Objective To explore the diagnostic value of exhaled volatile organic compounds (VOCs) for cystic fibrosis (CF). Methods A systematic search was conducted in PubMed, EMbase, Web of Science, Cochrane Library, CNKI, Wanfang, VIP, and SinoMed databases up to August 7, 2024. Studies that met the inclusion criteria were selected for data extraction and quality assessment. The quality of included studies was assessed by the Newcastle-Ottawa Scale (NOS), and the risk of bias and applicability of included prediction model studies were assessed by the prediction model risk of bias assessment tool (PROBAST). Results A total of 10 studies were included, among which 5 studies only identified specific exhaled VOCs in CF patients, and another 5 developed 7 CF risk prediction models based on the identification of VOCs in CF. The included studies reported a total of 75 exhaled VOCs, most of which belonged to the categories of acylcarnitines, aldehydes, acids, and esters. Most models (n=6, 85.7%) only included exhaled VOCs as predictive factors, and only one model included factors other than VOCs, including forced expiratory flow at 75% of forced vital capacity (FEF75) and modified Medical Research Council scale for the assessment of dyspnea (mMRC). The accuracy of the models ranged from 77% to 100%, and the area under the receiver operating characteristic curve ranged from 0.771 to 0.988. None of the included studies provided information on the calibration of the models. The results of the Prediction Model Risk of Bias Assessment Tool (PROBAST) showed that the overall bias risk of all predictive model studies was high, and the overall applicability was unclear. Conclusion The exhaled VOCs reported in the included studies showed significant heterogeneity, and more research is needed to explore specific compounds for CF. In addition, risk prediction models based on exhaled VOCs have certain value in the diagnosis of CF, but the overall bias risk is relatively high and needs further optimization from aspects such as model construction and validation.

BACKGROUND:There is a significant correlation between sperm DNA fragmentation index and fertilization,embryonic development potential,embryo implantation,miscarriage,and offspring safety.However,its clinical reference value is affected by many factors,resulting in extremely limited clinical significance.This study took live birth as the outcome,corrected other confounding factors through propensity score matching,constructed the best clinical cutoff value of sperm DNA fragmentation index and live birth,and conducted internal and external tests on it,which has good predictive value and clinical application efficiency. OBJECTIVE:To investigate the reference threshold and offspring short-term security of in vitro fertilization-embryo transfer sperm DNA fragmentation index based on live birth. METHODS:A total of 1 921 patients who received in vitro fertilization and embryo transfer in Changzhou Maternal and Child Health Area Hospital from May 2019 to May 2021 were selected.On the basis of tendency matching tolerance of 0.02 and propensity score matching of 1:1,540 cases were successfully matched in each live birth group and non-live birth group,and the model group was established.135 patients who received in vitro fertilization and embryo transfer in Nanxishan Hospital of Guangxi Zhuang Autonomous Region were selected as the external validation group.The optimal clinical cutoff value of sperm DNA fragmentation index for live birth was investigated by the receiver operating characteristic curve.The accuracy and clinical application efficacy of the cutoff value were evaluated by restricted cubic spline curve,standard curve,clinical decision curve,clinical impact curve and internal and external validation tests. RESULTS AND CONCLUSION:(1)The DNA fragmentation index of sperm in the non-live birth group was significantly higher than that in the live birth group and had a significant negative correlation with live birth(r=-0.444,P<0.001).(2)Receiver operating characteristic curve results showed that the optimal cut-off value of DNA fragmentation index for live birth was 24.33%;the area under the curve was 0.775(0.746,0.804);the specificity was 72.60%;the sensitivity was 78.90%,and the accuracy was 75.70%.(3)Restricted cubic spline curve fitting the results of Logistic regression showed that when the sperm DNA fragmentation index was greater than 24.57%,the risk of clinical non-live birth increased.(4)The probability of Logistic regression analysis results showed that sperm DNA fragmentation index was a risk factor for live birth[OR(95%CI)=0.916(0.904,0.928),P<0.001],and when sperm DNA fragmentation index was greater than 27.78%,the probability of clinical live birth would be less than 50%.With the increase of sperm DNA fragmentation index by 1 unit,the probability of a live birth fell by 8.4%.(5)Internal and external to the validation of the clinical cutoff value showed that the cutoff point had certain clinical predictive value and accuracy.(6)Clinical decision curve and clinical impact curve results exhibited that the prediction model based on the clinical cut-off value had the maximum clinical net benefit value when the threshold probability was 0.22-0.73,and the ratio of loss to gain within the threshold probability range was always less than 1,which confirmed that the prediction model had good clinical application effectiveness.(7)The results of sperm DNA fragmentation index and offspring short-term security analysis showed that sperm DNA fragmentation index had no significant differences with preterm birth,body weight,deformity and sex.(8)These findings suggest that the optimal clinical cut-off value of sperm DNA fragmentation index for in vitro fertilization-embryo transfer live birth was 24.33%.The established clinical prediction model has good differentiation,accuracy and clinical application effectiveness.Sperm DNA fragmentation index has no significant impact on offspring short-term security,but large samples and long-term follow-up evaluation are still needed.

