was observed (OR > 1, aOR > 1), notably significant after 6 years of freezing time [aOR = 4.141, 95% confidence intervals (1.013-16.921), P = .05]. Cryopreservation exceeding 1 year was associated with an increased risk of early miscarriage and preterm birth (OR > 1, aOR > 1). No statistically significant differences were observed in birth weight or sex between groups. However, male infant birth rates were consistently higher than those of female infants across all groups. In conclusion, favorable pregnancy outcomes align with embryo cryopreservation durations within 1 year, while freezing for more than 1 year may diminish clinical pregnancy and LBRs, concurrently elevating the risk of ectopic pregnancy and preterm birth.

Age at menarche and risk of ovarian hyperstimulation syndrome in women undergoing IVF/ICSI cycles: a retrospective cohort study.

OBJECTIVES: We aimed to explore the association between age at menarche (AAM) and ovarian hyperstimulation syndrome (OHSS) in fresh in vitro fertilisation (IVF)/intracytoplasmic sperm injection (ICSI) cycles. DESIGN: A retrospective cohort study. SETTING: Data were collected from a large obstetrics and gynaecology hospital in Sichuan, China. PARTICIPANTS: This study included 17 419 eligible women aged ≤40 years who underwent the first IVF/ICSI cycles from January 2015 to December 2021. Women were divided into three groups according to their AAM: ≤12 years (n=5781), 13-14 years (n=9469) and ≥15 years (n=2169). RESULTS: The means of age at recruitment and AAM were 30.4 years and 13.1 years, respectively. Restricted cubic spline models suggested that early menarche age increased the risk of OHSS. The multivariable logistic analysis showed that women with menarche age ≤12 years were more likely to suffer from OHSS (OR 1.321, 95% CI 1.113 to 1.567) compared with those aged 13-14 years among the whole cohort. This significant relationship remained in women administered with different ovarian stimulation protocols and gonadotrophin doses. When stratified by female age, this correlation was presented only in patients aged ≤30 years (OR 1.362, 95% CI 1.094 to 1.694). And the mediation analysis showed that the relationship between AAM and OHSS was totally mediated by antral follicle counts (AFC). CONCLUSION: Menarche age earlier than 12 years may increase the OHSS risk in women aged ≤30 years through the mediation of AFC. More prospective studies are required to verify the results.

Knocking out Fkbp51 decreases CCl4-induced liver injury through enhancement of mitochondrial function and Parkin activity.

BACKGROUND AND AIMS: Previously, we found that FK506 binding protein 51 (Fkbp51) knockout (KO) mice resist high fat diet-induced fatty liver and alcohol-induced liver injury. The aim of this research is to identify the mechanism of Fkbp51 in liver injury. METHODS: Carbon tetrachloride (CCl4)-induced liver injury was compared between Fkbp51 KO and wild type (WT) mice. Step-wise and in-depth analyses were applied, including liver histology, biochemistry, RNA-Seq, mitochondrial respiration, electron microscopy, and molecular assessments. The selective FKBP51 inhibitor (SAFit2) was tested as a potential treatment to ameliorate liver injury. RESULTS: Fkbp51 knockout mice exhibited protection against liver injury, as evidenced by liver histology, reduced fibrosis-associated markers and lower serum liver enzyme levels. RNA-seq identified differentially expressed genes and involved pathways, such as fibrogenesis, inflammation, mitochondria, and oxidative metabolism pathways and predicted the interaction of FKBP51, Parkin, and HSP90. Cellular studies supported co-localization of Parkin and FKBP51 in the mitochondrial network, and Parkin was shown to be expressed higher in the liver of KO mice at baseline and after liver injury relative to WT. Further functional analysis identified that KO mice exhibited increased ATP production and enhanced mitochondrial respiration. KO mice have increased mitochondrial size, increased autophagy/mitophagy and mitochondrial-derived vesicles (MDV), and reduced reactive oxygen species (ROS) production, which supports enhancement of mitochondrial quality control (MQC). Application of SAFit2, an FKBP51 inhibitor, reduced the effects of CCl4-induced liver injury and was associated with increased Parkin, pAKT, and ATP production. CONCLUSIONS: Downregulation of FKBP51 represents a promising therapeutic target for liver disease treatment.

