Oral dydrogesterone for prevention of miscarriage in threatened miscarriage: a randomized, double-blind, placebo-controlled trial.

OBJECTIVE: To determine the effectiveness of oral dydrogesterone in preventing miscarriage in threatened miscarriage. METHODS: A randomized, controlled trial study was conducted among pregnant Thai women at the gestational age of six to less than 20 weeks who visited King Chulalongkorn Memorial Hospital, Department of Obstetrics and Gynecology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand with threatened miscarriage from August 2021 to August 2022. These pregnant women were randomized to receive oral dydrogesterone 20 mg per day or placebo twice a day until one week after vaginal bleeding stopped or otherwise for a maximum of six weeks. RESULTS: A total of 100 pregnancies were recruited. Fifty of them were assigned to receive oral dydrogesterone and 50 were assigned to receive placebo. The rate of continuing pregnancy beyond 20 weeks of gestational age was 90.0% (45 out of 50 women) in the dydrogesterone group and 86.0% (43 out of 50 women) in the placebo group (p = 0.538). The incidence of adverse events did not differ significantly between the groups. CONCLUSION: Oral dydrogesterone 20 mg/day could not prevent miscarriages in women with threatened miscarriage.

The effect of progesterone supplementation in women with threatened miscarriage on fetal fraction in non-invasive prenatal testing: A matched case-control study.

AIM: To evaluate the effect of progesterone use on fetal fraction (FF) in non-invasive prenatal testing (NIPT) due to the threat of first trimester miscarriage. METHODS: This case control study included the pregnant who were referred to our clinic for non-invasive prenatal testing. The patients were categorized into three groups: Pregnant women with vaginal bleeding and using progesterone, pregnant women with vaginal bleeding and not using progesterone, and pregnant women without bleeding. The groups were formed by matching gestational week. Women with multiple pregnancy, BMI (body mass index) ≥25, abnormal fetal karyotype, and chronic disease were excluded from the study. Maternal characteristics, FF of the NIPT were recruited from the computer based medical records. RESULTS: A total of 10,275 NIPT tests were performed during the study period. 3% of the patients (n = 308) were found at risk of miscarriage. 100 patients with a vaginal bleeding and 50 control patients were matched. The median value of the fetal fraction ratio was found to be 6.55 in pregnant women without vaginal bleeding, 7.05 in pregnant women who had vaginal bleeding and using progesterone, and 7.3 in pregnant women who had vaginal bleeding and did not use progesterone. Although the fetal fraction ratio was found to be higher in pregnant women with vaginal bleeding and lower in progesterone users, this situation could not reach the level of statistical significance (p = 0.351). CONCLUSIONS: The fetal fraction rate in maternal blood is not affected in pregnant women who use progesterone due to vaginal bleeding in early gestational weeks.

Shoutai Wan regulates glycolysis imbalance at the maternal-fetal interface in threatened abortion mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Threatened abortion is a common disease among women of childbearing age. Its high incidence rate and unclear etiology, seriously threaten women's physical and mental health. Shoutai Wan (STW) is a traditional Chinese medicine decoction for treating abortion. It has a long history of treating threatened abortion by tonifying the kidney and calming the fetus. However, the mechanism of STW remains unclear. AIM OF STUDY: To study the mechanism and potential benefit of STW in pregnant mice with hydrocortisone and mifepristone-induced threatened abortion. MATERIALS AND METHODS: The STW compounds were identified using gas chromatography-mass spectrometry analysis. STW-H, STW-M, or STW-L was separately given 3 mg/ml, 1.5 mg/ml and 0.75 mg/ml STW in the morning, and 2 mg/ml hydrocortisone in the afternoon from gestation day (D) 1-9 and once with 0.4 mg/kg mifepristone on D10. Didroxyprogesterone (0.1 mg/ml) and equal dose pure water were used to replace STW in didroxyprogesterone (DYD) group and model group respectively. The control group used pure water to replace STW, hydrocortisone, and mifepristone. We performed morphological and histological analyses of the maternal-fetal interface on day 10. RESULTS: The embryo loss rate in the STW-H and DYD groups was lower than that in the model group. Hematoxylin and eosin (HE) staining suggested that the morphology of maternal-fetal interface was improved in the STW-H and DYD groups. Immunohistochemical (IHC), Quantitative Reverse Transcription Polymerase Chain Reactionstaining (qRT-PCR), and Western blot (WB) results indicated that HIF-1α expression in the maternal-fetal interface of the STW-H and DYD groups was higher than that in model group. The activities of HK, PKM, LDH and the concentration of lactic acid in the STW-H and DYD groups were higher than those in model group. Furthermore, the protein and mRNA levels of HK2, PKM2, LDHA, MCT4, and GPR81 were higher in the STW-H and DYD groups than those in the model group. CONCLUSIONS: STW can reduce the pregnancy loss rate by regulating the glycolysis balance at the maternal-fetal interface of kidney deficiency threatened abortion model mice.

