Poria acid inhibit the growth and metastasis of renal cell carcinoma by inhibiting the PI3K/akt/NF-κb signaling pathway.

Background: Poria acid (PAC) is a triterpene compound found in Poria cocos, a traditional Chinese medicine (TCM). The current study aims to explore the therapeutic effects and potential mechanisms of PAC on the migration and proliferation of human renal cell carcinoma (RCC) cells as well as tumor growth in animal model. Methods: Cell viability and proliferative capacity of normal renal cells and RCC cells were investigated by MTT assay. In addition, 786-O cells were divided into four groups and treated with different concentrations of PAC (0, 20, 40, and 60 µM) for 48 h. Cell scratch test and cell invasion assay were performed to evaluate the effects of PAC on the invasion and migration of RCC cells, respectively. The effects of PAC on apoptosis of RCC cells and expression levels of PI3K/Akt/NF-kB signaling pathway-related biomarkers were investigated using TUNEL staining and Western blotting methods, respectively. Effects of PAC on the inhibitory activity of RCC tumor in mice were evaluated in a 786-O CDX model. Results: The study found that PAC inhibited the viability of RCC cells in a dose-dependent manner, as demonstrated by in vitro cell assays (p < 0.05). However, PAC showed no significant inhibitory effect on normal renal cells (p > 0.05). PAC also significantly inhibited the migration and invasion of RCC via EMT/MMP signaling pathways (p < 0.05). Immunofluorescence and immunoblotting results showed that PAC induced the apoptosis of RCC, which was accompanied by changes in the expression levels of apoptosis-related proteins (p < 0.05). Moreover, PAC significantly downregulated the PI3K/Akt/NF-kB signaling pathway in a concentration-dependent manner (p < 0.05). The effect of PAC on RCC apoptosis was dramatically reversed by 740Y-P (PI3K agonist) (p < 0.05) but significantly enhanced in the presence of LY294002 (PI3K inhibitor) (p < 0.05). The results of in vivo experiment also demonstrated that the antitumor activity of PAC was achieved by affecting the PI3K/Akt/NF-kB signaling pathway. Conclusions: PAC can effectively suppress the proliferation, invasion and migration of RCC cells, and exhibit anti-tumor effects in RCC model by inhibiting the PI3K/Akt/NF-kB signaling pathway.

How changes in landscape patterns affect the carbon emission: a case study in the Chengdu-Chongqing Economic Circle, China.

The construction of low-carbon cities is an optimal means to balance the competing interests of economic growth and carbon emission reduction. This study focuses on the optimization of land use patterns with a low carbon orientation, taking the Chengdu-Chongqing Economic Circle (CCEC), the fourth-largest economic growth pole in China, as an example. The panel data regression analysis is carried out to identify the dynamic correlations between the landscape changes and the carbon emission induced by land use and land cover change (LICE) of each city, each year, for the last 20 years. The results show that the CCEC has witnessed a 142.85% increase in carbon emissions during the period studied, with the growth of built-up land contributing 94% of total carbon emissions from 2000 to 2020. By constructing the panel regression model, this study finds that the intensity of carbon emissions increases significantly as the urban built-up land area and the agglomeration of artificial structures increase. The conversion of cropland, which dominates the landscape pattern, to built-up land has led to further fragmentation of the landscape pattern and a reduction in LPI, thus increasing carbon emissions. And a more complex regional landscape pattern will have a positive impact on carbon emission reduction. Based on the above findings, suggestions are articulated for carbon emission reduction.

Effects of chromosomal translocation characteristics on fertilization and blastocyst development - a retrospective cohort study.

OBJECTIVE: To determine the effect of different translocation characteristics on fertilization rate and blastocyst development in chromosomal translocation patients. METHODS: This retrospective cohort study was conducted at the Third Affiliated Hospital of Zhengzhou University From January 2017 to December 2022.All couples were diagnosed as reciprocal translocation or Robertsonian translocation by karyotype of peripheral blood lymphocytes test. After adjusting for confounding factors, the effect of chromosomal rearrangement characteristics, such as carrier sex, translocation type, chromosome length and break sites, on fertilization rate and embryo development were analysed separately using multiple linear regression. RESULTS: In cases of Robertsonian translocation (RobT), the carrier sex plays an independent role in fertilization rate, and the male carriers was lower than that of female carriers (76.16% vs.86.26%, P = 0.009). In reciprocal translocation (RecT), the carrier sex, chromosome types and break sites had no influence on fertilization rate, blastocyst formation rate (P > 0.05). However, patients with human longer chromosomal (chromosomes 1-5) translocation have a lower available blastocyst formation rate (Group AB vs. Group CD: 41.49%vs.46.01%, P = 0.027). For male carriers, the translocation types was an independent factor affecting the fertilization rate, and the RobT was the negative one (B = - 0.075, P = 0 0.009). In female carriers, we did not observe this difference (P = 0.227). CONCLUSIONS: In patients with chromosomal translocation, the fertilization rate may be influenced by carrier sex and translocation type, chromosomes 1-5 translocation may adversely affect the formation of available blastocysts. Break sites have no role in fertilization and blastocyst development.