Effect of GnRH agonist trigger with or without low-dose hCG on reproductive outcomes for PCOS women with freeze-all strategy: a propensity score matching study.

PURPOSE: This study aimed to compare the effect of gonadotropin-releasing hormone agonist (GnRHa) trigger alone versus dual trigger comprising GnRHa and low-dose human chorionic gonadotropin (hCG) on reproductive outcomes in patients with polycystic ovary syndrome (PCOS) who received the freeze-all strategy. METHODS: A total of 615 cycles were included in this retrospective cohort study. Propensity score matching (PSM) was performed to control potential confounding factors between GnRHa-trigger group (0.2 mg GnRHa) and dual-trigger group (0.2 mg GnRHa plus 1000/2000 IU hCG) in a 1:1 ratio. Multivariate logistic regression was applied to estimate the association between trigger methods and reproductive outcomes. RESULTS: After PSM, patients with dual trigger (n = 176) had more oocytes retrieved, mature oocytes, and 2PN embryos compared to that with GnRHa trigger alone. However, the oocytes maturation rate, normal fertilization rate, and frozen embryos between the two groups were not statistically different. The incidence of ovarian hyperstimulation syndrome (OHSS) (14.8% vs. 2.8%, P < 0.001) and moderate/severe OHSS (11.4% vs. 1.7%, P < 0.001) were significantly higher in dual-trigger group than in GnRHa-alone group. Logistic regression analysis showed the adjusted odds ratio of dual trigger was 5.971 (95% confidence interval 2.201-16.198, P < 0.001) for OHSS. The pregnancy and single neonatal outcomes were comparable between the two groups (P > 0.05). CONCLUSION: For PCOS women with freeze-all strategy, GnRHa trigger alone decreased the risk of OHSS without damaging oocyte maturation and achieved satisfactory pregnancy outcomes.

The association of post-embryo transfer SARS-CoV-2 infection with early pregnancy outcomes in in vitro fertilization: a prospective cohort study.

BACKGROUND: The influence of SARS-CoV-2 infection after embryo transfer on early pregnancy outcomes in in vitro fertilization or intracytoplasmic sperm injection-embryo transfer treatment remains inadequately understood. This knowledge gap endures despite an abundance of studies investigating the repercussions of preceding SARS-CoV-2 infection on early pregnancy outcomes in spontaneous pregnancies. OBJECTIVE: This study aimed to investigate the association between SARS-CoV-2 infection within 10 weeks after embryo transfer and early pregnancy outcomes in patients undergoing in vitro fertilization/intracytoplasmic sperm injection treatment. STUDY DESIGN: This prospective cohort study was conducted at a single public in vitro fertilization center in China. Female patients aged 20 to 39 years, with a body mass index ranging from 18 to 30 kg/m2, undergoing in vitro fertilization/intracytoplasmic sperm injection treatment, were enrolled between September 2022 and December 2022, with follow-up extended until March 2023. The study tracked SARS-CoV-2 infection time (≤14 days, ≤28 days, and ≤10 weeks after embryo transfer), symptoms, vaccination status, the interval between vaccination and embryo transfer, and early pregnancy outcomes, encompassing biochemical pregnancy rate, implantation rate, clinical pregnancy rate, and early miscarriage rate. The study used single-factor analysis and multivariate logistic regression to examine the association between SARS-CoV-2 infection status, along with other relevant factors, and the early pregnancy outcomes. RESULTS: A total of 857 female patients undergoing in vitro fertilization/intracytoplasmic sperm injection treatment were analyzed. In the first stage, SARS-CoV-2 infection within 14 days after embryo transfer did not have a significant negative association with the biochemical pregnancy rate (adjusted odds ratio, 0.74; 95% confidence interval, 0.51-1.09). In the second stage, SARS-CoV-2 infection within 28 days after embryo transfer had no significant association with the implantation rate (36.6% in infected vs 44.0% in uninfected group; P=.181). No statistically significant association was found with the clinical pregnancy rate after adjusting for confounding factors (adjusted odds ratio, 0.69; 95% confidence interval, 0.56-1.09). In the third stage, SARS-CoV-2 infection within 10 weeks after embryo transfer had no significant association with the early miscarriage rate (adjusted odds ratio, 0.77; 95% confidence interval, 0.35-1.71). CONCLUSION: Our study suggests that SARS-CoV-2 infection within 10 weeks after embryo transfer may not be negatively associated with the biochemical pregnancy rate, implantation rate, clinical pregnancy rate, and early miscarriage rate in patients undergoing in vitro fertilization/intracytoplasmic sperm injection treatment. It is important to note that these findings are specific to the target population of in vitro fertilization/intracytoplasmic sperm injection patients aged 20 to 39 years, without previous SARS-CoV-2 infection, and with a body mass index of 18 to 30 kg/m2. This information offers valuable insights, addressing current concerns and providing a clearer understanding of the actual risk associated with SARS-CoV-2 infection after embryo transfer.

