Vitrification preservation of good-quality blastocysts for more than 5 years reduces implantation and live birth rates.

STUDY QUESTION: Does vitrification cryopreservation of embryos for more than 5 years affect the pregnancy outcomes after frozen embryo transfer (FET)? SUMMARY ANSWER: Vitrification cryopreservation of good-quality blastocysts for more than 5 years is associated with a decrease in the implantation rate (IR) and live birth rate (LBR). WHAT IS KNOWN ALREADY: Previous studies have predominantly focused on embryos cryopreserved for relatively short durations (less than 5 years), yet the impact of extended cryopreservation duration on pregnancy outcomes remains a controversial issue. There is a relative scarcity of data regarding the efficacy and safety of storing embryos for 5 years or longer. STUDY DESIGN, SIZE, DURATION: This retrospective study involved 36 665 eligible vitrified-thawed embryo transfer cycles from 1 January 2016 to 31 December 2022, at a single fertility center in China. PARTICIPANTS/MATERIALS, SETTING, METHODS: Patients were divided into three groups according to embryo storage time: Group 1 consisted of 31 565 cycles, with storage time of 0-2 years; Group 2 consisted of 4458 cycles, with a storage time of 2-5 years; and Group 3 included 642 cycles, with storage time exceeding 5 years. The main outcome measures were IR and LBR. Secondary outcome variables included rates of biochemical pregnancy, multiple pregnancy, ectopic pregnancy, and miscarriage, as well as neonatal outcomes. Reproductive outcomes were analyzed as binary variables. Multivariate logistic regression analysis was used to explore the effect of preservation time on pregnancy outcomes after correcting for confounding factors. In addition, we also assessed neonatal outcomes, such as large for gestational age (LGA) and small for gestational age (SGA). MAIN RESULTS AND THE ROLE OF CHANCE: IRs in the three groups (0-2, 2-5, and >5 years) were 37.37%, 39.03%, and 35.78%, respectively (P = 0.017), and LBRs in the three groups were 37.29%, 39.09%, and 34.91%, respectively (P = 0.028). After adjustment for potential confounding factors, compared with the 0-2 years storage group, prolonged embryo vitrification preservation time (2-5 years or >5 years) did not affect secondary outcomes such as rates of biochemical pregnancy, multiple pregnancy, ectopic pregnancy, and miscarriage (P > 0.05). But cryopreservation of embryos for more than 5 years reduced the IR (adjusted odds ratio (aOR) 0.82, 95% CI 0.69-0.97, P = 0.020) and LBR (aOR 0.76, 95% CI 0.64-0.91, P = 0.002). Multivariate stratified analysis also showed that prolonging the cryopreservation time of blastocysts (>5 years) reduced the IR (aOR 0.78, 95% CI 0.62-0.98, P = 0.033) and LBR (aOR 0.68, 95% CI 0.53-0.87, P = 0.002). However, no effect on cleavage embryos was observed (P > 0.05). We further conducted stratified analyses based on the number and quality of frozen blastocysts transferred, and the results showed that the FET results after transfers of good-quality blastocysts in the >5 years storage group were negatively affected. However, the storage time of non-good-quality blastocysts was not significantly associated with pregnancy outcomes. Regarding the neonatal outcomes (of singletons), embryo vitrification preservation time had no effect on preterm birth rates, fetal birth weight, or neonatal sex ratios. However, as the storage time increased, rates of SGA (5.60%, 4.10%, and 1.18%) decreased, while rates of LGA (5.22%, 6.75%, and 9.47%) increased (P < 0.05). After adjusting for confounding factors, the increase in LGA and the decrease in SGA were significantly correlated with the duration of storage time. LIMITATIONS, REASONS FOR CAUTION: This was a retrospective study using data from a single fertility center, even though the data had been adjusted, our findings still need to be validated in further studies. WIDER IMPLICATIONS OF THE FINDINGS: With the full implementation of the two-child policy in China, there may be more patients whose embryos have been frozen for a longer time in the future. Patients should be aware that the IR and LBR of blastocysts are negatively affected when the cryopreservation time is longer than 5 years. Couples may therefore consider shortening the time until FET treatment. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by the National Nature Science Foundation of China (No. 82101672), Science and Technology Projects in Guangzhou (No. 2024A03J0180), General Guidance Program for Western Medicine of Guangzhou Municipal Health Commission (No. 20231A011096), and the Medical Key Discipline of Guangzhou (2021-2023). None of the authors have any conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

Causal effect of beta-blockers on the risk of lung cancer: a Mendelian randomization study.