Comparison of the neonatal outcomes of progestin-primed ovarian stimulation and flexible GnRH antagonist protocols: a propensity score-matched cohort study.

Objective: To compare the neonatal outcomes of progestin-primed ovarian stimulation (PPOS) and flexible gonadotropin-releasing hormone (GnRH) antagonist protocols. Methods: This was a retrospective propensity score-matched (PSM) cohort study. Women who underwent their first frozen embryo transfer (FET) cycle with freezing of all embryos followed by PPOS or GnRH antagonist protocols between January 2016 and January 2022 were included. Patients using PPOS were matched with the patients using GnRH antagonist at a 1:1 ratio. The main focus of this study was the neonatal outcomes of singleton live births, including preterm birth (PTB), low birth weight (LBW), small for gestational age (SGA), macrosomia and large for gestational age (LGA). Results: After 1:1 PSM, a total of 457 PPOS and 457 GnRH antagonist protocols were included for analysis. The average starting dose of gonadotropin (275.1 ± 68.1 vs. 249.3 ± 71.3, P<0.01) and total dose of gonadotropin (2799.6 ± 579.9 vs. 2634.4 ± 729.1, P<0.01) were significantly higher in the PPOS protocol than in the GnRH antagonist protocol. The other baseline and cycle characteristics were comparable between the two protocols. The rates of PTB (P=0.14), LBW (P=0.11), SGA (P=0.31), macrosomia (P=0.11) and LGA (P=0.49) did not differ significantly between the two groups. A total of 4 patients in the PPOS group and 3 patients in the GnRH antagonist group qualified as having congenital malformations. Conclusion: PPOS resulted in singleton neonatal outcomes similar to those of a GnRH antagonist protocol. The application of the PPOS protocol is a safe option for infertility patients.

Anti­PD1 therapy­associated distal renal tubular acidosis: A case report.

Distal renal tubular acidosis (RTA) is a rare adverse reaction to immune checkpoint inhibitors, which only occurs in a small number of cases. To the best of our knowledge, distal RTA caused by sintilimab, a programmed cell death protein 1 (PD-1) inhibitor, has not been previously reported. In the present study, the case of a 62-year-old man with metastatic cardiac carcinoma treated with sintilimab anti-PD-1 therapy was reported. After the fourth administration of sintilimab, the treatment course was interrupted by metabolic hyperchloraemic acidosis with hypokalaemia. Following urine and blood tests, immunotherapy-induced distal RTA was suspected. Treatment with sintilimab and chemotherapy was stopped, and treatment with sodium bicarbonate and potassium citrate was started, which resulted in an adequate response. The present study provides the first case of distal RTA secondary to sintilimab treatment.

TSH levels after fresh embryo transfer are associated with reproductive outcomes in euthyroid women undergoing the first IVF/ICSI cycles.

To investigate whether there is a relationship between TSH levels on the 14th day post embryo transfer (D14 TSH levels) and the reproductive outcomes in euthyroid women who are free from levothyroxine (LT4) treatment and undergo the first in vitro fertilization /intracytoplasmic sperm injection embryo transfer (IVF/ICSI-ET) cycles with the homogeneous ovarian stimulation protocols. This was a prospective study including a total of 599 euthyroid women undergoing the first IVF/ICSI ET cycles. Serum samples were collected and frozen on the 14th day post embryo transfer. TSH levels were measured after the confirmation of clinical pregnancy. The patients were divided into three groups (low-normal ≤ 2.5 mIU/L; high-normal 2.5-4.2 mIU/L; and high > 4.2 mIU/L) based on D14 TSH levels. Reproductive outcomes were compared among the three groups. Binary logistic regression analyses and generalized additive mixed models with smoothing splines were used to investigate the relationship between TSH levels and reproductive outcomes. D14 TSH levels were significantly elevated compared to basal TSH levels, and the degree of TSH elevation was significantly higher in pregnant women compared to that in non-pregnant women. The clinical pregnancy and live birth rates increased significantly in the high-normal D14 TSH groups, and doubled in the high D14 TSH groups compared to the low TSH groups. When adjusted by age, basal TSH, AMH, E2, endometrial thickness, type and causes of infertility, and transferred embryos, the dose-dependent relationships between D14 TSH and clinical pregnancy and live birth were observed. Obstetric outcomes in singleton or twins live birth among the different D14 TSH groups were similar. Elevated D14 TSH levels were associated with better clinical pregnancy and live birth rates, and were not associated with worse obstetric outcomes. The mechanisms to explain the phenomenon remained to be studied.

Is it necessary for young patients with recurrent implantation failure to undergo preimplantation genetic testing for aneuploidy?