Identification of AP002498.1 and LINC01871 as prognostic biomarkers and therapeutic targets for distant metastasis of colorectal adenocarcinoma.

BACKGROUND: Increasing evidence suggests that lncRNA (Long non-coding RNA, lncRNA)-mediated ceRNA (competing endogenous RNA, ceRNA) networks are involved in the occurrence and progression of colorectal cancer (CRC). However, the roles of the lncRNA-miRNA-mRNA ceRNA network in distant metastasis of CRC are still unclear. METHODS: In this study, we constructed a specific ceRNA network to identify potential biomarkers and therapeutic targets for distant metastasis of CRC. Specifically, RNA-Seq data from The Cancer Genome Atlas (TCGA) were used to screen for differentially expressed lncRNAs (DElncRNAs) and mRNAs (DEmRNAs) related to metastasis. After validation and selection by qRT-PCR and univariate and multivariate analysis of the metastasis- and prognosis-related lncRNAs, the regulated microRNAs (miRNAs) and coexpressed mRNAs were used to construct a ceRNA network for distant metastasis of CRC. RESULTS: Two key distant metastasis-related DElncRNAs, AP002498.1 and LINC01871, were identified by univariate and multivariate analysis in combination with analyses of clinical data and expression levels. Furthermore, lncRNA-associated ceRNA subnetworks were constructed from the predicted miRNAs and 13 coexpressed DEmRNAs (SERPINA1, ITLN1, REG4, L1TD1, IGFALS, MUC5B, CIITA, CXCL9, CXCL10, GBP4, GNLY, IDO1, and NOS2). The AP002498.1- and LINC01871-associated ceRNA subnetworks regulated the expression of the target genes SERPINA1 and MUC5B and GNLY, respectively, through the associated miRNAs. CONCLUSION: The DElncRNA AP002498.1 and the LINC01871/miR-4644 and miR-185-5p/GNLY axes were identified as being closely associated with distant metastasis and could represent independent prognostic biomarkers or therapeutic targets in colorectal adenocarcinoma.

Young obese patients may benefit from GnRH-a long protocol contributing to higher implantation rate and live birth rate of fresh IVF-ET cycles.

Introduction: Obesity has detrimental influences on women reproductive health. There is little experience in optimizing controlled ovarian hyperstimulation (COH) protocols to treat Chinese obese patients who are undergoing in vitro fertilization and embryo transfer (IVF-ET) therapy. Methods: The clinical outcome differences were retrospectively analyzed among obese patients who received gonadotrophin-releasing hormone agonist (GnRH-a), GnRH antagonist (GnRH-ant), micro dose GnRH-a (mGnRH-a) and GnRH-a long protocol in IVF-ET cycle at Chengdu Jinjiang Hospital for Women's and Children's Health from January 2014 to December 2019. Results: The transplantation rate of the GnRH-a long protocol group (59.1%) was higher than that of the GnRH-ant (25.9%) and mGnRH-a (36.7%) groups. The total live birth rate of the GnRH-a long protocol group (46.2%) was higher than that of the GnRH-a group (25.9%) and GnRH-ant group (40.3%). The total number of frozen embryos in the GnRH-ant group was higher than in the other groups (P < 0.05). After adjusting for confounding factors, the logistic regression analysis showed that the GnRH-a long protocol group had higher probabilities of biochemical pregnancy, clinical pregnancy, and live birth than the GnRH-a protocol group. The Gn dose in the mGnRH-a group was higher than the other three groups. Whether single or twin, there were similar neonatal outcomes among the four groups including premature birth rate, Apgar score, newborn weight, and length. Conclusion: For young obese patients undergoing IVF-ET, the GnRH-a long protocol for COH gives better pregnancy outcomes.