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Objective:To explore the risk factors and their interation in the incidence of monozygotic twins dur-ing in vitro fertilization-embryo transfer(IVF-ET).Methods:The cohort for this investigation comprised 4537 pa-tients who underwent IVF-ET with single embryo transfer,resulting in live births at Changzhou Maternal and Child Health Care Hospital spanning from January 2011 to December 2021.Among this cohort,76 paitients with monozygotic twins were enrolled in the monozygotic twin group.Employing a 5∶1 propensity score matching strategy,380 patients with monozygotic singletons were enrolled in monozygotic singleton group.Using single fac-tor and Lasso regression analysis to correct for the influencing factors of monozygotic twins,using multiple factor Logistic regression to screen for independent risk factors of monozygotic twins and analyze their impact weights,and then performing multiplication and addition interaction analysis on them.Results:The results of univariate analysis showed that there were statistically significant differences(P＜0.05)between the two groups of patients in terms of age,fertilization method,assisted hatching,embryo type for transfer,embryo transfer method,embryo culture duration,and HCG day estradiol(E2)level.The results of multivariate Logistic regression showed that blas-tocyst transfer(OR 2.847,95％CI 1.559-5.199),frozen-thawed embryo transfer(OR 2.640,95％CI 1.354-5.145),and HCG day E2 level(OR 1.783,95％CI 1.033-3.077)were independent risk factors for monozygotic twins(P＜0.05),demonstrating a hierarchical impact sequence of blastocyst transfer(11.60)＞frozen-thawed embryo transfer(6.54)＞HCG day E2(4.32)level.Notably,there was a significant positive additive interaction between embryo transfer type and HCG day E2 level,with an interaction index(S)of 4.690(95％CI 1.896-11.598),relative excess risk due to interaction(RERI)of 4.128(95％CI 2.236-6.019),and attributable propor-tion due to interaction(AP)of 0.661(95％CI 0.536-0.786).Conclusions:Blastocyst transfer,frozen-thawed embryo transfer,and HCG day E2 level are risk factors for monozygotic twins,and there is a significant positive additive interaction between embryo transfer type and HCG day E2 level.

