ObjectiveTo systematically review the association between C677T and A1298C polymorphisms of methylenetetrahydrofolate reductase (MTHFR) gene and the risk of unexplained recurrent spontaneous abortion (URSA). MethodsWe searched PubMed, EMbase, CBM, CNKI, VIP and WanFang Data from inception to May 2015 to collect case-control studies about the association between the MTHFR gene C677T and A1298C polymorphisms and the risk of URSA. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies. Then, meta-analysis was performed using RevMan 5.0 and Stata 12.0 software. ResultsA total of 42 case-control studies involving 3 970 URSA patients and 5 297 controls were included. The results of meta-analysis showed that MTHFR C677T polymorphism was associated with the increased risk of URSA (T vs. C: OR=1.34, 95% CI 1.16 to1.54, P < 0.000 01; TT vs. TC+CC: OR=1.70, 95% CI 1.36 to 2.12, P < 0.000 01; TT+TC vs. CC: OR=1.34, 95% CI 1.11 to 1.62, P=0.002; TC vs. CC: OR=1.19, 95% CI 0.99 to 1.43, P=0.061; TT vs. CC: OR=1.95, 95% CI 1.48 to 2.56, P < 0.000 01). Subgroup analysis by ethnicity indicated that the MTHFR C677T polymorphism was associated with the increased risk of URSA in east Asians (T vs. C: OR=1.61, 95% CI 1.39 to 1.87, P < 0.000 01; TT vs. TC+CC: OR=2.05, 95% CI 1.54 to 2.71, P < 0.000 01; TT+TC vs. CC: OR=1.76, 95% CI 1.41 to 2.19, P < 0.000 01; TC vs. CC: OR=1.53, 95% CI 1.21 to 1.94, P < 0.000 01; TT vs. CC: OR=2.77, 95% CI 1.94 to 3.97, P < 0.000 01) but was not associated with the increased risk of URSA in Caucasians. The results of meta-analysis also showed that there was no significant association between the MTHFR A1298C polymorphism and the URSA in all population. ConclusionCurrent evidence indicates that significant association is found between MTHFR C677T mutation and URSA in east Asians but not in Caucasians. Further study indicates that women carrying TT or TC gene significantly increases the risk of URSA and TT mutant gene carriers have a higher URSA risk. There is no significant association between MTHFR A1298C mutation and URSA in all population. Due to the quantity and quality limitations of included studies, more high quality case-control or cohort studies are needed to verify the above conclusions.
ObjectivesTo systematically review the association between the level of blocking antibody and recurrent spontaneous abortions.MethodsPubMed, CNKI, CBM, WanFang Data and VIP databases were searched online to collect case-control studies on the association between the level of blocking antibody and recurrent spontaneous abortions from inception to May, 2017. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies, then meta-analysis was performed by using RevMan 5.3 software.ResultsA total of 12 case-control studies involving 3 413 patients were included. The results of meta-analysis showed that: there was a strong association between the blocking antibody negative and recurrent spontaneous abortions with statistical significance (OR=6.10, 95%CI 2.40 to 15.51, P=0.000 1).ConclusionsCurrent evidence shows that the blocking antibody negative is a risk factor for recurrent spontaneous abortions. Due to limited quality and quantity of the included studies, more high quality studies are required to verify above conclusions.