Efficient plant genome engineering using a probiotic sourced CRISPR-Cas9 system.

Among CRISPR-Cas genome editing systems, Streptococcus pyogenes Cas9 (SpCas9), sourced from a human pathogen, is the most widely used. Here, through in silico data mining, we have established an efficient plant genome engineering system using CRISPR-Cas9 from probiotic Lactobacillus rhamnosus. We have confirmed the predicted 5'-NGAAA-3' PAM via a bacterial PAM depletion assay and showcased its exceptional editing efficiency in rice, wheat, tomato, and Larix cells, surpassing LbCas12a, SpCas9-NG, and SpRY when targeting the identical sequences. In stable rice lines, LrCas9 facilitates multiplexed gene knockout through coding sequence editing and achieves gene knockdown via targeted promoter deletion, demonstrating high specificity. We have also developed LrCas9-derived cytosine and adenine base editors, expanding base editing capabilities. Finally, by harnessing LrCas9's A/T-rich PAM targeting preference, we have created efficient CRISPR interference and activation systems in plants. Together, our work establishes CRISPR-LrCas9 as an efficient and user-friendly genome engineering tool for diverse applications in crops and beyond.

Effect of serum progesterone on human chorionic gonadotropin trigger day / metaphase II oocyte ratio on pregnancy and neonatal outcomes in women undergoing ICSI cycle.

BACKGROUND: The serum progesterone on human chorionic gonadotropin trigger day / metaphase II oocyte (P/MII) ratio might be a more predictable indicator of pregnancy and neonatal outcomes as compare to P/estradiol (E2) or P alone. Hence, we conducted a larger population study to compare the pregnancy and neonatal outcomes in the low and high P/MII ratio. METHODS: A retrospective, single-center, larger population cohort study between January 2015 and August 2021. Calculate the threshold effect of P/MII ratio on clinical pregnancy rate according to the construct smooth curve fitting. Divide data into two groups by threshold for comparison. RESULTS: 3566 fresh ICSI-ET cycles were included, in which 929 singleton delivery and 676 twin deliveries. Compare to P/MII ≤ 0.367 group, it indicated that the P/MII > 0.367 group had a lower clinical pregnancy rate and live birth rate, furthermore, a significantly higher rate of LBW and SGA were observed in the singleton and twin deliveries. No deleterious impact of high P/MII ratio on embryo quality and undesirable pregnancy outcomes was shown. CONCLUSIONS: When P/MII is higher than 0.367, may have adverse impacts on pregnancy and neonatal outcomes for ICSI cycle.

Preoperative systemic inflammation response index is an independent prognostic marker for BCG immunotherapy in patients with non-muscle-invasive bladder cancer.

BACKGROUND: The Systemic Inflammatory Response Index (SIRI) is a novel prognostic biomarker based on peripheral blood counts of neutrophils, monocytes, and lymphocytes. Recent evidence suggests that it is associated with poor prognosis in various cancers. However, the predictive value of the SIRI in non-muscle-invasive bladder cancer (NMIBC) patients treated with intravesical Bacillus Calmette-Guerin (BCG) immunotherapy remains elusive. Therefore, this study aimed to evaluate the potential of SIRI as a prognostic factor in these patients. METHODS: A total of 540 patients with NMIBC who underwent BCG immunotherapy following transurethral resection of bladder tumor (TURBT) were enrolled in this study. Using receiver operating characteristic (ROC) curves and the Youden index, patients were divided into high and low SIRI groups based on the cutoff values. Univariable and multivariable logistic regression analyses were performed to identify independent predictors of BCG non-response. Thereafter, propensity score matching (PSM) was used to eliminate bias due to confounding factors between the low and high SIRI groups. Finally, the Kaplan-Meier method was used to compare recurrence-free survival (RFS) and progression-free survival (PFS) between the two groups. RESULTS: Multivariable logistic regression analysis revealed that high SIRI (p = 0.001), high MLR (p = 0.015), and high tumor pathological T stage (p = 0.015) were significantly correlated with non-response to BCG therapy. In addition, both RFS and PFS were shorter in the high SIRI group than in the other group before and after PSM (both p < 0.05). Collectively, our results indicate that the combination of tumor pathological T staging and the SIRI can enhance the predictive power of BCG response. CONCLUSION: Pretreatment peripheral blood SIRI can be employed to predict the response to BCG immunotherapy and the prognosis of NMIBC patients. Taken together, the combination of T stage and SIRI demonstrated robust performance in predicting the response to BCG immunotherapy in NMIBC patients.