Objective:To explore the risk factors and their interation in the incidence of monozygotic twins dur-ing in vitro fertilization-embryo transfer(IVF-ET).Methods:The cohort for this investigation comprised 4537 pa-tients who underwent IVF-ET with single embryo transfer,resulting in live births at Changzhou Maternal and Child Health Care Hospital spanning from January 2011 to December 2021.Among this cohort,76 paitients with monozygotic twins were enrolled in the monozygotic twin group.Employing a 5∶1 propensity score matching strategy,380 patients with monozygotic singletons were enrolled in monozygotic singleton group.Using single fac-tor and Lasso regression analysis to correct for the influencing factors of monozygotic twins,using multiple factor Logistic regression to screen for independent risk factors of monozygotic twins and analyze their impact weights,and then performing multiplication and addition interaction analysis on them.Results:The results of univariate analysis showed that there were statistically significant differences(P＜0.05)between the two groups of patients in terms of age,fertilization method,assisted hatching,embryo type for transfer,embryo transfer method,embryo culture duration,and HCG day estradiol(E2)level.The results of multivariate Logistic regression showed that blas-tocyst transfer(OR 2.847,95％CI 1.559-5.199),frozen-thawed embryo transfer(OR 2.640,95％CI 1.354-5.145),and HCG day E2 level(OR 1.783,95％CI 1.033-3.077)were independent risk factors for monozygotic twins(P＜0.05),demonstrating a hierarchical impact sequence of blastocyst transfer(11.60)＞frozen-thawed embryo transfer(6.54)＞HCG day E2(4.32)level.Notably,there was a significant positive additive interaction between embryo transfer type and HCG day E2 level,with an interaction index(S)of 4.690(95％CI 1.896-11.598),relative excess risk due to interaction(RERI)of 4.128(95％CI 2.236-6.019),and attributable propor-tion due to interaction(AP)of 0.661(95％CI 0.536-0.786).Conclusions:Blastocyst transfer,frozen-thawed embryo transfer,and HCG day E2 level are risk factors for monozygotic twins,and there is a significant positive additive interaction between embryo transfer type and HCG day E2 level.

Objective:To explore the risk factors and their interation in the incidence of monozygotic twins dur-ing in vitro fertilization-embryo transfer(IVF-ET).Methods:The cohort for this investigation comprised 4537 pa-tients who underwent IVF-ET with single embryo transfer,resulting in live births at Changzhou Maternal and Child Health Care Hospital spanning from January 2011 to December 2021.Among this cohort,76 paitients with monozygotic twins were enrolled in the monozygotic twin group.Employing a 5∶1 propensity score matching strategy,380 patients with monozygotic singletons were enrolled in monozygotic singleton group.Using single fac-tor and Lasso regression analysis to correct for the influencing factors of monozygotic twins,using multiple factor Logistic regression to screen for independent risk factors of monozygotic twins and analyze their impact weights,and then performing multiplication and addition interaction analysis on them.Results:The results of univariate analysis showed that there were statistically significant differences(P＜0.05)between the two groups of patients in terms of age,fertilization method,assisted hatching,embryo type for transfer,embryo transfer method,embryo culture duration,and HCG day estradiol(E2)level.The results of multivariate Logistic regression showed that blas-tocyst transfer(OR 2.847,95％CI 1.559-5.199),frozen-thawed embryo transfer(OR 2.640,95％CI 1.354-5.145),and HCG day E2 level(OR 1.783,95％CI 1.033-3.077)were independent risk factors for monozygotic twins(P＜0.05),demonstrating a hierarchical impact sequence of blastocyst transfer(11.60)＞frozen-thawed embryo transfer(6.54)＞HCG day E2(4.32)level.Notably,there was a significant positive additive interaction between embryo transfer type and HCG day E2 level,with an interaction index(S)of 4.690(95％CI 1.896-11.598),relative excess risk due to interaction(RERI)of 4.128(95％CI 2.236-6.019),and attributable propor-tion due to interaction(AP)of 0.661(95％CI 0.536-0.786).Conclusions:Blastocyst transfer,frozen-thawed embryo transfer,and HCG day E2 level are risk factors for monozygotic twins,and there is a significant positive additive interaction between embryo transfer type and HCG day E2 level.