Shoutai pills for threatened abortion: A protocol for systematic review and meta-analysis.

BACKGROUND: Threatened abortions are a serious health risk for women. Deferiprone tablets are commonly used in the treatment of clinical delivery. Traditional Chinese medicine, a characteristic medical system inherited for thousands of years, often applies Shoutai pills in the treatment of Threatened abortion and has achieved good results. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of Shoutai pills combined with dedrogesterone tablets for the treatment of early preterm abortion. METHODS: Electronic searches of clinical randomized controlled trials in PubMed, Web of Science, MEDLINE, EMBASE, China National Knowledge Infrastructure, Wanfang database, and China Scientific Journal Database (VIP) were conducted. References to the included literature, gray literature in Open Grey, and other relevant literature such as clinical studies registered in ClinicalTrials.gov, were also manually searched. Relevant data were extracted, and a meta-analysis was performed using Reviewer Manager 5.4. RESULTS: The results of this study will be submitted to peer-reviewed journals. CONCLUSION: This study provides high-quality evidence on the efficacy and safety of Shoutai pills in combination with dedrogesterone tablets for the treatment of preterm abortion.

Progesterone for women with threatened miscarriage (STOP trial): a placebo-controlled randomized clinical trial.

STUDY QUESTION: In women with threatened miscarriage, does progesterone supplementation until the completion of the first trimester of pregnancy increase the probability of live birth? SUMMARY ANSWER: In women with threatened miscarriage, 400 mg vaginal progesterone nightly, from onset of bleeding until 12 weeks, did not increase live birth rates. WHAT IS KNOWN ALREADY: Limited evidence has indicated that vaginal micronized progesterone may make little or no difference to the live birth rate when compared with placebo in women with threatened miscarriage. Subgroup analysis of one recent randomized trial reported that in women with bleeding and at least one previous miscarriage, progesterone might be of benefit. STUDY DESIGN, SIZE, DURATION: We performed a randomized, double-blinded, placebo-controlled trial between February 2012 and April 2019. Eligible pregnant women under 10 weeks gestation, experiencing a threatened miscarriage as apparent from vaginal bleeding were randomized into two groups in a 1:1 ratio: the intervention group received 400 mg progesterone as vaginal pessaries, the control group received placebo vaginal pessaries, both until 12 weeks gestation. The primary endpoint was live birth. We planned to randomize 386 women (193 per group). The study was stopped at a planned interim analysis for futility after randomization of 278 women. PARTICIPANTS/MATERIALS, SETTING, METHODS: This trial was conducted at the Mater Mothers' Hospital, a tertiary centre for maternity care in South Brisbane, Queensland, Australia. We randomized 139 women to the intervention group and 139 women to the placebo group. Primary outcome data were available for 136 women in the intervention group and 133 women in the placebo group. MAIN RESULTS AND THE ROLE OF CHANCE: The live birth rates were 82.4% (112/136) and 84.2% (112/133) in the intervention group and placebo group, respectively (risk ratio (RR) 0.98, 95% CI 0.88 to 1.09; risk difference -0.02, 95% CI -0.11 to 0.07; P = 0.683). Among women with at least one previous miscarriage, live birth rates were 80.6% (54/67) and 84.4% (65/77) (RR 0.95, 95% CI 0.82-1.11; P = 0.550). No significant effect was seen from progesterone in women with two (RR 1.28, 95% CI 0.96-1.72; P = 0.096) or more (RR 0.79, 95% CI 0.53-1.19; P = 0.267) previous miscarriages. Preterm birth rates were 12.9% and 9.3%, respectively (RR 1.38; 95% CI 0.69 to 2.78; P = 0.361). Median birth weight was 3310 vs 3300 g (P = 0.992). There were also no other significant differences in obstetric and perinatal outcomes. LIMITATIONS, REASONS FOR CAUTION: Our study was single centre and did not reach the planned sample size because it was stopped prematurely at an interim analysis. WIDER IMPLICATIONS OF THE FINDINGS: We did not find evidence supporting the treatment effect of vaginal progesterone in women with threatened miscarriage. Progesterone in this setting should not be routinely used for threatened miscarriage. The treatment effect in women with threatened miscarriage after previous miscarriages warrants further research. STUDY FUNDING/COMPETING INTEREST(S): Mothers' and babies Golden Casket Clinical Fellowship (L.A.M.). Progesterone and placebo pessaries were provided by Perrigo Australia.B.W.J.M. reports grants from NHMRC, personal fees from ObsEva, personal fees from Merck KGaA, personal fees from Guerbet, personal fees from iGenomix, outside the submitted work. TRIAL REGISTRATION NUMBER: ACTRN12611000405910. TRIAL REGISTRATION DATE: 19 April 2011. DATE OF FIRST PATIENT'S ENROLMENT: 06 February 2012.