Effects of sequential cleavage and blastocyst embryo transfer on pregnancy outcomes in patients with poor ovarian response.

The management of patients with poor ovarian response (POR) remains a major challenge for fertility specialists in in vitro fertilization-embryo transfer (IVF-ET). In this retrospective cohort study, we aimed to evaluate the clinical effect of sequential transfer on pregnancy outcomes in patients with POR. A total of 3579 POR patients who underwent the first frozen embryo transfer (FET) cycle were enrolled from January 2018 to April 2021. The patients were divided into three groups according to the embryo transfer (ET) strategy adopted: a study group that included POR patients in whom a cleavage-stage embryo (day 3) and a blastocyst (day 5/6) were transferred (sequential transfer group), and two control groups in whom two cleavage-stage embryos (D3-dET group) or two blastocysts (D5/6-dET group) were transferred. The study group was matched with the control groups at a ratio of 1:4 by propensity score matching (PSM). The main pregnancy outcomes measured were the live birth rate and multiple pregnancy rate. After PSM, the live birth rate in the sequential transfer group was significantly higher than that in the D3-dET group (44.2% vs. 34.3%, P = 0.019), and was similar to that in the D5/6-dET group (44.2% vs. 45.3%; P = 0.90). In addition, there was no increase in the risk of multiple pregnancy among POR patients undergoing sequential transfer compared with both D3-dET (26.7% vs. 25.6%, P = 0.85) and D5/6-dET (26.7% vs. 28.4%, P = 0.97) groups. These findings imply that sequential transfer is an effective option for POR patients and could be utilized after careful consideration.

Assessment of cumulative cancer risk attributable to diagnostic X-ray radiation: a large cohort study.

OBJECTIVE: To assess the risk of cancer induced by diagnostic X-ray exposure in multiple radiological examinations and to explore the relevant influences to provide a reference for rational usage of X-ray examinations. METHODS: Data for all adult patients who underwent X-ray examinations from August 2004 to April 2020 in a general hospital was collected, including sex, age, primary diagnosis, and X-ray examination. Based on the Biological Effects of Ionizing Radiations report, age and sex and effective dose for a single X-ray examination were used to calculate the lifetime attributable risk (LAR). Patients whose cancer LAR values were in the top 5% were considered to have a high cancer risk; the factors influencing this status were explored by using multivariate logistic regression analyses. RESULTS: In total, 1,143,413 patients with 3,301,286 X-ray examinations were included. LARs of cancer incidence and death were < 0.2% and < 0.13% among 95% of patients and they were > 1% among 0.21% and 0.07% of patients. High risks of incidence and death were significantly associated with corrected exposure frequency (odds ratio [OR], 1.080 and 1.080), sex (OR, male vs. female, 0.421 and 0.372), and year of birth (OR, 1.088 and 1.054), with all p values < 0.001. Among 20 disease categories, congenital disease (OR, 3.792 and 4.024), genitourinary disease (OR, 3.608 and 3.202), digestive disease (OR, 3.247 and 3.272), and tumor disease (OR, 2.706 and 2.767) had the strongest associations with high risks of incidence and death (all p values < 0.001). CONCLUSIONS: Cancer risk induced by diagnostic X-ray examinations can be considered acceptable clinically. Patients having certain diseases are potentially at a relative higher risk due to recurrent examinations. KEY POINTS: • It was the first large-scale investigation of cumulative X-ray exposure in China, involving more than 3.3 million X-ray scans of all types of diagnostic X-ray examinations for about 1.1 million patients during the past 16 years. • The study revealed that the incidence risk of cancer induced by X-ray-related examinations was 0.01% on average, which was substantially lower than that of cancer induced by non-X-ray radiation. The risk could be considered acceptable clinically. • Patients having certain diseases were potentially at a relatively higher cancer risk due to recurrent X-ray examinations. The cumulative effect of X-ray exposure could not be ignored and was worthy of attention.