Objective To evaluate and select essential medicine for abortion using evidence-based approaches based on the burden of disease. Methods By means of the approaches, criteria, and workflow set up in the second article of this series, we referred to the recommendations of evidence-based or authority guidelines from inside and outside China, collected relevant evidence from domestic clinical studies, and recommended essential medicine based on evidence-based evaluation. Data were analyzed by Review Manager (RevMan) 5.1 and GRADE profiler 3.6 to evaluate quality of evidence. Results (1) Four guidelines on medicine for abortion were included, two of which are based on evidence. (2) Included guidelines referred to eight essential medicines used in drug abortion and four antibiotics used after abortion surgery. (3) According to WHOEML (2011), NEML (2009), CNF (2010), other guideline and the quantity and quality of evidence, we offered a b recommendation for misoprostol, mifepristone, oxytocin except prostaglandins used in abortion. (4) Published literature on oxytocin, misoprostol and mifepristone were found. Oxytocin with the dosage form and specification corresponding to guidelines has been marketed in China. Oxytocin (in vial, 10 U∶1 mL) cost 1.5 yuan/injection. Mifepristone (tablet, 25 mg×1) cost 13.0 to 27.5 yuan/tablet. Misoprostol (0.2 mg×3) cost 2.8 to 3.7 yuan/ tablet. (5) Results of domestic studies indicated that mifepristone combined with misoprostol and oxytocin was safe, efficient, convenient and applicable to the treatment of abortion. Conclusion For abortion: (1) We make a recommendation for mifepristone plus misoprostol. Mifepristone (25 to 50 mg/tablet) is orally taken twice a day, continually for 2 to 3 days, the total dose of 150 mg for three days. Misoprostol (0.2 mg/ tablet) 0.6 mg is orally given on an empty stomach within 36 to 48 hours after the intake of mifepristone. (2) Oxytocin (5 to 10 U in vial) injected after delivering the placenta can reduce the volume and time of vaginal bleeding. In future, clinical study should be standardized in order to improve design and implementation quality.
【摘要】 目的 调查分析有家庭成员在汶川地震中伤亡的再生育夫妇自然流产的相关危险因素。 方法 通过回顾性问卷调查方式，2008年9月-2011年3月收集整理44对震后有自然流产的再生育夫妇基本资料和自然流产相关危险因素，分析该类人群震后自然流产危险因素特点。 结果 自然流产发生率占总妊娠比例的22.9%，11.1%的女性出现了震后月经改变，有人流史妇女与无人流史妇女震后月经改变率比较，差异无统计学意义（χ2=0.58，Pgt;0.05）。 结论 震后女性易发生月经改变，地震后再生育夫妇的自然流产发生率显著高于正常人群中的自然流产发生率，环境、高龄等因素可能是该人群自然流产高发的主要危险因素。【Abstract】 Objective To explore the risk factors of spontaneous abortion related in reproduction-needed couples after the earthquake. Methods Between September 2008 and March 2011, 44 pairs of reproduction-needed couples were investigated by retrospective questionnaire. The risk factors of spontaneous abortion were analyzed. Results The spontaneous abortion rate was 22.9%; 11.1% females had the menstruation changes. The difference in the rate of the menstruation changes between the females had spontaneous abortion history and the ones didn′t had the history was not significant (χ2=0.58，Pgt;0.05). Conclusions The females after the earthquake may have menstruation changes; the spontaneous abortion rate in reproduction-needed couples after the earthquake is obviously higher than that in the normal couples. The risk factors may include the environment and the age.
Objective To systematically review the association between exposure to bisphenol A during pregnancy and spontaneous abortion. Methods The PubMed, Web of Science, EMbase, CNKI, WanFang Data and VIP databases were electronically searched to identify cohort studies and case-control studies related to bisphenol A exposure and spontaneous abortion from inception to April 1st, 2022. Two reviewers independently screened the literature, extracted data, and assessed the risk of bias of the included studies. Meta-analysis was then performed using Stata 16.0 software. Results A total of 7 case-control studies and 1 cohort study were included, with a total of 1 179 subjects. The results of meta-analysis showed that there was a statistically significant difference in bisphenol A concentrations between the spontaneous abortion group and the control group regardless of whether the sample source was serum or urine (SMD serum=1.05, 95%CI 0.34 to 1.77, P=0.004; SMD urine=0.20, 95%CI 0.02 to 0.38, P=0.027). Conclusion The current evidence shows that exposure to bisphenol A during pregnancy may lead to unexplained recurrent spontaneous abortion. Due to the limited quantity and quality of the included studies, more high-quality studies are needed to verify the above conclusion.