Objective:To explore the risk factors and their interation in the incidence of monozygotic twins dur-ing in vitro fertilization-embryo transfer(IVF-ET).Methods:The cohort for this investigation comprised 4537 pa-tients who underwent IVF-ET with single embryo transfer,resulting in live births at Changzhou Maternal and Child Health Care Hospital spanning from January 2011 to December 2021.Among this cohort,76 paitients with monozygotic twins were enrolled in the monozygotic twin group.Employing a 5∶1 propensity score matching strategy,380 patients with monozygotic singletons were enrolled in monozygotic singleton group.Using single fac-tor and Lasso regression analysis to correct for the influencing factors of monozygotic twins,using multiple factor Logistic regression to screen for independent risk factors of monozygotic twins and analyze their impact weights,and then performing multiplication and addition interaction analysis on them.Results:The results of univariate analysis showed that there were statistically significant differences(P＜0.05)between the two groups of patients in terms of age,fertilization method,assisted hatching,embryo type for transfer,embryo transfer method,embryo culture duration,and HCG day estradiol(E2)level.The results of multivariate Logistic regression showed that blas-tocyst transfer(OR 2.847,95％CI 1.559-5.199),frozen-thawed embryo transfer(OR 2.640,95％CI 1.354-5.145),and HCG day E2 level(OR 1.783,95％CI 1.033-3.077)were independent risk factors for monozygotic twins(P＜0.05),demonstrating a hierarchical impact sequence of blastocyst transfer(11.60)＞frozen-thawed embryo transfer(6.54)＞HCG day E2(4.32)level.Notably,there was a significant positive additive interaction between embryo transfer type and HCG day E2 level,with an interaction index(S)of 4.690(95％CI 1.896-11.598),relative excess risk due to interaction(RERI)of 4.128(95％CI 2.236-6.019),and attributable propor-tion due to interaction(AP)of 0.661(95％CI 0.536-0.786).Conclusions:Blastocyst transfer,frozen-thawed embryo transfer,and HCG day E2 level are risk factors for monozygotic twins,and there is a significant positive additive interaction between embryo transfer type and HCG day E2 level.

Objective:To explore the risk factors and their interation in the incidence of monozygotic twins dur-ing in vitro fertilization-embryo transfer(IVF-ET).Methods:The cohort for this investigation comprised 4537 pa-tients who underwent IVF-ET with single embryo transfer,resulting in live births at Changzhou Maternal and Child Health Care Hospital spanning from January 2011 to December 2021.Among this cohort,76 paitients with monozygotic twins were enrolled in the monozygotic twin group.Employing a 5∶1 propensity score matching strategy,380 patients with monozygotic singletons were enrolled in monozygotic singleton group.Using single fac-tor and Lasso regression analysis to correct for the influencing factors of monozygotic twins,using multiple factor Logistic regression to screen for independent risk factors of monozygotic twins and analyze their impact weights,and then performing multiplication and addition interaction analysis on them.Results:The results of univariate analysis showed that there were statistically significant differences(P＜0.05)between the two groups of patients in terms of age,fertilization method,assisted hatching,embryo type for transfer,embryo transfer method,embryo culture duration,and HCG day estradiol(E2)level.The results of multivariate Logistic regression showed that blas-tocyst transfer(OR 2.847,95％CI 1.559-5.199),frozen-thawed embryo transfer(OR 2.640,95％CI 1.354-5.145),and HCG day E2 level(OR 1.783,95％CI 1.033-3.077)were independent risk factors for monozygotic twins(P＜0.05),demonstrating a hierarchical impact sequence of blastocyst transfer(11.60)＞frozen-thawed embryo transfer(6.54)＞HCG day E2(4.32)level.Notably,there was a significant positive additive interaction between embryo transfer type and HCG day E2 level,with an interaction index(S)of 4.690(95％CI 1.896-11.598),relative excess risk due to interaction(RERI)of 4.128(95％CI 2.236-6.019),and attributable propor-tion due to interaction(AP)of 0.661(95％CI 0.536-0.786).Conclusions:Blastocyst transfer,frozen-thawed embryo transfer,and HCG day E2 level are risk factors for monozygotic twins,and there is a significant positive additive interaction between embryo transfer type and HCG day E2 level.