Objective: To determine whether preimplantation genetic testing for aneuploidy (PGT-A) can improve the pregnancy outcomes of patients aged under 38 years who have a history of recurrent implantation failure(RIF). Design: Retrospective cohort study. Methods: We retrospectively studied the pregnancy outcomes of RIF patients aged under 38 years from January 2017 to December 2021.178 patients were divided into two groups according to whether they underwent PGT-A: the PGT-A group(n=59)and the control group(n=119).In the PGT-A group, we compared the euploidy rate of the different quality and developmental rate blastocysts. In both groups,the patients were the first frozen-thaw single blastocysts transfer after the diagnosis of RIF. Among the pregnancy outcomes, the clinical pregnancy rate was assessed as the primary outcome. The spontaneous abortion rate and ongoing pregnancy rate were the secondry outcomes. The generalized estimation equation was used to adjust for the blastocysts derived from the same patients. Multivariate logistic analysis models were used to compare the pregnancy outcomes between the two groups. Results: In the PGT-A group, 293 blastocysts obtained from59 patients underwent PGT-A. The proportions of euploidy, aneuploidy and mosaic blastocysts were 56.31%, 25.60% and 18.09%, respectively. A comparison of the euploidy rates of different quality blastocysts showed that the rate of good-quality blastocysts was significantly higher than that of poor-quality blastocysts (67.66% vs 46.88%; odds ratio [OR], 2.203; 95%confidence interval[CI], 0.943-3.612; P=0.002). However, no significant difference was observed in the different developmental rates blastocysts. Compared with Day 5 blastocysts, the euploidy rates of Day 6 and Day 7 blastocysts were not significantly different(61.54%vs51.91%; OR,0.945; 95%CI, 0.445-2.010; P=0.884; and 61.54%vs47.37%; OR, 1.106; 95%CI, 0.774-1.578; P=0.581, respectively).As for the pregnancy outcomes, the clinical pregnancy rate was significantly increase after the use of PGT-A compared with the control group(71.19%vs56.30%; OR, 0.538; 95%CI, 0.262-1.104; P=0.039). However, the spontaneous abortion rates and ongoing pregnancy rates were not significantly different between the control and PGT-A groups (21.43% vs 19.40%; aOR,0.727; 95%CI,0.271-1.945; P=0.525; and55.93% vs 45.38%; aOR, 0.649; 95%CI, 0.329-1.283; P = 0.214,respectively). Conclusion: PGT-A improved the clinical pregnancy rate after blastocyst transfer in RIF patients aged under 38 years.

Acute liver injury induced by drug interaction between dacomitinib and metoprolol due to the inhibition of CYP2D6 by dacomitinib.

INTRODUCTION: In recent years, oral antineoplastic agents are commonly used in antitumor therapy. The interaction between drugs may affect the efficacy of drugs or lead to adverse reactions. We describe the case of a patient who presented acute liver injury, possibly induced by the concomitant use of metoprolol and dacomitinib. CASE REPORT: A 62-year-old male patient with non-small cell lung cancer was admitted for anti-cancer treatment. He regularly took metoprolol tartrate 12.5 mg, 2/day for hypertension. He was treated with dacomitinib according to EGFR Exon21 L858R positive. After 3 days of dacomitinib, the patient's alanine aminotransferase (ALT) and glutathione aminotransferase (AST) increased, and the heart rate and systolic blood pressure of the patient decreased significantly. The patient was diagnosed with acute liver injury. MANAGEMENT AND OUTCOMES: Dacomitinib was discontinued and glutathione, magnesium isoglycyrrhizinate were given to treat acute liver injury. Two days after discontinued dacomitinib, the patient's heart rate increased, but the ALT and AST of the patient elevated again. Metoprolol tartrate was subsequently discontinued and the ALT and AST gradually decreased and the patient discharged from the hospital eight days later with his liver function improved. DISCUSSION: To our knowledge, this is the first case in the literature of acute liver injury possibly induced by the interaction between metoprolol and dacomitinib. The interaction most likely arose because dacomitinib is a CYP2D6 strong inhibitor and could therefore impair the metabolism of metoprolol (a CYP2D6 substrate) and increase its serum concentration. Therefore, hepatic function should be carefully monitored in patients treated with dacomitinib and metoprolol and other inhibitors or inducers of CYP2D6.

Effect of a 60-day weight reduction intervention prior to IVF/ICSI on perinatal outcomes in overweight or obese infertile women.

Purpose: The aim of this study was to determine whether a 60-day weight reduction intervention prior to in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) and a higher weight loss ratio effectively improved perinatal outcomes for infertile overweight or obese women. Methods: This was a retrospective cohort study conducted at a university-affiliated fertility center. Two thousand three hundred and eighty-one overweight or obese infertile women who underwent or did not undergo a 60-day weight reduction intervention prior to IVF/ICSI between February 27, 2017 and November 11, 2020 were included in this study. All of these women achieved clinical pregnancy and delivered a single child after assisted reproductive technology (ART). Primary outcomes included neonatal birth weight and the incidence of pregnancy complications, premature delivery, and low birth weight. Results: The body mass index (BMI), blood glucose concentration, serum insulin level, and homeostasis model assessment of insulin resistance (HOMA-IR) of the intervention group decreased significantly after the weight reduction intervention. Neonatal birth weight was significantly higher in the intervention group (3519.6 g ±484.8 g) than the control group (3406.8 g ± 554.2 g; P < 0.001). There was no significant difference in the incidence of pregnancy complications between the two groups. Linear regression analysis found that the weight reduction intervention prior to IVF/ICSI and lower HOMA-IR at ovulation induction were associated with increased birth weight. As the weight loss ratio increased, the incidence of hypertensive disorders of pregnancy, premature membrane rupture, premature delivery, stillbirth, and low birth weight showed a downward trend. Conclusions: A 60-day weight reduction intervention prior to IVF/ICSI may increase neonatal birth weight, reduce maternal blood glucose concentration, and improve maternal insulin resistance in infertile overweight or obese women. This results require to be further verified by prospective randomized controlled trials with a larger sample size.