Meta analysis of the effect of phloroglucinol combined with progesterone in the treatment of threatened miscarriage before 20 weeks of gestation: A protocol for a systematic review.

BACKGROUND: Threatened miscarriage (TM) is an important factor endangering the health of pregnant women. It not only affects women's physical and mental health, but also destroys family happiness. To treat this disease, it is necessary to find a treatment with better clinical efficacy and fewer side effects. The purpose of this systematic study was to evaluate the efficacy and safety of phloroglucinol (PHL) combined with progesterone in the treatment of TM before 20 weeks of pregnancy. METHODS: Electronic databases (EMBASE, PubMed, Cochrane Central Register of Controlled Trials, Web of Science, Elsevier, China National Knowledge Infrastructure, Chongqing VIP, and WanFang Data) were searched from inception until September. 2022. Randomized controlled trials of PHL combined with progesterone in the treatment of TM before 20 weeks of gestation will be included, and all articles will be independently screened and collected by 2 reviewers. Revman 5.3.5 software will be used for meta-analysis. The specific process is described in the Cochrane Handbook for Systematic Reviews. RESULTS: The efficacy and safety of PHL combined with progesterone for the treatment of threatened abortion were comprehensively evaluated in terms of efficacy, efficiency, time of symptom relief, length of hospital stay, and incidence of adverse events. CONCLUSION: This study provides reliable evidence for the clinical application of PHL combined with progesterone for the treatment of TM.

Network pharmacological analysis and molecular docking of Huangqin-Baizhu herb pair in the treatment of threatened abortion.

BACKGROUND: The incidence of threatened abortion (TA) is increasing due to poor diet and living habits, which brings great pressure to pregnant women and their families. Huangqin-Baizhu herb pair recorded in ancient books of traditional Chinese medicine has been widely used in the treatment of TA with remarkable effect. In this study, we will use the network pharmacology method to predict the target and mechanism of Huangqin-Baizhu herb pair. METHODS: Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform database was used to screen the active components of Huangqin-Baizhu herb pair. Pubchem and Swiss Target Prediction databases were used to predict the action targets. Genecards, OMIM, and Drugbank databases were used to predict the related targets of TA. The intersection of drug target and disease target was selected and the intersection genes were uploaded to STRING database to construct protein-protein interaction network and conduct module analysis. Metascape database was used for Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, which was imported into Cytoscape software to construct component-pathway-gene network and finally verified by molecular docking. Ethical approval and informed consent of patients are not required because the data used in this study is publicly available and does not involve individual patient data or privacy. RESULTS: The main active components of the herb pair are baicalein, flavanone, and norwogonin, etc. The main targets are AKT1, VEGFA, STAT3, MAPK1, SRC, etc. Cluster module analysis shows that the targets are related to cell metabolism, immune regulation and hormone level regulation. There were 2073, 3169, and 161 KEGG pathways involved in the biological processes, cell components, and molecular functions of Gene Ontology analysis, respectively. The main KEGG pathways involved in the intervention were HIF1 signaling pathway, PI3K-Akt signaling pathway, and Rap1 signaling pathway. Molecular docking showed that the main active components of the herb pair were well combined with the key targets. CONCLUSIONS: In this study, 42 active components, 152 potential targets and 11 key targets of Huangqin-Baizhu herb pair for the treatment of TA were revealed, participating in multiple signaling pathways such as PI3K-Akt, providing a theoretical basis for further experimental research.