Objective More and more women without child and female adolescents are undergoing medical abortion (MA), MA effect on subsequent pregnancy has been brought into focus. This research will evaluate the effect of MA on subsequent pregnancy. Methods To searched Medline, Embase, Cochrane Library, Chinese Biomed-database, correlative websites and nine Chinese medical journals. The studies that were included in the reference list were additionally searched. Only RCTs (randomized control trials), CCTs (clinical control trials) and prospective cohort studies were included. Two researchers evaluated the quality of the literature and combined the evidence independently. Revman 4.1 was used for meta-analysis. Results Eight prospective cohort studies with 2 934 cases were included. The incidences of miscarriage, postpartum hemorrhage and placental abnormality occurred in MA group were significantly lower than those occurred in SA group, and their OR (with 95%CI) were 0.42 (0.22 to 0.83), 0.58 (0.39 to 0.85) and 0.68 (0.54 to 0.87), respectively. No other significant differences were observed between the two artificial abortions groups. Though the tendency indicates that medical abortion has a probable influence on subsequent pregnancy, there was no significant difference about subsequent pregnancy between MA and first pregnancy. Conclusion Unnecessary abortion should be avoided. MA is safer than SA on subsequent pregnancy, so MA is the preferred option for women without child and female adolescent to terminate their unwilling pregnancy. However, as all the studies included were prospective cohort studies, further high-quality RCTs should be conducted.
Objective To evaluate the efficacy and safety of anticoagulant agents, such as aspirin and heparin, in women with a history of at least two spontaneous miscarriages or one later intrauterine fetal death without apparent causes other than inherited thrombophilias. Methods We searched the Cochrane Pregnancy and Childbirth Group trials register (March 2004), the Central Register of Controlled Trials (The Cochrane Library, Issue 1, 2004), MEDLINE (January 1966 to March 2004), and EMBASE (1980 to March 2004). We scanned bibliographies of all located articles for any unidentified articles. Randomised and quasi-randomised controlled trials that assessed the effect of anticoagulant treatment on the live-birth rate in women with a history of at least two spontaneous miscarriages or one later intrauterine fetal death without apparent causes other than inherited thrombophilias were eligible. Interventions included aspirin, unfractionated heparin, and low molecular weight heparin for the prevention of birth loss. One treatment could be compared with another or with placebo. Two authors assessed the trials for inclusion in the review and extracted the data. Data were entered into the Review Manager software and double checked. Results Two studies (242 participants) were included in the review and for both of them data were extracted for the subgroups of women fulfiling the inclusion criteria of the review. In one study, 54 pregnant women with recurrent spontaneous abortion without detectable anticardiolipin antibodies were randomised to low-dose aspirin or placebo. Similar live-birth rates were observed with aspirin and placebo [relative risk (RR) 1.00, 95% confidence interval (CI) 0.78 to 1.29]. In another study, a subgroup of 20 women who had had a previous fetal loss after the 20th week and had a thrombophilic defect were randomised to enoxaparin or aspirin. Enoxaparin treatment resulted in an increased live-birth rate, as compared to low-dose aspirin, RR 10.00, 95% CI 1.56 to 64.20). Conclusions The evidence on the efficacy and safety of thromboprophylaxis with aspirin and heparin in women with a history of at least two spontaneous miscarriages or one later intrauterine fetal death without apparent causes other than inherited thrombophilias is too limited to recommend the use of anticoagulants in this setting. Large, randomised, placebo-controlled trials are urgently needed.