Background: It remains uncertain whether there is a causal association of the use of beta-blockers (BBs) on lung cancer risk. We used a two-sample Mendelian randomization (MR) approach to identify the causal association of BBs and lung cancer risk. Methods: Twenty-two BB-related single-nucleotide polymorphisms (SNPs) were obtained from the UK Biobank as the instrumental variables (IVs). Genetic summary data information of lung cancer was extracted from the International Lung Cancer Consortium, with a total of 11,348 cases and 15,861 controls. We adopted the inverse-variance weighted (IVW) approach to conduct the MR analyses. Egger-intercept analysis was further performed as sensitivity analysis for pleiotropy evaluation. Additionally, we investigated whether BBs could causally affect the risk of lung cancer through their pharmacological effects. Results: The current IVW analysis suggested a decreased lung cancer risk in BB users [odds ratio (OR) =0.83; 95% confidence interval (CI): 0.73-0.95; P<0.01]. Results of Egger-intercept analysis demonstrated that no pleiotropy was found (P=0.94), which suggested the robustness of the causality. However, there was little evidence that pharmacological effects mediate the association between BBs and lung cancer. Conclusions: The current analysis suggested that BBs could decrease the risk of lung cancer but may be not via its pharmacological effects. Further research is in need for elucidating the underlying mechanisms.

Radiomics features on radiotherapy treatment planning CT can predict patient survival in locally advanced rectal cancer patients.

This retrospective study was to investigate whether radiomics feature come from radiotherapy treatment planning CT can predict prognosis in locally advanced rectal cancer patients treated with neoadjuvant chemoradiation followed by surgery. Four-hundred-eleven locally advanced rectal cancer patients which were treated with neoadjuvant chemoradiation enrolled in this study. All patients' radiotherapy treatment planning CTs were collected. Tumor was delineated on these CTs by physicians. An in-house radiomics software was used to calculate 271 radiomics features. The results of test-retest and contour-recontour studies were used to filter stable radiomics (Spearman correlation coefficient > 0.7). Twenty-one radiomics features were final enrolled. The performance of prediction model with the radiomics or clinical features were calculated. The clinical outcomes include local control, distant control, disease-free survival (DFS) and overall survival (OS). Model performance C-index was evaluated by C-index. Patients are divided into two groups by cluster results. The results of chi-square test revealed that the radiomics feature cluster is independent of clinical features. Patients have significant differences in OS (p = 0.032, log rank test) for these two groups. By supervised modeling, radiomics features can improve the prediction power of OS from 0.672 [0.617 0.728] with clinical features only to 0.730 [0.658 0.801]. In conclusion, the radiomics features from radiotherapy CT can potentially predict OS for locally advanced rectal cancer patients with neoadjuvant chemoradiation treatment.

[Expression of PTCH-1 and SMO mRNA in nasopharyngeal carcinoma].

AIM: to detect the expression of Hedgehog pathway components PTCH-1 and SMO mRNA in nasopharyngeal carcinoma (NPC), and discuss its biological significance. METHODS: expression of PTCH-1 and SMO mRNA was evaluated by real-time fluorescence quantitative PCR in 32 cases of NPC and 32 cases of nasopharyngitis. According to Livak (2(-delta;Ct);) relative quantitative analysis method, with nasopharyngitis as control, to calculate the expression level of PTCH-1 and SMO in NPC. RESULTS: all detected NPC and nasopharyngitis tissues had the expression of PTCH-1 and SMO. Compared with nasopharyngitis, the negative expression rate of PTCH-1 in NPC was 75% (24/32), and the positive expression rate of SMO in NPC was 68.8% (22/32), the differences were statistically significant (P<0.05). In addition, the positive expression rate of PTCH-1 in NPC was 18.7% (6/32), and the negative expression rate of SMO in NPC was 15.6% (5/32), the differences were not statistically significant (P>0.05). CONCLUSION: the expression level of SMO in NPC is generally high, but the expression level of PTCH-1 was relatively low. The down-regulate of PTCH-1 and up-regulate of SMO may cause the abnormal activation of hedgehog signaling pathway in NPC, speculated that the genesis and development of NPC may be associated with the abnormal activation of hedgehog signaling pathway.