Effects of Dydrogesterone Tablets Combined with Zishen Yutai Pills on Threatened Abortion in Early Pregnancy and Pregnancy Outcomes.

Objective: To explore the effect of dydrogesterone tablets combined with Zishen Yutai pills on threatened abortion in early pregnancy and pregnancy outcomes. Methods: This study retrospectively analyzed the clinical data of 100 patients with threatened abortion in early pregnancy who came to the Linhai Second People's Hospital/Taizhou Municipal Hospital from January 13, 2021, to January 13, 2022. According to different treatment methods, 48 patients treated with progesterone injection were assigned to the control group (CG), while 52 cases with the combined therapy of dydrogesterone tablets and Zishen Yutai pills were assigned to the observation group (OG). The two groups were compared in terms of the following parameters: treatment efficacy, whole blood high shear viscosity, hematocrit (HCT), plasma fibrinogen (FIB) level, spiral artery pulsatility index (PI), uterine spiral artery blood flow resistance index (RI), lumbar and abdominal pain relief time, hemostasis time, estrogen levels, pregnancy outcomes, neonatal adverse outcomes, and incidence of adverse reactions. Results: Compared with CG, the therapeutic effect in OG was observed to be evidently better, and its pain relief time and hemostasis time in the waist and abdomen were markedly shorter. After treatment, the whole blood high shear viscosity, FIB, RI, PI, and estrogen levels of both groups improved statistically compared with those before treatment, with more significant improvements in OG compared with CG. OG was also superior to CG with markedly lower incidence of preterm birth, miscarriage, neonatal adverse outcomes, and adverse reactions and a drastically higher full-term pregnancy rate. Conclusion: Zishen Yutai pill combined with dydrogesterone tablets is of remarkable therapeutic effect in treatment of early threatened abortion, which can significantly improve clinical symptoms and pregnancy outcomes of patients, with a high safety profile, which is worthy of clinical application.

The role of intraamniotic inflammation in threatened midtrimester miscarriage.

BACKGROUND: The assessment and management of patients with threatened midtrimester miscarriage is a clinical challenge because the etiology of this condition is poorly understood. OBJECTIVE: This study aimed to examine the frequency of intraamniotic infection or inflammation and the effect of antibiotics in patients presenting with regular uterine contractions and intact membranes before 20 weeks of gestation. STUDY DESIGN: This retrospective study comprised patients who met the following criteria: (1) singleton gestation, (2) gestational age before 20 weeks, (3) the presence of regular uterine contractions confirmed by a tocodynamometer (8 or more contractions in 60 minutes), (4) intact amniotic membranes, and (5) transabdominal amniocentesis performed for the evaluation of the microbiologic and inflammatory status of the amniotic cavity. Samples of amniotic fluid were cultured for aerobic and anaerobic bacteria and genital mycoplasmas, and polymerase chain reaction was performed to detect Ureaplasma species. Amniotic fluid was tested for white blood cell counts and matrix metalloproteinase-8 concentrations to diagnose intraamniotic inflammation. Patients with intraamniotic inflammation, or intraamniotic infection, were treated with antibiotics (a combination of ceftriaxone, clarithromycin, and metronidazole). Treatment success was defined as the resolution of intraamniotic infection/inflammation at the follow-up amniocentesis or delivery after 34 weeks of gestation. RESULTS: 1) Intraamniotic inflammation was present in 88% (15/17) of patients, whereas infection was detectable in only 2 cases; 2) objective evidence of resolution of intraamniotic inflammation after antibiotic treatment was demonstrated in 100% (4/4) of patients who underwent a follow-up amniocentesis; 3) 30% (5/15) of women receiving antibiotics delivered after 34 weeks of gestation (3 of the 5 patients had a negative follow-up amniocentesis, and 2 of the women were without a follow-up amniocentesis); 4) the overall treatment success of antibiotics was 40% (6/15; 4 cases of objective evidence of resolution of intra-amniotic inflammation and 5 cases of delivery after 34 weeks of gestation). CONCLUSION: The prevalence of intraamniotic inflammation in patients who presented with a threatened midtrimester miscarriage was 88% (15/17), and, in most cases, microorganisms could not be detected. Antibiotic treatment, administered to patients with intraamniotic inflammation, was associated with either objective resolution of intraamniotic inflammation or delivery after 34 weeks of gestation in 40% (6/15) of the cases.