Establishment of quantitative nested-PCR of Abelson interactor 1 transcript variant-11.

Abelson interactor 1 (ABI1), which presents 18 Transcript Variants (TSV), plays an important role in CRC metastasis. Different ABI1-TSVs play synergistic or antagonistic roles in the same pathophysiological events. ABI1 Transcript Variant-11 (ABI1-TSV-11) functionally promotes lymph node metastasis of left-sided colorectal cancer (LsCC) and is an independent molecular marker to evaluate the prognosis of patients with LsCC. However, there is still lack of a quick and accurate method to detect the expression of ABI-TSV-11, distinguishing ABI1-TSV-11 from other 17 TSVs. To establish a rapid method specific for ABI1-TSV-11detection, we developed a quantitative nested-PCR method composed of pre-amplification regular PCR using ABI1 universal primer pair and the followed Real Time (RT)-qPCR using ABI1-TSV-11 specific primer pair spanning exon-exon junction. ABI1-TSV-11-overexpressed SW480 and LoVo cell lines were used to verify the quantitative nested-PCR assay, and the sequencing data was used to evaluate the accuracy of ABI1-TSV-11 quantitative nested-PCR assay. The detection limit was 5.24×104 copies/ml. ABI1-TSV-11 quantitative nested-PCR provides a new technical means for the detection of ABI1-TSV-11.

Low LH level does not indicate poor IVF cycle outcomes with GnRh-a single trigger: a retrospective analysis.

OBJECTIVE: To compare the in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycle outcomes between patients with low and normal serum luteinizing hormone (LH) levels on the day after a gonadotropin-releasing hormone agonist (GnRH-a) single trigger. We further investigated the efficacy of human chorionic gonadotropin (hCG) retrigger on IVF cycle outcomes in patients with low LH levels after GnRH-a single trigger. METHODS: We retrospectively analyzed 957 infertile patients (tubal factor, ovulation disorders, male sperm factor, or unexplained infertility) who were treated with IVF/ICSI at the Chengdu Xinan Gynecology Hospital from July 2017 to December 2020. Patients received sufficient GnRH-a single trigger were divided into two groups based on the serum LH levels on the next day of trigger: normal serum LH levels (≥ 10 mIU/mL) group (control group, n = 906) and low LH levels (< 10 mIU/mL) group (experimental group, n = 51). And the efficacy of hCG retrigger on IVF/ICSI cycle outcomes in 10 patients with low LH levels after GnRH-a single trigger. RESULTS: There were no significant differences in IVF/ICSI cycle outcomes, including egg yield, two pronuclei fertilization rate, excellent embryo rate, or live birth rate of frozen-thawed embryos between patients with low and normal LH levels after GnRH-a trigger. It showed significantly higher risk of ovarian hyperstimulation syndrome in the group of low LH levels [ 0.7%(1/137) vs. 8.5%(4/47), P = 0.016] compared with the group of normal LH levels who received GnRH-a single trigger. The hCG retrigger had no obvious efficacy on cycle outcomes in patients with low LH levels, including oocytes retrieved, fertilization rate, embryo conditions, and live birth rate of frozen-thawed cycles. CONCLUSION: The IVF/ICSI cycle outcomes of patients with low LH levels on the day after GnRH-a administration were similar to those of patients with normal LH levels. Blood LH test might not be required on the day following the trigger. The hCG retrigger did not have any effect on the cycle outcomes, suggesting that immediate retriggering with hCG was unnecessary.

Nomogram models to predict low fertilisation rate and total fertilisation failure in patients undergoing conventional IVF cycles.

OBJECTIVES: To establish visualised prediction models of low fertilisation rate (LFR) and total fertilisation failure (TFF) for patients in conventional in vitro fertilisation (IVF) cycles. DESIGN: A retrospective cohort study. SETTING: Data from August 2017 to August 2021 were collected from the electronic records of a large obstetrics and gynaecology hospital in Sichuan, China. PARTICIPANTS: A total of 11 598 eligible patients who underwent the first IVF cycles were included. All patients were randomly divided into the training group (n=8129) and the validation group (n=3469) in a 7:3 ratio. PRIMARY OUTCOME MEASURE: The incidence of LFR and TFF. RESULTS: Logistic regressions showed that ovarian stimulation protocol, primary infertility and initial progressive sperm motility were the independent predictors of LFR, while serum luteinising hormone and P levels before human chorionic gonadotropin injection and number of oocytes retrieved were the critical predictors of TFF. And these indicators were incorporated into the nomogram models. According to the area under the curve values, the predictive ability for LFR and TFF were 0.640 and 0.899 in the training set and 0.661 and 0.876 in the validation set, respectively. The calibration curves also showed good concordance between the actual and predicted probabilities both in the training and validation group. CONCLUSION: The novel nomogram models provided effective methods for clinicians to predict LFR and TFF in traditional IVF cycles.