Perinatal outcomes of singleton live births after late moderate-to-severe ovarian hyperstimulation syndrome: A propensity score-matched study.

Objective: To evaluate whether singleton live births achieved following in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) in women with late moderate-to-severe ovarian hyperstimulation syndrome (OHSS) is associated with adverse perinatal outcomes. Methods: This was a single-center retrospective cohort study conducted from January 2016 to June 2021. A total of 4,012 IVF/ICSI-fresh embryo transfer cycles that achieved singleton live births were included. According to the diagnosis of OHSS, the cycles were divided into two groups: late moderate-to-severe OHSS (MS-OHSS) group (n = 114) and non-OHSS group (n = 3,898). Multiple baseline covariates were controlled by propensity score matching, yielding 114 late MS-OHSS singleton live births matched to 337 non-OHSS singleton live births. The primary outcome of the study was normal term infant. The secondary outcomes were perinatal complications, gestational age at birth, birth weight, and birth height. Results: Before propensity score matching, no significant difference in perinatal outcomes was identified between late MS-OHSS group and non-OHSS group. After matching maternal age, BMI, basal serum FSH level, basal serum AMH level, basal antral follicle count, type of stimulation protocol, day of embryo development for embryo transfer, number of embryo transfer, and number of oocytes retrieved, there was still no significant difference in obstetric outcomes and neonatal outcomes between the two groups. Conclusions: The findings demonstrate that the perinatal outcomes were similar between the two groups. However, because the sample size of patients with late MS-OHSS was limited in this study, further investigations are warranted using a larger sample size.

A redox switch regulates the assembly and anti-CRISPR activity of AcrIIC1.

Anti-CRISPRs (Acrs) are natural inhibitors of bacteria's CRISPR-Cas systems, and have been developed as a safeguard to reduce the off-target effects of CRISPR gene-editing technology. Acrs can directly bind to CRISPR-Cas complexes and inhibit their activities. However, whether this process is under regulation in diverse eukaryotic cellular environments is poorly understood. In this work, we report the discovery of a redox switch for NmeAcrIIC1, which regulates NmeAcrIIC1's monomer-dimer interconversion and inhibitory activity on Cas9. Further structural studies reveal that a pair of conserved cysteines mediates the formation of inactive NmeAcrIIC1 dimer and directs the redox cycle. The redox switch also applies to the other two AcrIIC1 orthologs. Moreover, by replacing the redox-sensitive cysteines, we generated a robust AcrIIC1 variant that maintains potent inhibitory activity under various redox conditions. Our results reveal a redox-dependent regulation mechanism of Acr, and shed light on the design of superior Acr for CRISPR-Cas systems.

The application of single beta-human chorionic gonadotropin (ß-hCG) level measurement in women undergoing single blastocyst transfer.

We previously explored the associations between ß-hCG on the 14th day post-embryo transfer (ET) and reproductive outcomes and established a series of cutoff values to predict different outcomes. The aim of this study was to explore the parameters associated with ß-hCG levels and establish ß-hCG cutoff values in women undergoing single blastocyst transfer. The patients were transferred with either fresh or frozen-thawed blastocysts. Serum ß-hCG levels were compared among different groups. Cutoff values of ß-hCG were established and applied to divide the patients into different groups, among which the ß-hCG groups were compared. Develop day negatively affected ß-HCG levels in those who were pregnant or gave live birth (P < 0.001, 0.008). Inner cell mass significantly affected ß-hCG levels in women who were pregnant or gave live birth (P = 0.013, 0.044). Trophectoderm significantly affected ß-hCG levels in women with most reproductive outcomes, except biochemical pregnancy (BP) (P = 0.184). The cutoff values of ß-hCG for predicting positive outcomes were 194.1, 503.0, 1048.0, and 2590.5 mIU/L. BP rates and adverse pregnancy outcome rates were significantly lower in the higher ß-hCG groups (P < 0.001). Shorter gestational age and lower birth weight and length (P = 0.005, 0.041, 0.003) were observed in the lowest-concentration ß-hCG group. The application of a single ß-hCG measurement was sufficient to predict reproductive outcome in women undergoing blastocyst transfer, under the full consideration of blastocyst parameters. However, the association between ß-hCG and obstetric outcomes remains to be investigated and fully explained.

