1.Investigation on the Current Situation of Referral for Critically Ⅲ Pregnant Women in Beijing and Chongqing
Jing HU ; Yike YANG ; Yan WANG
Journal of Practical Obstetrics and Gynecology 2025;41(8):654-659
Objective:To investigate the current status of referral for critically ill pregnant women in Beijing and Chongqing,provide improvement strategies for the management of referral for critically ill pregnant women.Meth-ods:From May 2022 to June 2024,a self-made questionnaire was used to survey medical staff at different levels of midwifery institutions in Beijing and Chongqing through the internet.The survey targets 18 midwifery institutions in Haidian District and Changping District of Beijing,as well as 50 midwifery institutions in 25 districts and counties of Chongqing.Collect and analyze basic information of the surveyed subjects,the operation of the referral process for critically ill pregnant women(including familiarity and rationality of the referral process),referral indications,dif-ficulties and problems encountered during the referral process,etc.Results:①In this study,a total of 761 valid questionnaires were collected,of which 539 were from Beijing and 222 were from Chongqing.Among 761 surveyed individuals,physicians accounted for 51.4%and nurses(including midwives)accounted for 48.6%;39.7%of the cases came from third level midwifery institutions,while 60.3%came from second level or lower midwifery institu-tions.②93.1%of the surveyed medical staff were familiar with the referral process,with 92.8%in Beijing and 94.2%in Chongqing.There was no statistically significant difference between the two regions(x2=2.843,P=0.241);98.3%of the surveyed medical staff believed that the referral process in their unit was reasonable,with 98.9%in Beijing and 96.8%in Chongqing.There was no statistically significant difference between the two re-gions(x2=4.121,P=0.127).③ The main problems encountered by referral institutions were delayed patient ref-errals(51.0%)and unclear case reporting(42.9%),while the most common difficulties encountered by referral institutions were poor referral transportation(29.5%),inability to respond to referral requests in a timely manner(17.9%),and difficulties in inter hospital communication(17.7%).Conclusions:Medical staff in Beijing and Chongqing are familiar with the referral system for critically ill pregnant women and have achieved good operation-al results.In response to the main problems and difficulties in the current referral process,it is recommended to combine online and on-set consultations to promote continuous communication,standardize referral case records,establish a two-way referral model and regular feedback mechanism,and strengthen targeted personnel commu-nication.
2.The Study of Preoperative Routine Multichannel Urodynamic Testing for Un-complicated Stress Urinary Incontinence
Aixin WANG ; Xiuli SUN ; Xin YANG
Journal of Practical Obstetrics and Gynecology 2025;41(8):649-653
Objective:To investigate the effectiveness of multi-channel urodynamic testing(MUT)in preopera-tive evaluation of stress urinary incontinence(SUI),and its impact on postoperative complications and treatment efficacy.Methods:The clinical data of 120 patients were collected.They were hospitalized for SUI and received surgical treatment in the gynecology department of Peking University People's Hospital from May 2020 to June 2022.Among them,60 cases(no-MUT group)were evaluated only by the six-step preoperative evaluation of un-complicated SUI recommended by the American College of Obstetrics and Gynecology without routine MUT,and another 60 cases(MUT gruop)underwent routine MUT and clinical evaluation.Both groups of patients underwent tension-free vaginal tape(TVT-E).The differences in general conditions,intraoperative conditions,postoperative complications,and subjective and objective cure rates between the two groups were compared.Pelvic floor dis-tress inventory-20(PFDI-20)and incontinence quality of life(l-QOL)were used to evaluate the quality of life,and patient-initiated sexual questiornaire-12(PISQ-12)was used to evaluate patients' quality of sex life.Results:①The positive rate of urodynamic SUI diagnosis was 53.3%(32/60)in MUT group.②The subjective cure rates of both groups were 96.7%;the objective cure rate was 98.3%and 96.7%respectively.No significant difference was observed in the postoperative subjective and objective cure rate of patients between two groups(P>0.05).③After the removal of the urinary catheter,the rate of voiding dysfunction was 5.0%in the no-MUT group and 8.3%in the MUT group.The rate of sling release was 1.7%and 3.3%respectively.The rate of newly developed overactive bladder(OAB)was 1.7%and 3.3%,respectively,with no statistically significant differences(P>0.05).④No significant difference was observed in the postoperative complications,sexual activity,and quality of life scores between the two groups(P>0.05).Conclusions:Patients with uncomplicated SUI assessed by the six step preoperative evaluation method can skip routine MUT without increasing surgical complications,and the treatment effect is comparable to that of routine MUT.