Strongly enhanced THz generation enabled by a graphene hot-carrier fast lane.

Semiconductor photoconductive switches are useful and versatile emitters of terahertz (THz) radiation with a broad range of applications in THz imaging and time-domain spectroscopy. One fundamental challenge for achieving efficient ultrafast switching, however, is the relatively long carrier lifetime in most common semiconductors. To obtain picosecond ultrafast pulses, especially when coupled with waveguides/transmission lines, semiconductors are typically engineered with high defect density to reduce the carrier lifetimes, which in turn lowers the overall power output of the photoconductive switches. To overcome this fundamental trade-off, here we present a new hybrid photoconductive switch design by engineering a hot-carrier fast lane using graphene on silicon. While photoexcited carriers are generated in the silicon layer, similar to a conventional switch, the hot carriers are transferred to the graphene layer for efficient collection at the contacts. As a result, the graphene-silicon hybrid photoconductive switch emits THz fields with up to 80 times amplitude enhancement compared to its graphene-free counterpart. These results both further the understanding of ultrafast hot carrier transport in such hybrid systems and lay the groundwork toward intrinsically more powerful THz devices based on 2D-3D hybrid heterostructures.

Quantitative evaluation of diaphragmatic motion during forced breathing in chronic obstructive pulmonary disease patients using dynamic chest radiography.

Objective: To quantitatively evaluate the bilateral diaphragmatic motion difference during forced breathing between chronic obstructive pulmonary disease (COPD) patients and healthy individuals using dynamic chest radiography technique. Methods: This prospective study included the COPD patients (n: 96, f/m: 17/79, age: 66 ± 8 years old) and healthy individuals (n: 50, f/m: 42/8, age: 53 ± 5 years old) that underwent dynamic chest radiography with a flat panel X-ray detector system during forced breathing in a standing position. After analyzing the excursions, duration and velocity of diaphragmatic motion were automatically calculated using the postprocessing software. The parameters of diaphragmatic motion including excursion, duration, velocity, inhalation/exhalation times were assessed in all subjects for both diaphragms. The correlation between lung function parameters and diaphragmatic motion excursions were further evaluated. Results: The excursions of diaphragmatic motion in COPD patients were significantly decreased in COPD patients compared with healthy individuals during forced breathing (P < 0.05). The excursion in COPD patients was 35.93 ± 13.07 mm vs. 41.49 ± 12.07 mm in healthy individuals in the left diaphragm, and 32.05 ± 12.29 mm in COPD patients vs. 36.88 ± 10.96 mm in healthy individuals in the right diaphragm. The duration of diaphragmatic motion significantly decreased in COPD patients, compared with the healthy individuals (P < 0.05). The inhalation time in COPD patients was 2.03 ± 1.19 s vs. 2.53 ± 0.83 s in healthy individuals in the left diaphragm and 1.94 ± 1.32 s in COPD patients vs. 2.23 ± 1.21 s in healthy individuals in the right diaphragm. The exhalation time was 4.77 ± 1.32 s in COPD patients vs. 6.40 ± 2.73 s in healthy individuals in the left diaphragm and 4.94 ± 3.30 s in COPD patients vs. 6.72 ± 2.58 s in healthy individuals in the right diaphragm. The peak velocity of diaphragmatic motion showed no significant difference between COPD and healthy groups. The excursions of bilateral diaphragmatic motion showed moderate correlation with FEV1/FVC (r = 0.44, P < 0.001). Multi-linear regression analysis showed that the excursions of bilateral diaphragm are significantly associated with COPD occurrence (P < 0.05). Conclusion: The excursions and duration of diaphragmatic motion during forced breathing are significantly decreased in COPD patients, compared with healthy individuals. Our study showed that precise bilateral diaphragmatic motion activity can be evaluated by dynamic chest radiography.

