| 【Background】Asthenospermia(AS)is one of the main causes of male infertility,defined as decreased sperm motility in fresh semen(progressive motility(PR)<32%,or total motility<40%).With the development of social and economy,great changes have taken place in people’s life style and working environment.And there are great differences in population characteristics,cultural customs and environmental factors in different regions,which may lead to different influencing factors of AS in different regions.At present,the predictive model of AS is very rare,and there is no predictive model for clinical diagnosis and treatment of AS.Besides,the epidemiological data of AS in Xi’an is relatively a few in recent years.Therefore,it is necessary to explore the influencing factors of AS in Xi’an.In recent years,much attention has been paid to the role of oxidative stress(OS)in the pathological mechanism of AS.OS of male reproductive system can be caused not only by genetic and biological/disease-related factors,but also by modern lifestyle and environmental occupational exposure-related factors.OS can easily cause lipid peroxidation of germ cells,damage sperm motility,increase sperm DNA fragments and apoptosis,and then reduce male sperm quality.However,most of the previous studies focused on the macroscopic effects of OS on sperm quality or on sperm cell biology.There are relatively few studies on the specific parameters of microcosmic parameters such as sperm movement velocity and trajectory that affect male fertility by OS.【Objective】1.The influencing factors of AS in men of childbearing age in Xi’an were analyzed,and the prediction model of AS in men of childbearing age was established according to the related factors of lifestyle habits and environmental occupational exposure.The purpose of this study is to provide a reference basis for the identification and prevention and treatment of AS in Xi’an.2.To explore the correlation between seminal plasma OS level and sperm concentration,motility,velocity and trajectory,so as to provide evidence for accurate intervention of AS.【Methods】1.In the first part,a multicenter case-control study was designed.1.1 A questionnaire on the influencing factors of AS in men of childbearing age was developed through document reviews,small-scale investigation and two rounds of expert consultation,including personal basic information,marriage and childbearing history,lifestyle,environmental and occupational exposure and so on.1.2 Recruit men of childbearing age who were examined before pregnancy in the urology or reproductive medicine centers of Xi’an Xijing Hospital,Tangdu Hospital,Northwest Women and Children Hospital and Air Force 986 Hospital from August 2020to December 2021.The semen quality examination data and questionnaire information of volunteers were collected,and the database was established by using Excel.1.3 The data were analyzed by SPSS 22 and R4.1.2 statistical software.The subjects were selected according to the inclusion and exclusion criteria,and were divided into AS group and normal control group.Univariate logistic regression was used to screen the variables related to AS.The statistically significant variables in univariate analysis were included in multivariate logistic regression analysis.The prediction model was established by Wald forward method,and the nomograms was drawn.1.4 Volunteers from the above four hospitals in Xi’an from January 2022 to August2022 were collected to validate the model externally,and the discrimination was evaluated according to the area under the receiver operating characteristic curve(ROC)area under curve(AUC));the best cut-off value was calculated according to the ROC curve analysis and Youden index;and the calibration was evaluated by calibration curve and Hosmer-Lemeshow(H-L)goodness-of-fit test.The clinical effectiveness was evaluated by decision curve analysis(DCA).All the statistical analysis showed that the difference was statistically significant(P<0.05).2.The second part adopted the cross-sectional research design.From May to July 2022,120 volunteers were recruited in the urology clinic of Xijing Hospital.All the subjects completed the questionnaire developed in the first part of the study.Semen samples were collected,and computer-aided sperm analysis system was used to detect sperm density parameters(sperm concentration,linear motility),sperm motility(total sperm motility,PR,non-progressive motility(NP)),sperm motility velocity(curvilinear velocity(VCL),straight-line velocity(VSL),average path velocity(VAP))and sperm motility trajectory parameters(mean amplitude of lateral head displacement(ALH),frequency of head displacement(BCF),mean angular displacement(MAD),linearity coefficient(LIN),wobble coefficient(WOB),straightness coefficient(STR)).The levels of oxidative stress of malondialdehyde(MDA)and reduced glutathione(GSH)in seminal plasma samples were detected by kits.General linear model(GLM)was used to evaluate the correlation between OS and sperm quality.【Results】1.The first part of the study included 630 subjects,aged from 21 to 48 years old(30.79±3.99 years),including 199 patients with AS and 431 normal controls.There was no significant difference in age,nationality,occupation,average monthly income,marital status,fertility,time of abstinence and frequency of sexual life between the two groups.There are differences between the two groups in terms of education level and residence.The body mass index(BMI)of AS group(24.80(4.19)kg/m~2)was higher than that in the normal control group(23.46(3.24)kg/m~2)(P<0.001).The results of semen quality examination between the two groups showed that the sperm concentration,PR,NP,total sperm motility and normal sperm shape rate in normal group were higher than those in AS group(P<0.05).There was no significant difference in semen volume and p H value between the two groups(P>0.05).By univariate logistic regression analysis,19 variables related to AS were screened out.Including age,BMI(24.0-27.9 vs 