3.Analysis of Obstetric Factors in Adverse Outcomes of Preterm Infants with Preterm Premature Rupture of Membranes
Fan WU ; Yifei CAI ; Shaofang HUA
Journal of Practical Obstetrics and Gynecology 2025;41(8):666-671
Objective:To explore the association between adverse outcomes of preterm infants and obstetric factors such as infection,maternal disease and treatment measures in patients with preterm premature rupture of membranes(PPROM),so as to provide more accurate and effective prediction and intervention methods for im-proving maternal and infant prognosis.Methods:A retrospective analysis was conducted on the clinical data of 534 PPROM patients who gave births in the obstetrics department of The Second Hospital of Tianjin Medical Uni-versity from January 1,2018,to August 31,2023.Based on the presence of severe preterm birth complications in premature infants(including bronchopulmonary dysplasia,necrotizing enterocolitis,retinopathy of prematurity,neonatal infectious pneumonia,neonatal respiratory distress syndrome,neonatal hypoxic-ischemic encephalopa-thy,and neonatal sepsis)or death,the patients were divided into two groups:the adverse outcome group(n=121)and the non-adverse outcome group(n=413).The study compared differences between the two groups in general conditions,pregnancy complications and comorbidities,treatment and management,amniotic fluid and pla-cental infections.Logistics regression analysis was used to identify obstetric factors associated with adverse out-comes in preterm infants.Results:Univariate analysis revealed that patients in the adverse outcome group had smaller gestational weeks at delivery,longer intervals between membrane rupture and delivery,and a lower rate of vaginal delivery compared to those in the non-adverse outcome group.They also had a higher proportion of con-current cervical insufficiency,antepartum hemorrhage,hypertensive disorders of pregnancy,and anemia of preg-nancy.The use of prenatal magnesium sulfate and glucocorticoids for fetal lung maturity promotion before delivery was higher,and the effective coverage rates of prophylactic antibiotics was lower.The positive rates of amniotic fluid bacterial culture,the proportion of clinical chorioamnionitis,and histological chorioamnionitis were higher.All of the above differences were statistically significant(P<0.05).Multivariate analysis revealed that positive amniotic fluid bacterial culture(OR 4.602,95%CI 2.303-9.196,P<0.05),anemia of pregnancy(OR 4.192,95%CI 2.064-8.510,P<0.05),and cervical insufficiency(OR 9.435,95%CI 1.138-78.261,P<0.05)were independ-ent risk factors for adverse outcomes in preterm infants among PPROM patients,while gestational weeks at deliv-ery(OR0.466,95%CI 0.370-0.586,P<0.05),effective coverage of prophylactic antibiotics before delivery(OR 0.286,95%CI 0.121-0.673,P<0.05),and treatment for lung maturity promotion(OR 0.225,95%CI 0.107-0.474,P<0.05)were protective factors for adverse outcomes in premature infants in PPROM patients.Conclu-sions:The adverse outcomes of preterm infants in PPROM patients are closely related to obstetric factors such as infection,maternal diseases,and treatment measures.Among these,positive amniotic fluid bacterial culture,a-nemia during pregnancy,and cervical insufficiency are independent risk factors for adverse outcomes in premature infants in PPROM patients.On the other hand,gestational age at deli very,effective coverage of prenatal antibiot-ics,and pulmonary maturity promotion therapy are protective factors.