Objective To evaluate the effectiveness of mifepristone concomitant with misoprostol for medical abortion. Methods We searched the related original studies worldwide, and controlled prospective studies and systematic reviews based on randomized controlled trials （RCTs）. Nine electronic databases were searched. Ten journals and reference lists of eligible studies were handsearched. Two reviewers independently screened the studies for eligibility, evaluated the quality, and extracted the data from eligible studies, with confirmation by cross checking. Any disputes were decided by a third person. Meta-analysis was conducted using statistical software RevMan 4.2. After heterogeneity test was done （α=0.05 ） , data without heterogeneity were pooled using a fixed effect model, and those with heterogeneity could be solved by sensitivity＂ analysis, subgroup analysis or random effect model. Results We found eight original trials （n = 3 348 ） that compared medical abortion with surgical abortion, nine trials （n =6 116） that investigating the effect of gestational ages on medical abortion, five trials （n = 1 934） on the use of mifepristone and two trials （n =2381 ） on intervals of administration of mifepristone and misoprostol were located. Quality of foreign studies was better than that of Chinese studies. Therate of complete abortion was higher in surgical abortion group than that in medical abortion group with odds ratio （OR） 0. 18 and 95% confidence interval （CI） 0. 11 to 0.27. The rate of incomplete abortion and abortion failure was higher in medical abortion group with OR 3.32, and 95% CI 1.79 to 6.17, OR 7.36, 95% CI 4. 17 to 12.98, respectively. The rate of complete abortion in the group with gestational age over 49 days was lower than that with gestational age under 49 days with OR 0.51 and 95% CI 0.43 to 0.61. The rate of incomplete abortion and abortion failure was higher in the group with gestational age over 49 days with OR 1.66, 95% CI 1.32 to 2.09 and OR 3.37, 95% CI 2.30 to 4. 94.There were no significant differences observed in the rates of complete abortion, incomplete abortion, abortion failed, time of expelling pregnant sac and time of menses recovery between the single and multi-dosage of mifepristone. Except for the rate of complete abortion, which was higher in 〈48h group, there was a comparable effectiveness for different intervals of mifepristone and ntisoprostol. Conclusions This review showes that it is important to improve the quality of Chinese original studies. Although the effectiveness is better in the surgical abortion group, the rate of complete abortion of medical abortion achieved is 91.6% （1 648/1 800）. This is acceptable for clinicians and women who do not want to be pregnance. The rate of complete abortion is lower in the gestation over 49 days, which had a statistically difference, but little clinical significance. It is necessary to consider increasing the gestational age of medical abortion, especially for those women who have contradictions of surgical abortion or are afraid of operation. Effectiveness of single dosage of mifeprostone is similar to that ofmulti-dosage, but single dosage might be more convenient. This review suggests that shortening the interval ofmifepristone and misoprostol administration should be considered and the best and shortest interval time need to be identified with better evidence.
ObjectiveTo systematically evaluate the efficacy and safety of different low-molecular-weight heparins (LMWHs) in improving pregnancy outcomes in patients with recurrent abortion. MethodsThe PubMed, EMbase, Cochrane Library, CBM, CNKI, VIP and WanFang Data databases were electronically searched to collect randomized controlled trials (RCTs) related to the objectives from inception to July 2022. Two reviewers independently screened literature, extracted data and assessed the risk of bias of the included studies. Meta-analysis was then performed by using Stata 16.0 software. ResultsA total of 25 RCTs involving 4 631 patients were included. Enoxaparin, dalteparin, nadroparin, and tinzaparin were included. The results of network meta-analysis showed that the live birth rate of the tinzaparin was higher than that of enoxaparin and dalteparin. The live birth rate in nadroparin was higher than that in enoxaparin and dalteparin. The cumulative sorting probability showed that tinzaparin ranked best for improving the live birth rate, nadroparin ranked best for reducing the miscarriage rate, and enoxaparin ranked best for reducing the preterm birth rate. ConclusionCurrent evidence suggests that tinzaparin and nadroparin may be the best choice for improving pregnancy outcomes in patients with recurrent abortion. Due to the limited quality and quantity of the included studies, more high quality studies are needed to verify the above conclusion.