18.5-23.9 and≥28.0 vs 18.5-23.9(kg/m~2)),education(junior college or undergraduate vs junior high school or below),average monthly income(5000-10000 vs<3000 yuan),residence(urban vs rural areas),actual sleep time,sedentary time,time spent using mobile phone/computer,smoking,drinking,sauna/hot bath,plastic/foam hot food,secondhand smoke exposure,high temperature exposure,heavy metal exposure,radiation exposure,radar/signal base station exposure,hair dye exposure,machine/diesel/asphalt exposure and so on.Through multivariate logistic regression analysis,it was found that the risk factors of AS in men of childbearing age were age increasing(OR=1.06,95%CI=1.01-1.12,P=0.016),BMI(24.0-27.9 vs 18.5-23.9(kg/m~2),OR=2.30,95%CI=1.49-3.57,P<0.001)and(≥28.0 vs18.5-23.9(kg/m~2),OR=3.05,95%CI=1.44-6.43,P=0.003).Prolonged use of mobile phone/computer(OR=1.18,95%CI=1.09-1.28,P<0.001),frequent drinking(OR=1.93,95%CI=1.22-3.06,P=0.005),sauna/hot bath(OR=2.25,95%CI=1.59-3.19,P<0.001),plastic/foam hot food(OR=1.65,95%CI=1.29-2.12,P<0.001),secondhand smoke exposure(OR=1.42,95%CI=1.10-1.82,P=0.007),radiation exposure(OR=2.63,95%CI=1.72-4.02,P<0.001),hair dye exposure(OR=1.64,95%CI=1.10-2.43,P=0.014),engine/diesel/asphalt exposure(OR=1.44,95%CI=1.05-1.99,P=0.025).Residence(urban vs rural,OR=0.47,95%CI=0.30-0.76,P=0.002)and increased actual sleep time(OR=0.80,95%CI=0.66-0.97,P=0.023)were protective factors for AS in men of childbearing age.A nomogram was drawn according to the influencing factors of AS screened by multivariate logistic regression analysis.324 men of childbearing age were included as the verification group to verify the predictive model.The results showed that the AUC of ROC curve in the model group was 0.838(95%CI=0.805-0.870),and the AUC of ROC curve in the verification group was 0.853(95%CI=0.812-0.894).The best cut-off values of the two groups are calculated by Youden index,the best cut-off value in the model group is 0.320,and the best cut-off value in the verification group is 0.403,indicating that the prediction model has a good degree of discrimination.the correction curve in the model group is close to the calibration curve in the ideal state,and the correction curve in the verification group is similar to that in the model group,indicating that the correction function of the prediction model is better.The goodness-of-fit test of H-L shows that the modeling group is 0.526 and the verification group is 0.539,which indicates that the prediction model established in this study has a good degree of fitting with the ideal model.The DCA of the line chart of the risk of AS in men of childbearing age was used to evaluate the clinical effectiveness of the prediction model,suggesting that if the threshold probability of volunteers and doctors was between 10%and 79%,the use of the line chart to predict the risk of AS showed clinical net benefits.2.In the second part,there were 60 cases of AS and 60 cases of normal control,the sperm PR,NP,total sperm motility and normal sperm shape rate in AS group were significantly lower than those in normal control group(P<0.001),but there was no significant difference in semen volume,semen p H value and sperm concentration between the two groups.The level of MDA in AS group(4.21±1.83nmol/ml)was higher than that in normal control group(2.94±1.03 nmol/ml)(P<0.001).The level of GSH in AS group(94.44±32.21μg/ml)was lower than that in control group(121.05±49.98μg/ml).There were significant differences in sauna/hot bubble bath,plastic/foam hot food and secondhand smoke exposure between the two groups(P<0.05).There was no significant difference in other basic personal conditions,lifestyle habits and working environment exposure(P>0.05).It is suggested that exposure to unhealthy lifestyle or environmental risk factors may affect sperm motility by increasing the level of seminal plasma OS,leading to AS.In the correlation between MDA level and sperm quality parameters,there was no correlation between MDA and sperm size and sperm concentration(P>0.05),but there was a negative correlation between MDA and linear motility sperm concentration(P<0.05),MDA level was negatively correlated with PR,NP and total sperm motility(P<0.05),and MDA level was negatively correlated with VCL,VSL and VAP in sperm velocity(P<0.05).In terms of sperm motility trajectory,MDA was negatively correlated with ALH,BCF,MAD,LIN,WOB and STR(P<0.05).In terms of the correlation between GSH level and sperm quality parameters,GSH was not related to sperm size,GSH level was positively correlated with sperm concentration and linear motility sperm density(P<0.05),and GSH level was positively correlated with PR,NP and total sperm motility(P<0.05).In terms of sperm motility speed,GSH level was positively correlated with sperm VSL and VAP(P<0.05);and sperm motility trajectory,GSH level was positively correlated with sperm ALH,BCF,MAD,LIN,WOB and STR(P<0.05).【Conclusion】1.A multicenter case-control study was conducted to screen the influencing factors of AS in men of childbearing age in Xi’an.It provides an epidemiological basis for the prevention and treatment of AS in men of childbearing age in Xi’an.According to the related factors of lifestyles and environmental occupational exposure,a predictive model of AS in men of childbearing age in Xi’an was established,and the stability of the model was verified,which provides a reference tool for the identification of high-risk groups of AS in Xi’an.2.Through cross-sectional study,it was found that exposure to bad lifestyle or environmental risk factors may affect sperm motility and lead to AS by increasing seminal plasma OS levels,and that higher OS levels are related to lower sperm motility,slower sperm movement velocity and more adverse changes in sperm trajectory.In view of the increasingly serious male reproductive problems,this study provides scientific basis for precise intervention of AS and protection of Chinese fertility rate. |
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