4.Shunt Effect of ATP10a Methylation Assay in Patients with Cervical Cytological Abnormalities
Lichang CHEN ; Yiman TANG ; Sisi CHEN ; Haihong JIN
Journal of Practical Obstetrics and Gynecology 2025;41(8):672-677
Objective:To investigate the role of adenosine triphosphatase phospholipid transporter 10a(ATP10a)methylation assay in the triage of atypical squamous cell of undetermined significance(ASC-US)and low-grade squamous intraepithelial lesions(LSIL)in cervical cytology.Methods:188 patients with cervical exfolia-ted cells of ASC-US and LSIL were selected,and High-risk human papilloma virus(HR-HPV)typing and cervical biopsy results of the patients were collected at the same time.The cervical biopsy pathology results were used as the gold standard,and they were divided into inflammation,LSIL,high grade squamous intraepithelial lesions(HSIL)and cervical squamous cell carcinoma(SCC).Classify inflammation and LSIL as LSIL-group,HSIL and SCC as HSIL+group to compare the efficacy of ATP10a methylation and HR-HPV testing for diagnosis of HSIL+in this population(including HSIL and SCC).Results:The methylation detection value of ATP10a in the inflam-mation,LSIL,HSIL,and SCC patients were 19.035(16.478,20.823),13.446(5.890,20.674),10.336(4.733,17.336),4.223(1.713,7.754),respectively.The methylation detection value of ATP10a in the LSIL-group was 17.812(10.787,20.686),while that in the HSIL+group was 7.251(3.170,14.194).There was a statistically sig-nificant difference between the groups(Z=-5.824,P<0.001).The proportion of HR-HPV positivity in the LSIL-group was 70.9%,which was lower than that of the HSIL+group(88.2%),and the difference was statistically significant(Z=-2.887,P=0.004).The specificity,negative predictive value(NPV),and area under the receiver operating characteristic(ROC)curve(AUC)of ATP10A methylation diagnosis of HSIL+(66.0%,79.1%,and 0.747)were higher than those of HR-HPV detection(29.1%,50.7%,0.587).Sensitivity and positive predictive value(PPV)(78.8%and 65.7%)were lower than those of HR-HPV testing(88.2%and 75.0%).when using ATP10a methylation instead of HR-HPV detection for triage of cytological abnormalities(ASC-US,LSIL),the col-poscopy referral rate could be reduced to 54.3%.In the ASC-US population,the AUC(0.683)for the diagnosis of HSIL+by ATP10a methylation test was higher than that of HR-HPV test(0.599),and the difference was statisti-cally significant(P=0.028).In the LSIL population,the AUC(0.828)for the diagnosis of HSIL+by ATP10a methylation test was still higher than that of HR-HPV test(0.563),and the difference was statistically significant(P=0.005).Conclusions:ATP10a methylation levels increased with the severity of cervical lesions,and the di-agnostic efficacy of ATP10a methylation detection for the severity of cervical lesions may not be lower than HR-HPV typing.
5.The Relationship between Serum Histone Deacetylase-3 and the Severity of En-dometriosis
XinYue ZHANG ; Xiaoxia ZHANG ; Jianjun LU
Journal of Practical Obstetrics and Gynecology 2025;41(8):678-682
Objective:To investigate the relationship between serum histone deacetylase-3(HDAC3)and the severity of endometriosis(EMT).Methods:The clinical data of 109 EMT patients admitted to the Affiliated Hospi-tal of Inner Mongolia Medical University from June 1,2021 to November 30,2023 were extracted and analyzed.Pa-tients were divided into stage Ⅰ/Ⅱ group(56 cases)and stage Ⅲ/Ⅳ group(53 cases)according to the revised EMT staging criteria of the American Society for Reproductive Medicine(ASRM).Univariate analysis and binary Logistic regression were used to analyze the correlation factors between serum HDAC3 and the severity of EMT patients,and receiver operating characteristic(ROC)curve was plotted and the area under the curve(AUC)was calculated to evaluate the diagnostic value of stage Ⅲ/Ⅳ EMT.Results:The levels of serum HDAC3,human epididymal protein 4(HE4),serum carbohydrate antigen 125(CA125),vascular endothelial growth factor(VEGF),platelet to lymphocyte count ratio(PLR),and fibrinogen(Fib)in stage Ⅲ/Ⅳ patients were significantly higher than those in stage Ⅰ/Ⅱ patients,with statistical significant differences(P<0.05).Binary Logistic regres-sion analysis showed that serum HDAC3,CA125,and VEGF were related factors affecting stage Ⅲ/Ⅳ EMT pa-tients(OR>1,P<0.05).The ROC curve showed that the AUC of serum HDAC3,CA125,and VEGF for phaseⅢ/Ⅳ EMT evaluation were 0.898,0.701,and 0.795,respectively,and the AUC for combined detection evaluation was 0.956.Conclusions:The serum HDAC3 level is related to the severity of EMT patients,and gradually increa-ses with the increase of EMT staging.HDAC3 combined with CA125 and VEGF has a high preoperative evaluation value for stage Ⅲ/Ⅳ EMT patients.