Objective:To explore the risk factors and their interation in the incidence of monozygotic twins dur-ing in vitro fertilization-embryo transfer(IVF-ET).Methods:The cohort for this investigation comprised 4537 pa-tients who underwent IVF-ET with single embryo transfer,resulting in live births at Changzhou Maternal and Child Health Care Hospital spanning from January 2011 to December 2021.Among this cohort,76 paitients with monozygotic twins were enrolled in the monozygotic twin group.Employing a 5∶1 propensity score matching strategy,380 patients with monozygotic singletons were enrolled in monozygotic singleton group.Using single fac-tor and Lasso regression analysis to correct for the influencing factors of monozygotic twins,using multiple factor Logistic regression to screen for independent risk factors of monozygotic twins and analyze their impact weights,and then performing multiplication and addition interaction analysis on them.Results:The results of univariate analysis showed that there were statistically significant differences(P＜0.05)between the two groups of patients in terms of age,fertilization method,assisted hatching,embryo type for transfer,embryo transfer method,embryo culture duration,and HCG day estradiol(E2)level.The results of multivariate Logistic regression showed that blas-tocyst transfer(OR 2.847,95％CI 1.559-5.199),frozen-thawed embryo transfer(OR 2.640,95％CI 1.354-5.145),and HCG day E2 level(OR 1.783,95％CI 1.033-3.077)were independent risk factors for monozygotic twins(P＜0.05),demonstrating a hierarchical impact sequence of blastocyst transfer(11.60)＞frozen-thawed embryo transfer(6.54)＞HCG day E2(4.32)level.Notably,there was a significant positive additive interaction between embryo transfer type and HCG day E2 level,with an interaction index(S)of 4.690(95％CI 1.896-11.598),relative excess risk due to interaction(RERI)of 4.128(95％CI 2.236-6.019),and attributable propor-tion due to interaction(AP)of 0.661(95％CI 0.536-0.786).Conclusions:Blastocyst transfer,frozen-thawed embryo transfer,and HCG day E2 level are risk factors for monozygotic twins,and there is a significant positive additive interaction between embryo transfer type and HCG day E2 level.

Objective:To explore the risk factors and their interation in the incidence of monozygotic twins dur-ing in vitro fertilization-embryo transfer(IVF-ET).Methods:The cohort for this investigation comprised 4537 pa-tients who underwent IVF-ET with single embryo transfer,resulting in live births at Changzhou Maternal and Child Health Care Hospital spanning from January 2011 to December 2021.Among this cohort,76 paitients with monozygotic twins were enrolled in the monozygotic twin group.Employing a 5∶1 propensity score matching strategy,380 patients with monozygotic singletons were enrolled in monozygotic singleton group.Using single fac-tor and Lasso regression analysis to correct for the influencing factors of monozygotic twins,using multiple factor Logistic regression to screen for independent risk factors of monozygotic twins and analyze their impact weights,and then performing multiplication and addition interaction analysis on them.Results:The results of univariate analysis showed that there were statistically significant differences(P＜0.05)between the two groups of patients in terms of age,fertilization method,assisted hatching,embryo type for transfer,embryo transfer method,embryo culture duration,and HCG day estradiol(E2)level.The results of multivariate Logistic regression showed that blas-tocyst transfer(OR 2.847,95％CI 1.559-5.199),frozen-thawed embryo transfer(OR 2.640,95％CI 1.354-5.145),and HCG day E2 level(OR 1.783,95％CI 1.033-3.077)were independent risk factors for monozygotic twins(P＜0.05),demonstrating a hierarchical impact sequence of blastocyst transfer(11.60)＞frozen-thawed embryo transfer(6.54)＞HCG day E2(4.32)level.Notably,there was a significant positive additive interaction between embryo transfer type and HCG day E2 level,with an interaction index(S)of 4.690(95％CI 1.896-11.598),relative excess risk due to interaction(RERI)of 4.128(95％CI 2.236-6.019),and attributable propor-tion due to interaction(AP)of 0.661(95％CI 0.536-0.786).Conclusions:Blastocyst transfer,frozen-thawed embryo transfer,and HCG day E2 level are risk factors for monozygotic twins,and there is a significant positive additive interaction between embryo transfer type and HCG day E2 level.