Analysis of cumulative live birth rate and perinatal outcomes in young patients with low anti-müllerian hormone levels using two ovulation promotion protocols: A cohort study.

Objective: To compare cumulative live birth rates and perinatal outcomes of young IVF/ICSI patients with low anti-Mullerian hormone (AMH) levels on a gonadotropin-releasing hormone antagonist (GnRH-ant) regimen with those on a high progesterone state of ovulation (PPOS) regimen. Methods: We retrospectively analyzed 798 patients who underwent in vitro fertilization (IVF) or intracytoplasmic sperm microinjection (ICSI) between January 2015 and December 2020 at the Third Affiliated Hospital of Zhengzhou University. A total of 798 cycles of complete clinical data from patients who underwent in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) at the Reproductive Medicine Center of Zhengzhou University Hospital between January 2015 and December 2020 and were eligible for AMH < 1.2 ng/ml at age < 35 years, Group A1: very low AMH levels (AMH < 0.5 ng/mL) and GnRH antagonist regimen; Group A2, very low AMH level (AMH < 0.5 ng/mL) and PPOS regimen; Group B1, low AMH level (0.5 ng/mL ≤ AMH < 1.2 ng/mL) and GnRH antagonist regimen; and Group B2, low AMH level (0.5 ng/mL ≤ AMH < 1.2 ng/mL), and the PPOS regimen. Results: At very low levels of AMH (< 0.5 ng/mL), the CLBR of the GnRH antagonist regimen was not significantly different from that of the PPOS regimen (P > 0.05), at 0.5 ng/mL ≤ AMH < 1.2 ng/mL. Statistics showed that the CLBR of the GnRH antagonist regimen was significantly higher than that of the PPOS regimen (49.7% vs. 35.7%, P=0.002). Logistic regression analysis showed that in Group A: the younger the female partner, the higher the CLBR (OR = 0.972, 95% CI = 0.923-1.042, P = 0.022), and the more the AFC, the higher the CLBR (OR = 1.166, 95% CI = 1.091-1.336, P < 0.001). Group B: the higher the number of good-quality embryos, the higher the CLBR (OR = 2.227, 95% CI = 1.869-2.654, P < 0.001). Compared with PPOS regimens, the antagonist regimen was able to increase the CLBR. The analysis of Group A showed that the antagonist regimen had a shorter TTP than the PPOS regimen (P < 0.001); however, the PPOS regimen had a lower cost of ovulation (4311.91 vs. 4903.81, P = 0.023). The antagonist regimen in Group B had a shorter TTP than the PPOS regimen, and there was no significant difference in the cost of ovulation. In the analysis of perinatal outcomes, there were no statistically significant differences in preterm birth, low birth weight, very low birth weight, and pregnancy complications among the four groups. Conclusion: Young patients with very low AMH levels (< 0. 5 ng/mL), the GnRH antagonist regimen was comparable to the PPOS regimen in CLBR outcomes; the antagonist regimen shortens the time to clinical pregnancy, and the PPOS regimen is more cost-effective. In young patients with low AMH levels of 0.5 ng/mL and <1.2 ng/mL, the GnRH antagonist regimen can more appropriate to improve CLBR, and the perinatal outcomes were similar for both regimens.

Diagnostic value of a single ß-hCG test in predicting reproductive outcomes in women undergoing cleavage embryo transfer: a retrospective analysis from a single center.

PURPOSE: The present study investigated the role of ß-hCG in predicting reproductive outcomes and established optimal ß-hCG cutoff values in women undergoing cleavage embryo transfer. METHODS: The patients were transferred with fresh or frozen-thawed embryos and had serum ß-hCG levels tested on the 14th day post-embryo transfer. Serum ß-hCG levels were compared between different groups. Different cutoff values of ß-hCG were established and used to divide the patients into different groups. Reproductive outcomes between groups based on ß-hCG levels were compared. RESULTS: Significant discrepancies in general characteristics were observed in the subgroups. The cutoff values of ß-hCG for predicting the presence/absence of pregnancy, biochemical pregnancy/clinical pregnancy, presence/absence of adverse pregnancy outcomes, and singleton/twin live birth in the cleavage groups were 89.6, 241.1, 585.9, and 981.1 mIU/L, respectively. Biochemical pregnancy rates and adverse pregnancy outcome rates significantly decreased from the low ß-hCG group to the higher ß-hCG group in sequence. Significantly higher full-term live birth rates were observed in the highest ß-hCG group (P < 0.001). CONCLUSION: Serum ß-hCG levels were strongly associated with reproductive outcomes. However, the interpretation of ß-hCG levels must consider the number and quality of embryos and transfer protocols. When ß-hCG was tested on a fixed day post-ET, different cutoff values were required for the prediction of early clinical outcomes. The association between ß-hCG and obstetric outcomes must be investigated.