6.The Relationship between Molecular Typing and Prognosis of Ovarian Endom-etrioid Adenocarcinoma
Rongyu LIU ; Chang LIU ; Xinlin HE ; Zhengyu LI
Journal of Practical Obstetrics and Gynecology 2025;41(8):660-665
Objective:To investigate the molecular typing characteristics of patients with ovarian endometrioid adenocarcinoma(OEA)and its relationship with prognosis.Methods:A retrospective analysis was performed on the clinical medical records and follow-up outcomes of 176 patients with OEA admitted to the gynecology depart-ment of West China Second University Hospital of Sichuan University from June 1,2011 to December 31,2019.Based on the results of genetic testing and pathological immunohistochemical data,the molecular subtypes of the patients were determined and divided into three groups:mismatch repair deficiency(dMMR)group(22 cases),no specific molecular profile(NSMP)group(71 cases),and p53 mutation(p53abn)group(83 cases).The differences in clinicopathological characteristics among the three subgroups were compared.Kaplan-Meier method was used to draw survival curves.The overall survival(OS)and progression free survival(PFS)curves of pa-tients were compared in different molecular subtypes and different age groups using Log-rank test.Results:①There were no statistically significant differences among the three groups in age,body mass index(BMI),meno-pause,and the presence of internal medical comorbidities(P>0.05).②There were no statistically significant differences among the three groups in tumor differentiation degree,International Federation of Gynecology and Obstetrics(FIGO)staging,preoperative carbohydrate antigen 125(CA125)level,preoperative neoadjuvant chemo-therapy,para-aortic lymph node metastasis,pelvic lymph node metastasis,concurrent endometrial cancer,and malignant transformation of ovarian endometriotic cysts(P>0.05).③There were statistically significant differ-ences in 5-year OS and PFS among the three groups(P<0.05).The 5-year OS and PFS of the dMMR group were superior to those of the p53abn group(P<0.05).Conclusions:There were no significant differences in the baseline characteristics and the clinicopathological features of tumors among patients with different molecular sub-types of OEA.Patients with dMMR-type OEA exhibited more prominent advantages in PFS and OS compared with those with p53abn type.Formulating individualized treatment strategies based on the molecular typing charac-teristics of OEA may improve the clinical prognosis of patients.
7.The Predictive Value of TYG Index and TYG-BMI Index for Polycystic Ovarian Syndrome Combined with Metabolic Syndrome
Wenxin LIU ; Shan LI ; Xiaoli LI
Journal of Practical Obstetrics and Gynecology 2025;41(8):693-698
Objective:To explore the predictive value of triglyceride-glucose(TYG)index and triglyceride-glu-cose-body mass index(TYG-BMI)for polycystic ovarian syndrome(PCOS)combined with metabolic syndrome(MetS).Methods:Clinical data of 109 PCOS patients who visited Xingtai People's Hospital from January 1,2022 to December 31,2023 were collected as the training group.They were divided into the MetS combined group(32 cases)and the non-Mets combined group(77 cases)according to whether they were combined with MetS.U-sing univariate and multivariate Logistic regression analysis to investigate the influencing factors of PCOS com-bined with MetS,as well as the predictive value of TYG index and TYG-BMI index for PCOS combined with MetS.In addition,according to a ratio of 7∶3 between the training group and the validation group,the clinical data of 47 patients with PCOS who visited the hospital from January 1,2024 to September 30,2024 were collected as the vali-dation group to conduct external validation of the prediction model.Results:①The serum testosterone(T),lute-inizing hormone(LH),low-density lipoprotein cholesterol(LDL-C),steady-state model insulin resistance index(HOMA-IR),TYG index,and TYG-BMI index in the MetS group were higher than those in the non MetS group(P<0.05).② Multivariate Logistic regression analysis showed that abnormal values of LH,HOMA-IR,TYG in-dex,and TYG-BMI index were influencing factors for PCOS patients with MetS(OR>1,P<0.05).③The area under the curve(AUC)predicted by TYG index and TYG-BMI index for PCOS combined with MetS was 0.812 and 0.763,respectively.④Constructing predictive models for TYG index,TYG-BMI index,LH,and HOMA-IR,the clinical decision curve showed a maximum net benefit rate of 0.294.The column chart model showed that the con-sistency index(C-index)for predicting the presence of MetS in PCOS patients was 0.875.⑤The external valida-tion results of the prediction model show that the AUC of the model predicting PCOS patients with MetS was 0.948.Conclusions:TYG index and TYG-BMI index can be used for predicting MetS in PCOS patients.The risk prediction model constructed with LH and HOMA-IR can visualize the risk and has ideal predictive value.