Chemical profile and miscarriage prevention evaluation of Jiao-Ai Decoction, a classical traditional Chinese formula.

Jiao-Ai Decoction (JAD), a classical traditional Chinese formula composed of seven Chinese herbs, has been widely used in clinical practice for the treatment of abortion for a long time. However, the material basis and pharmacological mechanism remain unclear. An integrative method combining ultra-performance liquid chromatography coupled with mass spectrometry (UPLC-MS/MS) analysis and therapeutic effect evaluation based on the hypothalamus-pituitary-ovarian axis (HPOA) was employed to elaborate these problems. Firstly, the chemical profile of JAD was identified by UPLC-Q-TOF-MS. Secondly, the main target ingredients from JAD were determined by UPLC-T-Q-MS. Finally, the miscarriage prevention of JAD on threatened abortion pregnant rats induced by mifepristone was investigated. Threatened abortion model in rats were replicated, uterine bleeding quantity (UBQ) and histopathological sections were measured, the contents of luteinizing hormone (LH), follicular stimulating hormone (FSH), estradiol (E2) and progesterone (P) were determined by ELISA, related genes and protein expression levels were detected by RT-PCR and western blotting. As a result, a total of 101 compounds were identified and 27 ingredients were determined to evaluate the quality of JAD. In the model rats, JAD could effectively regulate the HPOA to achieve miscarriage prevention, and the mechanism might be related to the regulation of gene and protein expression on the HPOA. This work could provide a novel and valuable approach for the quality evaluation of JAD and were expected to provide ideas and methods for the basic research on the scientific application of similar traditional Chinese medicine prescriptions.

Efficacy and safety of Yunkang oral liquid combined with conventional therapy for threatened miscarriage of first-trimester pregnancy a protocol for systematic review and meta-analysis.

INTRODUCTION: Threatened miscarriages is a common complication of first-trimester pregnancy. Due to the beneficial effects, there are increasing clinical studies on Yunkang oral liquid(YKOL). However, the efficacy and safety of YKOL are still unknown. The aim of this systematic review was to assess the efficacy and safety of YKOL in the treatment of threatened miscarriage during the first-trimester pregnancy (TMFP). METHODS: This protocol will be prepared according to the preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) statement. The systematic review will include all randomized controlled trials (RCTs) studies published until April 2021. Electronic sources including CNKI, WF, VIP, CBM, MEDLINE(PubMed), Embase, Cochrane Library, and Web of Science will be searched for potentially eligible studies. The international clinical trial registration platform and the Chinese clinical trial registration platform of controlled trials will be searched from their inception until April 1st, 2021. According to the inclusion and exclusion criteria, screening literature, extraction data will be conducted by two researchers independently. Statistical analysis will use RevMan 5.3.5 software. The strength of evidence from the studies will be evaluated with the Grading of Recommendation, Assessment, Development and Evaluation (GRADE) methods. RESULTS: This study will provide evidence for YKOL combined with conventional therapy for TMFP. CONCLUSION: The efficacy and safety of YKOL combined with conventional therapy for TMFP will be assessed. SYSTEMATIC REVIEW REGISTRATION: INPLASY202140105 (https://www.doi.org/10.37766/inplasy2021.4.0105).

The effects of exogenous oral micronized progesterone on first trimester aneuploidy screening markers in women with threatened miscarriage: a matched case control study.

OBJECTIVES: To evaluate the effect of using progesterone due to early vaginal bleeding on aneuploidy screening markers in the first trimester. MATERIAL AND METHODS: This case control study includes the pregnant women who applied to our clinic in order to have a screening test for Down syndrome in the weeks of 11°/7-136/7. The patients were divided into three groups. Self reported vaginal bleeding with progesterone therapy (Bl+, Prg+, n:70), Self reported vaginal bleeding without progesterone therapy (Bl+, Prg-, n:70) and as a control group pregnant women who had no vaginal bleeding. (NoBl, NoPrg, n:70). In all patients, free beta-human chorionic gonadotrophin (ß-hCG), pregnancy associated plasma protein-A (PAPP-A) levels and nuchal translucency (NT) thickness were analyzed. Mean MoMs of the markers were compared between three groups. RESULTS: In the two groups with vaginal bleeding (Bl+, Prg + and Bl+, Prg-) the free ß-Hcg MoM values were statistically higher (1.22 ± 0.72, 0.98 ± 0.45, respectively) compared to the No Bleeding/No Progesterone group (0.81 ± 0.52) (p ≤ 0.001, p ≤ .01, respectively). However, no significant difference was found between the free ß-hCG MoM value of women with Bl+, Prg + group (1.22 ± 0.72) and Bl+, Prg - group (0.98 ± 0.45). (p: .053, significance level limitation with Bonferroni correction p: .017). PAPP-A and NT thickness did not differ significantly between the groups. CONCLUSION: Our data did not find an association between the use of oral progesterone and any alternations in first trimester screening parameters. Regardless of the progesterone usage, vaginal bleeding in the first trimester pregnancies increased the free ß-hCG MoM values compared to pregnancies without vaginal bleeding during pregnancy.