To investigate the association between ß-hCG and reproductive and obstetrical outcomes in women with cleavage ET and to establish different ß-hCG cutoff values for the prediction of reproductive outcomes, this study retrospectively included 6909 infertile women who were divided into different groups based on the number and quality of transferred embryos, age, and transfer protocols. The cutoff values of ß-hCG for predicting the presence/absence of pregnancy, biochemical pregnancy/clinical pregnancy, presence/absence of adverse pregnancy outcomes, singleton/twin live birth in the cleavage groups were 89.6, 241.1, 585.9, and 981.1 mIU/L, respectively. Biochemical pregnancy rates and adverse pregnancy outcome rates decreased significantly in the higher ß-hCG groups. In conclusion, the interpretation of ß-hCG levels must consider the number and quality of embryos and transfer protocols. When ß-hCG was tested on a fixed day post-ET, different cutoff values were required for the prediction of early clinical outcomes.

Effect of Blastocyst Morphology and Developmental Rate on Euploidy and Live Birth Rates in Preimplantation Genetic Testing for Aneuploidy Cycles With Single-Embryo Transfer.

Objective: The aim of this study was to investigate whether blastocyst morphology and developmental rate are associated with euploidy and live birth rates (LBRs) in single euploid frozen-thawed embryo transfer (FET) cycles. Design: Retrospective cohort study. Methods: This study included 431 preimplantation genetic testing for aneuploidy (PGT-A) cycles followed by 393 FET cycles performed at our center from June 2017 to March 2021. All cycles were analyzed for euploidy based on blastocyst morphology (good, average and poor), developmental stage (day 5 and 6) and maternal age (< 35 and ≥ 35 years old). Multivariate logistic analysis models were used to identify the independent effects of conventional blastocyst morphology, developmental rate and morphological parameters (degree of blastocoele expansion, and grade of inner cell mass and trophectoderm (TE)) on LBRs. Results: In the group of women aged < 35 years, compared with poor-quality blastocysts, good-quality blastocysts (62.90% vs. 32.46%; odds ratio (OR) 3.163, 95% confidence interval (CI) 2.247-4.451; P < 0.001) and average-quality blastocysts (46.70% vs. 32.46%; OR 1.665, 95% CI 1.287-2.154; P < 0.001) had significantly higher euploidy rates. Additionally, day 5 blastocysts were associated with higher euploidy rates than day 6 blastocysts (49.28% vs. 35.02%; OR 1.506, 95% CI 1.191-1.903; P= 0.001). In the group of women aged ≥ 35 years, euploidy rates were also associated with blastocyst morphology, with 41.86%, 45.65% and 24.39% of good, average and poor-quality embryos, respectively, exhibiting euploidy. However, no relationship was seen between euploidy and blastocyst developmental rate. Multiple logistic regression analysis show that overall blastocyst morphology of euploid embryos was not associated with LBR, only embryos with A-grade TE had significantly higher LBRs than those with C-grade TE (62.71% vs. 45.40%; OR 2.189, 95% CI 1.166-4.109; P=0.015). Similarly, LBRs were significantly higher when day 5 blastocysts were transferred than when day 6 blastocysts were transferred (57.75% vs. 41.67%; OR 2.132, 95% CI 1.370-3.318; P = 0.001). Conclusion: Poor-quality embryos have reduced rates of euploidy. However, blastocyst developmental rate only significantly associates with euploidy rates in women aged younger than 35. Furthermore, only TE grade and blastocyst developmental rate are significantly associated with LBRs following FET cycles.

Comparison of Perinatal Outcomes of Letrozole-Induced Ovulation and Hormone Replacement Therapy Protocols in Patients With Abnormal Ovulation Undergoing Frozen-Thawed Embryo Transfer: A Propensity Score Matching Analysis.

Background: With the increasing use of frozen embryo transfer (FET), the best endometrial preparation protocol is continuously being discussed. The hormone replacement therapy (HRT) cycle and letrozole-induced ovulation (L-OI) cycle are available protocols for patients with abnormal ovulation. Previous comparisons of the two protocols have focused on pregnancy outcomes, with less attention to perinatal outcomes, and population heterogeneity was large; thus, convincing conclusions about which protocol is more appropriate could not be drawn. Methods: We performed a retrospective cohort study using propensity score matching (PSM) analysis for a population of patients undergoing FET cycles in the reproductive center of the Third Affiliated Hospital of Zhengzhou University from January 2016 to September 2020. The main outcome measures were clinical pregnancy rate, live birth rate, very preterm delivery (VPTD), preterm delivery (PTD), low birth weight (LBW), macrosomia, small for gestational age (SGA), large for gestational age (LGA), hypertensive disorders of pregnancy (HDP), gestational diabetes mellitus (GDM), premature rupture of membranes (PROM), placenta previa, and congenital abnormality. Results: A total of 8010 women were enrolled. Due to the large heterogeneity among the patients, we conducted 1:1 PSM, and 1461 women matched in each group. Compared with the HRT group, the L-OI group had a smaller proportion of thin endometrium (27.38% vs. 41.07%) and thicker endometrium on the day of embryo transfer (9.63 ± 1.82 vs. 8.91 ± 1.38). There were no significant differences in clinical pregnancy rate, early abortion rate or live birth rate between the groups. There was no significant difference in perinatal outcomes of singleton live birth, including VPTD, PTD, postterm delivery, LBW, macrosomia, SGA, LGA, GDM, HDP, placenta previa, and congenital malformation. Conclusion: For women with abnormal ovulation, the pregnancy and perinatal outcomes of HRT and L-OI protocols are reassuring. It seems that both protocols are safe and effective for endometrial preparation in frozen-thawed embryo transfer in the clinic.