8.Analysis of Vaginal Microflora Examination Results in 19322 Initial Visit Infertil-ity Women
Zhenhua CHANG ; Shuwei YAN ; Xiaoyan REN ; Baohua MIN ; Xiaojuan XIE ; Zhenhua LU ; Sanhua WEI
Journal of Practical Obstetrics and Gynecology 2025;41(7):563-567
Objective:To investigate the characteristic distribution of vaginal microbiota in infertile women.Methods:We collected the results of vaginal microbiological examinations from 19322 initial visit infertile women who visited the Reproductive Medicine Center of the Department of Obstetrics and Gynecology,the Second Affili-ated Hospital of Air Force Medical University from March 1,2023 to July 31,2024.The vaginal microbiota infection status of patients was compared in different age groups(<25 years old,25-<30 years old,30-<35 years old,35-<40 years old,≥40 years old)and different seasons(spring,summer,autumn,winter).Results:①Among 19322 women,6027 cases(31.19%)showed abnormal vaginal microecology.Pathogenic microorganisms were detected in 3093 cases,including 2882 cases of single vaginitis,211 cases of mixed vaginitis,3764 cases with vagi-nal cleanliness grade Ⅲ-Ⅳ,and 3965 cases with abnormal lactobacilli.Among patients with single vaginitis,1349 cases(46.81%)were diagnosed with vulvovaginal candidiasis(VVC),which was the highest proportion.Aerobic vaginitis(AV)followed with 752 cases(26.09%),and bacterial vaginosis(BV)had 671 cases(23.28%),trichomonal vaginitis(TV)with 110 cases(3.82%).Among patients with mixed vaginitis,AV+BV was the most common with 96 cases(45.49%).②The detection rates of cleanliness grade Ⅲ-Ⅳ,abnormal lactobacilli,abnor-mal microorganisms(unclear pathogen),single vaginitis(BV,VVC and TV),and mixed vaginitis showed statisti-cally significant differences across different seasons(P<0.05).Specifically,the detection rates of cleanliness grade Ⅲ-Ⅳ and abnormal microorganisms(unclear pathogens)were significantly higher in autumn than in other seasons(P<0.05),while the detection rate of abnormal lactobacilli was higher in spring than in other seasons(P<0.05).③The detection rates of abnormal lactobacilli,abnormal microorganisms(unclear pathogen),single vaginitis(BV,VVC and AV),and mixed vaginitis showed significant differences among different age groups(P<0.05).Specifically,the detection rate of abnormal microorganisms(unclear pathogen)was higher in the age group<25 years than in other age groups(P<0.05),while the detection rate of BV among single vaginitis cases was higher in the age group≥40 years than in other age groups(P<0.05).Conclusions:The vaginal microecol-ogy of infertile women varies in terms of infection rates across different age groups and seasons.Patients with simple vaginitis have the highest rate of VVC,while those with mixed vaginitis have the highest proportion of AV+BV infection.