A pairwise and network meta-analysis comparing the efficacy and safety of progestogens in threatened abortion.

BACKGROUND: Progesterone is widely used to prevent threatened miscarriage. OBJECTIVE: To determine the efficacy and safety of progestogens in the treatment of threatened miscarriage. SEARCH STRATEGY: PubMed, Cochrane Library, EMBASE, CNKI, CBM, and WanFang databases were searched for randomized controlled trials (RCTs) published from the date of inception of the database to August 2020. The search terms included "abortion, threatened," "progesterone," and "progestogens." SELECTION CRITERIA: A network meta-analysis was conducted of all the RCTs on threatened abortion so far to compare the efficacy and safety of different progestogens in the treatment of threatened abortion. DATA COLLECTION AND ANALYSIS: Odds ratios for dichotomous data with 95% confidence intervals were calculated and the data were pooled using a random-effects model. The surface under the cumulative ranking area (SUCRA) was calculated for efficacy and safety with different interventions. MAIN RESULTS: A total of 59 RCTs with 10 424 participants were included. Oral dydrogesterone (DYD) had the lowest risk of miscarriage (SUCRA 100.0%), followed by vaginal progesterone (SUCRA 67.9%). Oral micronized progesterone had the highest risk of miscarriage (SUCRA 15.7%). CONCLUSION: Oral DYD is effective in the treatment of threatened miscarriage. The results of the present study can help patients make informed decisions about treatment options for threatened miscarriage.

Dydrogesterone indications beyond menopausal hormone therapy: an evidence review and woman's journey.

Dydrogesterone is an orally active synthetic progestogen, with a molecular structure similar to that of natural progesterone. As dydrogesterone does not inhibit ovulation at standard doses, is devoid of estrogenic or androgenic properties, and does not induce metabolic side effects, it is suitable for use throughout a woman's lifetime, from adolescence to older age, for conditions associated with altered levels of endogenous progesterone. Aside from its well established role as a component of menopausal hormone therapy, dydrogesterone is indicated in younger women for treatment of dysmenorrhea, irregular menstrual cycles, premenstrual syndrome, and threatened or recurrent miscarriage; and is effective as luteal phase support during assisted reproduction techniques. In this narrative review, evidence is examined for use of dydrogesterone across a range of disorders affecting menses and pregnancy. A case study woven into the review illustrates the clinical uses of dydrogesterone during a young woman's journey to become a mother.

Research on the medication rules of Chinese herbal formulas on treatment of threatened abortion.

BACKGROUNDS: Threatened abortion (TA) is the most common complication during early pregnancy affecting 20%-25% pregnancies. A variety of Chinese herbal medicines have shown good protective effects against TA. OBJECTIVE: To analyze the different prescriptions for TA and summarize the medication rules for such treatment. METHODS: Data mining methods including frequency analysis, cluster analysis, factor analysis and association rule learning were used in this study. RESULTS: In total, 171 herbs and 398 formulas were collected. The most frequently used herbs are Dipsaci Radix (Xuduan, accounts for 7.58%). The top three categories were deficiency-tonifying herbs (29.24%), wind-damp dispelling herbs (12.87%) and heat-clearing herbs (9.94%). Eleven factors and 8 clusters with clinical significance for prescription were formed by factor and cluster analyses. CONCLUSIONS: Tonification methods including spleen and kidney nourishment are the main principles for TA treatment and Shoutai Pill can be used as the basic formula for clinical addition or subtraction.

Atosiban Combined with Ritodrine for Late Threatened Abortion or Threatened Premature Labor Patients with No Response to Ritodrine: A Clinical Trial.