Perinatal Outcomes of Singleton Live Births Following Preimplantation Genetic Testing for Chromosomal Structural Rearrangements in Single Frozen-Thawed Blastocyst Transfer Cycles: a Retrospective Cohort Study.

This study investigated whether singleton pregnancies conceived after preimplantation genetic testing for chromosomal structural rearrangements (PGT-SR) are associated with a higher risk of adverse perinatal outcomes than singleton pregnancies conceived after intracytoplasmic sperm injection (ICSI). We collected data on singleton live births after PGT-SR (n = 107) and ICSI (n = 585) in our hospital from January 2017 to August 2020. Multivariable analyses were used to adjust for maternal age, body mass index, gravidity and parity, paternal age, ovulatory disorder, and recurrent spontaneous abortion. The unadjusted results showed a significantly higher risk of hypertensive disorders of pregnancy (HDP) (odds ratio (OR) = 2.47; 95% confidence interval (CI): 1.10-5.54; P = 0.029) associated with PGT-SR singleton pregnancies than with ICSI singleton pregnancies. However, after adjusting for potential confounders, there were no longer any significant differences in the risk of HDP (adjusted OR = 2.24; 95% CI: 0.92-5.48; P = 0.077) between PGT-SR and ICSI singleton pregnancies. There were no significant differences between PGT-SR and ICSI singleton pregnancies in terms of gestational diabetes, preterm premature rupture of membranes, placenta previa, cesarean delivery, gestational age (weeks), preterm delivery (< 37 weeks), very preterm delivery (≥ 28 weeks and < 32 weeks), birth weight (g), low birth weight (< 2500 g), very low birth weight (< 1500 g), birth height (cm), birth defects, and 1-min and 5-min Apgar scores. In conclusion, for single frozen-thawed blastocyst cycles, there were no significant differences in adverse perinatal outcomes between PGT-SR and ICSI singleton pregnancies. However, due to the limited sample size, these conclusions need to be confirmed by further studies.

Comparison of Dydrogesterone and Medroxyprogesterone in the Progestin-Primed Ovarian Stimulation Protocol for Patients With Poor Ovarian Response.

Objective: To compare the clinical outcomes of dydrogesterone (DYG) and medroxyprogesterone (MPA) in the progestin-primed ovarian stimulation (PPOS) protocol for patients with poor ovarian response (POR). Patients and Methods: This was a retrospective cohort study. Women with POR who underwent IVF/ICSI at the Reproductive Center of Third Affiliated Hospital of Zhengzhou University between January 2020 and January 2021 were included. The primary outcome measure of our study was the number of oocytes retrieved. The secondary outcome measures in the present study were the number of 2PN, number of available embryos, oocyte retrieval rate, fertilization rate, viable embryo rate per oocyte retrieved, cancellation rate and pregnancy outcomes of the first embryo transfer cycle, including the biochemical pregnancy, clinical pregnancy and miscarriage rates. Results: In total, 118 women underwent hMG +DYG protocols, and 692 women who underwent hMG +MPA met the Bologna criteria for POR. After baseline characteristics were balanced using the PSM model, 118 hMG +DYG protocols were matched to 118 hMG +MPA protocols, and the baseline characteristics were comparable between the two groups. The numbers of oocytes retrieved, 2PN, and available embryos and the oocyte retrieval rate, fertilization rate, viable embryo rate per oocyte retrieved and cancellation rate of the hMG+DYG and hMG+MPA protocols were comparable. Altogether, 66 women in the hMG+DYG group and 87 women in the hMG+MPA group underwent first embryo transfers. In the hMG+DYG group, 81.8% (54/66) of the patients underwent cleavage embryo transfers; similarly, 79.3% (69/87) of patients in the hMG+MPA group had cleavage embryo transfers (P=0.70).The biochemical pregnancy rate of the hMG+DYG group was 42.4%, and this was comparable to the rate in the hMG+DYG group, at 34.5% (P=0.32). The clinical pregnancy rates were similar between the two groups (36.4% vs. 31.0%, P=0.49), and there was no significant difference in the rate of miscarriage between the two groups (12.5% vs. 29.6%, P=0.14). Conclusion: For women with POR, the clinical outcome of the hMG + DYG group was similar to that of the hMG + MPA group, indicating that both combinations can be useful options for PPOS protocols.

[Occurrence, Distribution, and Ecological Risk Assessment of Pharmaceutical and Personal Care Products in the Aquatic Environment of Sanya City, China].