9.Study on the Correlation between the Expression of PD-1 and VISTA and the Imbalance of Th1/Th2,Th17/Treg,Th22 in the Microenvironment of Endometri-al Cancer
Jing CHAI ; Jiahong ZHANG ; Mengxue LI
Journal of Practical Obstetrics and Gynecology 2025;41(7):574-579
Objective:To investigate the correlation of programmed death receptor-1(PD-1)and V-domain im-munoglobulin suppressor of T-cell activation(VISTA)expression with the imbalance of helper T lymphocytes(Th)1/Th2,Th17/regulatory T cells(Treg),and Th22 in the microenvironment of endometrial cancer(EC).Methods:From March 1,2020 to June 30,2023,94 patients with EC(EC group),94 patients with atypical hyperplasia of the endometrium(AH),and 94 controls without uterine and endometrial diseases such as EC and AH(control group)were selected for treatment at the Tangshan Maternal and Child Health Hospital.The expression of PD-1 and VIS-TA in various tissues and the levels of Th1/Th2,Th17/Treg,and Th22 in the endometrial microenvironment were compared.Pearson analysis was used to investigate the correlation between the expression of PD-1 and VISTA in tissues and the imbalance of Th1/Th2,Th17/Treg,and Th22 in the EC microenvironment.The positive expression of PD-1 and VISTA in tissues of patients with different pathological characteristics was also compared.Results:①The expression of PD-1 and VISTA was higher in EC group and AH group than that in the control group,and high-er in EC group than AH group,with statistically significant differences(P<0.05).In both EC group and AH group,Th1/Th2 and Th17/Treg levels in the microenvironment were lower than those in the control group,while Th22 level was higher.EC group showed lower Th1/Th2 and Th17/Treg levels but higher Th22 level than AH group,with statistically significant differences(P<0.05).②No correlation was found between the expression of PD-1 and VISTA and the Th1/Th2,Th17/Treg,and Th22 in the microenvironment in control group(P>0.05).In AH group and EC group,the expression of PD-1 and VISTA was negatively correlated with the Th1/Th2 and Th17/Treg lev-els in the microenvironment(r<0,P<0.05),but positively correlated with Th22 level in the microenvironment(r>0,P<0.05).③In EC patients,the expression of PD-1 was related with clinical stage,invasion depth,and lymph node metastasis(P<0.05);VISTA expression was related with clinical stage and lymph node metastasis(P<0.05).Conclusions:The high expression of PD-1 and VISTA in EC is closely associated with the imbalance of Th1/Th2,Th17/Treg,and Th22 in the tumor microenvironment,as well as the tumor ivasiveness.The dual inhibi-tion strategy targeting PD-1 and VISTA immune checkpoints may offer a novel approach for EC treatment.
10.A Two-sample Mendelian Randomization Study on the Causal Relationship Be-tween Plasma Proteins and Spontaneous Abortion
Qian LIU ; Mei DU ; Jing LI ; Yamei LI ; Jianying PEI
Journal of Practical Obstetrics and Gynecology 2025;41(7):580-585
Objective:To investigate the causal relationship between plasma proteins and spontaneous abor-tion using a two-sample Mendelian randomization method.Methods:Using genome-wide association study(GWAS)data from an Icelandic population as an exposure factor and spontaneous abortion data from the Finn-ish Genetic Research Project(FinnGen)as an outcome,the causal relationship between plasma proteins and the risk of developing spontaneous abortion was analyzed using a Mendelian randomization(MR)study.The inverse variance weighting(IVW)method was used as the primary study method,with MR-Egger,weighted median and weighted mode complementing the results;and sensitivity analyses were performed using Cochrane's Q test,MR-Egger intercept testand leave-one-out method to validate the reliability of the data.Results:Seven plasma proteins were identified as potentially correlated with the risk of spontaneous abortion of which fucosyltransferase 10(FUT10)(OR 0.955,95%CI 0.915-0.996,P=0.034),plexin B2(PLXNB2)(OR 0.947,95%CI 0.902-0.995,P=0.030),and interleukin-11 receptor alpha(IL-11Rα)(OR0.905,95%CI 0.848-0.966,P=0.003)were associ-ated with a reduced risk of SA development,while plasma proteins soluble L-selectin(SL-selectin)(OR 1.076,95%CI 1.021-1.134,P=0.006),Cripto protein(OR 1.039,95%CI 1.008-1.071,P=0.012),dendritic cell-specif-ic intercellular adhesion molecule 3-grabbing non-integrin(DC-SIGN)(OR 1.051,95%CI 1.022-1.082,P=0.001),and protein Z-dependent protease inhibitor(ZPI)(OR 1.035,95%CI 1.001-1.071,P=0.045)levels were positively associated with the risk of developing SA.No heterogeneity or horizontal pleiotropy was detected(Co-chrane's Q test and MR-Egger intercept test,P>0.05),and leave-one-out analysis showed that there were no individual single-nucleotide polymorphisms that had a large impact on the overall data.Conclusions:This Mende-lian randomization analyses confirmed the causal relationship between multiple plasma proteins and spontaneous abortion,which is potentially clinically valuable for studying the correlation between plasma proteins and spontane-ous abortion.
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