BACKGROUND Premature labor is an important cause of infant death and long-term disability. This study aimed to explore the safety and effectiveness of combining the tocolytic agents atosiban and ritodrine to extend gestation. MATERIAL AND METHODS The study included 52 patients with late threatened abortion and threatened premature labor between 20°â¸7 and 336⸍7 weeks' gestation who were administrated continuous tocolytic agents for 48 h. Patients were divided into a research group receiving ritodrine combined with atosiban, owing to having no response to ritodrine alone (n=30), and a control group receiving ritodrine alone (n=22). The mean infusion rate and duration of tocolytic administration, gestation extension, pregnancy outcomes, and adverse effects were recorded. Routine blood tests, including C-reactive protein, and cultures for leukorrhea, candida, and mycoplasma were performed before and 1 week after treatment. RESULTS Patients receiving ritodrine with atosiban had a mean gestation extension of 42.53±31.70 days. The extension of gestation of the research group was statistically shorter than that of the control group (P<0.05). The fetal loss rate, newborn birth weight, and Apgar score at 1 min were similar between the 2 groups (all, P>0.05). The research group had a lower incidence of palpitations than the control group (P<0.05). CONCLUSIONS For patients with late threatened abortion or threatened premature labor not controlled with ritodrine alone, ritodrine combined with atosiban extends gestation and improves pregnancy outcomes. For patients with abnormal uterine contractions, routine testing for reproductive tract infection should be performed. When infection is present, anti-infective therapy should be administered.

Efficacy and safety of traditional Chinese herbal medicine in the treatment of threatened abortion: A protocol for systematic review and meta-analysis.

BACKGROUND: Threatened abortion (TA) is the commonest complication that occurs in early pregnancy, especially in 8-12 gestational weeks when the secretion of estrogen and progesterone shifts from corpus luteum to placental. Conventional therapies are little evidence of their value. In China, traditional Chinese herbal medicine has been widely used for the treatment of TA for a long time. The lack of strong scientific evidences make this a priority area for research. We aim to evaluate the efficacy and safety of traditional Chinese herbal medicine in the treatment of TA, provide medical staffs with more useful information, and provide patients with better advises. METHODS: We will search 8 databases and additional sources, including the Web of Science, PubMed, Cochrane Library, Embase, CBM, Wanfang, VIP, CNKI, and WHO ICTRP, ChiCTR, Clinical Trials, Grey Literature Database, for potentially eligible studies. Literature search, screening and retrieval are performed independently by two researchers. In the event of a dispute, a third party will be consulted to support the judgment. We will use RevmanV.5.3 to perform a fixed-effect meta-analysis for clinical homogeneity study data, and the level of evidence will be assessed using the GRADE method. RESULTS: This systematic review and meta-analysis will put a high-quality synthesis of the efficacy and safety of traditional Chinese herbal medicine in the treatment of TA. CONCLUSION: The conclusion of this systematic review will provide evidence to assess traditional Chinese herbal medicine therapy whether is an efficacy and safe intervention to treat TA. ETHICS AND DISSEMINATION: Since this article does not contain patient personal information, ethical approval is not required. The contract is distributed by a peer-reviewed journal or conference report. REGISTRATION NUMBER: 10.17605/OSF.IO/DG3T8.

Efficacy of progesterone on threatened miscarriage: an updated meta-analysis of randomized trials.

PURPOSE: The efficacy of progesterone supplementation in the treatment of threatened miscarriage is controversial. This meta-analysis was to evaluate the correlation between progesterone and improving pregnancy outcomes in women with threatened miscarriage. METHODS: We searched PubMed, EMBASE, and the Cochrane Library for relevant randomized controlled trials (RCTs) to demonstrate the efficacy of progesterone on the threatened miscarriage pregnancy. The outcomes were miscarriage, preterm birth, and live birth. RESULTS: Nine RCTs comparing 4907 patients were included in this study. Compared with placebo or no treatment, progesterone supplementation had a relationship with a reduction in the rate of miscarriage [RR 0.70 95% Cl (0.52, 0.94)]. There was no significant difference between progesterone supplementation and placebo or no treatment in preterm birth [RR 0.87 95% Cl (0.52, 1.47) and live birth (RR 1.02 95% Cl (0.98, 1.07)]. CONCLUSION: Progesterone supplementation did not significantly improve the incidence of preterm and live birth, so progesterone treatment of threatened miscarriage may be unhelpful.

Use of oral progestogen in women with threatened miscarriage in the first trimester: a randomized double-blind controlled trial.