The occurrence, distribution, and risk of 11 typical pharmaceutical and personal care products(PPCPs) were investigated in the major rivers and bay areas of Sanya City. The results showed that the significant seasonal variations in eleven PPCPs in major rivers of the city were affected by intense tourism alongside reduced annual runoff. In winter, all 11 PPCPs had 100% detection frequencies, of which CFI had the highest concentration at 1449.10 ng·L-1. The highest concentration of MTP was 427.06 ng·L-1 and highest concentration of RTM was 311.59 ng·L-1. In summer, all 11 PPCPs were again detected, with a lowest detection rate of 87.5%, of which CFI, MTP, RTM, ETM, and OFL were predominant. All 11 PPCPs were also detected in the surface seawater of the main bay areas, with detection frequencies of 85.7%, 57.1%, and 71.4% for SMX, MTP, and CFI respectively; the other eight PPCPs had 100% detection frequencies. CFI had the highest concentration at 220.78 ng·L-1. An ecological risk assessment of the 11 PPCPs showed that the risk quotients(RQ) of STZ at Yuechuan Bridge and RTM at Fenghuang Road were higher than 1 in winter, posing a high risk to the aquatic ecology. This was mainly attributed to the discharge of water from nearby hospitals and sewage treatment plants. In summer, the RQ of STZ at Sanya Bridge and RTM at Hongsha Wharf was between 0.1 and 1, which indicates a medium level of risk to the aquatic environment in Sanya City.

Obstetric and neonatal outcomes of pregnancies resulting from preimplantation genetic testing: a systematic review and meta-analysis.

BACKGROUND: Preimplantation genetic testing (PGT) includes methods that allow embryos to be tested for severe inherited diseases or chromosomal abnormalities. In addition to IVF/ICSI and repeated freezing and thawing of the embryos, PGT requires a biopsy to obtain embryonic genetic material for analysis. However, the potential effects of PGT on obstetric and neonatal outcomes are currently uncertain. OBJECTIVE AND RATIONALE: This study aimed to investigate whether pregnancies conceived after PGT were associated with a higher risk of adverse obstetric and neonatal outcomes compared with spontaneously conceived (SC) pregnancies or pregnancies conceived after IVF/ICSI. SEARCH METHODS: PubMed, EMBASE, MEDLINE, Web of Science and The Cochrane Library entries from January 1990 to January 2021 were searched. The primary outcomes in this study were low birth weight (LBW) and congenital malformations (CMs), and the secondary outcomes included gestational age, preterm delivery (PTD), very preterm delivery (VPTD), birth weight (BW), very low birth weight (VLBW), neonatal intensive care unit (NICU) admission, hypertensive disorders of pregnancy (HDP), gestational diabetes, placenta previa and preterm premature rupture of membranes (PROM). We further pooled the results of PGT singleton pregnancies. Subgroup analyses included preimplantation genetic diagnosis (PGD), preimplantation genetic screening (PGS), cleavage-stage biopsy combined with fresh embryo transfer (CB-ET) and blastocyst biopsy combined with frozen-thawed embryo transfer (BB-FET). OUTCOMES: This meta-analysis included 15 studies involving 3682 babies born from PGT pregnancies, 127 719 babies born from IVF/ICSI pregnancies and 915 222 babies born from SC pregnancies. The relative risk (RR) of LBW was higher in PGT pregnancies compared with SC pregnancies (RR = 3.95, 95% confidence interval [CI]: 2.32-6.72), but the risk of CMs was not different between the two groups. The pooled results for the risks of LBW and CMs were similar in PGT and IVF/ICSI pregnancies. The risks of PTD (RR = 3.12, 95% CI: 2.67-3.64) and HDP (RR = 3.12, 95% CI: 2.18-4.47) were significantly higher in PGT pregnancies compared with SC pregnancies. Lower gestational age (mean difference [MD] = -0.76 weeks, 95% CI -1.17 to -0.34) and BW (MD = -163.80 g, 95% CI: -299.35 to -28.24) were also noted for PGT pregnancies compared with SC pregnancies. Nevertheless, compared with IVF/ICSI pregnancies, the risks of VPTD and VLBW in PGT pregnancies were significantly decreased by 41% and 30%, respectively, although the risk of HDP was still significantly increased by 50% in PGT pregnancies compared with IVF/ICSI pregnancies. The combined results of obstetric and neonatal outcomes of PGT and IVF/ICSI singleton pregnancies were consistent with the overall results. Further subgroup analyses indicated that both PGD and PGS pregnancies were associated with a higher risk of PTD and a lower gestational age compared with SC pregnancies. WIDER IMPLICATIONS: This meta-analysis showed that PGT pregnancies may be associated with increased risks of LBW, PTD and HDP compared with SC pregnancies. The overall obstetric and neonatal outcomes of PGT pregnancies are favourable compared with those of IVF/ICSI pregnancies, although PGT pregnancies were associated with a higher risk of HDP. However, because the number of studies that could be included was limited, more randomised controlled trials and prospective cohort studies are needed to confirm these conclusions.