An Individualized Recommendation for Controlled Ovary Stimulation Protocol in Women Who Received the GnRH Agonist Long-Acting Protocol or the GnRH Antagonist Protocol: A Retrospective Cohort Study.

Background: The GnRH agonist long-acting protocol and GnRH antagonist protocol are widely used in ovarian stimulation. Which protocol eliciting higher live birth rate for IVF/ICSI patients with different ages, different ovarian reserves and different body mass index (BMI) has not been studied. However, among these protocols, the one that elicits higher live birth in IVF/ICSI patients with different ages, ovarian reserves and body mass indexes (BMI) has not been identified. Methods: This was a retrospective cohort study about 8579 women who underwent the first IVF-ET from January, 2018 to August, 2021. Propensity Score Matching (PSM) was used to improve the comparability between two protocols. Results: After PSM, significant higher live birth rates were found in the GnRH agonist long-acting protocol compared to GnRH antagonist protocol (44.04% vs. 38.32%) (p<0.001). Stratified analysis showed that for those with AMH levels between 3 ng/ml and 6 ng/ml, with BMI ≥ 24 kg/m2 and were aged ≥ 30 years old, and for those women with BMI < 24kg/m2 and were aged ≥30 years whose AMH levels were ≤ 3ng/ml, the GnRH agonist long-acting protocol was more likely to elicit live births [OR (95%CI), 2.13(1.19,3.80)], [OR (95%CI), 1.41(1.05,1.91)]. However, among women with BMI ≥ 24kg/m2 and were aged ≥30 years whose AMH levels were ≤ 3ng/ml, the GnRH agonist long-acting protocol had a lower possibility of eliciting live births [OR (95%CI), 0.54(0.32,0.90)]. Also, among women with AMH levels between 3 ng/ml and 6 ng/ml, with BMI ≥ 24 kg/m2 and with age < 30 years and for those with AMH levels between 3 ng/ml and 6 ng/ml, regardless of age, and with BMI<24kg/m2,, the possibility of live births was similar between the two protocols [OR (95%CI), 1.06(0.60,1.89)], [OR (95%CI), 1.38(0.97,1.97)], [OR (95%CI), 0.99(0.72,1.37)]. Among the women with AMH levels ≤ 3 ng/ml and with were aged < 30years, regardless of BMI, the possibility of live birth was similar between the two protocols [OR (95%CI), 1.02(0.68,1.54)], [OR (95%CI), 1.43(0.68,2.98)]. Moreover, among women with AMH levels ≥ 6ng/ml, the possibility of live birth was similar between the two protocols [OR (95%CI),1.42(0.75,2.69)], [OR (95%CI),1.02(0.19,5.35)], [OR (95%CI), 1.68(0.81,3.51)], [OR (95%CI), 0.51(0.10,2.55)]. Conclusions: The suitability of the GnRH agonist long-acting protocol or GnRH antagonist protocol to infertility patients is dependent on specific biological characteristics of the patients.

Genome-wide analyses of PAM-relaxed Cas9 genome editors reveal substantial off-target effects by ABE8e in rice.

PAM-relaxed Cas9 nucleases, cytosine base editors and adenine base editors are promising tools for precise genome editing in plants. However, their genome-wide off-target effects are largely unexplored. Here, we conduct whole-genome sequencing (WGS) analyses of transgenic plants edited by xCas9, Cas9-NGv1, Cas9-NG, SpRY, nCas9-NG-PmCDA1, nSpRY-PmCDA1 and nSpRY-ABE8e in rice. Our results reveal that Cas9 nuclease and base editors, when coupled with the same guide RNA (gRNA), prefer distinct gRNA-dependent off-target sites. De novo generated gRNAs by SpRY editors lead to additional, but insubstantial, off-target mutations. Strikingly, ABE8e results in ~500 genome-wide A-to-G off-target mutations at TA motif sites per transgenic plant. ABE8e's preference for the TA motif is also observed at the target sites. Finally, we investigate the timeline and mechanism of somaclonal variation due to tissue culture, which chiefly contributes to the background mutations. This study provides a comprehensive understanding on the scale and mechanisms of off-target and background mutations occurring during PAM-relaxed genome editing in plants.