STUDY QUESTION: Will use of oral progestogen in women with threatened miscarriage in the first trimester reduce the miscarriage rate when compared with placebo? SUMMARY ANSWER: Use of oral progestogen in women with threatened miscarriage in the first trimester did not reduce miscarriage before 20 weeks when compared with placebo. WHAT IS KNOWN ALREADY: Miscarriage is a common complication of pregnancy and occurs in 15-20% of clinically recognized pregnancies. Use of vaginal progestogens is not effective in reducing miscarriage but there is still no good evidence to support use of oral progestogen for the treatment of threatened miscarriage. STUDY DESIGN, SIZE, DURATION: This was a randomized double-blind controlled trial. A total of 406 women presenting with threatened miscarriage in the first trimester were recruited from 30 March 2016 to May 2018. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women attending Early Pregnancy Assessment Clinics because of vaginal bleeding during the first trimester were recruited and randomly assigned to use dydrogesterone 40 mg orally, followed by 10 mg orally three times a day or placebo until 12 completed weeks of gestation or 1 week after the bleeding stopped, whichever was later. The primary outcome was the miscarriage rate before 20 weeks of gestation. MAIN RESULTS AND THE ROLE OF CHANCE: The two groups of women had comparable age, BMI, number of previous miscarriages, gestation and ultrasound findings at presentation. The miscarriage rate before 20 weeks of gestation was similar in both groups, being 12.8% (26/203) in the progestogen group and 14.3% (29/203) in the placebo group (relative risk 0.897, 95% CI 0.548-1.467; P = 0.772). The live birth rate was 81.3% in the progestogen group versus 83.3% in the placebo group (P = 0.697). No significant differences were found between the two groups in terms of obstetric outcomes and side effects. LIMITATIONS, REASONS FOR CAUTION: The primary outcome was the miscarriage rate, rather than the live birth rate. Women were recruited from Early Pregnancy Assessment Clinics and those with heavy vaginal bleeding might be admitted into wards directly instead of attending Early Pregnancy Assessment Clinic. The severity of vaginal bleeding was subjectively graded by women themselves. The sample size was not adequate to demonstrate a smaller difference in the miscarriage rate between the progestogen and placebo groups. We did not exclude women with multiple pregnancy, which increased the risk of miscarriage although there was only one set of twin pregnancy in the placebo group. WIDER IMPLICATIONS OF THE FINDINGS: Use of oral progestogen is not recommended in women with threatened miscarriage in the first trimester. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by the Health and Medical Research Fund, HKSAR (reference number 12132341). All authors declared no conflict of interest. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov with an identifier NCT02128685. TRIAL REGISTRATION DATE: 1 May 2014. DATE OF FIRST PATIENT'S ENROLMENT: 30 March 2016.

The effects of progesterone treatment on nuchal translucency in women with threatened miscarriage.

This study aims to investigate the effects of progesterone on the possible changes in nuchal translucency (NT) levels for patients diagnosed with threatened miscarriage. The study group was composed of 125 patients diagnosed with threatened miscarriage and taking 400 mg/day micronized orally progesterone at least for two weeks, the control group was composed of 160 healthy pregnant women not taking any progesterone. Crown rump length (CRL) NT thickness, Pregnancy-associated plasma protein-A (PAPP-A), free beta human chorionic gonadotropin (Beta-HCG) levels of patients were measured for assessment of aneuploidy risk. Both of the groups were divided into four subgroups to determine the relationship between thickness of NT and progesterone use for specific CRL measurements. CRL in the first, second, third and fourth group was 45-55 mm, 55-65 mm, 65-75 mm, 75-84 mm, respectively. The two groups were age and BMI matched. In all groups of CRL there were no significant difference in Mom levels of NT thickness, PAPP-A and free Beta-HCG between the study and control groups. There havent been any relation between NT thickness and progesterone use.IMPACT STATEMENTWhat is already known about this subject? Recently some studies have claimed that progesterone use might have caused atypical blood flow pattern on foetal circulation, which could possibly increase NT. If the NT thickness is affected by the use of progesterone, then the false positive rate of detecting Down Syndrome screening tests would increase.What the results of this study add? In this study we did not found any relation between NT thickness and progesterone use.What the implications are of these findings for clinical practice and/or further research? Using orally progesterone due to threatened miscarriage do not change NT thickness levels. Further studies have to be done with a large number of participants.